Clinical Reference Guide: Bronchial Asthma Management

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

# ── Colour palette ──────────────────────────────────────────────────────────
NAVY      = HexColor("#0D3B66")
SKY       = HexColor("#1A8FE3")
TEAL      = HexColor("#0F7B6C")
ORANGE    = HexColor("#E87722")
RED_ALERT = HexColor("#C0392B")
AMBER     = HexColor("#F39C12")
GREEN     = HexColor("#27AE60")
LIGHT_BG  = HexColor("#EAF4FC")
LIGHT_GRN = HexColor("#E8F8F0")
LIGHT_YLW = HexColor("#FEF9E7")
LIGHT_RED = HexColor("#FDEDEC")
LIGHT_GRY = HexColor("#F4F6F7")
WHITE     = colors.white
BLACK     = HexColor("#1A1A2E")
MED_GRY   = HexColor("#7F8C8D")

PAGE_W, PAGE_H = A4
MARGIN = 14 * mm

OUTPUT = "/home/daytona/workspace/asthma-guide/Asthma_Management_Quick_Reference.pdf"

# ── Document ─────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=MARGIN, rightMargin=MARGIN,
    topMargin=12*mm, bottomMargin=14*mm,
    title="Bronchial Asthma – Clinical Quick-Reference Guide",
    author="Orris Medical Reference",
)

# ── Styles ───────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

def S(name, parent="Normal", **kw):
    return ParagraphStyle(name, parent=base[parent], **kw)

TITLE_S   = S("title_s",   fontName="Helvetica-Bold",  fontSize=20, textColor=WHITE,
               spaceAfter=2, alignment=TA_CENTER)
SUBTITLE_S= S("sub_s",     fontName="Helvetica",       fontSize=9,  textColor=HexColor("#D0E8FA"),
               alignment=TA_CENTER)
H1        = S("h1",        fontName="Helvetica-Bold",  fontSize=11, textColor=WHITE,
               spaceAfter=2, alignment=TA_LEFT)
H2        = S("h2",        fontName="Helvetica-Bold",  fontSize=9.5, textColor=NAVY,
               spaceBefore=4, spaceAfter=2)
BODY      = S("body",      fontName="Helvetica",       fontSize=7.8, textColor=BLACK,
               leading=11, spaceAfter=2)
BODY_BOLD = S("body_b",    fontName="Helvetica-Bold",  fontSize=7.8, textColor=BLACK, leading=11)
SMALL     = S("small",     fontName="Helvetica",       fontSize=6.8, textColor=MED_GRY, leading=9)
BULLET    = S("bullet",    fontName="Helvetica",       fontSize=7.8, textColor=BLACK,
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TH        = S("th",        fontName="Helvetica-Bold",  fontSize=7.5, textColor=WHITE,
               alignment=TA_CENTER, leading=10)
TD        = S("td",        fontName="Helvetica",       fontSize=7.2, textColor=BLACK,
               alignment=TA_LEFT, leading=10)
TD_C      = S("td_c",      fontName="Helvetica",       fontSize=7.2, textColor=BLACK,
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TD_B      = S("td_b",      fontName="Helvetica-Bold",  fontSize=7.2, textColor=BLACK,
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LABEL     = S("label",     fontName="Helvetica-Bold",  fontSize=7,   textColor=WHITE,
               alignment=TA_CENTER)
FOOTER_S  = S("footer",    fontName="Helvetica",       fontSize=6.2, textColor=MED_GRY,
               alignment=TA_CENTER)

# ── Helpers ───────────────────────────────────────────────────────────────────
def sp(h=3):
    return Spacer(1, h*mm)

def hr(color=NAVY, thickness=0.6):
    return HRFlowable(width="100%", thickness=thickness, color=color, spaceAfter=2, spaceBefore=2)

def section_header(text, color=NAVY):
    """Coloured section banner."""
    data = [[Paragraph(text, H1)]]
    t = Table(data, colWidths=[PAGE_W - 2*MARGIN])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
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        ("RIGHTPADDING",  (0,0), (-1,-1), 8),
        ("ROUNDEDCORNERS", [3]),
    ]))
    return t

def info_box(title, rows_html, bg=LIGHT_BG, title_color=SKY):
    """Titled info box with bullet-like rows."""
    content = [Paragraph(title, S("ib_title", fontName="Helvetica-Bold", fontSize=8.2,
                                   textColor=title_color, spaceAfter=3))]
    for r in rows_html:
        content.append(Paragraph(r, BULLET))
    data = [[content]]
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    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,-1), bg),
        ("TOPPADDING",    (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING",   (0,0), (-1,-1), 8),
        ("RIGHTPADDING",  (0,0), (-1,-1), 8),
        ("BOX",           (0,0), (-1,-1), 0.5, title_color),
    ]))
    return t

