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Drug-induced lung diseases: A state-of-the-art review

Drug-induced lung diseases: A state-of-the-art review

ABSTRACT: Drug-induced lung disease (DILD) can be caused by a variety of agents, including chemotherapeutic drugs, antiarrhythmic agents, antibiotics, and NSAIDs. The clinical syndromes associated with DILD include alveolar hypoventilation, acute bronchospasm, organizing pneumonia, and hypersensitivity reactions. Amiodarone lung toxicity often manifests as a chronic fibrosing alveolitis, characterized by an insidious onset of cough, dyspnea, and weight loss. Important components of the workup include chest radiography, pulmonary function testing, and bronchoscopy with bronchoalveolar lavage (BAL). BAL is particularly helpful in identifying eosinophilic pneumonia and diffuse alveolar hemorrhage and in ruling out infectious causes. Management includes drug withdrawal and, in some cases, corticosteroid therapy. Before starting corticosteroids, it is important to rule out infectious causes of lung disease, particularly in patients receiving chemotherapy. (J Respir Dis. 2009;30[1])

Osler first described heroin-induced pulmonary edema in 1880 during an autopsy.1,2 Since the late 19th century, a growing number of agents have been linked to pulmonary toxicity. Currently, more than 350 agents are associated with iatrogenic lung diseases.3,4

Drug-induced lung diseases (DILDs) vary in their pathophysiology, presentation, and prognosis. Proper diagnosis requires a high index of suspicion and familiarity with the clinical syndromes associated with DILD. Most cases of pulmonary toxicity are idiosyncratic, and literature searches yield only small numbers of case reports for a given exposure.

Therapies for DILD are usually recommended on the basis of expert opinion rather than on well-designed clinical studies. Moreover, DILD is typically a diagnosis of exclusion. Therefore, before starting adjuvant therapies, such as corticosteroids, for presumed DILD, alternative causes of respiratory illness, such as infection, must be excluded.

DILD represents a heterogeneous group of diseases that, at least initially, is an imposing field to master. However, in this review, we hope to organize and clarify the myriad of lung diseases. We will limit our discussion to the most common DILDs encountered by health care professionals. We will first describe the typical clinical syndromes and diagnostic tests and then review the common agents associated with pulmonary toxicity, including chemotherapeutic drugs, antiarrhythmic drugs, antibiotics, anticonvulsants, anti-inflammatory agents, and illicit drugs.

CLINICAL SYNDROMES
Several clinical syndromes are associated with pulmonary toxicity. Organizing the vast number of potentially toxic drugs by clinical syndromes allows the health professional to link clinical presentations with the likely drug toxicity. The syndromes most often encountered and examples of the offending agents are listed in the Table.5

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