Vitamin D supplementation blocks pulmonary structural and functional changes in a rat model of perinatal vitamin D deficiency

Abstract

Whereas epidemiological data strongly link vitamin D (VD) deficiency to childhood asthma, the underlying molecular mechanisms remain unknown. Although VD is known to stimulate alveolar epithelial-mesenchymal interactions, promoting perinatal lung maturation, whether VD supplementation during this period protects against childhood asthma has not been demonstrated experimentally. Using an in vivo rat model, we determined the effects of perinatal VD deficiency on overall pulmonary function and the tracheal contraction as a functional marker of airway contractility. One month before pregnancy, rat dams were put on either a no cholecalciferol-added or a 250, 500, or 1,000 IU/kg cholecalciferol-added diet, which was continued throughout pregnancy and lactation. At postnatal day 21, offspring plasma 25(OH)D levels and pulmonary function (whole body plethysmography and tracheal contraction response to acetylcholine) were determined. 25(OH)D levels were lowest in the no cholecalciferol-supplemented group, increasing incrementally in response to cholecalciferol supplementation. Compared with the 250 and 500 IU/kg VD-supplemented groups, the no cholecalciferol-supplemented group demonstrated a significant increase in airway resistance following methacholine challenge. However, the cholecalciferol deficiency-mediated increase in tracheal contractility in the cholecalciferol-depleted group was only blocked by supplementation with 500 IU/kg cholecalciferol. Therefore, in addition to altering alveolar epithelial-mesenchymal signaling, perinatal VD deficiency also alters airway contractility, providing novel insights to asthma pathogenesis in perinatally VD-deficient offspring. Perinatal VD supplementation at 500 IU/kg appears to effectively block these effects of perinatal VD deficiency in the rat model used, providing a strong clinical rationale for effective perinatal VD supplementation for preventing childhood asthma.

Vitamin D deficiency and its impact on asthma severity in asthmatic children

“…Vitamin D Receptor (VDR) activation inhibits IgE expression in B cells and enhances IL-10 expression, which studies show can protect against atopic conditions [23–25]. Besides, it has been shown that 1,25-dihydroxycholecalciferol, the active form of vitamin D, is a paracrine factor that modulates fetal lung maturation and airway smooth muscle cell proliferation and differentiation [26, 27]. In one survey D supplementation associated with asthma controllers could significantly improve FEV 1 in mild to moderate persistent asthma after 24 weeks (2).…”

Effects of vitamin D supplementation on pulmonary function in postmenopausal women following an aquatic exercise program

“…These results were obtained by analyzing the forces generated by the elastic recoil of the lungs in rats with vitamin D deficiency by plethysmography and histological analysis of the lung tissue, respectively (28). Rats born to females not supplemented with vitamin D displayed structural changes, such as a significant increase in airways resistance, and changes in mesenchymal differentiation markers of the trachea compared to rats born to supplemented females (33). The direct effects of active vitamin D on lung tissue observed in these experimental studies could explain our findings in this population of women supplemented with vitamin D, even in the absence of physical training (CDG group).…”

Inhaled Vitamin D: A Novel Strategy to Enhance Neonatal Lung Maturation

“…Hematoxylin and eosin-stained lung sections were examined by a blinded investigator to determine radial alveolar counts and mean liner intercept using the previously described methods [13, 15]. Briefly, randomly selected nonoverlapping fields from sections obtained from similar regions of each lung for each treatment group were examined.…”

“…Moreover, a higher maternal VD intake during pregnancy or in early life has been shown to correlate inversely with childhood asthma [12]. Importantly, using a rodent model, we have recently mechanistically linked perinatal VD deficiency to increased airway hyper-responsiveness, and we showed that optimal VD supplementation prevented VD deficiency-associated childhood asthma phenotype [13]. …”