Amiodarone pulmonary toxicity: cytopathology, ultrastructure, and immunocytochemistry

One hundred ninety cardiac patients were prospectively enrolled in an amiodarone protocol. Over a 10-year period, 16 patients developed new or progressive respiratory symptoms while taking amiodarone. These symptoms included dyspnea associated with abnormal chest radiographs or new or worsening abnormalities on pulmonary function testing. Specimens for microscopic examination were obtained by fiberoptic bronchoscopy with transbronchial lung biopsy (TBB), bronchoalveolar lavage (BAL), open lung biopsy (OLB), or autopsy. Large foamy macrophages with characteristic lamellated cytoplasmic inclusions were noted in all specimens, regardless of other evidence of pulmonary toxicity, suggesting that foamy macrophages represent a routine drug effect. Foamy macrophages were not present in BAL specimens from 53 normal controls and were rarely seen in specimens from 27 patients who had other interstitial lung diseases. When present, the foamy macrophages were less prominent than those seen in specimens from patients receiving amiodarone. Fibrosis was noted in 11 of 16 histological specimens, whereas type II-cell-hyperplasia was observed in 7 of the 16 specimens. Four of the 16 patients with respiratory symptoms died, and their autopsy revealed a combination of foamy macrophages with fibrosis and type II cell hyperplasia reflective of amiodarone pulmonary toxicity. Hyperplastic type II cells were not found in the absence of fibrosis. Immunocytochemistry allowed differentiation between foamy macrophages and type II cells and represents a useful tool for future investigations of the pathogenesis of amiodarone-induced pulmonary disease.