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Bronchial Asthma & Related Syndromes — Complete Study Guide (Questions 35–52)

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35. Etiological Factors Contributing to the Development of Asthmatic Syndrome

Host (Internal) Factors

Environmental (External) Factors

Triggers (things that worsen existing asthma): exercise, cold air, emotional stress, GERD, menstruation.

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36. Classification of Bronchial Asthma

By Etiology

1. Atopic (extrinsic/allergic) — IgE-mediated, triggered by identifiable allergens
2. Non-atopic (intrinsic) — No identifiable allergen; triggered by infection, irritants, exercise
3. Mixed — Features of both
4. Occupational asthma — Caused by workplace exposures
5. Drug-induced — Aspirin/NSAID-induced, beta-blocker-induced

By Severity (GINA / NHLBI)

By Control Level (GINA 2023)

• Well-controlled — Minimal symptoms, no limitations
• Partly controlled — Some daytime symptoms, minor limitation
• Uncontrolled — Frequent symptoms, significant limitation

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37. Role of Allergic Factors in the Development of Bronchial Asthma

Sensitization Phase

• Allergen (e.g., dust mite proteins) enters the airway
• Antigen-presenting cells (dendritic cells) activate Th2 lymphocytes
• Th2 cells release IL-4, IL-5, IL-13 → B cells produce IgE
• IgE binds to mast cells and basophils (sensitization complete — no symptoms yet)

Early-Phase Reaction (minutes after re-exposure)

• Re-exposure → allergen cross-links IgE on mast cells
• Mast cells degranulate → release:
  • Histamine — bronchoconstriction, mucus secretion
  • Leukotrienes (LTC₄, LTD₄) — potent, sustained bronchoconstriction
  • Prostaglandins, tryptase
• Peak effect: 15–30 minutes; resolves in 1–2 hours

Late-Phase Reaction (3–12 hours later)

• Eosinophils, T cells, neutrophils recruited
• IL-5 drives eosinophil activation → airway inflammation, epithelial damage
• This phase causes prolonged symptoms and airway hyperresponsiveness
• Repeated cycles → airway remodeling (fibrosis, smooth muscle hypertrophy, goblet cell hyperplasia)

Key Mediators Summary

• IgE — master switch for allergic asthma
• Eosinophils — main effector cells causing chronic inflammation
• Leukotrienes — most potent bronchoconstrictors (target of montelukast)
• Th2 cytokines (IL-4, IL-5, IL-13) — drive the entire allergic cascade

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38. Influence of Occupational Hazards on the Development of Bronchial Asthma

Two Mechanisms

• Latency period of months to years before symptoms appear
• IgE-mediated (high-molecular-weight agents) or non-IgE immune (low-molecular-weight agents)
• Symptoms recur/worsen on workdays and improve on weekends/holidays (key clue)

• Caused by a single massive exposure to irritant gas/fume
• Symptoms begin within 24 hours
• No latency period, no IgE involvement

High-Risk Occupations & Agents

Diagnostic Clues

• Symptoms correlate with workdays (better on weekends/vacation)
• Serial peak flow monitoring at and away from work
• Specific inhalation challenge (gold standard)
• Positive skin prick test or specific IgE to occupational allergen

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39. Hereditary Predisposition to Bronchial Asthma

Evidence for Genetic Basis

• Concordance in identical twins: ~60%
• If one parent has asthma: child's risk ~25%
• If both parents have asthma: child's risk ~50%

Key Genetic Associations

What Is Inherited?

1. Atopy — genetic tendency to produce IgE
2. Airway hyperresponsiveness — airways overreact to stimuli
3. Susceptibility to specific allergens (HLA-linked)

Note: Genetics sets the susceptibility; environment determines whether asthma actually develops.