def two_col(left_w, right_w, left_content, right_content, bg_l=WHITE, bg_r=WHITE):
    data = [[left_content, right_content]]
    t = Table(data, colWidths=[left_w, right_w])
    t.setStyle(TableStyle([
        ("VALIGN",        (0,0), (-1,-1), "TOP"),
        ("BACKGROUND",    (0,0), (0,-1), bg_l),
        ("BACKGROUND",    (1,0), (1,-1), bg_r),
        ("LEFTPADDING",   (0,0), (-1,-1), 4),
        ("RIGHTPADDING",  (0,0), (-1,-1), 4),
        ("TOPPADDING",    (0,0), (-1,-1), 3),
        ("BOTTOMPADDING", (0,0), (-1,-1), 3),
    ]))
    return t

def styled_table(headers, rows, col_widths, header_bg=NAVY, stripe=True, fontsize=7.2):
    th_style = S(f"_th{id(headers)}", fontName="Helvetica-Bold", fontSize=fontsize,
                  textColor=WHITE, alignment=TA_CENTER, leading=10)
    td_style = S(f"_td{id(rows)}",   fontName="Helvetica",       fontSize=fontsize,
                  textColor=BLACK, alignment=TA_LEFT, leading=10)
    td_c_sty = S(f"_tdc{id(rows)}",  fontName="Helvetica",       fontSize=fontsize,
                  textColor=BLACK, alignment=TA_CENTER, leading=10)

    data = [[Paragraph(str(h), th_style) for h in headers]]
    for ri, row in enumerate(rows):
        data.append([Paragraph(str(c), td_c_sty if i > 0 else td_style)
                     for i, c in enumerate(row)])

    style_cmds = [
        ("BACKGROUND",    (0,0), (-1,0), header_bg),
        ("ROWBACKGROUNDS",(0,1), (-1,-1),
         [HexColor("#F0F7FF"), WHITE] if stripe else [WHITE]),
        ("GRID",          (0,0), (-1,-1), 0.3, HexColor("#BDC3C7")),
        ("TOPPADDING",    (0,0), (-1,-1), 3),
        ("BOTTOMPADDING", (0,0), (-1,-1), 3),
        ("LEFTPADDING",   (0,0), (-1,-1), 4),
        ("RIGHTPADDING",  (0,0), (-1,-1), 4),
        ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ]
    t = Table(data, colWidths=col_widths)
    t.setStyle(TableStyle(style_cmds))
    return t

def zone_badge(label, bg, fg=WHITE):
    data = [[Paragraph(label, S(f"z{label}", fontName="Helvetica-Bold", fontSize=7.5,
                                 textColor=fg, alignment=TA_CENTER))]]
    t = Table(data, colWidths=[18*mm], rowHeights=[6*mm])
    t.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,-1), bg),
        ("TOPPADDING",    (0,0), (-1,-1), 1),
        ("BOTTOMPADDING", (0,0), (-1,-1), 1),
        ("LEFTPADDING",   (0,0), (-1,-1), 2),
        ("RIGHTPADDING",  (0,0), (-1,-1), 2),
        ("BOX",           (0,0), (-1,-1), 0.3, bg),
    ]))
    return t

# ═══════════════════════════════════════════════════════════════════════════
# PAGE HEADER / FOOTER callbacks
# ═══════════════════════════════════════════════════════════════════════════
def header_footer(canvas, doc):
    canvas.saveState()
    w, h = A4
    # Top banner
    canvas.setFillColor(NAVY)
    canvas.rect(0, h - 10*mm, w, 10*mm, fill=1, stroke=0)
    canvas.setFillColor(SKY)
    canvas.rect(0, h - 10.8*mm, w, 0.8*mm, fill=1, stroke=0)
    canvas.setFont("Helvetica-Bold", 9)
    canvas.setFillColor(WHITE)
    canvas.drawString(MARGIN, h - 7*mm, "BRONCHIAL ASTHMA — Clinical Quick-Reference Guide")
    canvas.setFont("Helvetica", 7.5)
    canvas.drawRightString(w - MARGIN, h - 7*mm, f"Page {doc.page}")
    # Bottom footer
    canvas.setFillColor(LIGHT_GRY)
    canvas.rect(0, 0, w, 9*mm, fill=1, stroke=0)
    canvas.setFont("Helvetica", 6)
    canvas.setFillColor(MED_GRY)
    canvas.drawCentredString(w/2, 3.5*mm,
        "Sources: Murray & Nadel's Respiratory Medicine · Fishman's Pulmonary Diseases · Washington Manual · "
        "Katzung Pharmacology 16e · Rosen's Emergency Medicine · Family Medicine 9e    |    For clinical use — verify against current guidelines")
    canvas.restoreState()

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

# ── COVER BAND ───────────────────────────────────────────────────────────────
cover_data = [[
    Paragraph("BRONCHIAL ASTHMA", TITLE_S),
    Paragraph("Clinical Quick-Reference Guide", SUBTITLE_S),
    Paragraph("GINA 2024 · NHLBI · Murray & Nadel · Katzung · Rosen's EM", SUBTITLE_S),
]]
cover_table = Table([[
    Paragraph("BRONCHIAL ASTHMA", TITLE_S),
]], colWidths=[PAGE_W - 2*MARGIN])
cover_table.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), NAVY),
    ("TOPPADDING",    (0,0), (-1,-1), 8),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING",   (0,0), (-1,-1), 10),
]))
cover_sub = Table([[
    Paragraph("Clinical Quick-Reference Guide  |  GINA 2024 · NHLBI · Pharmacology & Emergency Medicine", SUBTITLE_S),
]], colWidths=[PAGE_W - 2*MARGIN])
cover_sub.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), SKY),
    ("TOPPADDING",    (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
]))
story += [cover_table, cover_sub, sp(4)]

