Link between vitamin D and airway remodeling

Abstract

In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.

Keywords: airway remodeling; airway smooth muscle; asthma; supplementation; vitamin D.

Figure 1

Potential pathways involving vitamin D in airway remodeling. Airway remodeling can be defined as changes in the composition, content, and organization of the cellular and molecular constituents of the airway wall. These structural changes include epithelial detachment, subepithelial fibrosis, increased ASM mass, goblet cell hyperplasia, mucous gland hyperplasia, and proliferation of blood vessels. Asthma exacerbation is triggered by allergens or viruses, inducing T-helper cell-driven inflammation and resulting in production of growth factors (TGF-β, TNF-α, and VEGF), profibrotic mediators (TGF-β, LTs, PG), MMPs, and ECM protein. Vitamin D insufficiency is associated with alteration in lung development, cellular senescence with inflammation and MMP release, and ASM hyperplasia. Potential beneficial effects of vitamin D are increasing Treg activity, improving innate immunity against viruses, decreasing release of induced mediators, and decreasing production of LTs, PG, MMP, TNF-α and TGF-β, resulting in decreased subepithelial fibrosis and ASM hypertrophy. Abbreviations: ASM, airway smooth muscle; ECM, extracellular matrix; MMP, matrix metalloproteinase; LTs, leukotrienes; IL, interleukin; Tregs, regulatory T-cells; TGF-β, transforming growth factor-beta; IFNγ, interferon gamma; TNF-α, tumor necrosis factor alpha; PG, prostaglandin; VEGF, vascular endothelial growth factor; Th2, T-helper 2; MBP, major basic protein.