Asthma Prevalence and Phenotyping in the General Population: The LEAD (Lung, hEart, sociAl, boDy) Study.

Journal of Asthma and Allergy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Asthma Prevalence and Phenotyping in the General Population: The LEAD (Lung, hEart, sociAl, boDy) Study Caspar Schiffers 1 , Emiel FM Wouters 1,2 , Robab Breyer-Kohansal 1,3 , Roland Buhl 4 , Wolfgang Pohl 5 , Charles G Irvin 6 , Marie-Kathrin Breyer 1,7 , Sylvia Hartl 1,7,8 1 Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; 2NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands; 3Department of Respiratory and Pulmonary Diseases, Clinic Hietzing, Vienna Healthcare Group, Vienna, Austria; 4Pulmonology Department, Mainz University Hospital, Mainz, Germany; 5Karl Landsteiner Gesellschaft, Institute for Clinical and Experimental Pneumology, Vienna, Austria; 6Pulmonary and Critical Care, Larner College of Medicine, University of Vermont, Burlington, VT, USA; 7Department of Respiratory and Pulmonary Diseases, Clinic Penzing, Vienna Healthcare Group, Vienna, Austria; 8Sigmund Freud University, Faculty for Medicine, Vienna, Austria Correspondence: Caspar Schiffers, Ludwig Boltzmann Institute for Lung Health, Vienna, 1140, Austria, Email Background: Asthma is a chronic heterogeneous respiratory disease involving differential pathophysiological pathways and conse quently distinct asthma phenotypes. Objective and Methods: In the LEAD Study, a general population cohort (n=11.423) in Vienna ranging from 6–82 years of age, we addressed the prevalence of asthma and explored inflammatory asthma phenotypes that included allergic and non-allergic asthma, and within these phenotypes, an eosinophilic (eosinophils ≥300 cells/µL, or ≥150 cells/µL in the presence of ICS medication) or noneosinophilic (eosinophils <300 cells/µL, or <150 cells/µL in the presence of ICS) phenotype. In addition, we compared various factors related to biomarkers, body composition, lung function, and symptoms in control subjects versus subjects with current asthma (current doctor’s diagnosis of asthma). Results: An overall prevalence of 4.6% was observed for current asthma. Furthermore, an age-dependent shift from allergic to nonallergic asthma was found. The non-eosinophilic phenotype was more prominent. Obesity was a prevalent condition, and body composition including visceral adipose tissue (VAT), is affected in current asthma versus controls. Conclusion: This broad-aged and large general population cohort identified differential patterns of inflammatory asthma phenotypes that were age-dependent. The presence of eosinophilia was associated with worse asthma control, increased asthma medication, increased VAT, and lower lung function, the opposite was found for the presence of an allergic asthma. Keywords: asthma, prevalence, phenotyping, pulmonary function testing, spirometry, general population, body composition Introduction Asthma is a chronic heterogeneous disease characterized by chronic airway inflammation, variable expiratory airflow limitation and respiratory symptoms including wheeze, shortness of breath, chest tightness and cough that may vary over time and in intensity.1 The prevalence of asthma increased in the last decades and asthma is presently a highly prevalent disease affecting over 399 million people globally, or 4.3% of the population.1–3 However, these figures range from 1–22% dependent on country and/or age ranges studied.3 In children, (allergic) asthma is the highest prevalent chronic respiratory condition and is studied extensively;4 conversely, data on asthma prevalence in the elderly are more scarce5 although it is associated with increased morbidity6 and mortality.7 Differential underlying pathophysiological pathways in asthma are associated with distinct asthma phenotypes. These phenotypes can be classified by their clinical phenotype, such as early-onset, late-onset, and obesity-associated asthma, or by their inflammatory phenotype, including allergic and non-allergic eosinophilic (Th2-high) or non-eosinophilic (Th2Journal of Asthma and Allergy 2023:16 367–382 Received: 29 December 2022 Accepted: 15 March 2023 Published: 8 April 2023 367 © 2023 Schiffers et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Dovepress Schiffers et al low) asthma,8,9 and are largely derived from cohorts that included participants with severe asthma.10–12 As such, these phenotypes are poorly studied in primary care,13 and data on these phenotypes in the general population are lacking. International GINA recommendations14 suggest asthma can be characterized by different stages of severity, ranging from mild to severe asthma and by variable asthma control being either well-controlled, partly-controlled, or uncontrolled.3 In this study, we sought to determine the prevalence of asthma and inflammatory asthma phenotypes in the general population between 6 and 82 years. In addition, the presence of asthma was related to asthma control, medication use and body composition. Methods Study Design and Participants The LEAD (Lung, hEart, sociAl, boDy) Study (NCT01727518; http://clinicaltrials.gov) is a single-centered longitudinal, observational, population-based cohort study that aims to provide a comprehensive database of measured parameters of the function of the respiratory, cardiovascular, and metabolic system in a general population. In the first study phase, from 2012 to 2016, a random sample (stratified by age, gender, and residential area) of 11,423 subjects (males 47.6%, females 52.4%), aged 6–82 years, from Vienna and lower Austria has been investigated. A detailed study protocol is available online.15 Ever asthma was defined as doctor’s diagnosis (Positive response to the following question: “Has a doctor or other health professional ever told you that you have asthma?”) and current asthma defined by a current doctor’s diagnosis (Positive response to the following question: “Do you still have the diagnosis of asthma?”).16,17 Control subjects were all subjects with complete lung function data (pre- and post-bronchodilation (BD)) excluding those diagnosed with COPD, emphysema, or chronic bronchitis and current/ever asthma. The Asthma Control Test™ was performed according to the guidelines.18 The presence of asthma medication was used as a proxy to assess severity of asthma according to GINA, wi (...truncated)