Related Articles

The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.

PLoS One. 2013;8(11):e80257

Authors: Wagener AH, Zwinderman AH, Luiten S, Fokkens WJ, Bel EH, Sterk PJ, van Drunen CM

Abstract
BACKGROUND: The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium.
OBJECTIVE: Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles.
METHODS: This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used.
RESULTS: The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions.
CONCLUSIONS: Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be potential targets for future drug development.

PMID: 24282527 [PubMed - in process]

Related Articles

Eczema and Sensitization to Common Allergens in the United States: A Multiethnic, Population-Based Study.

Pediatr Dermatol. 2013 Nov 27;

Authors: Fu T, Keiser E, Linos E, Rotatori RM, Sainani K, Lingala B, Lane AT, Schneider L, Tang JY

Abstract
The relationship between food and environmental allergens in contributing to eczema risk is unclear on a multiethnic population level. Our purpose was to determine whether sensitization to specific dietary and environmental allergens as measured according to higher specific immunoglobulin E (IgE) levels is associated with eczema risk in children. National Health and Nutrition Examination Survey participants ages 1 to 17 years were asked whether they had ever received a diagnosis of eczema from a physician (n = 538). Total and specific serum IgE levels for four dietary allergens (egg, cow's milk, peanut, and shrimp) and five environmental allergens (dust mite, cat, dog, Aspergillus, and Alternaria) were measured. Logistic regression was used to examine the association between eczema and IgE levels. In the United States, 10.4 million children (15.6%) have a history of eczema. Eczema was more common in black children (p < 0.001) and in children from families with higher income and education (p = 0.01). The median total IgE levels were higher in children with a history of eczema than in those without (66.4 vs 50.6 kU/L, p = 0.004). In multivariate analysis adjusted for age, race, sex, family income, household education, and physician-diagnosed asthma, eczema was significantly associated with sensitization to cat dander (odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.05, 1.4, p = 0.009) and dog dander (OR = 1.5, 95% CI, 1.2, 1.7, p < 0.001). After correction for multiple comparisons, only sensitization to dog dander remained significant. U.S. children with eczema are most likely to be sensitized to dog dander. Future prospective studies should further explore this relationship.

PMID: 24283549 [PubMed - as supplied by publisher]

Clinical and Epidemiologic Phenotypes of Childhood Asthma.

Am J Respir Crit Care Med. 2013 Nov 27;

Authors: Depner M, Fuchs O, Genuneit J, Karvonen AM, Hyvärinen A, Kaulek V, Roduit C, Weber J, Schaub B, Lauener R, Kabesch M, Pfefferle PI, Frey U, Pekkanen J, Dalphin JC, Riedler J, Braun-Fahrländer C, von Mutius E, Ege MJ, The PASTURE Study Group

Abstract
Rationale: Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes. Objective: To compare epidemiologic phenotype definitions identified by latent class analysis (LCA) with clinical phenotypes based on patient histories, diagnostic work-up and treatment responses. To relate phenotypes to genetic and environmental determinants as well as diagnostic and treatment related parameters. Methods: LCA was performed in an international multi-center birth cohort based on yearly questions about current wheeze until age six. Associations of wheeze-classes and clinical phenotypes with asthma-related characteristics such as atopy, lung function, fraction of exhaled nitric oxide and medication use were calculated using regression models. Results: LCA identified 5 classes, which verified the clinically defined wheeze phenotypes with high sensitivity and specificity; the respective receiver operating characteristics curves displayed an area under the curve (AUC) ranging from 84 (frequent wheeze) over 85 (asthma diagnosis) and 87 (unremitting wheeze) to 97 (recurrent unremitting wheeze). Recurrent unremitting wheeze was the most specific and unremitting wheeze at least once the most sensitive definition. The latter identified a subgroup of children with decreased lung function, increased genetic risk, in utero smoke exposure (odds ratio 2.03 (1.12-3.68); p=0.0191), but without established asthma diagnosis and treatment. Conclusion: Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby we identified clinically conspicuous but undiagnosed children. Because of their high AUC values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies.

PMID: 24283801 [PubMed - as supplied by publisher]

Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

Drug Des Devel Ther. 2013;7:1387-1398

Authors: Theron AJ, Steel HC, Tintinger GR, Feldman C, Anderson R

Abstract
Beta2-adrenoreceptor agonists (β2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled β2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of β2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of β2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of β2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3',5'-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells.

PMID: 24285920 [PubMed - as supplied by publisher]