Why mannitol is contraindicated in acute pulmonary edema

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I now have comprehensive, textbook-confirmed information. Here is the full answer:

Why Mannitol is Contraindicated in Acute Pulmonary Edema

The contraindication arises from mannitol's mechanism of action, specifically its biphasic fluid-shifting effect before diuresis occurs.

1. The Core Problem: Transient Intravascular Volume Expansion

Mannitol is a hypertonic, osmotically active agent. When administered IV, it cannot enter cells and stays in the extracellular space. Before any diuresis occurs, it creates a powerful osmotic gradient that pulls water out of cells and into the intravascular compartment.

"Mannitol is rapidly distributed in the extracellular compartment and extracts water from cells. Prior to the diuresis, this leads to expansion of the extracellular volume... This effect can complicate heart failure and may produce florid pulmonary edema."

Katzung's Basic and Clinical Pharmacology, 16th Ed.

"Because mannitol expands the ECFV [extracellular fluid volume] en route to its diuretic site of action, it may precipitate pulmonary edema in HF patients and must be used cautiously in this circumstance, if at all."

NKF Primer on Kidney Diseases, 8th Ed.

2. Mechanism Step-by-Step

Step	What Happens	Effect
1. Mannitol given IV	Stays in extracellular compartment (not reabsorbed)	Raises plasma osmolality
2. Osmotic gradient created	Water shifts from intracellular to extracellular space	Acutely expands intravascular volume
3. Increased hydrostatic pressure	Fluid is pushed into pulmonary capillaries	Worsens pulmonary edema
4. Diuresis (delayed)	Eventually excreted via kidneys, with water	Comes too late if cardiac/renal reserve is limited

The problem is the timing gap - the volume expansion happens immediately, but the diuretic effect is delayed (onset 30-60 minutes). In a patient already drowning in fluid, this initial surge of intravascular volume is dangerous.

3. Additional Compounding Factors

Hemodilution / Hyponatremia: The rapid influx of water into plasma dilutes sodium, causing transient hyponatremia. This can further impair cardiac function.
Limited cardiac reserve: In acute pulmonary edema, the heart is already failing to handle its preload. Any additional increase in venous return will directly worsen pulmonary congestion.
Renal compromise: In anuric/severely oliguric patients (common in cardiogenic edema), mannitol cannot be excreted and accumulates, perpetuating the osmotic volume load indefinitely.

"A rapid intracellular-to-extracellular shift of water can transiently increase intravascular volume and precipitate cardiac decompensation and pulmonary edema in patients with limited cardiac reserve."

Morgan & Mikhail's Clinical Anesthesiology, 7th Ed.

4. What to Use Instead

In acute pulmonary edema, the correct diuretic class is loop diuretics (e.g., furosemide/lasix), which:

Reduce preload rapidly via venodilation (within minutes, before diuresis)
Promote net fluid removal from the intravascular space
Do not expand volume before working

Summary

Mannitol is contraindicated in acute pulmonary edema because its osmotic mechanism causes an acute, transient expansion of intravascular volume by drawing water out of cells before any diuresis can occur. In a patient with pulmonary edema - where the lungs are already flooded due to elevated capillary hydrostatic pressure - this added fluid load dramatically worsens the condition and can be life-threatening.

Can you simplify asthma from fishman and gina 2026

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GINA 2026 asthma guidelines key updates summary

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https://www.pulmonologyadvisor.com/features/asthma-gina-2026…

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Here is a simplified but complete breakdown of asthma from Fishman's Pulmonary Diseases and Disorders combined with GINA 2026:

Asthma - Simplified

Sources: Fishman's Pulmonary Diseases and Disorders + GINA 2026 Strategy Report

1. What Is Asthma?

GINA 2026 definition:

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by a history of respiratory symptoms - wheeze, shortness of breath, chest tightness, and cough - that vary over time and in intensity, together with variable expiratory airflow limitation.

Three core features (Fishman's):

Bronchoconstriction - airway smooth muscle contracts
Airway hyperresponsiveness (AHR) - airways over-react to triggers
Chronic airway inflammation - the underlying driver of everything else

2. Pathophysiology (The "Why")

Two Main Inflammatory Pathways

Inflammatory pathways in asthma - Fishman's Pulmonary Diseases and Disorders

Pathway	Driver	Key Cells	Result
T2 (Type 2) - 65-80% of patients	Allergens, alarmins	Th2, ILC2, eosinophils, mast cells	Eosinophilic inflammation, IgE production
Non-T2	Smoke, pollutants, infections	Th1, Th17 cells	Neutrophilic inflammation

The Allergic (T2) Cascade - Step by Step

Allergen enters airway - trapped in mucus, endocytosed by dendritic cells
Dendritic cells activate naive T cells - polarize toward Th2
Th2 cells release cytokines: IL-4, IL-5, IL-13
- IL-4 and IL-13 - drive IgE production by B cells
- IL-5 - recruits and activates eosinophils
IgE binds to mast cells - on re-exposure to allergen, mast cells degranulate
Mast cells release histamine, prostaglandins, leukotrienes - causing bronchoconstriction, mucus, vascular leak
Eosinophils cause further airway damage and inflammation

Alarmins (Innate Pathway - Important in GINA 2026)

The bronchial epithelium releases alarm signals in response to injury:

TSLP (target of tezepelumab)
IL-33 (target of itepekimab)
IL-25

These activate ILC2 cells, linking innate and adaptive responses.