# ════════════════════════════════════════════════════════════════════════════
# SECTION 1 — DEFINITION & PATHOPHYSIOLOGY
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("1.  DEFINITION & PATHOPHYSIOLOGY"))
story.append(sp(2))

def_box = info_box(
    "Definition",
    [
        "Chronic <b>inflammatory</b> disorder of the airways with marked <b>temporal variability in airflow obstruction</b>, often reversible spontaneously or with treatment.",
        "Presents with recurrent <b>wheezing, chest tightness, cough, dyspnea</b> and heightened airway hyperresponsiveness (AHR).",
        "Heterogeneous disease — multiple endotypes; distinct pathophysiologic mechanisms; interplay of genetic and environmental factors.",
    ],
    bg=LIGHT_BG, title_color=SKY
)
story.append(def_box)
story.append(sp(2))

path_rows = [
    ("Bronchoconstriction", "Airway smooth muscle spasm → lumen narrowing"),
    ("Mucosal Oedema",      "Increased vascular permeability, inflammatory cell infiltration"),
    ("Mucus Hypersecretion","Goblet-cell hypertrophy; mucus plugging of small airways"),
    ("Eosinophilic Inflammation", "IL-5 driven; correlates with AHR; T2 phenotype"),
    ("Airway Remodelling",  "Sub-epithelial fibrosis, smooth muscle hypertrophy (chronic/severe disease)"),
]
story.append(styled_table(
    ["Pathologic Feature", "Mechanism / Consequence"],
    path_rows,
    [60*mm, PAGE_W - 2*MARGIN - 60*mm],
    header_bg=TEAL
))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 2 — RISK FACTORS & TRIGGERS
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("2.  RISK FACTORS & TRIGGERS", color=TEAL))
story.append(sp(2))

rf_headers = ["Endogenous Factors", "Environmental Factors", "Acute Triggers"]
rf_rows = [
    ("Atopy / genetic predisposition",   "Indoor allergens (dust mite, cockroach, pet dander)", "Viral URTI (most common trigger)"),
    ("Airway hyperresponsiveness",        "Outdoor allergens (pollens, moulds)",                 "Allergen exposure"),
    ("Gender (boys > girls pre-puberty; women > men post-puberty)", "Tobacco smoke (active & passive)", "Cold/dry air, exercise"),
    ("Obesity",                           "Occupational sensitizers",                            "NSAIDs / aspirin (AERD ~5–10%)"),
    ("",                                  "Respiratory viral infections (early childhood)",       "ACE inhibitors, β-blockers"),
    ("",                                  "Low socioeconomic status",                            "Emotional stress, strong odours"),
]
story.append(styled_table(rf_headers, rf_rows,
    [(PAGE_W - 2*MARGIN)/3]*3, header_bg=NAVY))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 3 — DIAGNOSIS
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("3.  DIAGNOSIS", color=SKY))
story.append(sp(2))

cw2 = (PAGE_W - 2*MARGIN - 4*mm) / 2

left_dx = [
    Paragraph("Spirometry Criteria", H2),
    Paragraph("• FEV₁/FVC ratio <b>reduced</b> (obstructive pattern)", BULLET),
    Paragraph("• Bronchodilator reversibility: FEV₁ ↑ <b>≥12% AND ≥200 mL</b> after SABA", BULLET),
    Paragraph("• PEF diurnal variability <b>>20%</b> supports diagnosis", BULLET),
    Paragraph("• Low FEV₁ = strong predictor of future exacerbations", BULLET),
    sp(2),
    Paragraph("FeNO (Fractional Exhaled NO)", H2),
    Paragraph("• >25 ppb suggests eosinophilic airway inflammation", BULLET),
    Paragraph("• Guides ICS dose titration and biologic selection", BULLET),
]

right_dx = [
    Paragraph("Key Differentials to Exclude", H2),
    Paragraph("• COPD / Asthma-COPD Overlap (ACO)", BULLET),
    Paragraph("• Vocal cord dysfunction / inducible laryngeal obstruction", BULLET),
    Paragraph("• Heart failure", BULLET),
    Paragraph("• GERD-related cough / postnasal drip", BULLET),
    Paragraph("• Bronchiectasis", BULLET),
    Paragraph("• ACE inhibitor cough", BULLET),
    sp(2),
    Paragraph("Validated Control Scores", H2),
    Paragraph("• Asthma Control Test (ACT) — ≤19 = not well controlled", BULLET),
    Paragraph("• Asthma Control Questionnaire (ACQ)", BULLET),
    Paragraph("• Asthma Therapy Assessment Questionnaire (ATAQ)", BULLET),
]

