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🫁 ASTHMA - Complete Notes

Sources: Murray & Nadel's Textbook of Respiratory Medicine + GINA 2025 Guidelines

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PART 1: DEFINITION

"Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation." — GINA 2025 / Murray & Nadel (Chapter 62)

• Chronic inflammation - ongoing swelling inside airways
• Variable obstruction - airflow blockage that comes and goes
• Bronchial hyperresponsiveness (BHR) - airways react to things that don't bother normal people (cold air, exercise, dust)
• Heterogeneous - different patients have different types/triggers

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PART 2: PATHOPHYSIOLOGY (How it happens)

2.1 Normal vs Asthmatic Airway

2.2 The Inflammatory Cascade (T2-High / Allergic Asthma)

1. Allergen enters the airway (dust mite, pollen, animal dander)
2. Airway epithelial cells release alarm signals: TSLP, IL-33, IL-1
3. Mast cells & basophils get activated (IgE cross-linking)
4. They release: histamine, PGD2, leukotrienes → BRONCHOCONSTRICTION (early allergic reaction, within minutes)
5. Eosinophils are recruited (via IL-5 from Th2 cells and ILC2s) → LATE PHASE REACTION (hours later)
6. Repeated episodes → airway remodeling (permanent structural changes)

2.3 Key Cells in Asthma

2.4 Key Mediators

• Histamine → bronchoconstriction, mucus, itch
• Leukotrienes (LTC4, LTD4) → powerful bronchoconstriction + mucus
• IL-5 → eosinophil growth + survival
• IL-13 → mucus hypersecretion + airway hyperresponsiveness
• IL-4 → IgE production (switches B cells to make IgE)
• IgE → sits on mast cells, triggers degranulation when allergen binds

2.5 Airway Remodeling (Chronic Changes)

• Subepithelial fibrosis (thickening below the lining)
• Smooth muscle hypertrophy (muscle gets bigger)
• Angiogenesis (new blood vessels form)
• Goblet cell hyperplasia (more mucus-producing cells)
• These changes may make obstruction partially irreversible over time

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PART 3: PHENOTYPES (Types of Asthma)

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PART 4: DIAGNOSIS

4.1 Diagnostic Algorithm (Murray & Nadel, Fig. 62.1)

1. Suspect asthma (symptoms: wheeze, SOB, chest tightness, cough)
2. Take history + physical + spirometry with bronchodilator test
3. POSITIVE (FEV1 or FVC increases by ≥12% AND ≥200 mL after bronchodilator) → Asthma confirmed
4. NEGATIVE/Atypical → Methacholine challenge test
   • Positive methacholine → Likely asthma
   • Negative methacholine → Consider alternative diagnosis

4.2 GINA 2025 - 4 Cardinal Symptoms

• Wheezing
• Shortness of breath
• Chest tightness
• Cough (often worse at night or early morning)

• Symptoms vary (better and worse at different times)
• Symptoms triggered by exercise, cold air, smoke, allergens
• Symptoms worse at night or early morning
• Personal/family history of atopy (eczema, hay fever)
• Symptoms respond to bronchodilators

4.3 Spirometry Findings in Asthma

4.4 Other Tests (GINA 2025)

4.5 Differential Diagnosis (What else looks like asthma?)

• COPD (fixed obstruction, smoking history, older patients)
• Vocal cord dysfunction (stridor, paradoxical vocal cord movement)
• Heart failure ("cardiac asthma" - orthopnea, elevated BNP)
• Bronchiectasis (daily productive cough, recurrent infections)
• Cystic fibrosis (young patients, pancreatic involvement)
• GERD-related cough
• Sarcoidosis

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PART 5: ASSESSMENT AND CLASSIFICATION

5.1 GINA Asthma Symptom Control (past 4 weeks)

1. Daytime symptoms more than twice per week?
2. Any night waking due to asthma?
3. Reliever used more than twice per week?
4. Any activity limitation due to asthma?

5.2 GINA Severity Classification (retrospective - based on treatment needed)

Important: Severity is assessed AFTER treatment is started, not at diagnosis!

