Two novel, severe asthma phenotypes identified during childhood using a clustering approach.

Unsupervised cluster analysis has already been used to identify severe phenotypes of childhood asthma, but without taking into account inflammatory markers. The aim of this study was to define independent homogeneous phenotypic clusters of severe asthma in a cohort of asthmatic children. Cluster analysis was applied to 19 variables from 315 children enrolled in the Trousseau Asthma Program in Paris, France. Three independent clusters of asthma were identified. Cluster 1, asthma with severe exacerbations and multiple allergies: 103 children had more sensitisations to inhaled allergens and food allergens, more blood eosinophils and basophils, more uncontrolled asthma despite high doses of inhaled corticosteroid and more hospitalisations for exacerbation. Cluster 2, severe asthma with bronchial obstruction: 72 children were significantly older, had the highest body mass index, a lower forced expiratory volume in 1 s, more pronounced blood neutrophils and significantly higher levels of all classes of immunoglobulin (Ig), except IgE. Cluster 3, mild asthma: 140 children did not show statistically significant features. These results could lead to improved management of severe asthma in children by optimising treatment strategies, i.e. anti-allergic drugs, such as anti-IgE for children with the allergic phenotype, and anti-neutrophil drugs, such as macrolides for those with the obstructive phenotype.

Grass pollen counts, air pollution levels and allergic rhinitis severity.

BACKGROUND: Little is known about the relation between allergic rhinitis severity and airborne pollen in combination with air pollutants. OBJECTIVE: To model the risk of suffering from severe seasonal allergic rhinitis (SAR) as a function of both pollen count and air pollution levels in a large nationwide sample of patients whose SAR was diagnosed by a physician and confirmed by skin prick test positivity or specific immunolglobulin E to common aeroallergens. METHODS: The severity of SAR symptoms was estimated with the Symptomatic Global Score (SGS) among 36,397 patients suffering from an untreated and uncomplicated SAR between May and August 2004 in metropolitan France. Patients who had an SGS in the upper third quartile were classified as suffering from severe SAR. A multilevel model relating SAR severity, pollen and air pollution was used to take into account the hierarchical data structure. RESULTS: 18.9% of the 17,567 urban patients retained for the analysis suffered from severe rhinitis. At the Lag0 (day of the visit), a rise of 60 grass pollen grains/m(3) increased the risk of suffering from a severe SAR form by 8% in the multileveled model after adjusting for potential confounders and air pollution levels. Results were also confirmed in the subsample of individuals with documented sensitization to grass pollen. CONCLUSION: Grass pollen count aggravated SAR in terms of symptoms in our nationwide sample. These findings confirm the need for proper treatment and preventive measures in SAR patients sensitized to grass pollen.

Exploring endocrine GH pattern in mice using rank plot analysis and random blood samples.

GH plays important pleiotropic roles in development, growth, metabolism, and aging of vertebrate species. Mouse mutants with altered GH signaling have been increasingly instrumental in studying somatotropic pathophysiology. However, the pulsatile characteristics of GH secretion are difficult to study in mice because catheterization is cumbersome and long-term serial sampling is limited by small body size and blood volume. We therefore developed an approach routinely applicable to mice, which detects endogenous, physiological GH pattern from randomly obtained spot samples. We determined individual hormone concentration in large groups of mice, ranked the data by magnitude, and statistically analyzed the resulting profiles. This revealed that the nadir-to-peak distribution of plasma GH concentration in mice was similar to other mammals, and that nycthemeral and sex differences existed as well. We found handling stress to be a potent immediate downregulator of circulating GH. We showed that samples need to be taken within seconds to reflect true endogenous levels, unaffected by stress. GH receptor/Janus kinase 2/signal transducer and activator of transcription 5 activation measured in the liver correlated strongly with plasma GH levels, but peak concentrations did not further increase the pathway activation. We applied this rank plot analysis to the GH-deficient and long-lived brain-specific IGF-1 receptor knockout (bIGF1RKO(+/-)) mouse mutant and found a high proportion of low GH concentrations, indicative of extended trough periods and rare peaks. Taken together, we showed that rank plot analysis is a useful method that allows straightforward studies of circadian endogenous GH levels in mice.