story.append(two_col(cw2, cw2, left_dx, right_dx, bg_l=LIGHT_BG, bg_r=LIGHT_GRN))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 4 — SEVERITY CLASSIFICATION
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("4.  SEVERITY CLASSIFICATION  (NHLBI/GINA — Adults ≥12 years)", color=ORANGE))
story.append(sp(2))

sev_h = ["Component", "Intermittent", "Mild Persistent", "Moderate Persistent", "Severe Persistent"]
sev_r = [
    ("Daytime symptoms",    "≤2 days/week",  ">2 d/wk, not daily",  "Daily",            "Throughout day"),
    ("Night awakenings",    "≤2×/month",     "3–4×/month",          ">1×/wk, not nightly","Often 7×/week"),
    ("Rescue SABA use",     "≤2 days/week",  ">2 d/wk, not daily",  "Daily",            "Several times/day"),
    ("Activity limitation", "None",          "Minor",               "Some",             "Extremely limited"),
    ("FEV₁ (% predicted)",  ">80%",          ">80%",                ">60% but <80%",    "<60%"),
    ("FEV₁/FVC",            "Normal",        "Normal",              "Reduced 5%",       "Reduced 5%"),
    ("OCS exacerbations",   "0–1/year",      "≥2/year",             "—",                "—"),
    ("Start at Step →",     "Step 1",        "Step 2",              "Step 3",           "Step 4–5"),
]
cw_sev = [(PAGE_W-2*MARGIN)*x for x in [0.24, 0.19, 0.19, 0.19, 0.19]]
story.append(styled_table(sev_h, sev_r, cw_sev, header_bg=ORANGE))
story.append(sp(2))

# GINA Control
gina_note = info_box("GINA Control Categories (for ongoing monitoring — use these after initiating therapy)",
    [
        "<b>Controlled</b> — All criteria met: no daytime sx >2×/wk, no awakenings, no limitation, SABA ≤2×/wk, normal lung function → Maintain or step down",
        "<b>Partly Controlled</b> — 1–2 criteria present → Consider step up",
        "<b>Uncontrolled</b> — 3–4 criteria present → Step up until controlled",
        "<b>Exacerbation</b> — Treat per acute exacerbation algorithm",
    ], bg=LIGHT_YLW, title_color=ORANGE)
story.append(gina_note)
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 5 — STEPWISE CHRONIC MANAGEMENT
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("5.  STEPWISE CHRONIC MANAGEMENT  (GINA 2024)", color=NAVY))
story.append(sp(2))

story.append(Paragraph("▶  TRACK 1 (Preferred) — ICS-Formoterol as Reliever", H2))
story.append(Paragraph(
    "Using ICS-formoterol as reliever <b>reduces exacerbation risk</b> vs. SABA reliever — recommended by GINA as the preferred track.",
    BODY))
story.append(sp(1))

t1_h = ["Step", "Preferred Controller", "Preferred Reliever", "Notes"]
t1_r = [
    ("Step 1", "As-needed low-dose ICS-formoterol", "As-needed low-dose ICS-formoterol", "Mild intermittent; no daily controller needed"),
    ("Step 2", "Low-dose ICS (daily), OR as-needed ICS-formoterol", "As-needed low-dose ICS-formoterol", "Persistent symptoms; add daily ICS"),
    ("Step 3", "Low-dose ICS-formoterol (maintenance)", "As-needed low-dose ICS-formoterol", "Single inhaler therapy (MART)"),
    ("Step 4", "Medium-dose ICS-formoterol (maintenance)", "As-needed low-dose ICS-formoterol", "Uncontrolled on Step 3"),
    ("Step 5", "High-dose ICS-LABA + add-on LAMA;\nRefer for phenotyping ± biologic", "As-needed low-dose ICS-formoterol", "Severe refractory; see biologic table"),
]
cw_t1 = [(PAGE_W-2*MARGIN)*x for x in [0.08, 0.31, 0.28, 0.33]]
story.append(styled_table(t1_h, t1_r, cw_t1, header_bg=NAVY))
story.append(sp(2))

story.append(Paragraph("▶  TRACK 2 (Alternative) — SABA Reliever  (if adherence with daily ICS is likely)", H2))
t2_r = [
    ("Step 1", "Take ICS whenever SABA taken (concomitant use)", "SABA as needed"),
    ("Step 2", "Low-dose ICS daily", "SABA as needed"),
    ("Step 3", "Low-dose ICS-LABA daily", "SABA as needed"),
    ("Step 4", "Medium-dose ICS-LABA daily", "SABA as needed"),
    ("Step 5", "High-dose ICS-LABA + add-ons ± biologic", "SABA as needed"),
]
cw_t2 = [(PAGE_W-2*MARGIN)*x for x in [0.08, 0.54, 0.38]]
story.append(styled_table(["Step", "Controller", "Reliever"], t2_r, cw_t2, header_bg=TEAL))
story.append(sp(2))

