06 Dec Vitamin D and asthma: supplementation to prevent exacerbations
Vitamin D deficiency has been associated with a wide range of disorders and diseases including cancer, cardiovascular disease, metabolic disorders, infectious diseases, autoimmune diseases, pregnancy-related outcomes, skeletal disorders, respiratory disease, multiple sclerosis, mental health disorders, and inflammation, as well as mortality.1,2 If causal, vitamin D deficiency could pose a significant burden on health care systems, particularly in populations in which vitamin D deficiency is prevalent. As such, it may be suggested that vitamin D supplementation could have widespread therapeutic and cost benefits for both patients and government health care systems.
Recently British researchers investigated vitamin D supplementation in relation to asthma. A systematic review and meta-analysis of individual participant data, funded by the Health Technology Assessment Program, National Institute for Health Research, was conducted. They found that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. It was not determined however whether this effect is restricted to patients with low baseline vitamin D status or if effects differed across subgroup of patients. The methods of their investigation and findings as published in THE LANCET Respiratory Medicine are included as below:
For this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo-controlled, randomised controlled trials of vitamin D3 or vitamin D2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953.
Our search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0·74, 95% CI 0·56–0·97; p=0·03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation. Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0·33, 0·11–0·98; p=0·046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0·77, 0·58–1·03; p=0·08; 764 participants in six studies; moderate-quality evidence; pinteraction=0·25). p values for interaction for all other subgroup analyses were also higher than 0·05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I2=0·0, p=0·56).
Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. David A Jolliffe, Lauren Greenberg, Richard L Hooper, Christopher J Griffiths, Carlos A Camargo Jr, Conor P Kerley, Megan E Jensen, David Mauger, Iwona Stelmach, Mitsuyoshi Urashima, Adrian R Martineau. THE LANCET Respiratory Medicine. Published online October 3, 2017. www.thelancet.com/respiratory. http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30306-5/fulltext
- Autier, P, Boniol, M, Pizot, C, and Mullie, P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014; 2: 76–89
- Theodoratou, E, Tzoulaki, I, Zgaga, L, and Ioannidis, JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014; 348: g2035