5.3 Risk Factors for Exacerbations (GINA 2025)

• Uncontrolled symptoms
• Frequent SABA use (>2x/week)
• Not on ICS
• Poor inhaler technique or adherence
• Smoking, allergen exposure
• Obesity, chronic rhinosinusitis, GERD
• Low FEV1 (<60% predicted)
• Previous severe exacerbation or ICU admission

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PART 6: TREATMENT (GINA Stepwise Approach)

6.1 Big Picture Concept

6.2 The 5-Step Treatment Ladder

6.3 Drug Classes Explained Simply

A. Inhaled Corticosteroids (ICS) - BACKBONE of treatment

• Examples: Budesonide, Fluticasone, Beclomethasone
• Work by: Reducing airway inflammation
• Use: Daily controller therapy
• Key point: Most important single drug in asthma management

B. Long-Acting Beta-2 Agonists (LABA) - always with ICS

• Examples: Formoterol, Salmeterol, Vilanterol
• Work by: Relaxing airway smooth muscle (bronchodilation)
• Use: Combined with ICS for moderate-severe asthma
• Warning: NEVER use LABA alone without ICS in asthma

C. Short-Acting Beta-2 Agonists (SABA) - rescue use

• Examples: Salbutamol (albuterol), Terbutaline
• Work by: Quick bronchodilation (within minutes)
• Use: Reliever for acute symptoms
• Warning: Overuse (>2x/week) = poor control = increase therapy

D. Leukotriene Receptor Antagonists (LTRA) - add-on

• Examples: Montelukast
• Work by: Blocking leukotriene receptors
• Use: Add-on at Step 2-3; good for aspirin-sensitive asthma, exercise-induced asthma, allergic rhinitis with asthma

E. Theophylline - older add-on

• Low-dose has anti-inflammatory effect
• Narrow therapeutic window, multiple interactions
• Less preferred today

F. Short-Acting Muscarinic Antagonist (SAMA)

• Examples: Ipratropium
• Used in acute severe asthma (added to SABA in ER)

G. Long-Acting Muscarinic Antagonist (LAMA) - Step 4-5 add-on

• Examples: Tiotropium
• Added to ICS-LABA in uncontrolled severe asthma

6.4 Biologics (Step 5 - Severe Asthma Only)

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PART 7: ACUTE EXACERBATIONS (Asthma Attack)

7.1 Severity Assessment

7.2 Acute Management (GINA Primary Care)

1. Bronchodilator: Inhaled SABA (salbutamol) 4-10 puffs via spacer every 20 min x 3 in first hour
   • Severe: Add ipratropium (SAMA)
2. Oxygen: Titrate to SpO2 93-95%
3. Systemic corticosteroids: Oral prednisolone 40-50 mg/day (or IV hydrocortisone) for 5-7 days
4. Reassess after 1 hour:
   • Good response → discharge with action plan
   • Poor response → admit or escalate
5. Magnesium sulfate (IV): For severe exacerbations not responding to bronchodilators
6. Heliox, NIV, intubation: For life-threatening exacerbations

7.3 Discharge Checklist

• ✅ Prescribe or adjust controller treatment (ICS or ICS-LABA)
• ✅ Ensure SABA reliever provided
• ✅ Ensure good inhaler technique demonstrated
• ✅ Give written asthma action plan
• ✅ Follow up within 1 week
• ✅ Address risk factors

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PART 8: SPECIAL SITUATIONS

8.1 Asthma in Pregnancy

• Affects 3.7-8.4% of pregnancies
• Uncontrolled asthma is MORE dangerous than the medications
• 1/3 worsen, 1/3 improve, 1/3 unchanged
• Safe drugs in pregnancy: ICS (budesonide preferred), SABA, LABA (with ICS)
• Avoid: High-dose oral steroids if possible (risk of growth restriction, cleft palate)
• Principle: Treat to keep asthma controlled - same stepwise approach

