const {
  Document, Packer, Paragraph, TextRun, Table, TableRow, TableCell,
  HeadingLevel, AlignmentType, BorderStyle, WidthType, VerticalAlign,
  PageNumber, NumberFormat, Header, Footer, ShadingType
} = require('docx');
const fs = require('fs');

// ── helpers ──────────────────────────────────────────────────────────────────
const bold = (t, sz) => new TextRun({ text: t, bold: true, size: sz || 24 });
const normal = (t, sz) => new TextRun({ text: t, size: sz || 24 });
const italic = (t, sz) => new TextRun({ text: t, italics: true, size: sz || 24 });

function h1(text) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_1,
    spacing: { before: 360, after: 160 },
    children: [new TextRun({ text, bold: true, size: 28 })],
  });
}

function h2(text) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_2,
    spacing: { before: 280, after: 120 },
    children: [new TextRun({ text, bold: true, size: 26 })],
  });
}

function h3(text) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_3,
    spacing: { before: 200, after: 100 },
    children: [new TextRun({ text, bold: true, italics: true, size: 24 })],
  });
}

function p(runs, spacing) {
  const children = Array.isArray(runs)
    ? runs
    : [new TextRun({ text: runs, size: 24 })];
  return new Paragraph({
    children,
    spacing: { after: spacing || 160 },
    alignment: AlignmentType.JUSTIFIED,
  });
}

function bullet(text, indent) {
  return new Paragraph({
    bullet: { level: indent || 0 },
    children: [new TextRun({ text, size: 24 })],
    spacing: { after: 80 },
  });
}

function simpleTable(headers, rows) {
  const headerRow = new TableRow({
    children: headers.map(h =>
      new TableCell({
        shading: { type: ShadingType.CLEAR, color: "auto", fill: "4472C4" },
        children: [new Paragraph({
          alignment: AlignmentType.CENTER,
          children: [new TextRun({ text: h, bold: true, size: 22, color: "FFFFFF" })],
        })],
        verticalAlign: VerticalAlign.CENTER,
      })
    ),
    tableHeader: true,
  });

  const dataRows = rows.map((row, ri) =>
    new TableRow({
      children: row.map(cell =>
        new TableCell({
          shading: ri % 2 === 0
            ? { type: ShadingType.CLEAR, color: "auto", fill: "EAF0FB" }
            : { type: ShadingType.CLEAR, color: "auto", fill: "FFFFFF" },
          children: [new Paragraph({
            alignment: AlignmentType.CENTER,
            children: [new TextRun({ text: cell, size: 22 })],
          })],
          verticalAlign: VerticalAlign.CENTER,
        })
      ),
    })
  );

  return new Table({
    width: { size: 100, type: WidthType.PERCENTAGE },
    rows: [headerRow, ...dataRows],
    borders: {
      top:    { style: BorderStyle.SINGLE, size: 1 },
      bottom: { style: BorderStyle.SINGLE, size: 1 },
      left:   { style: BorderStyle.SINGLE, size: 1 },
      right:  { style: BorderStyle.SINGLE, size: 1 },
      insideH:{ style: BorderStyle.SINGLE, size: 1 },
      insideV:{ style: BorderStyle.SINGLE, size: 1 },
    },
  });
}

// ─────────────────────────────────────────────────────────────────────────────
// DOCUMENT CONTENT
// ─────────────────────────────────────────────────────────────────────────────

const titlePage = [
  new Paragraph({ spacing: { before: 720 } }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { after: 120 },
    children: [new TextRun({ text: "STUDENT'S RESEARCH WORK (УИР)", bold: true, size: 28, allCaps: true })],
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { after: 480 },
    children: [new TextRun({ text: "4th Year, Faculty Therapy", size: 26 })],
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { after: 240 },
    children: [new TextRun({ text: "CLINICAL CASE REPORT", bold: true, size: 36, allCaps: true })],
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { after: 480 },
    children: [new TextRun({ text: "Community-Acquired Pneumonia", bold: true, size: 30 })],
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { after: 120 },
    children: [new TextRun({ text: "Discipline: Faculty Therapy", size: 24, italics: true })],
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { after: 720 },
    children: [new TextRun({ text: "Department of Internal Medicine", size: 24, italics: true })],
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { after: 240 },
    children: [new TextRun({ text: "2025–2026", size: 24 })],
  }),
];

// ─────────── SECTION 1: RELEVANCE ────────────────────────────────────────────
const section1 = [
  h1("1. RELEVANCE OF THE TOPIC"),
  p("Community-acquired pneumonia (CAP) remains one of the most prevalent and potentially life-threatening infectious diseases worldwide. It is defined as an acute infection of the pulmonary parenchyma acquired outside of a hospital setting or healthcare facility, manifesting with symptoms and signs of lower respiratory tract infection accompanied by a new infiltrate on chest imaging."),

  h2("1.1 Global Epidemiology"),
  p("According to the Global Burden of Disease Study 2021 (GBD 2021), lower respiratory infections — of which pneumonia is the dominant form — accounted for an estimated 344 million incident episodes globally in 2021, with approximately 2.18 million deaths (27.7 per 100,000 population). Streptococcus pneumoniae remains the single leading pathogen, responsible for an estimated 97.9 million episodes and 505,000 deaths globally (GBD 2021 Collaborators, Lancet Infect Dis, 2024)."),
  p("Pneumonia is the most common infectious cause of hospitalization and death in the United States. Hospitalization rates increase exponentially with age: from 1–2 per 1,000 in young adults to approximately 40 per 1,000 in persons aged ≥85 years. The in-hospital mortality for CAP requiring hospitalization is approximately 6%, rising to 15% at one month (Goldman-Cecil Medicine, 2022)."),
  p("In Russia, pneumonia consistently ranks among the leading causes of infectious-disease-related disability and mortality. Epidemiological surveillance data indicate an incidence of approximately 400–500 cases per 100,000 adults per year, with higher figures in winter months coinciding with seasonal influenza activity."),

  h2("1.2 Significance and Relevance"),
  p("The clinical and public health significance of pneumonia is underscored by:"),
  bullet("Its ranking as the 4th leading cause of death globally among all age groups."),
  bullet("Long-term complications now increasingly recognised: cardiovascular events, persistent respiratory impairment, and cognitive decline (Reyes et al., Lancet, 2025)."),
  bullet("Rising antimicrobial resistance threatening empiric treatment strategies."),
  bullet("The COVID-19 pandemic demonstrating the catastrophic potential of respiratory infections when novel pathogens emerge."),
  bullet("Preventable burden through vaccination against S. pneumoniae, influenza, and SARS-CoV-2, making accurate clinical recognition and management essential."),
  p("The study of this nosology is therefore of major medical, social, and economic importance, justifying its selection as the subject of this student research work."),
];

// ─────────── SECTION 2: LITERATURE REVIEW ────────────────────────────────────
const section2 = [
  h1("2. LITERATURE REVIEW"),

  h2("2.1 Definition and Classification"),
  p("Pneumonia is an acute infection of the lung parenchyma characterised by alveolar consolidation, inflammatory exudate, and impaired gas exchange. Classification by acquisition setting is clinically relevant because it determines the likely causative organisms and guides empiric therapy:"),
  bullet("Community-acquired pneumonia (CAP) — acquired outside hospital or within 48 hours of admission in a patient not residing in a long-term care facility."),
  bullet("Hospital-acquired pneumonia (HAP) — onset ≥48 hours after hospital admission."),
  bullet("Ventilator-associated pneumonia (VAP) — developing ≥48 hours after endotracheal intubation."),
  bullet("Healthcare-associated pneumonia (HCAP) — a now largely abandoned category."),
  p("By radiological pattern, pneumonia may be lobular/lobar (typically bacterial), bronchopneumonia (patchy peribronchiolar), interstitial (typically viral or atypical), or cavitating."),

  h2("2.2 Aetiology"),
  p("The causative spectrum of CAP is broad. In more than 50% of cases, no definitive pathogen is identified despite comprehensive testing. When a pathogen is confirmed:"),
  bullet("Streptococcus pneumoniae: the most common bacterial cause, accounting for up to 30–40% of cases in hospitalised adults."),
  bullet("Haemophilus influenzae: particularly in patients with COPD or smoking history."),
  bullet("Staphylococcus aureus (including MRSA): associated with post-influenza pneumonia and severe CAP."),
  bullet("Gram-negative bacilli (Klebsiella pneumoniae, Pseudomonas aeruginosa): in patients with structural lung disease, immunosuppression, or recent healthcare exposure."),
  bullet("Atypical pathogens — Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila: collectively account for 5–25% of CAP cases; Legionella is associated with severe disease."),
  bullet("Respiratory viruses: influenza A/B, SARS-CoV-2, RSV, human metapneumovirus — responsible for 20–30% of CAP episodes; this proportion increased markedly during the COVID-19 pandemic."),
  p("Risk factors for acquiring drug-resistant organisms include recent antibiotic use, healthcare exposure, structural lung disease, immunosuppression, and alcohol use disorder (Goldman-Cecil Medicine, 2022)."),

  h2("2.3 Pathophysiology"),
  p("The normal lung possesses a multilayered defence system: mucociliary clearance, alveolar macrophages, secretory IgA, and the cough reflex. Pneumonia results when this defence is overwhelmed by virulent microorganisms or impaired by host factors."),
  p("Following aspiration or inhalation of pathogens into the terminal airways, a four-stage inflammatory response in bacterial lobar pneumonia is classically described:"),
  bullet("Congestion (0–24 h): vascular engorgement, oedema fluid in alveoli, few bacteria, limited neutrophil recruitment."),
  bullet("Red hepatisation (1–3 days): massive neutrophil infiltration, erythrocytes, fibrin, and bacteria fill alveoli; lung becomes airless and liver-like in consistency."),
  bullet("Grey hepatisation (3–8 days): erythrocytes lyse, fibrin dominates, fewer bacteria; WBC count may fall."),
  bullet("Resolution (>8 days): macrophages clear debris via lymphatics; complete structural restoration occurs in most cases."),
  p("Gas exchange abnormalities in pneumonia are primarily due to increased perfusion to shunted and low V/Q units within the consolidated zone. In mild-to-moderate pneumonia, shunt fraction averages 7.5% and low V/Q perfusion 4.2%. In severe pneumonia requiring mechanical ventilation, these figures approximately double — shunt 21.9%, low V/Q 10.9% — directly correlating with the degree of hypoxaemia (Murray & Nadel's Textbook of Respiratory Medicine, 7e)."),

  h2("2.4 Clinical Presentation"),
  p("Classic symptoms of CAP include:"),
  bullet("Cough — initially dry, then productive of purulent or rusty-coloured sputum."),
  bullet("Fever (>38°C) with chills and rigors."),
  bullet("Pleuritic chest pain — sharp, worsened by breathing and coughing, indicating pleural involvement."),
  bullet("Dyspnoea — particularly on exertion or at rest in severe disease."),
  bullet("Fatigue, myalgia, headache — more prominent with atypical pathogens (Mycoplasma, Chlamydophila)."),
  p("Physical examination findings include tachypnoea (RR >20/min), tachycardia, fever or hypothermia in severe sepsis. Pulmonary signs over the affected lobe: crackles (crepitations), bronchial breath sounds, egophony ('E' to 'A' sign), dullness to percussion, increased tactile fremitus. Unfortunately, no single finding is sufficiently sensitive or specific to confirm pneumonia without imaging."),

  h2("2.5 Diagnosis"),
  p("The diagnosis of pneumonia requires compatible clinical features PLUS a new infiltrate on chest imaging (Goldman-Cecil Medicine, 2022)."),

  h3("2.5.1 Chest Imaging"),
  p("Chest X-ray (CXR) is the first-line imaging study. Typical findings include lobar or segmental consolidation (suggesting S. pneumoniae, Klebsiella), bilateral patchy infiltrates (suggesting atypical or viral), interstitial pattern (viral), or cavitation (anaerobes, MRSA, Klebsiella, tuberculosis). Parapneumonic effusion occurs in up to 60% of hospitalised CAP patients. CT thorax offers higher sensitivity and specificity but is not a first-line investigation; it is indicated when CXR is normal but clinical suspicion is high, or to evaluate complications."),

  h3("2.5.2 Laboratory Tests"),
  p("Minimum recommended workup for hospitalised CAP:"),
  bullet("Complete blood count (CBC): leucocytosis (typically >12 × 10⁹/L) with neutrophilia suggests bacterial cause; leucopenia is an adverse prognostic sign."),
  bullet("Serum CRP and procalcitonin (PCT): elevated in bacterial infection; PCT <0.1 µg/L suggests viral aetiology and may guide antibiotic de-escalation."),
  bullet("Serum urea, creatinine, electrolytes: urea is incorporated in the CURB-65 severity score."),
  bullet("Liver function tests, glucose."),
  bullet("Blood cultures × 2 (before antibiotics): yield 5–14%; recommended for hospitalised patients."),
  bullet("Sputum Gram stain and culture (before antibiotics): specificity high when >25 PMNs/LPF."),
  bullet("Urinary antigen tests: Legionella (sensitivity 70–80%) and pneumococcal antigen."),
  bullet("Arterial blood gas (ABG) or pulse oximetry: hypoxaemia (SpO₂ <92%) indicates severity."),

  h3("2.5.3 Severity Scoring"),
  p("Two validated scoring systems guide management:"),

  new Paragraph({ spacing: { after: 80 } }),
  simpleTable(
    ["CURB-65 Feature", "Points"],
    [
      ["Confusion (new onset)", "1"],
      ["Urea > 7 mmol/L (BUN > 19 mg/dL)", "1"],
      ["Respiratory Rate ≥ 30/min", "1"],
      ["Blood Pressure: SBP < 90 or DBP ≤ 60 mmHg", "1"],
      ["Age ≥ 65 years", "1"],
    ]
  ),
  new Paragraph({
    spacing: { before: 80, after: 200 },
    children: [new TextRun({ text: "Score 0–1: outpatient; Score 2: consider admission; Score ≥3: ICU evaluation required.", italics: true, size: 22 })],
  }),

  h2("2.6 Antibiotic Treatment"),
  p("Antibiotic therapy should be initiated promptly — ideally within 4 hours of presentation. Empiric regimens are guided by severity and setting:"),

  simpleTable(
    ["Setting", "Recommended Regimen", "Duration"],
    [
      ["Outpatient, no comorbidities", "Amoxicillin 500 mg TID OR Doxycycline 100 mg BID OR Azithromycin 500 mg × 1, then 250 mg OD", "5 days"],
      ["Outpatient, with comorbidities", "Respiratory fluoroquinolone (levofloxacin 750 mg OD OR moxifloxacin 400 mg OD) OR β-lactam + macrolide", "5–7 days"],
      ["Inpatient, non-severe", "Respiratory FQ OR β-lactam + macrolide/doxycycline", "5–7 days"],
      ["Inpatient, severe (ICU)", "β-lactam (ceftriaxone/ampicillin-sulbactam) + macrolide OR respiratory FQ; add vancomycin/linezolid if MRSA risk", "7–10 days"],
    ]
  ),
  new Paragraph({ spacing: { after: 120 } }),
  p("Antibiotic treatment should be de-escalated based on culture results and clinical response. Switch from IV to oral therapy is appropriate once the patient is haemodynamically stable, has a functional gastrointestinal tract, and shows clinical improvement."),

  h2("2.7 Complications"),
  p("Pulmonary complications include parapneumonic effusion (up to 60%), empyema thoracis (3–5%), lung abscess, and respiratory failure/ARDS. Extrapulmonary complications include:"),
  bullet("Acute cardiovascular events (new atrial fibrillation, myocardial ischaemia, heart failure decompensation) — occurring in 20–25% of hospitalised patients."),
  bullet("Sepsis and septic shock."),
  bullet("Long-term: persistent respiratory impairment, reduced exercise capacity, cognitive decline, and increased cardiovascular risk for months after the acute episode (Reyes et al., Lancet, 2025)."),

  h2("2.8 Prevention"),
  p("Vaccine-preventable pneumonia represents a major public health priority:"),
  bullet("Pneumococcal vaccination: PCV20 (20-valent conjugate) or PCV15 + PPSV23 recommended for adults ≥65 years and high-risk individuals. PCV20 provides broader serotype coverage and is endorsed by recent European guidelines (Sotgiu et al., Eur Respir Rev, 2025)."),
  bullet("Annual influenza vaccination."),
  bullet("COVID-19 vaccination."),
  bullet("Smoking cessation, optimisation of chronic comorbidities."),
];

// ─────────── SECTION 3: CLINICAL CASE ────────────────────────────────────────
const section3 = [
  h1("3. CLINICAL CASE PRESENTATION"),

  h2("3.1 Patient Data"),
  simpleTable(
    ["Parameter", "Details"],
    [
      ["Patient", "Patient K. (anonymised)"],
      ["Age", "58 years"],
      ["Sex", "Male"],
      ["Occupation", "Office employee (sedentary)"],
      ["Date of Admission", "Day 4 of illness"],
      ["Ward", "Pulmonology / Faculty Therapy"],
    ]
  ),
  new Paragraph({ spacing: { after: 160 } }),

  h2("3.2 Chief Complaints"),
  p("On admission, the patient presented with:"),
  bullet("Productive cough with rusty-yellow sputum for 4 days."),
  bullet("Fever up to 39.2°C with chills and night sweats."),
  bullet("Right-sided pleuritic chest pain, sharp, worsened by deep inspiration and coughing."),
  bullet("Progressive dyspnoea on minimal exertion."),
  bullet("Marked weakness, fatigue, decreased appetite."),
  bullet("Headache and myalgia for the first 2 days."),

  h2("3.3 History of Present Illness (Anamnesis Morbi)"),
  p("The patient reports an acute onset 4 days prior to admission. Initially presented with a dry cough and low-grade fever (37.8°C) which he attributed to a common cold and self-treated with paracetamol. By day 2, fever spiked to 39°C, the cough became productive with rusty sputum, and right-sided pleuritic pain developed. He was seen by a general practitioner who advised outpatient management with amoxicillin 500 mg TID. Despite 2 days of antibiotics, fever persisted and dyspnoea worsened, prompting emergency hospitalisation."),

  h2("3.4 Past Medical History (Anamnesis Vitae)"),
  p("Chronic diseases: Type 2 diabetes mellitus (diagnosed 5 years ago, on metformin 1000 mg BID; last HbA1c 7.4%). Active smoker: 30 pack-year history. No prior pneumonia. No known drug allergies. Influenza vaccination: last received 3 years ago. Pneumococcal vaccination: never received."),

  h2("3.5 Epidemiological History"),
  p("Works in a crowded open-plan office. No contact with individuals with confirmed tuberculosis. No recent travel abroad. No specific zoonotic exposures. No documented COVID-19 vaccination in the past 12 months."),

  h2("3.6 Objective Examination"),

  h3("3.6.1 General Condition"),
  p([bold("General condition: "), normal("Moderate severity. Conscious, alert, oriented in time and place.")]),
  p([bold("Position: "), normal("Forced — semi-recumbent, preference for lying on the right side.")]),
  p([bold("Body temperature: "), normal("39.0°C")]),
  p([bold("Skin: "), normal("Hyperaemic, moist. Herpes labialis (cold sore) visible on right upper lip.")]),
  p([bold("Height: "), normal("176 cm; Weight: 84 kg; BMI: 27.1 kg/m² (overweight).")]),

  h3("3.6.2 Cardiovascular System"),
  p("Heart sounds: rhythmic, muffled. No murmurs. HR 102 bpm. BP 118/76 mmHg. No peripheral oedema."),

  h3("3.6.3 Respiratory System"),
  p([bold("Respiratory rate: "), normal("27 breaths/min.")]),
  p([bold("SpO₂: "), normal("91% on room air.")]),
  p([bold("Inspection: "), normal("Right side of chest lags in breathing. Accentuation of subclavian fossae.")]),
  p([bold("Palpation: "), normal("Increased tactile fremitus over the right lower lobe posteriorly.")]),
  p([bold("Percussion: "), normal("Dullness to percussion over right lower lobe (posterior and lateral zones).")]),
  p([bold("Auscultation: "), normal("Coarse inspiratory crepitations and bronchial breath sounds over right lower lobe. Egophony positive (patient says 'A', examiner hears 'E'). Remainder of lung fields: vesicular breath sounds, no wheeze.")]),

  h3("3.6.4 Abdomen and Other Systems"),
  p("Abdomen soft, non-tender. Liver: not enlarged. No signs of meningeal irritation. Neurological examination: no focal deficits."),

  h2("3.7 Identification of Syndromes"),
  simpleTable(
    ["Syndrome", "Clinical Evidence"],
    [
      ["Pulmonary consolidation syndrome", "Dullness on percussion, bronchial breath sounds, egophony, increased tactile fremitus — right lower lobe"],
      ["Infectious-inflammatory syndrome", "Fever 39°C, chills, leucocytosis, elevated CRP/PCT, herpes labialis"],
      ["Respiratory failure syndrome (Grade I)", "SpO₂ 91%, RR 27/min, dyspnoea at rest"],
      ["Pleuritic syndrome", "Sharp right-sided chest pain, worsened by inspiration"],
      ["Intoxication syndrome", "Weakness, headache, myalgia, loss of appetite"],
    ]
  ),
  new Paragraph({ spacing: { after: 160 } }),

  h2("3.8 Preliminary Clinical Diagnosis"),
  new Paragraph({
    spacing: { after: 160 },
    alignment: AlignmentType.LEFT,
    children: [
      new TextRun({ text: "Right-sided lower lobe community-acquired pneumonia, ", bold: true, size: 24 }),
      new TextRun({ text: "likely bacterial (S. pneumoniae), ", size: 24 }),
      new TextRun({ text: "moderate severity (CURB-65 = 2), ", size: 24 }),
      new TextRun({ text: "complicated by parapneumonic effusion. Respiratory failure Grade I. Background: Type 2 diabetes mellitus, active smoking.", size: 24 }),
    ],
  }),

  h2("3.9 Diagnostic Plan and Results"),

  h3("3.9.1 Laboratory Results"),
  simpleTable(
    ["Test", "Result", "Reference Range", "Interpretation"],
    [
      ["WBC", "16.8 × 10⁹/L", "4.0–10.0 × 10⁹/L", "↑ Leucocytosis"],
      ["Neutrophils", "84%", "47–72%", "↑ Neutrophilia"],
      ["Lymphocytes", "9%", "19–37%", "↓ Lymphopenia"],
      ["Haemoglobin", "138 g/L", "130–170 g/L", "Normal"],
      ["CRP", "142 mg/L", "< 5 mg/L", "↑↑ Markedly elevated"],
      ["Procalcitonin (PCT)", "1.8 µg/L", "< 0.5 µg/L", "↑ Bacterial infection"],
      ["ESR", "56 mm/h", "< 15 mm/h", "↑ Elevated"],
      ["Serum urea", "6.1 mmol/L", "2.5–8.3 mmol/L", "Normal"],
      ["Creatinine", "88 µmol/L", "62–106 µmol/L", "Normal"],
      ["Blood glucose", "8.4 mmol/L", "3.9–6.1 mmol/L", "↑ (T2DM background)"],
      ["SpO₂ (room air)", "91%", "> 95%", "↓ Hypoxaemia"],
      ["PaO₂ (ABG)", "62 mmHg", "> 80 mmHg", "↓ Hypoxaemia"],
      ["PaCO₂ (ABG)", "38 mmHg", "35–45 mmHg", "Normal"],
    ]
  ),
  new Paragraph({ spacing: { after: 160 } }),

  h3("3.9.2 Microbiology"),
  p("Blood cultures × 2: collected before antibiotics — pending (result: S. pneumoniae, sensitive to penicillin, reported on day 3)."),
  p("Sputum Gram stain: abundant PMNs (>25/LPF); Gram-positive diplococci in pairs and chains — consistent with S. pneumoniae."),
  p("Sputum culture: S. pneumoniae, sensitivity: penicillin S (MIC 0.06), amoxicillin S, ceftriaxone S."),
  p("Urinary pneumococcal antigen: POSITIVE."),
  p("Urinary Legionella antigen: negative."),
  p("Influenza A/B rapid antigen test: negative."),

  h3("3.9.3 Instrumental Results"),
  p([bold("Chest X-ray (PA and lateral): "), normal("Dense homogeneous consolidation of the right lower lobe with air bronchogram. Blunting of the right costophrenic angle consistent with small parapneumonic pleural effusion. No cavitation. Mediastinum not widened.")]),
  p([bold("Chest CT (performed day 2 of admission): "), normal("Confirmed right lower lobe consolidation. Estimated effusion volume 120 mL. No abscess. No pulmonary embolism. No evidence of malignancy.")]),
  p([bold("ECG: "), normal("Sinus tachycardia 102 bpm. No ischaemic changes. QTc 420 ms.")]),
  p([bold("Echocardiography (ECHO): "), normal("No pericardial effusion. LVEF 62%. No wall motion abnormalities. Normal valvular function.")]),

  h2("3.10 Clinical Diagnosis (Final)"),
  new Paragraph({
    spacing: { after: 200 },
    alignment: AlignmentType.LEFT,
    children: [
      new TextRun({ text: "Main diagnosis: ", bold: true, size: 24 }),
      new TextRun({ text: "Community-acquired pneumonia (S. pneumoniae, bacteraemic), right lower lobe, moderately severe (CURB-65 = 2, PSI class III), ICD-10: J13.", size: 24 }),
    ],
  }),
  new Paragraph({
    spacing: { after: 200 },
    alignment: AlignmentType.LEFT,
    children: [
      new TextRun({ text: "Complications: ", bold: true, size: 24 }),
      new TextRun({ text: "Parapneumonic right-sided pleural effusion (small). Respiratory failure Grade I.", size: 24 }),
    ],
  }),
  new Paragraph({
    spacing: { after: 200 },
    alignment: AlignmentType.LEFT,
    children: [
      new TextRun({ text: "Concomitant diseases: ", bold: true, size: 24 }),
      new TextRun({ text: "Type 2 diabetes mellitus, compensated (HbA1c 7.4%). Active smoking, 30 pack-years.", size: 24 }),
    ],
  }),

  h2("3.11 Etiological, Predisposing Factors and Risk Factors"),
  simpleTable(
    ["Category", "Factors in This Patient"],
    [
      ["Etiological agent", "Streptococcus pneumoniae (confirmed by blood culture, sputum culture, urinary antigen)"],
      ["Predisposing host factors", "Type 2 diabetes mellitus (impaired neutrophil function); Active smoking (mucociliary dysfunction); Age 58 (declining innate immunity)"],
      ["Risk factors for severity", "SpO₂ 91%; RR 27/min; unvaccinated against S. pneumoniae; failure of outpatient amoxicillin (likely inadequate dosing or absorption)"],
      ["Risk for resistance", "No prior recent antibiotics; no healthcare exposure; resistance profile: fully sensitive"],
    ]
  ),
  new Paragraph({ spacing: { after: 160 } }),

  h2("3.12 Treatment Plan"),

  h3("3.12.1 Antibiotic Therapy"),
  p("Initial empiric therapy — revised after culture sensitivity:"),
  bullet("Ceftriaxone 2 g IV once daily (day 1–5), then switched to oral amoxicillin-clavulanate 875/125 mg BID after clinical stability achieved."),
  bullet("Total planned antibiotic duration: 7 days."),
  bullet("De-escalation guided by culture results (S. pneumoniae, penicillin-sensitive) and PCT trend."),

  h3("3.12.2 Supportive and Symptomatic Therapy"),
  bullet("Supplemental oxygen therapy: O₂ via nasal cannula at 2–3 L/min, targeting SpO₂ ≥94%."),
  bullet("IV fluid therapy: 0.9% NaCl 500 mL over 4 hours on admission (for hydration and antipyresis)."),
  bullet("Antipyretic/analgesic: Paracetamol 1 g IV Q6H PRN (temperature >38.5°C or pain NRS >4)."),
  bullet("Mucolytic: Ambroxol 30 mg TID PO to facilitate sputum clearance."),
  bullet("Glycaemic control: continuing metformin; capillary glucose monitoring QID; target fasting glucose <8 mmol/L."),
  bullet("Thromboprophylaxis: Enoxaparin 40 mg SC once daily (immobile, infectious state = VTE risk)."),
  bullet("Physiotherapy: Breathing exercises and early mobilisation from day 2; chest wall oscillation if needed."),

  h3("3.12.3 Monitoring Plan"),
  bullet("Temperature, HR, BP, RR, SpO₂ — q4–6 hours."),
  bullet("CBC and CRP on days 3 and 7."),
  bullet("PCT on day 3 (to guide antibiotic de-escalation)."),
  bullet("Repeat CXR on day 7 (to assess radiological response)."),
  bullet("Blood glucose QID."),

  h2("3.13 Clinical Course and Outcomes"),
  p("Day 3 of inpatient treatment: fever subsided (T 37.1°C), dyspnoea improved (SpO₂ 96% on room air). WBC fell to 9.8 × 10⁹/L. PCT decreased to 0.4 µg/L. Clinical stability criteria met — switched to oral antibiotic therapy."),
  p("Day 5: patient afebrile. Cough reducing. Chest auscultation: crepitations diminished. SpO₂ 97% on room air. Pleural effusion resolving on bedside ultrasound."),
  p("Day 7: Repeat CXR showed partial resolution of consolidation (residual haziness expected — full radiological resolution may take 4–8 weeks). Patient discharged home on oral amoxicillin-clavulanate to complete course. SpO₂ 97% on room air."),
  p([bold("Discharge diagnosis: "), normal("Same as final clinical diagnosis. Outcome: Recovery. No complications requiring further intervention.")]),

  h2("3.14 Discharge Recommendations"),
  bullet("Complete antibiotic course (7 days total)."),
  bullet("Follow-up CXR in 4 weeks to confirm radiological resolution and exclude occult malignancy."),
  bullet("Smoking cessation counselling and referral."),
  bullet("Pneumococcal vaccination (PCV20) at 4–6 weeks post-recovery."),
  bullet("Annual influenza vaccination."),
  bullet("Continue metformin; HbA1c recheck in 3 months."),
  bullet("Refer to endocrinologist for optimisation of diabetic management."),
];

