Amiodarone pulmonary toxicity: functional and ultrastructural evaluation.

Pulmonary function, chest radiographic appearances, and the cellular composition of bronchoalveolar lavage fluid were assessed in 13 patients who were receiving amiodarone treatment. Eight of the patients had developed clinical and radiological evidence of lung disease and five were symptom free. The proportions of lymphocytes (mean 8.6 (SD 6.9)) and neutrophils (mean 3.4 (3.3)) obtained by bronchoalveolar lavage were similar in patients with and without lung complications. Electron microscopic examination of alveolar macrophages showed intralysosomal inclusion bodies in all subjects, regardless of clinical state. There was no significant difference in the mean number of inclusion bodies per macrophage transection between those with and those without lung disease. The differential cell count in bronchoalveolar lavage fluid and the presence of macrophage inclusion bodies were therefore not useful as markers of disease activity. Among those who developed clinical and radiological evidence of lung disease, the cumulative drug dose per kilogram of body weight and the duration of treatment (mean 16.5 (SD 9.0) months) were significantly correlated with the degree of lung restriction as measured by total lung capacity and forced vital capacity. It is concluded that, while the severity of the restrictive pulmonary defect that is induced by amiodarone is largely dose related, the development of lung toxicity is to some extent idiosyncratic.