Risk factors for atopic and non-atopic asthma in school-aged children from high, and low and middle income countries

Background Although it is well established that there are different asthma phenotypes, little is known about risk factors and mechanisms for non-atopic asthma. We compared risk factors for atopy, atopic asthma (AA) in atopics, and non-atopic asthma (NAA) in non-atopics, in children in a wide variety of countries. Methods Using four studies, across 23 countries, we assessed asthma status and atopy (skin prick tests) for children aged 6-17, plus risk factors from housing, heating, animals, family, diet, and air-quality categories. Using mixed effects logistic regression models we assessed 4 pathways to asthma: Pathway 1: comparing NAA with non-atopic non-asthma (risk factors for NAA among non-atopics); Pathway 2: comparing atopic non-asthma with non-atopic non-asthma (risk factors for atopy); Pathway 3: comparing AA with atopic non-asthma (risk factors for AA among atopics); Pathway 4: comparing AA with non-atopic non-asthma (risk factors for AA among non-atopics). Results Our final sample of 32,741 children comprised 67% non-atopic non-asthmatics, 15% atopic non-asthmatics, 8% with AA and 10% with NAA. Risk factors were similar for AA in atopic individuals and NAA in non-atopic individuals (Pearson’s correlation r=0.81). In contrast, risk factors for atopy in non-asthmatics differed from those for AA in atopic individuals (r=-0.06). Discussion These findings indicate that although atopy increases the risk of asthma, the risk factors for subsequently developing asthma are generally the same in atopics and non-atopics. This raises important questions about the role of atopy in asthma, particularly whether it is an inherent part of the aetiological process or is coincidental. Key messages 1. The risk factors for developing asthma in atopic children are generally similar to risk factors for asthma in non-atopic children 2. Risk factors for asthma (in atopic or non-atopic children) are generally different from risk factors for atopy 3. These findings are consistent across high-income countries and low-and-middle-income countries ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The CAMERA project was supported by the European Research Council under ERC grants 668954, and 101020088. The SCAALA study was supported by the Wellcome Trust under grant 072405/Z/03/Z/WT. Work in Salvador was also supported by: Fundacao de Amparo a Pesquisa do Estado da Bahia (FAPESB) under grants PNE0003/2014 and PNX0001/2014; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) under finance code 001; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) under grant 308521/2019 and CNPq/ CONFAP/FAPESB under grant 40314. Work in Wellington was supported by the Health Research Council (HRC) of New Zealand and CB was supported by an HRC Sir Charles Hercus Fellowship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the London School of Hygiene & Tropical Medicine gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes ISAAC data are publicly available at the UK Data Service archive . ALSPAC data can be accessed after application to the ALSPAC Executive Team; application instructions and data use agreements are available at . The relevant data from the WASP study and SCAALA study will be shared on reasonable request to the corresponding author.