Vitamin D Deficiency Alters Lung Function But Does Not Have An Effect On Airway Smooth Muscle Mass

Rationale: Vitamin D deficiency is increasing all over the world. Studies in children with asthma have revealed that reduced levels of vitamin D are associated with reduced lung function, airway remodeling and poor asthma control. The aim of this study was to determine if vitamin D deficiency alters lung function resulting in airway hyperresponsiveness (AHR) and/or causes alterations in airway smooth muscle (ASM) mass.

Methods: A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on either a vitamin D-deficient or -replete diet. Studies were carried out on offspring from deficient and replete mice of both sexes at 8 weeks of age. Lung function and thoracic gas volume (TGV) were measured by the forced oscillation technique (FOT) and plethysmography, respectively. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Formalin-fixed lungs embedded in paraffin were cut into 5 μm thick sections. Sections were stained with Masson’s Trichrome for ASM visualization. Images for morphometric analysis were taken using an Olympus DP72 microscope and camera and ASM mass measured using the newCast image analysis software (Visiopharm, Denmark).

Results: Vitamin D-deficient females had a smaller TGV compared to replete controls (p < 0.05). At 20 cm H2O transrespiratory pressure, vitamin D-deficient mice had a smaller lung volume compared to controls (females, p = 0.024; males, p = 0.028). There were no significant differences in airway resistance, however tissue damping was higher for vitamin D-deficient mice (females, p = 0.03; males, p = 0.006). There were no significant differences between vitamin D-deficient and –replete mice for airway resistance to methacholine at the maximum dose however the dose of methacholine required to cause a doubling in airway resistance was lower in female vitamin D-deficient mice (p = 0.03). There were no significant alterations to ASM mass.

Conclusions: Vitamin D deficiency can lead to deficits in lung function and an increased sensitivity to bronchoconstricting agents but does not alter ASM mass.