What are the differentials and management options for reactive airway disease?

Differential Diagnosis of Reactive Airway Disease

The differential diagnosis for reactive airway disease includes classic asthma, cough-variant asthma, exercise-induced bronchoconstriction, occupational asthma, reactive airways dysfunction syndrome (RADS), allergic rhinitis with lower airway involvement, bronchiolitis (particularly in Sjögren's syndrome), bronchiectasis, and drug-induced bronchospasm. 1, 2

Primary Differentials

Classic Asthma vs. Cough-Variant Asthma

• Classic asthma presents with recurrent wheezing, breathlessness, chest tightness, and coughing (particularly nocturnal or early morning), with documented variable airflow obstruction on spirometry 1
• Cough-variant asthma manifests as persistent cough without audible wheeze, but demonstrates airway hyperresponsiveness on bronchoprovocation testing and responds to asthma medications 3
• Both conditions share underlying chronic inflammation involving mast cells, eosinophils, neutrophils, T lymphocytes, macrophages, and epithelial cells 1, 2

Exercise-Induced Bronchoconstriction

• Triggered by cold/dry air inhalation, high allergen environments, or specific exposures like trichloramines in indoor pool air 2
• Inflammatory mediators (histamine, tryptase, leukotrienes) are released during exercise or exposure challenges 2
• Pretreatment with short-acting beta-agonists, leukotriene receptor antagonists, cromolyn, or nedocromil is recommended 1

Occupational Asthma vs. RADS

• Occupational asthma develops after weeks to years of workplace exposure to high-molecular-weight allergens or low-molecular-weight agents, accounting for 15-25% of adult asthma 2
• Symptoms improve away from workplace, with 100% of workers sensitized to high-molecular-weight proteins developing rhinitis 4
• RADS occurs after a single high-level irritant exposure (gas, vapors, fumes), causing persistent bronchial hyperreactivity within hours to minutes of exposure 5, 6
• RADS is nonimmunologic, can persist for years, and shows positive methacholine challenge testing 5

Secondary Differentials

Allergic Rhinitis with Lower Airway Disease

• The "united airway" concept demonstrates that nasal inflammation from allergens triggers parallel lower airway responses 4
• Presents with clear rhinorrhea, nasal congestion, pale nasal mucosa, red/watery eyes, plus respiratory symptoms 4
• Indoor allergens (house-dust mites, animal proteins, cockroaches, fungi) and outdoor allergens (pollen, molds) induce both IgE-mediated inflammation and airway hyperresponsiveness 2

Sjögren's-Associated Airway Disease

• Small airway disease may represent follicular or constrictive bronchiolitis with variable inflammation (neutrophilic, lymphocytic, eosinophilic) 4
• Bronchiectasis shows atypical airway dilation larger than accompanying bronchial artery on imaging 4
• Xerotrachea causes chronic cough (>8 weeks) and requires evaluation for common causes before attributing to Sjögren's 4

Drug-Induced Bronchospasm

• Beta-blockers cause bronchospasm and are contraindicated in reactive airway disease 4
• However, cardioselective beta-blockers produce only a 7.46% decrease in FEV1 with single doses and no significant change with continued treatment, maintaining beta-agonist responsiveness 7
• Other culprits include ACE inhibitors, NSAIDs/aspirin, and rhinitis medicamentosa from overuse of intranasal decongestants 4

Diagnostic Approach Algorithm

Step 1: Establish Temporal Pattern

• Acute onset (hours to minutes): Consider RADS from single high-level irritant exposure 5, 6
• Subacute (weeks to months): Consider occupational asthma with workplace correlation 4, 2
• Chronic/recurrent: Consider classic asthma, cough-variant asthma, or allergic rhinitis 1, 3

Step 2: Identify Predominant Symptoms

• Wheezing + chest tightness + dyspnea: Classic asthma 1
• Isolated persistent cough without wheeze: Cough-variant asthma requiring bronchoprovocation testing 3
• Symptoms only with exercise: Exercise-induced bronchoconstriction 2
• Nasal symptoms + respiratory symptoms: Allergic rhinitis with lower airway involvement 4

Step 3: Objective Testing

• Spirometry with bronchodilator: Document reversible airflow obstruction (≥12% and ≥200 mL FEV1 improvement) 1
• Peak flow monitoring: ≥20% variability with minimum 60 L/min change suggests asthma even without wheeze 3
• Methacholine challenge: Confirms airway hyperresponsiveness when spirometry is normal 1, 3, 5
• Specific IgE testing (skin or blood): Identify causative allergens when diagnosis is uncertain or empiric treatment fails 4

Step 4: Exposure Assessment

• Workplace temporal relationship: Symptoms at work improving away suggests occupational asthma 4
• Single high-level irritant event: RADS diagnosis requires documented exposure 5, 6
• Environmental allergens: Indoor (dust mites, pets, cockroaches, mold) or outdoor (pollen) 2, 8
• Medication review: Beta-blockers, ACE inhibitors, NSAIDs, intranasal decongestant overuse 4, 7

Critical Pitfalls to Avoid

• Do not exclude reactive airway disease based on absence of wheezing—cough-variant asthma is a distinct presentation requiring the same diagnostic rigor 3
• Do not assume normal spirometry between episodes rules out asthma—peak flow monitoring and bronchoprovocation testing are essential 3
• Do not withhold cardioselective beta-blockers in mild-to-moderate reactive airway disease when indicated for heart failure, arrhythmias, or hypertension, as they produce minimal respiratory effects and maintain beta-agonist responsiveness 7
• Do not overlook occupational exposures—15-25% of adult asthma is work-related, and removal from exposure is the best treatment 2
• Do not diagnose RADS without documented single high-level irritant exposure—this is a specific syndrome distinct from typical occupational asthma 5, 6