8.2 Asthma + Obesity

• More difficult to control
• Less eosinophilic
• Poor response to ICS
• Weight loss significantly improves asthma control
• OSA is common comorbidity - treat with CPAP

8.3 Asthma + OSA (Sleep Apnea)

• OSA worsens asthma control
• Mechanisms: OSA causes oxidative stress → bronchoconstriction; upper airway closure → vagal reflex bronchoconstriction
• Treat OSA with CPAP → improves asthma quality of life, reduces exacerbations

8.4 Occupational Asthma

• New-onset or worsening asthma due to workplace exposure
• Common causes: isocyanates, flour, latex, animal proteins
• Key: Remove from exposure - treatment is secondary

8.5 Exercise-Induced Bronchoconstriction (EIB)

• Peaks 5-15 min after exercise, resolves within 30-60 min
• Diagnosis: >10% fall in FEV1 after exercise challenge
• Prevention: Pre-exercise inhaled SABA OR ICS-formoterol

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PART 9: MONITORING AND FOLLOW-UP

9.1 Validated Tools to Assess Control

• Asthma Control Test (ACT) - 5 questions, score 5-25 (≥20 = well controlled)
• Asthma Control Questionnaire (ACQ) - 7 items
• GINA symptom control - the 4 YES/NO questions (above)

9.2 What to Check at Every Visit

• Symptom control (GINA 4 questions)
• Exacerbation frequency
• SABA use
• Inhaler technique (check every time!)
• Adherence to controller medication
• Lung function (spirometry at least annually)
• Trigger avoidance

9.3 When to Step Down Treatment

• Good control for at least 3 months
• Low risk of exacerbation
• Step down slowly, one step at a time
• Don't step down ICS completely in most patients

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PART 10: GINA 2025 KEY UPDATES (New This Year)

1. New asthma definition - updated wording to reflect heterogeneity
2. New diagnostic flowchart - clearer pathway using spirometry + biomarkers
3. T2 biomarkers emphasized - Blood eosinophils + FeNO to assess Type 2 inflammation before starting/adjusting treatment
4. Population vs patient level treatment - New figure distinguishing population-level recommendations from individualized decisions
5. No SABA-only at Step 1 - ICS-formoterol as preferred reliever at ALL steps
6. Children <5 years: New explicit 3-criteria diagnosis:
   • Recurrent wheezing episodes
   • No other likely cause
   • Clinical response to asthma medications
7. Severe exacerbations in <5y: New SpO2 threshold + nebulized magnesium added
8. Climate change acknowledged as risk factor for exacerbations
9. Biomarkers appendix - sputum eos, blood eos, FeNO, IgE, periostin - how to use in clinical context

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QUICK MEMORY AID

ASTHMA = 
A - Airway inflammation (chronic)
S - Symptoms: wheeze, SOB, chest tightness, cough
T - Triggers: allergens, exercise, cold, smoke, infections
H - Hyperresponsiveness (airways overreact)
M - Mostly reversible obstruction
A - Anti-inflammatory therapy (ICS) is the cornerstone

GINA CONTROL = 4 questions in 4 weeks
0 YES = Well controlled
1-2 YES = Partly controlled  
3-4 YES = Uncontrolled

STEPS 1-5:
Step 1 = As-needed ICS-formoterol
Step 2 = Low-dose ICS daily
Step 3 = Low-dose ICS-LABA
Step 4 = Medium-dose ICS-LABA
Step 5 = High-dose ICS-LABA + Biologic

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• Murray & Nadel's Textbook of Respiratory Medicine (Chapter 62 - Diagnosis and Treatment of Asthma; Chapter 60 - Molecular Immunology of Asthma)
• GINA 2025 Global Strategy Report - Updated November 2025
• GINA 2025 Key Updates Summary

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🫁 ASTHMA - Complete Notes

Sources: Fishman's Pulmonary Diseases & Disorders + GINA 2026 (Published May 5, 2026)

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PART 1: DEFINITION & OVERVIEW

Fishman's Definition:

"Asthma is a chronic inflammatory disease of the airways characterized by persistent variable symptoms that include shortness of breath, cough, and wheezing. It is the most common chronic lung disease and one of the most prevalent diseases in the United States, affecting more than 20 million adults and 7 million children."

