Am. J. Respir. Crit. Care Med., Volume 156, Number 5, November 1997, 1523-1529

Cromolyn Sodium Prophylaxis Inhibits Pulmonary Proinflammatory Cytokines in Infants at High Risk for Bronchopulmonary Dysplasia

ROSE M. VISCARDI, JEFFREY D. HASDAY, KARL F. GUMPPER, VICKI TACIAK, ANDREW B. CAMPBELL, and TIMOTHY W. PALMER

Division of Neonatology, Department of Pediatrics, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Department of Radiology, and UMAB Cytokine Core Laboratory, University of Maryland School of Medicine; and University of Maryland Medical Systems Department of Pharmacy Services, Baltimore, Maryland

An imbalance of proinflammatory cytokines such as TNF-, IL-1, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has anti-inflammatory effects in asthma, a disease with many similarities with BPD. In a prospective, randomized, blinded study, we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk ( 75% probability) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were randomized to nebulized DSCG 20 mg (n = 13) or 2 cc NS (control, n = 13) every 6 h from Day 3 to Day 28. Lung lavage was collected on Day 3 (pre-study) and Day 7 and analyzed for cell count and differential and TNF-, sTNFR1, sTNFR2, IL-1, IL-1ra, and IL-8 concentrations. The groups' pre-study lavage cytokine concentrations were similar, but TNF- and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group. Soluble TNF receptors were unaffected by DSCG. There was a trend towards lower IL-1 levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected by DSCG therapy. Three control subjects, but no DSCG-treated infants, died during the study period (p = 0.07). There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d (100% control subjects; 85% DSCG). These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants  1,000 g at risk for BPD.

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