Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1 beta and IL-6, were increased in the bronchoalveolar lavage fluid obtained from nine infants (median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four (38 wk, 2690 g) control infants. IL-1 beta and IL-6 protein were both increased in the bronchoalveolar lavage fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1 beta, 4.6 versus 1.1 ng/mL, p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p < 0.05). Immunocytochemistry of lavage cells for IL-1 beta, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from lavage cells. IL-6 mRNA expression was increased in lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1 beta and IL-8 mRNA was similar in both groups. These results suggest that IL-1 beta, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.

Background Rates of preterm birth have increased in most industrialised countries but data on later lung function of late preterm births are limited. A study was undertaken to compare lung function at 8e9 and 14e17 years in children born late preterm (33e34 and 35e36 weeks gestation) with children of similar age born at term ($37 weeks gestation). Children born at 25e32 weeks gestation were also compared with children born at term. Methods All births from the Avon Longitudinal Study of Parents and Children (n¼14 049) who had lung spirometry at 8e9 years of age (n¼6705) and/or 14e17 years of age (n¼4508) were divided into four gestation groups. Results At 8e9 years of age, all spirometry measures were lower in the 33e34-week gestation group than in controls born at term but were similar to the spirometry decrements observed in the 25e32-week gestation group. The 35e36-week gestation group and term group had similar values. In the late preterm group, at 14e17 years of age forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were not significantly different from the term group but FEV 1 /FVC and forced expiratory flow at 25e75% FVC (FEF 25e75% ) remained significantly lower than term controls. Children requiring mechanical ventilation in infancy at 25e32 and 33e34 weeks gestation had in general lower airway function (FEV 1 and FEF 25e75 ) at both ages than those not ventilated in infancy. Conclusions Children born at 33e34 weeks gestation have significantly lower lung function values at 8e9 years of age, similar to decrements observed in the 25e32-week group, although some improvements were noted by 14e17 years of age.

Interleukin-8 (IL-8), soluble intercellular adhesion molecule-i (sICAM), elastase and neutrophils were assessed in bronchoalveolar lavage fluid from nine infants who developed chronic lung disease (CLD) after respiratory distress syndrome (RDS), seven who had recovered from RDS, and in four control infants. IL-8, sICAM, elastase and neutrophils in bronchoalveolar lavage fluid were increased in the CLD group, the differences being most pronounced at 10 days of age. When babies with and without CLD were compared at 10 days of age, bronchoalveolar lavage fluid from the babies with CLD had significantly increased (114.0 vs 12*7 nglml), sICAM (19.0 vs 1*1 ,ug/ml), elastase (6.9 vs 0*9 ,ug/ml) and neutrophils (1.9 vs 0.4X109/1). In serum the increased concentration of IL-8 observed at birth in the CLD (247 pg/ml) and RDS (192 pg/ml) groups decreased over three weeks to the concentrations observed in the controls (<70 pg/ml). Persistent inflammation could be a major contributory factor in the development of CLD.