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40. Diagnostic Criteria for Infectious-Allergic (Non-Atopic / Intrinsic) Bronchial Asthma

Typical Features

• Age of onset: Usually >35–40 years (adult onset)
• No personal/family history of atopic diseases (eczema, allergic rhinitis, urticaria)
• Skin prick tests: Negative
• Serum IgE: Normal or mildly elevated
• Blood eosinophilia: May be present (despite no allergy)
• Triggers: Respiratory infections (viral URIs, sinusitis), cold air, irritants, exercise, stress
• Pattern: Perennial (year-round), no seasonal variation
• Response to allergen avoidance: No improvement
• Sputum: Eosinophils ± neutrophils; often purulent during infections

Diagnostic Criteria

1. Obstructive spirometry (low FEV₁/FVC) reversible with bronchodilator (≥12% and ≥200 mL)
2. Airway hyperresponsiveness (methacholine/histamine challenge if needed)
3. No evidence of IgE-mediated sensitization (negative allergy tests)
4. Symptoms triggered by infections or non-allergic stimuli
5. Eosinophilia in blood or sputum (helps distinguish from pure infective exacerbation)

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41. Diagnostic Criteria for Atopic (Extrinsic/Allergic) Bronchial Asthma

Typical Features

• Age of onset: Childhood or young adult (but any age)
• Personal/family history of atopy (eczema, allergic rhinitis, food allergy)
• Skin prick tests: Positive to common aeroallergens
• Serum total IgE: Elevated (>100 IU/mL typically)
• Specific IgE (RAST/ImmunoCAP): Positive to offending allergen
• Blood eosinophilia: Often >4% or >300 cells/μL
• Triggers: Specific allergens (dust, pollen, pets), plus non-specific triggers
• Pattern: May be seasonal (pollen) or perennial (dust mite, pets)
• Exhaled NO (FeNO): Elevated (>25 ppb) — marker of eosinophilic airway inflammation

Diagnostic Criteria

1. Obstructive spirometry reversible with bronchodilator (FEV₁ increase ≥12% and ≥200 mL) — or positive methacholine challenge
2. Typical symptoms: episodic wheeze, shortness of breath, chest tightness, cough
3. Positive allergy workup: skin prick test or specific IgE to relevant allergen
4. Elevated total IgE and/or eosinophilia
5. Clinical correlation — symptoms match allergen exposure pattern

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42. Diagnostic Criteria for Status Asthmaticus

Clinical Features

Objective Criteria

• PEFR or FEV₁ <25–40% predicted despite treatment
• SpO₂ <90% on room air (or PaO₂ <60 mmHg)
• PaCO₂ normal or elevated (>42 mmHg in acute setting = danger — indicates fatigue, CO₂ retention, impending failure)
• pH <7.35 (respiratory acidosis = near-respiratory arrest)

A rising PaCO₂ in a tachypneic asthmatic is an emergency — the patient is tiring out.

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43. Signs and Symptoms of Cardiac Asthma as a Polyetiological Syndrome

Pathophysiology

• Elevated left ventricular end-diastolic pressure → pulmonary venous hypertension → pulmonary edema
• Peribronchial edema narrows airways → wheezing (mimics asthma)
• Reduced lung compliance (may be 1/10 of normal during acute episode)
• Increased airway resistance (both inspiratory and expiratory)

Causes (Polyetiological)

• Ischemic heart disease / acute MI
• Hypertensive heart disease
• Dilated cardiomyopathy
• Mitral stenosis/regurgitation
• Aortic stenosis
• Arrhythmias (especially rapid AF)
• Fluid overload

Classic Presentation

• Paroxysmal Nocturnal Dyspnea (PND): Patient wakes 1–3 hours after sleep, gasping, sits bolt upright, opens window for air
• Orthopnea: Must sleep with multiple pillows
• Audible wheeze (inspiratory + expiratory) — called "cardiac asthma"
• Pink frothy sputum (frank pulmonary edema)
• Profuse sweating
• History of heart disease, hypertension
• Bi-basal crackles on auscultation
• Raised JVP, peripheral edema (signs of heart failure)

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44. Differential Diagnosis: Bronchial Asthma vs. Cardiac Asthma

Key rule: BNP + CXR + clinical history quickly differentiate the two.

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45. Differential Diagnosis: Bronchial Asthma vs. COPD

Overlap syndrome (ACO — Asthma-COPD Overlap): smoker with asthma features + incomplete reversibility.

