Fractional exhaled nitric oxide in acute exacerbations of chronic obstructive pulmonary disease: A meta-analysis with meta-regressions

Background Fractional exhaled nitric oxide (FeNO) has emerged as a useful tool for monitoring airway inflammation in chronic obstructive pulmonary disease (COPD) patients. We designed a systematic review and meta-analysis to evaluate the impact of acute exacerbations of COPD (AECOPD) on FeNO levels compared to healthy controls and stable patients. Methods A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was completed on February 20th, 2025, and no language restrictions were applied. Using the random effects method, differences between cases and controls were expressed as mean differences (MD) with 95 % confidence intervals (95 %CI). The protocol was submitted to PROSPERO with identification number CRD42023378704. Results Nineteen articles were included. FeNO levels were significantly higher in AECOPD compared with stable COPD (MD: 4.86 ppb; 95 %CI: 1.26–8.46; P = 0.008) and healthy controls (MD: 8.68 ppb; 95 %CI: 2.47–14.89; P = 0.006). In patients evaluated before and after clinical stabilization, FeNO levels declined significantly following treatment (MD: 6.27 ppb; 95 %CI: 3.57–8.97; P < 0.001), with greater impairment in FEV1/FVC being associated with a larger effect size (Z-score:6.92; P < 0.001). These findings were consistent across sensitivity and subgroup analyses, with no evidence of publication bias. Conclusions AECOPD is associated with a significant increase in FeNO levels, particularly when functional impairment is more severe, which then return to lower baseline values once clinical stability is achieved.