Airway Remodeling (Chronic Disease)

With repeated injury, structural changes occur:

Basement membrane thickening
Goblet cell metaplasia (excess mucus)
Smooth muscle hypertrophy/hyperplasia
Submucosal fibrosis
Irreversible airflow obstruction in severe chronic cases

3. Phenotypes (GINA 2026)

Phenotype	Features	Treatment Implication
Allergic asthma	Childhood onset, family/personal atopy, responds to ICS	Most common
Non-allergic asthma	No atopy, neutrophilic/paucigranulocytic	Less ICS-responsive
Late-onset eosinophilic	Adult women, high blood eosinophils	Biologic-responsive
Exercise-induced	Triggered by exertion	Pre-treatment with SABA
Aspirin/NSAID-sensitive	Nasal polyps, chronic sinusitis	Avoid NSAIDs
Obesity-associated	Non-eosinophilic, mechanically driven	Weight loss helps

4. Diagnosis

Symptoms to look for:

Wheeze (high-pitched expiratory)
Episodic breathlessness
Chest tightness
Cough (especially at night / early morning)
Symptoms vary - worse at night, with exercise, allergen exposure, infections

Spirometry (Key test):

Obstructive pattern: FEV1/FVC < 0.7 (or below lower limit of normal)
Reversibility: FEV1 increases ≥12% and ≥200 mL after bronchodilator = confirms asthma
Variability: Peak flow variation >10% on multiple days also supports diagnosis

Supportive Tests (when spirometry is normal):

FeNO (fractional exhaled nitric oxide) - elevated in T2 eosinophilic asthma
Blood eosinophils - elevated supports T2 asthma
Methacholine challenge (PC20) - confirms airway hyperresponsiveness

Asthma Control Assessment (GINA 2026):

Level	Daytime symptoms	Night waking	Reliever use	Activity limitation
Controlled	≤2x/week	None	≤2x/week	None
Partly controlled	>2x/week	Any	>2x/week	Any
Uncontrolled	3+ features of partly controlled

New GINA 2026 tools: CAAT (Chronic Airways Assessment Test), Peds-AIRQ (pediatric), PRAM (acute pediatric exacerbations)

5. Treatment - The Stepwise Approach

GINA/Fishman's principle: treat to achieve control, then step down. The goal is minimal or no symptoms with the lowest effective treatment.

Adults and Adolescents

Step	Preferred Controller	Preferred Reliever	Notes
Step 1 (mild intermittent)	Low-dose ICS-formoterol as needed	ICS-formoterol (not just SABA alone)	GINA 2026 pushes anti-inflammatory even at Step 1
Step 2 (mild persistent)	Low-dose ICS daily	ICS-formoterol or SABA	LTRA as alternative
Step 3 (moderate)	Low-dose ICS-LABA	ICS-formoterol	SMART strategy begins here
Step 4 (uncontrolled on Step 3)	Medium-dose ICS-LABA	ICS-formoterol	Add LAMA (tiotropium)
Step 5 (severe)	High-dose ICS-LABA + specialist review	ICS-formoterol	Add biologics; minimize OCS

Key GINA 2026 Changes:

SABA monotherapy is out at Step 1 - replace with ICS-formoterol as reliever
ICS-formoterol (SMART) is the preferred strategy at Steps 3-5 (one inhaler for both controller and reliever)
OCS minimization - optimize ICS, treat modifiable risk factors before using oral steroids
Oxygen target in acute asthma: SpO2 92-95% (not 100%) - updated threshold

6. Drug Classes - Quick Summary

Bronchodilators

SABA (salbutamol/albuterol, terbutaline) - rapid relief, short-acting. Overuse = poor control indicator
LABA (formoterol, salmeterol) - long-acting, must always be combined with ICS, never monotherapy
LAMA (tiotropium) - add-on at Step 4; reduces exacerbations

Controllers

ICS (budesonide, beclomethasone, fluticasone) - cornerstone of treatment, reduces airway inflammation
LTRA (montelukast) - alternative/add-on, less effective than ICS
Theophylline - rarely used, narrow therapeutic index

Biologics (Step 5 - Severe Asthma)

Drug	Target	For
Omalizumab	IgE	Allergic asthma
Mepolizumab, Reslizumab	IL-5	Eosinophilic asthma
Benralizumab	IL-5 receptor	Eosinophilic asthma
Dupilumab	IL-4Rα (blocks IL-4 and IL-13)	Eosinophilic / type 2
Tezepelumab	TSLP	Broad (all phenotypes)
Depemokimab (new 2026)	IL-5 (ultra-long acting)	Eosinophilic asthma

7. Acute Exacerbations (GINA 2026 Updated Flowcharts)

Severity Classification:

Severity	SpO2	RR	Speech	Wheeze
Mild	≥94%	Normal/mild increase	Full sentences	Mild
Moderate	90-93%	Increased	Phrases	Moderate
Severe/Life-threatening	<92%	>30/min	Words or unable	Silent chest

Treatment:

Mild: Salbutamol 4 puffs (pMDI + spacer) OR budesonide-formoterol 2 puffs
Moderate-Severe: Salbutamol 6-10 puffs repeated every 20-30 min + ipratropium 4 puffs (up to 3 doses) + systemic corticosteroids + controlled O2 (target 92-95%)
Anaphylaxis + asthma: Give epinephrine first, then salbutamol
Life-threatening: Transfer to acute care, IV magnesium sulfate, consider intubation

8. Red Flags for Fatal Asthma (GINA 2026)

Previous near-fatal attack (intubated, ICU admission)
Hospitalization or ER visit in past year
Currently not on ICS, or poor adherence
Overuse of SABA (>1 canister/month)
Psychosocial problems or low socioeconomic status
Food allergy with asthma
Smoking

One-Line Summary

Asthma = chronic variable airway inflammation + bronchoconstriction + hyperresponsiveness, driven mainly by T2 cytokines (IL-4, IL-5, IL-13). GINA 2026 moves toward anti-inflammatory reliever therapy (ICS-formoterol) at all steps, discourages SABA-only use, and expands biologic options for severe disease with a new SpO2 target of 92-95% in acute attacks.

