The effects of inhaled beclomethasone dipropionate on lung function and histamine responsiveness in recurrently wheezy infants.

Inhaled steroids improve pulmonary function and bronchial responsiveness in older asthmatics. Data from studies using subjective outcome measures to determine the effectiveness of inhaled steroids in infants with recurrent wheezing are equivocal. Therefore, this study tested the hypothesis that beclomethasone dipropionate improves pulmonary function, including bronchial responsiveness to histamine, in recurrently wheezy infants. The study was double blind, placebo controlled lasting nine weeks. After the first baseline week, pulmonary function was measured using the rapid thoracoabdominal compression technique and bronchial responsiveness assessed with a histamine challenge test. Infants were then randomly allocated to receive doses of placebo or beclomethasone dipropionate (100 micrograms/puff) from metered aerosols. Two puffs of test aerosol were administered twice daily for eight weeks via a large volume spacer fitted with a facemask. Symptoms were recorded daily and pulmonary function and bronchial responsiveness assessed at the end of the treatment period; 50 infants, median age 12 months (range 5 to 18 months), were recruited. Twenty three in the beclomethasone dipropionate group and 15 in the placebo group completed the study and had pairs of pulmonary function measurements. Three were probable treatment failures (one beclomethasone dipropionate, two placebo), three were possible treatment failures (placebo), and others were non-compliant with study protocol. Baseline variables were not significantly different between those infants who completed the study and those who did not. Beclomethasone dipropionate and placebo groups were similar in all respects at baseline. Lung function and symptoms improved for both groups of infants during the study. Bronchial responsiveness increased significantly in the placebo group but there were not statistically significant differences between groups for any of the other outcome measures. It is concluded that beclomethasone dipropionate (400 microgram daily) via a large volume spacer does not significantly improve lung function or symptoms in recurrently wheezy infants but might hav a beneficial effect on bronchial responsiveness

Influence of driving pressure on raised-volume forced expiration in infants

The raised-volume forced-expiration technique measures infant lung function over an extended volume range. To improve comparisons between individuals and populations, we investigated the influence of jacket pressure on outcome variables in 21 infants. To quantify pressure transmitted from the jacket to the pleural space at a given lung volume, the jacket was inflated against an occluded airway, and the increase in pressure at the mouth was measured. Flow-volume curves were recorded at transmitted pressure (Ptrans) values ranging from 0 to 41.9 cm H2O. The effect of Ptrans on the FEV measures of FEV05%, FEV0.75 and FVC, and on the forced expiratory flow measures of FEF25% , FEF50%, and FEF75% was assessed. At Ptrans values between 0 to 20 cm H2O, a significant positive relationship existed between transmitted pressure (Ptrans) and all outcome variables except FVC. At higher Ptrans values, all outcome variables demonstrated pressure independence, with the exception of FEF25% (which remained positive) and FVC (which was negative in a subgroup of wheezy infants). FEF75%, values tended to decrease at Ptrans values > 25 cm H2O. At Ptrans values between 20 and 25 cm H2O, most outcome variables are pressure independent. This range is therefore the most suitable for use with the raised-volume forced expiration technique

Association of CD14 Promoter Polymorphism with Otitis Media and Pneumococcal Vaccine Responses

Innate immunity is of particular importance for protection against infection during early life, when adaptive immune responses are immature. CD14 plays key roles in innate immunity, including in defense against pathogens associated with otitis media, a major pediatric health care issue. The T allele of the CD14 C-159T polymorphism has been associated with increased serum CD14 levels. Our objective was to investigate the hypothesis that the CD14 C-159T allele is protective against recurrent acute otitis media in children. The association between the CD14 promoter genotype and the number of acute otitis media episodes was evaluated both retrospectively and prospectively in a cohort of 300 children. Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal vaccinations were examined according to CD14 genotype to compare immune responsiveness across genotypes. An age-dependent association was found: compared with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had fewer episodes of acute otitis media (79 versus 41%, respectively; P = 0.004); this relationship was absent in older children. Additionally, TT homozygotes showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data suggest that genetic variation in CD14, a molecule at the interface of innate and adaptive immune responses, plays a key role in the defense against middle ear disease in childhood and in pneumococcal vaccine responsiveness. These findings are likely to be important to these and other immune-mediated outcomes in early life