Reactive Airways Dysfunction Syndrome

Reactive airways dysfunction syndrome is asthma-like illness that begins after a single, high-level exposure to an irritating gas, smoke, fume or vapor, and persists for at least 3 months. It is the most clearly defined form of irritant-induced asthma. There is no latency and no prior sensitization. Exposure may be industrial (chlorine, ammonia, acids, welding fumes, floor sealants, paint strippers), domestic (mixing bleach and acid cleaners) or from fires and spills.

Criteria

• No previous respiratory complaints
• Onset of symptoms after a single exposure to a very high concentration of an irritant
• Onset within 24 hours of exposure
• Symptoms resembling asthma (cough, wheeze, dyspnea), persisting for at least 3 months
• Airflow obstruction on spirometry, or nonspecific bronchial hyperresponsiveness on methacholine challenge
• Exclusion of other pulmonary diseases

Mechanism: direct epithelial injury, desquamation, neurogenic inflammation and airway remodeling with subepithelial fibrosis. The natural history is improvement in the first 1 to 2 years, but 30 to 50% have persistent hyperreactivity for years, and some have fixed obstruction. Complications: chronic asthma, steroid dependence, exacerbations, anxiety and loss of work capacity.

• Within hours: cough, wheeze, chest tightness, dyspnea, burning of the eyes, nose and throat
• Sputum with bronchospasm, and sometimes hoarseness and stridor
• Persistent symptoms on exertion, cold air, smoke and strong smells, weeks to months after exposure
• Normal examination between episodes in many patients
• Red flags: stridor, hemoptysis, pulmonary edema, hypoxemia and a patient who cannot leave the exposure

1. Exposure history: the agent, concentration (if known), duration, ventilation, protective equipment and time to the first symptom.
2. Spirometry: obstruction (FEV1 to FVC ratio under 0.70) with variable reversibility, or normal.
3. Methacholine challenge: a provocative concentration causing a 20% fall in FEV1 of 8 mg/mL or lower confirms airway hyperresponsiveness (a normal test makes the diagnosis unlikely).
4. Chest radiograph: usually normal early, and used to exclude pneumonitis and edema. High-resolution CT if symptoms are atypical, showing air trapping or bronchial wall thickening.
5. Exclusion of other causes: pre-existing asthma, vocal cord dysfunction, bronchiolitis obliterans, hypersensitivity pneumonitis and cardiac disease.
6. Peak flow diary to document variability.

Differentials: pre-existing asthma exacerbated by exposure, sensitizer-induced occupational asthma, vocal cord dysfunction, bronchiolitis obliterans, post-infectious cough and anxiety hyperventilation.

1. Acute management after exposure: remove from the source, give oxygen to maintain saturation over 94%, and salbutamol 2.5 to 5 mg nebulized every 20 minutes for 3 doses. Observe for at least 6 to 24 hours after a large exposure, since pulmonary edema may be delayed.
2. Corticosteroids for acute symptoms: prednisolone 40 mg orally once daily for 5 to 7 days (children 1 mg/kg, maximum 40 mg).
3. Maintenance inhaled therapy:
   • Budesonide-formoterol 200/6 micrograms, 1 to 2 inhalations twice daily, adjusted to control.
   • Salbutamol 100 micrograms, 2 puffs as a reliever.
   • Montelukast 10 mg orally once daily at night as an add-on.
   • Tiotropium 5 micrograms once daily when control is incomplete.
4. Severe or persistent disease: step up to high-dose inhaled steroid, and consider omalizumab 150 to 375 mg SC every 2 to 4 weeks or mepolizumab 100 mg SC every 4 weeks if allergic or eosinophilic features are present.
5. Avoid further irritant exposures: respiratory protection, workplace changes and avoidance of smoke and strong irritants.
6. Smoking cessation, with varenicline 0.5 mg orally once daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks.
7. Psychological support for anxiety and post-traumatic symptoms.
8. Occupational management: notification, workplace investigation and compensation, with modified duties.

Follow-up at 4 to 6 weeks, 3 months and 6 months with spirometry, and then yearly. Stepping down treatment is possible after 6 to 12 months of stability. Counsel that improvement may continue for 2 years.