TY - JOUR
T1 - Clinical and epidemiologic phenotypes of childhood asthma
AU - Depner, Martin
AU - Fuchs, Oliver
AU - Genuneit, Jon
AU - Karvonen, Anne M.
AU - Hyvärinen, Anne
AU - Kaulek, Vincent
AU - Roduit, Caroline
AU - Weber, Juliane
AU - Schaub, Bianca
AU - Lauener, Roger
AU - Kabesch, Michael
AU - Pfefferle, Petra Ina
AU - Frey, Urs
AU - Pekkanen, Juha
AU - Dalphin, Jean Charles
AU - Riedler, Josef
AU - Braun-Fahrländer, Charlotte
AU - Von Mutius, Erika
AU - Ege, Markus J.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/1/15
Y1 - 2014/1/15
N2 - Rationale: Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes. Objectives: 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 multicenter birth cohort based on yearly questions about current wheeze until age 6 years. 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. Measurements and Main Results: LCA identified five 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 ranging from 84% (frequent wheeze) to 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, and in utero smoke exposure (odds ratio, 2.03; 95% confidence interval, 1.12-3.68; P = 0.0191), but without established asthma diagnosis and treatment. Conclusions: Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby, we identified children with clinically conspicuous but undiagnosed disease. Because of their high area under the curve values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies. 2014
AB - Rationale: Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes. Objectives: 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 multicenter birth cohort based on yearly questions about current wheeze until age 6 years. 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. Measurements and Main Results: LCA identified five 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 ranging from 84% (frequent wheeze) to 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, and in utero smoke exposure (odds ratio, 2.03; 95% confidence interval, 1.12-3.68; P = 0.0191), but without established asthma diagnosis and treatment. Conclusions: Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby, we identified children with clinically conspicuous but undiagnosed disease. Because of their high area under the curve values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies. 2014
UR - http://www.scopus.com/inward/record.url?scp=84892663006&partnerID=8YFLogxK
U2 - 10.1164/rccm.201307-1198OC
DO - 10.1164/rccm.201307-1198OC
M3 - Journal articles
C2 - 24283801
AN - SCOPUS:84892663006
SN - 1073-449X
VL - 189
SP - 129
EP - 138
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 2
ER -
