Bleomycin-induced pulmonary toxicity.

1019 dverse drug reactions are an important cause of morbidity and mortality, accounting for an estimated 5% of all hospitalizations and 0.3% of hospital deaths [1]. Recognition of drug-induced lung disease is difficult because the clinical, radiologic, and histologic findings are nonspecific [1, 2]. The diagnosis is based on a history of drug exposure, histologic evidence of lung damage, and exclusion of other causes of lung injury. High-resolution CT is superior to radiography in the depiction of the presence and distribution of parenchymal abnormalities. In one study of 23 patients with drug-induced lung disease, abnormal findings were detected on high-resolution CT in all patients and on radiography in 17 patients (74%) [3]. Abnormalities most commonly overlooked on radiography included groundglass opacities and mild fibrosis [3]. We illustrate the spectrum of abnormalities seen on high-resolution CT in patients with drug-induced lung disease.

https://www.ajronline.org/doi/pdfplus/10.2214/ajr.175.4.1751019

Drug-Induced Lung Disease

https://www.ajronline.org/doi/pdf/10.2214/ajr.175.4.1751019

Drug-induced lung disease: high-resolution CT findings.

Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or fema...

Vinblastine, bleomycin, and methotrexate: an effective adjuvant in favorable Hodgkin's disease.

The above authors have founded a clinical study group known as the GEPPI (Groupe d'Etudes de la Pathologie Pulmonaire Iatrogene. Address: Professor Ph. Camus, Service de Pneumologie, CHU, BP 1542, F-21034 Dijon, France; fax: 33 3 80 29 32 51; e-mail: pneumo.dijon@ planetb.fr). The purpose of this group is to provide information regarding individual cases, collect and update literature on drug-induced lung disease, publish updated lists of offending compounds, and formulate warnings when new side-effects of drugs are recognized. Thus, the present table may be subjected to update in the future in this Journal. The number of drugs which have been shown to damage the respiratory system in some instances continues to increase. The clinical pattern of involvement from drugs is diverse and difficult to memorize accurately. Table 1 is designed to provide the information currently available on such drugs in a readily accessible form. A good way of obtaining broad information on druginduced respiratory disease is to refer to general articles and reviews on the topic. Many such papers have been available in the literature in the recent years [1–37]. Another method is to scrutinize the literature regarding any given drug. We considered that the preparation of a table listing most drugs capable of injuring the respiratory system was appropriate. The present table includes: 1) generic drug name (no trade name is provided); 2) clinical pattern of involvement, according to the types described in the legend; 3) a rough estimate of frequency of the adverse effect from each compound (*: isolated case reports which await confirmation; **: about 10 cases available; ***: 20–100 cases available; ****: >100 cases reported); 4) relevant references. Obviously, not all references for a given compound have been mentioned, because the overall list would have been too long. For example, references regarding pulmonary adverse effects from bleomycin total 114, and 135 for nitrofurantoin. No attempt has been made to validate the case histories quoted here. Often, most if not all drugs from the same pharmacological category are likely to induce the same adverse effect in the lung. As an example, angiotensin-converting enzyme (ACE) inhibitors may induce cough [38], β-blockers may induce bronchospasm [35], nonsteroidal anti-inflammatory drugs may induce bronchospasm or eosinophilic pneumonia [39], and ergoline drugs may induce chronic pleural thickening or effusion [40]. A few compounds have been listed despite the fact that they were recalled or withdrawn from the market earlier (e.g. aminorex, hexamethonium, mecamylamine, practolol or tryptophan). There are several reasons for this: 1) disease from drugs such as I-tryptophan leave long-term sequelae and patients may still be seen with persistent illness from the drug; 2) the clinical picture (e.g. bronchiolitis obliterans organizing pneumonia (BOOP)) from classic drugs, such as hexamethonium or meca-mylamine, may be seen with newer drugs, such as penicillamine, gold or amiodarone; and 3) clinical pictures long thought to have vanished (e.g. pulmonary hypertension from the appetite suppresant, aminorex) have regained interest because similar newer compounds (e.g. fenfluramine) may induce the same adverse effect [41]. Contraceptive pills may induce varied changes in the pulmonary circulation [42–44], but the aetiological link is too weak to make it possible to blame one particular formulation or brand. The field of drug-induced pulmonary infections and cancer, as well as the complications of illicit drug use and abuse have been deliberately omitted. This list of drugs is available on a continuously updated Web page at: http://www.pneumotox.com/lungdrug. For further comments, see the editorial in this issue of the Journal. CURRENT UPDATE

https://erj.ersjournals.com/content/erj/10/2/265.full.pdf

Drugs that may injure the respiratory system

Twenty patients with pulmonary complications associated with combination chemotherapy regimens containing bleomycin were studied to determine common patterns of pulmonary radiographic abnormalities. All patients were receiving bleomycin on one of two different regimens of combination chemotherapy. Ten patients with non-Hodgkin lymphoma received a relatively low dose (22-64 mg total) and 10 patients with testicular cancer received a higher dose (360 mg total). The high-dose group showed subclinical radiographic lung toxicity changes in eight (80%) patients during and after therapy. Chronic pulmonary abnormalities were seen in nine (90%) patients in the high-dose group but in only three (30%) patients in the low-dose group. These was no significant difference in the pattern and distribution of lung infiltrates in these two groups. Infiltrates involving mainly the costophrenic triangle were seen in 18 (90%) patients; in six (33%) of these the changes were confined to the costophrenic triangles bilaterally and nearly symmetrically. Five (25%) patients had infiltrates at the periphery of the lungs. Elevation of the diaphragm was seen in 16 (80%) patients. A pleural reaction without gross effusion was seen in nine (45%) patients, of whom five (55%) demonstrated thickening of the interlobar fissures. Chronic lung changes were mostly confined to the bases in the form of failure of reexpansion of the costophrenic triangle (55%), persistent elevation of the diaphragm (35%), and a reticular meshwork of fibrosis at the costophrenic triangles (25%). Minimal lung disease was manifest as ground glass appearance at the lung bases and as fine, linear or reticulonodular densities that involved the costophrenic triangles.

Pulmonary complications of chemotherapy regimens containing bleomycin

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Pulmonary complications of chemotherapy regimens containing bleomycin