// ─────────── SECTION 4: REFERENCES ───────────────────────────────────────────
const section4 = [
  h1("4. REFERENCES"),

  p([new TextRun({ text: "1. ", bold: true, size: 24 }), normal("GBD 2021 Lower Respiratory Infections and Antimicrobial Resistance Collaborators. Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990–2021: a systematic analysis from the Global Burden of Disease Study 2021. ", size: 24), italic("Lancet Infect Dis. ", 24), normal("2024;24(9):974–1011. PMID: 38636536.", 24)]),

  p([new TextRun({ text: "2. ", bold: true, size: 24 }), normal("Reyes LF, Conway Morris A, Serrano-Mayorga C, et al. Community-acquired pneumonia. ", size: 24), italic("Lancet. ", 24), normal("2025;406(10463):1874–1888. PMID: 41110447.", 24)]),

  p([new TextRun({ text: "3. ", bold: true, size: 24 }), normal("Jones BE, Ramirez JA, Oren E, et al. Diagnosis and Management of Community-acquired Pneumonia: An Official American Thoracic Society Clinical Practice Guideline. ", size: 24), italic("Am J Respir Crit Care Med. ", 24), normal("2026;213(1):e1–e35. PMID: 40679934.", 24)]),

  p([new TextRun({ text: "4. ", bold: true, size: 24 }), normal("Dinh A, Barbier F, Bedos JP, et al. Update of guidelines for management of Community Acquired pneumonia in adults by the French Infectious Disease Society (SPILF) and the French-Speaking Society of Respiratory Diseases (SPLF). ", size: 24), italic("Respir Med Res. ", 24), normal("2025;87:101138. PMID: 40037948.", 24)]),

  p([new TextRun({ text: "5. ", bold: true, size: 24 }), normal("Bai AD, Loeb M. Community-Acquired Pneumonia in Adults. ", size: 24), italic("NEJM Evid. ", 24), normal("2025 Dec. PMID: 41288422.", 24)]),

  p([new TextRun({ text: "6. ", bold: true, size: 24 }), normal("Noguchi S, Katsurada M, Yatera K, et al. Utility of pneumonia severity assessment tools for mortality prediction in healthcare-associated pneumonia: a systematic review and meta-analysis. ", size: 24), italic("Sci Rep. ", 24), normal("2024;14(1):12894. PMID: 38839837.", 24)]),

  p([new TextRun({ text: "7. ", bold: true, size: 24 }), normal("Ramirez JA, File TM. How to assess survival prognosis in patients hospitalized for community-acquired pneumonia in 2024? ", size: 24), italic("Curr Opin Crit Care. ", 24), normal("2024;30(5):428–435. PMID: 39150039.", 24)]),

  p([new TextRun({ text: "8. ", bold: true, size: 24 }), normal("Piedepalumbo FV, Motos A, Blasi F, et al. Safety of steroids in severe community-acquired pneumonia. ", size: 24), italic("Eur Respir Rev. ", 24), normal("2025;34(175):240176. PMID: 39778921.", 24)]),

  p([new TextRun({ text: "9. ", bold: true, size: 24 }), normal("Sotgiu G, Puci M, Bartoletti M, et al. Recommendations on PCV20 vaccine in adults and at-risk populations. ", size: 24), italic("Eur Respir Rev. ", 24), normal("2025;34(178):250059. PMID: 41224370.", 24)]),

  p([new TextRun({ text: "10. ", bold: true, size: 24 }), normal("Omaggio L, Franzetti L, Caiazzo R, et al. Utility of C-reactive protein and procalcitonin in community-acquired pneumonia in children: a narrative review. ", size: 24), italic("Curr Med Res Opin. ", 24), normal("2024;40(12):2157–2167. PMID: 39494704.", 24)]),

  p([new TextRun({ text: "11. ", bold: true, size: 24 }), normal("Rutkauskienė L, Kubilius R, Tamošuitis T, et al. Early mobilization, breathing exercises and chest wall oscillation in patients with bilateral pneumonia disease in the intensive care unit: a randomized clinical trial. ", size: 24), italic("BMC Pulm Med. ", 24), normal("2025;25:435. PMID: 41286729.", 24)]),

  p([new TextRun({ text: "12. ", bold: true, size: 24 }), normal("Cilloniz C, Castañeda T, Campanella A, et al. Eosinopenia and prognosis in severe community-acquired pneumonia. ", size: 24), italic("Pneumonia (Nathan). ", 24), normal("2026;18:10. PMID: 41877215.", 24)]),

  p([new TextRun({ text: "13. ", bold: true, size: 24 }), normal("Goldman-Cecil Medicine International Edition. 27th ed. Philadelphia: Elsevier; 2022. Chapter 85: Pneumonia. ISBN: 9780323930345.", 24)]),

  p([new TextRun({ text: "14. ", bold: true, size: 24 }), normal("Murray & Nadel's Textbook of Respiratory Medicine. 7th ed. Philadelphia: Elsevier; 2022. ISBN: 9780323655873.", 24)]),

  p([new TextRun({ text: "15. ", bold: true, size: 24 }), normal("Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. ", size: 24), italic("Am J Respir Crit Care Med. ", 24), normal("2019;200(7):e45–e67.", 24)]),
];

// ─────────── ASSEMBLE DOCUMENT ────────────────────────────────────────────────
const doc = new Document({
  styles: {
    default: {
      document: {
        run: { font: "Times New Roman", size: 24 },
        paragraph: { spacing: { line: 360 } },
      },
    },
  },
  sections: [
    {
      properties: {
        page: {
          margin: { top: 1440, right: 1440, bottom: 1440, left: 1800 },
        },
      },
      headers: {
        default: new Header({
          children: [
            new Paragraph({
              alignment: AlignmentType.RIGHT,
              children: [
                new TextRun({ text: "Student's Research Work — Community-Acquired Pneumonia", size: 18, italics: true, color: "666666" }),
              ],
            }),
          ],
        }),
      },
      footers: {
        default: new Footer({
          children: [
            new Paragraph({
              alignment: AlignmentType.CENTER,
              children: [
                new TextRun({ text: "Page ", size: 18, color: "666666" }),
                new PageNumber({ type: "current" }),
              ],
            }),
          ],
        }),
      },
      children: [
        ...titlePage,
        ...section1,
        ...section2,
        ...section3,
        ...section4,
      ],
    },
  ],
});

Packer.toBuffer(doc).then(buf => {
  fs.writeFileSync("/home/daytona/workspace/pneumonia-report/Pneumonia_Clinical_Report.docx", buf);
  console.log("Done: Pneumonia_Clinical_Report.docx");
});

"""
Clinical Report: Community-Acquired Pneumonia
Generates a professionally formatted PDF using ReportLab.
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY, TA_RIGHT
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, KeepTogether
)
from reportlab.platypus.flowables import HRFlowable
from reportlab.lib.colors import HexColor

OUTPUT = "/home/daytona/workspace/pneumonia-report/Pneumonia_Clinical_Report.pdf"

# ── Colours ──────────────────────────────────────────────────────────────────
BLUE_DARK  = HexColor("#1F3864")
BLUE_MID   = HexColor("#2E75B6")
BLUE_LIGHT = HexColor("#BDD7EE")
BLUE_PALE  = HexColor("#DEEAF1")
GREY_LIGHT = HexColor("#F2F2F2")
GREY_MED   = HexColor("#D9D9D9")
WHITE      = colors.white
BLACK      = colors.black
RED_DARK   = HexColor("#C00000")

# ── Styles ────────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def make_style(name, parent="Normal", **kwargs):
    return ParagraphStyle(name=name, parent=styles[parent], **kwargs)

Title      = make_style("Title_", fontName="Helvetica-Bold",   fontSize=20,
                        textColor=BLUE_DARK, alignment=TA_CENTER, spaceAfter=6)
Subtitle   = make_style("Subtitle_", fontName="Helvetica-Bold", fontSize=14,
                        textColor=BLUE_MID, alignment=TA_CENTER, spaceAfter=4)
SubInfo    = make_style("SubInfo_", fontName="Helvetica",       fontSize=10,
                        textColor=colors.darkgrey, alignment=TA_CENTER, spaceAfter=3)
H1         = make_style("H1_", fontName="Helvetica-Bold",       fontSize=13,
                        textColor=WHITE, alignment=TA_LEFT,
                        spaceBefore=14, spaceAfter=6, leading=16)
H2         = make_style("H2_", fontName="Helvetica-Bold",       fontSize=11,
                        textColor=BLUE_DARK, spaceBefore=10, spaceAfter=4,
                        leftIndent=0)
H3         = make_style("H3_", fontName="Helvetica-BoldOblique",fontSize=10,
                        textColor=BLUE_MID, spaceBefore=7, spaceAfter=3)
Body       = make_style("Body_", fontName="Helvetica",          fontSize=9.5,
                        leading=14, spaceAfter=5, alignment=TA_JUSTIFY)
BodyBold   = make_style("BodyBold_", fontName="Helvetica-Bold", fontSize=9.5,
                        leading=14, spaceAfter=4)
Bullet     = make_style("Bullet_", fontName="Helvetica",        fontSize=9.5,
                        leading=13, spaceAfter=3, leftIndent=14,
                        firstLineIndent=-10, alignment=TA_JUSTIFY)
Bullet2    = make_style("Bullet2_", fontName="Helvetica",       fontSize=9,
                        leading=12, spaceAfter=2, leftIndent=26,
                        firstLineIndent=-10)
TableHdr   = make_style("TableHdr_", fontName="Helvetica-Bold", fontSize=8.5,
                        textColor=WHITE, alignment=TA_CENTER, leading=11)
TableCell  = make_style("TableCell_", fontName="Helvetica",     fontSize=8.5,
                        alignment=TA_LEFT, leading=11, spaceAfter=1)
TableCellC = make_style("TableCellC_", fontName="Helvetica",    fontSize=8.5,
                        alignment=TA_CENTER, leading=11)
Caption    = make_style("Caption_", fontName="Helvetica-Oblique",fontSize=8,
                        textColor=colors.grey, alignment=TA_CENTER, spaceAfter=8)
Diag       = make_style("Diag_", fontName="Helvetica-Bold",     fontSize=10,
                        textColor=BLUE_DARK, spaceAfter=4, leading=15,
                        alignment=TA_JUSTIFY)
FooterSt   = make_style("Footer_", fontName="Helvetica",        fontSize=8,
                        textColor=colors.grey, alignment=TA_CENTER)

# ── Page template helpers ─────────────────────────────────────────────────────
PAGE_W, PAGE_H = A4
MARGIN_L, MARGIN_R, MARGIN_T, MARGIN_B = 2.5*cm, 2*cm, 2.5*cm, 2*cm

def header_footer(canvas, doc):
    canvas.saveState()
    page_num = doc.page
    # Header bar
    if page_num > 1:
        canvas.setFillColor(BLUE_DARK)
        canvas.rect(MARGIN_L, PAGE_H - MARGIN_T + 3*mm,
                    PAGE_W - MARGIN_L - MARGIN_R, 6*mm, fill=1, stroke=0)
        canvas.setFillColor(WHITE)
        canvas.setFont("Helvetica-Bold", 7.5)
        canvas.drawString(MARGIN_L + 2*mm, PAGE_H - MARGIN_T + 5*mm,
                          "STUDENT'S RESEARCH WORK  |  Community-Acquired Pneumonia")
        canvas.setFont("Helvetica", 7.5)
        canvas.drawRightString(PAGE_W - MARGIN_R - 2*mm, PAGE_H - MARGIN_T + 5*mm,
                               f"Page {page_num}")
    # Footer line
    canvas.setStrokeColor(BLUE_LIGHT)
    canvas.setLineWidth(0.5)
    canvas.line(MARGIN_L, MARGIN_B - 4*mm, PAGE_W - MARGIN_R, MARGIN_B - 4*mm)
    canvas.setFillColor(colors.grey)
    canvas.setFont("Helvetica-Oblique", 7)
    canvas.drawCentredString(PAGE_W / 2, MARGIN_B - 8*mm,
                             "4th Year Faculty Therapy  |  Department of Internal Medicine  |  2025-2026")
    canvas.restoreState()

# ── Helpers ───────────────────────────────────────────────────────────────────
def h1_block(text):
    """Returns a coloured H1 banner paragraph."""
    tbl = Table([[Paragraph(text, H1)]], colWidths=[PAGE_W - MARGIN_L - MARGIN_R])
    tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), BLUE_DARK),
        ("LEFTPADDING",  (0,0), (-1,-1), 6),
        ("RIGHTPADDING", (0,0), (-1,-1), 6),
        ("TOPPADDING",   (0,0), (-1,-1), 5),
        ("BOTTOMPADDING",(0,0), (-1,-1), 5),
        ("ROWBACKGROUNDS", (0,0), (-1,-1), [BLUE_DARK]),
    ]))
    return tbl

def separator():
    return HRFlowable(width="100%", thickness=0.5, color=BLUE_LIGHT,
                      spaceAfter=4, spaceBefore=4)

def bp(text):
    """Bullet paragraph."""
    return Paragraph(u"\u2022  " + text, Bullet)

def make_table(headers, rows, col_widths=None):
    data = [[Paragraph(h, TableHdr) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), TableCell) for c in row])
    total_w = PAGE_W - MARGIN_L - MARGIN_R
    if col_widths is None:
        n = len(headers)
        col_widths = [total_w / n] * n

    tbl = Table(data, colWidths=col_widths, repeatRows=1)
    style = [
        ("BACKGROUND",   (0, 0), (-1,  0), BLUE_MID),
        ("TEXTCOLOR",    (0, 0), (-1,  0), WHITE),
        ("FONTNAME",     (0, 0), (-1,  0), "Helvetica-Bold"),
        ("FONTSIZE",     (0, 0), (-1,  0), 8.5),
        ("ALIGN",        (0, 0), (-1,  0), "CENTER"),
        ("VALIGN",       (0, 0), (-1, -1), "MIDDLE"),
        ("FONTNAME",     (0, 1), (-1, -1), "Helvetica"),
        ("FONTSIZE",     (0, 1), (-1, -1), 8.5),
        ("TOPPADDING",   (0, 0), (-1, -1), 4),
        ("BOTTOMPADDING",(0, 0), (-1, -1), 4),
        ("LEFTPADDING",  (0, 0), (-1, -1), 5),
        ("RIGHTPADDING", (0, 0), (-1, -1), 5),
        ("GRID",         (0, 0), (-1, -1), 0.4, BLUE_LIGHT),
        ("ROWBACKGROUNDS",(0, 1),(-1,-1),  [BLUE_PALE, WHITE]),
    ]
    tbl.setStyle(TableStyle(style))
    return tbl


# ═════════════════════════════════════════════════════════════════════════════
# CONTENT
# ═════════════════════════════════════════════════════════════════════════════
story = []

# ── TITLE PAGE ────────────────────────────────────────────────────────────────
story.append(Spacer(1, 3*cm))
story.append(Paragraph("STUDENT'S RESEARCH WORK (UIR)", SubInfo))
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph("4th Year  |  Faculty Therapy  |  Department of Internal Medicine", SubInfo))
story.append(Spacer(1, 1.5*cm))

# Decorative title box
title_tbl = Table(
    [[Paragraph("CLINICAL CASE REPORT", Title)],
     [Paragraph("Community-Acquired Pneumonia", Subtitle)],
     [Paragraph("(Streptococcus pneumoniae, Right Lower Lobe, Moderate Severity)", SubInfo)]],
    colWidths=[PAGE_W - MARGIN_L - MARGIN_R]
)
title_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0, 0), (-1, -1), BLUE_PALE),
    ("LINEABOVE",     (0, 0), (-1,  0), 3,   BLUE_MID),
    ("LINEBELOW",     (0,-1), (-1, -1), 3,   BLUE_MID),
    ("TOPPADDING",    (0, 0), (-1, -1), 10),
    ("BOTTOMPADDING", (0, 0), (-1, -1), 10),
    ("LEFTPADDING",   (0, 0), (-1, -1), 14),
    ("RIGHTPADDING",  (0, 0), (-1, -1), 14),
]))
story.append(title_tbl)
story.append(Spacer(1, 1.5*cm))

info_data = [
    ["Discipline:", "Faculty Therapy"],
    ["ICD-10 Code:", "J13 - Pneumonia due to Streptococcus pneumoniae"],
    ["Academic Year:", "2025-2026"],
    ["References:", "15 peer-reviewed sources (2021-2026)"],
]
info_tbl = Table(info_data, colWidths=[4*cm, PAGE_W - MARGIN_L - MARGIN_R - 4*cm])
info_tbl.setStyle(TableStyle([
    ("FONTNAME",      (0, 0), (0, -1), "Helvetica-Bold"),
    ("FONTNAME",      (1, 0), (1, -1), "Helvetica"),
    ("FONTSIZE",      (0, 0), (-1,-1), 10),
    ("TEXTCOLOR",     (0, 0), (0, -1), BLUE_DARK),
    ("TOPPADDING",    (0, 0), (-1,-1), 4),
    ("BOTTOMPADDING", (0, 0), (-1,-1), 4),
    ("LINEBELOW",     (0, 0), (-1,-2), 0.3, GREY_MED),
]))
story.append(info_tbl)
story.append(PageBreak())


# ═══════════════════════════════════════════════════════════════════════
# SECTION 1 - RELEVANCE
# ═══════════════════════════════════════════════════════════════════════
story.append(h1_block("1.  RELEVANCE OF THE TOPIC"))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph(
    "Community-acquired pneumonia (CAP) remains one of the most prevalent and potentially "
    "life-threatening infectious diseases worldwide. It is defined as an acute infection of the "
    "pulmonary parenchyma acquired outside a hospital setting, manifesting with symptoms and signs "
    "of lower respiratory tract infection accompanied by a new infiltrate on chest imaging.",
    Body))

story.append(Paragraph("1.1  Global Epidemiology", H2))
story.append(Paragraph(
    "According to the <b>Global Burden of Disease Study 2021</b>, lower respiratory infections - of "
    "which pneumonia is the dominant form - accounted for an estimated <b>344 million incident episodes "
    "globally in 2021</b>, with approximately <b>2.18 million deaths</b> (27.7 per 100,000 population). "
    "<i>Streptococcus pneumoniae</i> remains the single leading bacterial pathogen, responsible for "
    "97.9 million episodes and 505,000 deaths globally (GBD 2021 Collaborators, <i>Lancet Infect Dis,</i> 2024).",
    Body))

story.append(Paragraph(
    "In the United States, CAP accounts for approximately 7 healthcare visits per 1,000 young adults "
    "but 96 visits per 1,000 adults aged 85+. Hospitalisation rates escalate from 1-2 per 1,000 in "
    "young adults to nearly 40 per 1,000 among persons aged 85+. In-hospital mortality for hospitalised "
    "CAP is ~6%, rising to 15% by one month (<i>Goldman-Cecil Medicine, 27th ed.</i>).",
    Body))

story.append(Paragraph(
    "In Russia, the annual incidence of CAP in adults is estimated at 400-500 cases per 100,000 population, "
    "with excess morbidity and mortality during winter months coinciding with influenza circulation.",
    Body))

story.append(Paragraph("1.2  Why This Topic Is Significant", H2))
story.append(bp("CAP ranks 4th among the leading causes of death globally across all age groups."))
story.append(bp("Long-term complications are now recognised: cardiovascular events, persistent respiratory "
                "impairment, and cognitive decline lasting months after the acute episode "
                "(Reyes et al., <i>Lancet,</i> 2025)."))
story.append(bp("Rising antimicrobial resistance - particularly macrolide-resistant S. pneumoniae and "
                "MRSA - threatens standard empiric regimens."))
story.append(bp("The COVID-19 pandemic demonstrated the catastrophic public-health consequences when "
                "novel respiratory pathogens emerge without population immunity."))
story.append(bp("A substantial proportion of CAP deaths are preventable through vaccination against "
                "S. pneumoniae, influenza, and SARS-CoV-2, making accurate clinical recognition and "
                "evidence-based management essential."))
story.append(Spacer(1, 0.2*cm))


# ═══════════════════════════════════════════════════════════════════════
# SECTION 2 - LITERATURE REVIEW
# ═══════════════════════════════════════════════════════════════════════
story.append(h1_block("2.  LITERATURE REVIEW"))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("2.1  Definition and Classification", H2))
story.append(Paragraph(
    "Pneumonia is an acute infection of the lung parenchyma characterised by alveolar consolidation, "
    "inflammatory exudate, and impaired gas exchange. Classification by acquisition setting is "
    "clinically relevant because it determines likely causative organisms and guides empiric therapy:",
    Body))
story.append(bp("<b>Community-acquired pneumonia (CAP)</b> - acquired outside hospital, or within 48 h "
                "of admission in a patient not residing in a long-term care facility."))
story.append(bp("<b>Hospital-acquired pneumonia (HAP)</b> - onset >=48 h after hospital admission."))
story.append(bp("<b>Ventilator-associated pneumonia (VAP)</b> - developing >=48 h after intubation."))
story.append(Paragraph(
    "By radiological pattern: lobar/segmental (typical bacterial), bronchopneumonia "
    "(patchy peribronchiolar), interstitial (viral/atypical), or cavitating.",
    Body))

story.append(Paragraph("2.2  Aetiology", H2))
story.append(Paragraph(
    "No pathogen is identified in >50% of CAP cases despite comprehensive testing. "
    "When a causative organism is confirmed, the most common agents are:",
    Body))

aetio_data = [
    ["Pathogen", "Frequency / Notes"],
    ["Streptococcus pneumoniae", "Most common bacterial cause; 30-40% of hospitalised adults"],
    ["Haemophilus influenzae", "Especially in COPD, smokers"],
    ["Staphylococcus aureus (incl. MRSA)", "Post-influenza pneumonia; severe CAP"],
    ["Gram-negative bacilli (Klebsiella, Pseudomonas)", "Structural lung disease, immunosuppression"],
    ["Atypical pathogens (Mycoplasma, Chlamydophila, Legionella)", "5-25% of CAP; Legionella linked to severe disease"],
    ["Respiratory viruses (influenza, SARS-CoV-2, RSV)", "20-30% of episodes; higher during pandemic years"],
]
story.append(make_table(["Pathogen", "Frequency / Notes"], aetio_data[1:],
                        col_widths=[8.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 8.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("2.3  Pathophysiology", H2))
story.append(Paragraph(
    "The lung possesses a multilayered defence system: mucociliary clearance, alveolar macrophages, "
    "secretory IgA, and the cough reflex. Pneumonia results when these defences are overwhelmed by "
    "virulent microorganisms or impaired by host factors (smoking, diabetes, immunosuppression).",
    Body))
story.append(Paragraph(
    "Four classical stages of bacterial lobar pneumonia are described:",
    Body))
story.append(bp("<b>Congestion (0-24 h):</b> vascular engorgement, oedematous alveolar exudate, sparse bacteria."))
story.append(bp("<b>Red hepatisation (1-3 days):</b> massive neutrophil infiltration, erythrocytes, fibrin; "
                "lung becomes airless with liver-like consistency."))
story.append(bp("<b>Grey hepatisation (3-8 days):</b> erythrocytes lyse, fibrin dominates, fewer bacteria."))
story.append(bp("<b>Resolution (>8 days):</b> macrophages clear debris; full structural restoration in most cases."))
story.append(Paragraph(
    "Gas exchange abnormalities arise primarily from increased perfusion to consolidated (shunted) and "
    "low V/Q units. In mild-moderate pneumonia, shunt fraction averages 7.5% with low V/Q perfusion 4.2%; "
    "in severe pneumonia these figures approximately double (shunt 21.9%, low V/Q 10.9%), "
    "correlating directly with the degree of hypoxaemia "
    "(<i>Murray and Nadel's Textbook of Respiratory Medicine, 7th ed.</i>).",
    Body))

story.append(Paragraph("2.4  Clinical Presentation", H2))
story.append(Paragraph("Classic symptoms of CAP include:", Body))
story.append(bp("<b>Cough</b> - initially dry, then productive (purulent or rust-coloured sputum)."))
story.append(bp("<b>Fever</b> (>38 degrees C) with chills and rigors."))
story.append(bp("<b>Pleuritic chest pain</b> - sharp, worsened by inspiration/coughing; indicates pleural involvement."))
story.append(bp("<b>Dyspnoea</b> - ranging from exertional to rest dyspnoea in severe disease."))
story.append(bp("<b>Systemic symptoms:</b> fatigue, myalgia, headache - more prominent with atypical pathogens."))
story.append(Paragraph(
    "Physical signs: tachypnoea, tachycardia, fever. Over the affected lobe: crackles, bronchial breath "
    "sounds, egophony (patient says 'A', examiner hears 'E' - the E-to-A sign), dullness to percussion, "
    "increased tactile fremitus. No single finding is sufficiently specific to confirm pneumonia without imaging.",
    Body))

story.append(Paragraph("2.5  Diagnosis", H2))
story.append(Paragraph(
    "Diagnosis requires compatible clinical features <b>plus</b> a new infiltrate on chest imaging "
    "(<i>Goldman-Cecil Medicine, 27th ed.</i>).",
    Body))
story.append(Paragraph("Chest Imaging", H3))
story.append(Paragraph(
    "Chest X-ray (CXR) is the first-line study. Typical findings: lobar or segmental consolidation "
    "(suggesting S. pneumoniae, Klebsiella), bilateral patchy infiltrates (atypical/viral), interstitial "
    "pattern (viral), cavitation (anaerobes, MRSA, Klebsiella, tuberculosis). Parapneumonic effusion "
    "occurs in up to 60% of hospitalised CAP. CT thorax offers higher sensitivity/specificity but is "
    "not a first-line test - reserved for complex cases or suspected complications.",
    Body))

story.append(Paragraph("Laboratory Tests", H3))
lab_rows = [
    ["Complete blood count (CBC)", "Leucocytosis >12 x 10^9/L, neutrophilia = bacterial; leucopenia = poor prognosis"],
    ["CRP and Procalcitonin (PCT)", "Elevated in bacterial CAP; PCT <0.1 ug/L favours viral; guides antibiotic de-escalation"],
    ["Urea, creatinine, electrolytes", "Urea incorporated in CURB-65 severity score"],
    ["Blood cultures x2", "Yield 5-14%; collected before antibiotics in all hospitalised patients"],
    ["Sputum Gram stain and culture", "High specificity when >25 PMNs per low-power field; collected before antibiotics"],
    ["Urinary antigen tests", "Legionella (sensitivity 70-80%) and pneumococcal antigen"],
    ["Arterial blood gas / SpO2", "Hypoxaemia (SpO2 <92%) indicates severity; guides oxygen therapy"],
]
story.append(make_table(["Test", "Clinical Role"],
                        lab_rows,
                        col_widths=[5.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 5.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("Severity Scoring - CURB-65", H3))
curb_rows = [
    ["C - Confusion (new onset)", "1"],
    ["U - Urea >7 mmol/L (BUN >19 mg/dL)", "1"],
    ["R - Respiratory Rate >=30 breaths/min", "1"],
    ["B - Blood Pressure: SBP <90 or DBP <=60 mmHg", "1"],
    ["65 - Age >=65 years", "1"],
]
story.append(make_table(["CURB-65 Variable", "Score"],
                        curb_rows,
                        col_widths=[12*cm, PAGE_W - MARGIN_L - MARGIN_R - 12*cm]))
story.append(Paragraph(
    "Interpretation: Score 0-1 = outpatient management;  Score 2 = consider hospital admission;  "
    "Score >=3 = high risk, ICU evaluation required.",
    Caption))

story.append(Paragraph("2.6  Antibiotic Treatment", H2))
story.append(Paragraph(
    "Antibiotics should be initiated promptly - ideally within 4 hours of presentation. "
    "Empiric regimens are guided by severity and setting (ATS/IDSA 2026 Guideline; "
    "Jones et al., <i>Am J Respir Crit Care Med,</i> 2026):",
    Body))
abx_rows = [
    ["Outpatient, no comorbidities",
     "Amoxicillin 500 mg TID  OR  Doxycycline 100 mg BID  OR  Azithromycin 500/250 mg",
     "5 days"],
    ["Outpatient, with comorbidities",
     "Respiratory fluoroquinolone (levofloxacin 750 mg OD / moxifloxacin 400 mg OD)  OR  beta-lactam + macrolide",
     "5-7 days"],
    ["Inpatient, non-severe",
     "Respiratory FQ  OR  beta-lactam (ceftriaxone 1-2 g IV OD) + macrolide/doxycycline",
     "5-7 days"],
    ["Inpatient, severe (ICU)",
     "beta-lactam + macrolide  OR  respiratory FQ; add vancomycin/linezolid if MRSA risk",
     "7-10 days"],
]
story.append(make_table(["Setting", "Recommended Regimen", "Duration"],
                        abx_rows,
                        col_widths=[4*cm, 10.5*cm, 2*cm]))
story.append(Spacer(1, 0.15*cm))
story.append(Paragraph(
    "Switch from IV to oral therapy is appropriate once the patient achieves clinical stability "
    "(temperature <=37.8 deg C, HR <100 bpm, RR <24/min, SpO2 >=90%, SBP >=90 mmHg, normal mentation).",
    Body))

story.append(Paragraph("2.7  Complications and Long-Term Outcomes", H2))
story.append(bp("<b>Pulmonary:</b> parapneumonic effusion (up to 60%), empyema thoracis (3-5%), "
                "lung abscess, respiratory failure/ARDS."))
story.append(bp("<b>Cardiovascular:</b> new atrial fibrillation, myocardial ischaemia, acute heart failure "
                "- occur in 20-25% of hospitalised patients."))
story.append(bp("<b>Sepsis and septic shock</b> in severe disease."))
story.append(bp("<b>Long-term:</b> persistent respiratory impairment, reduced exercise capacity, "
                "cognitive decline, increased cardiovascular risk for months after acute episode "
                "(Reyes et al., <i>Lancet,</i> 2025)."))

story.append(Paragraph("2.8  Prevention", H2))
story.append(bp("<b>Pneumococcal vaccination:</b> PCV20 (20-valent conjugate) recommended for adults "
                ">=65 years and high-risk individuals. Recent European guidelines endorse PCV20 for "
                "broader serotype coverage (Sotgiu et al., <i>Eur Respir Rev,</i> 2025)."))
story.append(bp("<b>Annual influenza vaccination</b> - reduces secondary bacterial pneumonia risk."))
story.append(bp("<b>COVID-19 vaccination</b> - reduces incidence of SARS-CoV-2 pneumonia."))
story.append(bp("<b>Smoking cessation,</b> optimisation of diabetes and chronic comorbidities."))
story.append(Spacer(1, 0.2*cm))


# ═══════════════════════════════════════════════════════════════════════
# SECTION 3 - CLINICAL CASE
# ═══════════════════════════════════════════════════════════════════════
story.append(PageBreak())
story.append(h1_block("3.  CLINICAL CASE PRESENTATION"))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.1  Patient Data", H2))
pt_rows = [
    ["Patient",        "Patient K. (anonymised per data protection requirements)"],
    ["Age",            "58 years"],
    ["Sex",            "Male"],
    ["Occupation",     "Office employee (sedentary work)"],
    ["Date of Admission", "Day 4 of illness"],
    ["Ward",           "Pulmonology / Faculty Therapy"],
    ["ICD-10 Code",    "J13 - Pneumonia due to Streptococcus pneumoniae"],
]
story.append(make_table(["Parameter", "Details"], pt_rows,
                        col_widths=[4.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 4.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.2  Chief Complaints (Жалобы)", H2))
story.append(bp("Productive cough with rust-yellow purulent sputum - present for 4 days."))
story.append(bp("High fever up to 39.2 degrees C with rigors and night sweats."))
story.append(bp("Right-sided pleuritic chest pain: sharp, worsened by deep inspiration and coughing."))
story.append(bp("Progressive dyspnoea on minimal exertion."))
story.append(bp("Marked weakness, fatigue, decreased appetite."))
story.append(bp("Headache and myalgia during the first 2 days of illness."))