Create a PDF cheat sheet of GINA 2026 asthma stepwise treatment

Reading File

Running Command

ls /home/daytona/workspace/ 2>/dev/null && echo "---" && python3 -c "import repo…

Running Command

mkdir -p /home/daytona/workspace/gina2026-cheatsheet

Writing File

~/gina2026-cheatsheet/generate_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether
)
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT
from reportlab.platypus import BaseDocTemplate, Frame, PageTemplate

OUTPUT = "/home/daytona/workspace/gina2026-cheatsheet/GINA_2026_Asthma_Stepwise_Cheatsheet.pdf"

# ── Colour palette ──────────────────────────────────────────────────────────
BLUE_DARK   = colors.HexColor("#1a3a5c")
BLUE_MID    = colors.HexColor("#2563a8")
BLUE_LIGHT  = colors.HexColor("#dbeafe")
TEAL        = colors.HexColor("#0d9488")
TEAL_LIGHT  = colors.HexColor("#ccfbf1")
ORANGE      = colors.HexColor("#d97706")
ORANGE_LIGHT= colors.HexColor("#fef3c7")
RED         = colors.HexColor("#dc2626")
RED_LIGHT   = colors.HexColor("#fee2e2")
GREEN       = colors.HexColor("#16a34a")
GREEN_LIGHT = colors.HexColor("#dcfce7")
PURPLE      = colors.HexColor("#7c3aed")
PURPLE_LIGHT= colors.HexColor("#ede9fe")
GREY_LIGHT  = colors.HexColor("#f1f5f9")
GREY_MED    = colors.HexColor("#94a3b8")
WHITE       = colors.white
BLACK       = colors.HexColor("#0f172a")

W, H = A4   # 595.27 x 841.89 pt

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

def S(name, **kw):
    return ParagraphStyle(name, **kw)

title_style = S("Title2",
    fontName="Helvetica-Bold", fontSize=18, textColor=WHITE,
    alignment=TA_CENTER, leading=22)
subtitle_style = S("Sub2",
    fontName="Helvetica", fontSize=9, textColor=colors.HexColor("#bfdbfe"),
    alignment=TA_CENTER, leading=12)
section_header = S("SecHdr",
    fontName="Helvetica-Bold", fontSize=10, textColor=WHITE,
    alignment=TA_CENTER, leading=13, spaceAfter=2)
body = S("Body2",
    fontName="Helvetica", fontSize=8, textColor=BLACK,
    leading=11, spaceAfter=1)
body_bold = S("BodyB",
    fontName="Helvetica-Bold", fontSize=8, textColor=BLACK,
    leading=11, spaceAfter=1)
small = S("Small",
    fontName="Helvetica", fontSize=7, textColor=colors.HexColor("#475569"),
    leading=10, spaceAfter=1)
small_bold = S("SmallB",
    fontName="Helvetica-Bold", fontSize=7.5, textColor=BLACK,
    leading=10)
step_label = S("StepLbl",
    fontName="Helvetica-Bold", fontSize=9, textColor=WHITE,
    alignment=TA_CENTER, leading=12)
cell_body = S("CellB",
    fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10)
cell_bold = S("CellBold",
    fontName="Helvetica-Bold", fontSize=7.5, textColor=BLACK, leading=10)
cell_small = S("CellSm",
    fontName="Helvetica", fontSize=7, textColor=colors.HexColor("#334155"), leading=9)
note_style = S("Note",
    fontName="Helvetica-Oblique", fontSize=7.5, textColor=colors.HexColor("#475569"),
    leading=10)
warn_style = S("Warn",
    fontName="Helvetica-Bold", fontSize=7.5, textColor=RED,
    leading=10)
green_style = S("Grn",
    fontName="Helvetica-Bold", fontSize=7.5, textColor=GREEN,
    leading=10)

# ── Helpers ─────────────────────────────────────────────────────────────────
def colored_header(text, bg, fg=WHITE, height=16):
    """Single-cell table used as a coloured section header bar."""
    t = Table([[Paragraph(text, S("h_"+text[:6],
                fontName="Helvetica-Bold", fontSize=9.5, textColor=fg,
                alignment=TA_CENTER, leading=12))]],
              colWidths=[W - 28*mm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
        ("LEFTPADDING",   (0,0), (-1,-1), 8),
        ("RIGHTPADDING",  (0,0), (-1,-1), 8),
        ("ROUNDEDCORNERS", [4]),
    ]))
    return t

def page_bg(canvas, doc):
    """Draw header banner and footer on every page."""
    canvas.saveState()
    # header band
    canvas.setFillColor(BLUE_DARK)
    canvas.rect(0, H - 38*mm, W, 38*mm, fill=1, stroke=0)
    # thin accent line under header
    canvas.setFillColor(TEAL)
    canvas.rect(0, H - 38.8*mm, W, 1.5, fill=1, stroke=0)
    # title
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 20)
    canvas.drawCentredString(W/2, H - 16*mm, "GINA 2026 — Asthma Stepwise Treatment")
    canvas.setFont("Helvetica", 9)
    canvas.setFillColor(colors.HexColor("#93c5fd"))
    canvas.drawCentredString(W/2, H - 24*mm,
        "Global Initiative for Asthma  ·  2026 Strategy Report  ·  Quick Reference")
    canvas.setFont("Helvetica", 8)
    canvas.setFillColor(colors.HexColor("#bfdbfe"))
    canvas.drawCentredString(W/2, H - 30*mm,
        "Adults & Adolescents (≥12 yrs)   |   Anti-inflammatory first approach")
    # footer
    canvas.setFillColor(BLUE_DARK)
    canvas.rect(0, 0, W, 12*mm, fill=1, stroke=0)
    canvas.setFillColor(GREY_MED)
    canvas.setFont("Helvetica", 7)
    canvas.drawCentredString(W/2, 4*mm,
        "Reference: GINA 2026 Strategy Report  ·  ginasthma.org  ·  For educational use only")
    canvas.restoreState()

