Until 20 years ago it was widely believed that asthma was an allergic/atopic disease involving atopic inflammation of the airways. Work that I and others have done has now shown that non-atopic asthma is much more important than was previously recognised. This has been confirmed by my ERC-funded AsthmaPhenotypes study, in both high-income countries (HICs) and low-and-middle-income countries (LMICs). This is important both in terms of the prevention of non-atopic asthma, and also in terms of its treatment. I therefore propose to study the Causes and MEchanisms foR non-atopic Asthma in children (CAMERA) in four different settings where I have shown that NAA is common: New Zealand (HIC, high prevalence), Brazil (LMIC, high prevalence), Ecuador (LMIC, medium prevalence), and Uganda (LMIC, low prevalence). Work-package 1 (WP1): involves a case-control study of risk factors for atopic and non-atopic asthma in these four settings, as well as similar analyses in other available and comparable data sets. Together, these studies have comparable data on asthma, atopy, and a large number of asthma risk factors, on a total of 48,000 participants. I will conduct innovative analyses exploring the different causal pathways in these different settings. Work package II: in each centre, we will then select 160 participants (40 atopic asthmatics, 40 non-atopic asthmatics, 40 atopic non-asthmatic, 40 non-atopic non-asthmatics) for further clinical investigation with regards to three mechanisms that may be particularly relevant to non-atopic asthma: capsaicin challenge, cold-air challenge, and response to interferon-gamma. The unique features of this study include: (i) the inclusion of both high and low prevalence centres from HICs and LMICs; (ii) new analyses of risk factors for NAA, contrasting the findings in various pathways; and (iii) the investigation of three mechanisms which may be involved in non-atopic pathways.