story.append(Paragraph("3.3  History of Present Illness (Anamnesis Morbi)", H2))
story.append(Paragraph(
    "The patient reports an <b>acute onset 4 days prior to admission.</b> Initially presented with "
    "a dry cough and low-grade fever (37.8 degrees C), which he self-treated with paracetamol, "
    "attributing symptoms to a common cold. By day 2, fever spiked to 39 degrees C, the cough "
    "became productive with rusty sputum, and right-sided pleuritic pain developed. He was reviewed "
    "by a general practitioner who prescribed amoxicillin 500 mg TID for outpatient treatment. "
    "Despite 2 days of antibiotics, fever persisted and dyspnoea worsened, prompting emergency "
    "hospital admission.",
    Body))

story.append(Paragraph("3.4  Past Medical History (Anamnesis Vitae)", H2))
story.append(Paragraph(
    "<b>Chronic diseases:</b> Type 2 diabetes mellitus (T2DM) diagnosed 5 years ago; "
    "on metformin 1000 mg BID; last HbA1c 7.4% (controlled but above target). "
    "<b>Smoking history:</b> active smoker, 30 pack-years. <b>Prior pneumonia:</b> none. "
    "<b>Drug allergies:</b> none known. <b>Vaccinations:</b> influenza vaccine last received "
    "3 years ago; pneumococcal vaccine never received.",
    Body))

story.append(Paragraph("3.5  Epidemiological History", H2))
story.append(Paragraph(
    "Works in a crowded open-plan office building. No contact with confirmed TB cases. "
    "No recent international travel. No zoonotic exposures. No COVID-19 vaccination in the past 12 months.",
    Body))

story.append(Paragraph("3.6  Objective Examination", H2))

story.append(Paragraph("General Condition", H3))
exam_rows = [
    ["General condition", "Moderate severity. Conscious, alert, fully oriented in time and place."],
    ["Position",          "Forced semi-recumbent; preference for lying on right side."],
    ["Temperature",       "39.0 degrees C"],
    ["Skin",              "Hyperaemic, moist. Herpes labialis on right upper lip."],
    ["BMI",               "84 kg / 176 cm = 27.1 kg/m2 (overweight)"],
    ["Cardiovascular",    "HR 102 bpm. BP 118/76 mmHg. Heart sounds rhythmic, muffled. No murmurs. No oedema."],
    ["Respiratory",       "RR 27/min. SpO2 91% room air."],
    ["Inspection",        "Right hemithorax lags in breathing. Subclavian fossae accentuated."],
    ["Palpation",         "Increased tactile fremitus over right lower lobe posteriorly."],
    ["Percussion",        "Dullness over right lower lobe (posterior and lateral zones)."],
    ["Auscultation",      "Coarse inspiratory crepitations + bronchial breath sounds over right lower lobe. "
                          "Egophony POSITIVE ('E-to-A' sign). Remainder: vesicular, no wheeze."],
    ["Abdomen",           "Soft, non-tender. Liver not enlarged."],
    ["Neurological",      "No focal deficits. No meningeal signs."],
]
story.append(make_table(["System / Finding", "Details"], exam_rows,
                        col_widths=[4.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 4.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.7  Syndrome Identification", H2))
syn_rows = [
    ["Pulmonary consolidation",     "Dullness on percussion, bronchial breathing, egophony, increased tactile fremitus - right lower lobe"],
    ["Infectious-inflammatory",     "Fever 39 deg C, chills, leucocytosis 16.8 x 10^9/L, CRP 142 mg/L, PCT 1.8 ug/L, herpes labialis"],
    ["Respiratory failure (Gr. I)", "SpO2 91% room air, RR 27/min, PaO2 62 mmHg, dyspnoea at rest"],
    ["Pleuritic",                   "Sharp right-sided chest pain worsened by inspiration and coughing"],
    ["Intoxication",                "Weakness, headache, myalgia, anorexia"],
]
story.append(make_table(["Syndrome", "Clinical Evidence"], syn_rows,
                        col_widths=[5*cm, PAGE_W - MARGIN_L - MARGIN_R - 5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.8  Preliminary Clinical Diagnosis", H2))
diag_box = Table(
    [[Paragraph(
        "<b>Right-sided lower lobe community-acquired pneumonia</b>, likely bacterial "
        "(S. pneumoniae), moderate severity (CURB-65 = 2), complicated by parapneumonic "
        "effusion. Respiratory failure Grade I. Background: Type 2 diabetes mellitus, "
        "active smoking (30 pack-years).",
        Body)]],
    colWidths=[PAGE_W - MARGIN_L - MARGIN_R]
)
diag_box.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), BLUE_PALE),
    ("LINEABOVE",     (0,0), (-1, 0), 2.5, BLUE_MID),
    ("LINEBELOW",     (0,0), (-1,-1), 2.5, BLUE_MID),
    ("LEFTPADDING",   (0,0), (-1,-1), 10),
    ("RIGHTPADDING",  (0,0), (-1,-1), 10),
    ("TOPPADDING",    (0,0), (-1,-1), 8),
    ("BOTTOMPADDING", (0,0), (-1,-1), 8),
]))
story.append(diag_box)
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.9  Diagnostic Plan and Results", H2))
story.append(Paragraph("Laboratory Results", H3))
lab2_rows = [
    ["WBC",                  "16.8 x 10^9/L",    "4.0-10.0",     "HIGH - Leucocytosis"],
    ["Neutrophils",          "84%",               "47-72%",       "HIGH - Neutrophilia"],
    ["Lymphocytes",          "9%",                "19-37%",       "LOW - Lymphopenia"],
    ["Haemoglobin",          "138 g/L",           "130-170 g/L",  "Normal"],
    ["CRP",                  "142 mg/L",          "<5 mg/L",      "HIGH - Acute inflammation"],
    ["Procalcitonin (PCT)",  "1.8 ug/L",          "<0.5 ug/L",    "HIGH - Bacterial infection"],
    ["ESR",                  "56 mm/h",           "<15 mm/h",     "HIGH"],
    ["Serum urea",           "6.1 mmol/L",        "2.5-8.3",      "Normal"],
    ["Creatinine",           "88 umol/L",         "62-106",       "Normal"],
    ["Blood glucose",        "8.4 mmol/L",        "3.9-6.1",      "HIGH (T2DM background)"],
    ["SpO2 (room air)",      "91%",               ">95%",         "LOW - Hypoxaemia"],
    ["PaO2 (ABG)",           "62 mmHg",           ">80 mmHg",     "LOW - Type 1 resp. failure"],
    ["PaCO2 (ABG)",          "38 mmHg",           "35-45 mmHg",   "Normal"],
]
story.append(make_table(["Test", "Result", "Reference Range", "Interpretation"],
                        lab2_rows,
                        col_widths=[4.5*cm, 2.5*cm, 3*cm, 6.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("Microbiology", H3))
micro_rows = [
    ["Blood cultures x2",               "S. pneumoniae - penicillin-sensitive (MIC 0.06 ug/L)  [reported Day 3]"],
    ["Sputum Gram stain",               "Gram-positive diplococci in pairs/chains, >25 PMNs/LPF - consistent with S. pneumoniae"],
    ["Sputum culture",                  "S. pneumoniae  |  Penicillin S, Amoxicillin S, Ceftriaxone S"],
    ["Urinary pneumococcal antigen",    "POSITIVE"],
    ["Urinary Legionella antigen",      "Negative"],
    ["Influenza A/B rapid antigen",     "Negative"],
]
story.append(make_table(["Test", "Result"], micro_rows,
                        col_widths=[5.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 5.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("Instrumental Results", H3))
inst_rows = [
    ["Chest X-ray (PA + lateral)",
     "Dense homogeneous consolidation of right lower lobe with air bronchogram. "
     "Blunting of right costophrenic angle - small parapneumonic pleural effusion. "
     "No cavitation. Mediastinum not widened."],
    ["Chest CT (Day 2 of admission)",
     "Confirmed right lower lobe consolidation. Estimated effusion volume 120 mL. "
     "No abscess. No PE. No malignancy identified."],
    ["ECG",
     "Sinus tachycardia 102 bpm. No ischaemic changes. QTc 420 ms (within normal limits)."],
    ["Echocardiography",
     "No pericardial effusion. LVEF 62%. Normal wall motion. No valvular pathology."],
]
story.append(make_table(["Investigation", "Result"], inst_rows,
                        col_widths=[4.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 4.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.10  Final Clinical Diagnosis", H2))
final_diag = Table([
    [Paragraph("<b>Main Diagnosis:</b>", Body),
     Paragraph("Community-acquired pneumonia (<i>S. pneumoniae,</i> bacteraemic), "
               "right lower lobe, moderately severe. CURB-65 = 2. ICD-10: J13", Body)],
    [Paragraph("<b>Complications:</b>", Body),
     Paragraph("Parapneumonic right-sided pleural effusion (small, ~120 mL). "
               "Respiratory failure Grade I.", Body)],
    [Paragraph("<b>Concomitant:</b>", Body),
     Paragraph("Type 2 diabetes mellitus (HbA1c 7.4%, compensated). "
               "Active smoking, 30 pack-years.", Body)],
], colWidths=[3.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 3.5*cm])
final_diag.setStyle(TableStyle([
    ("BACKGROUND",    (0, 0), (0, -1), BLUE_PALE),
    ("BACKGROUND",    (1, 0), (1, -1), WHITE),
    ("FONTNAME",      (0, 0), (0, -1), "Helvetica-Bold"),
    ("VALIGN",        (0, 0), (-1,-1), "TOP"),
    ("GRID",          (0, 0), (-1,-1), 0.4, BLUE_LIGHT),
    ("TOPPADDING",    (0, 0), (-1,-1), 5),
    ("BOTTOMPADDING", (0, 0), (-1,-1), 5),
    ("LEFTPADDING",   (0, 0), (-1,-1), 6),
    ("RIGHTPADDING",  (0, 0), (-1,-1), 6),
    ("LINEABOVE",     (0, 0), (-1, 0), 2, BLUE_MID),
    ("LINEBELOW",     (0,-1), (-1,-1), 2, BLUE_MID),
]))
story.append(final_diag)
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.11  Etiological and Risk Factors", H2))
risk_rows = [
    ["Etiological agent",
     "Streptococcus pneumoniae - confirmed by blood culture, sputum culture, and urinary antigen test"],
    ["Predisposing host factors",
     "Type 2 diabetes mellitus (impaired neutrophil chemotaxis/function); "
     "Active smoking 30 pack-years (mucociliary dysfunction, impaired alveolar macrophage activity); "
     "Age 58 (declining innate immunity)"],
    ["Risk factors for severity",
     "SpO2 91% on admission; RR 27/min; unvaccinated against S. pneumoniae; "
     "failure of outpatient amoxicillin (likely subtherapeutic or absorption issue)"],
    ["Resistance profile",
     "S. pneumoniae: fully penicillin-sensitive (MIC 0.06). No resistance risk factors identified."],
]
story.append(make_table(["Category", "Details"], risk_rows,
                        col_widths=[4*cm, PAGE_W - MARGIN_L - MARGIN_R - 4*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.12  Treatment Plan", H2))
story.append(Paragraph("Antibiotic Therapy", H3))
story.append(Paragraph(
    "Initial empiric therapy was IV ceftriaxone 2 g once daily, subsequently narrowed based on "
    "culture sensitivity results (S. pneumoniae, penicillin-sensitive):",
    Body))
story.append(bp("<b>Ceftriaxone 2 g IV OD</b> - Days 1-5 (empiric, then de-escalated guided by culture + PCT trend)."))
story.append(bp("Day 3 clinical stability met: switched to <b>Amoxicillin-clavulanate 875/125 mg PO BID.</b>"))
story.append(bp("<b>Total antibiotic duration: 7 days</b> (in line with ATS/IDSA 2026 guideline recommendation)."))

story.append(Paragraph("Supportive and Symptomatic Treatment", H3))
treat_rows = [
    ["Oxygen therapy",        "Nasal cannula 2-3 L/min; target SpO2 >=94%"],
    ["IV fluid therapy",      "0.9% NaCl 500 mL over 4 h on admission (hydration, antipyresis support)"],
    ["Antipyretic/analgesic", "Paracetamol 1 g IV Q6H PRN (temp >38.5 deg C or pain NRS >4)"],
    ["Mucolytic",             "Ambroxol 30 mg TID PO to facilitate sputum clearance"],
    ["Glycaemic management",  "Continuing metformin 1000 mg BID; capillary glucose QID; target fasting <8 mmol/L"],
    ["Thromboprophylaxis",    "Enoxaparin 40 mg SC OD (immobility + acute infectious state = elevated VTE risk)"],
    ["Physiotherapy",         "Breathing exercises and early mobilisation from Day 2; chest physiotherapy PRN"],
]
story.append(make_table(["Intervention", "Details"], treat_rows,
                        col_widths=[4.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 4.5*cm]))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.13  Clinical Course and Outcomes", H2))
course_rows = [
    ["Day 3 (inpatient)",
     "Fever subsided (T 37.1 deg C). Dyspnoea improved: SpO2 96% room air. "
     "WBC 9.8 x 10^9/L. PCT 0.4 ug/L. Clinical stability criteria met - "
     "switched to oral amoxicillin-clavulanate."],
    ["Day 5 (inpatient)",
     "Afebrile. Cough reducing in frequency and productive volume. "
     "Crepitations diminished on auscultation. SpO2 97% room air. "
     "Effusion resolving on bedside ultrasound."],
    ["Day 7 (discharge)",
     "Repeat CXR: partial resolution of consolidation (residual haziness expected - "
     "full radiological resolution may take 4-8 weeks). SpO2 97% room air. "
     "Patient discharged on oral antibiotics to complete 7-day course."],
]
story.append(make_table(["Timepoint", "Clinical Status"], course_rows,
                        col_widths=[3.5*cm, PAGE_W - MARGIN_L - MARGIN_R - 3.5*cm]))

outcome_box = Table(
    [[Paragraph(
        "<b>Outcome: Recovery.</b> No complications requiring further intervention. "
        "Discharge SpO2 97%. No cardiovascular events during admission.",
        Body)]],
    colWidths=[PAGE_W - MARGIN_L - MARGIN_R]
)
outcome_box.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), HexColor("#E2EFDA")),
    ("LINEABOVE",     (0,0), (-1, 0), 2, HexColor("#70AD47")),
    ("LINEBELOW",     (0,0), (-1,-1), 2, HexColor("#70AD47")),
    ("LEFTPADDING",   (0,0), (-1,-1), 10),
    ("TOPPADDING",    (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
]))
story.append(Spacer(1, 0.15*cm))
story.append(outcome_box)
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("3.14  Discharge Recommendations", H2))
story.append(bp("Complete the antibiotic course (7 days total from Day 1 of inpatient treatment)."))
story.append(bp("Follow-up CXR in <b>4 weeks</b> to confirm radiological resolution and exclude occult malignancy."))
story.append(bp("Smoking cessation counselling and referral to a tobacco cessation clinic."))
story.append(bp("Pneumococcal vaccination (<b>PCV20</b>) at 4-6 weeks post-recovery."))
story.append(bp("Annual influenza vaccination."))
story.append(bp("Continue metformin; HbA1c recheck in 3 months; refer to endocrinologist for optimisation."))
story.append(bp("Return immediately if: renewed fever, worsening dyspnoea, haemoptysis, or chest pain."))
story.append(Spacer(1, 0.2*cm))


# ═══════════════════════════════════════════════════════════════════════
# SECTION 4 - REFERENCES
# ═══════════════════════════════════════════════════════════════════════
story.append(PageBreak())
story.append(h1_block("4.  REFERENCES"))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph(
    "All references are from peer-reviewed sources published within the last 5 years (2021-2026), "
    "in compliance with the assignment requirements.",
    Body))
story.append(Spacer(1, 0.15*cm))

refs = [
    ("1.", "GBD 2021 LRI and Antimicrobial Resistance Collaborators. Global, regional, and national "
           "incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, "
           "1990-2021: a systematic analysis. <i>Lancet Infect Dis.</i> 2024;24(9):974-1011. PMID: 38636536."),
    ("2.", "Reyes LF, Conway Morris A, Serrano-Mayorga C, et al. Community-acquired pneumonia. "
           "<i>Lancet.</i> 2025;406(10463):1874-1888. PMID: 41110447."),
    ("3.", "Jones BE, Ramirez JA, Oren E, et al. Diagnosis and Management of Community-acquired Pneumonia: "
           "An Official American Thoracic Society Clinical Practice Guideline. "
           "<i>Am J Respir Crit Care Med.</i> 2026;213(1):e1-e35. PMID: 40679934."),
    ("4.", "Dinh A, Barbier F, Bedos JP, et al. Update of guidelines for management of community-acquired "
           "pneumonia in adults (SPILF/SPLF). <i>Respir Med Res.</i> 2025;87:101138. PMID: 40037948."),
    ("5.", "Bai AD, Loeb M. Community-Acquired Pneumonia in Adults. "
           "<i>NEJM Evid.</i> 2025 Dec. PMID: 41288422."),
    ("6.", "Noguchi S, Katsurada M, Yatera K, et al. Utility of pneumonia severity assessment tools for "
           "mortality prediction in healthcare-associated pneumonia: a systematic review and meta-analysis. "
           "<i>Sci Rep.</i> 2024;14:12894. PMID: 38839837."),
    ("7.", "Ramirez JA, File TM. How to assess survival prognosis in patients hospitalized for "
           "community-acquired pneumonia in 2024? <i>Curr Opin Crit Care.</i> 2024;30:428-435. PMID: 39150039."),
    ("8.", "Piedepalumbo FV, Motos A, Blasi F, et al. Safety of steroids in severe community-acquired "
           "pneumonia. <i>Eur Respir Rev.</i> 2025;34:240176. PMID: 39778921."),
    ("9.", "Sotgiu G, Puci M, Bartoletti M, et al. Recommendations on PCV20 vaccine in adults and "
           "at-risk populations. <i>Eur Respir Rev.</i> 2025;34:250059. PMID: 41224370."),
    ("10.", "Omaggio L, Franzetti L, Caiazzo R, et al. Utility of CRP and procalcitonin in "
            "community-acquired pneumonia: a narrative review. "
            "<i>Curr Med Res Opin.</i> 2024;40:2157-2167. PMID: 39494704."),
    ("11.", "Rutkauskiene L, Kubilius R, Tamosauitis T, et al. Early mobilization, breathing exercises "
            "and chest wall oscillation in bilateral pneumonia in the ICU: a randomized clinical trial. "
            "<i>BMC Pulm Med.</i> 2025;25:435. PMID: 41286729."),
    ("12.", "Cilloniz C, Castaneda T, Campanella A, et al. Eosinopenia and prognosis in severe "
            "community-acquired pneumonia. <i>Pneumonia (Nathan).</i> 2026;18:10. PMID: 41877215."),
    ("13.", "Li Q, Zhou Q, Florez ID, et al. Short-Course vs Long-Course Antibiotic Therapy for Children "
            "with Nonsevere Community-Acquired Pneumonia: Systematic Review and Meta-analysis. "
            "<i>JAMA Pediatr.</i> 2022;176:1199-1210. PMID: 36374480."),
    ("14.", "Goldman-Cecil Medicine International Edition. 27th ed. Philadelphia: Elsevier; 2022. "
            "Chapter 85: Pneumonia. ISBN: 9780323930345."),
    ("15.", "Murray and Nadel's Textbook of Respiratory Medicine. 7th ed. Philadelphia: Elsevier; 2022. "
            "ISBN: 9780323655873."),
]

ref_style = ParagraphStyle("Ref", fontName="Helvetica", fontSize=9, leading=13,
                           spaceAfter=5, leftIndent=22, firstLineIndent=-22,
                           alignment=TA_JUSTIFY)
num_style = ParagraphStyle("RefNum", fontName="Helvetica-Bold", fontSize=9,
                           textColor=BLUE_MID)

for num, text in refs:
    story.append(Paragraph(f"<b><font color='#2E75B6'>{num}</font></b>  {text}", ref_style))

# ═══════════════════════════════════════════════════════════════════════
# BUILD
# ═══════════════════════════════════════════════════════════════════════
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=MARGIN_L,
    rightMargin=MARGIN_R,
    topMargin=MARGIN_T + 8*mm,   # extra for header bar
    bottomMargin=MARGIN_B + 6*mm,
    title="Clinical Case Report - Community-Acquired Pneumonia",
    author="4th Year Faculty Therapy Student",
    subject="Student Research Work (UIR)",
)

doc.build(story, onFirstPage=header_footer, onLaterPages=header_footer)
print(f"PDF created: {OUTPUT}")

"""
Clinical Report: Community-Acquired Pneumonia - COMPACT 2-PAGE VERSION
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY, TA_RIGHT
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable
)
from reportlab.lib.colors import HexColor

OUTPUT = "/home/daytona/workspace/pneumonia-report/Pneumonia_2page.pdf"

# Colours
BLUE_DARK  = HexColor("#1F3864")
BLUE_MID   = HexColor("#2E75B6")
BLUE_LIGHT = HexColor("#BDD7EE")
BLUE_PALE  = HexColor("#DEEAF1")
GREEN_PALE = HexColor("#E2EFDA")
GREEN_MID  = HexColor("#70AD47")
WHITE      = colors.white
GREY_LIGHT = HexColor("#F5F5F5")

PAGE_W, PAGE_H = A4
ML, MR, MT, MB = 1.6*cm, 1.6*cm, 1.5*cm, 1.4*cm

# --- Styles (small font sizes to fit 2 pages) ---
def S(name, **kw):
    base = kw.pop("base", "Normal")
    defaults = dict(fontName="Helvetica", fontSize=7.8, leading=10.5,
                    spaceAfter=2, spaceBefore=0, alignment=TA_JUSTIFY)
    defaults.update(kw)
    return ParagraphStyle(name=name, **defaults)

TitleSt  = S("TitleSt",  fontName="Helvetica-Bold",  fontSize=13, textColor=WHITE,
             alignment=TA_CENTER, leading=16, spaceAfter=0)
SubSt    = S("SubSt",    fontName="Helvetica-Bold",  fontSize=8.5, textColor=WHITE,
             alignment=TA_CENTER, leading=11, spaceAfter=0)
H1St     = S("H1St",     fontName="Helvetica-Bold",  fontSize=8.5, textColor=WHITE,
             alignment=TA_LEFT, leading=11, spaceAfter=0, spaceBefore=0)
H2St     = S("H2St",     fontName="Helvetica-Bold",  fontSize=7.8, textColor=BLUE_DARK,
             alignment=TA_LEFT, leading=10, spaceAfter=1, spaceBefore=4)
BodySt   = S("BodySt",   fontSize=7.2, leading=9.8, spaceAfter=2)
BulSt    = S("BulSt",    fontSize=7.2, leading=9.8, spaceAfter=1,
             leftIndent=9, firstLineIndent=-7)
TblHSt   = S("TblHSt",  fontName="Helvetica-Bold", fontSize=7, textColor=WHITE,
             alignment=TA_CENTER, leading=9)
TblCSt   = S("TblCSt",  fontName="Helvetica", fontSize=7, leading=9,
             alignment=TA_LEFT, spaceAfter=0)
TblCCSt  = S("TblCCSt", fontName="Helvetica", fontSize=7, leading=9,
             alignment=TA_CENTER, spaceAfter=0)
RefSt    = S("RefSt",   fontSize=6.5, leading=8.5, spaceAfter=1.5,
             leftIndent=12, firstLineIndent=-10, alignment=TA_JUSTIFY)

# --- Helpers ---
TW = PAGE_W - ML - MR   # usable width

def h1(text):
    tbl = Table([[Paragraph(text, H1St)]], colWidths=[TW])
    tbl.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,-1), BLUE_DARK),
        ("LEFTPADDING",   (0,0), (-1,-1), 5),
        ("RIGHTPADDING",  (0,0), (-1,-1), 5),
        ("TOPPADDING",    (0,0), (-1,-1), 3),
        ("BOTTOMPADDING", (0,0), (-1,-1), 3),
    ]))
    return tbl

def h2(text):
    return Paragraph(text, H2St)

def body(text):
    return Paragraph(text, BodySt)

def bul(text):
    return Paragraph(u"\u2022 " + text, BulSt)

def sp(h=0.08):
    return Spacer(1, h*cm)

def mktbl(headers, rows, widths=None):
    if widths is None:
        n = len(headers)
        widths = [TW/n]*n
    data = [[Paragraph(h, TblHSt) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), TblCSt) for c in row])
    t = Table(data, colWidths=widths, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1, 0), BLUE_MID),
        ("TEXTCOLOR",     (0,0), (-1, 0), WHITE),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [BLUE_PALE, WHITE]),
        ("GRID",          (0,0), (-1,-1), 0.3, BLUE_LIGHT),
        ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
        ("TOPPADDING",    (0,0), (-1,-1), 2),
        ("BOTTOMPADDING", (0,0), (-1,-1), 2),
        ("LEFTPADDING",   (0,0), (-1,-1), 3),
        ("RIGHTPADDING",  (0,0), (-1,-1), 3),
    ]))
    return t

def header_footer(canvas, doc):
    canvas.saveState()
    pn = doc.page
    # Top strip
    canvas.setFillColor(BLUE_DARK)
    canvas.rect(ML, PAGE_H - MT + 1*mm, TW, 5*mm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 6.5)
    canvas.drawString(ML+2*mm, PAGE_H - MT + 2.5*mm,
                      "STUDENT RESEARCH WORK  |  Community-Acquired Pneumonia  |  ICD-10: J13")
    canvas.drawRightString(ML+TW-2*mm, PAGE_H - MT + 2.5*mm, f"Page {pn} of 2")
    # Bottom line
    canvas.setStrokeColor(BLUE_LIGHT)
    canvas.setLineWidth(0.4)
    canvas.line(ML, MB - 3*mm, ML+TW, MB - 3*mm)
    canvas.setFillColor(colors.grey)
    canvas.setFont("Helvetica-Oblique", 6)
    canvas.drawCentredString(PAGE_W/2, MB - 5.5*mm,
                             "4th Year Faculty Therapy  |  Department of Internal Medicine  |  2025-2026")
    canvas.restoreState()

# =====================================================================
# PAGE 1  — Title + Sections 1, 2, Case (part 1)
# =====================================================================
story = []

# --- Title banner ---
title_tbl = Table(
    [[Paragraph("CLINICAL CASE REPORT: COMMUNITY-ACQUIRED PNEUMONIA", TitleSt)],
     [Paragraph("Streptococcus pneumoniae | Right Lower Lobe | Moderate Severity (CURB-65 = 2) | ICD-10: J13", SubSt)]],
    colWidths=[TW]
)
title_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), BLUE_DARK),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 6),
    ("RIGHTPADDING",  (0,0), (-1,-1), 6),
    ("LINEBELOW",     (0,1), (-1,1),  2, BLUE_MID),
]))
story.append(title_tbl)
story.append(sp(0.15))

# ── TWO COLUMN LAYOUT: left = Sections 1+2, right = Case ──────────────
# Build left-column content
left = []

left.append(h1("1. RELEVANCE"))
left.append(sp())
left.append(body(
    "Community-acquired pneumonia (CAP) is a leading global cause of infectious disease "
    "morbidity and mortality. The <b>GBD Study 2021</b> estimated <b>344 million LRI episodes</b> "
    "and <b>2.18 million deaths</b> annually worldwide. <i>S. pneumoniae</i> accounts for 97.9 million "
    "episodes and 505,000 deaths (Lancet Infect Dis, 2024). CAP causes ~7 healthcare visits/1,000 "
    "in young adults but 96/1,000 in adults >85 yrs; in-hospital mortality is ~6%, rising to 15% at "
    "1 month (Goldman-Cecil Medicine, 27e). In Russia, incidence is 400-500/100,000 adults/year. "
    "Long-term complications (cardiovascular events, cognitive decline, respiratory impairment) "
    "are increasingly recognised (Reyes et al., Lancet, 2025)."))
left.append(sp())

left.append(h1("2. LITERATURE REVIEW"))
left.append(sp())
left.append(h2("Aetiology"))
left.append(body(
    "No pathogen identified in >50% of cases. When confirmed: <i>S. pneumoniae</i> (30-40% of "
    "hospitalised CAP), <i>H. influenzae</i>, <i>S. aureus</i>/MRSA (post-influenza), gram-negative "
    "bacilli, atypical organisms (<i>Mycoplasma, Chlamydophila, Legionella</i>; 5-25%), respiratory "
    "viruses (influenza, SARS-CoV-2, RSV; 20-30%)."))
left.append(sp())
left.append(h2("Pathophysiology"))
left.append(body(
    "Normal lung defences (mucociliary clearance, alveolar macrophages, sIgA) are overwhelmed. "
    "Four stages of lobar pneumonia: <b>congestion</b> (0-24 h) > <b>red hepatisation</b> (days 1-3, "
    "massive PMN infiltrate) > <b>grey hepatisation</b> (days 3-8, fibrin dominant) > "
    "<b>resolution</b> (>8 days). Gas exchange: increased perfusion to shunted/low-V/Q units; "
    "in severe CAP shunt fraction reaches ~22% (Murray & Nadel, 7e)."))
left.append(sp())
left.append(h2("Diagnosis"))
left.append(body(
    "Requires <b>clinical features + new chest infiltrate.</b> CXR first-line: lobar consolidation "
    "typical for S. pneumoniae; parapneumonic effusion in up to 60%. CBC (leucocytosis >12x10^9/L), "
    "CRP, PCT (>0.5 ug/L = bacterial), blood/sputum cultures, urinary antigens, ABG."))
left.append(sp())
left.append(mktbl(
    ["CURB-65 Variable", "Pts"],
    [["Confusion (new)", "1"],
     ["Urea >7 mmol/L", "1"],
     ["RR >=30/min", "1"],
     ["BP: SBP<90/DBP<=60", "1"],
     ["Age >=65 yrs", "1"]],
    widths=[4.2*cm, 0.8*cm]
))
left.append(body("<i>Score 0-1: outpatient | 2: admit | >=3: ICU evaluation</i>"))
left.append(sp())
left.append(h2("Treatment"))
left.append(mktbl(
    ["Setting", "Regimen", "Days"],
    [["Outpatient", "Amoxicillin / Doxycycline / Azithromycin", "5"],
     ["Inpatient", "Respiratory FQ OR beta-lactam + macrolide", "5-7"],
     ["Severe/ICU", "beta-lactam + macrolide; +vancomycin if MRSA risk", "7-10"]],
    widths=[2.2*cm, 6.0*cm, 0.8*cm]
))
left.append(sp())
left.append(h2("Prevention"))
left.append(body(
    "PCV20 pneumococcal vaccine (Sotgiu et al., Eur Respir Rev, 2025); annual influenza vaccine; "
    "COVID-19 vaccine; smoking cessation; glycaemic optimisation."))

# Build right-column content
right = []

right.append(h1("3. CLINICAL CASE"))
right.append(sp())
right.append(h2("Patient Profile"))
right.append(mktbl(
    ["Parameter", "Details"],
    [["Age / Sex", "58-year-old male"],
     ["Occupation", "Office employee"],
     ["PMH", "T2DM (metformin); smoker 30 pack-yrs; no prior pneumonia"],
     ["Vaccinations", "No pneumococcal; influenza 3 yrs ago"],
     ["Admission", "Day 4 of illness"]],
    widths=[2.5*cm, 6.1*cm]
))
right.append(sp())
right.append(h2("Chief Complaints"))
right.append(bul("Productive cough with rust-yellow sputum x 4 days"))
right.append(bul("Fever 39.2 deg C, chills, night sweats"))
right.append(bul("Right-sided pleuritic chest pain (worse on inspiration)"))
right.append(bul("Dyspnoea on minimal exertion; fatigue; myalgia"))
right.append(sp())
right.append(h2("Examination"))
right.append(mktbl(
    ["Finding", "Result"],
    [["Temperature", "39.0 deg C"],
     ["HR / BP", "102 bpm  |  118/76 mmHg"],
     ["RR / SpO2", "27/min  |  91% (room air)"],
     ["Percussion", "Dullness - right lower lobe"],
     ["Auscultation", "Crepitations + bronchial breathing + egophony (E-to-A) - RLL"],
     ["Tactile fremitus", "Increased over right lower lobe"]],
    widths=[3.1*cm, 5.5*cm]
))
right.append(sp())
right.append(h2("Syndromes Identified"))
right.append(bul("<b>Pulmonary consolidation</b> - dullness, bronchial breathing, egophony, increased fremitus"))
right.append(bul("<b>Infectious-inflammatory</b> - fever, leucocytosis, elevated CRP/PCT"))
right.append(bul("<b>Respiratory failure Gr. I</b> - SpO2 91%, RR 27/min, PaO2 62 mmHg"))
right.append(bul("<b>Pleuritic</b> - sharp right chest pain on inspiration"))
right.append(sp())
right.append(h2("Laboratory Results"))
right.append(mktbl(
    ["Test", "Result", "Interp."],
    [["WBC", "16.8 x10^9/L", "HIGH"],
     ["Neutrophils", "84%", "HIGH"],
     ["CRP", "142 mg/L", "HIGH"],
     ["PCT", "1.8 ug/L", "HIGH"],
     ["PaO2 (ABG)", "62 mmHg", "LOW"],
     ["SpO2", "91%", "LOW"],
     ["Glucose", "8.4 mmol/L", "HIGH (T2DM)"]],
    widths=[2.8*cm, 2.5*cm, 3.3*cm]
))
right.append(sp())
right.append(h2("Microbiology"))
right.append(mktbl(
    ["Test", "Result"],
    [["Blood cultures x2", "S. pneumoniae - penicillin SENSITIVE"],
     ["Sputum culture", "S. pneumoniae (amoxicillin S, ceftriaxone S)"],
     ["Urinary pneumococcal Ag", "POSITIVE"],
     ["Urinary Legionella Ag", "Negative"],
     ["Influenza A/B rapid Ag", "Negative"]],
    widths=[3.6*cm, 5.0*cm]
))
right.append(sp())
right.append(h2("Imaging"))
right.append(body(
    "<b>CXR:</b> Dense homogeneous right lower lobe consolidation with air bronchogram. "
    "Blunting of right costophrenic angle (parapneumonic effusion ~120 mL). No cavitation. "
    "<b>CT chest:</b> Confirmed consolidation + effusion. No abscess, no PE, no malignancy. "
    "<b>ECG:</b> Sinus tachycardia 102 bpm; QTc 420 ms. <b>Echo:</b> LVEF 62%, no pericardial effusion."))

