Drugs have long been recognized as having the potential to cause pulmonary injury. The precise incidence of drug-induced lung disease is difficult to ascertain, because the signs and symptoms of disease are shared by many other pulmonary conditions and diseases. An analysis of a database of approximately 9 million patients from the United Kingdom describes an incidence density of 0.7 per 100,0000 patient years for interstitial disease related to drugs over a 12-year period (1997–2008).1 These data reflect only a portion of the impact of drug-induced respiratory disease, because the alveoli, upper and lower airways, pleura, pulmonary vasculature, muscles of respiration, and the central nervous system governing respiratory control are all susceptible to injury from ingested, inhaled, and parenterally administered agents. As the categories and varieties of therapeutic drugs continue to increase, clinicians will encounter disease from new culprit drugs in addition to well-established drug reactions. Web-based data repositories, such as www.pneumotox.com, can serve as useful tools for the clinician, as they provide frequent updates based on the emerging literature on drug toxicities.
As the clinician-scientist explores the literature on drug-induced lung injury, it is critical to recognize that not all associations between drug use and respiratory dysfunction imply a definitive causal link between a specific drug and the injury pattern described. The literature needs to be cautiously interpreted before concluding that the reported associations are actually due to the implicated drug rather than a confluence of clinical conditions. This chapter addresses a broad array of drug classes implicated in pulmonary toxicity. Chemotherapeutic agents are discussed separately.
General Principles of Drug-Induced Lung Disease
The lung has an enormous surface area on which blood-borne substances (therapeutic medications, nutritional supplements, illicit drugs, or toxins) actively interact with lung tissue. Drug-related pulmonary toxicity, however, is a rare event. Reactions typically occur in a small minority of individuals exposed to a given agent. In most cases, lung injury appears to be an idiosyncratic event and cannot be predicted by dose, latency from drug initiation, duration of exposure, or pharmacologic characteristics of the drug. Often, there is no characteristic clinical presentation or pathognomonic histologic pattern of injury associated with a given drug, although certain histologic patterns of lung injury may occur more frequently than others. Thus, establishment of a diagnosis of lung toxicity is frequently a diagnosis of exclusion (see Table 66-1).
Table 66-1General Principles of Drug-Induced Lung Injury |Favorite Table|Download (.pdf) Table 66-1General Principles of Drug-Induced Lung Injury
|Clinical presentation is nonspecific |
|Injury occurs with variable latency from drug initiation |
|Lung injury is often dose-independent |
|Pulmonary toxicity may be unrelated to the drug’s pharmacologic properties |
|Acute, subacute, and chronic reactions may be caused by a drug |
|A variety of histopathologic patterns may be induced by a drug |
|Diagnosis of drug-induced injury is often made by exclusion |
|Resolution of injury may ...|