Respiratory disease induced by drugs.

Collectively, of approximately 2,650 clinical articles published so far, 32% are related to chemotherapeutic agents: bleomycin (226 papers); busulphan (58); cyclophosphamide (75); methotrexate (129); and nitrosoureas (46). Adverse pulmonary effects from: amiodarone (214 articles); ergolines (54); gold salts (133); minocycline (35); nitrofurantoin (135); nonsteroidal anti-inflammatory drugs (NSAIDs) (58); and sulphasalazine (22) point to all these drugs as being common offenders of the respiratory system, in addition to angiotensin-converting enzyme (ACE) inhibitors. On this basis, a brief historical perspective on DIRD is warranted. The first notice of adverse effects of drugs on the respiratory system dates back to the years 1920–1930, when it was realized that aspirin could induce severe asthma attacks and even death [2]. In the 1940s, the then newer antibiotic drugs were associated with allergic pneumonia with or without eosinophilia or angiitis [3, 4], and gold was linked to the development of interstitial lung disease [5], although most of the literature on "gold lung" was published later [6–8]. The 1950s was an innovative decade, with the description of such varied and important drug-induced patterns as: lipoid pneumonia [9]; allergic pneumonia from para-aminosalicylic acid [10]; other anti-tuberculosis agents [11]; or nitrofurantoin [12]; the lupus erythematosus syndrome induced by hydralazine [13]; acute allergic pulmonary oedema from salicylates [14]; mediastinal lymphadenopathy or lymphoma from anticonvulsants [15]; and a severe diffuse pattern of organizing pneumonia, very reminiscent of what is now called diffuse bronchiolitis obliterans organizing pneumonia (BOOP), in patients exposed to hexamethonium [16]. The 1960–1969 decade was dominated by an overwhelming number of reports on nitrofurantoin lung. In addition, a worrisome picture of medication-induced pulmonary hypertension emerged, and an epidemic of this devastating illness in young females was ascribed to the appetite-suppressant, aminorex, which was withdrawn from the market [17]. For the first time, it became clear that one drug could induce more than one pattern of respiratory reactions. In the case of nitrofurantoin, these patterns included: acute allergic pneumonia, with or without eosinophilia in the blood [18]; subacute/chronic interstitial pneumonia, with or without a desquamative or eosinophilic pattern at histology [19–21]; bronchospasm [22]; anaphylaxis [23]; and pleural effusion [24]. In that decade also, alkylating agents [25], other antineoplastic drugs, including bleomycin [26] and methotrexate [27], imipramine [28], and sulphasalazine [29] emerged Eur Respir J 1997; 10: 260–264 DOI: 10.1183/09031936.97.10020260 Printed in UK all rights reserved Copyright ERS Journals Ltd 1997 European Respiratory Journal ISSN 0903 1936