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    SCIENTIFIC EXHIBIT - Continuing Medical Education

    Pulmonary Drug Toxicity: Radiologic and Pathologic Manifestations

    Published Online:Sep 1 2000https://doi.org/10.1148/radiographics.20.5.g00se081245

    Abstract

    Pulmonary drug toxicity is increasingly being diagnosed as a cause of acute and chronic lung disease. Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity. The clinical and radiologic manifestations of these drugs generally reflect the underlying histopathologic processes and include diffuse alveolar damage (DAD), nonspecific interstitial pneumonia (NSIP), bronchiolitis obliterans organizing pneumonia (BOOP), eosinophilic pneumonia, obliterative bronchiolitis, pulmonary hemorrhage, edema, hypertension, or veno-occlusive disease. DAD is a common manifestation of pulmonary drug toxicity and is frequently caused by cytotoxic drugs, especially cyclophosphamide, bleomycin, and carmustine. It manifests radiographically as bilateral hetero- or homogeneous opacities usually in the mid and lower lungs and on high-resolution computed tomographic (CT) scans as scattered or diffuse areas of ground-glass opacity. NSIP occurs most commonly as a manifestation of carmustine toxicity or of toxicity from noncytotoxic drugs such as amidarone. At radiography, it appears as diffuse areas of heterogeneous opacity, whereas early CT scans show diffuse ground-glass opacity and late CT scans show fibrosis in a basal distribution. BOOP, which is commonly caused by bleomycin and cyclophosphamide (as well as gold salts and methotrexate), appears on radiographs as hetero- and homogeneous peripheral opacities in both upper and lower lobes and on CT scans as poorly defined nodular consolidation, centrilobular nodules, and bronchial dilatation. Knowledge of these manifestations and of the drugs most frequently involved can facilitate diagnosis and institution of appropriate treatment.