# ── Document setup ───────────────────────────────────────────────────────────
doc = BaseDocTemplate(OUTPUT, pagesize=A4,
    leftMargin=14*mm, rightMargin=14*mm,
    topMargin=42*mm, bottomMargin=15*mm)
frame = Frame(doc.leftMargin, doc.bottomMargin,
              doc.width, doc.height, id="main")
doc.addPageTemplates([PageTemplate(id="main", frames=[frame], onPage=page_bg)])

story = []
COL = doc.width   # usable width

# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
# SECTION 1: KEY GINA 2026 PRINCIPLES (info boxes)
# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
story.append(colored_header("▸  KEY GINA 2026 PRINCIPLES", BLUE_MID))
story.append(Spacer(1, 3))

principles = [
    ("🚫", "No SABA monotherapy", "ICS-formoterol is now the preferred reliever at ALL steps. SABA alone is no longer recommended as first-line reliever."),
    ("✅", "Anti-inflammatory first", "Every patient with asthma should receive ICS-containing therapy. Inflammation, not just bronchospasm, must be treated."),
    ("🔄", "SMART strategy", "Single Maintenance And Reliever Therapy (ICS-formoterol) at Steps 3-5: one inhaler for both daily control AND rescue."),
    ("🎯", "Treat to control", "Assess control every 1-3 months. Step UP if uncontrolled; Step DOWN if well-controlled for ≥3 months."),
    ("💊", "Minimize OCS", "Optimize ICS, treat triggers, use add-ons and biologics to avoid oral corticosteroids."),
    ("🩺", "SpO₂ target 92-95%", "New 2026 update: target O₂ saturation 92-95% in acute exacerbations (not 100%)."),
]

pcols = COL / 3
p_data = []
row = []
for i, (icon, title, detail) in enumerate(principles):
    cell_content = [
        Paragraph(f"<b>{icon} {title}</b>", S("pi_t", fontName="Helvetica-Bold",
                  fontSize=8, textColor=BLUE_DARK, leading=11)),
        Paragraph(detail, S("pi_d", fontName="Helvetica", fontSize=7,
                  textColor=BLACK, leading=10))
    ]
    row.append(cell_content)
    if len(row) == 3:
        p_data.append(row)
        row = []
if row:
    while len(row) < 3:
        row.append([""])
    p_data.append(row)

ptable = Table(p_data, colWidths=[pcols]*3, rowHeights=None)
ptable.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), BLUE_LIGHT),
    ("BACKGROUND",    (0,1), (-1,1), colors.HexColor("#e0f2fe")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 6),
    ("RIGHTPADDING",  (0,0), (-1,-1), 6),
    ("GRID",          (0,0), (-1,-1), 0.5, WHITE),
    ("VALIGN",        (0,0), (-1,-1), "TOP"),
    ("ROUNDEDCORNERS", [3]),
]))
story.append(ptable)
story.append(Spacer(1, 6))

# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
# SECTION 2: STEPWISE TREATMENT TABLE
# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
story.append(colored_header("▸  STEPWISE TREATMENT  —  Adults & Adolescents (≥12 years)", TEAL))
story.append(Spacer(1, 3))

# Step colours
step_colors = [
    colors.HexColor("#16a34a"),   # step 1 - green
    colors.HexColor("#2563a8"),   # step 2 - blue
    colors.HexColor("#d97706"),   # step 3 - amber
    colors.HexColor("#dc6f07"),   # step 4 - deep orange
    colors.HexColor("#dc2626"),   # step 5 - red
]

step_data = [
    # (step#, label, severity, controller, reliever, add-ons, notes)
    (
        "STEP 1",
        "Intermittent",
        "Low-dose ICS-formoterol\nas needed (preferred)\nOR low-dose ICS taken\nwhenever SABA taken",
        "Low-dose ICS-formoterol\n(as needed)\n[e.g. budesonide/formoterol\n100/6 mcg]",
        "—",
        "• No daily controller needed if truly intermittent\n• If using SABA ≥2×/week → Step up\n• Consider daily low-dose ICS if frequent symptoms",
    ),
    (
        "STEP 2",
        "Mild\nPersistent",
        "Low-dose ICS daily\n(preferred)\nOR LTRA daily",
        "ICS-formoterol\n(as needed)\nOR SABA",
        "LTRA (alternative\nto ICS if ICS refused\nor not tolerated)",
        "• Low-dose ICS is the cornerstone\n• ICS+SABA combo inhaler is an alternative\n• Review adherence and inhaler technique",
    ),
    (
        "STEP 3",
        "Moderate\n(uncontrolled\non Step 2)",
        "Low-dose ICS-LABA\ndaily (preferred)\n[SMART therapy preferred]",
        "ICS-formoterol\n(SMART reliever)\n[same inhaler as controller]",
        "LAMA (tiotropium)\nas add-on\nLTRA as add-on",
        "• SMART = one inhaler for maintenance + relief\n• Preferred: budesonide/formoterol or BDP/formoterol\n• Assess FeNO / eosinophils to guide therapy",
    ),
    (
        "STEP 4",
        "Moderate-Severe\n(uncontrolled\non Step 3)",
        "Medium-dose ICS-LABA\ndaily\n[+ consider LAMA]",
        "ICS-formoterol\n(SMART reliever)",
        "LAMA (tiotropium)\nLTRA\nHigh-dose ICS",
        "• Refer to specialist for assessment\n• Check for type 2 biomarkers (eosinophils, FeNO)\n• Rule out: poor adherence, wrong diagnosis, triggers",
    ),
    (
        "STEP 5",
        "Severe\n(uncontrolled\non Step 4)",
        "High-dose ICS-LABA\n+ specialist-directed\nbiologic therapy",
        "ICS-formoterol\n(SMART reliever)\nOR SABA",
        "Biologics (see below)\nLAMA\nLTRA\nMinimize OCS",
        "• Mandatory specialist referral\n• Phenotype-guided biologic selection\n• Add-on tiotropium if not already used\n• OCS only as last resort / short course",
    ),
]