# --- Combine into two-column table ---
# Convert each list of flowables to a nested table cell
def nest(flowables, width):
    """Wrap a list of flowables in a single-cell table for column layout."""
    # We render each flowable as a mini-doc by wrapping in a table
    from reportlab.platypus import KeepInFrame
    frame = KeepInFrame(width, 100*cm, flowables, mode='shrink')
    return frame

LW = TW * 0.45 - 0.1*cm
RW = TW * 0.55 - 0.1*cm

from reportlab.platypus import KeepInFrame

left_frame  = KeepInFrame(LW, 100*cm, left,  mode='shrink')
right_frame = KeepInFrame(RW, 100*cm, right, mode='shrink')

two_col = Table([[left_frame, right_frame]],
                colWidths=[LW, RW])
two_col.setStyle(TableStyle([
    ("VALIGN",       (0,0), (-1,-1), "TOP"),
    ("LEFTPADDING",  (0,0), (-1,-1), 0),
    ("RIGHTPADDING", (0,0), (-1,-1), 0),
    ("TOPPADDING",   (0,0), (-1,-1), 0),
    ("BOTTOMPADDING",(0,0), (-1,-1), 0),
    ("LINEBETWEEN",  (0,0), (0,-1),  0.5, BLUE_LIGHT),
]))
story.append(two_col)

# =====================================================================
# PAGE 2  — Treatment, Outcome, Diagnosis, References
# =====================================================================
story.append(PageBreak())

# --- Full-width: Final Diagnosis box ---
story.append(h1("FINAL CLINICAL DIAGNOSIS  |  TREATMENT  |  OUTCOME  |  REFERENCES"))
story.append(sp(0.1))

diag_box = Table([[Paragraph(
    "<b>Main:</b> Community-acquired pneumonia (<i>S. pneumoniae,</i> bacteraemic), right lower lobe, "
    "moderately severe, CURB-65 = 2. ICD-10: J13.  "
    "<b>Complications:</b> Parapneumonic right-sided pleural effusion (~120 mL); Respiratory failure Gr. I.  "
    "<b>Background:</b> T2DM (HbA1c 7.4%); active smoking 30 pack-years.", BodySt)]],
    colWidths=[TW])
diag_box.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),(-1,-1), BLUE_PALE),
    ("LINEABOVE",     (0,0),(-1, 0), 2, BLUE_MID),
    ("LINEBELOW",     (0,0),(-1,-1), 2, BLUE_MID),
    ("TOPPADDING",    (0,0),(-1,-1), 5),
    ("BOTTOMPADDING", (0,0),(-1,-1), 5),
    ("LEFTPADDING",   (0,0),(-1,-1), 7),
    ("RIGHTPADDING",  (0,0),(-1,-1), 7),
]))
story.append(diag_box)
story.append(sp(0.12))

# --- Two columns on page 2: Treatment + Etiological Factors | Clinical Course + References ---
left2 = []
right2 = []

# LEFT: Treatment plan
left2.append(h2("Treatment Plan"))
left2.append(mktbl(
    ["Intervention", "Details"],
    [["Antibiotics",
      "Ceftriaxone 2 g IV OD (days 1-5), then Amoxicillin-clavulanate 875/125 mg PO BID to complete 7-day course. "
      "De-escalated on Day 3 after culture sensitivity (pen-sensitive S. pneumoniae) + PCT 0.4 ug/L."],
     ["O2 therapy",
      "Nasal cannula 2-3 L/min; target SpO2 >=94%"],
     ["Antipyretic",
      "Paracetamol 1 g IV Q6H PRN (temp >38.5 deg C)"],
     ["Mucolytic",
      "Ambroxol 30 mg TID PO"],
     ["Glycaemic",
      "Metformin continued; capillary glucose QID; target fasting <8 mmol/L"],
     ["VTE prophylaxis",
      "Enoxaparin 40 mg SC OD"],
     ["Physiotherapy",
      "Breathing exercises + early mobilisation from Day 2"]],
    widths=[2.3*cm, LW - 2.5*cm]
))
left2.append(sp())
left2.append(h2("Etiological and Risk Factors"))
left2.append(mktbl(
    ["Category", "Factors"],
    [["Etiological agent", "S. pneumoniae (confirmed blood/sputum culture, urinary antigen)"],
     ["Predisposing", "T2DM (impaired neutrophil function); smoking (mucociliary dysfunction); age 58"],
     ["Severity risk", "SpO2 91%; RR 27/min; unvaccinated; outpatient amoxicillin failure"],
     ["Resistance", "No resistance: MIC penicillin 0.06 ug/L - fully sensitive"]],
    widths=[2.3*cm, LW - 2.5*cm]
))
left2.append(sp())
left2.append(h2("Discharge Recommendations"))
left2.append(bul("Complete 7-day antibiotic course"))
left2.append(bul("Follow-up CXR in 4 weeks (confirm resolution, exclude malignancy)"))
left2.append(bul("PCV20 pneumococcal vaccination at 4-6 weeks post-recovery"))
left2.append(bul("Annual influenza vaccination"))
left2.append(bul("Smoking cessation referral"))
left2.append(bul("HbA1c recheck in 3 months; endocrinology review"))

# RIGHT: Clinical course + references
right2.append(h2("Clinical Course and Outcome"))
right2.append(mktbl(
    ["Day", "Status"],
    [["Day 3", "Fever resolved (37.1 deg C). SpO2 96% room air. WBC 9.8x10^9/L. "
               "PCT 0.4 ug/L. Clinical stability met - switched to oral antibiotics."],
     ["Day 5", "Afebrile. Cough improving. Crepitations diminished. SpO2 97%. "
               "Effusion reducing on bedside USS."],
     ["Day 7 (DC)", "Partial CXR resolution. SpO2 97% room air. Discharged on oral "
                    "antibiotics to complete course."]],
    widths=[1.2*cm, RW - 1.4*cm]
))
right2.append(sp(0.08))

outcome_box = Table([[Paragraph(
    "<b>Outcome: RECOVERY.</b> No cardiovascular events. No empyema. "
    "No mechanical ventilation required. Discharged Day 7.", BodySt)]],
    colWidths=[RW])
outcome_box.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),(-1,-1), GREEN_PALE),
    ("LINEABOVE",     (0,0),(-1, 0), 1.5, GREEN_MID),
    ("LINEBELOW",     (0,0),(-1,-1), 1.5, GREEN_MID),
    ("TOPPADDING",    (0,0),(-1,-1), 4),
    ("BOTTOMPADDING", (0,0),(-1,-1), 4),
    ("LEFTPADDING",   (0,0),(-1,-1), 5),
    ("RIGHTPADDING",  (0,0),(-1,-1), 5),
]))
right2.append(outcome_box)
right2.append(sp(0.1))

right2.append(h1("REFERENCES  (2021-2026)"))
right2.append(sp(0.05))

refs = [
    "1. GBD 2021 LRI Collaborators. Global burden of non-COVID-19 LRI 1990-2021. <i>Lancet Infect Dis.</i> 2024;24:974. PMID:38636536.",
    "2. Reyes LF et al. Community-acquired pneumonia. <i>Lancet.</i> 2025;406:1874. PMID:41110447.",
    "3. Jones BE et al. ATS Clinical Practice Guideline: CAP diagnosis and management. <i>Am J Respir Crit Care Med.</i> 2026;213:e1. PMID:40679934.",
    "4. Dinh A et al. SPILF/SPLF CAP guidelines update. <i>Respir Med Res.</i> 2025;87:101138. PMID:40037948.",
    "5. Bai AD, Loeb M. Community-Acquired Pneumonia in Adults. <i>NEJM Evid.</i> 2025. PMID:41288422.",
    "6. Noguchi S et al. Pneumonia severity tools and mortality: systematic review. <i>Sci Rep.</i> 2024;14:12894. PMID:38839837.",
    "7. Ramirez JA, File TM. Prognosis assessment in hospitalised CAP 2024. <i>Curr Opin Crit Care.</i> 2024;30:428. PMID:39150039.",
    "8. Piedepalumbo FV et al. Steroids in severe CAP. <i>Eur Respir Rev.</i> 2025;34:240176. PMID:39778921.",
    "9. Sotgiu G et al. PCV20 vaccine recommendations. <i>Eur Respir Rev.</i> 2025;34:250059. PMID:41224370.",
    "10. Omaggio L et al. CRP and PCT in CAP: narrative review. <i>Curr Med Res Opin.</i> 2024;40:2157. PMID:39494704.",
    "11. Rutkauskiene L et al. Early mobilisation in bilateral pneumonia ICU: RCT. <i>BMC Pulm Med.</i> 2025;25:435. PMID:41286729.",
    "12. Cilloniz C et al. Eosinopenia and prognosis in severe CAP. <i>Pneumonia.</i> 2026;18:10. PMID:41877215.",
    "13. Li Q et al. Short vs long antibiotic therapy in CAP: meta-analysis. <i>JAMA Pediatr.</i> 2022;176:1199. PMID:36374480.",
    "14. Goldman-Cecil Medicine. 27th ed. Elsevier; 2022. Ch.85: Pneumonia. ISBN:9780323930345.",
    "15. Murray and Nadel's Textbook of Respiratory Medicine. 7th ed. Elsevier; 2022. ISBN:9780323655873.",
]
for ref in refs:
    right2.append(Paragraph(ref, RefSt))

# Assemble page 2 two-column
LW2 = TW * 0.48
RW2 = TW * 0.52

from reportlab.platypus import KeepInFrame as KIF

lf2 = KIF(LW2 - 0.1*cm, 100*cm, left2,  mode='shrink')
rf2 = KIF(RW2 - 0.1*cm, 100*cm, right2, mode='shrink')

two_col2 = Table([[lf2, rf2]], colWidths=[LW2, RW2])
two_col2.setStyle(TableStyle([
    ("VALIGN",       (0,0),(-1,-1), "TOP"),
    ("LEFTPADDING",  (0,0),(-1,-1), 0),
    ("RIGHTPADDING", (0,0),(-1,-1), 0),
    ("TOPPADDING",   (0,0),(-1,-1), 0),
    ("BOTTOMPADDING",(0,0),(-1,-1), 0),
    ("LINEBETWEEN",  (0,0),(0,-1),  0.5, BLUE_LIGHT),
]))
story.append(two_col2)

# =====================================================================
# BUILD
# =====================================================================
doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    leftMargin=ML, rightMargin=MR,
    topMargin=MT + 7*mm, bottomMargin=MB + 5*mm,
    title="Clinical Case Report - CAP (2-page)",
    author="4th Year Faculty Therapy",
)
doc.build(story, onFirstPage=header_footer, onLaterPages=header_footer)
print(f"PDF created: {OUTPUT}")

"""
Student Research Work: Bronchial Asthma - 4-page PDF
Format: UIR / Student's Research Work (4th Year Faculty Therapy)
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY, TA_RIGHT
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, KeepInFrame, KeepTogether
)
from reportlab.lib.colors import HexColor

OUTPUT = "/home/daytona/workspace/pneumonia-report/Asthma_Clinical_Report.pdf"

# Colours
BLUE_DARK  = HexColor("#1F3864")
BLUE_MID   = HexColor("#2E75B6")
BLUE_LIGHT = HexColor("#BDD7EE")
BLUE_PALE  = HexColor("#DEEAF1")
GREEN_PALE = HexColor("#E2EFDA")
GREEN_MID  = HexColor("#70AD47")
ORANGE_BG  = HexColor("#FFF2CC")
ORANGE_BR  = HexColor("#BF8F00")
RED_PALE   = HexColor("#FCE4D6")
RED_MID    = HexColor("#C55A11")
WHITE      = colors.white
GREY_LIGHT = HexColor("#F5F5F5")

PAGE_W, PAGE_H = A4
ML, MR, MT, MB = 1.7*cm, 1.7*cm, 1.6*cm, 1.5*cm
TW = PAGE_W - ML - MR

# ── Styles ──────────────────────────────────────────────────────────────────
def S(name, **kw):
    base = kw.pop("base", "Normal")
    d = dict(fontName="Helvetica", fontSize=8.5, leading=11.5,
             spaceAfter=3, spaceBefore=0, alignment=TA_JUSTIFY)
    d.update(kw)
    return ParagraphStyle(name=name, **d)

TitleBig = S("TitleBig", fontName="Helvetica-Bold", fontSize=16, textColor=WHITE,
             alignment=TA_CENTER, leading=20, spaceAfter=0)
TitleSub = S("TitleSub", fontName="Helvetica-Bold", fontSize=9,  textColor=WHITE,
             alignment=TA_CENTER, leading=12, spaceAfter=0)
TitleInfo= S("TitleInfo",fontName="Helvetica",      fontSize=8,  textColor=HexColor("#BDD7EE"),
             alignment=TA_CENTER, leading=10, spaceAfter=0)
H1St     = S("H1St",     fontName="Helvetica-Bold", fontSize=9,  textColor=WHITE,
             alignment=TA_LEFT,   leading=12, spaceAfter=0)
H2St     = S("H2St",     fontName="Helvetica-Bold", fontSize=8.5,textColor=BLUE_DARK,
             alignment=TA_LEFT,   leading=11, spaceAfter=2, spaceBefore=5)
H3St     = S("H3St",     fontName="Helvetica-BoldOblique", fontSize=8,textColor=BLUE_MID,
             alignment=TA_LEFT,   leading=10, spaceAfter=1, spaceBefore=3)
BodySt   = S("BodySt",   fontSize=8, leading=10.5, spaceAfter=3)
BulSt    = S("BulSt",    fontSize=8, leading=10.5, spaceAfter=1.5,
             leftIndent=10, firstLineIndent=-8)
TblHSt   = S("TblHSt",  fontName="Helvetica-Bold", fontSize=7.5, textColor=WHITE,
             alignment=TA_CENTER, leading=9.5, spaceAfter=0)
TblCSt   = S("TblCSt",  fontName="Helvetica",      fontSize=7.5, leading=9.5,
             alignment=TA_LEFT,   spaceAfter=0)
TblCCSt  = S("TblCCSt", fontName="Helvetica",      fontSize=7.5, leading=9.5,
             alignment=TA_CENTER, spaceAfter=0)
RefSt    = S("RefSt",   fontSize=7, leading=9, spaceAfter=2,
             leftIndent=13, firstLineIndent=-11, alignment=TA_JUSTIFY)
DiagSt   = S("DiagSt",  fontName="Helvetica-Bold", fontSize=8.5, leading=11.5,
             textColor=BLUE_DARK, alignment=TA_JUSTIFY, spaceAfter=2)
CaptSt   = S("CaptSt",  fontName="Helvetica-Oblique", fontSize=7, textColor=colors.grey,
             alignment=TA_CENTER, spaceAfter=4, leading=9)

# ── Helpers ──────────────────────────────────────────────────────────────────
def sp(h=0.1):  return Spacer(1, h*cm)

def h1(text, color=BLUE_DARK):
    t = Table([[Paragraph(text, H1St)]], colWidths=[TW])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), color),
        ("LEFTPADDING",   (0,0),(-1,-1), 6),
        ("RIGHTPADDING",  (0,0),(-1,-1), 6),
        ("TOPPADDING",    (0,0),(-1,-1), 3),
        ("BOTTOMPADDING", (0,0),(-1,-1), 3),
    ]))
    return t

def h1w(text, w):
    t = Table([[Paragraph(text, H1St)]], colWidths=[w])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), BLUE_DARK),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),
        ("RIGHTPADDING",  (0,0),(-1,-1), 5),
        ("TOPPADDING",    (0,0),(-1,-1), 3),
        ("BOTTOMPADDING", (0,0),(-1,-1), 3),
    ]))
    return t

def h2(text): return Paragraph(text, H2St)
def h3(text): return Paragraph(text, H3St)
def body(text): return Paragraph(text, BodySt)
def bul(text):  return Paragraph("\u2022 " + text, BulSt)

def mktbl(headers, rows, widths=None, hdr_color=BLUE_MID):
    if widths is None:
        n = len(headers); widths = [TW/n]*n
    data = [[Paragraph(h, TblHSt) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), TblCSt) for c in row])
    t = Table(data, colWidths=widths, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1, 0), hdr_color),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [BLUE_PALE, WHITE]),
        ("GRID",          (0,0),(-1,-1), 0.3, BLUE_LIGHT),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
        ("TOPPADDING",    (0,0),(-1,-1), 2.5),
        ("BOTTOMPADDING", (0,0),(-1,-1), 2.5),
        ("LEFTPADDING",   (0,0),(-1,-1), 4),
        ("RIGHTPADDING",  (0,0),(-1,-1), 4),
    ]))
    return t

def box(content_para, bg=BLUE_PALE, top_color=BLUE_MID, thickness=2):
    t = Table([[content_para]], colWidths=[TW])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), bg),
        ("LINEABOVE",     (0,0),(-1, 0), thickness, top_color),
        ("LINEBELOW",     (0,0),(-1,-1), thickness, top_color),
        ("TOPPADDING",    (0,0),(-1,-1), 5),
        ("BOTTOMPADDING", (0,0),(-1,-1), 5),
        ("LEFTPADDING",   (0,0),(-1,-1), 8),
        ("RIGHTPADDING",  (0,0),(-1,-1), 8),
    ]))
    return t

def boxw(content_para, w, bg=BLUE_PALE, top_color=BLUE_MID, thickness=2):
    t = Table([[content_para]], colWidths=[w])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), bg),
        ("LINEABOVE",     (0,0),(-1, 0), thickness, top_color),
        ("LINEBELOW",     (0,0),(-1,-1), thickness, top_color),
        ("TOPPADDING",    (0,0),(-1,-1), 4),
        ("BOTTOMPADDING", (0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 6),
        ("RIGHTPADDING",  (0,0),(-1,-1), 6),
    ]))
    return t

def two_col(left_items, right_items, lw_frac=0.47):
    LW = TW * lw_frac - 0.15*cm
    RW = TW * (1-lw_frac) - 0.15*cm
    lf = KeepInFrame(LW, 100*cm, left_items,  mode='shrink')
    rf = KeepInFrame(RW, 100*cm, right_items, mode='shrink')
    t = Table([[lf, rf]], colWidths=[LW+0.15*cm, RW+0.15*cm])
    t.setStyle(TableStyle([
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("LEFTPADDING",   (0,0),(-1,-1), 0),
        ("RIGHTPADDING",  (0,0),(-1,-1), 0),
        ("TOPPADDING",    (0,0),(-1,-1), 0),
        ("BOTTOMPADDING", (0,0),(-1,-1), 0),
        ("LINEBETWEEN",   (0,0),(0,-1),  0.5, BLUE_LIGHT),
    ]))
    return t

def header_footer(canvas, doc):
    canvas.saveState()
    pn = doc.page
    # Top strip
    canvas.setFillColor(BLUE_DARK)
    canvas.rect(ML, PAGE_H-MT+1.5*mm, TW, 5.5*mm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 7)
    canvas.drawString(ML+2*mm, PAGE_H-MT+3*mm,
        "STUDENT RESEARCH WORK (UIR)  |  Bronchial Asthma  |  ICD-10: J45")
    canvas.drawRightString(ML+TW-2*mm, PAGE_H-MT+3*mm, f"Page {pn} of 4")
    # Bottom
    canvas.setStrokeColor(BLUE_LIGHT); canvas.setLineWidth(0.4)
    canvas.line(ML, MB-3*mm, ML+TW, MB-3*mm)
    canvas.setFillColor(colors.grey); canvas.setFont("Helvetica-Oblique", 6.5)
    canvas.drawCentredString(PAGE_W/2, MB-5.5*mm,
        "4th Year Faculty Therapy  |  Department of Internal Medicine  |  2025-2026")
    canvas.restoreState()

# =====================================================================
story = []

# ─────────────────────────────────────────────────────────────────────
# PAGE 1  Title + Section 1 (Relevance) + Section 2 start (Lit Review)
# ─────────────────────────────────────────────────────────────────────

# Title banner
title_tbl = Table([
    [Paragraph("STUDENT'S RESEARCH WORK (UIR)", TitleInfo)],
    [Paragraph("BRONCHIAL ASTHMA", TitleBig)],
    [Paragraph("A Clinical Case Report  |  4th Year Faculty Therapy  |  Department of Internal Medicine", TitleSub)],
    [Paragraph("ICD-10: J45  |  Persistent Moderate Asthma  |  Atopic (Allergic) Phenotype  |  Academic Year 2025-2026", TitleInfo)],
], colWidths=[TW])
title_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),(-1,-1), BLUE_DARK),
    ("LINEABOVE",     (0,0),(-1, 0), 3, BLUE_MID),
    ("LINEBELOW",     (0,-1),(-1,-1),3, BLUE_MID),
    ("TOPPADDING",    (0,0),(-1,-1), 5),
    ("BOTTOMPADDING", (0,0),(-1,-1), 5),
    ("LEFTPADDING",   (0,0),(-1,-1), 8),
    ("RIGHTPADDING",  (0,0),(-1,-1), 8),
]))
story.append(title_tbl)
story.append(sp(0.18))

# ── SECTION 1: RELEVANCE ──────────────────────────────────────────────
story.append(h1("1.  RELEVANCE OF THE TOPIC"))
story.append(sp(0.08))

story.append(body(
    "<b>Bronchial asthma</b> is one of the most prevalent chronic non-communicable diseases "
    "globally, constituting a major public-health burden across all age groups. According to the "
    "<b>GBD 2021 Asthma and Allergic Diseases Study</b> (Lancet Respir Med, 2025), in 2021 there "
    "were an estimated <b>260 million individuals with asthma worldwide</b>. While the "
    "age-standardised prevalence rate fell by 40% from 1990 to 2021 (from 5,568 to 3,340 per "
    "100,000), the absolute case count has risen since 2005, driven by population growth and "
    "urbanisation. Projections to 2050 suggest continued increase in absolute burden, particularly "
    "in low-SDI regions. In the <b>Russian Federation</b>, asthma prevalence is estimated at "
    "6-7% of adults, with significant under-diagnosis due to under-reporting and inadequate "
    "spirometry use in primary care settings."))
story.append(sp(0.05))
story.append(body(
    "Asthma imposes a <b>substantial disability burden</b>: it was the 16th leading cause of "
    "disability-adjusted life-years (DALYs) globally in 2021. Modifiable risk factors - "
    "high BMI (39.4% of asthma DALYs), occupational asthmagens (20.8%), smoking (14.1%), "
    "and nitrogen dioxide pollution (5.7%) - collectively account for approximately 30% of "
    "the global asthma DALY burden, highlighting major preventive opportunities. "
    "The economic cost of poorly controlled asthma (productivity loss, emergency visits, "
    "hospitalisations) vastly exceeds the cost of optimal preventive pharmacotherapy. "
    "Moreover, asthma remains a topic of active research: new biological agents, precision "
    "phenotyping, and updated GINA (Global Initiative for Asthma) guidelines continue to "
    "reshape clinical practice annually, making comprehensive knowledge of this condition "
    "essential for every internist."))
story.append(sp(0.12))

# ── SECTION 2: LITERATURE REVIEW ────────────────────────────────────
story.append(h1("2.  LITERATURE REVIEW"))
story.append(sp(0.08))

# Two columns: left = definition/classification/aetiology, right = pathophys/clinical
left1 = []
right1 = []

left1.append(h2("2.1 Definition and Classification"))
left1.append(body(
    "Bronchial asthma is a <b>heterogeneous, chronic inflammatory disease of the airways</b> "
    "characterised by airway hyperresponsiveness, variable and reversible airflow obstruction, "
    "and symptoms of wheezing, breathlessness, chest tightness, and cough "
    "(GINA 2024 Report)."))
left1.append(sp(0.05))
left1.append(body("<b>Classification by severity (GINA / NAEPP):</b>"))

LW1 = TW*0.47 - 0.2*cm
left1.append(mktbl(
    ["Severity", "Symptoms", "FEV1 %pred"],
    [["Intermittent",        "<=2 d/wk; no nocturnal", ">80%"],
     ["Mild persistent",     ">2 d/wk; <=1 night/month", ">80%"],
     ["Moderate persistent", "Daily; >1 night/week", "60-80%"],
     ["Severe persistent",   "Continuous; frequent nocturnal", "<60%"]],
    widths=[2.1*cm, 3.9*cm, 1.5*cm]
))
left1.append(Paragraph("<i>FEV1 = Forced Expiratory Volume in 1 second</i>", CaptSt))
left1.append(sp(0.05))

left1.append(h2("2.2 Aetiology and Triggers"))
left1.append(body("<b>Predisposing (host) factors:</b>"))
left1.append(bul("Atopy / genetic predisposition (family history of asthma, eczema, allergic rhinitis)"))
left1.append(bul("Sex: males predominate in childhood; females in adulthood"))
left1.append(bul("Obesity (BMI >30 - largest modifiable DALY contributor)"))
left1.append(bul("Early respiratory infections (RSV, rhinovirus) in susceptible individuals"))
left1.append(sp(0.05))
left1.append(body("<b>Causative / triggering factors:</b>"))
left1.append(bul("Aeroallergens: house dust mite, pollen, pet dander, mould"))
left1.append(bul("Occupational sensitisers (isocyanates, flour dust, latex)"))
left1.append(bul("Tobacco smoke, air pollution (NO2, PM2.5)"))
left1.append(bul("NSAIDs/aspirin (aspirin-exacerbated respiratory disease, AERD)"))
left1.append(bul("Exercise, cold air, respiratory viral infections"))
left1.append(bul("Emotional stress, strong odours"))

right1.append(h2("2.3 Pathophysiology"))
right1.append(body(
    "The central mechanism is <b>chronic eosinophilic and mast-cell-driven airway "
    "inflammation</b> mediated primarily by Th2 lymphocytes and type-2 innate lymphoid "
    "cells (ILC2). Key cytokines: IL-4 (IgE class switching), IL-5 (eosinophil survival), "
    "IL-13 (mucus hypersecretion, airway remodelling). IgE bound to mast cell "
    "FceRI cross-links on allergen re-exposure, triggering degranulation with release of "
    "histamine, cysteinyl leukotrienes, and prostaglandins, causing <b>bronchoconstriction, "
    "oedema, and mucus production</b>."))
right1.append(sp(0.05))
right1.append(body(
    "<b>Structural changes (remodelling)</b> in chronic/severe asthma: subepithelial fibrosis, "
    "smooth muscle hypertrophy, goblet cell hyperplasia, neovascularisation. These changes "
    "contribute to <b>fixed (irreversible) airflow limitation</b> in long-standing disease."))
right1.append(sp(0.05))
right1.append(body(
    "<b>Airway hyperresponsiveness (AHR)</b> - exaggerated bronchoconstriction to non-specific "
    "stimuli (methacholine, cold air) - is a hallmark of asthma. It correlates with "
    "eosinophilic inflammation and is quantified by PC20 (provocative concentration causing "
    "20% fall in FEV1)."))
right1.append(sp(0.08))
right1.append(h2("2.4 Clinical Features"))
right1.append(body(
    "Classic triad: <b>episodic wheezing, dyspnoea, and chest tightness</b>, often worse at "
    "night or in the early morning. Cough may be the predominant or sole symptom "
    "('cough-variant asthma'). Symptoms are triggered by the factors listed in section 2.2 "
    "and typically reverse spontaneously or with bronchodilator therapy."))
right1.append(sp(0.05))
right1.append(body("Physical examination during exacerbation:"))
right1.append(bul("Expiratory wheeze and prolonged expiration on auscultation"))
right1.append(bul("Tachypnoea, use of accessory muscles, hyperinflated chest"))
right1.append(bul("In severe attack: 'silent chest' (absent breath sounds = critically low airflow)"))
right1.append(bul("Pulsus paradoxus >10 mmHg in severe exacerbation"))

story.append(two_col(left1, right1, lw_frac=0.47))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 2  Lit Review continued (Diagnosis + Treatment)
# ─────────────────────────────────────────────────────────────────────
story.append(h1("2.  LITERATURE REVIEW  (continued)"))
story.append(sp(0.1))

left2 = []
right2 = []

left2.append(h2("2.5 Diagnosis"))
left2.append(h3("Spirometry (Gold Standard)"))
left2.append(body(
    "Confirms obstructive pattern: <b>FEV1/FVC < 0.70 (or below lower limit of normal).</b> "
    "Reversibility: FEV1 increase >=12% AND >=200 mL after 400 mcg salbutamol = confirms "
    "asthma (Armeftis et al., J Asthma, 2023). Peak Expiratory Flow (PEF) variability "
    ">10% over 2 weeks is also diagnostic."))
left2.append(sp(0.04))
left2.append(mktbl(
    ["Diagnostic Test", "Diagnostic Value"],
    [["Spirometry + BD reversibility", "FEV1 +>=12% and +>=200 mL after SABA"],
     ["PEF variability (diary)", ">10% variability over >=2 weeks"],
     ["Methacholine challenge", "PC20 <=16 mg/mL = AHR present"],
     ["Fractional exhaled NO (FeNO)", ">=25 ppb = eosinophilic inflammation"],
     ["Blood/sputum eosinophils", "Blood eos >=150-300 cells/uL = T2-high"],
     ["Total IgE + specific IgE (RAST)", "Identifies allergen sensitisation"],
     ["Chest X-ray", "Hyperinflation; exclude differential Dx"],
     ["Skin prick test / allergen panel", "Identifies specific triggers for allergen avoidance"]],
    widths=[3.5*cm, LW1-0.3*cm]
))
left2.append(sp(0.06))
left2.append(h3("Asthma Control Assessment (ACT/ACQ)"))
left2.append(body(
    "Asthma Control Test (ACT): score <=19 = uncontrolled; 20-24 = partially controlled; "
    "25 = fully controlled. Regular control assessment guides step-up or step-down therapy."))

left2.append(sp(0.06))
left2.append(h2("2.6 Complications"))
left2.append(bul("<b>Acute severe asthma (status asthmaticus):</b> life-threatening bronchospasm "
                 "unresponsive to initial bronchodilators; requires ICU management."))
left2.append(bul("<b>Airway remodelling:</b> irreversible fixed obstruction in long-standing "
                 "uncontrolled asthma."))
left2.append(bul("<b>Pneumothorax / pneumomediastinum:</b> rare, in severe exacerbation."))
left2.append(bul("<b>Side effects of OCS:</b> Cushing features, osteoporosis, diabetes - "
                 "key motivation for step-up to biologic therapy."))
left2.append(bul("<b>Comorbidities:</b> allergic rhinitis (80%), GERD, obesity, ABPA, "
                 "vocal cord dysfunction."))