step_up_box = info_box(
    "⚠  Before Stepping Up — Exclude These Modifiable Factors First",
    [
        "<b>Non-adherence to ICS</b> — most common cause of poor control; linked to exacerbations, hospitalisation, accelerated lung-function decline",
        "<b>Incorrect inhaler technique</b> — reassess at every visit",
        "<b>Ongoing allergen / irritant exposure</b> — occupational, domestic",
        "<b>Comorbidities:</b> Obesity · Sinonasal disease / rhinitis · GERD · OSA · Depression / anxiety",
        "<b>Alternative diagnosis</b> — see differential list (Section 3)",
    ], bg=LIGHT_YLW, title_color=ORANGE)
story.append(step_up_box)
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 6 — PHARMACOLOGY
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("6.  PHARMACOLOGICAL AGENTS", color=TEAL))
story.append(sp(2))

pharm_h  = ["Drug Class", "Examples", "Mechanism", "Key Clinical Notes"]
pharm_r = [
    ("SABA\n(Reliever)",
     "Albuterol (salbutamol)\nLevalbuterol",
     "β₂ agonist → ↑cAMP → smooth muscle relaxation; also ↓vascular permeability",
     "Rapid onset; peak 60–90 min. >2×/wk = inadequate control → step up. Risk of receptor desensitisation with overuse."),
    ("LABA\n(Controller — always with ICS)",
     "Formoterol\nSalmeterol\nVilanterol",
     "Long-acting β₂ agonist. Formoterol has faster onset; ultra-LABAs once-daily.",
     "NEVER as monotherapy. Formoterol enables MART regimen. Improve FEV₁, symptoms, exacerbation frequency."),
    ("ICS\n(Cornerstone)",
     "Beclomethasone\nBudesonide\nFluticasone\nCiclesonide",
     "Suppress airway eosinophilic inflammation; ↓AHR; ↓mucus",
     "Start low-to-medium dose (e.g., BDP 200 µg BID). Non-adherence = #1 risk factor for exacerbations and death."),
    ("ICS-LABA Combo",
     "Budesonide/formoterol\nFluticasone/salmeterol\nFluticasone/vilanterol",
     "Combined anti-inflammatory + bronchodilator",
     "Preferred fixed-dose combination from Step 3 onward. MART = maintenance AND reliever therapy (budesonide/formoterol only)."),
    ("LAMA\n(Add-on Step 4–5)",
     "Tiotropium\nUmeclidinium",
     "Long-acting muscarinic antagonist → bronchodilation via M3 blockade",
     "Add-on to ICS-LABA; improves FEV₁ and reduces exacerbations. Once-daily inhaled."),
    ("Leukotriene\nModifiers",
     "Montelukast 10 mg OD\nZafirlukast 20 mg BD\nZileuton 1200 mg BD SR",
     "Block CysLT receptors (montelukast, zafirlukast) or inhibit 5-lipoxygenase (zileuton) → ↓bronchoconstriction, oedema, mucus",
     "Oral route. Less effective than ICS alone. Particularly effective in AERD and exercise-induced asthma. Montelukast approved ≥12 months."),
    ("Methylxanthines",
     "Theophylline",
     "Phosphodiesterase inhibitor → ↑cAMP; also anti-inflammatory at low doses",
     "Last-line only. Narrow therapeutic window (target 5–15 µg/mL). Multiple drug interactions. Monitor levels."),
]
cw_ph = [(PAGE_W-2*MARGIN)*x for x in [0.14, 0.18, 0.28, 0.40]]
story.append(styled_table(pharm_h, pharm_r, cw_ph, header_bg=TEAL, fontsize=7.0))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 7 — BIOLOGIC THERAPIES
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("7.  BIOLOGIC THERAPIES  (Step 5 — Severe Refractory Asthma)", color=HexColor("#6C3483")))
story.append(sp(2))
story.append(Paragraph(
    "Phenotypic assessment required before biologic selection: <b>blood eosinophil count, total IgE, FeNO, allergen sensitisation (RAST/skin prick).</b>",
    BODY))
story.append(sp(1))