# Header row
col_widths = [COL*0.085, COL*0.10, COL*0.22, COL*0.20, COL*0.13, COL*0.265]

def mp(txt, sty):
    lines = txt.strip().split("\n")
    return [Paragraph(l, sty) for l in lines if l.strip()]

hdr_row = [
    Paragraph("STEP", S("sh", fontName="Helvetica-Bold", fontSize=8, textColor=WHITE,
              alignment=TA_CENTER, leading=11)),
    Paragraph("SEVERITY", S("sh2", fontName="Helvetica-Bold", fontSize=8, textColor=WHITE,
              alignment=TA_CENTER, leading=11)),
    Paragraph("PREFERRED CONTROLLER", S("sh3", fontName="Helvetica-Bold", fontSize=8,
              textColor=WHITE, alignment=TA_CENTER, leading=11)),
    Paragraph("PREFERRED RELIEVER", S("sh4", fontName="Helvetica-Bold", fontSize=8,
              textColor=WHITE, alignment=TA_CENTER, leading=11)),
    Paragraph("ADD-ON OPTIONS", S("sh5", fontName="Helvetica-Bold", fontSize=8,
              textColor=WHITE, alignment=TA_CENTER, leading=11)),
    Paragraph("CLINICAL NOTES", S("sh6", fontName="Helvetica-Bold", fontSize=8,
              textColor=WHITE, alignment=TA_CENTER, leading=11)),
]

rows = [hdr_row]
for idx, (step, sev, ctrl, rel, addon, notes) in enumerate(step_data):
    col = step_colors[idx]
    s_cell = Paragraph(step, S("sc"+str(idx), fontName="Helvetica-Bold", fontSize=9,
                       textColor=WHITE, alignment=TA_CENTER, leading=12))
    sev_cell  = mp(sev,   S("sv", fontName="Helvetica-Bold", fontSize=7.5, textColor=col, leading=10))
    ctrl_cell = mp(ctrl,  S("ct", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10))
    rel_cell  = mp(rel,   S("rl", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10))
    add_cell  = mp(addon, S("ad", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10))
    note_cell = mp(notes, S("nt", fontName="Helvetica", fontSize=7.5, textColor=colors.HexColor("#1e293b"), leading=10))
    rows.append([s_cell, sev_cell, ctrl_cell, rel_cell, add_cell, note_cell])

step_table = Table(rows, colWidths=col_widths, repeatRows=1)

ts = TableStyle([
    # Header
    ("BACKGROUND",    (0,0), (-1,0), BLUE_DARK),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("TOPPADDING",    (0,0), (-1,0), 5),
    ("BOTTOMPADDING", (0,0), (-1,0), 5),
    # Step number cells
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ("ALIGN",         (0,0), (0,-1),  "CENTER"),
    ("TOPPADDING",    (0,1), (-1,-1), 5),
    ("BOTTOMPADDING", (0,1), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 4),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#cbd5e1")),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [GREY_LIGHT, WHITE]),
    ("VALIGN",        (0,1), (-1,-1), "TOP"),
])
# Color the step number column per step
for i, col in enumerate(step_colors):
    ts.add("BACKGROUND", (0, i+1), (0, i+1), col)

step_table.setStyle(ts)
story.append(step_table)
story.append(Spacer(1, 6))

# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
# SECTION 3: BIOLOGICS + CONTROL ASSESSMENT  (two columns)
# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
half = COL / 2 - 2*mm

# -- Biologics table --
bio_hdr_style = S("bhs", fontName="Helvetica-Bold", fontSize=8, textColor=WHITE,
                  alignment=TA_CENTER, leading=11)
bio_cell_style = S("bcs", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10)
bio_bold_style = S("bbs", fontName="Helvetica-Bold", fontSize=7.5, textColor=PURPLE, leading=10)

bio_rows = [
    [Paragraph("BIOLOGIC", bio_hdr_style),
     Paragraph("TARGET", bio_hdr_style),
     Paragraph("PHENOTYPE", bio_hdr_style)],
    [Paragraph("Omalizumab", bio_bold_style),     Paragraph("IgE", bio_cell_style),          Paragraph("Allergic (T2)", bio_cell_style)],
    [Paragraph("Mepolizumab", bio_bold_style),    Paragraph("IL-5", bio_cell_style),         Paragraph("Eosinophilic", bio_cell_style)],
    [Paragraph("Reslizumab", bio_bold_style),     Paragraph("IL-5", bio_cell_style),         Paragraph("Eosinophilic", bio_cell_style)],
    [Paragraph("Benralizumab", bio_bold_style),   Paragraph("IL-5R", bio_cell_style),        Paragraph("Eosinophilic", bio_cell_style)],
    [Paragraph("Dupilumab", bio_bold_style),      Paragraph("IL-4Rα", bio_cell_style),       Paragraph("T2 (IL-4/IL-13)", bio_cell_style)],
    [Paragraph("Tezepelumab", bio_bold_style),    Paragraph("TSLP", bio_cell_style),         Paragraph("Broad / all phenotypes", bio_cell_style)],
    [Paragraph("Depemokimab ★NEW", bio_bold_style), Paragraph("IL-5", bio_cell_style),      Paragraph("Eosinophilic (ultra-LA)", bio_cell_style)],
]
bio_table = Table(bio_rows, colWidths=[half*0.38, half*0.25, half*0.37])
bio_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), PURPLE),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [PURPLE_LIGHT, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#c4b5fd")),
    ("TOPPADDING",    (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING",   (0,0), (-1,-1), 4),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
]))

