Occupational Bronchiolitis Obliterans

Occupational bronchiolitis obliterans is fixed small airway obstruction from constrictive bronchiolitis caused by workplace inhalational exposures. Irritant gases, fumes and flavouring chemicals are the usual causes.

Causes. Diacetyl and 2,3-pentanedione, nitrogen oxides (silo filler's disease), chlorine, ammonia, sulphur dioxide, hydrochloric acid, phosgene, sulphur mustard, metal fume, fly ash and some plastic and acid anhydride exposures.

Epidemiology. Uncommon and often underdiagnosed. Disease follows an acute toxic inhalation or chronic repeated exposure.

Course. In acute inhalation injury, symptoms may settle and then recur weeks later with progressive obstruction. In silo filler's disease, relapse occurs about 2 to 6 weeks after the acute illness.

Prognosis. Obstruction is usually irreversible, with progression to respiratory failure in some patients.

Pathophysiology.

Toxic gases and particles injure the bronchiolar epithelium. Disordered repair leads to subepithelial fibrosis, luminal narrowing and obliteration of small airways.

Air trapping, hyperinflation and mosaic perfusion follow.

• Progressive dyspnoea, dry cough and wheeze, often after a documented inhalation event.
• Chest examination may be normal, or show wheeze or hyperinflation.
• Chronic exposure cases develop symptoms gradually.

Red flags.

• Progressive hypoxaemia, tachypnoea or respiratory failure.
• Relapse of dyspnoea or fever after initial recovery from a toxic gas exposure.

• Exposure history: agent, duration, ventilation, protection, accident events.
• Spirometry: obstruction with poor response to bronchodilator; raised residual volume.
• HRCT with expiratory images: mosaic attenuation, air trapping, bronchial wall thickening, bronchiectasis.
• Gas transfer normal or mildly reduced.
• Surgical lung biopsy showing constrictive bronchiolitis when features are atypical.
• Exclude infection, connective tissue disease and graft or drug related causes.

Differential diagnosis. Asthma, chronic obstructive pulmonary disease, hypersensitivity pneumonitis, post-infectious bronchiolitis, connective tissue disease associated bronchiolitis, drug induced bronchiolitis, graft related bronchiolitis.

• Remove from exposure and control sources.
• Smoking cessation; vaccination; pulmonary rehabilitation; inhaled bronchodilators for symptomatic obstruction.
• Evidence for drug therapy is limited to case series. Prednisolone 0.5 mg/kg orally once daily in the morning, maximum 40 mg daily, for 4 weeks as a test course. Continue with taper to the lowest effective dose over 8 to 12 weeks only if symptoms or spirometry improve; otherwise stop or taper over 2 weeks. Monitor glucose, blood pressure, weight, mood and infection. Exclude active tuberculosis first; caution in diabetes and peptic ulcer; no renal adjustment.
• Azithromycin 250 mg orally three times each week for a 3-month test course, continued to 12 months only if FEV1 stabilises or improves. Maximum 250 mg each dose. Exclude non-tuberculous mycobacterial infection first. Monitor ECG for QTc, liver enzymes and hearing. Avoid when QTc is over 470 ms or with other QT-prolonging drugs; caution when eGFR is under 10 and in significant liver disease.
• Long term oxygen when resting PaO2 is under 7.3 kPa, or 7.3 to 8 kPa with polycythaemia or cor pulmonale.
• Lung transplant assessment in severe progressive disease.

Monitoring. After acute toxic inhalation, review spirometry and symptoms at 2 weeks, 6 weeks and 3 months. Established disease: spirometry every 3 to 6 months, then yearly.

Referral and escalation. Respiratory and occupational physician; workplace investigation; transplant assessment for advanced disease; notification and compensation where required.