    References

    • 1 Cooper JA, Jr. Drug-induced lung disease. Adv Intern Med 1997; 42:231-268. Medline, Google Scholar
    • 2 Meyers JL. Pathology of drug-induced lung disease. In: Katzenstein AA, Askin FB, eds. Katzenstein and Askin's surgical pathology of non-neoplastic lung disease. 3rd ed. Philadelphia, Pa: Saunders, 1997; 4:81-111. Google Scholar
    • 3 Pietra GG. Pathologic mechanisms of drug-induced lung disorders. J Thorac Imaging 1991; 6:1-7. Crossref, Medline, Google Scholar
    • 4 Kay JM. Drug-induced lung disease. In: Hasleton PS, eds. Spencer's pathology of the lung. 5th ed. New York, NY: McGraw-Hill, 1996; 551-595. Google Scholar
    • 5 Smith GJ. The histopathology of pulmonary reactions to drugs. Clin Chest Med 1990; 11:95-117. Medline, Google Scholar
    • 6 Kuhlman JE, Teigen C, Ren H, Hurban RH, Hutchins GM, Fishman EK. Amiodarone pulmonary toxicity: CT findings in symptomatic patients. Radiology 1990; 177:121-125. Link, Google Scholar
    • 7 Holoye P, Jenkins D, Greensberg S. Pulmonary toxicity in long-term administration of BCNU. Cancer Treat Rep 1976; 60:1691-1694. Medline, Google Scholar
    • 8 Cooper JA, Jr, White DA, Matthay RA. Drug-induced pulmonary disease. 1. Cytotoxic drugs. Am Rev Resp Dis 1986; 133:321-340. Google Scholar
    • 9 Kennedy J, Myers J, Plumb V, Fulmer J. Amiodarone pulmonary toxicity: clinical, radiologic, and pathologic correlations. Arch Intern Med 1987; 147:50-55. Crossref, Medline, Google Scholar
    • 10 McAdams HP, Rosado-de-Christenson ML, Wehunt WD, Fishback NF. The alphabet soup revisited: the chronic interstitial pneumonias in the 1990s. RadioGraphics 1996; 16:1009-1033. Link, Google Scholar
    • 11 Rosenow EC, Myers JL, Swensen SJ, Pisani RJ. Drug-induced pulmonary disease: an update. Chest 1992; 102:239-250. Crossref, Medline, Google Scholar
    • 12 Epler GR, Colby TV, McLoud TC, Carington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med 1985; 312:152-158. Crossref, Medline, Google Scholar
    • 13 Boggess KA, Benedetti TJ, Raghu G. Nitrofurantoin-induced pulmonary toxicity during pregnancy: a report of a case and review of the literature. Obstet Gynecol Surv 1996; 51:367-370. Crossref, Medline, Google Scholar
    • 14 Ginsberg S, Comis R. The pulmonary toxicity of antineoplastic agents. Semin Oncol 1982; 9:34-51. Medline, Google Scholar
    • 15 Sostman H, Matthay R, Putman C, Smith G. Methotrexate-induced pneumonitis. Medicine (Baltimore) 1976; 55:371-388. Crossref, Medline, Google Scholar
    • 16 Malik SW, Myers JL, De Remee RA, Specks U. Lung toxicity associated with cyclophosphamide use: two distinct patterns. Am J Respir Crit Care Med 1996; 154:1851-1856. Crossref, Medline, Google Scholar
    • 17 Burke D, Stoddart J, Ward M, Simpson C. Fatal pulmonary fibrosis occurring during treatment with cyclophosphamide. Br Med J (Clin Res Ed) 1982; 285:696. Crossref, Medline, Google Scholar
    • 18 Spector J, Zimbler H, Ross J. Early-onset cyclophosphamide-induced interstitial pneumonitis. JAMA 1979; 242:2852-2854. Crossref, Medline, Google Scholar
    • 19 Aronin P, Mahaley M, Rudnick S. Prediction of BCNU pulmonary toxicity in patients with malignant gliomas: an assessment of risk factors. N Engl J Med 1980; 303:183-188. Crossref, Medline, Google Scholar
    • 20 Litam J, Dail D, Spitzer G. Early pulmonary toxicity after administration of high-dose BCNU. Cancer Treat Rep 1981; 65:39-44. Google Scholar
    • 21 Iacovino J, Leitner J, Abbas A. Fatal pulmonary reaction from low doses of bleomycin: an idiosyncratic tissue response. JAMA 1976; 235:1253-1255. Crossref, Medline, Google Scholar
    • 22 Rosenow EC, III. Drug-induced pulmonary disease. Dis Mon 1994; 15:255-310. Google Scholar
    • 23 Aronchick JM, Gefter WB. Drug-induced pulmonary disorders. Semin Roentgenol 1995; 30:18-34. Crossref, Medline, Google Scholar
    • 24 Cooper JA, Jr, White DA, Matthay RA. Drug-induced pulmonary disease. 2. Noncytotoxic drugs. Am Rev Resp Dis 1986; 133:488-505. Google Scholar
    • 25 Fraire AE, Guntupalli KK, Greenberg SD, Cartwright J, Jr, Chasen MH. Amiodarone pulmonary toxicity: a multidisciplinary review of current status. South Med J 1993; 86:67-77. Crossref, Medline, Google Scholar
    • 26 Chai JL, Patz EF, Jr. CT of the lung: patterns of calcification and other high-attenuation abnormalities. AJR Am J Roentgenol 1994; 162:1063-1066. Crossref, Medline, Google Scholar
    • 27 Scott DL, Bradby GV, Aitman TJ, Zaphiropoulos GC, Hawkins CF. Relationship of gold and penicillamine therapy to diffuse interstitial lung disease. Ann Rheum Dis 1981; 40:136-141. Crossref, Medline, Google Scholar
    • 28 Everts CS, Wescott JL, Bragg DG. Methotrexate therapy and pulmonary disease. Radiology 1973; 107:539-543. Link, Google Scholar
    • 29 Cannon GW. Methotrexate pulmonary toxicity. Rheum Dis Clin North Am 1997; 23:917-937. Crossref, Medline, Google Scholar
    • 30 Padley SP, Adler B, Hansell DM, Müller NL. High-resolution computed tomography of drug-induced lung disease. Clin Radiol 1992; 46:232-236. Crossref, Medline, Google Scholar
    • 31 Morrison DA, Goldman AL. Radiologic patterns of drug-induced lung disease. Radiology 1979; 131:299-304. Link, Google Scholar
    • 32 Ramanathan RK, Reddy VV, Holbert JM, Belani CP. Pulmonary infiltrates following administration of paclitaxel. Chest 1996; 110:289-292. Crossref, Medline, Google Scholar
    • 33 Eisenhauer EA, Vermorken JB. The taxoids: comparative clinical pharmacology and therapeutic potential. Drugs 1998; 55:5-30. Crossref, Medline, Google Scholar

    Article History

    Published in print: Sept 2000