Sufficient vitamin D status positively modified ventilatory function in asthmatic children following a Mediterranean diet enriched with fatty fish intervention study

Abstract

Asthma in children is the most prevalent allergic disease worldwide that has become a major public health priority. The objective of this study was to examine the relationship between baseline serum vitamin D status, spirometry, and fractional exhaled nitric oxide levels (FeNO) in 64 Greek children with ‘mild asthma’ aged 5 to 12 years (51.6% male) in a dietary intervention study. We hypothesized that baseline serum vitamin D levels modify the beneficial response of fatty fish intake on pulmonary function in asthmatic children following a Mediterranean diet. The intervention group consumed 2 fatty fish meals/week (≥150 g cooked filleted fish/meal) as part of the Mediterranean diet for six months, and the control group consumed their usual diet. Baseline serum 25(OH)D was determined using enzyme-linked immunoassay and defined as sufficient levels of 25(OH)D ≥25 ng/mL. Only 36% of children were graded as sufficient in 25(OH)D levels on entry into the study with a higher proportion of girls insufficient than boys (61% vs 39% respectively). Participants with sufficient levels of serum 25(OH)D at baseline, consuming the intervention diet increased FEV₁/FVC by 4.89 units (β = 4.89; 95%CI: 1.19-8.61; p = 0.013) and FEF_25-75% by 12.83 units (β = 12.83; 95%CI: 4.27-21.40; p = 0.006) compared to controls. No significant differences in pulmonary function or FeNO were observed for those with insufficient levels of 25(OH) D in the intervention or control groups. In conclusion, sufficient serum vitamin D levels enhanced ventilatory function in response to a dietary intervention in asthmatic children.

Introduction

There is general consensus that asthma is the most prevalent allergic disease affecting 6.3 million children worldwide [1]. It is a chronic inflammatory disorder of the airways associated with increased morbidity, patient burden, and poor quality of life as well as substantial health care and societal costs, rapidly becoming a public health priority [2]. Studies show that asthma control is poor in children with fewer than 50% of children adhering to prescribed asthma therapy [3].

Asthma is unequivocally caused by a complex combination of genetic and environmental factors [2]. Poor nutrition has been implicated as one of these factors, contributing to increasing asthma prevalence along with vitamin D deficiency in children [4,5]. It is hypothesized that the increasing prevalence of vitamin D deficiency may be linked to the asthma epidemic which has stimulated research interest in the role of vitamin D in asthma pathophysiology. Recent studies have demonstrated that airway epithelia, lung fibroblasts, airway smooth muscle cells, and immune cells (T and B cells, macrophages, monocytes, dendritic cells) contain vitamin D receptors and high levels of the enzyme, 1a-hydroxylase [6]. Vitamin D receptors regulate the transcription of various genes implicated in inflammation and immunomodulation of respiratory epithelium [1]. Vitamin D suppresses pro-inflammatory cytokines Interleukin-17 (IL-17) and IL-13 and promotes anti-inflammatory cytokines such as IL-10 [1]. Thus, vitamin D has a number of biological and immunomodulatory effects that might be important in regulating key mechanisms in asthma.

Low vitamin D status has been reported to be common among children with asthma in a variety of settings [1,7,8]. According to a recent systematic review and meta-analysis undertaken by Jat et al (2017), emerging evidence from observational studies suggest a link between vitamin D deficiency and asthma in children [9]. Data analysis of 23 relevant studies including 13,160 children under 18 years revealed that vitamin D deficiency and insufficiency was prevalent in 28.5% and 26.7% of asthmatic children, respectively. Asthmatic children had lower 25(OH)D levels as compared to non-asthmatic children. Although mixed results were reported for correlations between 25(OH)D and asthma incidence, asthma control, and lung function. Plausible explanations for diversity amongst studies included heterogeneity in study designs, techniques used to measure serum vitamin D, sample size, age, population variability, geographic location, asthma diagnosis at variable ages, and partial controlling for confounders. Similar findings have been published in another systematic review [10], reporting a 36% decreased risk of asthma exacerbation in children. In addition, a beneficial effect of vitamin D supplementation on asthma exacerbations in children has been documented in systematic reviews and meta-analyses [11] .

In our latest randomized controlled trial (RCT) designed to examine the efficacy of a Mediterranean diet supplemented with fatty fish, we found that increased fatty fish intake reduced bronchial inflammation in asthmatic children [12]. The objective of this study was to examine the relationship between baseline serum vitamin D status, spirometry, and fractional exhaled nitric oxide levels (FeNO) in children with ‘mild asthma’ following a Mediterranean diet enriched with fatty fish intervention study versus the control with a habitual diet. Using data from this trial, we conducted a sub-analysis testing the hypothesis that baseline serum vitamin D levels modify the beneficial response of fatty fish intake on pulmonary function in asthmatic children following a Mediterranean diet and extend further to our work on diet and lung function in childhood asthma.