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Prior Bleomycin Exposure


  • Bleomycin (BLM) is an antitumor antibiotic used to treat mostly germ cell tumors and Hodgkin lymphomas

  • Mechanism of action: works by inducing breaks in DNA through a complex of bleomycin, ferrous iron and oxygen

  • BLM is inactivated in the body by BLM-hydrolase (BLM-h)

    • BLM-h activity is lowest in skin and lungs

    • Skin and lungs are the organs most susceptible to BLM toxicity

  • Pathophys. of toxicity is poorly understood but likely through a combination of:

    • Oxidative damage via oxygen free radicals

    • Relative deficiency of BLM-h

    • Genetic susceptibility

    • Subsequent inflammatory cascade

  • 80% renally cleared

Bleomycin-Induced Lung Injury 

  • Life-threatening interstitial pulmonary fibrosis AKA BLM-induced lung injury

  • Signs and Symptoms:

    • Dyspnea (earliest sx), cough, chest pain, crackles

    • Chest opacities on CXR

    • Asymptomatic decline in DLCO

  • Develops subacutely, over days to weeks, within 1-6 months of bleomycin exposure

  • Assess PFTs

    • ↓ DLCO

    • Restrictive pattern: ↓ FVC, TLC and FRC

  • Co-morbid conditions:

    • Testicular or ovarian germ cell tumor

    • Ovarian sex cord-stromal tumor

    • Hodgkin lymphoma

  • Risk factors:

    • ↑ age

    • Renal insufficiency

    • ↑ cumulative drug dose (rare if dose exceeds 270 IU)

    • Severity of underlying malignancy

    • ↑ FiO2 use

    • Concomitant radiation therapy (i.e. thoracic irradation)

    • Treatment with other chemo agents (i.e. cisplatin)

    • Cigarette Smoking



  • Avoid exposure to high FiO2

    • Evidence is largely anecdotal

    • High FiO2 even years after BLM exposure can increase risk for BLM-induced lung injury

    • If hypoxemic, titrate minimal amount of oxygen to maintain O2 sat 89-92%

  • Minimize IV fluids to avoid volume overload



  • Limper, AH. (2022) Chapter 99: Drug-Induced Pulmonary Disease. In Murray & Nadel's Textbook of Respiratory Medicine, 7th Ed. p1378-1394.e16

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