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Cytotoxic drug-induced pulmonary disease in infants and children
B Fauroux1, A Meyer-Milsztain, L Boccon-Gibod
1Department of Pediatric Pulmonology, Hôpital d'Enfants Armand Trousseau, Paris, France.
Insights
Pediatric drug-induced pulmonary diseases (DIPD) present in three main patterns: acute hypersensitivity, chronic pneumonitis/fibrosis, and pulmonary edema. Early recognition and treatment are crucial for favorable outcomes in children with cancer.
Area of Science:
- Pediatric Pulmonology
- Oncology
- Pharmacology
Background:
- Increased survival rates in pediatric malignancies necessitate managing treatment-related toxicities.
- Drug-induced pulmonary diseases (DIPD) are a significant concern in children undergoing aggressive cancer therapies.
Purpose of the Study:
- To retrospectively analyze the clinical presentation, diagnostic findings, and outcomes of DIPD in pediatric patients over a 10-year period.
- To identify distinct patterns of DIPD in children treated for malignant diseases.
Main Methods:
- Retrospective review of 15 pediatric patients diagnosed with DIPD over 10 years.
- Analysis of clinical data, including underlying malignancy, specific drugs, bronchoalveolar lavage (BAL) findings, lung function tests, and treatment outcomes.
- Categorization of DIPD into acute hypersensitivity lung disease, chronic pneumonitis/fibrosis, and noncardiogenic pulmonary edema.
Main Results:
- Three patterns emerged: 1) Acute hypersensitivity lung disease (methotrexate, azathioprine) with favorable outcomes. 2) Chronic pneumonitis/fibrosis (cyclophosphamide, bleomycin, BCNU, melphalan) with variable outcomes, including mortality. 3) Noncardiogenic pulmonary edema (recombinant interleukin II) with rapid recovery.
- BAL analysis revealed hypercellularity and increased lymphocytes in acute cases, and moderate cell increases in chronic cases.
- Lung function tests consistently showed a restrictive pattern across all DIPD types.
Conclusions:
- DIPD in children presents with distinct clinical and pathological patterns based on causative agents.
- Prompt diagnosis and appropriate management are essential for improving outcomes in pediatric DIPD.
- Further research into specific drug toxicities and preventative strategies is warranted.
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)