Abstract
Background: In chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g., non-typeable Heamophilus influenzae (NTHi). Accumulating evidence also associates vitamin D deficiency with the severity of COPD and exacerbation frequency. However, it is still unclear whether vitamin D deficiency when combined with cigarette smoking would worsen and prolong exacerbations caused by repeated infections with the same bacterial strain. Methods: vitamin D sufficient (VDS) and deficient (VDD) mice were exposed to nose-only cigarette smoke (CS) for 14 weeks and oropharyngeally instilled with NTHi at week 6, 10 and 14. Three days after the last instillation, mice were assessed for lung function, remodeling, inflammation and immunity. The impact of VDD and CS on inflammatory cells and immunoglobulin (Ig) production was also assessed in non-infected animals while serum Ig production against NTHi and dsDNA was measured in COPD patients before and 1 year after supplementation with Vitamin D3. Results: VDD enhanced NTHi eradication, independently of CS and complete eradiation was reflected by decreased anti-NTHi Ig’s within the lung. In addition, VDD led to an increase in total lung capacity (TLC), lung compliance (Cchord), MMP12/TIMP1 ratio with a rise in serum Ig titers and anti-dsDNA Ig’s. Interestingly, in non-infected animals, VDD exacerbated the CS-induced anti-NTHi Ig’s, anti-dsDNA Ig’s and inflammatory cells within the lung. In COPD patients, serum Ig production was not affected by vitamin D status but anti-NTHi IgG increased after vitamin D3 supplementation in Vitamin D insufficient patients before treatment. Conclusion: During repeated infections, VDD facilitated NTHi eradication and resolution of local lung inflammation through production of anti-NTHi Ig, independently of CS but it also produced autoantibodies. In COPD patients, vitamin D supplementation might be protective against NTHi infections in vitamin D insufficient patient. Future research is needed to decipher the protective or self-destructive effects of VDD on adaptive immunity.Trail registration: ClinicalTrails, NCT00666367. Registered 23 April 2008, https://www.clinicaltrials.gov/ct2/show/study/NCT00666367
Effect of vitamin D on lung function assessed by forced oscillation technique in asthmatic children with vitamin D deficiency: A randomized double-blind placebo-controlled trial
