Drug-induced pulmonary disease

Abstract

Drug-induced disease of any system or organ can be associated with high morbidity and mortality, and it is tremendously costly to the health care of our country. More than 100 medications are known to affect the lungs adversely, including the airways in the form of cough and asthma, the interstitium with interstitial pneumonitis and noncardiac pulmonary edema, and the pleura with pleural effusions. Patients commonly do not even know what medications they are taking, do not bring them to the physician's office for identification, and usually do not relate over-the-counter medications with any problems they have. They assume that all nonprescription drugs are safe. Patients also believe that if they are taking prescription medications at their discretion, meaning on an as-needed basis, then these medications are also not important. This situation stresses just how imperative it is for the physician to take an accurate drug history in all patients seen with unexplained medical situations. Cardiovascular drugs that most commonly produce a pulmonary abnormality are amiodarone, the angiotensin-converting enzyme inhibitors, and β-blockers. Pulmonary complications will develop in 6% of patients taking amiodarone and 15% taking angiotensin converting enzyme inhibitors, with the former associated with interstitial pneumonitis that can be fatal and the latter associated with an irritating cough that is not associated with any pathologic or physiologic sequelae of consequence. The β-blockers can aggrevate obstructive lung disease in any patient taking them. Of the antiinflammatory agents, acetylsalicylic acid can produce several different airway and parenchymal complications, including aggravation of asthma in up to 5% of patients with asthma, a noncardiac pulmonary edema when levels exceed 40 mg/dl, and a pseudosepsis syndrome. More than 200 products contain aspirin. Low-dose methotrexate is proving to be a problem because granulomatous interstitial pneumonitis develops in 5% of those patients receiving it. This condition occurs most often in patients receiving the drug for rheumatoid arthritis, but it has been reported in a few patients receiving it for refractory asthma. Chemotherapeutic drug-induced lung disease is almost always associated with fever, thus mimicking opportunistic infection, which is the most common cause of pulmonary complications in the immunocompromised host. However, in 10% to 15% of patients, the pulmonary infiltrate is due to an adverse effect from a chemotherapeutic agent. This complication is frequently fatal even when recognized early. Some medications produce a cytotoxic effect, meaning an atypia of the type I and II pneumocytes, whereas others produce a noncardiac pulmonary edema, microangiopathic hemolytic anemia with pulmonary edema, an eosinophilic pneumonitis, or a granulomatous reaction. The clinician responsible for these patients must relate to the pathologist what medications the patient may be taking. Illicit drugs, especially heroin and cocaine, are tremendous problems to the physician in the emergency department. The use of these drugs must be kept in mind when the patient has unexplained acute pulmonary symptoms. Nitrofurantoin is by far the most common antibiotic-induced lung disease, with the acute reaction having been reported in more than 1000 cases around the world. It is associated with acute onset of dyspnea, cough, and fever but rapidly resolves with discontinuation. The long-term side effect is a separate reaction that mimics idiopathic interstitial pneumonitis and fibrosis except that it usually responds slowly to discontinuation and sometimes to the addition of corticosteroids. Numerous other medications are associated with adverse drug reactions affecting the lungs, airways, and pleura, and they must be kept in mind when confronted with the patient who has an unexplained pulmonary problem.