探討口服維生素D3相較於安慰劑是否能降低慢性阻塞性肺疾病病人急性惡化率

Efficacy of Oral Vitamin D3 Supplementation versus Placebo in Reducing Acute Exacerbation Rates among Patients with Chronic Obstructive Pulmonary Disease

背景：
慢性阻塞性肺疾病病人常因氣候變化而引發呼吸困難、咳嗽、痰液增多等症狀，增加急性惡化風險。儘管補充維生素D3在某些研究中顯示出潛在益處，但其在預防急性惡化上的臨床實證仍存在爭議。本文透過實證方法，探討口服維生素D3相較於安慰劑是否能降低慢性阻塞性肺疾病病人急性惡化率，為護理實務提供參考依據。
方法：
運用PICO策略設定關鍵字：P（慢性阻塞性肺疾病病人）、I（口服維生素D3）、C（安慰劑）、O（急性惡化率），並結合布林邏輯（OR／AND）搜尋至2025年12月29日前所有發表於PubMed、Cochrane Library、CINAHL及華藝線上圖書館資料庫的文獻。納入研究類型包括系統性文獻回顧、統合分析與隨機對照試驗，語言為中文、英文，排除合併氣喘之病人、介入措施合併其他治療（其他營養素）、僅會議摘要或研究計畫書。文獻品質評估運用2024年版CASP工具，並依據Oxford CEBM（2011）標準評定文獻證據等級，評估4篇RCT證據等級均為Level 2。
結論：
本文納入4篇隨機對照試驗，總計643位COPD病人，族群涵蓋比利時、英國、伊朗、荷蘭，追蹤期為6個月至1年不等，實驗組均接受口服維生素D3，但研究中劑量不盡相同，對照組接受花生油與安慰劑。整體結果顯示，針對慢性阻塞性疾病病人接受口服維生素D3較安慰劑或花生油使用，沒有明確證據顯示能有效降低慢性阻塞性疾病病人急性惡化率。然而，次群組分析發現，基準期血清25（OH）D濃度< 10 ng／mL病人補充維生素D3顯著降低急性惡化率（RR = 0.57，95% CI [0.33，0.98]，p = .042）；另一篇研究則發現血清25（OH）D濃度< 50 nmol／L病人補充維生素D3可降低43%發生中重度急性惡化風險（HR = 0.57，95% CI [0.35，0.92]，p =.021）。結果之異質性可能源自於探討COPD族群的疾病嚴重度不同、維生素D3的補充劑量與頻率以及研究時間長短上存在差異，這些因素會影響結果的解釋力。臨床應用上不建議所有COPD病人補充維生素D3。應優先針對頻繁惡化或疑似維生素D缺乏的病人測量血清25-（OH）D濃度。當基準期濃度<50 nmol／L或< 20 ng／mL病人，補充維生素D3可能獲得預防惡化的臨床效益。為了提升證據品質與臨床實務的可行性，建議未來研究應擴大樣本規模，並針對不同嚴重度的COPD族群進行更深入的成效評估，並為臨床決策提供更明確的實證依據。

Background:
Patients with chronic obstructive pulmonary disease often experience symptoms such as dyspnea, cough, and increased sputum production triggered by climatic changes, which elevates their risk of acute exacerbations. Although some studies suggest that vitamin D3 supplementation may offer potential benefits, its clinical efficacy in preventing acute exacerbations remains a subject of debate. This study utilizes an evidence-based approach to investigate whether oral vitamin D3 supplementation, compared to a placebo, can effectively reduce the rate of acute exacerbations in COPD patients, thereby providing a robust clinical reference for nursing practice.
Methods:
Search terms were defined using the PICO framework: Participants (Chronic obstructive pulmonary disease), Intervention (Oral Vitamin D3), Comparison (Placebo), and Outcome (Acute exacerbation rate). A comprehensive search was performed using Boolean operators (OR/AND) across PubMed, the Cochrane Library, CINAHL, and Airiti Library for literature published up to December 29, 2025. Inclusion criteria comprised systematic reviews, meta-analyses, and randomized controlled trials (RCTs) published in English or Chinese. Exclusion criteria were (1) patients with comorbid asthma, (2) interventions combined with other nutrients, and (3) conference abstracts or research protocols. Methodological quality was appraised using the 2024 version of the Critical Appraisal Skills Programme (CASP) tool, and the level of evidence was determined using the 2011 Oxford Centre for Evidence-Based Medicine (CEBM) Levels of Evidence. Based on these evaluations, all four included RCTs were classified as Level 2 evidence.
Conclusion :
Four randomized controlled trials (RCTs) involving a total of 643 COPD patients across Belgium, the United Kingdom, Iran, and the Netherlands were included, with follow-up periods ranging from six months to one year. While the experimental groups received oral vitamin D3, dosages varied across studies; control groups received either placebo or peanut oil. Overall findings indicated no definitive evidence that oral vitamin D3 supplementation significantly reduces the rate of acute exacerbations in the general COPD population compared to placebo or oil.
However, subgroup analyses revealed significant benefits for specific populations. Supplementation in patients with baseline serum 25(OH)D levels < 10 ng/mL significantly lowered exacerbation rates (RR = 0.57, 95% CI [0.33, 0.98], p = .042). Another study found that for patients with serum 25(OH)D concentrations < 50 nmol/L, vitamin D3 supplementation reduced the risk of moderate-to-severe exacerbations by 43% (HR = 0.57, 95% CI [0.35, 0.92], p =.021). The observed heterogeneity may stem from variations in disease severity, vitamin D3 dosage and frequency, and study duration, all of which impact the interpretability of the results. In clinical practice, universal vitamin D3 supplementation for all COPD patients is not recommended. Priority should be given to patients with frequent exacerbations or suspected vitamin D deficiency by measuring serum 25(OH)D levels. Clinical benefits in preventing exacerbations are most likely realized when baseline concentrations are < 50 nmol/L (or < 20 ng/mL). To enhance evidence quality and clinical feasibility, future research should utilize larger sample sizes and conduct in-depth efficacy assessments across different COPD severity levels to provide clearer evidence-based guidance for clinical decision-making.