Association of serum vitamin D levels with disease severity, systemic inflammation, prior lung function loss and exacerbations in a cohort of patients with chronic obstructive pulmonary disease (COPD)

Abstract

Background: Vitamin D deficiency has been associated with chronic disorders including chronic obstructive pulmonary disease (COPD) but the relationships with inflammation, exacerbations and disease progression remain unclear. Methods: In this monocentric cross-sectional observational study we analyzed the disease status, systemic inflammation, prior exacerbation frequency and loss in lung function in relation to serum 25-hydroxyvitamin D (25-OHD) levels in a cohort of 94 patients with COPD. Serum 25-OHD, C-reactive protein, interleukin-6 and tumor necrosis factor-α were quantified. Exacerbation frequencies and sunlight exposure were assessed. These parameters were analyzed in correlation to the current forced expiratory volume in 1 s (FEV 1 ), the individual average 3-year FEV 1 decline and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Results:We observed fair correlation between serum 25-OHD and the current FEV 1 (r=0.38, P<0.001). Furthermore, mean serum 25-OHD was significantly altered between patients of GOLD stages I-IV (P=0.013). There was weak negative correlation of 25-OHD and the average annual change of the FEV 1 (r=−0.26, P<0.05). Furthermore, we observed fair negative correlation between 25-OHD and C-reactive protein (r=−0.32, P<0.01) as well as weak negative correlation with interleukin-6 (r=−0.23, P<0.05). While the exacerbation frequency significantly differed between GOLD stages (P=0.04), there was no direct association between exacerbations and 25-OHD levels. Conclusion:Our data confirm frequent vitamin D deficiency in COPD and point out correlations between 25-OHD levels, systemic inflammation, disease severity and progression.

Vitamin D deficiency in chronic obstructive pulmonary disease

“…This may be modified by the severity of VDD: Soeroto et al [16 ▪ ] found that the number of exacerbations was inversely correlated with serum 25(OH)D 3 levels ( r = 0.639, P < 0.001), while Ulucoban et al [15] found that the annual rate of exacerbation was 1.6 per year in severely deficient patients and Lokesh et al [17] found that all patients with severe deficiency [serum 25(OH)D 3 levels <15 ng/ml] experienced more than three exacerbations per year. However, these observations were not confirmed by other recent studies: a retrospective chart review of 117 COPD patients found that patients with severe VDD did not have an increased exacerbation frequency compared with those without VDD [26], and another cross-sectional study found no association between exacerbation frequency and VDD [7]. Nevertheless, the majority of studies support an association between severe VDD and exacerbation frequency.…”

“…A well-functioning immune system is essential to respiratory health, and vitamin D has an important role in promoting and regulating immune function, including cellular proliferation, inflammation, and wound healing. A 2021 cross-sectional observational study found an inverse relationship between serum 25(OH)D 3 levels and C-reactive protein (CRP) and IL-6 levels but not with TNF-α [7], which suggests that VDD is associated with a systemic inflammatory state. This inverse relationship with CRP was also found in a prospective observational study in patients with COPD [8].…”

Testing for Vitamin D in High-Risk COPD in Outpatient Clinics in Spain: A Cross-Sectional Analysis of the VITADEPOC Study

“…With regard to supplementation and its monitoring, it is important to mention that the dose and frequency required will depend on the severity of the deficit, its causes, and also the used vitamin D form [ 30 ]. In our study, there was a limited number of patients with high-risk COPD who had received vitamin D supplements, despite the beneficial effects of vitamin D in reducing the risk of exacerbation [ 42 , 43 ]. In our analysis, the factors related to a history of vitamin D supplementation were having lower vitamin D levels and a history of hospitalization.…”

Changes in vitamin D metabolites at the time of critical illness and 6 months later—A prospective observational study

“…2,3 It is common amongst elderly patients with chronic illnesses and risk of malnutrition, so its association with adverse outcomes is not surprising. [4][5][6] The relationship between low-vitamin D levels and critical illness has been of interest for more than a decade. Early cohort studies indicated that low 25(OH)D-vitamin levels were frequent on admission and in the year preceding ICU admission, and were associated with adverse outcomes.…”

“…Vitamin D insufficiency (commonly defined as 25(OH)D‐vitamin under 50 nmol/L or 20 ng/ml) 1 is common despite public awareness and widespread availability of supplements 2,3 . It is common amongst elderly patients with chronic illnesses and risk of malnutrition, so its association with adverse outcomes is not surprising 4–6 . The relationship between low‐vitamin D levels and critical illness has been of interest for more than a decade.…”