Which agent is most likely responsible for pulmonary fibrosis with reticulonodular pattern in a patient treated for Hodgkin lymphoma?

Which agent is most likely responsible for pulmonary fibrosis with reticulonodular pattern in a patient treated for Hodgkin lymphoma?

• A. Bleomycin
• B. Doxorubicin
• C. Paclitaxel
• D. Cyclophosphamide

Answer: (A)

Bleomycin toxicity to the lungs is the clue here. Bleomycin, a component of Hodgkin lymphoma regimens, is known for causing dosing-related pulmonary injury that can progress from inflammatory pneumonitis to fibrosis. The lungs are particularly susceptible because they have relatively low levels of bleomycin hydrolase, an enzyme that inactivates the drug, so oxidative injury accumulates in the alveolar and interstitial spaces. That injury leads to interstitial inflammation and eventual fibrotic changes, which on imaging often appear as a reticulonodular pattern from widespread interstitial thickening and scarring, frequently in the lung bases. Risk factors that raise this danger include a higher cumulative dose, older age, existing lung disease, kidney impairment (which slows clearance), prior chest radiation, and exposure to high concentrations of supplemental oxygen. Among the other drugs listed, the main toxicities differ: doxorubicin tends toward cardiomyopathy, paclitaxel commonly causes hypersensitivity reactions and neuropathy, and cyclophosphamide has other prominent toxicities like bladder irritation and marrow suppression. The combination of Hodgkin treatment history and the characteristic lung imaging pattern points to bleomycin as the best explanation.

Bleomycin toxicity to the lungs is the clue here. Bleomycin, a component of Hodgkin lymphoma regimens, is known for causing dosing-related pulmonary injury that can progress from inflammatory pneumonitis to fibrosis. The lungs are particularly susceptible because they have relatively low levels of bleomycin hydrolase, an enzyme that inactivates the drug, so oxidative injury accumulates in the alveolar and interstitial spaces. That injury leads to interstitial inflammation and eventual fibrotic changes, which on imaging often appear as a reticulonodular pattern from widespread interstitial thickening and scarring, frequently in the lung bases.

Risk factors that raise this danger include a higher cumulative dose, older age, existing lung disease, kidney impairment (which slows clearance), prior chest radiation, and exposure to high concentrations of supplemental oxygen. Among the other drugs listed, the main toxicities differ: doxorubicin tends toward cardiomyopathy, paclitaxel commonly causes hypersensitivity reactions and neuropathy, and cyclophosphamide has other prominent toxicities like bladder irritation and marrow suppression. The combination of Hodgkin treatment history and the characteristic lung imaging pattern points to bleomycin as the best explanation.