Exposure to commonly prescribed drugs and the etiology of cryptogenic fibrosing alveolitis: A case-control study

Cryptogenic fibrosing alveolitis is an interstitial lung disease of unknown etiology. Since pulmonary fibrosis is a recognized, if rare, complication of certain drug exposures, including antidepressants, betablockers, antibiotics, anticonvulsants, and nonsteroidal antiinflammatory drugs (NSAIDs), we tested the hypothesis that exposure to these drugs might contribute to the etiology of cryptogenic fibrosing alveolitis. Lifetime drug exposure data were collected from general practitioner records for 141 cases of cryptogenic fibrosing alveolitis and 246 age-, sex-, and community-matched control subjects from the Trent region of England. Additional data on lifetime smoking habits were obtained by postal questionnaire. The odds of disease in relation to ever exposure to antidepressants, betablockers, antibiotics, anticonvulsants, and NSAIDs were calculated by conditional logistic regression. For drug groups significantly associated with cryptogenic fibrosing alveolitis, subset analyses were performed to investigate the effects of individual drugs. Cryptogenic fibrosing alveolitis was associated with exposure to antidepressants (odds ratio [OR] 1.79 [95% Cl 1.09-2.95], p = 0.022) and specifically to imipramine (OR 4.79 [1.50-15.3], p = 0.01), dothiepin (OR 2.37 [0.99-5.69], p = 0.05), and mianserin (OR 3.27 [1.11-9.61], p = 0.03). The magnitude of the overall effect of antidepressants was not changed by excluding all drug exposures within the 5 yr preceding the diagnosis of cryptogenic fibrosing alveolitis (OR 1.62 [0.94-2.77], p = 0.081), nor were the strong individual effects of imipramine (OR 5.72 [1.54-21.2], p = 0.009) and dothiepin (OR 5.58 [1.12-27.8], p = 0.036). These estimates were not appreciably affected by controlling for smoking history. The attributable risk for antidepressant exposure was in the region of 9-14%. No significant association was noted between cryptogenic fibrosing alveolitis and the four other drug groups in the primary hypothesis. The results of this study suggest that some antidepressant drugs can cause cryptogenic fibrosing alveolitis.