Respiratory Bronchiolitis-Associated Interstitial Lung Disease

Respiratory bronchiolitis associated interstitial lung disease is a smoking related disease in which pigmented macrophages accumulate in respiratory bronchioles and adjacent alveoli and cause symptoms and interstitial changes. Respiratory bronchiolitis alone, without symptoms, is a common incidental finding in smokers and is not a disease.

It occurs at 30 to 40 years, more in men, in heavy smokers with 30 or more pack years. It has a mild course and usually improves with smoking cessation.

Pathophysiology. Inhaled smoke particles are taken up by macrophages around the respiratory bronchioles, causing a patchy, bronchiolocentric chronic inflammation and mild fibrosis. Emphysema and other smoking related interstitial changes often coexist.

Gradual cough and exertional dyspnoea, sometimes with wheeze, and a smoking history. Examination may show basal crackles, and clubbing is rare. Severe respiratory failure is unusual.

Rapid worsening, fever or hypoxaemia suggests another process and needs prompt evaluation.

• High resolution CT: centrilobular nodules with ground glass opacity, bronchial wall thickening and upper zone emphysema, with air trapping.
• Lung function: mild restriction or mixed pattern with reduced transfer factor.
• Bronchoalveolar lavage: pigmented macrophages without other abnormalities, and exclusion of infection.
• Biopsy is rarely needed: pigmented macrophages in respiratory bronchioles with mild fibrosis.
• Exclude hypersensitivity pneumonitis, occupational exposure, connective tissue disease and drug causes.

Differential diagnosis.

• Desquamative interstitial pneumonia
• Hypersensitivity pneumonitis
• Pulmonary Langerhans cell histiocytosis
• Nonspecific interstitial pneumonia
• Smoking related emphysema or chronic bronchitis
• Asymptomatic respiratory bronchiolitis in smokers

• Stop smoking, the main treatment, with varenicline 0.5 mg daily for days 1 to 3, 0.5 mg twice daily for days 4 to 7, then 1 mg twice daily for 12 weeks (reduce to 0.5 mg twice daily at eGFR under 30), plus behavioural support, or nicotine replacement. Many patients improve within months.
• Corticosteroid for persisting or progressive symptoms after smoking cessation: prednisolone 0.5 mg/kg daily (30 to 40 mg) for 4 weeks, then tapered over 3 to 6 months.
• Inhaled bronchodilators for airflow limitation, for example tiotropium 5 micrograms (two inhalations) once daily.
• Vaccination against influenza, pneumococcus and COVID-19.
• Screen for lung cancer in eligible current and former smokers with annual low dose CT.

Complications and prognosis. Excellent outlook, with stable or improved disease in most, and persisting disease in those who continue to smoke. Progression is uncommon.

Monitoring. Review at 3 months and 6 months with spirometry and DLCO, and CT if symptoms persist or worsen.

Referral and escalation. Refer to a respiratory physician if symptoms persist after smoking cessation or the diagnosis is unclear.