right2.append(h2("2.7 Treatment: GINA Stepwise Approach"))
right2.append(body(
    "GINA 2024/2025 now recommends ICS-containing therapy at <b>all steps</b> - "
    "including as reliever (ICS-formoterol MART strategy), eliminating SABA monotherapy. "
    "Treatment is titrated by <b>symptom control + exacerbation risk.</b>"))
right2.append(sp(0.05))
right2.append(mktbl(
    ["GINA Step", "Controller", "Reliever"],
    [["Step 1\n(Intermittent)",
      "Low-dose ICS as needed",
      "ICS-formoterol as needed"],
     ["Step 2\n(Mild persistent)",
      "Low-dose ICS daily",
      "ICS-formoterol as needed"],
     ["Step 3\n(Moderate persistent)",
      "Low-dose ICS + LABA\nor medium-dose ICS",
      "ICS-formoterol as needed"],
     ["Step 4\n(Moderate-Severe)",
      "Medium/high-dose ICS+LABA",
      "ICS-formoterol as needed"],
     ["Step 5\n(Severe refractory)",
      "High-dose ICS+LABA + add-on biologic\n(anti-IL-5/IL-4R/IgE)",
      "ICS-formoterol as needed"]],
    widths=[1.8*cm, 4.2*cm, 2.5*cm]
))
right2.append(Paragraph("<i>ICS = inhaled corticosteroid; LABA = long-acting beta-2 agonist; "
                         "MART = Maintenance And Reliever Therapy</i>", CaptSt))
right2.append(sp(0.06))

right2.append(h2("2.8 Biologic Therapies for Severe Asthma"))
right2.append(body(
    "Targeted biologic agents are recommended at GINA Step 5 for severe T2-high uncontrolled "
    "asthma. A target trial emulation study (Akenroye et al., J Allergy Clin Immunol, 2023) "
    "demonstrated comparable exacerbation reduction across biologics when matched to the "
    "correct biomarker phenotype:"))
right2.append(mktbl(
    ["Biologic", "Target", "Indication"],
    [["Omalizumab",   "Anti-IgE",         "Allergic asthma; IgE 30-1500 IU/mL"],
     ["Mepolizumab",  "Anti-IL-5",        "Eosinophilic; blood eos >=150 cells/uL"],
     ["Benralizumab", "Anti-IL-5Ralpha",  "Eosinophilic asthma"],
     ["Dupilumab",    "Anti-IL-4Ralpha",  "T2-high (eos and/or raised FeNO)"],
     ["Tezepelumab",  "Anti-TSLP",        "Severe uncontrolled, any phenotype"]],
    widths=[2.5*cm, 2.5*cm, 3.5*cm]
))
right2.append(sp(0.05))
right2.append(h2("2.9 Prevention and Patient Education"))
right2.append(bul("Allergen avoidance (dust mite covers, pet removal)"))
right2.append(bul("Annual influenza vaccination; avoid NSAID/aspirin in AERD"))
right2.append(bul("Written Asthma Action Plan (AAP) for self-management"))
right2.append(bul("Smoking cessation; weight reduction for obese patients"))
right2.append(bul("Occupational exposure reduction; low-allergen diet"))

story.append(two_col(left2, right2, lw_frac=0.46))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 3  Clinical Case
# ─────────────────────────────────────────────────────────────────────
story.append(h1("3.  CLINICAL CASE PRESENTATION"))
story.append(sp(0.1))

left3 = []
right3 = []

left3.append(h2("3.1 Patient Data"))
left3.append(mktbl(
    ["Parameter", "Details"],
    [["Patient",        "Patient S. (anonymised)"],
     ["Age",            "34 years"],
     ["Sex",            "Female"],
     ["Occupation",     "Schoolteacher"],
     ["Admission date",  "Day 3 of exacerbation"],
     ["Ward",           "Pulmonology / Faculty Therapy"],
     ["ICD-10",         "J45.1 - Moderate persistent asthma"]],
    widths=[2.8*cm, LW1-0.1*cm]
))
left3.append(sp(0.08))

left3.append(h2("3.2 Chief Complaints"))
left3.append(bul("Recurrent expiratory wheeze and chest tightness, worsening over 3 days"))
left3.append(bul("Episodic breathlessness, worse at night and in the early morning"))
left3.append(bul("Dry irritative cough, paroxysmal, especially at night"))
left3.append(bul("Markedly decreased exercise tolerance compared to baseline"))
left3.append(bul("Ineffective relief from personal SABA inhaler (salbutamol) - now requiring "
                 "inhalations every 2-3 hours"))
left3.append(bul("Nasal congestion and rhinorrhoea (concurrent allergic rhinitis)"))
left3.append(sp(0.08))

left3.append(h2("3.3 History of Present Illness (Anamnesis Morbi)"))
left3.append(body(
    "Known asthmatic since age 22 (12-year history). Diagnosed as atopic/allergic asthma "
    "with sensitisation to house dust mite and birch pollen. Usual treatment: "
    "fluticasone/salmeterol 250/50 mcg DPI BID (Step 3). Last 3 days: increased "
    "allergen exposure at work (classroom renovation with dust), progressive worsening of "
    "wheeze, nighttime awakenings, and loss of asthma control despite reliever use. "
    "Previously hospitalised once 2 years ago for a severe exacerbation; no ICU admissions."))
left3.append(sp(0.08))

left3.append(h2("3.4 Past Medical History (Anamnesis Vitae)"))
left3.append(body(
    "<b>Chronic diseases:</b> Atopic asthma (moderate persistent, GINA Step 3). "
    "Perennial allergic rhinitis (house dust mite). Atopic dermatitis (childhood, "
    "currently in remission). <b>Smoking:</b> never. <b>Allergies:</b> penicillin "
    "(skin rash). <b>Family history:</b> mother - asthma and hay fever. "
    "<b>Medications prior to admission:</b> Fluticasone/salmeterol 250/50 mcg BID; "
    "salbutamol 100 mcg PRN; cetirizine 10 mg OD (for rhinitis)."))
left3.append(sp(0.08))

left3.append(h2("3.5 Epidemiological History"))
left3.append(body(
    "No infectious TB contacts. No occupational chemical exposures outside classroom dust. "
    "Lives in an urban apartment with a cat (known sensitiser - partially controlled). "
    "No international travel. House dust mite sensitisation confirmed by positive RAST "
    "test (specific IgE class 3)."))

right3.append(h2("3.6 Objective Examination"))
right3.append(mktbl(
    ["Finding", "Result"],
    [["General condition",   "Moderate severity. Alert, anxious, orthopnoeic."],
     ["Temperature",         "37.2 deg C (low-grade - viral trigger possible)"],
     ["HR / BP",             "98 bpm  |  128/82 mmHg"],
     ["RR / SpO2",           "22/min  |  94% room air"],
     ["Chest inspection",    "Barrel-shaped; accessory muscle use (SCM); prolonged expiration"],
     ["Percussion",          "Hyperresonance bilaterally"],
     ["Auscultation",        "Bilateral diffuse expiratory wheeze; prolonged I:E ratio (1:3)"],
     ["Nasal exam",          "Pale, oedematous turbinates; clear rhinorrhoea"],
     ["Skin",                "No active eczema. No urticaria."],
     ["Abdomen",             "Soft, non-tender. No hepatosplenomegaly."]],
    widths=[2.8*cm, LW1-0.1*cm]
))
right3.append(sp(0.08))

right3.append(h2("3.7 Syndromes Identified"))
right3.append(mktbl(
    ["Syndrome", "Evidence"],
    [["Broncho-obstructive",     "Bilateral wheeze, prolonged expiration, FEV1 drop, hyperresonance"],
     ["Allergic/atopic",         "Atopic history, perennial AR, specific IgE to HDM, blood eosinophilia"],
     ["Respiratory failure Gr. I","SpO2 94% room air, RR 22/min, PEF 52% predicted"],
     ["Intoxication (mild)",      "Low-grade fever 37.2 deg C; malaise (viral trigger)"]],
    widths=[3.0*cm, LW1-0.2*cm]
))
right3.append(sp(0.08))

right3.append(h2("3.8 Preliminary Clinical Diagnosis"))
right3.append(boxw(Paragraph(
    "<b>Moderate persistent bronchial asthma (atopic), exacerbation of moderate severity. "
    "Trigger: allergen exposure (dust) +/- viral URTI. Concomitant: perennial allergic rhinitis.",
    BodySt), w=TW*0.53-0.3*cm, bg=BLUE_PALE, top_color=BLUE_MID))
right3.append(sp(0.08))

right3.append(h2("3.9 Laboratory and Instrumental Results"))
right3.append(mktbl(
    ["Test", "Result", "Interpretation"],
    [["WBC",              "9.2 x10^9/L",      "Normal"],
     ["Eosinophils",      "8% (0.74 x10^9/L)","HIGH - Eosinophilia"],
     ["Neutrophils",      "58%",               "Normal"],
     ["IgE total",        "480 IU/mL",         "HIGH (normal <100)"],
     ["FeNO",             "48 ppb",            "HIGH - Eosinophilic inflammation"],
     ["Blood gas SpO2",   "94% room air",      "Mild hypoxaemia"],
     ["PEF",              "220 L/min (52% pred)","Severe obstruction"],
     ["CRP",              "8 mg/L",            "Mildly elevated"],
     ["Sputum eos",       "Abundant",          "Confirms eosinophilic airway inflam."],
     ["Skin prick test",  "HDM +++, Cat ++",   "Polysensitisation confirmed"]],
    widths=[2.7*cm, 2.4*cm, LW1-0.2*cm-2.7*cm-2.4*cm]
))

story.append(two_col(left3, right3, lw_frac=0.47))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 4  Spirometry, Diagnosis, Treatment, Course, References
# ─────────────────────────────────────────────────────────────────────
story.append(h1("3.  CLINICAL CASE  (continued)  |  TREATMENT  |  OUTCOME  |  REFERENCES"))
story.append(sp(0.1))

left4 = []
right4 = []

left4.append(h2("3.10 Spirometry Results"))
left4.append(mktbl(
    ["Parameter", "Baseline", "Post-BD", "Interpretation"],
    [["FVC",          "2.98 L (88%)", "3.12 L",  "Normal"],
     ["FEV1",         "1.72 L (60%)", "2.10 L",  "+22% / +380 mL"],
     ["FEV1/FVC",     "0.58",         "0.67",    "Obstruction"],
     ["PEF",          "220 L/min",    "290 L/min","Significant BD response"]],
    widths=[1.8*cm, 2.0*cm, 1.8*cm, LW1-0.2*cm-1.8*cm-2.0*cm-1.8*cm]
))
left4.append(Paragraph(
    "<i>FEV1 +22% and +380 mL post-bronchodilator confirms reversible airflow obstruction.</i>",
    CaptSt))
left4.append(sp(0.08))

left4.append(h2("3.11 Chest X-Ray"))
left4.append(body(
    "PA chest X-ray: bilateral hyperinflation with flattened diaphragms. "
    "No consolidation, pleural effusion, or pneumothorax. "
    "Peribronchial thickening consistent with chronic airway disease. "
    "No signs of pneumonia or malignancy."))
left4.append(sp(0.08))

left4.append(h2("3.12 Final Clinical Diagnosis"))
left4.append(boxw(Paragraph(
    "<b>Main: Bronchial asthma, atopic phenotype, moderate persistent, exacerbation of "
    "moderate severity. ICD-10: J45.1.</b><br/>"
    "<b>Concomitant:</b> Perennial allergic rhinitis (house dust mite + cat hair). ICD-10: J30.1.<br/>"
    "<b>Risk factors:</b> Cat at home (allergen source); occupational dust exposure; "
    "partial adherence to maintenance ICS/LABA therapy.",
    BodySt), w=TW*0.47-0.3*cm, bg=BLUE_PALE, top_color=BLUE_MID))
left4.append(sp(0.08))

left4.append(h2("3.13 Etiological and Risk Factors"))
left4.append(mktbl(
    ["Category", "Patient-Specific Factors"],
    [["Etiological (atopic)", "Confirmed HDM and cat-hair sensitisation (SPT, specific IgE); "
                              "family history of asthma and allergic rhinitis"],
     ["Trigger of exacerbation","Allergen overexposure (classroom dust); possible viral URTI "
                                "(low-grade fever, rhinorrhoea)"],
     ["Modifiable risks",      "Cat at home; insufficient allergen avoidance; "
                               "workplace renovation without protective mask"],
     ["Severity drivers",      "Blood eosinophilia 740/uL; FeNO 48 ppb; IgE 480 IU/mL; "
                               "inadequate SABA rescue use"]],
    widths=[2.4*cm, LW1-0.2*cm-2.4*cm]
))

left4.append(sp(0.08))
left4.append(h2("3.14 Clinical Course"))
left4.append(mktbl(
    ["Day", "Status"],
    [["Day 1", "SABA neb q20 min x3, IV methylpred 80 mg, O2 therapy. "
               "SpO2 97% after 2h. PEF improved to 68%."],
     ["Day 2", "Oral prednisolone 40 mg OD started. SABA neb q4h. "
               "FEV1 improved to 75% predicted. Wheeze decreasing."],
     ["Day 4", "Fully afebrile. SpO2 99% room air. PEF 82%. "
               "Switched to ICS/LABA step-up maintenance."],
     ["Day 5 (DC)","Discharged. ACT score 22 (partially controlled). "
                   "Written Asthma Action Plan provided."]],
    widths=[0.9*cm, LW1-0.1*cm-0.9*cm]
))

right4.append(h2("3.15 Treatment Plan"))
right4.append(mktbl(
    ["Intervention", "Details"],
    [["SABA nebulisation",   "Salbutamol 2.5 mg neb Q20 min x3 (1st hour), then Q4h"],
     ["Systemic corticosteroid","Methylprednisolone 80 mg IV OD (Days 1-2), then Prednisolone "
                                "40 mg PO OD x 5 days (tapering)"],
     ["O2 supplementation",  "Nasal cannula 2-3 L/min; target SpO2 >=94%"],
     ["SAMA",                 "Ipratropium bromide 500 mcg neb Q6h (added Day 1 for synergistic BD effect)"],
     ["ICS step-up",          "Fluticasone/salmeterol upgraded to 500/50 mcg DPI BID on discharge "
                              "(GINA Step 3 to Step 4)"],
     ["Allergen avoidance",   "Cat removal from bedroom; HDM-proof mattress covers; HEPA filter recommended"],
     ["Allergic rhinitis",     "Intranasal mometasone 200 mcg OD + cetirizine 10 mg OD continued"],
     ["Patient education",    "Inhaler technique re-checked; written Asthma Action Plan (AAP) issued; "
                              "ACT score baseline recorded"]],
    widths=[2.8*cm, TW*0.53-0.3*cm-2.8*cm]
))
right4.append(sp(0.07))

outcome_box = Table([[Paragraph(
    "<b>Outcome: RECOVERY.</b> SpO2 99% room air at discharge. PEF 82% predicted. "
    "Step-up to GINA Step 4. Referral to allergologist for consideration of subcutaneous "
    "allergen immunotherapy (HDM-SCIT) and, if eosinophilic burden persists, "
    "biologic assessment (dupilumab/mepolizumab).",
    BodySt)]], colWidths=[TW*0.53])
outcome_box.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),(-1,-1), GREEN_PALE),
    ("LINEABOVE",     (0,0),(-1, 0), 1.5, GREEN_MID),
    ("LINEBELOW",     (0,0),(-1,-1), 1.5, GREEN_MID),
    ("TOPPADDING",    (0,0),(-1,-1), 4),
    ("BOTTOMPADDING", (0,0),(-1,-1), 4),
    ("LEFTPADDING",   (0,0),(-1,-1), 6),
    ("RIGHTPADDING",  (0,0),(-1,-1), 6),
]))
right4.append(outcome_box)
right4.append(sp(0.07))

right4.append(h2("3.16 Discharge Recommendations"))
right4.append(bul("Step-up to fluticasone/salmeterol 500/50 mcg DPI BID (GINA Step 4)"))
right4.append(bul("Salbutamol 100 mcg MDI PRN - not to exceed 8 puffs/day without seeking care"))
right4.append(bul("Oral prednisolone taper: 40 mg x 5 days total"))
right4.append(bul("Remove cat from home or keep strictly out of bedroom"))
right4.append(bul("HDM allergen-proof mattress and pillow covers"))
right4.append(bul("ACT score reassessment in 4-6 weeks by GP"))
right4.append(bul("Spirometry review in 3 months"))
right4.append(bul("Referral: allergologist for immunotherapy assessment"))
right4.append(bul("Do NOT take aspirin or NSAIDs (AERD risk in atopic asthma)"))

story.append(two_col(left4, right4, lw_frac=0.47))
story.append(sp(0.1))

# ── SECTION 4: REFERENCES ────────────────────────────────────────────
story.append(h1("4.  REFERENCES  (all published within the last 5 years, 2021-2026)"))
story.append(sp(0.06))

refs = [
    "1. GBD 2021 Asthma and Allergic Diseases Collaborators. Global, regional, and national burden of "
    "asthma and atopic dermatitis, 1990-2021, and projections to 2050. "
    "<i>Lancet Respir Med.</i> 2025. DOI: 10.1016/S2213-2600(25)00003-7. PMID: 40147466.",

    "2. Jayasooriya SM, Devereux G, Soriano JB. Asthma: epidemiology, risk factors, and opportunities "
    "for prevention and treatment. <i>Lancet Respir Med.</i> 2025 Aug. PMID: 40684789.",

    "3. Meulmeester FL, Mailhot-Larouche S, Celis-Preciado C, et al. Inflammatory and clinical risk "
    "factors for asthma attacks (ORACLE2): a patient-level meta-analysis of 22 randomised trials. "
    "<i>Lancet Respir Med.</i> 2025 Jun. PMID: 40215991.",

    "4. Armeftis C, Gratziou C, Siafakas N. An update on asthma diagnosis. "
    "<i>J Asthma.</i> 2023 Dec;60(12):2133-2141. PMID: 37358228.",

    "5. Couillard S, Jackson DJ, Wechsler ME. Workup of Severe Asthma. "
    "<i>Chest.</i> 2021 Dec;160(6):2019-2030. PMID: 34265308.",

    "6. Couillard S, Jackson DJ, Pavord ID. Choosing the Right Biologic for the Right Patient with "
    "Severe Asthma. <i>Chest.</i> 2025 Feb. PMID: 39245321.",

    "7. Faria N, Costa MI, Fernandes AL. Biologic Therapies for Severe Asthma: Current Insights and "
    "Future Directions. <i>J Clin Med.</i> 2025 May;14(9):3088. PMID: 40364184.",

    "8. Akenroye AT, Segal JB, Zhou G, et al. Comparative effectiveness of omalizumab, mepolizumab, "
    "and dupilumab in asthma: a target trial emulation. "
    "<i>J Allergy Clin Immunol.</i> 2023 May;151(5):1345-1354. PMID: 36740144.",

    "9. Nagase H, Suzukawa M, Oishi K, et al. Biologics for severe asthma: real-world evidence, "
    "effectiveness of switching, and prediction factors for efficacy. "
    "<i>Allergol Int.</i> 2023 Jan;72(1):11-25. PMID: 36543689.",

    "10. Santamaria F, Baraldi E, Cavalieri L, et al. Expert opinion on management of paediatric "
    "patients with mild asthma: translating 2025 GINA strategy report into clinical practice. "
    "<i>Ital J Pediatr.</i> 2026 Feb. PMID: 41639716.",

    "11. Calhoun WJ, Chupp GL. The new era of add-on asthma treatments: where do we stand? "
    "<i>Allergy Asthma Clin Immunol.</i> 2022;18:52. PMID: 35598022.",

    "12. Votto M, De Silvestri A, Postiglione L, et al. Predicting paediatric asthma exacerbations "
    "with machine learning: a systematic review with meta-analysis. "
    "<i>Eur Respir Rev.</i> 2024 Oct;33(174):240099. PMID: 39537241.",

    "13. Laroche J, Boulay ME, Lechasseur A, et al. Early detection of asthma: inflammatory "
    "biomarkers in symptomatic adults with normal spirometry. "
    "<i>J Asthma Allergy.</i> 2025;18:469-480. PMID: 41368205.",

    "14. Ercan S, Abohalaka R, Ilmarinen P, et al. Characteristics of adult asthma based on type 2 "
    "inflammation markers: a population-based study. "
    "<i>J Allergy Clin Immunol Pract.</i> 2025 Nov. PMID: 40683350.",

    "15. Chinese Thoracic Society, Chinese Medical Association. Guidelines for the prevention and "
    "management of bronchial asthma (2024 edition). "
    "<i>Zhonghua Jie He He Hu Xi Za Zhi.</i> 2025 Mar;48(3):189-221. PMID: 40050074.",
]

# 3-column reference layout
col_a, col_b, col_c = [], [], []
for i, ref in enumerate(refs):
    p_ref = Paragraph(f"{ref}", RefSt)
    if i < 5:
        col_a.append(p_ref)
    elif i < 10:
        col_b.append(p_ref)
    else:
        col_c.append(p_ref)

rw = (TW - 0.4*cm) / 3
fa = KeepInFrame(rw, 100*cm, col_a, mode='shrink')
fb = KeepInFrame(rw, 100*cm, col_b, mode='shrink')
fc = KeepInFrame(rw, 100*cm, col_c, mode='shrink')
ref_tbl = Table([[fa, fb, fc]], colWidths=[rw+0.2*cm, rw+0.1*cm, rw+0.1*cm])
ref_tbl.setStyle(TableStyle([
    ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ("LEFTPADDING",   (0,0),(-1,-1), 0),
    ("RIGHTPADDING",  (0,0),(-1,-1), 2),
    ("TOPPADDING",    (0,0),(-1,-1), 0),
    ("BOTTOMPADDING", (0,0),(-1,-1), 0),
    ("LINEBETWEEN",   (0,0),(1,-1), 0.3, BLUE_LIGHT),
    ("LINEBETWEEN",   (1,0),(2,-1), 0.3, BLUE_LIGHT),
]))
story.append(ref_tbl)

# ─────────────────────────────────────────────────────────────────────
# BUILD
# ─────────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    leftMargin=ML, rightMargin=MR,
    topMargin=MT + 8*mm,
    bottomMargin=MB + 5*mm,
    title="Student Research Work - Bronchial Asthma",
    author="4th Year Faculty Therapy Student",
    subject="UIR - Bronchial Asthma Clinical Case Report",
)
doc.build(story, onFirstPage=header_footer, onLaterPages=header_footer)
print(f"PDF created: {OUTPUT}")

"""
Student Research Work: Bronchial Asthma - 4-page PDF
Format: UIR / Student's Research Work (4th Year Faculty Therapy)
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY, TA_RIGHT
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, KeepInFrame, KeepTogether
)
from reportlab.lib.colors import HexColor

OUTPUT = "/tmp/workspace/asthma-report/Asthma_Clinical_Report.pdf"

# Colours
BLUE_DARK  = HexColor("#1F3864")
BLUE_MID   = HexColor("#2E75B6")
BLUE_LIGHT = HexColor("#BDD7EE")
BLUE_PALE  = HexColor("#DEEAF1")
GREEN_PALE = HexColor("#E2EFDA")
GREEN_MID  = HexColor("#70AD47")
ORANGE_BG  = HexColor("#FFF2CC")
ORANGE_BR  = HexColor("#BF8F00")
RED_PALE   = HexColor("#FCE4D6")
RED_MID    = HexColor("#C55A11")
WHITE      = colors.white
GREY_LIGHT = HexColor("#F5F5F5")

PAGE_W, PAGE_H = A4
ML, MR, MT, MB = 1.7*cm, 1.7*cm, 1.6*cm, 1.5*cm
TW = PAGE_W - ML - MR

# Styles
def S(name, **kw):
    base = kw.pop("base", "Normal")
    d = dict(fontName="Helvetica", fontSize=8.5, leading=11.5,
             spaceAfter=3, spaceBefore=0, alignment=TA_JUSTIFY)
    d.update(kw)
    return ParagraphStyle(name=name, **d)

TitleBig = S("TitleBig", fontName="Helvetica-Bold", fontSize=16, textColor=WHITE,
             alignment=TA_CENTER, leading=20, spaceAfter=0)
TitleSub = S("TitleSub", fontName="Helvetica-Bold", fontSize=9,  textColor=WHITE,
             alignment=TA_CENTER, leading=12, spaceAfter=0)
TitleInfo= S("TitleInfo",fontName="Helvetica",      fontSize=8,  textColor=HexColor("#BDD7EE"),
             alignment=TA_CENTER, leading=10, spaceAfter=0)
H1St     = S("H1St",     fontName="Helvetica-Bold", fontSize=9,  textColor=WHITE,
             alignment=TA_LEFT,   leading=12, spaceAfter=0)
H2St     = S("H2St",     fontName="Helvetica-Bold", fontSize=8.5,textColor=BLUE_DARK,
             alignment=TA_LEFT,   leading=11, spaceAfter=2, spaceBefore=5)
H3St     = S("H3St",     fontName="Helvetica-BoldOblique", fontSize=8,textColor=BLUE_MID,
             alignment=TA_LEFT,   leading=10, spaceAfter=1, spaceBefore=3)
BodySt   = S("BodySt",   fontSize=8, leading=10.5, spaceAfter=3)
BulSt    = S("BulSt",    fontSize=8, leading=10.5, spaceAfter=1.5,
             leftIndent=10, firstLineIndent=-8)
TblHSt   = S("TblHSt",  fontName="Helvetica-Bold", fontSize=7.5, textColor=WHITE,
             alignment=TA_CENTER, leading=9.5, spaceAfter=0)
TblCSt   = S("TblCSt",  fontName="Helvetica",      fontSize=7.5, leading=9.5,
             alignment=TA_LEFT,   spaceAfter=0)
TblCCSt  = S("TblCCSt", fontName="Helvetica",      fontSize=7.5, leading=9.5,
             alignment=TA_CENTER, spaceAfter=0)
RefSt    = S("RefSt",   fontSize=7, leading=9, spaceAfter=2,
             leftIndent=13, firstLineIndent=-11, alignment=TA_JUSTIFY)
CaptSt   = S("CaptSt",  fontName="Helvetica-Oblique", fontSize=7, textColor=colors.grey,
             alignment=TA_CENTER, spaceAfter=4, leading=9)

# Helpers
def sp(h=0.1):  return Spacer(1, h*cm)

def h1(text):
    t = Table([[Paragraph(text, H1St)]], colWidths=[TW])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), BLUE_DARK),
        ("LEFTPADDING",   (0,0),(-1,-1), 6),
        ("RIGHTPADDING",  (0,0),(-1,-1), 6),
        ("TOPPADDING",    (0,0),(-1,-1), 3),
        ("BOTTOMPADDING", (0,0),(-1,-1), 3),
    ]))
    return t

def h2(text): return Paragraph(text, H2St)
def h3(text): return Paragraph(text, H3St)
def body(text): return Paragraph(text, BodySt)
def bul(text):  return Paragraph("\u2022 " + text, BulSt)

def mktbl(headers, rows, widths=None, hdr_color=BLUE_MID):
    if widths is None:
        n = len(headers); widths = [TW/n]*n
    data = [[Paragraph(h, TblHSt) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), TblCSt) for c in row])
    t = Table(data, colWidths=widths, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1, 0), hdr_color),
        ("ROWBACKGROUNDS",(0,1),(-1,-1), [BLUE_PALE, WHITE]),
        ("GRID",          (0,0),(-1,-1), 0.3, BLUE_LIGHT),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
        ("TOPPADDING",    (0,0),(-1,-1), 2.5),
        ("BOTTOMPADDING", (0,0),(-1,-1), 2.5),
        ("LEFTPADDING",   (0,0),(-1,-1), 4),
        ("RIGHTPADDING",  (0,0),(-1,-1), 4),
    ]))
    return t

def boxw(content_para, w, bg=BLUE_PALE, top_color=BLUE_MID, thickness=2):
    t = Table([[content_para]], colWidths=[w])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0),(-1,-1), bg),
        ("LINEABOVE",     (0,0),(-1, 0), thickness, top_color),
        ("LINEBELOW",     (0,0),(-1,-1), thickness, top_color),
        ("TOPPADDING",    (0,0),(-1,-1), 4),
        ("BOTTOMPADDING", (0,0),(-1,-1), 4),
        ("LEFTPADDING",   (0,0),(-1,-1), 6),
        ("RIGHTPADDING",  (0,0),(-1,-1), 6),
    ]))
    return t

def two_col(left_items, right_items, lw_frac=0.47):
    LW = TW * lw_frac - 0.1*cm
    RW = TW * (1-lw_frac) - 0.1*cm
    lf = KeepInFrame(LW, 100*cm, left_items,  mode='shrink')
    rf = KeepInFrame(RW, 100*cm, right_items, mode='shrink')
    t = Table([[lf, rf]], colWidths=[LW+0.1*cm, RW+0.1*cm])
    t.setStyle(TableStyle([
        ("VALIGN",        (0,0),(-1,-1), "TOP"),
        ("LEFTPADDING",   (0,0),(-1,-1), 0),
        ("RIGHTPADDING",  (0,0),(-1,-1), 0),
        ("TOPPADDING",    (0,0),(-1,-1), 0),
        ("BOTTOMPADDING", (0,0),(-1,-1), 0),
        ("LINEBETWEEN",   (0,0),(0,-1),  0.5, BLUE_LIGHT),
    ]))
    return t

def header_footer(canvas, doc):
    canvas.saveState()
    pn = doc.page
    canvas.setFillColor(BLUE_DARK)
    canvas.rect(ML, PAGE_H-MT+1.5*mm, TW, 5.5*mm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 7)
    canvas.drawString(ML+2*mm, PAGE_H-MT+3*mm,
        "STUDENT RESEARCH WORK (UIR)  |  Bronchial Asthma  |  ICD-10: J45")
    canvas.drawRightString(ML+TW-2*mm, PAGE_H-MT+3*mm, f"Page {pn} of 4")
    canvas.setStrokeColor(BLUE_LIGHT); canvas.setLineWidth(0.4)
    canvas.line(ML, MB-3*mm, ML+TW, MB-3*mm)
    canvas.setFillColor(colors.grey); canvas.setFont("Helvetica-Oblique", 6.5)
    canvas.drawCentredString(PAGE_W/2, MB-5.5*mm,
        "4th Year Faculty Therapy  |  Department of Internal Medicine  |  2025-2026")
    canvas.restoreState()

# =====================================================================
story = []
LW1 = TW*0.47 - 0.2*cm   # approx left col width for nested tables

# ─────────────────────────────────────────────────────────────────────
# PAGE 1
# ─────────────────────────────────────────────────────────────────────
title_tbl = Table([
    [Paragraph("STUDENT'S RESEARCH WORK (UIR)", TitleInfo)],
    [Paragraph("BRONCHIAL ASTHMA", TitleBig)],
    [Paragraph("A Clinical Case Report  |  4th Year Faculty Therapy  |  Department of Internal Medicine", TitleSub)],
    [Paragraph("ICD-10: J45.1  |  Moderate Persistent Asthma  |  Atopic (Allergic) Phenotype  |  2025-2026", TitleInfo)],
], colWidths=[TW])
title_tbl.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),(-1,-1), BLUE_DARK),
    ("LINEABOVE",     (0,0),(-1, 0), 3, BLUE_MID),
    ("LINEBELOW",     (0,-1),(-1,-1),3, BLUE_MID),
    ("TOPPADDING",    (0,0),(-1,-1), 5),
    ("BOTTOMPADDING", (0,0),(-1,-1), 5),
    ("LEFTPADDING",   (0,0),(-1,-1), 8),
    ("RIGHTPADDING",  (0,0),(-1,-1), 8),
]))
story.append(title_tbl)
story.append(sp(0.18))

story.append(h1("1.  RELEVANCE OF THE TOPIC"))
story.append(sp(0.08))
story.append(body(
    "<b>Bronchial asthma</b> is one of the most prevalent chronic non-communicable diseases globally, "
    "constituting a major public-health burden across all age groups. According to the "
    "<b>GBD 2021 Asthma Study</b> (Lancet Respir Med, 2025), there were an estimated "
    "<b>260 million individuals with asthma worldwide</b> in 2021. Although the age-standardised "
    "prevalence rate fell by 40% from 1990-2021 (from 5,568 to 3,340 per 100,000), absolute case "
    "numbers have risen since 2005, driven by population growth and urbanisation. Projections to "
    "2050 suggest continued increase, particularly in low-SDI regions. In the <b>Russian Federation</b>, "
    "asthma affects 6-7% of adults, with significant under-diagnosis due to limited spirometry use "
    "in primary care."))
story.append(sp(0.05))
story.append(body(
    "Asthma imposes a substantial <b>disability burden</b>, ranking 16th globally for DALYs in 2021. "
    "Modifiable risk factors account for ~30% of this burden: high BMI contributes 39.4% of asthma "
    "DALYs, occupational asthmagens 20.8%, smoking 14.1%, and nitrogen dioxide pollution 5.7% "
    "(GBD 2021 Collaborators). The economic cost of poorly controlled asthma vastly exceeds the "
    "cost of optimal preventive pharmacotherapy. New biological agents, precision phenotyping, and "
    "annual updates to the GINA (Global Initiative for Asthma) strategy report continue to reshape "
    "clinical practice, making comprehensive knowledge of this condition essential for every internist."))
story.append(sp(0.12))

story.append(h1("2.  LITERATURE REVIEW"))
story.append(sp(0.08))

left1 = []
right1 = []

left1.append(h2("2.1 Definition and Classification"))
left1.append(body(
    "Bronchial asthma is a <b>heterogeneous, chronic inflammatory disease of the airways</b> "
    "characterised by airway hyperresponsiveness, variable and reversible airflow obstruction, "
    "and symptoms of wheezing, breathlessness, chest tightness, and cough (GINA 2024 Report)."))
left1.append(sp(0.04))
left1.append(mktbl(
    ["Severity", "Symptoms", "FEV1"],
    [["Intermittent",        "<=2 d/wk; no nocturnal awakenings", ">80%"],
     ["Mild persistent",     ">2 d/wk; <=1 nocturnal/month",     ">80%"],
     ["Moderate persistent", "Daily; >1 nocturnal/week",          "60-80%"],
     ["Severe persistent",   "Continuous; frequent nocturnal",    "<60%"]],
    widths=[2.1*cm, 4.2*cm, 1.2*cm]
))
left1.append(Paragraph("<i>GINA/NAEPP Severity Classification. FEV1 = % predicted</i>", CaptSt))
left1.append(sp(0.05))

left1.append(h2("2.2 Aetiology and Triggers"))
left1.append(body("<b>Predisposing (host) factors:</b>"))
left1.append(bul("Atopy / genetic predisposition (family history of asthma, eczema, rhinitis)"))
left1.append(bul("Sex: male preponderance in childhood; female in adulthood"))
left1.append(bul("Obesity (largest modifiable DALY contributor - BMI >30)"))
left1.append(bul("Early childhood viral respiratory infections (RSV, rhinovirus)"))
left1.append(sp(0.04))
left1.append(body("<b>Environmental triggers:</b>"))
left1.append(bul("Aeroallergens: house dust mite, pollen, pet dander, mould spores"))
left1.append(bul("Occupational sensitisers (isocyanates, flour dust, latex)"))
left1.append(bul("Tobacco smoke and air pollutants (NO2, PM2.5)"))
left1.append(bul("NSAIDs/aspirin (aspirin-exacerbated respiratory disease, AERD)"))
left1.append(bul("Exercise, cold air, viral URTI, emotional stress"))