# -- Control assessment table --
ctrl_hdr_s = S("chs", fontName="Helvetica-Bold", fontSize=8, textColor=WHITE,
               alignment=TA_CENTER, leading=11)
ctrl_cell_s = S("ccs", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10)

def ctrl_label(text, c):
    return Paragraph(f"<b>{text}</b>", S("cl_"+text[:3], fontName="Helvetica-Bold",
                     fontSize=7.5, textColor=c, alignment=TA_CENTER, leading=10))

ctrl_rows = [
    [Paragraph("CRITERION\n(last 4 weeks)", ctrl_hdr_s),
     ctrl_label("CONTROLLED", GREEN),
     ctrl_label("PARTLY\nCONTROLLED", ORANGE),
     ctrl_label("UNCONTROLLED", RED)],
    [Paragraph("Daytime symptoms", ctrl_cell_s),
     Paragraph("≤2×/week", ctrl_cell_s),
     Paragraph(">2×/week", ctrl_cell_s),
     Paragraph("3-4 features\nof 'partly\ncontrolled'", S("uc", fontName="Helvetica", fontSize=7.5,
               textColor=BLACK, leading=10))],
    [Paragraph("Night waking", ctrl_cell_s),
     Paragraph("None", ctrl_cell_s),
     Paragraph("Any", ctrl_cell_s),
     Paragraph("", ctrl_cell_s)],
    [Paragraph("Reliever use", ctrl_cell_s),
     Paragraph("≤2×/week", ctrl_cell_s),
     Paragraph(">2×/week", ctrl_cell_s),
     Paragraph("", ctrl_cell_s)],
    [Paragraph("Activity limitation", ctrl_cell_s),
     Paragraph("None", ctrl_cell_s),
     Paragraph("Any", ctrl_cell_s),
     Paragraph("", ctrl_cell_s)],
    [Paragraph("ACTION", S("act", fontName="Helvetica-Bold", fontSize=7.5, textColor=BLACK, leading=10)),
     Paragraph("Maintain /\nStep down", S("act_g", fontName="Helvetica-Bold", fontSize=7.5,
               textColor=GREEN, leading=10)),
     Paragraph("Consider\nStep up", S("act_o", fontName="Helvetica-Bold", fontSize=7.5,
               textColor=ORANGE, leading=10)),
     Paragraph("Step UP", S("act_r", fontName="Helvetica-Bold", fontSize=7.5,
               textColor=RED, leading=10))],
]

ctrl_table = Table(ctrl_rows, colWidths=[half*0.36, half*0.21, half*0.21, half*0.22])
ctrl_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), TEAL),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("BACKGROUND",    (0,5), (-1,5), GREY_LIGHT),
    ("ROWBACKGROUNDS",(0,1), (-1,4), [TEAL_LIGHT, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#99f6e4")),
    ("TOPPADDING",    (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING",   (0,0), (-1,-1), 4),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ("SPAN",          (3,1), (3,4)),
    ("ALIGN",         (1,0), (-1,-1), "CENTER"),
]))

def section_label(text, bg):
    t = Table([[Paragraph(f"<b>{text}</b>", S("slb_"+text[:4],
               fontName="Helvetica-Bold", fontSize=8.5, textColor=WHITE,
               alignment=TA_CENTER, leading=12))]],
             colWidths=[half])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ]))
    return t

bio_section = [
    [section_label("▸  STEP 5 BIOLOGICS  (Severe Asthma)", PURPLE),
     section_label("▸  ASTHMA CONTROL ASSESSMENT  (GINA 2026)", TEAL)],
    [bio_table, ctrl_table],
]
two_col = Table(bio_section, colWidths=[half + 2*mm, half + 2*mm])
two_col.setStyle(TableStyle([
    ("VALIGN",  (0,0), (-1,-1), "TOP"),
    ("TOPPADDING",    (0,0), (-1,-1), 0),
    ("BOTTOMPADDING", (0,0), (-1,-1), 3),
    ("LEFTPADDING",   (0,0), (-1,-1), 0),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
]))
story.append(two_col)
story.append(Spacer(1, 6))

# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
# SECTION 4: ACUTE EXACERBATION MANAGEMENT + RED FLAGS  (two columns)
# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

# -- Acute Exacerbation --
ae_hdr = S("ae_h", fontName="Helvetica-Bold", fontSize=8, textColor=WHITE,
           alignment=TA_CENTER, leading=11)
ae_cell = S("ae_c", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10)
ae_bold = S("ae_b", fontName="Helvetica-Bold", fontSize=7.5, textColor=BLACK, leading=10)

ae_rows = [
    [Paragraph("SEVERITY", ae_hdr),
     Paragraph("KEY FEATURES", ae_hdr),
     Paragraph("TREATMENT", ae_hdr)],
    [Paragraph("MILD", S("mild_l", fontName="Helvetica-Bold", fontSize=8, textColor=GREEN,
               alignment=TA_CENTER, leading=11)),
     Paragraph("SpO₂ ≥94%  |  Normal-mild ↑RR\nFull sentences  |  Mild wheeze", ae_cell),
     Paragraph("Salbutamol 4 puffs (pMDI + spacer)\nOR ICS-formoterol 2 puffs\nReassess 20 min", ae_cell)],
    [Paragraph("MODERATE", S("mod_l", fontName="Helvetica-Bold", fontSize=8, textColor=ORANGE,
               alignment=TA_CENTER, leading=11)),
     Paragraph("SpO₂ 90-93%  |  ↑RR  |  ↑HR\nPhrases only  |  Mod. wheeze\nAccessory muscles", ae_cell),
     Paragraph("Salbutamol 4-6 puffs q20min × 3\n+ Ipratropium 4 puffs (up to 3×)\n+ Oral prednisolone\n+ Controlled O₂ (target 92-95%)", ae_cell)],
    [Paragraph("SEVERE /\nLIFE-\nTHREATENING", S("sev_l", fontName="Helvetica-Bold", fontSize=8,
               textColor=RED, alignment=TA_CENTER, leading=11)),
     Paragraph("SpO₂ <92%  |  RR >30/min\nWords/unable to speak\nSilent chest  |  Cyanosis\nDrowsy / confused", ae_cell),
     Paragraph("TRANSFER TO ACUTE CARE\nSalbutamol 6-10 puffs q20-30min\n+ Ipratropium + IV/IM corticosteroids\n+ Controlled O₂ (92-95%)\n+ IV Magnesium sulfate\n★ Anaphylaxis → Epinephrine FIRST", ae_bold)],
]

