Background Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. Objectives To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. Data sources MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. Study selection Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. Study appraisal Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. Results We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Limitations Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. Conclusions Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. Study registration This study is registered as PROSPERO CRD42014013953. Funding The National Institute for Health Research Health Technology Assessment programme.
Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25).
Meta-analysis of a modest number of trials in people with predominantly mild to moderate asthma suggests that vitamin D is likely to reduce both the risk of severe asthma exacerbation and healthcare use. It is as yet unclear whether these effects are confined to people with lower baseline vitamin D status; further research, including individual patient data meta-analysis of existing datasets, is needed to clarify this issue. Children and people with frequent severe asthma exacerbations were under-represented; additional primary trials are needed to establish whether vitamin D can reduce the risk of severe asthma exacerbation in these groups.
Asthma is a chronic respiratory disorder which is associated with airway inflammation. Environmental factors, in association with genetic susceptibility, play a critical role in asthma pathophysiology. Inhaled allergens, smoke exposure, indoor and outdoor air pollution are common triggers of asthma symptoms. Although the role of diet has clearly established mechanisms in diseases such as cardiovascular disease, type 2 diabetes, and cancer, it is not commonly identified as a causal factor in asthma. However, some dietary patterns, such as the Western diet, which includes a high intake of refined grains, processed and red meats, and desserts, have pro-inflammatory effects. On the contrary, the Mediterranean diet, with high intake of fruits and vegetables has anti-inflammatory properties. The influence of food on asthma outcomes is of growing interest, but dietary habits of asthma patients are not commonly investigated in clinical practice. In this review, we focus on the impact of diet on asthma risk and asthma control. We also detail the influence of diet on obese patients with asthma.
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