Periodic Reporting for period 2 - CAMERA (Causes and MEchanisms foR non-atopic Asthma in children)
Periodo di rendicontazione: 2023-04-01 al 2024-09-30
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 am therefore investigating 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 2 (WP2): 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.
I am therefore investigating 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 2 (WP2): 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.
Work package 1: An analysis of demographic, lifestyle, and environmental risk factors for atopic and non-atopic asthma has been completed and a paper submitted for publication. This included existing questionnaire data for 32,741 children from the AsthmaPhenotypes study (my previous ERC Advanced Grant, which includes the four CAMERA centres), the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II, the Social Change, Asthma and Allergy in Latin America Study (SCAALA), and the Avon Longitudinal Study of Parents and Children (ALSPAC). Risk factors for the four different pathways to atopic asthma and non-atopic asthma were assessed and compared.
An analysis to investigate associations between life-course stress and atopic and non-atopic asthma is well underway. Data on psychosocial variables, such as types of intrafamilial violence, suspected maternal common mental disorder and behaviour problems in children have been included from the SCAALA study in Brazil and Ecuador. The results will be compared with similar analyses of data from the ALSPAC cohort in the UK.
Work package 2 (WP2): Detailed protocols were developed for each procedure in WP2 and ethical approvals were obtained from LSHTM and local and national committees for each centre. The Brazil CAMERA centre hosted an in-person 3-day training meeting in Salvador in June 2023 to provide detailed training in each WP2 procedure, involving research staff from each centre.
Recruitment is underway in each centre, inviting previous AsthmaPhenotypes study participants, as well as recruitment of new participants. An electronic data collection interface has been set up using KoboCollect, to facilitate data collection and transfer to LSHTM.
An analysis to investigate associations between life-course stress and atopic and non-atopic asthma is well underway. Data on psychosocial variables, such as types of intrafamilial violence, suspected maternal common mental disorder and behaviour problems in children have been included from the SCAALA study in Brazil and Ecuador. The results will be compared with similar analyses of data from the ALSPAC cohort in the UK.
Work package 2 (WP2): Detailed protocols were developed for each procedure in WP2 and ethical approvals were obtained from LSHTM and local and national committees for each centre. The Brazil CAMERA centre hosted an in-person 3-day training meeting in Salvador in June 2023 to provide detailed training in each WP2 procedure, involving research staff from each centre.
Recruitment is underway in each centre, inviting previous AsthmaPhenotypes study participants, as well as recruitment of new participants. An electronic data collection interface has been set up using KoboCollect, to facilitate data collection and transfer to LSHTM.
Our novel approach to the analysis of risk factors for atopic and non-atopic asthma using data on over 32,000 children has made an important contribution to understanding the relationship between atopy and asthma. Ongoing work will elucidate the role of stress as a cause of atopic and non-atopic asthma.
The results of clinical investigations currently underway will make significant contributions to our understanding of the mechanisms involved in non-atopic asthma.
The results of clinical investigations currently underway will make significant contributions to our understanding of the mechanisms involved in non-atopic asthma.