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🫁 Asthma - Comprehensive Notes

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1. Definition

"Asthma 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."

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2. Epidemiology

• Affects 4-8% of the general population
• Most common pulmonary disorder in pregnancy (3.7-8.4% of pregnancies)
• Often presents first in childhood; can arise at any age
• Risk factors for childhood onset: family history of asthma, personal/family history of atopy (atopic dermatitis, allergic rhinitis, conjunctivitis)

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3. Pathophysiology

A. Airway Inflammation

• Eosinophilic inflammation - the classic Type 2 pathway, driven by IL-4, IL-13, and IL-5
• Non-eosinophilic (non-Type 2) inflammation - neutrophilic or paucigranulocytic; less responsive to corticosteroids
• Approximately 30-50% of asthmatics have non-eosinophilic inflammation with decreased response to ICS

B. Airway Hyperresponsiveness (AHR)

• Exaggerated bronchoconstriction response to stimuli (methacholine, exercise, cold air, allergens)
• Measured by PC20 (provocative concentration causing 20% fall in FEV1)

C. Airway Remodeling

• Structural changes from chronic inflammation: subepithelial fibrosis, smooth muscle hypertrophy/hyperplasia, goblet cell metaplasia, mucus hypersecretion
• Airway smooth muscle plays a major role - bronchial thermoplasty targets this

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4. Clinical Features

Symptoms

• Wheeze (expiratory > inspiratory)
• Shortness of breath
• Chest tightness
• Cough (especially nocturnal or with exercise)
• Symptoms vary over time and in intensity - this variability is a hallmark

Triggers

• Allergens (dust mites, pollen, animal dander)
• Respiratory infections (viral URTIs)
• Exercise and cold air
• Aspirin/NSAIDs (aspirin-exacerbated respiratory disease)
• Chemical exposures (occupational asthma)
• Gastroesophageal reflux, stress, obesity

Physical Examination

• May be normal between attacks
• During attack: expiratory wheeze on auscultation, prolonged expiration, use of accessory muscles
• Silent chest = very severe obstruction (ominous sign)

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5. Diagnosis

Step-by-step approach:

• Bronchodilator reversibility = FEV1 or FVC increases by ≥12% AND ≥200 mL post-bronchodilator → Diagnosis confirmed

• Perform methacholine challenge test
  • Positive (PC20 ≤ 8 mg/mL or equivalent) → Likely asthma
  • Negative → Consider alternative diagnosis; obtain lung volumes, DLCO, chest imaging

Differential Diagnosis

Biomarkers / Phenotyping

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6. Pulmonary Function Tests (PFTs)

ATS Impairment Rating for Asthma (3 domains scored 0-4):

• A. Post-bronchodilator FEV1 (0 = normal; 4 = <50% predicted)
• B. Reversibility / AHR (PC20)
• C. Minimum medication need (0 = none; 4 = daily oral steroids)

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7. Asthma Control & Monitoring

• Peak Expiratory Flow (PEF) monitoring: diurnal variability >20% = suboptimal control
• PEF correlates strongly with symptom burden (Asthma Control Test)
• PEF predominantly reflects large airway patency - may underestimate small airway involvement
• PEF ≈ 7% lower with peak flowmeters vs. spirometry
• Personal best PEF should be established after optimal therapy and re-evaluated frequently

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8. Management

Step Therapy (GINA-based)

Key GINA 2019 update: SABA-only treatment (without ICS) is no longer recommended even for mild intermittent asthma - all patients should receive ICS because even mild asthma shows chronic airway inflammation.

Drug Classes

• Salbutamol (albuterol), terbutaline
• Rapid bronchodilation for acute symptoms (rescue)
• Frequent SABA need signals worsening control

• Beclomethasone, budesonide, fluticasone, mometasone, ciclesonide
• Oral bioavailability: fluticasone ~1%, mometasone <1%, ciclesonide near 0% (activated only in lung tissue) - minimizes systemic effects
• Systemic absorption from lung itself can cause: growth suppression in children, decreased bone mineral density, cataracts
• Preferred controller for all persistent asthma

• Formoterol, salmeterol
• Should only be used with ICS (never as monotherapy in asthma)
• ICS/LABA combination inhalers are preferred

• Montelukast, zafirlukast
• Alternative to ICS for mild persistent asthma; adjunct therapy
• Particularly useful with concomitant allergic rhinitis

• Tiotropium - add-on for step 4-5

• Oral bronchodilator and mild anti-inflammatory
• Narrow therapeutic window; requires monitoring

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9. Special Situations

Asthma in Pregnancy

• Poorly controlled asthma risks: preeclampsia, preterm birth, low birth weight, IUGR, perinatal death
• Natural history: 22% worsen, 29% improve, 49% unchanged
• Preferred ICS in pregnancy: Budesonide (best safety data); beclomethasone and fluticasone also acceptable
• LABA only with concurrent ICS
• Objective spirometry + home PEF monitoring recommended
• Risks of poorly controlled asthma far outweigh risks of drug therapy

Asthma + Obesity

• Obese asthmatics are a distinct, difficult-to-control phenotype
• Obesity-associated asthma may be non-Type 2 / non-eosinophilic
• High prevalence of comorbid OSA in obese asthmatics

Asthma + OSA (Nocturnal Asthma)

• OSA prevalence is increased in asthmatic patients
• Mechanisms of interaction: sleep fragmentation, hypoxemia → oxidative stress → bronchoconstriction
• CPAP improves asthma quality of life, reduces exacerbations and bronchodilator use
• CPAP is not recommended in asthmatics without OSA

Occupational Asthma / Work-Exacerbated Asthma

• Sensitizer-induced (new-onset) vs. work-exacerbated (pre-existing worsened by work)
• Requires identifying occupational exposures; removing sensitizer exposure critical

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10. Inhaler Devices

• Peak Inspiratory Flow (PIF) ≥60 L/min is optimal for dry powder inhalers (DPIs)
• PIF <30 L/min = insufficient for DPI actuation
• Factors associated with low PIF: advanced age, female sex, reduced lung function
• High oropharyngeal deposition (up to 80% with pMDIs) → swallowed drug → importance of low oral bioavailability of ICS

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Key Points Summary

1. Asthma = chronic airway inflammation + variable airflow obstruction + AHR
2. Diagnosis confirmed by reversibility on spirometry (FEV1/FVC ↑ ≥12% + ≥200 mL)
3. Phenotyping (eosinophilic vs. non-eosinophilic) guides biologic selection
4. ICS is the cornerstone of controller therapy at all steps
5. GINA 2019: no SABA-only treatment - even mild asthma needs ICS
6. LABA must always be co-prescribed with ICS
7. PEF diurnal variability >20% = poor control
8. Biologics are reserved for Step 5 severe/refractory disease
9. Budesonide is the preferred ICS in pregnancy
10. Comorbidities (OSA, obesity, GERD, rhinosinusitis) must be addressed

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