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46. Laboratory and Instrumental Diagnostics of Bronchial Asthma

Spirometry (most important)

• FEV₁/FVC < 0.70 during attack = obstruction
• Bronchodilator reversibility: FEV₁ increases ≥12% AND ≥200 mL after salbutamol (inhaled)
• PEFR (peak expiratory flow rate): Simple, bedside; monitors severity and response to treatment
• Methacholine/histamine challenge: If spirometry is normal but asthma suspected; positive = PC₂₀ <8–16 mg/mL

Blood Tests

• Eosinophil count: Elevated (>300/μL in atopic/eosinophilic asthma)
• Total serum IgE: Elevated in atopic asthma
• Specific IgE (RAST/ImmunoCAP): Identifies causative allergen
• ABG (arterial blood gas): During acute attack:
  • Mild: ↓PaCO₂, ↑pH (hyperventilation)
  • Severe: Normal PaCO₂ (ominous — patient tiring)
  • Very severe: ↑PaCO₂, ↓pH (respiratory acidosis = near-arrest)

Sputum Analysis

• Eosinophils (hallmark of eosinophilic/allergic asthma)
• Charcot-Leyden crystals (breakdown products of eosinophils)
• Curschmann spirals (mucus casts of small airways)

Exhaled NO (FeNO)

• Elevated (>25 ppb) = eosinophilic airway inflammation
• Guides ICS therapy, predicts response to anti-IL-5 biologics

Allergy Testing

• Skin prick tests: Quick, reliable for IgE-mediated sensitization
• Patch tests: For contact/delayed hypersensitivity

Imaging

• Chest X-ray: Hyperinflation, flattened diaphragm (in severe/chronic asthma); used to exclude complications (pneumothorax, pneumonia)
• CT chest: Not routine; used to detect complications, bronchiectasis, or rule out alternatives

Peak Flow Monitoring

• Home peak flow diary: Diurnal variability >20% over 3 days is diagnostic of asthma

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47. Relief of Status Asthmaticus: Tactics and Drugs

Immediate Steps

1. Oxygen — target SpO₂ 94–98%
2. Continuous monitoring (SpO₂, RR, HR, PEFR, ABG)
3. IV access; position upright

Drug Treatment (Step-Up Approach)

• Salbutamol (albuterol) 2.5–5 mg via nebulizer every 15–20 min; or continuous nebulization
• Can use MDI + spacer (equally effective if technique is good)
• IV β-agonists offer no advantage and more side effects — avoid routinely

• Ipratropium bromide 0.5 mg nebulized every 20 min × 3, then every 4 hours
• Additive bronchodilation with SABAs; reduces hospitalization

• IV methylprednisolone 1 mg/kg OR oral prednisone 40–60 mg
• Effect begins in 4–8 hours; reduces inflammation, restores β₂ responsiveness
• Give early (within 1 hour of arrival)

• IV MgSO₄ 1.2–2 g over 20 min → smooth muscle relaxation
• Particularly effective in severe asthma (FEV₁ <25–30% predicted)

• Heliox (helium-oxygen): Reduces airflow turbulence, buys time
• Aminophylline: Rarely used now; narrow therapeutic window
• Ketamine: Bronchodilator properties — useful for intubation in status asthmaticus

• Indications: Exhaustion, altered consciousness, PaCO₂ rising, pH <7.25
• Use permissive hypercapnia strategy; risk of dynamic hyperinflation (auto-PEEP)

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48. Use of Bronchodilators in Bronchial Asthma

Classes of Bronchodilators

Key Principles

• Aerosol route preferred over IV or oral — delivers drug directly to airways, minimizes systemic side effects
• Only 15% of inhaled drug reaches the target airways even with optimal technique
• A spacer device significantly improves lung deposition with MDI
• SABAs are rescue/reliever inhalers; overuse (>2 canisters/month) signals poor control
• LABAs must always be combined with ICS — not used as monotherapy (risk of asthma death without ICS)
• Inhaled corticosteroids (ICS) are the cornerstone controller medication — bronchodilators alone do not treat underlying inflammation

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49. Basic Drugs and Principles of Intensive Therapy for Bronchial Asthma

Stepwise GINA Approach

Drug Categories in Intensive Therapy

1. ICS (Inhaled Corticosteroids) — cornerstone anti-inflammatory
   • Beclomethasone, budesonide, fluticasone, mometasone
   • Prevent asthma deaths; reduce exacerbations; improve FEV₁
   • After inhalation: rinse mouth to prevent oral candidiasis
2. ICS + LABA combinations — most common maintenance therapy
   • Fluticasone/salmeterol (Seretide), budesonide/formoterol (Symbicort)
3. Biological therapies (Step 5 — severe refractory asthma)
   • Omalizumab (anti-IgE): For atopic asthma with elevated IgE
   • Mepolizumab, reslizumab, benralizumab (anti-IL-5/IL-5Rα): For eosinophilic asthma
   • Dupilumab (anti-IL-4Rα): Blocks IL-4 and IL-13; for eosinophilic or OCS-dependent asthma
4. Leukotriene receptor antagonists (LTRAs)
   • Montelukast — useful as add-on, especially in aspirin-exacerbated and exercise-induced asthma
5. Oral corticosteroids (OCS) — last resort for severe uncontrolled asthma; minimize due to systemic effects