bio_h = ["Drug", "Target", "Phenotype / Indication", "Dosing", "Key Effect"]
bio_r = [
    ("Omalizumab",   "IgE",            "Moderate–severe atopic asthma\nElevated IgE + perennial allergen sensitisation",
     "SC q2–4wk\n(dose by IgE + weight)",     "↓exacerbations 88% hospitalisation rate; ↓OCS need"),
    ("Mepolizumab",  "IL-5",           "Severe eosinophilic asthma\nEos ≥300 cells/µL",
     "SC 100 mg q4wk",                        "↓exacerbations; ↓OCS dose; ↑FEV₁"),
    ("Reslizumab",   "IL-5",           "Severe eosinophilic asthma\nEos ≥400 cells/µL",
     "IV 3 mg/kg q4wk\n(20–50 min infusion)", "↑FEV₁; ↓exacerbations; risk of anaphylaxis (0.3%)"),
    ("Benralizumab", "IL-5Rα",         "Severe eosinophilic asthma\nEos ≥300 cells/µL",
     "SC 30 mg q4wk×3,\nthen q8wk",           "Depletes eosinophils from blood, airway, bone marrow; ↓OCS"),
    ("Dupilumab",    "IL-4Rα\n(IL-4+IL-13)", "Moderate–severe eosinophilic asthma\nOCS-dependent; atopic dermatitis; CRSwNP\nAge ≥12 yrs",
     "SC 200–300 mg\nq2wk (loading × 2 first)", "↓exacerbations; ↓OCS; ↑FEV₁. Transient eosinophilia first 4 months."),
    ("Tezepelumab",  "TSLP",           "Severe asthma\n(any phenotype — does not require eosinophilia)",
     "SC 210 mg q4wk",                        "Broad anti-inflammatory; ↓exacerbations regardless of T2 status"),
]
cw_bio = [(PAGE_W-2*MARGIN)*x for x in [0.13, 0.10, 0.25, 0.18, 0.34]]
story.append(styled_table(bio_h, bio_r, cw_bio, header_bg=HexColor("#6C3483"), fontsize=6.9))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 8 — ACUTE EXACERBATION MANAGEMENT
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("8.  ACUTE EXACERBATION MANAGEMENT", color=RED_ALERT))
story.append(sp(2))

# High-risk flags
risk_box = info_box(
    "🚨  High-Risk Features — Low Threshold for Admission / ICU",
    [
        "Prior intubation or mechanical ventilation for asthma",
        "ED visit or hospitalisation for asthma in past 12 months",
        "Currently on / recently stopped oral corticosteroids",
        "Not on ICS controller therapy",
        "Overuse of SABA (>1 canister/month)",
        "Poor adherence; no written asthma action plan; comorbid psychiatric illness",
        "Food allergy in a patient with asthma",
    ], bg=LIGHT_RED, title_color=RED_ALERT)
story.append(risk_box)
story.append(sp(2))

# ABG warning
abg_box = info_box(
    "ABG Interpretation in Acute Asthma",
    [
        "Early: <b>Mild hypoxaemia + respiratory alkalosis</b> (↓PaCO₂)",
        "<b>Normalising PaCO₂ in an unimproving patient = DANGER SIGN → impending respiratory failure</b>",
        "Late / severe: Rising PaCO₂ + metabolic acidosis (↑lactate) → urgent ITU review",
    ], bg=LIGHT_RED, title_color=RED_ALERT)
story.append(abg_box)
story.append(sp(2))

# Treatment table
tx_h = ["Severity", "Bronchodilator", "Corticosteroid", "Adjuncts / Disposition"]
tx_r = [
    ("Mild–Moderate\nPEF 40–70%\nSpO₂ ≥92%\nSpeech intact",
     "Albuterol 2–6 puffs MDI + spacer OR 2.5 mg neb q20min × 3\nAdd ipratropium 0.5 mg q20min",
     "Prednisone PO 40–60 mg/day (oral = IV if equivalent dose)",
     "Reassess after 60–90 min. If PEF >70% + good response → discharge with OCS 5–7 days + ICS ↑"),
    ("Severe\nPEF <40%\nSpO₂ <92%\nAccessory muscles\nCannot complete sentences",
     "Albuterol 2.5–5 mg + ipratropium 0.5 mg q20min neb\nOR continuous neb albuterol 10–15 mg/hr (with telemetry)\nConsider IV/SC epinephrine",
     "IV methylprednisolone 1–2 mg/kg\nOral equivalent acceptable if tolerated",
     "IV MgSO₄ 2 g over 20 min (refractory after 1 hr)\nHeliox 70:30 (refractory)\nHospital admission"),
    ("Life-threatening\nSilent chest\nCyanosis\nAltered consciousness\nFatigue",
     "Continuous neb bronchodilator\nConsider IV bronchodilator (salbutamol IV)",
     "IV methylprednisolone high-dose",
     "ITU / HDU admission\nNIV or mechanical ventilation\nPermissive hypercapnia\nAnaesthesia review"),
]
cw_tx = [(PAGE_W-2*MARGIN)*x for x in [0.16, 0.30, 0.22, 0.32]]
story.append(styled_table(tx_h, tx_r, cw_tx, header_bg=RED_ALERT, fontsize=7.0))
story.append(sp(2))

