title: Amiodarone pulmonary toxicity. Recognition and pathogenesis (Part 2).
abstract: The pulmonary toxicity associated with amiodarone therapy is clinically complex and likely reflects underlying mechanisms of lung injury that result from direct toxic effects of the drug (or its metabolites) as well as indirect inflammatory and immunologic processes induced by the drug therapy (Fig 2). A role for the direct toxicity of the drug is likely because (a) toxicity in part is related to dosage and duration of therapy, (b) many patients with amiodarone pulmonary toxicity have no evidence of an inflammatory or immune response in the lung, (c) in vitro studies indicate that amiodarone can be directly toxic to cultured lung cells or perfused isolated lung tissue, and (d) recent studies suggest plausible biochemical mechanisms that may explain in part the mechanism(s) of direct toxicity of the drug. A role for indirect inflammatory or immune processes within the lung of some patients with APT is supported by: (a) variable relationship of pulmonary toxicity to amiodarone dosages and blood levels, (b) preliminary studies suggest altered immunologic markers in the blood and lungs of some patients with APT, and (c) the cellular findings of bronchoalveolar lavage indicating a CD8 lymphocytosis with or without influx of polymorphonuclear leukocytes, which is consistent with previous studies of hypersensitivity reactions. As our understanding of the biochemical and cellular mechanisms of APT improve, a number of key clinical issues may be clarified: (1) risk factor assessment for APT, (2) criteria for early diagnosis of APT, and (3) improved therapeutic approach to patients with APT.
authors.affiliation: Mayo Clinic, Rochester, MN 55905.
authors.forename: W J
authors.initials: WJ
authors.lastname: Martin
authors.forename: E C
authors.initials: EC
authors.lastname: Rosenow
mesh_terms: D000638:Amiodarone / Q000009:adverse effects* / Q000493:pharmacokinetics; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced*; D008214:Lymphocytes / Q000145:classification
chemical_list: D000638:Amiodarone