• Fishman's Pulmonary Diseases & Disorders, Chapter 43

GINA 2026 Definition:

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

3 Core Features (Fishman's):

1. Bronchoconstriction + variable airflow obstruction - airways narrow and open up
2. Airway hyperresponsiveness (AHR) - airways overreact to triggers
3. Chronic airway inflammation - ongoing immune cell activity in the airways

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PART 2: PATHOPHYSIOLOGY (Fishman's - The Deep Dive)

2.1 The Inflammatory Pathways

2.2 How the Allergic Response Starts

1. Allergen hits bronchial epithelium
2. Epithelial cells release alarmins: TSLP, IL-25, IL-33
3. Alarmins activate dendritic cells → present allergen → naive T cell becomes Th2 cell
4. ILC2 (innate lymphoid cells) also activated by alarmins → release IL-5
5. Th2 cells produce: IL-4, IL-5, IL-13
6. B cells get IL-4 → produce IgE
7. IgE binds to mast cells → on re-exposure to allergen → mast cell degranulation
8. Release of histamine, tryptase, PGD2 → EARLY PHASE reaction (within minutes)
9. Eosinophils recruited (via IL-5) → LATE PHASE reaction (hours later)

2.3 Key Cells in Fishman's

Mast Cells

• First responders in allergic asthma
• Release histamine (bronchoconstriction, edema, mucus), tryptase (activates other cells), PGD2
• BAL histamine peaks at 12 minutes after allergen challenge
• Tryptase normalizes at 48h; histamine stays elevated (other cells take over)

Eosinophils

• Major effectors in T2 asthma
• Release toxic granule proteins: MBP (major basic protein), ECP, EDN, EPX
• MBP → bronchial hyperreactivity by interfering with muscarinic receptors
• Cause airway remodeling, mucus plugs
• Key insight (Fishman's): Eosinophilia plays variable roles in different patients - explains why anti-IL-5 worked in some but not all

Neutrophils

• Recruited by IL-8, IL-17, G-CSF
• Key in non-T2 / severe asthma
• Found in sputum during severe exacerbations and fatal asthma (autopsy)
• Patients with neutrophilic asthma: more often female, obese, steroid-resistant
• Neutrophils release elastase → mucus production

T Lymphocytes (Th2 cells)

• Produce IL-4, IL-5, IL-13
• Critical mediators of allergic (T2) inflammation
• Th17 cells → IL-17 → neutrophil recruitment (non-T2 pathway)

ILC2 (Innate Lymphoid Cells type 2)

• Innate counterpart of Th2 cells
• Activated by alarmins (TSLP, IL-33, IL-25) without needing allergen sensitization
• Important in non-allergic eosinophilic asthma and severe asthma with nasal polyps
• More steroid-resistant than Th2 cells

Airway Epithelial Cells

• Act as barrier AND as initiators of inflammation
• In asthma: defective tight junctions → allergens penetrate more easily
• Decreased type I interferon production → increased viral susceptibility → exacerbations
• Reduced antioxidant defense → more oxidative damage
• Release alarmins (TSLP, IL-25, IL-33) → link epithelium to T2 and non-T2 inflammation

2.4 Molecular Mediators (Fishman's)

Cytokines

Leukotrienes (Fishman's - arachidonic acid metabolites)

• Produced via 5-lipoxygenase pathway (FLAP is the activating protein)
• LTC4, LTD4, LTE4 → potent bronchoconstriction (much more potent than histamine)
• Also increase mucus secretion and vascular permeability
• Targeted by: LTRA (montelukast)

Prostanoids (from COX pathway)

• PGD2, PGF2a, TXA2 → bronchoconstrictors
• PGE2 → bronchodilatory (protective)
• PGD2 is the predominant prostanoid in asthma
• Acts via CRTH2 receptor on Th2 cells and ILC2 (target of fevipiprant)

Nitric Oxide (FeNO)

