Risk factors for cytotoxic lung injury:
(1) high doses
(2) long-term therapy (> 8 months)
(3) concurrent radiation therapy to the thorax
(4) continuation of therapy after onset of pulmonary toxicity
Pulmonary symptoms usually appear years after the drug was started. This interval may range from 1 to 10 years, with most cases around 4 years.
Clinical features:
(1) dry, nonproductive cough
(2) dyspnea
(3) fever
(4) tachypnea
(5) cyanosis in more severe disease
(6) rales
(7) hypoxemia with reduced PaO2
(8) restrictive pattern with reduced vital and total lung capacities
(9) decreased diffusing capacity for carbon monoxide
(10) progression despite drug discontinuation is common
Imaging findings may include:
(1) diffuse linear densities
(2) reticulonodular pattern
(3) isolated nodular pattern
(4) alveolar filling process (diffuse alveolar damage)
(5) pleural effusion
Histologic findings may include:
(1) cytologic atypia in alveolar and bronchiolar epithelial cells
(2) interstitial edema
(3) diffuse alveolar damage
(4) organizing interstitial pneumonia
(5) interstitial pulmonary fibrosis
(6) dystrophic calcification or ossification
Findings that would be unusual for busulfan toxicity and should suggest another diagnosis:
(1) hilar and/or mediastinal lymphadenopathy
(2) lobar or segmental pattern
