Drugs that may injure the respiratory system

The above authors have founded a clinical study group known as the GEPPI (Groupe d'Etudes de la Pathologie Pulmonaire Iatrogene. Address: Professor Ph. Camus, Service de Pneumologie, CHU, BP 1542, F-21034 Dijon, France; fax: 33 3 80 29 32 51; e-mail: pneumo.dijon@ planetb.fr). The purpose of this group is to provide information regarding individual cases, collect and update literature on drug-induced lung disease, publish updated lists of offending compounds, and formulate warnings when new side-effects of drugs are recognized. Thus, the present table may be subjected to update in the future in this Journal. The number of drugs which have been shown to damage the respiratory system in some instances continues to increase. The clinical pattern of involvement from drugs is diverse and difficult to memorize accurately. Table 1 is designed to provide the information currently available on such drugs in a readily accessible form. A good way of obtaining broad information on druginduced respiratory disease is to refer to general articles and reviews on the topic. Many such papers have been available in the literature in the recent years [1–37]. Another method is to scrutinize the literature regarding any given drug. We considered that the preparation of a table listing most drugs capable of injuring the respiratory system was appropriate. The present table includes: 1) generic drug name (no trade name is provided); 2) clinical pattern of involvement, according to the types described in the legend; 3) a rough estimate of frequency of the adverse effect from each compound (*: isolated case reports which await confirmation; **: about 10 cases available; ***: 20–100 cases available; ****: >100 cases reported); 4) relevant references. Obviously, not all references for a given compound have been mentioned, because the overall list would have been too long. For example, references regarding pulmonary adverse effects from bleomycin total 114, and 135 for nitrofurantoin. No attempt has been made to validate the case histories quoted here. Often, most if not all drugs from the same pharmacological category are likely to induce the same adverse effect in the lung. As an example, angiotensin-converting enzyme (ACE) inhibitors may induce cough [38], β-blockers may induce bronchospasm [35], nonsteroidal anti-inflammatory drugs may induce bronchospasm or eosinophilic pneumonia [39], and ergoline drugs may induce chronic pleural thickening or effusion [40]. A few compounds have been listed despite the fact that they were recalled or withdrawn from the market earlier (e.g. aminorex, hexamethonium, mecamylamine, practolol or tryptophan). There are several reasons for this: 1) disease from drugs such as I-tryptophan leave long-term sequelae and patients may still be seen with persistent illness from the drug; 2) the clinical picture (e.g. bronchiolitis obliterans organizing pneumonia (BOOP)) from classic drugs, such as hexamethonium or meca-mylamine, may be seen with newer drugs, such as penicillamine, gold or amiodarone; and 3) clinical pictures long thought to have vanished (e.g. pulmonary hypertension from the appetite suppresant, aminorex) have regained interest because similar newer compounds (e.g. fenfluramine) may induce the same adverse effect [41]. Contraceptive pills may induce varied changes in the pulmonary circulation [42–44], but the aetiological link is too weak to make it possible to blame one particular formulation or brand. The field of drug-induced pulmonary infections and cancer, as well as the complications of illicit drug use and abuse have been deliberately omitted. This list of drugs is available on a continuously updated Web page at: http://www.pneumotox.com/lungdrug. For further comments, see the editorial in this issue of the Journal. CURRENT UPDATE