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50. Principles of Treatment of Cardiac Asthma and Acute Pulmonary Edema

Key Principles

1. Position: Sit patient upright (legs dangling) — reduces venous return
2. Oxygen: High-flow O₂ (10–15 L/min); target SpO₂ ≥94%
3. Non-invasive ventilation: CPAP or BiPAP — reduces work of breathing and afterload, re-opens collapsed alveoli, reduces intubation need
4. Morphine (IV, 2–4 mg): Reduces anxiety, venodilation, reduces preload; use cautiously (may suppress respiration)
5. IV Loop diuretics (Furosemide): 40–80 mg IV → venodilation (within minutes) then diuresis (within 30 min) — reduces preload
6. Nitrates (GTN/isosorbide dinitrate): IV or sublingual — potent venodilators; reduce preload; contraindicated if SBP <90 mmHg
7. Treat the underlying cause:
   • Rapid AF → rate control (digoxin, amiodarone)
   • Acute MI → revascularization
   • Hypertensive emergency → IV antihypertensives
8. Inotropes (dobutamine, dopamine): If cardiogenic shock (low output failure) — increase cardiac contractility
9. Avoid: Beta-blockers (acute decompensation), excessive IV fluids

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51. Algorithm for Emergency Care During an Attack of Cardiac Asthma

PATIENT WITH ACUTE DYSPNEA + WHEEZE + HISTORY OF HEART DISEASE
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  [Sit upright, dangle legs; call for help]
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  High-flow O₂ via face mask (10-15 L/min)
               ↓
  IV access + monitoring (ECG, SpO₂, BP)
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  Sublingual GTN (nitroglycerine) 0.4 mg → repeat every 5 min if SBP >90
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  IV Furosemide 40-80 mg → reduces preload rapidly
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  IV Morphine 2-4 mg (slow) → anxiolysis + venodilation
  [OMIT if: hypotension, bradycardia, respiratory depression]
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  If SpO₂ still low / marked respiratory distress:
  → CPAP/BiPAP (Non-invasive ventilation)
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  Treat precipitating cause:
    - AF → rate control
    - Hypertension → IV nitrates/labetalol
    - MI → urgent PCI
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  If no response / shock → Inotropes (Dobutamine)
               ↓
  If respiratory failure → Intubation + mechanical ventilation

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52. Principles of Treatment of COPD

Non-Pharmacological

• Smoking cessation — single most important intervention; slows FEV₁ decline
• Pulmonary rehabilitation — improves exercise tolerance, quality of life
• Vaccinations: Influenza (annual), pneumococcal, COVID-19
• Nutrition and weight optimization
• Long-term oxygen therapy (LTOT): PaO₂ ≤55 mmHg; ≥15 hours/day → reduces mortality

Pharmacological (Stepwise)

Key Drug Classes

• SABAs: Salbutamol, terbutaline — rescue use
• SAMAs: Ipratropium — preferred over SABA in stable COPD (less tachycardia)
• LABAs: Salmeterol, formoterol, indacaterol
• LAMAs: Tiotropium (gold standard), umeclidinium, glycopyrronium
• ICS: Do NOT use alone in COPD; add only if blood eosinophils ≥300/μL or frequent exacerbations
• Phosphodiesterase-4 inhibitor: Roflumilast — reduces exacerbations in severe chronic bronchitic phenotype
• Azithromycin (low-dose, maintenance): Reduces exacerbation frequency in ex-smokers

COPD Exacerbation Treatment

• Oxygen: Controlled (target SpO₂ 88–92% — avoid hypercapnia with high-flow O₂)
• Short-acting bronchodilators (nebulized salbutamol + ipratropium)
• Systemic corticosteroids: Prednisolone 30–40 mg × 5 days
• Antibiotics: If purulent sputum, increased dyspnea, increased sputum volume (Amoxicillin, doxycycline, azithromycin)
• NIV (BiPAP): If pH <7.35 with hypercapnia — prevents intubation

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Quick Reference Comparison Card

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