Chest
Volume 120, Issue 2, August 2001, Pages 617-624
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Reviews
Bleomycin-Induced Pneumonitis

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The cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced cytokines and free radicals. Ultimately, BIP can progress in lung fibrosis. The diagnosis is established by a combination of clinical symptoms, radiographic alterations, and pulmonary function test results, while other disorders resembling BIP have to be excluded. Pulmonary function assessments most suitable for detecting BIP are those reflecting lung volumes. The widely used transfer capacity of the lungs for carbon monoxide appeared recently not to be specific when bleomycin is used in a polychemotherapeutic regimen. There are no proven effective treatments for BIP in humans, although corticosteroids are widely applied. When patients survive BIP, they almost always recover completely with normalization of radiographic and pulmonary function abnormalities. This review focuses on BIP, especially on the pathogenesis, risk factors, and its detection.

Section snippets

Clinical Features

Often, BIP starts gradually during treatment, but the development of BIP up to 6 months after discontinuation of bleomycin therapy has also been reported.20 The clinical diagnosis of BIP is rather hampered by its resemblance to other conditions often encountered in cancer patients, such as pneumonia, pulmonary metastases, or lymphangitic carcinoma.

Patients with BIP present initially with a nonproductive cough, exertional dyspnea, and sometimes fever. With progressive pneumonitis, dyspnea at

Pathogenesis

The pathogenesis of BIP has been intensively studied in animals, but data derived from human studies are scarce. In animals, the first event noted is endothelial damage of the lung vasculature accompanied by edema.26 This is followed by influx of inflammatory cells such as macrophages, lymphocytes, and neutrophils into the lung parenchyma and subsequently by fibroblasts leading to pulmonary fibrosis.26 Studies in patients who developed clinically evident BIP showed that alterations in lung

Pulmonary Function Assessments

Numerous methods such as cell counts in BAL fluid, gallium lung scanning, angiotensin-converting enzyme plasma levels, chest radiographs, or CT scans have been evaluated to detect BIP at an early stage, in order to avoid the further development of severe BIP by withholding further treatment with bleomycin.16 Pulmonary function assessments, however, seem to be the most proper tool.

Comis et al48 were the first to show a decrease in the transfer capacity of the lungs for carbon monoxide (Tlco)

Risk Factors

Many studies have been performed to identify risk factors for the development of BIP. However, most of these studies have used different criteria for its diagnosis. Furthermore, for establishing BIP, many studies used lung function assessments that have been shown later not to be specific for BIP when bleomycin is used in a multidrug regimen. In these circumstances and by these lung function assessments, pulmonary toxicity of bleomycin cannot be distinguished from pulmonary effects of other

Prevention and Treatment of BIP

Probably one of the most efficient ways to prevent BIP is to lower the total cumulative dose of bleomycin. Therefore, several studies188283 have been performed in good-prognosis germ-cell cancer to establish the role of bleomycin; these studies showed that bleomycin could not be omitted completely from combination chemotherapy. However, Einhorn et al84 showed that lowering the total dose of bleomycin from 360 to 270 mg does not reduce efficacy of the treatment of good-prognosis disseminated

Conclusion

BIP is a severe and sometimes fatal side effect of bleomycin therapy. Numerous studies have been performed to identify methods capable of detecting BIP at an early preclinical stage. Combined with clinical signs and symptoms, pulmonary function tests reflecting lung volume such as TLC and VC are probably most suitable for this purpose. Identification of risk factors has probably resulted in decreased bleomycin-induced morbidity and mortality, but this has never been examined (to my knowledge).

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