Pharmacotherapy: A Pathophysiologic Approach

The manifestations of drug-induced pulmonary diseases span the entire spectrum of pathophysiologic conditions of the respiratory tract. As with most drug-induced diseases, the pathologic changes are nonspecific. Therefore, the diagnosis is often difficult and, in most cases, is based on exclusion of all other possible causes. In addition, the true incidence of drug-induced pulmonary disease is difficult to assess as a result of the pathologic nonspecificity and the interaction between the underlying disease state and the drugs. Considering the physiologic and metabolic capacity of the lung, it is surprising that drug-induced pulmonary disease is not more common. The lung is the only organ of the body that receives the entire circulation. In addition, the lung contains a heterogeneous population of cells capable of various metabolic functions, including Nalkylation, N-dealkylation, N-oxidation, reduction of N-oxides, and C-hydroxylation. Evaluation of epidemiologic studies on adverse drug reactions provides a perspective on the importance of drug-induced pulmonary disease. In a 2-year prospective survey of a community-based general practice, 41% of 817 patients experienced adverse drug reactions.1 Four patients, or 0.5% of the total respondents, experienced adverse respiratory symptoms. Respiratory symptoms occurred in 1.2% of patients experiencing adverse drug reactions. In a recent retrospective analysis of clinical case series in France, 898 patients had reported drug allergy, with a bronchospasm incidence of 6.9%. When these patients were rechallenged with the suspected drug, only 241 (17.6%) tested positive. The incidence of bronchospasm in patients with positive provocation test was 7.9%.2 Adverse pulmonary reactions are uncommon in the general population but are among the most serious reactions, often requiring intervention. In a study of 270 adverse reactions leading to hospitalization from two populations, 3.0% were respiratory in nature.3 Of the reactions considered to be life-threatening, 12.3% were respiratory. An early report on death caused by drug reactions from the Boston Collaborative Drug Surveillance Program indicated that 7 of 27 drug-induced deaths were respiratory in nature.4 This was confirmed in a followup study in which 6 of 24 druginduced deaths were respiratory in nature.5