title: Cytotoxic drug-induced pulmonary disease in infants and children.
abstract: The increased survival rate of malignant diseases due to more aggressive treatments contributes to the occurrence of drug-induced pulmonary diseases (DIPD). We reviewed, retrospectively over a 10-year period, 15 children (8 girls) who presented a DIPD. Their mean age was 9 years (range, 1 to 17 years), with an underlying malignant disease in 14 (9 leukemias). Three typical patterns have emerged from this analysis: (1) acute hypersensitivity lung disease caused by methotrexate (in 6 patients) or azathioprine (in 1 patient). This acute syndrome consisted of alveolar-interstitial infiltrate with a hypercellularity on bronchoalveolar lavage (BAL) (mean, 714,286 cells/mL; range, 180,000-2,940,000 cells/mL) and an increase of lymphocyte counts (mean, 39%; range 11-64%) with predominantly CD8-suppressor/cytotoxic lymphocytes. Inhibition of leukocyte migration or leukocyte aggregation in the presence of low drug concentrations was positive in the 5 cases tested. Lung function tests showed a restrictive pattern and the outcome of DIPD was always favorable. (2) Chronic pneumonitis/fibrosis was seen in 6 patients who received a variable association of cyclophosphamide (3 patients), bleomycin (2 patients), BCNU (2 patients), and melphalan (1 patient). Symptoms of an alveolar-interstitial pneumonitis developed progressively. BAL showed a moderate increase of total cell numbers (mean, 495,000 cells/mL; range, 150,000-900,000 cells/mL). Lung function tests showed a restrictive pattern. Despite corticosteroid treatment in 4 children, one died after bleomycin lung injury and 2 had functional lung impairment. (3) Noncardiogenic pulmonary edema occurred in 2 patients with leukemia treated with recombinant interleukin II. BAL showed hypercellularity and outcome was rapidly favorable.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatric Pulmonology, Hôpital d'Enfants Armand Trousseau, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Fauroux
authors.forename: A
authors.initials: A
authors.lastname: Meyer-Milsztain
authors.forename: L
authors.initials: L
authors.lastname: Boccon-Gibod
authors.forename: G
authors.initials: G
authors.lastname: Leverger
authors.forename: A
authors.initials: A
authors.lastname: Clément
authors.forename: M
authors.initials: M
authors.lastname: Biour
authors.forename: G
authors.initials: G
authors.lastname: Tournier
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007223:Infant; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents