Flavouring-Related Lung Disease

Flavouring related lung disease is an occupational lung disease from inhaling volatile flavouring chemicals, chiefly diacetyl (2,3-butanedione) and the related 2,3-pentanedione. Its main form is constrictive bronchiolitis, with fixed airflow obstruction.

Exposure. Microwave popcorn and flavouring manufacture, bakery and dairy flavour mixing, coffee roasting and grinding, and heated e-cigarette liquid production.

Epidemiology. Cases cluster in single workplaces. Risk relates to exposure level, heating and mixing tasks, and poor ventilation.

Spectrum. Upper airway irritation, asthma like illness, and irreversible obstructive disease with bronchiolitis obliterans.

Prognosis. Obstruction is usually non-reversible, and progression to respiratory failure occurs. Early removal may slow decline.

Pathophysiology.

Volatile diketones deposit in the airway epithelium and injure bronchiolar epithelial cells. Repair is disordered, with submucosal fibrosis narrowing or occluding small airways.

The result is constrictive bronchiolitis with air trapping and obstruction.

• Cough, exertional dyspnoea and wheeze, often with eye, nose and throat irritation.
• Symptoms may begin weeks to years after starting work.
• Examination may be normal or show wheeze; clubbing is absent.
• Several affected co-workers suggest a workplace cause.

Red flags.

• Rapid decline in FEV1 or progressive dyspnoea.
• Resting hypoxaemia or respiratory failure.

• Exposure history with tasks, ventilation, respiratory protection and co-worker symptoms.
• Spirometry: obstruction with poor bronchodilator response; low FEV1 and FEV1/FVC, raised residual volume.
• Chest radiograph: normal or hyperinflated.
• HRCT with expiratory images: mosaic attenuation and air trapping.
• Gas transfer: normal or mildly reduced.
• Surgical lung biopsy showing constrictive bronchiolitis is rarely needed when exposure, spirometry and imaging agree.
• Workplace spirometry surveillance: flag FEV1 under the lower limit of normal or a fall of 10% or more between tests.

Differential diagnosis. Asthma, chronic obstructive pulmonary disease, hypersensitivity pneumonitis, post-infectious bronchiolitis, connective tissue disease associated bronchiolitis, other occupational bronchiolitis obliterans.

• Remove from exposure promptly and control sources by enclosure, ventilation and process change; respiratory protection as an adjunct.
• Smoking cessation; influenza and pneumococcal vaccination; pulmonary rehabilitation.
• 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 by sputum culture first. Monitor ECG for QTc at baseline and follow up, 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. Spirometry every 3 to 6 months initially, then yearly; surveillance of co-workers.

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