Two pilot investigations examined the hypothesis that MDI BEC administered in a tapering dosage schedule over the first 12 days of life reduces the incidence of BPD concomitant with modulation of BALF oxyradical inflammation. MDI BEC was dosed: 2 puffs QID × 3 days, then 2 puffs TID × 3 days, then 2 puffs BID × 3 days, then 2 puffs Q day × 3 days. Endotracheal tube aspirates were collected from mechanically ventilated premature infants on days 2, 4 and 6 of life. Biochemical variables assessed in endotracheal aspirates were normalized with respect of BALF urea dilution. In an initial group of 9 BEC-treated (777±113 g) and 9 historic controls (704±147 g) no differences in BALF total protein, lipid aldehydes or IL-8 could be demonstrated during the first week of life. BALF myeloperoxidase tended to be higher in controls on day 4 (p=0.075). BALF from control infants exhibited evidence of excess polyunsaturated fatty acid consumption on day 2 of life compared to BEC-treated infants. Significant differences were noted for% arachidonate (p=0.006), total polyunsaturated fatty acids (p=0.022), and ratio of polyunsaturated fatty acids to saturated fatty acids (p=0.027). Ratio of hydroxyl-linoleic acid to native linoleic acid tended to be higher in the control group on day 2 of life but was not statistically significant (p=0.158). For a subsequent group of 10 BEC-treated infants (903±203 g) and 10 control infants (834±205 g) a prospective, randomized, double blinded trial suggested that BEC-treated infants required fewer days of mechanical ventilation (31.9±16.6 vs 18.6±14.6, p=0.07). Need for O2 at 36 wks or home O2 also appeared to be lower in BEC-treated infants (55.6 vs 77.8% for both variables). Cosyntropin stimulation tests revealed no evidence of adrenal suppression in either group: cortisol levels pre/post cosyntropin (μg/dl) were: 6.9±4.2/20.8±8.4 and 9.7±6.5/21.0±9.6 for control and BEC-treated infants respectively. No other adverse effects of BEC were noted. MDI BEC in the dose utilized is safe, appears to reduce BALF oxyradical stress, and may have a beneficial clinical effect. Additional studies employing a higher dose of BEC and larger numbers of subjects are warranted.

(Supported by SCOR 1P50 HL46478, UW GCRC M01 PR03186, Thrasher Research Fund and Eleanor Naylor Dana Charitable Trust)