Genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis.

BACKGROUND: The nature of the association between severe respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous study, we showed that genetic variation in the IL-8-promoter region is associated with susceptibility to severe bronchiolitis. OBJECTIVE: The purpose of this study was to assess the association between wheezing post-bronchiolitis and the genetic variant of IL-8 gene. METHODS: We collected data from 134 children who had suffered from bronchiolitis, enrolled in our previous study. The occurrence of wheezing post-bronchiolitis was recorded from a questionnaire sent by post. The association between the genotype and wheezing phenotype was assessed by family-based and case-control approaches. RESULTS: Family-based association showed that the IL-8 variant was transmitted significantly more often than expected in the children who wheezed after the episode of bronchiolitis (transmission=56%, P=0.02). This effect was not observed in the group of children who had bronchiolitis but did not go on to wheeze. Moreover, the variant was significantly more frequent in post-bronchiolitis wheezers compared with the general population (odds ratio=1.6, 95% confidence interval 1.0-2.6). CONCLUSION: These preliminary results suggest that there is a genetic predisposition to wheeze following severe RSV bronchiolitis.

Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus.

Interleukin-8 (IL8) is believed to play a role in the pathogenesis of bronchiolitis, a common viral disease of infancy, and a recent U.K. family study identified an association between this disease and the IL8-251A allele. In the present study we report data, from a different set of families, which replicate this finding; combined analysis of 194 nuclear families through use of the transmission/disequilibrium test gives P = .001. To explore the underlying genetic cause, we identified nine single-nucleotide polymorphisms (SNPs) in a 7.6-kb segment spanning the IL8 gene and its promoter region and used six of these SNPs to define the haplotypic structure of the IL8 locus. The IL8-251A allele resides on two haplotypes, only one of which is associated with disease, suggesting that this may not be the functional allele. Europeans show an unusual haplotype genealogy that is dominated by two common haplotypes differing at multiple sites, whereas Africans have much greater haplotypic diversity. These marked haplotype-frequency differences give an F(ST) of.25, and, in the European sample, both Tajima's D statistic (D = 2.58, P = .007) and the Hudson/Kreitman/Aguade test (chi(2) = 4.9, P = .03) reject neutral equilibrium, suggesting that selective pressure may have acted on this locus.

Reproducibility of pulmonary function tests under laboratory and field conditions.

The reproducibility of pulmonary function tests in the laboratory and in a mobile field survey vehicle has been studied. Groups of laboratory workers were studied at base and a random sample of 38 coalminers was examined in the mobile laboratory. The intra-subject variability of some newer tests of lung function, including closing volume and maximum flow at low lung volumes, has been compared with that of well-established tests, such as lung volumes and forced expiratory volume from two measurements made more than one day apart. Most measurements were slightly less reproducible in the study of coalminers than in the laboratory personnel. Conventional tests, such as forced expiratory volume in one second, lung volumes, single breath CO transfer factor, and exercise ventilation were very reproducible, the coefficients of variation (cov) being generally between 5% and 10%. The closing volume test, maximum expiratory flow at low lung volumes, and the single breath N2 index were less reproducible: cov between 15% and 39% in the miners. The forced expired time and volume of isoflow, measured only on laboratory workers, however, exhibited greater reproducibility than previously reported (cov = 10% and 15% respectively). It is suggested that, when assessing the repeatability of lung function tests, account should be taken of the circumstances in which the intra-subject variability was measured.

Inertial deposition of particles in human branching airways.

This paper concerns the inertial deposition of aerosol particles in models of human branching airways. Homogeneous monodisperse aerosols of known characteristics were generated using a spinning disc atomizer. These were paused through simple bend systems of differing geometries, and the fractional deposition measured by a fluorimetric technique. The parameter characterizing 50 per cent deposition in the bend was found to agree with that predicted theoretically. Deposition in five models of bifurcating airways having geometries generally compatible with existing anatomical data was studied using essentially the same experimental procedure. The magnitude of the inertial deposit was measured and the overall effect of fluid-flow rate, particle size, branching angle and size of model determined. The results were compared with exsting theoretical estimates of impaction in a bifurcating airway.