Vitamin-D Supplementation as an Adjunct to Standard Treatment of Asthma in Children: A Randomized Controlled Trial (ViDASTA Trial)

Abstract

To determine the role of vitamin D supplementation as adjunct therapy in improving pediatric asthma control.Children aged 6 to 11 years with moderate persistent asthma (defined as step 3 per Global Initiative for Asthmas [GINA] guidelines) were enrolled. Individuals with coexisting pulmonary, cardiac, renal, and/or endocrine conditions that contributed to vitamin D deficiency or parathyroid disease and/or required vitamin D or calcium supplements in the previous 3 months were excluded.This 3-month randomized blinded placebo-controlled trial was conducted at a tertiary care hospital in Western India. Baseline clinical information was recorded, spirometry and fractional exhaled nitric oxide (FeNO) were performed as per American Thoracic Society and European Respiratory Society recommendations, and serum 25(OH)D level was measured. Subjects were randomly assigned to 2000 IU per day of vitamin D or placebo. Spirometry, FeNO, and a venous blood sample were repeated at 3 months post enrollment. During the study period, subjects in both groups were placed on budesonide-formoterol 100mcg/6mcg inhalation 2 puffs twice daily for maintenance, with a short-acting β agonist to use as needed. Participants recorded asthma symptoms and use of rescue inhaler daily. Asthma control using the childhood asthma control test (C-ACT) and compliance with maintenance treatment and intervention therapy (drug versus placebo) were assessed at monthly visits. Data were analyzed according to the intention-to-treat principle.A total of 60 children (intervention: 30; placebo: 30) were included in the study. Although 2 participants were lost to follow-up in each group (N = 56), all 60 children were analyzed as per the intention-to-treat protocol. Demographics, preenrollment asthma medication use, medical history, and vitamin D3 levels were similar between the 2 groups. The intervention group had significantly higher baseline C-ACT score, compared with that of the placebo group (18 vs 15.5; P = .001), although both groups had mean C-ACT scores <19, indicating similarly, poorly controlled asthma at baseline. Both groups had significant improvement in C-ACT score and forced expiratory volume in 1 second at the end of the study period, when compared with the baseline. However, no significant difference was observed between the 2 groups in terms of the C-ACT score, even after adjusting for baseline scores, forced expiratory volume in 1 second, FeNO, health care use (number of exacerbations, emergency visits, hospital admissions), and adverse effects (relating to intervention). The intervention group had improvement in serum vitamin D levels at 3-months (35.5 ng/mL vs 18.8; P < .001).Vitamin D supplementation as an add-on to standard maintenance therapy in children with moderate persistent asthma does not improve asthma control.Although vitamin D deficiency has been reportedly associated with more severe asthma exacerbations, steroid-refractory asthma, and lower pulmonary function, there continues to be conflicting literature regarding the impact of vitamin D supplementation on childhood asthma. Larger studies using different vitamin D doses in children with different asthma severities, over longer periods of time, and in different parts of the world will be needed to determine if, if any, there is utility for vitamin D supplements in asthma. In the meantime, ensuring compliance with daily inhaled corticosteroid therapy and regular follow-up with the clinicians remain the cornerstone of effective asthma management.