Amiodarone Pulmonary Toxicity

Abstract

To the Editor: We appreciate the comments of Dr. Akoun et al regarding our report on bronchoalveolar lavage in amiodarone pulmonary toxicity. Several points warrant further discussion. We agree that bronchoalveolar lavage will likely be useful in the assessment of amiodarone pulmonary toxicity. As noted in our report, however, the clinical utility of finding phospholipid inclusions in alveolar macrophages remains unclear. It seems likely that some patients receiving amiodarone will demonstrate inclusions in lung cells without exhibiting any evidence of pulmonary toxicity. It may be premature, however, to dismiss this finding as unrelated to the mechanisms of pulmonary toxicity. For example, a recent in vitro study from our laboratory suggests that there is a narrow range of safety between amiodarone concentrations which induce these characteristic inclusions in lung cells and concentrations of the drug which result in lethal cell injury.1Martin II, WJ Howard DM Amiodarone induced lung toxicity. In vitro evidence for the direct toxicity of the drug.Am J Path. 1985; 120: 344PubMed Google Scholar An important finding from this model of amiodarone pulmonary toxicity is that inclusions can form within lung cells using concentrations of amiodarone equivalent to therapeutic serum levels (1 to 3 μg/ml). Amiodarone, however, can be concentrated by lung tissue severalfold above serum levels,2Riva E Gerna M Neyroz P Urso R Bartosek I Guaitani A Pharmcokinetics of amiodarone in rats.J Cardiovasc Pharmacol. 1982; 4: 270-275Crossref PubMed Scopus (79) Google Scholar suggesting the potential for amiodarone to be directly toxic to the lung parenchyma.1Martin II, WJ Howard DM Amiodarone induced lung toxicity. In vitro evidence for the direct toxicity of the drug.Am J Path. 1985; 120: 344PubMed Google Scholar Alternatively, as Doctor Akoun et al have noted, some patients with amiodarone toxicity exhibit an increase in OKT8 + lymphocytes as determined by bronchoalveolar lavage. This is consistent with findings in our patient population, but it would appear the percentage of patients with a lymphocytic reaction may be less than previously described.3Israel-Biet D Venet A Caubarrere I Bonan G Dennewald G Pechaud D et al.Amiodarone pneumonitis mechanism: evaluation by bronchoalveolar lavage (BAL).Am Rev Respir Dis. 1985; 131: A74Google Scholar Approximately one third of our patients (five of 14) demonstrated an increased percentage of OKT8 + lymphocytes consistent with a hypersensitivity pneumonitis. The absence of an OKT8 + lymphocytosis by bronchoalveolar lavage, however, does not exclude the diagnosis of an adverse reaction. A prospective study of patients receiving amiodarone would provide insight into mechanisms of pulmonary toxicity and the relevance of bronchoalveolar lavage findings to the pathogenesis of the disorder. As yet, the pathogenesis of amiodarone lung toxicity remains unclear. There is evidence to suggest a role for the direct toxicity of the drug, as well as a role for hypersensitivity reactions in certain patients. It is likely that amiodarone toxicity in different patients may result from fundamentally different mechanisms, yet the clinical presentation may be quite similar. As further studies are initiated we hope that such mechanisms will be clarified. Amiodarone Pulmonary ToxicityCHESTVol. 89Issue 5PreviewTo the Editor: Full-Text PDF