• Low levels: bronchodilator, protective
• High levels in asthma (iNOS upregulated by TSLP, IL-13)
• FeNO reflects eosinophilic airway inflammation → used as biomarker for T2 asthma
• Higher FeNO = more eosinophils in airway wall

Granule Proteins

2.5 Airway Remodeling (Fishman's - Chronic Changes)

"Irreversible structural changes occur in the airway in asthma that are collectively called 'airway remodeling.' This involves the chronic cycle of 'injury-repair.'" - Fishman's Ch. 43

1. Epithelial changes - shedding, metaplasia, defective repair
2. Subepithelial fibrosis - from TGF-β, fibroblast/myofibroblast activity
3. Smooth muscle hypertrophy + hyperplasia - larger, more muscle → more bronchoconstriction
4. Increased angiogenesis - new blood vessels
5. Goblet cell hyperplasia - more mucus cells

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PART 3: ASTHMA PHENOTYPES (Fishman's)

Fishman's key quote: "The study of these factors has led to a greater understanding that different phenotypes of asthma exist, and treatment of asthma based on a patient's predominant phenotype may soon be possible."

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PART 4: DIAGNOSIS

4.1 Symptoms (GINA 2026)

• Wheeze (musical, expiratory sound)
• Shortness of breath
• Chest tightness
• Cough (often worse at night / early morning)

• Symptoms vary day to day, season to season
• Triggered by exercise, cold air, smoke, allergens, viral infections
• Respond to bronchodilators
• Personal/family history of atopy

4.2 Spirometry (GINA 2026)

4.3 Biomarkers (GINA 2026 - updated emphasis)

4.4 Bronchial Provocation Testing

• When spirometry is normal but asthma suspected
• Methacholine challenge: Positive if PC20 ≤16 mg/mL (or ≤8 for some labs)
• Exercise challenge: >10% FEV1 fall
• Very sensitive (negative = asthma unlikely); less specific

4.5 Diagnosis in Children <5 years (GINA 2026 - all 3 required)

1. Recurrent acute wheezing episodes
2. No other likely cause for respiratory symptoms
3. Timely clinical response to asthma medications

4.6 Differential Diagnosis

• COPD (fixed obstruction, older, smoker)
• Vocal cord dysfunction (inspiratory stridor, normal spirometry between episodes)
• Heart failure (cardiac asthma - elevated BNP, bilateral crackles)
• Bronchiectasis (daily productive cough)
• Cystic fibrosis (young, pancreatic, clubbing)
• GERD-related cough
• Hyperventilation syndrome

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PART 5: ASSESSMENT

5.1 GINA 2026 - Symptom Control (ask about past 4 weeks)

5.2 GINA 2026 - Severity (retrospective, after treatment)

5.3 New GINA 2026 Assessment Tools

• CAAT (Chronic Airways Assessment Test) - NEW addition to GINA 2026
• Peds-AIRQ (Pediatric Asthma Impairment and Risk Questionnaire) - NEW for children
• PRAM (Pediatric Respiratory Assessment Measure) - for acute exacerbations in children
• Also: ACQ (Asthma Control Questionnaire), ACT (Asthma Control Test) - existing tools

5.4 Risk Factors for Exacerbations (GINA 2026)

• Uncontrolled symptoms
• Frequent SABA use
• Not on ICS
• Poor inhaler technique or adherence
• Smoking or allergen exposure
• Obesity, rhinosinusitis, GERD, pregnancy
• Low FEV1 (<60% predicted)
• Previous severe exacerbation or near-fatal asthma

5.5 Red Flags for Fatal/Near-Fatal Asthma (NEW - GINA 2026)

• Previous near-fatal asthma requiring intubation
• Hospital or ER visit for asthma in the past year
• Not currently using ICS
• Currently using or recently stopped OCS
• Over-reliance on SABA (using >1 canister/month)
• Psychiatric illness or psychosocial problems
• Poor adherence or no written action plan
• Food allergy + asthma

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PART 6: TREATMENT - GINA 2026 STEPWISE APPROACH

6.1 The Two Tracks (BIG NEW CONCEPT - GINA 2026)

Key GINA 2026 message: ICS-formoterol as anti-inflammatory reliever (AIR) reduces severe exacerbations and hospitalizations by ~2/3 compared with SABA-alone treatment, even in patients considered "mild."