# Discharge criteria
dc_box = info_box(
    "Discharge Criteria & Plan",
    [
        "PEF or FEV₁ <b>≥70% predicted</b> (sustained ≥60 min after last bronchodilator)",
        "SpO₂ ≥92% on room air · Minimal symptoms · Tolerating oral medication",
        "<b>Discharge medications:</b> Prednisone 40 mg/day × 5–7 days + initiate or increase ICS dose",
        "Provide written Asthma Action Plan; review inhaler technique; arrange follow-up within 1–2 weeks",
    ], bg=LIGHT_GRN, title_color=TEAL)
story.append(dc_box)
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 9 — PEF ACTION PLAN ZONES
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("9.  PEAK FLOW (PEF) ACTION PLAN ZONES", color=GREEN))
story.append(sp(2))

zone_h = ["Zone", "PEF (% Personal Best)", "Symptoms", "Action"]
zone_r = [
    ("🟢 GREEN", ">80%",   "None or minimal; normal activity",        "Continue current medications; no change needed"),
    ("🟡 YELLOW","60–80%", "Some symptoms; activity may be limited",  "Increase rescue SABA; consider doubling ICS or starting OCS; contact clinician if no improvement in 24 hrs"),
    ("🔴 RED",   "<60%",   "Severe symptoms; activity severely limited","Immediate SABA; start OCS (prednisone 40–60 mg); SEEK EMERGENCY CARE if no rapid improvement"),
]
cw_z = [(PAGE_W-2*MARGIN)*x for x in [0.11, 0.18, 0.30, 0.41]]
story.append(styled_table(zone_h, zone_r, cw_z, header_bg=GREEN))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 10 — SPECIAL SITUATIONS
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("10.  SPECIAL SITUATIONS", color=HexColor("#1F618D")))
story.append(sp(2))

spec_h = ["Situation", "Key Considerations", "Specific Treatment"]
spec_r = [
    ("Exercise-Induced\nBronchoconstriction (EIB)",
     "Stimulus: airway dehydration → ↑osmolarity → histamine/LT/PG release → SM contraction",
     "SABA 5–10 min pre-exercise (first-line). ICS strongly recommended. LABA + ICS if ICS insufficient. Montelukast, cromolyn, ipratropium also effective."),
    ("Cough-Variant Asthma",
     "Chronic cough as sole manifestation; often nocturnal; confirm with methacholine challenge",
     "Treat as standard asthma. Exclude: ACE inhibitors, GERD, postnasal drip, laryngeal dysfunction."),
    ("AERD (Aspirin-Exacerbated\nRespiratory Disease)",
     "~5–10% of asthmatics. Triad: asthma + CRSwNP + NSAID sensitivity (COX-1 inhibition). Not IgE-mediated.",
     "Avoid all NSAIDs/aspirin. Leukotriene modifiers are especially effective. Consider aspirin desensitisation in specialist centre."),
    ("Occupational Asthma",
     "Sensitiser-induced (true OA) vs. irritant-induced. Variable patterns related to work schedule.",
     "Remove from exposure promptly. Standard pharmacotherapy. Serial PEF monitoring at/away from work."),
    ("Perimenstrual Asthma",
     "Affects ~40% of asthmatic women. Premenstrual worsening likely progesterone/oestrogen mediated.",
     "Optimise baseline controller. Consider short-course OCS premenstrually if severe. OCP may help in some."),
    ("Brittle Asthma",
     "Type I: chaotic daily PEF variability. Type II: normal baseline but abrupt catastrophic falls.",
     "Maximise controller therapy. SC epinephrine auto-injector at all times. Medical alert ID. Specialist referral."),
]
cw_sp = [(PAGE_W-2*MARGIN)*x for x in [0.17, 0.33, 0.50]]
story.append(styled_table(spec_h, spec_r, cw_sp, header_bg=HexColor("#1F618D"), fontsize=7.0))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 11 — NON-PHARMACOLOGICAL / PATIENT EDUCATION
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("11.  NON-PHARMACOLOGICAL MANAGEMENT & PATIENT EDUCATION", color=TEAL))
story.append(sp(2))

cw2b = (PAGE_W - 2*MARGIN - 4*mm) / 2
left_np = [
    Paragraph("Trigger Avoidance", H2),
    Paragraph("• House dust mite reduction — complete removal ↓ AHR", BULLET),
    Paragraph("• Pet allergen avoidance / removal from home", BULLET),
    Paragraph("• Occupational sensitiser removal (earlier = better prognosis)", BULLET),
    Paragraph("• Smoking cessation (active + passive smoke)", BULLET),
    Paragraph("• NSAID / aspirin avoidance in AERD", BULLET),
    sp(2),
    Paragraph("Vaccinations (CDC Recommendations)", H2),
    Paragraph("• Annual <b>influenza vaccine</b> (inactivated) for all adult asthmatics", BULLET),
    Paragraph("• <b>Pneumovax (PPSV23)</b> — single dose, adults 19–64 with chronic illness including asthma", BULLET),
    sp(2),
    Paragraph("Comorbidity Management", H2),
    Paragraph("• Obesity: weight loss improves control", BULLET),
    Paragraph("• GERD: PPI therapy; dietary modification", BULLET),
    Paragraph("• Rhinosinusitis / nasal polyps: intranasal ICS; consider biologic", BULLET),
    Paragraph("• OSA: CPAP therapy", BULLET),
    Paragraph("• Depression / anxiety: psychological support", BULLET),
]

