CROMOLYN SODIUM PROPHYLAXIS INHIBITS PULMONARY PROINFLAMMATORY CYTOKINES IN INFANTS AT HIGH-RISK FOR BRONCHOPULMONARY DYSPLASIA

An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta , and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., sol uble TNF receptors and IL-1ra) in the lung during the first week of li fe may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has ant i-inflammatory effects in asthma, a disease with many similarities wit h BPD. In a prospective, randomized, blinded study, we examined whethe r early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk (gre ater than or equal to 75% probability) for oxygen-dependency at 28 d b y a 12-h predictive score and survived 48 h were randomized to nebuliz ed 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-alpha, sTNFR1, s TNFR2, IL-1 beta, IL-1ra, and IL-8 concentrations. The groups' pre-stu dy ravage cytokine concentrations were similar, but TNF-alpha 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 wer e unaffected by DSCG. There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected b y DSCG therapy. Three control subjects, but no DSCG-treated infants, d ied during the study period (p = 0.07). There were no significant diff erences between survivors of the two groups for oxygen-dependency at 2 8 d (100% control subjects; 85% DSCG). These results suggest that nebu lized DSCG may exert an anti-inflammatory effect in the lungs of infan ts less than or equal to 1,000 g at risk for BPD.