6.2 GINA 2026 - Treatment Steps (Track 1 - Preferred)

6.3 GINA 2026 - Treatment Steps (Track 2 - Alternative)

6.4 Drug Classes - Simple Explanation

ICS (Inhaled Corticosteroids) - Most Important Drug

• Examples: Budesonide, Fluticasone (propionate + furoate), Beclometasone, Ciclesonide, Mometasone
• Action: Anti-inflammatory, reduce airway swelling, improve AHR
• Effect: Reduce symptoms, improve FEV1, reduce exacerbations and hospitalizations
• Key point from GINA 2026 Severe Asthma Guide: ICS are "the most effective anti-inflammatory medications for asthma"

LABA (Long-Acting Beta-2 Agonists)

• Examples: Formoterol (fast-onset), Salmeterol (slow-onset), Vilanterol
• Always combined with ICS - never alone in asthma
• Formoterol is special: fast-acting like SABA → can be used as reliever (basis of MART)

SABA (Short-Acting Beta-2 Agonists)

• Examples: Salbutamol (albuterol), Terbutaline
• Quick relief within minutes
• GINA 2026: Not recommended as sole reliever; overuse = poor control = danger

LAMA (Long-Acting Muscarinic Antagonists)

• Example: Tiotropium
• Add-on at Steps 4-5
• GINA 2026: Triple therapy (ICS-LABA-LAMA) reduces severe exacerbations less than biologic therapy but may benefit Step 5 patients who do not qualify for biologics

LTRA (Leukotriene Receptor Antagonists)

• Example: Montelukast
• Add-on at Steps 2-3
• Good for: aspirin-sensitive asthma, exercise-induced asthma, allergic rhinitis coexisting with asthma

OCS (Oral Corticosteroids) - Minimize!

• GINA 2026 new emphasis: Strongly recommends minimizing OCS use due to cumulative side effects
• Strategies: Treat modifiable risk factors, use ICS-formoterol as reliever, education, biologics first
• Short courses (5-7 days) acceptable for acute exacerbations

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PART 7: BIOLOGICS (Step 5 - Severe Asthma)

7.1 Overview (GINA 2026 updates)

7.2 Biologic Table (UPDATED GINA 2026)

7.3 DEPEMOKIMAB - New Addition in GINA 2026 ⭐

• Ultra-long-acting anti-IL-5 monoclonal antibody
• Dosing: Subcutaneous injection TWICE YEARLY (every 6 months!) - major convenience advantage
• Approved for severe eosinophilic asthma (≥12 years)
• Also approved for CRSwNP (≥18 years)
• Added to GINA 2026

7.4 Non-Asthma Indications (NEW TABLE - GINA 2026)

7.5 Biologic Decision Tree (GINA 2026 Update)

• Check for Type 2 inflammation (blood eos, FeNO)
• Consider comorbidities (nasal polyps, atopic dermatitis, urticaria, EGPA)
• Consider practical issues: cost, administration route, dosing frequency, patient preference
• Consider predictors of response (higher eos/FeNO = better response to anti-IL-5/anti-IL-4)

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PART 8: ACUTE EXACERBATIONS

8.1 Severity Assessment

GINA 2026 Update: SpO2 threshold for urgent management = <92% (previously debated)

8.2 Acute Management (GINA 2026)

1. Bronchodilator: Repeated rapid-acting inhaled SABA (or ICS-formoterol as alternative to SABA in mild exacerbations per GINA 2026)
2. +Ipratropium (SAMA): Add for severe exacerbations
3. Oxygen: Controlled flow; target SpO2 93-95%
4. Systemic corticosteroids: Oral prednisolone 40-50 mg/day OR IV hydrocortisone; 5-7 days
5. Magnesium sulfate IV: For severe exacerbations not responding; improves FEV1 and reduces hospitalization

