Examining relationships between vitamin D over the first decade of life and development of asthma and allergy

Hollams EM^a, Teo SM^b,c,d, Kusel M^a, Holt BJ^a, Holt KE^b,c, Inouye M^b,d, De Klerk NH^a, Zhang G^e, Sly PD^f, Hart PH^a, Holt PG^a.

 ^a The Kids Research Institute Australia, University of Western Australia, Perth, Australia
^b Centre for Systems Genomics, University of Melbourne, Melbourne, Australia
^c Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
^d School of BioSciences, University of Melbourne, Melbourne, Australia
^e School of Public Health, Curtin University, Perth, Australia
^f Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, Australia

To investigate the postulated but controversial link between vitamin D and childhood asthma, we tracked vitamin D levels from birth to age 10y in 233 members of the Perth Childhood Asthma Study (CAS). Using a highly specific, internationally-standardised method developed by Metabolomics Australia at the University of Western Australia, we measured the storage form of vitamin D (25(OH)D) from cryobanked CAS plasma samples collected at birth (cord blood), 6 months and 1, 2, 3, 4, 5, & 10 years. We have demonstrated that low 25(OH)D in infancy is linked with increased risk for concurrent allergy in early life, and that repeated periods of vitamin D deficiency in the first decade are associated with higher likelihood of experiencing asthma, allergy or eczema at age 10. To our knowledge this is the first study to extensively track 25(OH)D trajectories over childhood, and our findings highlight the limited utility of investigating just one or two ages in childhood for unraveling the relationship between vitamin D inadequacy and pediatric asthma.

Children in the CAS cohort were visited by the study doctor for every episode of respiratory infection up to age 5 years; nasopharyngeal aspirates were collected from participants at these visits as well as at the “healthy” visits during which blood was collected. While 25(OH)D levels of CAS children were not related to either the number or severity of respiratory infections experienced, they were related to timing of infection. Children with vitamin D deficiency at age 6 months tended to experience lower respiratory infections with fever earlier in life than children with higher vitamin D at 6 months, and this early incidence has been associated with an increased risk for developing asthma. In addition, as part of an ongoing collaboration with Dr. Kathryn Holt and Assoc. Prof. Michael Inouye in Melbourne, the microbial flora (microbiome) of the upper airways has been profiled for CAS children during the first year of life. When we examined whether vitamin D levels were related to differential colonisation of the upper airways, we found that children deficient in vitamin D at age 6 months showed higher levels of colonisation by Streptococcus species, which is in turn associated with higher risk for asthma development. We anticipate that the results of this study will be published in early 2017.

Plain language summary: Vitamin D is a strong regulator of the immune system that may offer protection against asthma development, but this field remains controversial due to the conflicting findings of human studies. We have addressed the current lack of knowledge about how vitamin D levels fluctuate over childhood in individuals, and how this relates to asthma risk, by examining 233 Perth children at high risk for asthma and allergy. We took vitamin D measurements from participants in the Childhood Asthma Study (CAS) at eight ages from birth to age 10. We found that allergic immune responses were more common in children with low current vitamin D in the first few years. Furthermore, repeated periods of vitamin D deficiency in the first decade were linked to higher rates of current asthma, allergy or eczema at age 10. Children with vitamin D deficiency at 6 months of age were more likely to experience two conditions previously associated with heightened asthma risk: increased colonisation of the upper airways by harmful bacteria and increased susceptibility to severe lower respiratory infections involving fever. This study shows for the first time the importance of considering vitamin D levels over a prolonged period during childhood, rather than at just one or two ages, when studying the interaction between vitamin D and asthma development.

Funders: Asthma Australia, Health Department of Western Australia, National Health and Medical Research Council of Australia