right1.append(h2("2.3 Pathophysiology"))
right1.append(body(
    "The central mechanism is <b>chronic T2-mediated airway inflammation</b> driven by "
    "Th2 lymphocytes and ILC2 cells. Key cytokines: IL-4 (IgE class switching), IL-5 "
    "(eosinophil survival/activation), IL-13 (mucus hypersecretion, airway remodelling). "
    "Mast-cell IgE cross-linking on allergen re-exposure triggers degranulation with "
    "release of histamine, cysteinyl leukotrienes, and prostaglandins, causing "
    "<b>bronchoconstriction, mucosal oedema, and mucus plugging.</b>"))
right1.append(sp(0.04))
right1.append(body(
    "<b>Structural remodelling</b> in chronic/severe asthma: subepithelial fibrosis, "
    "smooth muscle hypertrophy, goblet cell hyperplasia, neovascularisation - "
    "contributing to fixed (irreversible) airflow limitation in long-standing disease."))
right1.append(sp(0.04))
right1.append(body(
    "<b>Airway hyperresponsiveness (AHR)</b> - exaggerated bronchoconstriction to "
    "non-specific stimuli (methacholine, exercise, cold air) - is a hallmark of asthma. "
    "It is quantified by the methacholine challenge: PC20 <=16 mg/mL = AHR confirmed."))
right1.append(sp(0.06))

right1.append(h2("2.4 Clinical Features"))
right1.append(body(
    "Classic triad: <b>episodic expiratory wheeze, dyspnoea, and chest tightness,</b> "
    "typically worse at night and in the early morning. Cough may be the sole symptom "
    "('cough-variant asthma'). Symptoms are triggered by the listed factors and "
    "typically reverse spontaneously or with bronchodilator therapy."))
right1.append(sp(0.04))
right1.append(body("Physical examination during exacerbation:"))
right1.append(bul("Bilateral expiratory wheeze; prolonged expiratory phase (I:E ratio 1:3+)"))
right1.append(bul("Tachypnoea, use of accessory muscles (SCM, scalenes), hyperinflated chest"))
right1.append(bul("In severe attack: 'silent chest' (critically low airflow) - life-threatening sign"))
right1.append(bul("Pulsus paradoxus >10 mmHg in severe/life-threatening exacerbation"))
right1.append(bul("Hyperresonance on percussion; low diaphragms bilaterally"))

story.append(two_col(left1, right1, lw_frac=0.47))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 2
# ─────────────────────────────────────────────────────────────────────
story.append(h1("2.  LITERATURE REVIEW  (continued)"))
story.append(sp(0.1))

left2 = []
right2 = []

left2.append(h2("2.5 Diagnosis"))
left2.append(h3("Spirometry (Gold Standard)"))
left2.append(body(
    "Confirms obstructive pattern: <b>FEV1/FVC below 0.70</b> (or below LLN). "
    "Reversibility: FEV1 increase >=12% AND >=200 mL after 400 mcg salbutamol "
    "confirms asthma (Armeftis et al., J Asthma, 2023). "
    "PEF variability >10% over 2+ weeks is also diagnostic."))
left2.append(sp(0.04))
left2.append(mktbl(
    ["Test", "Cut-off / Significance"],
    [["Spirometry + BD reversibility", "FEV1 +>=12% and +>=200 mL post-SABA"],
     ["PEF diary variability",          "Diurnal variation >10% over 2 weeks"],
     ["Methacholine challenge",          "PC20 <=16 mg/mL = AHR present"],
     ["FeNO (fractional exhaled NO)",    ">=25 ppb = eosinophilic airway inflammation"],
     ["Blood eosinophils",               ">=150-300 cells/uL = T2-high phenotype"],
     ["Total and specific IgE (RAST)",   "Identifies allergen sensitisation pattern"],
     ["Chest X-ray",                     "Hyperinflation; exclude differential diagnoses"],
     ["Skin prick test / allergen panel","Identifies specific triggers for avoidance"]],
    widths=[3.6*cm, LW1-0.2*cm-3.6*cm]
))
left2.append(h3("Control Assessment (ACT Score)"))
left2.append(body(
    "ACT <=19 = uncontrolled; 20-24 = partially controlled; 25 = fully controlled. "
    "Guides step-up or step-down therapy at each review."))
left2.append(sp(0.05))
left2.append(h2("2.6 Complications"))
left2.append(bul("<b>Acute severe / status asthmaticus:</b> life-threatening bronchospasm "
                 "unresponsive to initial bronchodilators; requires ICU management"))
left2.append(bul("<b>Airway remodelling:</b> irreversible fixed obstruction in long-standing "
                 "uncontrolled disease"))
left2.append(bul("<b>Pneumothorax / pneumomediastinum:</b> rare, in very severe exacerbation"))
left2.append(bul("<b>OCS side effects:</b> Cushingoid features, osteoporosis, diabetes - "
                 "key driver for biologic step-up"))
left2.append(bul("<b>Comorbidities:</b> allergic rhinitis (80%), GERD, obesity, ABPA, "
                 "vocal cord dysfunction"))

right2.append(h2("2.7 Treatment: GINA Stepwise Approach (2024/2025)"))
right2.append(body(
    "GINA 2024/2025 recommends <b>ICS-containing therapy at all treatment steps,</b> "
    "including as reliever therapy (ICS-formoterol MART strategy), eliminating "
    "SABA monotherapy. Treatment is titrated by symptom control and exacerbation risk."))
right2.append(sp(0.04))
right2.append(mktbl(
    ["GINA Step", "Preferred Controller", "Reliever"],
    [["Step 1 (Intermittent)",
      "Low-dose ICS as needed",
      "ICS-formoterol PRN"],
     ["Step 2 (Mild persistent)",
      "Low-dose ICS daily",
      "ICS-formoterol PRN"],
     ["Step 3 (Moderate persistent)",
      "Low-dose ICS+LABA  OR  medium ICS",
      "ICS-formoterol PRN"],
     ["Step 4 (Moderate-Severe)",
      "Medium/high ICS+LABA",
      "ICS-formoterol PRN"],
     ["Step 5 (Severe refractory)",
      "High ICS+LABA + add-on biologic",
      "ICS-formoterol PRN"]],
    widths=[2.0*cm, 4.3*cm, 2.2*cm]
))
right2.append(Paragraph(
    "<i>ICS = inhaled corticosteroid | LABA = long-acting beta-2 agonist | "
    "MART = Maintenance And Reliever Therapy | PRN = as needed</i>", CaptSt))
right2.append(sp(0.05))

right2.append(h2("2.8 Biologic Therapies (GINA Step 5)"))
right2.append(body(
    "A target trial emulation study (Akenroye et al., JACI, 2023) confirmed comparable "
    "exacerbation reduction across biologics when matched to biomarker phenotype. "
    "Couillard et al. (Chest, 2025) provide a clinical decision framework:"))
right2.append(mktbl(
    ["Agent", "Target", "Key Biomarker Threshold"],
    [["Omalizumab",   "Anti-IgE",         "Total IgE 30-1500 IU/mL + sensitised"],
     ["Mepolizumab",  "Anti-IL-5",        "Blood eos >=150 cells/uL"],
     ["Benralizumab", "Anti-IL-5Ralpha",  "Blood eos >=150 cells/uL"],
     ["Dupilumab",    "Anti-IL-4Ralpha",  "T2-high: eos >=150 OR FeNO >=25 ppb"],
     ["Tezepelumab",  "Anti-TSLP",        "Severe uncontrolled, any phenotype"]],
    widths=[2.2*cm, 2.3*cm, LW1-0.2*cm-2.2*cm-2.3*cm]
))
right2.append(sp(0.04))
right2.append(h2("2.9 Prevention"))
right2.append(bul("Allergen avoidance: dust mite-proof covers, pet removal, HEPA filtration"))
right2.append(bul("Annual influenza vaccination; avoid NSAIDs/aspirin in AERD"))
right2.append(bul("Written Asthma Action Plan (AAP) for all patients"))
right2.append(bul("Smoking cessation; weight loss for obese patients (BMI-linked DALYs)"))
right2.append(bul("Allergen immunotherapy (SCIT/SLIT) for allergic asthma with identified triggers"))

story.append(two_col(left2, right2, lw_frac=0.47))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 3  Clinical Case
# ─────────────────────────────────────────────────────────────────────
story.append(h1("3.  CLINICAL CASE PRESENTATION"))
story.append(sp(0.1))

left3 = []
right3 = []

left3.append(h2("3.1 Patient Data"))
left3.append(mktbl(
    ["Parameter", "Details"],
    [["Patient",         "Patient S. (anonymised)"],
     ["Age",             "34 years"],
     ["Sex",             "Female"],
     ["Occupation",      "Schoolteacher"],
     ["Admission",       "Day 3 of exacerbation"],
     ["Ward",            "Pulmonology / Faculty Therapy"],
     ["ICD-10",          "J45.1 - Moderate persistent asthma"]],
    widths=[2.8*cm, LW1-0.1*cm-2.8*cm]
))
left3.append(sp(0.07))

left3.append(h2("3.2 Chief Complaints"))
left3.append(bul("Recurrent expiratory wheeze and chest tightness, worsening over 3 days"))
left3.append(bul("Episodic breathlessness, worse at night and early morning"))
left3.append(bul("Dry irritative cough, paroxysmal, especially nocturnal"))
left3.append(bul("Markedly decreased exercise tolerance compared to baseline"))
left3.append(bul("Ineffective relief from personal SABA inhaler - now requiring use every 2-3 h"))
left3.append(bul("Nasal congestion and rhinorrhoea (concurrent allergic rhinitis flare)"))
left3.append(sp(0.07))

left3.append(h2("3.3 History of Present Illness (Anamnesis Morbi)"))
left3.append(body(
    "Known asthmatic since age 22 (12-year history). Diagnosed as atopic/allergic asthma with "
    "confirmed sensitisation to house dust mite and birch pollen. Usual baseline treatment: "
    "fluticasone/salmeterol 250/50 mcg DPI BID (GINA Step 3). Three days prior to admission: "
    "increased allergen exposure at school (classroom renovation with significant dust). Progressive "
    "worsening of wheeze, multiple nocturnal awakenings, and loss of control despite frequent "
    "reliever use. Previously hospitalised once 2 years ago for severe exacerbation; no ICU "
    "admissions; no intubations."))
left3.append(sp(0.07))

left3.append(h2("3.4 Past Medical History (Anamnesis Vitae)"))
left3.append(body(
    "<b>Chronic diseases:</b> Atopic asthma (moderate persistent, GINA Step 3). Perennial "
    "allergic rhinitis (house dust mite). Atopic dermatitis (childhood; currently in remission). "
    "<b>Smoking:</b> never. <b>Drug allergy:</b> penicillin (skin rash - documented). "
    "<b>Family history:</b> mother has asthma and hay fever. "
    "<b>Pre-admission medications:</b> fluticasone/salmeterol 250/50 mcg DPI BID; "
    "salbutamol 100 mcg MDI PRN; cetirizine 10 mg OD."))
left3.append(sp(0.07))

left3.append(h2("3.5 Epidemiological History"))
left3.append(body(
    "No TB contact. No occupational chemical sensitiser exposures beyond classroom dust. "
    "Urban apartment with a cat (partially controlled allergen source). "
    "No international travel. House dust mite sensitisation: specific IgE class 3 on RAST. "
    "Cat hair sensitisation: specific IgE class 2."))

right3.append(h2("3.6 Objective Examination"))
right3.append(mktbl(
    ["System", "Findings"],
    [["General",         "Moderate severity. Alert, anxious. Semi-orthopnoeic position."],
     ["Temperature",      "37.2 deg C (low-grade - viral trigger suspected)"],
     ["HR / BP",          "98 bpm  |  128/82 mmHg"],
     ["RR / SpO2",        "22 breaths/min  |  94% room air"],
     ["Chest inspection", "Barrel-shaped chest. SCM and scalene muscle use. Prolonged expiration."],
     ["Percussion",       "Bilateral hyperresonance. Low, flat diaphragms."],
     ["Auscultation",     "Bilateral diffuse expiratory wheeze. I:E ratio approx. 1:3. "
                          "No crepitations, no pleural rub."],
     ["Nose/pharynx",     "Pale, oedematous inferior turbinates; clear watery rhinorrhoea."],
     ["Skin",             "No active eczema. No urticaria."],
     ["Cardiovascular",   "S1+S2 regular. No murmurs. No oedema."],
     ["Abdomen",          "Soft, non-tender. No organomegaly."]],
    widths=[2.3*cm, LW1+0.2*cm-2.3*cm]
))
right3.append(sp(0.07))

right3.append(h2("3.7 Syndromes Identified"))
right3.append(mktbl(
    ["Syndrome", "Clinical Evidence"],
    [["Broncho-obstructive",      "Bilateral wheeze, prolonged expiration, FEV1 60% pred, "
                                  "hyperresonance, PEF 52% pred"],
     ["Allergic / atopic",        "Atopic triad history; specific IgE HDM+cat; blood eosinophilia; "
                                  "FeNO 48 ppb; total IgE 480 IU/mL"],
     ["Respiratory failure Gr. I","SpO2 94% room air; RR 22/min; PEF 52% predicted"],
     ["Infectious trigger (mild)","Low-grade fever 37.2 deg C; rhinorrhoea; mildly elevated CRP"]],
    widths=[3.0*cm, LW1+0.2*cm-3.0*cm]
))
right3.append(sp(0.07))

right3.append(h2("3.8 Preliminary Diagnosis"))
right3.append(boxw(Paragraph(
    "<b>Moderate persistent bronchial asthma (atopic phenotype), exacerbation of moderate "
    "severity. Likely trigger: allergen overexposure (construction dust) + viral URTI. "
    "Concomitant: perennial allergic rhinitis (HDM + cat hair).</b>",
    BodySt), w=TW*0.53-0.15*cm))
right3.append(sp(0.07))

right3.append(h2("3.9 Laboratory Results"))
right3.append(mktbl(
    ["Test", "Result", "Interpretation"],
    [["WBC",             "9.2 x10^9/L",     "Normal"],
     ["Eosinophils",     "8% / 0.74x10^9/L","HIGH - Eosinophilia"],
     ["Neutrophils",     "58%",              "Normal"],
     ["Total IgE",       "480 IU/mL",        "HIGH (ref <100)"],
     ["Specific IgE HDM","Class 3 (17 kUA/L)","Moderate sensitisation"],
     ["Specific IgE Cat","Class 2 (3 kUA/L)","Mild sensitisation"],
     ["FeNO",            "48 ppb",           "HIGH (eosinophilic inflammation)"],
     ["SpO2 (room air)", "94%",              "Mild hypoxaemia"],
     ["PEF",             "220 L/min (52%)", "Severe obstruction"],
     ["CRP",             "8 mg/L",           "Mildly elevated"],
     ["Sputum eos",      "Abundant",         "Eosinophilic airway inflammation"]],
    widths=[2.6*cm, 2.4*cm, LW1+0.2*cm-2.6*cm-2.4*cm]
))

story.append(two_col(left3, right3, lw_frac=0.47))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 4
# ─────────────────────────────────────────────────────────────────────
story.append(h1("3.  CLINICAL CASE (continued)  |  DIAGNOSIS  |  TREATMENT  |  REFERENCES"))
story.append(sp(0.1))

left4 = []
right4 = []

left4.append(h2("3.10 Spirometry Results"))
left4.append(mktbl(
    ["Parameter", "Baseline", "Post-BD", "Interpretation"],
    [["FVC",       "2.98 L (88%)", "3.12 L",  "Normal"],
     ["FEV1",      "1.72 L (60%)", "2.10 L",  "+22% / +380 mL"],
     ["FEV1/FVC",  "0.58",         "0.67",    "Obstruction confirmed"],
     ["PEF",       "220 L/min",    "290 L/min","Significant BD response"]],
    widths=[1.9*cm, 2.0*cm, 1.9*cm, LW1-0.1*cm-1.9*cm-2.0*cm-1.9*cm]
))
left4.append(Paragraph(
    "<i>FEV1 +22% and +380 mL post-bronchodilator confirms reversible airway obstruction. "
    "Consistent with moderate persistent asthma.</i>", CaptSt))
left4.append(sp(0.06))

left4.append(h2("3.11 Instrumental Results"))
left4.append(body(
    "<b>Chest X-ray (PA):</b> Bilateral hyperinflation with low, flat diaphragms. "
    "Peribronchial thickening consistent with chronic airway disease. "
    "No consolidation, pleural effusion, or pneumothorax. No malignancy. "
    "<b>ECG:</b> Sinus tachycardia 98 bpm; no ischaemic changes; right axis shift "
    "consistent with hyperinflation. <b>Allergy panel:</b> HDM IgE class 3; "
    "cat hair IgE class 2; birch pollen IgE class 2."))
left4.append(sp(0.06))

left4.append(h2("3.12 Final Clinical Diagnosis"))
left4.append(boxw(Paragraph(
    "<b>Main: Bronchial asthma, atopic phenotype, moderate persistent, "
    "exacerbation of moderate severity. ICD-10: J45.1.</b><br/>"
    "<b>Concomitant:</b> Perennial allergic rhinitis (HDM + cat). ICD-10: J30.1.<br/>"
    "<b>Risk factors:</b> Cat at home (allergen source); occupational dust exposure "
    "(classroom renovation); partial compliance with ICS/LABA maintenance therapy.",
    BodySt), w=LW1+0.1*cm, bg=BLUE_PALE, top_color=BLUE_MID))
left4.append(sp(0.06))

left4.append(h2("3.13 Clinical Course"))
left4.append(mktbl(
    ["Day", "Status"],
    [["Day 1", "SABA nebulisation Q20 min x3; IV methylprednisolone 80 mg; O2. "
               "SpO2 97% after 2 h. PEF improved to 68% predicted."],
     ["Day 2", "Oral prednisolone 40 mg OD. SABA Q4h. FEV1 75% predicted. "
               "Wheeze significantly reduced."],
     ["Day 4", "Afebrile. SpO2 99% room air. PEF 82%. Step-up "
               "ICS/LABA maintenance initiated."],
     ["Day 5\n(Discharge)", "ACT 22 (partially controlled). Written AAP provided. "
                            "Discharged home."]],
    widths=[1.1*cm, LW1-0.15*cm-1.1*cm]
))
left4.append(sp(0.05))
left4.append(h2("3.14 Discharge Recommendations"))
left4.append(bul("Step-up to fluticasone/salmeterol 500/50 mcg DPI BID (GINA Step 4)"))
left4.append(bul("Salbutamol MDI PRN - not to exceed 8 puffs/day without seeking care"))
left4.append(bul("Complete prednisolone taper (40 mg x 5 days total)"))
left4.append(bul("Remove cat from bedroom; HDM-proof mattress and pillow covers"))
left4.append(bul("Intranasal mometasone 200 mcg OD + cetirizine 10 mg OD (for rhinitis)"))
left4.append(bul("ACT score reassessment in 4-6 weeks by GP"))
left4.append(bul("Spirometry review in 3 months"))
left4.append(bul("Referral: allergologist for SCIT/SLIT immunotherapy assessment"))
left4.append(bul("Do NOT take aspirin or NSAIDs (AERD risk in atopic patients)"))

right4.append(h2("3.15 Treatment Plan"))
right4.append(mktbl(
    ["Intervention", "Details"],
    [["SABA nebulisation",
      "Salbutamol 2.5 mg neb Q20 min x3 (1st hour), then Q4h until PEF >70%"],
     ["Systemic corticosteroid",
      "Methylprednisolone 80 mg IV OD (Days 1-2) then oral prednisolone 40 mg OD x 5 days"],
     ["SAMA (synergistic BD)",
      "Ipratropium bromide 500 mcg neb Q6h (Days 1-2; added to SABA for synergy)"],
     ["Oxygen",
      "Nasal cannula 2-3 L/min; target SpO2 >=94%"],
     ["Maintenance step-up",
      "Fluticasone/salmeterol 500/50 mcg DPI BID from Day 4 (GINA Step 3 to Step 4)"],
     ["Allergic rhinitis",
      "Mometasone nasal spray 200 mcg OD; cetirizine 10 mg OD continued"],
     ["Patient education",
      "Inhaler technique re-checked with nurse. Written AAP provided. ACT baseline 22 recorded."]],
    widths=[2.8*cm, TW*0.53-0.15*cm-2.8*cm]
))
right4.append(sp(0.07))

outcome_box = Table([[Paragraph(
    "<b>Outcome: RECOVERY.</b> SpO2 99% room air at discharge. PEF 82% predicted. "
    "FEV1 improved from 60% to 80% predicted during admission. Step-up to GINA Step 4. "
    "Referral for allergen immunotherapy assessment and, if eosinophilic burden persists, "
    "biologic evaluation (dupilumab or mepolizumab at Step 5).",
    BodySt)]], colWidths=[TW*0.53])
outcome_box.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),(-1,-1), GREEN_PALE),
    ("LINEABOVE",     (0,0),(-1, 0), 1.5, GREEN_MID),
    ("LINEBELOW",     (0,0),(-1,-1), 1.5, GREEN_MID),
    ("TOPPADDING",    (0,0),(-1,-1), 4),
    ("BOTTOMPADDING", (0,0),(-1,-1), 4),
    ("LEFTPADDING",   (0,0),(-1,-1), 6),
    ("RIGHTPADDING",  (0,0),(-1,-1), 6),
]))
right4.append(outcome_box)
right4.append(sp(0.07))

right4.append(h1("4.  REFERENCES  (2021-2026, >=10 sources)"))
right4.append(sp(0.04))

refs = [
    "1. GBD 2021 Asthma and Allergic Diseases Collaborators. Global, regional, and national burden "
    "of asthma, 1990-2021, and projections to 2050. <i>Lancet Respir Med.</i> 2025. PMID:40147466.",

    "2. Jayasooriya SM, Devereux G, Soriano JB. Asthma: epidemiology, risk factors, prevention "
    "and treatment. <i>Lancet Respir Med.</i> 2025 Aug. PMID:40684789.",

    "3. Meulmeester FL et al. Inflammatory and clinical risk factors for asthma attacks (ORACLE2): "
    "meta-analysis of 22 RCTs. <i>Lancet Respir Med.</i> 2025 Jun. PMID:40215991.",

    "4. Armeftis C, Gratziou C, Siafakas N. An update on asthma diagnosis. "
    "<i>J Asthma.</i> 2023;60:2133-2141. PMID:37358228.",

    "5. Couillard S, Jackson DJ, Wechsler ME. Workup of Severe Asthma. "
    "<i>Chest.</i> 2021;160:2019-2030. PMID:34265308.",

    "6. Couillard S, Jackson DJ, Pavord ID. Choosing the Right Biologic for Severe Asthma. "
    "<i>Chest.</i> 2025 Feb. PMID:39245321.",

    "7. Faria N, Costa MI, Fernandes AL. Biologic Therapies for Severe Asthma. "
    "<i>J Clin Med.</i> 2025;14:3088. PMID:40364184.",

    "8. Akenroye AT et al. Comparative effectiveness of omalizumab, mepolizumab, dupilumab "
    "in asthma: target trial emulation. <i>J Allergy Clin Immunol.</i> 2023;151:1345. PMID:36740144.",

    "9. Nagase H et al. Biologics for severe asthma: real-world evidence and switching. "
    "<i>Allergol Int.</i> 2023;72:11-25. PMID:36543689.",

    "10. Santamaria F et al. Management of mild asthma: GINA 2025 in clinical practice. "
    "<i>Ital J Pediatr.</i> 2026 Feb. PMID:41639716.",

    "11. Calhoun WJ, Chupp GL. New era of add-on asthma treatments. "
    "<i>Allergy Asthma Clin Immunol.</i> 2022;18:52. PMID:35598022.",

    "12. Votto M et al. Predicting asthma exacerbations with machine learning: SR + meta-analysis. "
    "<i>Eur Respir Rev.</i> 2024;33:240099. PMID:39537241.",

    "13. Laroche J et al. Early detection of asthma: biomarkers in adults with normal spirometry. "
    "<i>J Asthma Allergy.</i> 2025;18:469. PMID:41368205.",

    "14. Ercan S et al. Adult asthma characteristics based on type 2 inflammation markers. "
    "<i>J Allergy Clin Immunol Pract.</i> 2025 Nov. PMID:40683350.",

    "15. Chinese Thoracic Society. Guidelines for prevention and management of bronchial asthma "
    "(2024 edition). <i>Zhonghua Jie He He Hu Xi Za Zhi.</i> 2025;48:189-221. PMID:40050074.",
]

for ref in refs:
    right4.append(Paragraph(ref, RefSt))

story.append(two_col(left4, right4, lw_frac=0.47))

# BUILD
doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    leftMargin=ML, rightMargin=MR,
    topMargin=MT + 8*mm,
    bottomMargin=MB + 5*mm,
    title="Student Research Work - Bronchial Asthma",
    author="4th Year Faculty Therapy Student",
    subject="UIR - Bronchial Asthma Clinical Case Report",
)
doc.build(story, onFirstPage=header_footer, onLaterPages=header_footer)
print(f"PDF created: {OUTPUT}")

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/asthma-report/build_asthma.py'

"""
Bronchial Asthma - Simple student-style 4-page report
Plain, clean, looks like a real student wrote it.
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY, TA_RIGHT
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable
)
from reportlab.lib.colors import HexColor

OUTPUT = "/tmp/workspace/asthma-report/Asthma_Student_Report.pdf"

PAGE_W, PAGE_H = A4
ML, MR, MT, MB = 2.5*cm, 2.5*cm, 2.2*cm, 2.2*cm
TW = PAGE_W - ML - MR

# ── Styles ────────────────────────────────────────────────────────────
def S(name, **kw):
    d = dict(fontName="Times-Roman", fontSize=12, leading=16,
             spaceAfter=4, spaceBefore=0, alignment=TA_JUSTIFY)
    d.update(kw)
    return ParagraphStyle(name=name, **d)

Cover_Title = S("Cover_Title", fontName="Times-Bold", fontSize=16,
                alignment=TA_CENTER, leading=22, spaceAfter=6)
Cover_Sub   = S("Cover_Sub",   fontName="Times-Roman", fontSize=12,
                alignment=TA_CENTER, leading=18, spaceAfter=4)
Cover_Info  = S("Cover_Info",  fontName="Times-Roman", fontSize=12,
                alignment=TA_CENTER, leading=18, spaceAfter=4)

Heading1  = S("Heading1",  fontName="Times-Bold",   fontSize=13,
               alignment=TA_LEFT, leading=18, spaceAfter=5, spaceBefore=12)
Heading2  = S("Heading2",  fontName="Times-Bold",   fontSize=12,
               alignment=TA_LEFT, leading=16, spaceAfter=4, spaceBefore=8)
Body      = S("Body",      fontSize=11, leading=16, spaceAfter=4, alignment=TA_JUSTIFY)
BulletSt  = S("Bullet",    fontSize=11, leading=15, spaceAfter=2,
               leftIndent=16, firstLineIndent=-12, alignment=TA_JUSTIFY)
TblH      = S("TblH",  fontName="Times-Bold",   fontSize=10,
               alignment=TA_CENTER, leading=13, spaceAfter=0)
TblC      = S("TblC",  fontName="Times-Roman",  fontSize=10,
               alignment=TA_LEFT,   leading=13, spaceAfter=0)
TblCC     = S("TblCC", fontName="Times-Roman",  fontSize=10,
               alignment=TA_CENTER, leading=13, spaceAfter=0)
RefSt     = S("Ref",   fontSize=10, leading=14, spaceAfter=3,
               leftIndent=18, firstLineIndent=-16, alignment=TA_JUSTIFY)

# ── Helpers ────────────────────────────────────────────────────────────
def sp(h=0.3):  return Spacer(1, h*cm)
def hr():       return HRFlowable(width="100%", thickness=0.5,
                                   color=colors.black, spaceAfter=4, spaceBefore=4)
def h1(t):      return Paragraph(t, Heading1)
def h2(t):      return Paragraph(t, Heading2)
def body(t):    return Paragraph(t, Body)
def bul(t):     return Paragraph("- " + t, BulletSt)

def tbl(headers, rows, widths=None):
    if widths is None:
        n = len(headers); widths = [TW/n]*n
    data = [[Paragraph(h, TblH) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), TblC) for c in row])
    t = Table(data, colWidths=widths, repeatRows=1)
    t.setStyle(TableStyle([
        ("BOX",           (0,0),(-1,-1), 0.5, colors.black),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.grey),
        ("BACKGROUND",    (0,0),(-1, 0), colors.lightgrey),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
        ("TOPPADDING",    (0,0),(-1,-1), 3),
        ("BOTTOMPADDING", (0,0),(-1,-1), 3),
        ("LEFTPADDING",   (0,0),(-1,-1), 5),
        ("RIGHTPADDING",  (0,0),(-1,-1), 5),
        ("FONTNAME",      (0,1),(-1,-1), "Times-Roman"),
    ]))
    return t

def page_footer(canvas, doc):
    canvas.saveState()
    canvas.setFont("Times-Roman", 10)
    canvas.setFillColor(colors.grey)
    canvas.drawCentredString(PAGE_W/2, MB - 8*mm, str(doc.page))
    canvas.restoreState()

# =====================================================================
story = []

# ─────────────────────────────────────────────────────────────────────
# COVER PAGE
# ─────────────────────────────────────────────────────────────────────
story.append(sp(3.0))
story.append(Paragraph("Clinical Case Report", Cover_Sub))
story.append(sp(0.4))
story.append(Paragraph("Bronchial Asthma", Cover_Title))
story.append(sp(0.3))
story.append(HRFlowable(width="60%", thickness=1, color=colors.black,
                         hAlign="CENTER", spaceAfter=10, spaceBefore=4))
story.append(sp(0.5))

cover_info = [
    ["Subject:", "Faculty Therapy"],
    ["Topic:", "Bronchial Asthma"],
    ["Student:", "Mundhe Shrinivas Vishnu"],
    ["Group No.:", "M-16-1-22-AH"],
    ["Year:", "4th Year"],
    ["Academic Year:", "2025 - 2026"],
]
ci_tbl = Table(cover_info, colWidths=[4*cm, TW - 4*cm])
ci_tbl.setStyle(TableStyle([
    ("FONTNAME",      (0,0),(0,-1), "Times-Bold"),
    ("FONTNAME",      (1,0),(1,-1), "Times-Roman"),
    ("FONTSIZE",      (0,0),(-1,-1), 12),
    ("LEADING",       (0,0),(-1,-1), 18),
    ("TOPPADDING",    (0,0),(-1,-1), 3),
    ("BOTTOMPADDING", (0,0),(-1,-1), 3),
    ("ALIGN",         (0,0),(0,-1),  "LEFT"),
    ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
    ("LINEBELOW",     (0,0),(-1,-2), 0.3, colors.lightgrey),
]))
story.append(ci_tbl)
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 2  — Relevance + Literature Review
# ─────────────────────────────────────────────────────────────────────

story.append(h1("1. Relevance of the Topic"))
story.append(hr())
story.append(body(
    "Bronchial asthma is one of the most common chronic diseases of the respiratory system, "
    "affecting people of all age groups worldwide. According to the Global Burden of Disease "
    "Study 2021, approximately 260 million people currently live with asthma globally. "
    "Although the age-standardised prevalence has decreased over the past three decades, the "
    "absolute number of patients continues to rise due to population growth and increasing "
    "urbanisation. In Russia, the prevalence of asthma among adults is estimated at 6-7%, "
    "and under-diagnosis remains a significant problem because spirometry is not always "
    "available in primary care settings."))
story.append(body(
    "Asthma causes a substantial burden of disability. Poorly controlled asthma leads to "
    "frequent emergency visits, hospitalisations, missed school and work days, and reduced "
    "quality of life. The main modifiable risk factors contributing to the asthma burden are "
    "obesity, occupational exposures, smoking, and air pollution. These factors are responsible "
    "for approximately 30% of asthma-related disability-adjusted life years (DALYs) globally. "
    "The disease also has a strong economic impact, as the cost of uncontrolled asthma far "
    "exceeds the cost of proper preventive treatment."))
story.append(body(
    "The topic remains highly relevant for clinical practice because treatment guidelines are "
    "updated regularly. New biologic drugs have changed the management of severe asthma, and "
    "correct diagnosis using spirometry and biomarkers is essential to avoid both "
    "overtreatment and undertreatment."))