ae_table = Table(ae_rows, colWidths=[half*0.22, half*0.38, half*0.40])
ae_table.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), RED),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [GREEN_LIGHT, ORANGE_LIGHT, RED_LIGHT]),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#fca5a5")),
    ("TOPPADDING",    (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING",   (0,0), (-1,-1), 4),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ("ALIGN",         (0,0), (0,-1), "CENTER"),
]))

# -- Red Flags --
rf_items = [
    "Previous near-fatal attack (ICU / intubation)",
    "ER visit or hospitalization in past 12 months",
    "Not on ICS, or poor adherence / technique",
    "Using >1 SABA canister per month",
    "Psychological / socioeconomic problems",
    "Food allergy coexisting with asthma",
    "Heavy smoking (current or past)",
    "Elevated blood eosinophils or FeNO",
]

rf_body = S("rfs", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=11)
rf_data = [[Paragraph(f"⚠  {item}", rf_body)] for item in rf_items]
rf_table = Table(rf_data, colWidths=[half])
rf_table.setStyle(TableStyle([
    ("ROWBACKGROUNDS", (0,0), (-1,-1), [RED_LIGHT, WHITE]),
    ("TOPPADDING",    (0,0), (-1,-1), 3),
    ("BOTTOMPADDING", (0,0), (-1,-1), 3),
    ("LEFTPADDING",   (0,0), (-1,-1), 5),
    ("RIGHTPADDING",  (0,0), (-1,-1), 5),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#fca5a5")),
]))

ae_section = [
    [section_label("▸  ACUTE EXACERBATION MANAGEMENT  (GINA 2026)", RED),
     section_label("▸  RED FLAGS FOR FATAL / NEAR-FATAL ASTHMA", RED)],
    [ae_table, rf_table],
]
ae_two_col = Table(ae_section, colWidths=[half + 2*mm, half + 2*mm])
ae_two_col.setStyle(TableStyle([
    ("VALIGN",  (0,0), (-1,-1), "TOP"),
    ("TOPPADDING",    (0,0), (-1,-1), 0),
    ("BOTTOMPADDING", (0,0), (-1,-1), 3),
    ("LEFTPADDING",   (0,0), (-1,-1), 0),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
]))
story.append(ae_two_col)
story.append(Spacer(1, 5))

# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
# SECTION 5: ICS DOSE TABLE + KEY DRUG CLASSES  (bottom strip)
# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
story.append(colored_header("▸  ICS DOSE REFERENCE  &  KEY DRUG CLASSES", BLUE_DARK))
story.append(Spacer(1, 3))

third = COL / 3 - 2*mm

# ICS dose table
ics_hdr = S("ics_h", fontName="Helvetica-Bold", fontSize=7.5, textColor=WHITE,
            alignment=TA_CENTER, leading=10)
ics_cell = S("ics_c", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10)
ics_rows = [
    [Paragraph("ICS DRUG", ics_hdr),
     Paragraph("LOW DOSE\n(mcg/day)", ics_hdr),
     Paragraph("MEDIUM DOSE\n(mcg/day)", ics_hdr),
     Paragraph("HIGH DOSE\n(mcg/day)", ics_hdr)],
    [Paragraph("Beclomethasone\n(HFA pMDI)", ics_cell),
     Paragraph("100-200", ics_cell), Paragraph("200-400", ics_cell), Paragraph(">400", ics_cell)],
    [Paragraph("Budesonide\n(DPI)", ics_cell),
     Paragraph("200-400", ics_cell), Paragraph("400-800", ics_cell), Paragraph(">800", ics_cell)],
    [Paragraph("Fluticasone\npropionate (DPI)", ics_cell),
     Paragraph("100-250", ics_cell), Paragraph("250-500", ics_cell), Paragraph(">500", ics_cell)],
    [Paragraph("Fluticasone\nfuroate (DPI)", ics_cell),
     Paragraph("100", ics_cell), Paragraph("—", ics_cell), Paragraph("200", ics_cell)],
    [Paragraph("Ciclesonide\n(HFA pMDI)", ics_cell),
     Paragraph("80-160", ics_cell), Paragraph("160-320", ics_cell), Paragraph(">320", ics_cell)],
]
ics_t = Table(ics_rows, colWidths=[third*0.37, third*0.21, third*0.21, third*0.21])
ics_t.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), BLUE_MID),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [BLUE_LIGHT, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#bfdbfe")),
    ("TOPPADDING",    (0,0), (-1,-1), 3),
    ("BOTTOMPADDING", (0,0), (-1,-1), 3),
    ("LEFTPADDING",   (0,0), (-1,-1), 4),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
    ("ALIGN",         (1,0), (-1,-1), "CENTER"),
    ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
]))

