Perinatal Vitamin D Deficiency and Childhood Asthma: A Molecular Perspective

There is a large body of literature suggesting that the recent increase in the incidence of childhood asthma might be associated with vitamin D deficiency during lung development. There are also strong experimental animal data showing that vitamin D is one of the local alveolar paracrine factors that spatiotemporally modulates perinatal pulmonary maturation. However, the mechanistic link between vitamin D deficiency during pregnancy and childhood asthma is not known. In this review, we demonstrate how perinatal vitamin D deficiency could mechanistically drive both the proximal and distal airways to a myogenic phenotype, molecularly and structurally, predisposing the offspring to asthma. More specifically, we will review how perinatal vitamin D deficiency results in an increased abundance of mesenchymal myofibroblasts, a feature that is highly consistent with the pathophysiology of asthma. We also provide evolutionary insights as to how vitamin D deficiency might (re)activate the atavistic host defense mechanisms that could precipitate a lung phenotype consistent with asthma. Since vitamin D deficiency seems to alter the normal homeostatic epithelialmesenchymal signaling pathways in the developing lung, it offers a distinct translational opportunity to prevent this process through targeted molecular manipulations. While we wait for the results of on-going trials of vitamin D supplementation during pregnancy to get some definitive answers on its role in the pathogenesis of childhood asthma, we advocate studies to discover new vitamin D analogs and/or metabolites with optimal respiratory effects and without any significant side effects.