Bleomycin exposure

Learning objectives

Bleomycin is an antitumor antibiotic often used to treat germ cell tumors and Hodgkin’s disease
Side-effect: Potential for subacute pulmonary damage that can progress to life-threatening pulmonary fibrosis
Pulmonary toxicity occurs in 6–10% of patients
Exposure to high-inspired concentration oxygen therapy, even for short periods, can cause rapidly progressive pulmonary toxicity in patients previously treated with bleomycin
Lung injury typically develops within 6 months after the start of bleomycin treatment
The potential for high-inspired fractions of oxygen to provoke pulmonary toxicity remains a life-long risk in these patients
Symptoms of bleomycin-induced pulmonary toxicity include dry cough, breathlessness, pleuritic chest pain, and fever

Bleomycin oxidatively damages DNA by binding to metal ions such as iron, resulting in reactive oxygen species formation
Is inactivated by bleomycin hydrolase
Low concentrations of bleomycin hydrolase in skin and lung tissues contribute to the sensitivity to bleomycin of these tissues
Contributing factors to bleomycin pulmonary toxicity:
- Inflammatory cell infiltration into pulmonary endothelial cells
- Fibrotic changes with elevated collagen content
- Increased expression of fibrogenic mediators (TGF-beta, connective tissue growth factor, PDGF-C) in endothelial cells
- Decrease in thapsigargin-induced prostaglandin I2 and nitric oxide (vasodilators) in endothelial pneumocytes

Physical examination	Dyspnea
	Pulmonary crackles
	Hypoxemia
Radiology	Linear interstitial shadowing, which can look similar to Kerly B lines seen in pulmonary edema
	Confluent airspace shadowing, which may be diagnosed as infection if the diagnosis of bleomycin lung injury is not considered
	Pneumothorax and pneumomediastinum are recognized complications in severe bleomycin lung injury

Acoid oxygen therapy when possible
Avoid clinical procedures (and leisure activities) involving a high FiO2
If a patient is hypoxic, O2 therapy should be minimized to maintain O2 saturation of 88–92%
High oxygen concentrations should be used with extreme caution for immediate life-saving indications only (to maintain O2 saturation of 88–92%)
Minimize IV fluids to avoid volume overload