B3632 - Air pollution and childhood asthma potential role of common allergies as mediators - 19/10/2020

B number: 
B3632
Principal applicant name: 
Tiffany Yang | Bradford Institute for Health Research (United Kingdom)
Co-applicants: 
Title of project: 
Air pollution and childhood asthma: potential role of common allergies as mediators
Proposal summary: 

Asthma is a major non-communicable disease affecting over 12% of children and estimated to affect 339 million people worldwide (1,22). It is a multifaceted and heterogeneous disease with different patterns of incidence and prevalence between children and adults and between males and females (3). Its etiology is thought to be a complex interplay between environmental exposures (such as air pollution, mold, pollen, and the weather), genetic susceptibility, and host factors (such as infections and nutrition); the underlying mechanisms, while not fully understood, may include airway inflammation and control of reactivity and airway tone (4).

Exposure to outdoor air pollutants such as particulate matter (PM) and nitrogen dioxide (NO2) have been associated with both childhood asthma and allergies (5–12). However, whether allergies such as atopic dermatitis (eczema) and allergic rhinitis (hay fever) mediate the relationship has not been well-characterized.

The atopic march, the linear progression starting with eczema with subsequent allergic rhinitis and asthma in later childhood is a well-known concept but it may not capture the trajectories of most children (13–15). Asthma often co-occurs with allergies like eczema and allergic rhinitis but the causal nature of this progression is unknown. Studies suggest that a dysfunctional skin barrier may be a site for allergic sensitization and contributes to the onset of eczema and progression to allergic rhinitis and childhood asthma (16). Eczema has often been found to precede development of asthma, but this is not always the case, with only an estimated 1-in-3 children with eczema developing childhood asthma later on (17,18). Similarly, asthma often co-occurs with allergic rhinitis due to shared common physiology such as heightened reactivity and bronchial hyperresponsiveness (19,20). It is considered a risk factor for asthma, with a 23-year follow-up finding allergic rhinitis three times more likely to develop asthma than those without allergic rhinitis (14,15). However, the evolution of the two appear to be bidirectional; a study in Italy following 99 patients with only allergic rhinitis or allergic asthma over 10 years found that 31.8% of participants with allergic rhinitis developed asthma, while 50% of those with asthma went on to develop allergic rhinitis (21).

In this proposal, we hypothesize that relationships between early-life stressors such as exposure to air pollutants and childhood asthma are at least partly mediated by common allergies and allergic diseases.

REFERENCES
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2. Global Asthma Network. Global Asthma Report.; 2018. www.globalasthmanetwork.org
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10. Deng Q, Lu C, Li Y, Sundell J, Dan Norbäck. Exposure to outdoor air pollution during trimesters of pregnancy and childhood asthma, allergic rhinitis, and eczema. Environ Res. 2016;150:119-127. doi:10.1016/j.envres.2016.05.050
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13. Belgrave DCM, Granell R, Simpson A, et al. Developmental Profiles of Eczema, Wheeze, and Rhinitis: Two Population-Based Birth Cohort Studies. PLoS Med. 2014;11(10). doi:10.1371/journal.pmed.1001748
14. Settipane RJ, Hagy GW, Settipane GA. Long-term risk factors for developing asthma and allergic rhinitis: a 23-year follow-up study of college students. Allergy Proc. 15(1):21-25. doi:10.2500/108854194778816634
15. Wright AL, Holberg CJ, Martinez FD, Halonen M, Morgan W, Taussig LM. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994;94(6 Pt 1):895-901. http://www.ncbi.nlm.nih.gov/pubmed/7971008
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17. Burgess JA, Dharmage SC, Byrnes GB, et al. Childhood eczema and asthma incidence and persistence: A cohort study from childhood to middle age. J Allergy Clin Immunol. 2008;122(2):280-285. doi:10.1016/j.jaci.2008.05.018
18. van der Hulst AE, Klip H, Brand PLP. Risk of developing asthma in young children with atopic eczema: a systematic review. J Allergy Clin Immunol. 2007;120(3):565-569. doi:10.1016/j.jaci.2007.05.042
19. Khan DA. Allergic rhinitis and asthma: Epidemiology and common pathophysiology. Allergy Asthma Proc. 2014;35(5):357-361. doi:10.2500/aap.2014.35.3794
20. Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108(5 Suppl). doi:10.1067/mai.2001.118891
21. Lombardi C, Passalacqua G, Gargioni S, et al. The natural history of respiratory allergy: a follow-up study of 99 patients up to 10 years. Respir Med. 2001;95(1):9-12. doi:10.1053/rmed.2000.0945

Impact of research: 
The large sample size available as a result of the harmonization process carried out by LifeCycle cohorts will help increase the precision of our estimates and we hope the impact of this will be a better understanding of the relationships between our exposure and outcome and whether allergies play a role in mediating this relationship.
Date proposal received: 
Thursday, 8 October, 2020
Date proposal approved: 
Monday, 12 October, 2020
Keywords: 
Epidemiology, Allergy, Respiratory - asthma, Statistical methods, Environment - enviromental exposure, pollution