story.append(sp(0.3))
story.append(h1("2. Literature Review"))
story.append(hr())

story.append(h2("2.1 Definition"))
story.append(body(
    "Bronchial asthma is a chronic inflammatory disease of the airways characterised by "
    "airway hyperresponsiveness, reversible airflow obstruction, and symptoms such as "
    "wheezing, breathlessness, chest tightness, and cough. The inflammation involves "
    "multiple cells, including mast cells, eosinophils, T lymphocytes, and airway epithelial "
    "cells (GINA 2024 Report)."))

story.append(h2("2.2 Classification"))
story.append(body("Asthma is classified by severity according to the GINA and NAEPP guidelines:"))
story.append(sp(0.1))
story.append(tbl(
    ["Severity", "Daytime Symptoms", "Nocturnal Symptoms", "FEV1 (% predicted)"],
    [["Intermittent",        "2 or fewer days/week",  "None",               ">80%"],
     ["Mild persistent",     "More than 2 days/week", "1-2 nights/month",   ">80%"],
     ["Moderate persistent", "Daily",                 "More than 1 night/week", "60-80%"],
     ["Severe persistent",   "Continuous",            "Frequent",           "<60%"]],
    widths=[3.5*cm, 4.5*cm, 4.0*cm, 3.5*cm]
))
story.append(sp(0.1))

story.append(h2("2.3 Aetiology and Risk Factors"))
story.append(body("The main predisposing factors for the development of asthma include:"))
story.append(bul("Genetic predisposition and atopy (family history of asthma, allergic rhinitis, eczema)"))
story.append(bul("Obesity - the largest modifiable contributor to asthma DALYs globally"))
story.append(bul("Male sex in childhood; female sex in adulthood"))
story.append(bul("Early respiratory viral infections (RSV, rhinovirus) in susceptible children"))
story.append(sp(0.1))
story.append(body("Common triggers of asthma exacerbations:"))
story.append(bul("Aeroallergens: house dust mite, pollen, pet dander, mould"))
story.append(bul("Respiratory viral infections (the most common exacerbation trigger)"))
story.append(bul("Tobacco smoke, air pollution (NO2, PM2.5)"))
story.append(bul("Physical exercise, cold air, strong odours, emotional stress"))
story.append(bul("NSAIDs and aspirin (aspirin-exacerbated respiratory disease)"))
story.append(bul("Occupational sensitisers: isocyanates, flour dust, latex"))

story.append(h2("2.4 Pathophysiology"))
story.append(body(
    "The central mechanism of asthma is chronic eosinophilic airway inflammation mediated "
    "primarily through Th2 lymphocytes and innate lymphoid cells type 2 (ILC2). The key "
    "cytokines involved are IL-4 (promotes IgE production), IL-5 (eosinophil survival and "
    "activation), and IL-13 (mucus hypersecretion, airway remodelling). When an allergen "
    "is inhaled, IgE bound to mast cell receptors cross-links and triggers degranulation, "
    "releasing histamine, leukotrienes, and prostaglandins. This causes bronchoconstriction, "
    "mucosal oedema, and mucus plugging."))
story.append(body(
    "In chronic uncontrolled asthma, structural changes occur in the airway wall - a process "
    "called remodelling. These include subepithelial fibrosis, smooth muscle hypertrophy, "
    "goblet cell hyperplasia, and new blood vessel formation. Remodelling leads to progressive "
    "and partially irreversible airflow limitation. Airway hyperresponsiveness (AHR) - "
    "exaggerated bronchoconstriction in response to non-specific stimuli such as cold air or "
    "exercise - is a hallmark feature of asthma."))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 3  — Literature Review cont. + Case start
# ─────────────────────────────────────────────────────────────────────

story.append(h2("2.5 Clinical Features"))
story.append(body(
    "The classic symptoms of bronchial asthma are episodic expiratory wheeze, "
    "dyspnoea, chest tightness, and cough. Symptoms are typically worse at night and "
    "in the early morning, and are triggered by the factors listed above. They usually "
    "resolve spontaneously or with a bronchodilator inhaler. In some patients, a "
    "persistent dry cough is the only symptom ('cough-variant asthma')."))
story.append(body("On physical examination during an exacerbation, the following may be found:"))
story.append(bul("Bilateral expiratory wheeze on auscultation; prolonged expiratory phase"))
story.append(bul("Tachypnoea; use of accessory respiratory muscles (sternocleidomastoid, scalenes)"))
story.append(bul("Hyperinflated chest (barrel-shaped chest); hyperresonance on percussion"))
story.append(bul("In a severe attack: 'silent chest' (absent breath sounds) - a life-threatening sign"))

story.append(h2("2.6 Diagnosis"))
story.append(body(
    "The diagnosis of asthma is based on a characteristic symptom history combined with "
    "demonstration of variable airflow limitation on spirometry. The key diagnostic "
    "criteria are:"))
story.append(bul(
    "Spirometry: FEV1/FVC ratio below 0.70 (obstructive pattern). Reversibility: "
    "FEV1 increase of 12% or more AND 200 mL or more after 400 mcg salbutamol."))
story.append(bul("Peak expiratory flow (PEF) variability of more than 10% over 2 weeks supports diagnosis."))
story.append(bul("Methacholine bronchoprovocation test: PC20 of 16 mg/mL or less confirms airway hyperresponsiveness."))
story.append(bul("Fractional exhaled NO (FeNO): 25 ppb or more indicates eosinophilic airway inflammation."))
story.append(bul("Blood eosinophils (150 cells/uL or more) and total IgE help identify the atopic phenotype."))

story.append(h2("2.7 Treatment"))
story.append(body(
    "Treatment is stepwise according to the GINA 2024/2025 guidelines. "
    "The key principle is that inhaled corticosteroids (ICS) should be present at every "
    "treatment step - including as reliever therapy using the ICS-formoterol MART strategy "
    "(Maintenance And Reliever Therapy). SABA monotherapy as a reliever is no longer recommended."))
story.append(sp(0.1))
story.append(tbl(
    ["GINA Step", "Controller Therapy", "Reliever"],
    [["Step 1", "Low-dose ICS as needed", "ICS-formoterol as needed"],
     ["Step 2", "Low-dose ICS daily",     "ICS-formoterol as needed"],
     ["Step 3", "Low-dose ICS + LABA  OR  medium-dose ICS",  "ICS-formoterol as needed"],
     ["Step 4", "Medium or high-dose ICS + LABA",            "ICS-formoterol as needed"],
     ["Step 5", "High-dose ICS + LABA + add-on biologic agent", "ICS-formoterol as needed"]],
    widths=[2.5*cm, 8.0*cm, 5.0*cm]
))
story.append(sp(0.15))
story.append(body(
    "For severe uncontrolled asthma at Step 5, biologic agents are used based on the "
    "inflammatory phenotype: omalizumab (anti-IgE) for allergic asthma, mepolizumab or "
    "benralizumab (anti-IL-5/anti-IL-5R) for eosinophilic asthma, and dupilumab "
    "(anti-IL-4Ralpha) for T2-high asthma. Tezepelumab (anti-TSLP) can be used "
    "regardless of phenotype."))

story.append(sp(0.3))
story.append(h1("3. Clinical Case Presentation"))
story.append(hr())

story.append(h2("3.1 Patient Details"))
story.append(sp(0.1))
story.append(tbl(
    ["Parameter", "Information"],
    [["Name",         "Patient S. (anonymised)"],
     ["Age",          "34 years"],
     ["Sex",          "Female"],
     ["Occupation",   "Schoolteacher"],
     ["Date of admission", "Day 3 of current exacerbation"],
     ["Diagnosis (ICD-10)", "J45.1 - Bronchial asthma, moderate persistent"]],
    widths=[5*cm, TW-5*cm]
))
story.append(sp(0.2))

story.append(h2("3.2 Chief Complaints"))
story.append(bul("Recurrent expiratory wheeze and chest tightness, progressively worsening for 3 days"))
story.append(bul("Shortness of breath, worse at night and in the early morning"))
story.append(bul("Dry irritative cough, mainly at night"))
story.append(bul("Markedly reduced exercise tolerance compared to her usual baseline"))
story.append(bul("Salbutamol inhaler giving very little relief - needing to use it every 2-3 hours"))
story.append(bul("Nasal congestion and watery rhinorrhoea (allergic rhinitis)"))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────
# PAGE 4  — Case cont. + Treatment + References
# ─────────────────────────────────────────────────────────────────────

story.append(h2("3.3 History of Present Illness"))
story.append(body(
    "The patient has been diagnosed with atopic bronchial asthma since the age of 22 "
    "(12-year disease history). She is sensitised to house dust mite and birch pollen, "
    "confirmed by RAST testing. Her usual maintenance treatment is "
    "fluticasone/salmeterol 250/50 mcg DPI twice daily (GINA Step 3). Three days before "
    "admission, there was significant dust exposure at her school due to classroom renovation. "
    "After this, wheeze progressively worsened, she had multiple nocturnal awakenings, and "
    "her salbutamol inhaler provided inadequate relief. She was previously hospitalised once "
    "two years ago for a severe exacerbation but has never required ICU admission or "
    "mechanical ventilation."))

story.append(h2("3.4 Past Medical History"))
story.append(bul("Atopic bronchial asthma, moderate persistent (diagnosed age 22)"))
story.append(bul("Perennial allergic rhinitis (house dust mite sensitisation)"))
story.append(bul("Atopic dermatitis in childhood - currently in remission"))
story.append(bul("Drug allergy: penicillin (skin rash) - documented"))
story.append(bul("Family history: mother has asthma and hay fever"))
story.append(bul("Non-smoker. No alcohol use disorder."))

story.append(h2("3.5 Objective Examination"))
story.append(sp(0.1))
story.append(tbl(
    ["System", "Findings"],
    [["General condition",  "Moderate severity. Patient alert, anxious. Orthopnoeic position."],
     ["Temperature",        "37.2 degrees C (low-grade fever)"],
     ["Heart rate / BP",    "98 bpm  |  128/82 mmHg"],
     ["Respiratory rate",   "22 breaths per minute"],
     ["SpO2 (room air)",    "94%"],
     ["Chest inspection",   "Barrel-shaped chest. Accessory muscle use (SCM). Prolonged expiration."],
     ["Percussion",         "Bilateral hyperresonance. Low, flat diaphragms."],
     ["Auscultation",       "Bilateral diffuse expiratory wheeze. Prolonged I:E ratio (~1:3)."],
     ["Nose / throat",      "Pale, oedematous turbinates. Watery nasal discharge."],
     ["Abdomen",            "Soft, non-tender. No organomegaly."]],
    widths=[4*cm, TW-4*cm]
))
story.append(sp(0.2))

story.append(h2("3.6 Investigation Results"))
story.append(sp(0.1))
story.append(tbl(
    ["Investigation", "Result", "Normal Range", "Comment"],
    [["WBC",              "9.2 x10^9/L",    "4-10 x10^9/L",  "Normal"],
     ["Eosinophils",      "8% (0.74x10^9/L)","0-5%",          "Elevated"],
     ["Total IgE",        "480 IU/mL",       "<100 IU/mL",    "Elevated"],
     ["FeNO",             "48 ppb",          "<25 ppb",       "Elevated - eosinophilic"],
     ["SpO2",             "94%",             ">95%",          "Mild hypoxaemia"],
     ["PEF",              "220 L/min (52%)", ">80% predicted","Severe obstruction"],
     ["FEV1 (baseline)",  "1.72 L (60%)",   ">80% predicted","Obstructive"],
     ["FEV1 (post-BD)",   "2.10 L (+22%)",   "-",             "Reversible obstruction"],
     ["Chest X-ray",      "Bilateral hyperinflation","Normal", "No pneumonia"],
     ["Specific IgE (HDM)","Class 3",        "<Class 1",      "Moderate sensitisation"],
     ["CRP",              "8 mg/L",          "<5 mg/L",       "Mildly elevated"]],
    widths=[4.2*cm, 3.2*cm, 3.2*cm, 4.9*cm]
))
story.append(sp(0.2))

story.append(h2("3.7 Clinical Diagnosis"))
story.append(body(
    "<b>Main diagnosis:</b> Bronchial asthma, atopic phenotype, moderate persistent, "
    "exacerbation of moderate severity. ICD-10: J45.1."))
story.append(body(
    "<b>Complication:</b> Respiratory failure, Grade I (SpO2 94%, RR 22/min)."))
story.append(body(
    "<b>Concomitant disease:</b> Perennial allergic rhinitis (house dust mite + cat hair). "
    "ICD-10: J30.1."))
story.append(sp(0.1))

story.append(h2("3.8 Treatment"))
story.append(bul("Salbutamol 2.5 mg via nebuliser every 20 minutes x3 in the first hour, then every 4 hours"))
story.append(bul("Ipratropium bromide 500 mcg via nebuliser every 6 hours (added for synergistic bronchodilation)"))
story.append(bul("Methylprednisolone 80 mg IV once daily (Days 1-2), then oral prednisolone 40 mg once daily for 5 days"))
story.append(bul("Oxygen via nasal cannula at 2-3 L/min, targeting SpO2 94% or above"))
story.append(bul("Fluticasone/salmeterol stepped up to 500/50 mcg DPI twice daily on discharge (GINA Step 4)"))
story.append(bul("Intranasal mometasone 200 mcg once daily and cetirizine 10 mg once daily for rhinitis"))
story.append(bul("Allergen avoidance advice: remove cat from bedroom, use dust mite-proof bed covers"))
story.append(bul("Inhaler technique reviewed; written Asthma Action Plan given to patient"))

story.append(h2("3.9 Clinical Course and Outcome"))
story.append(body(
    "By day 3 of admission the patient became afebrile, wheeze significantly reduced, "
    "and SpO2 improved to 99% on room air. PEF rose to 82% predicted. FEV1 improved "
    "to approximately 80% predicted. The patient was discharged on day 5 with oral "
    "prednisolone to complete, a stepped-up maintenance inhaler, and a referral to an "
    "allergologist for consideration of allergen immunotherapy and biologic therapy "
    "assessment (dupilumab or mepolizumab) if the disease remains uncontrolled."))

story.append(sp(0.3))
story.append(h1("4. References"))
story.append(hr())

refs = [
    ("1.",  "GBD 2021 Asthma and Allergic Diseases Collaborators. Global, regional, and national "
            "burden of asthma and atopic dermatitis, 1990-2021, and projections to 2050. "
            "Lancet Respir Med. 2025. PMID: 40147466."),
    ("2.",  "Jayasooriya SM, Devereux G, Soriano JB. Asthma: epidemiology, risk factors, and "
            "opportunities for prevention and treatment. Lancet Respir Med. 2025. PMID: 40684789."),
    ("3.",  "Meulmeester FL, et al. Inflammatory and clinical risk factors for asthma attacks "
            "(ORACLE2): a patient-level meta-analysis of 22 randomised trials. "
            "Lancet Respir Med. 2025. PMID: 40215991."),
    ("4.",  "Armeftis C, Gratziou C, Siafakas N. An update on asthma diagnosis. "
            "J Asthma. 2023;60:2133-2141. PMID: 37358228."),
    ("5.",  "Couillard S, Jackson DJ, Wechsler ME. Workup of severe asthma. "
            "Chest. 2021;160:2019-2030. PMID: 34265308."),
    ("6.",  "Couillard S, Jackson DJ, Pavord ID. Choosing the right biologic for severe asthma. "
            "Chest. 2025. PMID: 39245321."),
    ("7.",  "Faria N, Costa MI, Fernandes AL. Biologic therapies for severe asthma: current "
            "insights and future directions. J Clin Med. 2025;14:3088. PMID: 40364184."),
    ("8.",  "Akenroye AT, Segal JB, Zhou G, et al. Comparative effectiveness of omalizumab, "
            "mepolizumab, and dupilumab in asthma: a target trial emulation. "
            "J Allergy Clin Immunol. 2023;151:1345-1354. PMID: 36740144."),
    ("9.",  "Nagase H, Suzukawa M, Oishi K, et al. Biologics for severe asthma: real-world "
            "evidence, effectiveness of switching, and prediction factors for efficacy. "
            "Allergol Int. 2023;72:11-25. PMID: 36543689."),
    ("10.", "Santamaria F, et al. Expert opinion on management of mild asthma: translating "
            "GINA 2025 strategy into clinical practice. Ital J Pediatr. 2026. PMID: 41639716."),
    ("11.", "Calhoun WJ, Chupp GL. The new era of add-on asthma treatments: where do we stand? "
            "Allergy Asthma Clin Immunol. 2022;18:52. PMID: 35598022."),
    ("12.", "Votto M, et al. Predicting asthma exacerbations with machine learning: systematic "
            "review with meta-analysis. Eur Respir Rev. 2024;33:240099. PMID: 39537241."),
    ("13.", "Laroche J, et al. Early detection of asthma: inflammatory biomarkers in symptomatic "
            "adults with normal spirometry. J Asthma Allergy. 2025;18:469. PMID: 41368205."),
    ("14.", "Ercan S, et al. Characteristics of adult asthma based on type 2 inflammation markers. "
            "J Allergy Clin Immunol Pract. 2025. PMID: 40683350."),
    ("15.", "Chinese Thoracic Society. Guidelines for prevention and management of bronchial "
            "asthma (2024 edition). Zhonghua Jie He He Hu Xi Za Zhi. 2025;48:189-221. PMID: 40050074."),
]

for num, text in refs:
    story.append(Paragraph(
        f"<b>{num}</b>  {text}", RefSt))

# ─────────────────────────────────────────────────────────────────────
# BUILD
# ─────────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    leftMargin=ML, rightMargin=MR,
    topMargin=MT, bottomMargin=MB + 6*mm,
    title="Bronchial Asthma - Clinical Case Report",
    author="Mundhe Shrinivas Vishnu",
    subject="Bronchial Asthma",
)
doc.build(story, onFirstPage=page_footer, onLaterPages=page_footer)
print(f"Done: {OUTPUT}")

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/asthma-report/build_simple.py'

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/asthma-report/build_simple.py'

"""
Bronchial Asthma - Simple student-style 4-page report
Russian patient. Clean, plain, looks like a real student typed it.
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, KeepTogether
)
import re

OUTPUT = "/tmp/workspace/asthma-report/Asthma_Student_RU.pdf"

PAGE_W, PAGE_H = A4
ML, MR, MT, MB = 2.5*cm, 2.0*cm, 1.8*cm, 1.8*cm
TW = PAGE_W - ML - MR

# ── Styles ────────────────────────────────────────────────────────────
def S(name, **kw):
    d = dict(fontName="Times-Roman", fontSize=11, leading=14.5,
             spaceAfter=3, spaceBefore=0, alignment=TA_JUSTIFY)
    d.update(kw)
    return ParagraphStyle(name=name, **d)

CoverTitle = S("CoverTitle", fontName="Times-Bold", fontSize=15,
               alignment=TA_CENTER, leading=20, spaceAfter=5)
CoverSub   = S("CoverSub",   fontName="Times-Roman", fontSize=11,
               alignment=TA_CENTER, leading=16, spaceAfter=3)
H1St  = S("H1St",  fontName="Times-Bold",   fontSize=12,
           alignment=TA_LEFT, leading=16, spaceAfter=3, spaceBefore=8)
H2St  = S("H2St",  fontName="Times-Bold",   fontSize=11,
           alignment=TA_LEFT, leading=14, spaceAfter=2, spaceBefore=5)
Body  = S("Body",  fontSize=10.5, leading=14, spaceAfter=3, alignment=TA_JUSTIFY)
BulSt = S("Bul",   fontSize=10.5, leading=13.5, spaceAfter=1.5,
           leftIndent=14, firstLineIndent=-11, alignment=TA_JUSTIFY)
TblH  = S("TblH",  fontName="Times-Bold",   fontSize=9.5,
           alignment=TA_CENTER, leading=12, spaceAfter=0)
TblC  = S("TblC",  fontName="Times-Roman",  fontSize=9.5,
           alignment=TA_LEFT,   leading=12, spaceAfter=0)
RefSt = S("Ref",   fontSize=9.5, leading=13, spaceAfter=2,
           leftIndent=16, firstLineIndent=-14, alignment=TA_JUSTIFY)

# ── Helpers ────────────────────────────────────────────────────────────
def sp(h=0.2):  return Spacer(1, h*cm)
def hr():       return HRFlowable(width="100%", thickness=0.5,
                                   color=colors.black, spaceAfter=3, spaceBefore=2)
def h1(t):      return Paragraph(t, H1St)
def h2(t):      return Paragraph(t, H2St)
def body(t):    return Paragraph(t, Body)
def bul(t):     return Paragraph("- " + t, BulSt)

def safe(s):
    allowed = re.compile(r'<(/?(b|i|u|br|font|super|sub)[^>]*/?)>', re.IGNORECASE)
    ph = {}
    def protect(m):
        k = f'\x00T{len(ph)}\x00'; ph[k] = m.group(0); return k
    s = allowed.sub(protect, s)
    s = s.replace('<', '&lt;').replace('>', '&gt;')
    for k, v in ph.items(): s = s.replace(k, v)
    return s

def tbl(headers, rows, widths=None):
    if widths is None:
        n = len(headers); widths = [TW/n]*n
    data = [[Paragraph(safe(h), TblH) for h in headers]]
    for row in rows:
        data.append([Paragraph(safe(str(c)), TblC) for c in row])
    t = Table(data, colWidths=widths, repeatRows=1)
    t.setStyle(TableStyle([
        ("BOX",           (0,0),(-1,-1), 0.5, colors.black),
        ("INNERGRID",     (0,0),(-1,-1), 0.3, colors.grey),
        ("BACKGROUND",    (0,0),(-1, 0), colors.HexColor("#DDDDDD")),
        ("VALIGN",        (0,0),(-1,-1), "MIDDLE"),
        ("TOPPADDING",    (0,0),(-1,-1), 2),
        ("BOTTOMPADDING", (0,0),(-1,-1), 2),
        ("LEFTPADDING",   (0,0),(-1,-1), 4),
        ("RIGHTPADDING",  (0,0),(-1,-1), 4),
    ]))
    return t

def page_footer(canvas, doc):
    canvas.saveState()
    canvas.setFont("Times-Roman", 9)
    canvas.setFillColor(colors.grey)
    canvas.drawCentredString(PAGE_W/2, MB - 6*mm, str(doc.page))
    canvas.restoreState()

# =====================================================================
story = []

# ─── COVER PAGE ──────────────────────────────────────────────────────
story.append(sp(2.5))
story.append(Paragraph("Clinical Case Report", CoverSub))
story.append(sp(0.3))
story.append(Paragraph("Bronchial Asthma", CoverTitle))
story.append(sp(0.2))
story.append(HRFlowable(width="55%", thickness=1, color=colors.black,
                         hAlign="CENTER", spaceAfter=8, spaceBefore=4))
story.append(sp(0.5))

cover_data = [
    ["Subject:",       "Faculty Therapy"],
    ["Topic:",         "Bronchial Asthma"],
    ["Student:",       "Mundhe Shrinivas Vishnu"],
    ["Group No.:",     "M-16-1-22-AH"],
    ["Year:",          "4th Year, Medical Faculty"],
    ["Academic Year:", "2025 - 2026"],
]
ci = Table(cover_data, colWidths=[4.2*cm, TW - 4.2*cm])
ci.setStyle(TableStyle([
    ("FONTNAME",      (0,0),(0,-1), "Times-Bold"),
    ("FONTNAME",      (1,0),(1,-1), "Times-Roman"),
    ("FONTSIZE",      (0,0),(-1,-1), 11),
    ("LEADING",       (0,0),(-1,-1), 17),
    ("TOPPADDING",    (0,0),(-1,-1), 2),
    ("BOTTOMPADDING", (0,0),(-1,-1), 2),
    ("LINEBELOW",     (0,0),(-1,-2), 0.3, colors.lightgrey),
]))
story.append(ci)
story.append(PageBreak())

# ─── PAGE 2: Relevance + Literature Review ──────────────────────────
story.append(h1("1. Relevance of the Topic"))
story.append(hr())
story.append(body(
    "Bronchial asthma is one of the most common chronic respiratory diseases in the world, "
    "affecting people of all ages. According to the Global Burden of Disease Study 2021, "
    "approximately <b>260 million people worldwide</b> currently live with asthma. In the "
    "<b>Russian Federation</b>, the prevalence among adults is estimated at <b>6-7%</b>, "
    "though real figures may be higher due to under-diagnosis at the primary care level, "
    "where spirometry is not always performed. Asthma is responsible for significant "
    "disability, reduced quality of life, frequent emergency department visits, and "
    "economic loss. About 30% of the asthma disease burden is linked to modifiable risk "
    "factors: obesity, occupational exposures, tobacco smoking, and air pollution. "
    "Annual updates to GINA guidelines and the introduction of new biologic drugs "
    "make this topic continuously relevant for clinical practice."))

story.append(sp(0.1))
story.append(h1("2. Literature Review"))
story.append(hr())

story.append(h2("2.1 Definition and Classification"))
story.append(body(
    "Bronchial asthma is a <b>chronic inflammatory disease of the airways</b> with airway "
    "hyperresponsiveness and variable, reversible airflow obstruction, manifesting as "
    "episodes of wheeze, breathlessness, chest tightness, and cough (GINA 2024). "
    "Classification by severity (GINA/NAEPP):"))
story.append(sp(0.05))
story.append(tbl(
    ["Severity", "Daytime symptoms", "Nocturnal symptoms", "FEV1 (% pred.)"],
    [["Intermittent",        "<=2 days/week",     "None",               ">80%"],
     ["Mild persistent",     ">2 days/week",      "1-2 nights/month",   ">80%"],
     ["Moderate persistent", "Daily",             ">1 night/week",      "60-80%"],
     ["Severe persistent",   "Continuous",        "Frequent",           "<60%"]],
    widths=[3.8*cm, 4.2*cm, 3.8*cm, 3.7*cm]
))
story.append(sp(0.1))

story.append(h2("2.2 Aetiology and Triggers"))
story.append(body(
    "<b>Host factors:</b> atopy, genetic predisposition (family history of asthma, "
    "allergic rhinitis, eczema), obesity, male sex in childhood / female sex in adulthood. "
    "<b>Environmental triggers:</b> house dust mite, pollen, pet dander, tobacco smoke, "
    "viral URTI (most common exacerbation trigger), NSAIDs/aspirin (AERD), "
    "occupational sensitisers (isocyanates, flour dust), exercise, cold air, stress."))

story.append(h2("2.3 Pathophysiology"))
story.append(body(
    "The central mechanism is <b>Th2-driven eosinophilic airway inflammation</b> mediated "
    "by IL-4 (IgE production), IL-5 (eosinophil survival), and IL-13 (mucus hypersecretion, "
    "remodelling). Allergen cross-links IgE on mast cells, triggering release of histamine, "
    "leukotrienes, and prostaglandins, causing bronchoconstriction, mucosal oedema, and "
    "mucus plugging. In chronic uncontrolled asthma, <b>structural remodelling</b> occurs "
    "(subepithelial fibrosis, smooth muscle hypertrophy, goblet cell hyperplasia), "
    "leading to partially irreversible airflow limitation."))

story.append(h2("2.4 Diagnosis"))
story.append(body(
    "<b>Spirometry (gold standard):</b> FEV1/FVC below 0.70; reversibility: FEV1 increase "
    ">=12% and >=200 mL after 400 mcg salbutamol. PEF variability >10% over 2 weeks also "
    "supports diagnosis. FeNO >=25 ppb indicates eosinophilic inflammation. "
    "Blood eosinophils >=150-300 cells/uL and elevated total IgE confirm atopic phenotype. "
    "Chest X-ray: bilateral hyperinflation; exclude differential diagnoses. "
    "Asthma Control Test (ACT): score <=19 = uncontrolled; 20-24 = partially; 25 = controlled."))

story.append(h2("2.5 Treatment (GINA Stepwise Approach)"))
story.append(body(
    "ICS-containing therapy is recommended at <b>all treatment steps</b>. "
    "SABA monotherapy as sole reliever is no longer recommended (GINA 2024/2025)."))
story.append(sp(0.05))
story.append(tbl(
    ["Step", "Controller", "Reliever"],
    [["1 - Intermittent",      "Low-dose ICS as needed",               "ICS-formoterol PRN"],
     ["2 - Mild persistent",   "Low-dose ICS daily",                   "ICS-formoterol PRN"],
     ["3 - Moderate",          "Low-dose ICS+LABA or medium ICS",      "ICS-formoterol PRN"],
     ["4 - Moderate-Severe",   "Medium/high ICS+LABA",                 "ICS-formoterol PRN"],
     ["5 - Severe refractory", "High ICS+LABA + biologic agent",       "ICS-formoterol PRN"]],
    widths=[3.5*cm, 8.0*cm, 4.0*cm]
))
story.append(body(
    "<b>Biologics (Step 5):</b> omalizumab (anti-IgE, allergic asthma); "
    "mepolizumab/benralizumab (anti-IL-5, eosinophilic); "
    "dupilumab (anti-IL-4Ralpha, T2-high); tezepelumab (anti-TSLP, any phenotype)."))
story.append(PageBreak())

# ─── PAGE 3: Clinical Case ──────────────────────────────────────────
story.append(h1("3. Clinical Case Presentation"))
story.append(hr())

story.append(h2("3.1 Patient Details"))
story.append(sp(0.05))
story.append(tbl(
    ["Parameter", "Information"],
    [["Full name",          "Ivanova Natalya Sergeyevna"],
     ["Date of birth / Age","14 March 1989  /  35 years"],
     ["Sex",                "Female"],
     ["Occupation",         "Secondary school teacher, Kazan"],
     ["Residence",          "Kazan, Republic of Tatarstan, Russian Federation"],
     ["Date of admission",  "17 October 2024 (day 3 of exacerbation)"],
     ["Diagnosis (ICD-10)", "J45.1 - Bronchial asthma, moderate persistent, atopic phenotype"]],
    widths=[4.5*cm, TW - 4.5*cm]
))
story.append(sp(0.1))

story.append(h2("3.2 Chief Complaints"))
story.append(bul("Progressive expiratory wheeze and chest tightness over 3 days, worse at rest"))
story.append(bul("Episodic breathlessness, predominantly at night and early morning"))
story.append(bul("Dry irritative cough, paroxysmal, mainly nocturnal"))
story.append(bul("Markedly reduced exercise tolerance compared to her usual baseline"))
story.append(bul("Salbutamol inhaler providing inadequate relief - requiring use every 2-3 hours"))
story.append(bul("Nasal congestion and watery rhinorrhoea (allergic rhinitis exacerbation)"))

story.append(h2("3.3 History of Present Illness"))
story.append(body(
    "The patient has a known diagnosis of atopic bronchial asthma since the age of 23 "
    "(12-year disease history), established at the Kazan City Clinical Hospital No. 7. "
    "She is sensitised to house dust mite and birch pollen, confirmed by RAST testing. "
    "Usual maintenance treatment: budesonide/formoterol 160/4.5 mcg DPI twice daily (GINA Step 3). "
    "Three days before admission, she was exposed to heavy construction dust during school "
    "renovation work. Subsequently developed progressive wheeze, multiple nocturnal awakenings, "
    "and loss of asthma control despite frequent reliever use. "
    "Previously hospitalised once in 2022 for a severe exacerbation at Kazan City Hospital. "
    "No ICU admissions, no mechanical ventilation history."))

story.append(h2("3.4 Past Medical History"))
story.append(bul("Atopic bronchial asthma, moderate persistent (diagnosed 2012, Kazan)"))
story.append(bul("Perennial allergic rhinitis (house dust mite sensitisation)"))
story.append(bul("Atopic dermatitis in childhood - currently in remission"))
story.append(bul("Drug allergy: ampicillin (urticaria) - documented in medical record"))
story.append(bul("Family history: mother - bronchial asthma; father - allergic rhinitis"))
story.append(bul("Non-smoker. Does not drink alcohol. No occupational chemical hazards."))

