Amiodarone pulmonary toxicity: clinical and subclinical features.

In a prospective study of lung function of 34 patients taking amiodarone, 24 showed no functional changes but 10 developed a sustained fall in CO transfer factor (TLCO) exceeding 15 per cent. These patients had on average received a higher dose of drug in the first three months of treatment. Seven showed no clinical or radiographic changes and TLCO improved with reduction in drug dose. The other three patients developed florid clinical and radiographic features of amiodarone pulmonary toxicity. All three had impaired TLCO before receiving amiodarone. During the course of the prospective study amiodarone pulmonary toxicity was diagnosed in four other patients. Lung tissue was examined in five of the seven patients with clinical toxicity and showed alveolar wall thickening, exudation and interstitial and intra-alveolar fibrosis with prominent 'foamy' macrophages. Electron microscopy of macrophages showed numerous lysosomal multilamellar bodies, which were demonstrated by energy dispersive X-ray analysis to contain iodine, a constituent of the amiodarone molecule. Two of the patients with clinical toxicity died of respiratory failure; the other five showed gradual improvement on withdrawal of the drug and treatment with corticosteroids. Subsequent withdrawal of steroids was associated with clinical and/or functional deterioration in five patients. A separate autopsy study of the lungs of eight patients dying during treatment with amiodarone, but without clinically-recognised toxicity, showed that an alveolitis had been present in two and prominent 'foamy' macrophages were seen in the lungs of six patients. We conclude that clinical and subclinical effects of amiodarone on the lung are common. The clinical syndrome may be easily misdiagnosed as pulmonary oedema. Subclinical changes in lung function are usually reversible, but whether they herald clinical toxicity if treatment is continued without modification is not established. The presence of 'foamy' macrophages may simply reflect exposure to the drug rather than clinically-important toxicity.