right_np = [
    Paragraph("Written Asthma Action Plan (AAP)", H2),
    Paragraph("• <b>Evidence-based</b>: ↓ ED visits, hospitalisations, morbidity", BULLET),
    Paragraph("• Most effective when combined with individual/group education sessions", BULLET),
    Paragraph("• Include: zone-based instructions, OCS self-start criteria, emergency contacts", BULLET),
    Paragraph("• Use simple language; tailor to patient's literacy and capability", BULLET),
    sp(2),
    Paragraph("Patient Education Must Cover", H2),
    Paragraph("• Nature of asthma (inflammatory vs. bronchospasm)", BULLET),
    Paragraph("• <b>Inhaler technique</b> — assess and correct at every visit", BULLET),
    Paragraph("• Controller vs. reliever distinction — common source of confusion", BULLET),
    Paragraph("• Trigger recognition and self-monitoring", BULLET),
    Paragraph("• When to step up / seek emergency care", BULLET),
    Paragraph("• Digital tools / apps may improve adherence and predict exacerbations", BULLET),
    sp(2),
    Paragraph("Follow-Up Schedule", H2),
    Paragraph("• 2–6 weeks after initiating therapy — assess control achieved", BULLET),
    Paragraph("• Every visit on controller — check control; consider step-down if controlled ≥3 months", BULLET),
    Paragraph("• Annually: spirometry, vaccination review, exacerbation history", BULLET),
    Paragraph("• Step-down: reduce ICS by ~25–50%; avoid during high-risk seasons", BULLET),
]

story.append(two_col(cw2b, cw2b, left_np, right_np, bg_l=LIGHT_GRN, bg_r=LIGHT_BG))
story.append(sp(4))

# ════════════════════════════════════════════════════════════════════════════
# SECTION 12 — QUICK REFERENCE CARD
# ════════════════════════════════════════════════════════════════════════════
story.append(section_header("12.  QUICK-REFERENCE SUMMARY CARD", color=NAVY))
story.append(sp(2))

qr_h = ["Clinical Situation", "First-Line Treatment", "Key Points"]
qr_r = [
    ("Mild intermittent (Step 1)", "As-needed low-dose ICS-formoterol (Track 1 preferred)", "No daily controller required; address triggers"),
    ("Mild–moderate persistent (Steps 2–3)", "Low-dose ICS daily ± LABA (formoterol combo); MART from Step 3", "Reassess adherence and technique before step-up"),
    ("Moderate–severe persistent (Steps 4–5)", "Medium–high dose ICS-LABA ± LAMA; biologic if refractory", "Phenotype assessment (eosinophils, IgE, FeNO)"),
    ("Acute mild–moderate exacerbation", "SABA q20min ×3 + ipratropium; oral prednisone 40–60 mg", "Reassess at 60–90 min; discharge if PEF >70%"),
    ("Acute severe exacerbation", "Continuous neb albuterol; IV methylprednisolone; IV MgSO₄ 2 g if refractory", "Admit; monitor PCO₂; ICU if deteriorating"),
    ("Life-threatening / impending respiratory failure", "Continuous bronchodilators; high-dose IV steroids; consider IV salbutamol", "ICU admission; mechanical ventilation; permissive hypercapnia"),
    ("Exercise-induced bronchoconstriction", "SABA 5–10 min pre-exercise; ICS daily; montelukast add-on", "Warm-up exercises; face mask in cold air"),
    ("AERD", "Avoid ALL NSAIDs; leukotriene modifiers (montelukast)", "Consider specialist aspirin desensitisation"),
    ("Allergic / T2-high severe asthma (Step 5)", "Omalizumab (anti-IgE) for elevated IgE + allergen sensitisation", "Sub-cut q2–4wk; dose adjusted by IgE + body weight"),
    ("Eosinophilic severe asthma (Step 5)", "Mepolizumab / benralizumab / reslizumab (anti-IL-5/IL-5R)", "Blood eos ≥300 cells/µL; ↓OCS dose; ↓exacerbations"),
    ("T2-high (eos + atopic) or OCS-dependent", "Dupilumab (anti-IL-4Rα) — blocks IL-4 + IL-13", "Effective regardless of eos in OCS-dependent disease"),
    ("Severe asthma, any phenotype", "Tezepelumab (anti-TSLP)", "Broadest eligibility; does not require eosinophilia"),
]
cw_qr = [(PAGE_W-2*MARGIN)*x for x in [0.22, 0.38, 0.40]]
story.append(styled_table(qr_h, qr_r, cw_qr, header_bg=NAVY, fontsize=7.2))
story.append(sp(3))

story.append(Paragraph(
    "Sources: Murray &amp; Nadel's Textbook of Respiratory Medicine · Fishman's Pulmonary Diseases and Disorders · "
    "The Washington Manual of Medical Therapeutics · Katzung's Basic and Clinical Pharmacology 16e · "
    "Rosen's Emergency Medicine · Textbook of Family Medicine 9e · Harriet Lane Handbook 23e",
    SMALL))

# ════════════════════════════════════════════════════════════════════════════
# BUILD
# ════════════════════════════════════════════════════════════════════════════
doc.build(story, onFirstPage=header_footer, onLaterPages=header_footer)
print(f"PDF saved to: {OUTPUT}")
print(f"Size: {os.path.getsize(OUTPUT):,} bytes")