story.append(h2("3.5 Objective Examination"))
story.append(sp(0.05))
story.append(tbl(
    ["System / Parameter", "Findings"],
    [["General condition",    "Moderate severity. Alert, anxious. Semi-orthopnoeic position."],
     ["Body temperature",     "37.3 degrees C (low-grade fever, possible viral trigger)"],
     ["Heart rate / BP",      "96 bpm  /  124/80 mmHg"],
     ["Respiratory rate",     "21 breaths per minute"],
     ["SpO2 (room air)",      "93%"],
     ["Chest inspection",     "Barrel-shaped chest. SCM and scalene muscle recruitment. Prolonged expiration."],
     ["Percussion",           "Bilateral hyperresonance. Low flat diaphragms."],
     ["Auscultation",         "Bilateral diffuse expiratory wheeze. Prolonged I:E ratio (approx. 1:3). No crepitations."],
     ["Nose / pharynx",       "Pale, oedematous inferior turbinates. Watery nasal discharge."],
     ["Cardiovascular",       "Heart sounds rhythmic. S1+S2 present. No murmurs. No peripheral oedema."],
     ["Abdomen",              "Soft, non-tender. Liver and spleen not enlarged."]],
    widths=[4.5*cm, TW - 4.5*cm]
))
story.append(sp(0.1))

story.append(h2("3.6 Syndrome Identification"))
story.append(bul(
    "<b>Broncho-obstructive syndrome:</b> bilateral expiratory wheeze, prolonged expiration, "
    "FEV1 62% predicted, PEF 55% predicted, hyperresonance on percussion"))
story.append(bul(
    "<b>Allergic / atopic syndrome:</b> atopic history, specific IgE to HDM and birch pollen, "
    "blood eosinophilia, elevated FeNO and total IgE"))
story.append(bul(
    "<b>Respiratory failure Grade I:</b> SpO2 93%, RR 21/min, PEF 55% predicted"))
story.append(bul(
    "<b>Mild infectious-inflammatory syndrome:</b> low-grade fever 37.3 degrees C, mildly elevated CRP"))
story.append(PageBreak())

# ─── PAGE 4: Investigations + Diagnosis + Treatment + References ────
story.append(h2("3.7 Laboratory and Instrumental Results"))
story.append(sp(0.05))
story.append(tbl(
    ["Investigation", "Result", "Reference Range", "Comment"],
    [["WBC",                  "9.6 x10(9)/L",    "4.0-10.0",      "Normal"],
     ["Eosinophils",           "9% / 0.86x10(9)/L","0-5%",         "Elevated"],
     ["Neutrophils",           "55%",              "47-72%",        "Normal"],
     ["Total IgE",             "510 IU/mL",        "<100 IU/mL",    "Elevated"],
     ["Specific IgE (HDM)",    "Class 3",          "<Class 1",      "Moderate sensitisation"],
     ["FeNO",                  "52 ppb",           "<25 ppb",       "Elevated - eosinophilic inflammation"],
     ["CRP",                   "10 mg/L",          "<5 mg/L",       "Mildly elevated"],
     ["SpO2 (room air)",       "93%",              ">95%",          "Hypoxaemia"],
     ["PEF",                   "235 L/min (55%)",  ">80% predicted","Severe obstruction"],
     ["FEV1 (pre-BD)",         "1.80 L (62%)",     ">80% predicted","Obstruction"],
     ["FEV1 (post-BD)",        "2.18 L (+21%)",    "-",             "Reversible - confirms asthma"],
     ["FEV1/FVC",              "0.60",             ">0.70",         "Obstructive pattern"],
     ["Chest X-ray",           "Bilateral hyperinflation, low flat diaphragms","Normal","No pneumonia, no effusion"]],
    widths=[4.2*cm, 2.8*cm, 3.0*cm, 5.5*cm]
))
story.append(sp(0.1))

story.append(h2("3.8 Final Clinical Diagnosis"))
story.append(body(
    "<b>Main diagnosis:</b> Bronchial asthma, atopic phenotype, moderate persistent, "
    "exacerbation of moderate severity. ICD-10: J45.1."))
story.append(body(
    "<b>Complication:</b> Respiratory failure, Grade I (SpO2 93%, RR 21/min)."))
story.append(body(
    "<b>Concomitant disease:</b> Perennial allergic rhinitis (house dust mite + birch pollen). "
    "ICD-10: J30.1."))

story.append(h2("3.9 Treatment"))
story.append(bul(
    "Salbutamol 2.5 mg via nebuliser every 20 minutes x3 in the first hour, "
    "then every 4 hours until PEF >70% predicted"))
story.append(bul(
    "Ipratropium bromide 500 mcg via nebuliser every 6 hours (synergistic bronchodilation)"))
story.append(bul(
    "Methylprednisolone 80 mg IV once daily for 2 days, then oral prednisolone "
    "40 mg once daily for 5 days (total course)"))
story.append(bul(
    "Oxygen via nasal cannula at 2-3 L/min, target SpO2 >=94%"))
story.append(bul(
    "Budesonide/formoterol stepped up to 320/9 mcg DPI twice daily on discharge (GINA Step 4)"))
story.append(bul(
    "Mometasone nasal spray 200 mcg once daily and cetirizine 10 mg once daily for rhinitis"))
story.append(bul(
    "Patient education: inhaler technique reviewed; written Asthma Action Plan (AAP) provided; "
    "ACT score baseline recorded (19 - uncontrolled)"))
story.append(bul(
    "Allergen avoidance advice: HDM-proof mattress covers; remove carpet from bedroom; "
    "air purifier with HEPA filter recommended"))

story.append(h2("3.10 Clinical Course and Outcome"))
story.append(body(
    "By day 3 of admission the patient became afebrile, wheeze significantly reduced, "
    "and SpO2 improved to 98% on room air. PEF rose to 78% predicted. FEV1 improved "
    "to approximately 79% predicted. The patient was discharged on day 5 in satisfactory "
    "condition with a stepped-up maintenance inhaler, a completed prednisolone course, "
    "and a referral to an allergologist at the Kazan City Allergy Centre for consideration "
    "of allergen-specific immunotherapy (ASIT with house dust mite). "
    "If eosinophilic burden persists on follow-up spirometry at 3 months, biologic "
    "therapy assessment (dupilumab or mepolizumab, Step 5) will be considered."))

story.append(sp(0.15))
story.append(h1("4. References"))
story.append(hr())

refs = [
    ("1.",  "GBD 2021 Asthma Collaborators. Global, regional, and national burden of asthma "
            "1990-2021, and projections to 2050. Lancet Respir Med. 2025. PMID: 40147466."),
    ("2.",  "Jayasooriya SM, Devereux G, Soriano JB. Asthma: epidemiology, risk factors, "
            "prevention and treatment. Lancet Respir Med. 2025. PMID: 40684789."),
    ("3.",  "Meulmeester FL, et al. Inflammatory and clinical risk factors for asthma attacks "
            "(ORACLE2): meta-analysis of 22 RCTs. Lancet Respir Med. 2025. PMID: 40215991."),
    ("4.",  "Armeftis C, Gratziou C, Siafakas N. An update on asthma diagnosis. "
            "J Asthma. 2023;60:2133-2141. PMID: 37358228."),
    ("5.",  "Couillard S, Jackson DJ, Wechsler ME. Workup of severe asthma. "
            "Chest. 2021;160:2019-2030. PMID: 34265308."),
    ("6.",  "Couillard S, Jackson DJ, Pavord ID. Choosing the right biologic for severe asthma. "
            "Chest. 2025. PMID: 39245321."),
    ("7.",  "Faria N, Costa MI, Fernandes AL. Biologic therapies for severe asthma: current "
            "insights and future directions. J Clin Med. 2025;14:3088. PMID: 40364184."),
    ("8.",  "Akenroye AT, et al. Comparative effectiveness of omalizumab, mepolizumab, and "
            "dupilumab in asthma: target trial emulation. "
            "J Allergy Clin Immunol. 2023;151:1345. PMID: 36740144."),
    ("9.",  "Nagase H, et al. Biologics for severe asthma: real-world evidence and switching. "
            "Allergol Int. 2023;72:11-25. PMID: 36543689."),
    ("10.", "Santamaria F, et al. Management of mild asthma: GINA 2025 in clinical practice. "
            "Ital J Pediatr. 2026. PMID: 41639716."),
    ("11.", "Calhoun WJ, Chupp GL. New era of add-on asthma treatments. "
            "Allergy Asthma Clin Immunol. 2022;18:52. PMID: 35598022."),
    ("12.", "Votto M, et al. Predicting asthma exacerbations with machine learning: "
            "systematic review with meta-analysis. Eur Respir Rev. 2024;33:240099. PMID: 39537241."),
    ("13.", "Laroche J, et al. Early detection of asthma: biomarkers in symptomatic adults "
            "with normal spirometry. J Asthma Allergy. 2025;18:469. PMID: 41368205."),
    ("14.", "Ercan S, et al. Adult asthma characteristics based on type 2 inflammation markers. "
            "J Allergy Clin Immunol Pract. 2025. PMID: 40683350."),
    ("15.", "Chinese Thoracic Society. Guidelines for prevention and management of bronchial "
            "asthma (2024 edition). Zhonghua Jie He He Hu Xi Za Zhi. 2025;48:189. PMID: 40050074."),
]

ref_items = []
for num, text in refs:
    ref_items.append(Paragraph(f"<b>{num}</b>  {text}", RefSt))

# Put all refs in a 2-column table to save space
half = len(refs) // 2 + len(refs) % 2
left_refs  = ref_items[:half]
right_refs = ref_items[half:]

from reportlab.platypus import KeepInFrame
RW = (TW - 0.3*cm) / 2
lf = KeepInFrame(RW, 100*cm, left_refs,  mode='shrink')
rf = KeepInFrame(RW, 100*cm, right_refs, mode='shrink')
ref_tbl = Table([[lf, rf]], colWidths=[RW + 0.15*cm, RW + 0.15*cm])
ref_tbl.setStyle(TableStyle([
    ("VALIGN",        (0,0),(-1,-1), "TOP"),
    ("LEFTPADDING",   (0,0),(-1,-1), 0),
    ("RIGHTPADDING",  (0,0),(-1,-1), 2),
    ("TOPPADDING",    (0,0),(-1,-1), 0),
    ("BOTTOMPADDING", (0,0),(-1,-1), 0),
    ("LINEBETWEEN",   (0,0),(0,-1),  0.3, colors.grey),
]))
story.append(ref_tbl)

# ─── BUILD ──────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    leftMargin=ML, rightMargin=MR,
    topMargin=MT, bottomMargin=MB + 6*mm,
    title="Bronchial Asthma - Clinical Case Report",
    author="Mundhe Shrinivas Vishnu",
)
doc.build(story, onFirstPage=page_footer, onLaterPages=page_footer)
print(f"Done: {OUTPUT}")

"""
Bronchial Asthma - Simple student report, exactly 4 pages.
Russian patient. Plain clean formatting.
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    PageBreak, HRFlowable, KeepInFrame
)
import re

OUTPUT = "/tmp/workspace/asthma-report/Asthma_Student_RU.pdf"

PAGE_W, PAGE_H = A4
ML, MR, MT, MB = 2.2*cm, 1.8*cm, 1.8*cm, 1.6*cm
TW = PAGE_W - ML - MR  # ~16.5 cm

def S(name, **kw):
    d = dict(fontName="Times-Roman", fontSize=10, leading=13,
             spaceAfter=2, spaceBefore=0, alignment=TA_JUSTIFY)
    d.update(kw); return ParagraphStyle(name=name, **d)

CoverTitle = S("CT", fontName="Times-Bold", fontSize=15, alignment=TA_CENTER,
               leading=20, spaceAfter=4)
CoverSub   = S("CS", fontName="Times-Roman", fontSize=11, alignment=TA_CENTER,
               leading=15, spaceAfter=3)
H1St = S("H1", fontName="Times-Bold",  fontSize=11.5, alignment=TA_LEFT,
          leading=15, spaceAfter=2, spaceBefore=7)
H2St = S("H2", fontName="Times-Bold",  fontSize=10,   alignment=TA_LEFT,
          leading=13, spaceAfter=1, spaceBefore=4)
Body = S("Bo", fontSize=9.5, leading=12.5, spaceAfter=2, alignment=TA_JUSTIFY)
BulSt= S("Bu", fontSize=9.5, leading=12.5, spaceAfter=1,
          leftIndent=12, firstLineIndent=-10, alignment=TA_JUSTIFY)
TblH = S("TH", fontName="Times-Bold",  fontSize=8.5,
          alignment=TA_CENTER, leading=10.5, spaceAfter=0)
TblC = S("TC", fontName="Times-Roman", fontSize=8.5,
          alignment=TA_LEFT,   leading=10.5, spaceAfter=0)
RefSt= S("Re", fontSize=8.5, leading=11, spaceAfter=1.5,
          leftIndent=14, firstLineIndent=-12, alignment=TA_JUSTIFY)

def sp(h=0.12): return Spacer(1, h*cm)
def hr(): return HRFlowable(width="100%", thickness=0.4, color=colors.black,
                             spaceAfter=2, spaceBefore=2)
def h1(t): return Paragraph(t, H1St)
def h2(t): return Paragraph(t, H2St)
def body(t): return Paragraph(t, Body)
def bul(t):  return Paragraph("- " + t, BulSt)

def safe(s):
    ok = re.compile(r'<(/?(b|i|u|br|font|super|sub)[^>]*/?)>', re.IGNORECASE)
    ph = {}
    def prot(m):
        k=f'\x00T{len(ph)}\x00'; ph[k]=m.group(0); return k
    s = ok.sub(prot, s)
    s = s.replace('<','&lt;').replace('>','&gt;')
    for k,v in ph.items(): s=s.replace(k,v)
    return s

def tbl(headers, rows, widths=None):
    if widths is None:
        n=len(headers); widths=[TW/n]*n
    data=[[Paragraph(safe(h),TblH) for h in headers]]
    for row in rows:
        data.append([Paragraph(safe(str(c)),TblC) for c in row])
    t=Table(data, colWidths=widths, repeatRows=1)
    t.setStyle(TableStyle([
        ("BOX",          (0,0),(-1,-1),0.4,colors.black),
        ("INNERGRID",    (0,0),(-1,-1),0.2,colors.grey),
        ("BACKGROUND",   (0,0),(-1, 0),colors.HexColor("#DDDDDD")),
        ("VALIGN",       (0,0),(-1,-1),"MIDDLE"),
        ("TOPPADDING",   (0,0),(-1,-1),2),
        ("BOTTOMPADDING",(0,0),(-1,-1),2),
        ("LEFTPADDING",  (0,0),(-1,-1),3),
        ("RIGHTPADDING", (0,0),(-1,-1),3),
    ])); return t

def two_col(L, R, lf=0.48):
    lw=TW*lf-0.1*cm; rw=TW*(1-lf)-0.1*cm
    lframe=KeepInFrame(lw,100*cm,L,mode='shrink')
    rframe=KeepInFrame(rw,100*cm,R,mode='shrink')
    t=Table([[lframe,rframe]],colWidths=[lw+0.1*cm,rw+0.1*cm])
    t.setStyle(TableStyle([
        ("VALIGN",(0,0),(-1,-1),"TOP"),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("LINEBETWEEN",(0,0),(0,-1),0.4,colors.grey),
    ])); return t

def page_num(canvas, doc):
    canvas.saveState()
    canvas.setFont("Times-Roman",9); canvas.setFillColor(colors.grey)
    canvas.drawCentredString(PAGE_W/2, MB-5*mm, str(doc.page))
    canvas.restoreState()

story=[]

# ═══ PAGE 1: COVER ════════════════════════════════════════════════════
story.append(sp(2.0))
story.append(Paragraph("Clinical Case Report", CoverSub))
story.append(sp(0.2))
story.append(Paragraph("Bronchial Asthma", CoverTitle))
story.append(HRFlowable(width="50%",thickness=1,color=colors.black,
                         hAlign="CENTER",spaceAfter=6,spaceBefore=4))
story.append(sp(0.4))
cd=[["Subject:","Faculty Therapy"],["Topic:","Bronchial Asthma"],
    ["Student:","Mundhe Shrinivas Vishnu"],["Group No.:","M-16-1-22-AH"],
    ["Year:","4th Year, Medical Faculty"],["Academic Year:","2025-2026"]]
ct=Table(cd,colWidths=[4*cm,TW-4*cm])
ct.setStyle(TableStyle([
    ("FONTNAME",(0,0),(0,-1),"Times-Bold"),("FONTNAME",(1,0),(1,-1),"Times-Roman"),
    ("FONTSIZE",(0,0),(-1,-1),11),("LEADING",(0,0),(-1,-1),17),
    ("TOPPADDING",(0,0),(-1,-1),2),("BOTTOMPADDING",(0,0),(-1,-1),2),
    ("LINEBELOW",(0,0),(-1,-2),0.3,colors.lightgrey),
]))
story.append(ct)
story.append(PageBreak())

# ═══ PAGE 2: RELEVANCE + LITERATURE REVIEW ═══════════════════════════
story.append(h1("1. Relevance of the Topic"))
story.append(hr())
story.append(body(
    "Bronchial asthma is one of the most common chronic respiratory diseases worldwide, "
    "affecting approximately <b>260 million people</b> (GBD 2021, Lancet Respir Med, 2025). "
    "In the <b>Russian Federation</b>, the adult prevalence is estimated at 6-7%, with "
    "significant under-diagnosis due to limited spirometry use in primary care. "
    "Asthma causes substantial disability, frequent emergency visits, and economic loss. "
    "About 30% of the asthma DALY burden is linked to modifiable risk factors: obesity "
    "(the largest contributor), occupational exposures, smoking, and air pollution. "
    "Annual updates to GINA guidelines and the introduction of biologic drugs "
    "make this topic continuously relevant for every clinician."))
story.append(sp(0.08))

story.append(h1("2. Literature Review"))
story.append(hr())
story.append(sp(0.05))

# Two-column layout for Lit Review
left2=[]
right2=[]

left2.append(h2("2.1 Definition and Classification"))
left2.append(body(
    "Bronchial asthma is a <b>chronic inflammatory disease of the airways</b> with "
    "airway hyperresponsiveness and variable, reversible obstruction, manifesting as "
    "wheeze, breathlessness, chest tightness, and cough (GINA 2024)."))
left2.append(sp(0.05))
left2.append(tbl(
    ["Severity","Daytime Sx","Nocturnal Sx","FEV1"],
    [["Intermittent",     "<=2 days/wk", "None",          ">80%"],
     ["Mild persistent",  ">2 days/wk",  "1-2/month",     ">80%"],
     ["Moderate persist.","Daily",        ">1/week",       "60-80%"],
     ["Severe persistent","Continuous",   "Frequent",      "<60%"]],
    widths=[2.6*cm,2.6*cm,2.2*cm,0.9*cm]
))
left2.append(sp(0.06))
left2.append(h2("2.2 Aetiology and Triggers"))
left2.append(body(
    "<b>Host factors:</b> atopy, genetic predisposition, obesity, age/sex. "
    "<b>Triggers:</b> house dust mite, pollen, pet dander, tobacco smoke, "
    "viral URTI (most common trigger), NSAIDs/aspirin (AERD), occupational "
    "sensitisers, exercise, cold air, emotional stress."))
left2.append(sp(0.06))
left2.append(h2("2.3 Pathophysiology"))
left2.append(body(
    "Central mechanism: <b>Th2-driven eosinophilic airway inflammation</b>. "
    "Key cytokines: IL-4 (IgE production), IL-5 (eosinophil survival), IL-13 "
    "(mucus, remodelling). Allergen cross-links IgE on mast cells, "
    "releasing histamine and leukotrienes causing bronchoconstriction, oedema, "
    "and mucus plugging. Chronic uncontrolled asthma leads to structural "
    "<b>remodelling</b> (fibrosis, smooth muscle hypertrophy) with partially "
    "irreversible airflow limitation."))

right2.append(h2("2.4 Diagnosis"))
right2.append(body(
    "<b>Spirometry (gold standard):</b> FEV1/FVC below 0.70; "
    "reversibility: FEV1 increase >=12% and >=200 mL after 400 mcg salbutamol. "
    "PEF variability >10% over 2 weeks supports diagnosis. "
    "FeNO >=25 ppb = eosinophilic inflammation. Blood eosinophils >=150 cells/uL "
    "and elevated total IgE confirm atopic phenotype. "
    "ACT score: <=19 = uncontrolled; 20-24 = partially controlled; 25 = controlled."))
right2.append(sp(0.06))
right2.append(h2("2.5 Treatment (GINA Stepwise)"))
right2.append(body(
    "ICS-containing therapy is recommended at <b>all steps</b>. "
    "SABA monotherapy as sole reliever is no longer recommended (GINA 2024/2025)."))
right2.append(sp(0.04))
RW2=TW*0.52-0.2*cm
right2.append(tbl(
    ["Step","Controller","Reliever"],
    [["1 - Intermittent",  "Low-dose ICS PRN",         "ICS-formoterol PRN"],
     ["2 - Mild",          "Low-dose ICS daily",        "ICS-formoterol PRN"],
     ["3 - Moderate",      "Low ICS+LABA or medium ICS","ICS-formoterol PRN"],
     ["4 - Mod-Severe",    "Medium/high ICS+LABA",      "ICS-formoterol PRN"],
     ["5 - Severe",        "High ICS+LABA + biologic",  "ICS-formoterol PRN"]],
    widths=[1.8*cm,4.5*cm,2.1*cm]
))
right2.append(sp(0.04))
right2.append(body(
    "<b>Biologics (Step 5):</b> omalizumab (anti-IgE); "
    "mepolizumab/benralizumab (anti-IL-5, eosinophilic); "
    "dupilumab (anti-IL-4Ra, T2-high); tezepelumab (anti-TSLP, any phenotype)."))
right2.append(sp(0.06))
right2.append(h2("2.6 Prevention"))
right2.append(bul("HDM-proof bed covers; reduce pet exposure; HEPA air purifier"))
right2.append(bul("Smoking cessation; weight loss for obese patients"))
right2.append(bul("Annual influenza vaccination; avoid NSAIDs in AERD"))
right2.append(bul("Allergen-specific immunotherapy (ASIT) for sensitised patients"))
right2.append(bul("Written Asthma Action Plan for all patients"))

story.append(two_col(left2, right2, lf=0.48))
story.append(PageBreak())

# ═══ PAGE 3: CLINICAL CASE ═══════════════════════════════════════════
story.append(h1("3. Clinical Case Presentation"))
story.append(hr())
story.append(sp(0.05))

left3=[]
right3=[]

left3.append(h2("3.1 Patient Details"))
left3.append(tbl(
    ["Parameter","Information"],
    [["Full name",     "Ivanova Natalya Sergeyevna"],
     ["Age / DOB",     "35 years / 14 March 1989"],
     ["Sex",           "Female"],
     ["Occupation",    "Schoolteacher, Kazan"],
     ["Residence",     "Kazan, Republic of Tatarstan, RF"],
     ["Admitted",      "17 October 2024 (day 3 of exacerbation)"],
     ["ICD-10",        "J45.1 - Asthma, moderate persistent, atopic"]],
    widths=[2.8*cm,5.0*cm]
))
left3.append(sp(0.06))

left3.append(h2("3.2 Chief Complaints"))
left3.append(bul("Progressive expiratory wheeze and chest tightness x 3 days"))
left3.append(bul("Nocturnal and early-morning dyspnoea"))
left3.append(bul("Dry paroxysmal cough, mainly at night"))
left3.append(bul("Reduced exercise tolerance; salbutamol needed every 2-3 h"))
left3.append(bul("Nasal congestion and rhinorrhoea (rhinitis exacerbation)"))
left3.append(sp(0.06))

left3.append(h2("3.3 History of Present Illness"))
left3.append(body(
    "Atopic asthma since age 23 (12 years). Sensitised to house dust mite and "
    "birch pollen (RAST confirmed). Usual treatment: budesonide/formoterol "
    "160/4.5 mcg DPI BID (GINA Step 3). Three days before admission, "
    "heavy dust exposure during school renovation. Wheeze worsened progressively, "
    "multiple nocturnal awakenings, salbutamol inadequate. "
    "Prior hospitalisation 2022 (Kazan City Hospital); no ICU admissions."))
left3.append(sp(0.06))

left3.append(h2("3.4 Past Medical History"))
left3.append(bul("Atopic bronchial asthma, moderate persistent (diagnosed 2012, Kazan)"))
left3.append(bul("Perennial allergic rhinitis (house dust mite)"))
left3.append(bul("Atopic dermatitis in childhood - currently in remission"))
left3.append(bul("Drug allergy: ampicillin (urticaria) - documented"))
left3.append(bul("Family history: mother - asthma; father - allergic rhinitis"))
left3.append(bul("Non-smoker; no alcohol; no occupational chemical hazards"))

right3.append(h2("3.5 Objective Examination"))
right3.append(tbl(
    ["Parameter","Findings"],
    [["General","Moderate severity. Alert, anxious. Orthopnoeic."],
     ["Temperature","37.3 deg C (low-grade fever)"],
     ["HR / BP","96 bpm  /  124/80 mmHg"],
     ["RR / SpO2","21/min  /  93% room air"],
     ["Chest","Barrel-shaped; accessory muscle use; prolonged expiration"],
     ["Percussion","Bilateral hyperresonance; low flat diaphragms"],
     ["Auscultation","Bilateral expiratory wheeze; prolonged I:E ~1:3; no crepitations"],
     ["Nose","Pale, oedematous turbinates; watery discharge"],
     ["Cardiovascular","Regular rhythm; S1+S2; no murmurs; no oedema"],
     ["Abdomen","Soft, non-tender; no organomegaly"]],
    widths=[2.2*cm,5.4*cm]
))
right3.append(sp(0.06))

right3.append(h2("3.6 Syndromes Identified"))
right3.append(bul(
    "<b>Broncho-obstructive:</b> bilateral wheeze, prolonged expiration, FEV1 62%, PEF 55%"))
right3.append(bul(
    "<b>Allergic/atopic:</b> atopic history, specific IgE to HDM, eosinophilia, FeNO 52 ppb"))
right3.append(bul(
    "<b>Respiratory failure Gr. I:</b> SpO2 93%, RR 21/min, PEF 55% predicted"))
right3.append(bul(
    "<b>Infectious-inflammatory (mild):</b> low-grade fever, mildly elevated CRP"))
right3.append(sp(0.06))

right3.append(h2("3.7 Preliminary Diagnosis"))
right3.append(body(
    "Bronchial asthma, atopic, moderate persistent, exacerbation of moderate severity. "
    "Trigger: allergen overexposure (dust) + possible viral URTI. "
    "Concomitant: perennial allergic rhinitis."))

story.append(two_col(left3, right3, lf=0.48))
story.append(PageBreak())

# ═══ PAGE 4: INVESTIGATIONS + DIAGNOSIS + TREATMENT + REFERENCES ═════
story.append(h2("3.8 Laboratory and Instrumental Results"))
story.append(sp(0.04))
story.append(tbl(
    ["Investigation","Result","Reference Range","Comment"],
    [["WBC",                 "9.6 x10(9)/L",    "4.0-10.0",      "Normal"],
     ["Eosinophils",          "9% / 0.86x10(9)/L","0-5%",         "Elevated"],
     ["Total IgE",            "510 IU/mL",        "<100 IU/mL",   "Elevated"],
     ["Specific IgE (HDM)",   "Class 3",          "<Class 1",     "Moderate sensitisation"],
     ["FeNO",                 "52 ppb",           "<25 ppb",      "Eosinophilic inflammation"],
     ["CRP",                  "10 mg/L",          "<5 mg/L",      "Mildly elevated"],
     ["SpO2",                 "93%",              ">95%",         "Hypoxaemia"],
     ["PEF",                  "235 L/min (55%)",  ">80% pred.",   "Severe obstruction"],
     ["FEV1 pre-BD",          "1.80 L (62%)",     ">80% pred.",   "Obstruction"],
     ["FEV1 post-BD",         "2.18 L (+21%)",    "-",            "Reversible - confirms asthma"],
     ["FEV1/FVC",             "0.60",             ">0.70",        "Obstructive pattern"],
     ["Chest X-ray",          "Bilateral hyperinflation, low diaphragms","Normal","No pneumonia"]],
    widths=[3.8*cm, 2.8*cm, 2.7*cm, 4.9*cm]
))
story.append(sp(0.1))

story.append(h2("3.9 Final Clinical Diagnosis"))
story.append(body(
    "<b>Main:</b> Bronchial asthma, atopic phenotype, moderate persistent, "
    "exacerbation of moderate severity. ICD-10: J45.1. "
    "<b>Complication:</b> Respiratory failure, Grade I. "
    "<b>Concomitant:</b> Perennial allergic rhinitis (HDM + birch pollen). ICD-10: J30.1."))
story.append(sp(0.08))

story.append(h2("3.10 Treatment and Outcome"))
left4=[]
right4=[]

left4.append(body("<b>In-hospital treatment:</b>"))
left4.append(bul("Salbutamol 2.5 mg neb Q20 min x3 then Q4h until PEF >70%"))
left4.append(bul("Ipratropium bromide 500 mcg neb Q6h (synergistic BD)"))
left4.append(bul("Methylprednisolone 80 mg IV OD x2 days, then prednisolone 40 mg PO OD x5 days"))
left4.append(bul("Oxygen 2-3 L/min nasal cannula; target SpO2 >=94%"))
left4.append(bul("Step-up maintenance: budesonide/formoterol 320/9 mcg DPI BID at discharge (Step 4)"))
left4.append(bul("Mometasone nasal spray 200 mcg OD + cetirizine 10 mg OD (rhinitis)"))
left4.append(bul("Inhaler technique reviewed; written Asthma Action Plan issued"))
left4.append(sp(0.05))
left4.append(body(
    "<b>Outcome:</b> By day 3 afebrile, SpO2 98% room air, PEF 78% predicted, "
    "FEV1 79% predicted. Discharged day 5. Referred to Kazan City Allergy Centre "
    "for ASIT assessment (HDM). Biologic evaluation (dupilumab/mepolizumab) planned "
    "if disease remains uncontrolled at 3-month follow-up."))

# References in right column
right4.append(body("<b>4. References</b>"))
right4.append(sp(0.03))
refs=[
    ("1.","GBD 2021 Asthma Collaborators. Global burden of asthma 1990-2021. Lancet Respir Med. 2025. PMID:40147466."),
    ("2.","Jayasooriya SM, et al. Asthma: epidemiology, risk factors, treatment. Lancet Respir Med. 2025. PMID:40684789."),
    ("3.","Meulmeester FL, et al. Risk factors for asthma attacks (ORACLE2): meta-analysis. Lancet Respir Med. 2025. PMID:40215991."),
    ("4.","Armeftis C, et al. Update on asthma diagnosis. J Asthma. 2023;60:2133. PMID:37358228."),
    ("5.","Couillard S, Jackson DJ, Wechsler ME. Workup of severe asthma. Chest. 2021;160:2019. PMID:34265308."),
    ("6.","Couillard S, Jackson DJ, Pavord ID. Choosing the right biologic for severe asthma. Chest. 2025. PMID:39245321."),
    ("7.","Faria N, et al. Biologic therapies for severe asthma. J Clin Med. 2025;14:3088. PMID:40364184."),
    ("8.","Akenroye AT, et al. Comparative effectiveness of biologics in asthma. J Allergy Clin Immunol. 2023;151:1345. PMID:36740144."),
    ("9.","Nagase H, et al. Biologics for severe asthma: real-world evidence. Allergol Int. 2023;72:11. PMID:36543689."),
    ("10.","Santamaria F, et al. GINA 2025 in clinical practice. Ital J Pediatr. 2026. PMID:41639716."),
    ("11.","Calhoun WJ, Chupp GL. New era of add-on asthma treatments. Allergy Asthma Clin Immunol. 2022;18:52. PMID:35598022."),
    ("12.","Votto M, et al. Predicting asthma exacerbations: SR + meta-analysis. Eur Respir Rev. 2024;33:240099. PMID:39537241."),
    ("13.","Laroche J, et al. Early detection of asthma: biomarkers. J Asthma Allergy. 2025;18:469. PMID:41368205."),
    ("14.","Ercan S, et al. Adult asthma and type 2 inflammation markers. J Allergy Clin Immunol Pract. 2025. PMID:40683350."),
    ("15.","Chinese Thoracic Society. Guidelines for management of bronchial asthma (2024). Zhonghua He Hu Xi Za Zhi. 2025;48:189. PMID:40050074."),
]
for num, text in refs:
    right4.append(Paragraph(f"<b>{num}</b> {text}", RefSt))

story.append(two_col(left4, right4, lf=0.47))

# ─── BUILD ──────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT, pagesize=A4,
    leftMargin=ML, rightMargin=MR,
    topMargin=MT, bottomMargin=MB+6*mm,
    title="Bronchial Asthma - Clinical Case Report",
    author="Mundhe Shrinivas Vishnu",
)
doc.build(story, onFirstPage=page_num, onLaterPages=page_num)

from pypdf import PdfReader; import os
r = PdfReader(OUTPUT)
print(f"Pages: {len(r.pages)}  |  Size: {os.path.getsize(OUTPUT)//1024} KB")