Features of asthma which provide meaningful insights for understanding the disease heterogeneity.

BACKGROUND: Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. OBJECTIVE: To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. METHODS: We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. RESULTS: Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. CONCLUSIONS AND CLINICAL RELEVANCE: An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes

food allergy and atopic dermatitis

Background/aim: Filaggrin is a protein complex involved in epidermal differentiation and skin barrier formation. Mutations of the filaggrin gene (FLG) arc associated with allergen sensitization and allergic diseases like atopic dermatitis (AD), allergic rhinitis, food allergy (FA), and asthma. The aim of the study is to reveal the frequency of change in the FIG gene and determine the association between FIG loss-of-function (LOF) mutations and FA and/or AD in Turkish children.Materials and methods: Four PLC loss-of-function (WO mutations known to be common in European populations were analyzed in 128 healthy children, 405 food-allergic children with or without atopic dermatitis, and 61 children with atopic dermatitis. PCRRFLP was performed for genotyping R501X, 2282del14, and R2447X mutations; 53247X was genotyped using a TaqMan-based allelic discrimination assay. Results were confirmed by DNA sequence analysis in 50 randomly chosen patients for all mutations.Results: A total of 466 patients [(67% male, 1 (0.7-2.8) years] and 128 healthy controls [59% male, 2.4 (1.4-3.5) years)] were included in this study. Two patients were heterozygous carriers of wild-type R501X, but none of the controls carried this mutation. Three patients and one healthy control were heterozygous carriers of wild-type 2282del4. Neither patients nor controls carried R2447X or S3247X PLC mutations. There were no combined mutations determined in heterozygous mutation carriers.Conclusions: Although R501X, 2282del4, R2447X, and S3247X mutations are very common in European populations, we found that FIG mutations were infrequent and there is no significant association with food allergy and/or atopic dermatitis in Turkish individuals.C1 [Acar, Nese Vardar; Karaaslan, Cagatay] Hacettepe Univ, Fac Sci, Dept Biol, Ankara, Turkey.[Cavkaytar, Ozlem; Yilmaz, Ebru Arik; Buyuktiryaki, Betul; Soyer, Ozge; Sahiner, Umit Murat; Sekerel, Bulent Enis] Hacettepe Univ, Fac Med, Dept Pediat Allergy, Ankara, Turkey.[Cavkaytar, Ozlem] Istanbul Medeniyet Univ, Fac Med, Dept Pediat Allergy & Immunol, Istanbul, Turkey.[Yilmaz, Ebru Arik] Pamukkale Univ, Fac Med, Dept Pediat Allergy, Denizli, Turkey.[Sackesen, Cansin] Koc Univ, Fac Med, Dept Pediat Allergy, Istanbul, Turkey