The independent effects of vitamin D deficiency and house dust mite exposure on lung function are sex-specific

Nailê K Nuñez,Graeme R Zosky,Ling Chen,Paulo Márcio Pitrez,Ellen Bennett

doi:10.1038/s41598-017-15517-z

Abstract

Vitamin D deficiency is increasing around the world and has been associated with the development of asthma. This study aims to evaluate the effect of dietary vitamin D deficiency at different life stages on lung function using a murine model of allergic airways disease. BALB/c mice were challenged intranasally with HDM or saline alone for 10 days. Twenty four hours after the last challenge, mice were anesthetized and lung function was measured using the forced oscillation technique (FOT). Mice were euthanized for assessment of inflammation in the bronchoalveolar lavage (BAL) and total collagen content in lung homogenates by ELISA. Vitamin D deficiency impaired lung function in both male and female mice, increasing tissue damping and elastance, however had no effect on HDM induced inflammation. The impact of vitamin D deficiency was more evident in females. HDM also decreased airway distensibility, but only in females and this response was not altered by vitamin D deficiency. Our data suggest that vitamin D deficiency and HDM exposure have independent effects on lung mechanics and that females are more susceptible to these effects. Vitamin D deficiency may exacerbate lung function deficits by having a direct, but independent, effect on parenchymal mechanics.

Highlights

Asthma is a chronic disease characterized by airway inflammation, airway remodeling and reversible deficits in lung function[1,2]
Correspondence and requests for materials should be addressed to N.K.N. www.nature.com/scientificreports/. Given that both vitamin D deficiency and House dust mite (HDM) may lead to deficits in lung function, we investigated the interaction between vitamin D deficiency and HDM, and their effects on lung function
We have previously found that vitamin D deficiency can increase collagen type 1 alpha 1 (COL1A1) expression in utero[24] which may impact on lung mechanics

Summary

Introduction

Asthma is a chronic disease characterized by airway inflammation, airway remodeling and reversible deficits in lung function[1,2]. We have shown that maternal vitamin D deficiency at 16–20 weeks’ gestation is associated with impaired lung function at 6 years of age in offspring[12] In line with this finding, we have shown that in utero vitamin D deficiency is sufficient to induce increased airway smooth muscle (ASM) mass and cause deficits in lung function in a mouse model[13,14,15]; both of which are key characteristics of the asthmatic phenotype[1]. While these observations point to a role for vitamin D deficiency in causing alterations in lung structure, the inflammatory process itself can lead to airway remodeling. We addressed this hypothesis by evaluating the effects of in utero, postnatal and whole life vitamin D deficiency on lung function in a murine model of HDM induced allergic airways disease

Objectives

Methods

Results

Conclusion