EFFECTIVENESS OF NUTRITIONAL INTERVENTIONS IN IMPROVING PULMONARY FUNCTION, INFLAMMATORY STATUS, AND FUNCTIONAL CAPACITY AMONG PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation, systemic inflammation, and nutritional depletion, which collectively contribute to disease progression and poor clinical outcomes. Nutritional interventions targeting these pathophysiological mechanisms have emerged as potential adjunct therapies, yet their efficacy remains incompletely characterized. We conducted a systematic review and meta-analysis to evaluate the effectiveness of nutritional interventions on pulmonary function, inflammatory biomarkers, and functional capacity in COPD patients. A comprehensive literature search was performed across MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science from inception through August 2024. Eligible studies were randomized controlled trials evaluating nutritional interventions (omega-3 fatty acids, vitamin D, antioxidants, protein/caloric supplementation, or combined nutritional support) in adults with COPD. Primary outcomes included pulmonary function parameters (forced expiratory volume in one second [FEV₁], forced vital capacity [FVC], FEV₁/FVC ratio), inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α]), and functional capacity measures (six-minute walk test [6MWT], handgrip strength, body mass index [BMI], fat-free mass index [FFMI]). Data were pooled using random-effects models with DerSimonian-Laird estimation. Fourteen randomized controlled trials comprising 892 participants (mean age 64.7 years, 58% male, predominantly GOLD stages II–III) met inclusion criteria. Nutritional interventions significantly improved FEV₁ (% predicted) with a pooled mean difference of 3.12% (95% CI: 0.87 to 5.37; I²=58%; P=0.006) and FVC (% predicted) with a mean difference of 2.48% (95% CI: 0.31 to 4.65; I²=49%; P=0.025), though the FEV₁/FVC ratio showed no significant change (mean difference 1.54%; 95% CI: −0.22 to 3.30; I²=63%; P=0.087). Inflammatory markers demonstrated substantial reductions: CRP decreased by 1.83 mg/L (95% CI: −3.06 to −0.60; I²=72%; P=0.003), IL-6 showed a standardized mean difference of −0.71 (95% CI: −1.14 to −0.28; I²=66%; P=0.001), and TNF-α exhibited a standardized mean difference of −0.54 (95% CI: −0.96 to −0.12; I²=61%; P=0.011). Functional capacity outcomes revealed significant improvements in 6MWT distance (mean difference 28.4 m; 95% CI: 12.6 to 44.2; I²=54%; P=0.001), handgrip strength (mean difference 2.1 kg; 95% CI: 0.4 to 3.8; I²=41%; P=0.016), and FFMI (mean difference 0.61 kg/m²; 95% CI: 0.14 to 1.08; I²=38%; P=0.011). Subgroup analyses indicated greater benefits with intervention durations ≥12 weeks and in patients with moderate COPD severity. Adverse events were mild and infrequent, predominantly gastrointestinal symptoms reported in fewer than 8% of participants. GRADE certainty of evidence ranged from low to moderate across outcomes, primarily limited by heterogeneity and imprecision. These findings suggest that nutritional interventions, particularly omega-3 fatty acids, vitamin D, and combined nutritional support, may provide clinically meaningful benefits in pulmonary function, systemic inflammation, and functional capacity in COPD patients. However, the hypothesis-generating nature of these results and moderate heterogeneity warrant further investigation through adequately powered, rigorously designed trials to establish optimal intervention protocols and identify patient subgroups most likely to benefit.