Bleomycin-Induced Lung Injury

Abstract

Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and Hodgkin's lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. The mechanism of bleomycin-induced pneumonitis (BIP) involves oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and the elaboration of inflammatory cytokines. Ultimately, BIP can progress to lung fibrosis. The diagnosis of BIP is established by the combination of systemic symptoms, radiological and histological findings, and respiratory function tests abnormalities, while other disorders should be excluded. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. In general, the clinical picture is extremely complex. A greater understanding of the BIP pathogenesis may lead to the development of new agents capable of preventing or even treating the injury already present. Physicians who prescribe bleomycin must be aware of the potential pulmonary toxicity, especially in the presence of risk factors. This review will focus on BIP, mainly regarding recent advances and perspectives in diagnosis and treatment.

Anti-Fibrotic Potential of Nicorandil in the Treatment of Bleomycin Induced Pulmonary Fibrosis

“…[12][13][14][15][16][17][18][19] The pathophysiology of Bleomycin-induced lung injury typically consisted of two overlapping stages; an early inflammatory phase characterized by leukocyte infiltration and injury to alveolar epithelial cells, and a subsequent fibro-proliferative phase with matrix remodeling and fibrosis. 20 Haematoxylin & Eosin (H&E) staining results in BLM control group showed that acute inflammations were prominent with moderate or severe hemorrhage, widened alveolar septa, and infiltration of numerous inflammatory cells predominated by macrophages, neutral granulocytes, and lymphocytes. The extent of fibrosis in nicorandil treated group was mild.…”

Bleomycin-Induced Reversible Acute Interstitial Pneumonia

“…Since 60-70% of drug is eliminated via kidneys careful monitoring and dose reduction is required in case of renal dysfunction. Side effects profile includes erythema, hyperpigmentation of the skin, discoloration of nail bed, hyperkeratosis, chills, hypotension, alopecia, stomatitis, myocardial infarction, stroke, and Raynaud's phenomenon [6].…”

“…Pulmonary syndromes associated with bleomycin includes bronchiolitis obliterans organizing pneumonia, eosinophilic hypersensitivity, and with most common being interstitial pneumonitis. The latter, bleomycin-induced pneumonitis (BIP) has an incidence ranging from 0% to 46% with a reasonable estimate of BIP incidence being 10% [6]. Mortality ranges up to 10% [7].…”

“…Membrane instability and inflammation due to fatty acid oxidation occurs due to free radical formation, cytokines such as interleukin-1, macrophage inflammatory protein-1, platelet-derived growth factor, and Transforming growth factor-beta are released from alveolar macrophages and this further causes proliferation of fibroblasts leading to pulmonary fibrosis. Other postulated mechanisms include loss of pulmonary immune tolerance, disruption of balance between collagen deposition and collagenolysis as well fibrin and fibrinolytic system resulting in excess collagen and fibrin deposition, respectively [6].…”

An Improved Method for Rapid Intubation of the Trachea in Mice

“…12 The need for direct contact between BLM and the pulmonary epithelium highlights the importance of a robust delivery route, and these concerns are also germane to a broad range of treatments targeted to the distal airways, including recombinant proteins, antibodies, siRNA, virus, bacteria, particulates, and more. Oropharyngeal aspiration (OPA) has been widely used for this purpose 13 , but a major a shortcoming of OPA is that some portion of the delivered agent may be swallowed into the gastrointestinal tract, thereby leading to imprecision in the administered dose.…”