Vitamin D Supplementation Efficacy in Severe Vitamin D-Deficient versus Insufficient COPD Patients: A Stratified Meta-Analysis of Exacerbation Risk

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and recurrent exacerbations that accelerate disease progression. Vitamin D deficiency is highly prevalent in this population and correlates with impaired macrophage function. However, randomized controlled trials regarding supplementation have yielded conflicting results. We hypothesized that efficacy is limited by a ceiling effect, where benefits are strictly restricted to patients with profound baseline deficiency. Methods: We conducted a systematic review and stratified meta-analysis of randomized controlled trials comparing Vitamin D supplementation to placebo in COPD. To ensure methodological homogeneity and avoid data duplication, we strictly included only primary RCTs and excluded aggregate IPD meta-analyses. Studies investigating acute treatment of active exacerbations were also excluded. Data were stratified by baseline serum 25-hydroxyvitamin D [25(OH)D] levels into Severe Deficiency (