8.3 NEW GINA 2026 Exacerbation Flowcharts

• New primary care flowcharts for managing exacerbations
• ICS-formoterol as alternative to SABA for mild exacerbations - can reduce need for OCS

8.4 Discharge Checklist (GINA 2026)

• ✅ Start/adjust ICS-containing controller
• ✅ Verify/step up to ICS-formoterol reliever
• ✅ Check inhaler technique (new GINA 2026 guidance on single-breath + tidal breathing techniques)
• ✅ Address triggers/modifiable risk factors
• ✅ Written asthma action plan
• ✅ Follow-up within 1 week

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PART 9: SPECIAL SITUATIONS

9.1 Vaccines (GINA 2026 Updated Evidence)

• Influenza vaccine: Recommended annually for all asthmatics
• RSV vaccine: Updated evidence incorporated in GINA 2026
• COVID-19 vaccine: Updated evidence incorporated in GINA 2026
• Vaccines reduce exacerbation risk in patients susceptible to viral triggers

9.2 GLP-1 Agonists (GINA 2026 - New Observation)

• Observational data (not yet definitive) suggesting GLP-1 agonists (like semaglutide) may improve asthma outcomes
• Likely mechanism: weight loss reduces obesity-related asthma
• GINA 2026 notes "potential future role" - watch this space

9.3 Asthma in Pregnancy

• Uncontrolled asthma > drug risk to fetus
• Continue ICS - budesonide is most-studied and preferred
• Step approach same as non-pregnant adults

9.4 Aspirin/NSAID-Exacerbated Asthma (AERD)

• Samter's Triad: Asthma + nasal polyps + aspirin sensitivity
• Add LTRA (montelukast) - blocks LTE4 pathway triggered by aspirin
• Consider aspirin desensitization
• Biologics effective (dupilumab, mepolizumab, tezepelumab also cover CRSwNP)

9.5 Allergic Bronchopulmonary Aspergillosis (ABPA)

• Fungal sensitization in asthma → extremely difficult to control
• GINA 2026: OCS ± antifungal agent
• Consider biologics for underlying eosinophilic asthma

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PART 10: INHALER TECHNIQUE (NEW GUIDANCE - GINA 2026)

• Spacer recommended with pMDI for all patients
• Check technique at EVERY clinic visit

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PART 11: GINA 2026 KEY UPDATES SUMMARY

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QUICK MEMORY AIDS

FISHMAN'S ASTHMA CORE = 3 Bs
B - Bronchoconstriction (variable, reversible airflow obstruction)
B - Bronchial Hyperresponsiveness (airway overreacts to triggers)
B - Bronchial inflammation (Chronic, T2 or non-T2)

INFLAMMATORY CELLS = MELT BEN
M - Mast cells (early phase)
E - Eosinophils (late phase, T2)
L - Lymphocytes (Th2 = IL-4/5/13; Th17 = neutrophils)
T - Th2 cells
B - Basophils
E - Epithelial cells (alarmins)
N - Neutrophils (severe/non-T2)

GINA 2026 CONTROL (past 4 weeks, 4 questions):
0 YES = Well controlled ✅
1-2 YES = Partly controlled ⚠️
3-4 YES = Uncontrolled ❌

GINA 2026 TRACKS:
Track 1 (PREFERRED) = ICS-formoterol as reliever at ALL steps
Track 2 (Alternative) = ICS-SABA or SABA as reliever

NEW BIOLOGIC 2026 = DEPEMOKIMAB
- Anti-IL-5
- Twice yearly (6-monthly) dosing
- ≥12 years for severe eosinophilic asthma

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• Fishman's Pulmonary Diseases and Disorders, 2-Volume Set (ISBN 9781260473940) - Chapter 43: Pathophysiology of Asthma
• GINA 2026 Global Strategy Report - Published May 5, 2026
• GINA 2026 Severe Asthma Guide v7.0 - May 2026
• GINA 2026 Key Updates Summary - Pulmonology Advisor