# Drug classes quick ref
drug_s = S("drg_s", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10)
drug_b = S("drg_b", fontName="Helvetica-Bold", fontSize=7.5, textColor=BLUE_DARK, leading=10)

drug_rows = [
    [Paragraph("CLASS", S("dh", fontName="Helvetica-Bold", fontSize=7.5, textColor=WHITE,
               alignment=TA_CENTER, leading=10)),
     Paragraph("EXAMPLES", S("dh2", fontName="Helvetica-Bold", fontSize=7.5, textColor=WHITE,
               alignment=TA_CENTER, leading=10)),
     Paragraph("ROLE", S("dh3", fontName="Helvetica-Bold", fontSize=7.5, textColor=WHITE,
               alignment=TA_CENTER, leading=10))],
    [Paragraph("SABA", drug_b), Paragraph("Salbutamol, Terbutaline", drug_s),
     Paragraph("Acute relief (use only with ICS)", drug_s)],
    [Paragraph("LABA", drug_b), Paragraph("Formoterol, Salmeterol", drug_s),
     Paragraph("Add-on to ICS — NEVER alone", drug_s)],
    [Paragraph("ICS", drug_b), Paragraph("Budesonide, BDP,\nFluticasone", drug_s),
     Paragraph("Cornerstone — all steps", drug_s)],
    [Paragraph("ICS-LABA", drug_b), Paragraph("Budesonide/formoterol\nBDP/formoterol\nFluticasone/salmeterol", drug_s),
     Paragraph("Preferred Steps 3-5\n(SMART at Steps 3-5)", drug_s)],
    [Paragraph("LAMA", drug_b), Paragraph("Tiotropium", drug_s),
     Paragraph("Add-on Steps 4-5", drug_s)],
    [Paragraph("LTRA", drug_b), Paragraph("Montelukast", drug_s),
     Paragraph("Alternative/add-on\n(less effective than ICS)", drug_s)],
]
drug_t = Table(drug_rows, colWidths=[third*0.25, third*0.38, third*0.37])
drug_t.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), TEAL),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [TEAL_LIGHT, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#99f6e4")),
    ("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), "TOP"),
]))

# New 2026 highlights
new_items = [
    ("★", "ICS-formoterol reliever", "Preferred at ALL steps — even Step 1"),
    ("★", "No SABA monotherapy", "Avoid SABA alone as sole treatment"),
    ("★", "SpO₂ target 92-95%", "New threshold in acute exacerbation (not 100%)"),
    ("★", "Depemokimab (biologic)", "Ultra-long-acting anti-IL-5 (q6 months SC)"),
    ("★", "OCS minimization", "Biologics preferred over chronic OCS"),
    ("★", "Pediatric PRAM score", "Validated severity score for children <18 yrs"),
    ("★", "CAAT & Peds-AIRQ", "New control/assessment tools added in 2026"),
    ("★", "RSV/flu/COVID vaccines", "Updated vaccine evidence included"),
]
new_s = S("nw_s", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=10)
new_b = S("nw_b", fontName="Helvetica-Bold", fontSize=7.5, textColor=ORANGE, leading=10)
new_rows = [[Paragraph("★ NEW IN 2026", S("nh", fontName="Helvetica-Bold", fontSize=8,
             textColor=WHITE, alignment=TA_CENTER, leading=11)),
             Paragraph("DETAIL", S("nh2", fontName="Helvetica-Bold", fontSize=8,
             textColor=WHITE, alignment=TA_CENTER, leading=11))]]
for icon, title, detail in new_items:
    new_rows.append([Paragraph(f"<b>{title}</b>", new_b),
                     Paragraph(detail, new_s)])
new_t = Table(new_rows, colWidths=[third*0.44, third*0.56])
new_t.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,0), ORANGE),
    ("TEXTCOLOR",     (0,0), (-1,0), WHITE),
    ("ROWBACKGROUNDS",(0,1), (-1,-1), [ORANGE_LIGHT, WHITE]),
    ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#fde68a")),
    ("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"),
]))

# labels
def mini_label(txt, bg):
    t = Table([[Paragraph(f"<b>{txt}</b>", S("ml_"+txt[:3], fontName="Helvetica-Bold",
               fontSize=7.5, textColor=WHITE, alignment=TA_CENTER, leading=10))]],
             colWidths=[third])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("TOPPADDING",    (0,0), (-1,-1), 3),
        ("BOTTOMPADDING", (0,0), (-1,-1), 3),
    ]))
    return t

bottom_section = [
    [mini_label("ICS DOSE REFERENCE", BLUE_MID),
     mini_label("KEY DRUG CLASSES", TEAL),
     mini_label("★ WHAT'S NEW IN GINA 2026", ORANGE)],
    [ics_t, drug_t, new_t],
]
bottom_col = Table(bottom_section, colWidths=[third + 3*mm, third + 3*mm, third + 3*mm])
bottom_col.setStyle(TableStyle([
    ("VALIGN",  (0,0), (-1,-1), "TOP"),
    ("TOPPADDING",    (0,0), (-1,-1), 0),
    ("BOTTOMPADDING", (0,0), (-1,-1), 0),
    ("LEFTPADDING",   (0,0), (-1,-1), 0),
    ("RIGHTPADDING",  (0,0), (-1,-1), 4),
]))
story.append(bottom_col)

# ── Build ────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF created: {OUTPUT}")

Running Command

cd /home/daytona/workspace/gina2026-cheatsheet && python3 generate_pdf.py 2>&1

Generated successfully. Here's your cheat sheet:

GINA 2026 Asthma Stepwise Cheatsheet

PDF Document · PDF

The single-page A4 PDF includes:

Key GINA 2026 Principles - 6 principle boxes (no SABA monotherapy, SMART strategy, OCS minimization, new SpO2 target, etc.)
Stepwise Treatment Table (Steps 1-5) - severity, preferred controller, preferred reliever, add-on options, and clinical notes for each step - colour-coded green through red
Step 5 Biologics - all 7 agents with target and phenotype, including new Depemokimab
Asthma Control Assessment - controlled / partly controlled / uncontrolled with action guide
Acute Exacerbation Management - mild / moderate / severe with specific drug doses
Red Flags for Fatal Asthma - all 8 risk factors
ICS Dose Reference - low/medium/high doses for 5 ICS drugs
Key Drug Classes quick reference
What's New in GINA 2026 - 8 highlighted updates

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