Predictors of fractional exhaled nitric oxide response to inhaled corticosteroid therapy in chronic obstructive pulmonary disease: A systematic review and meta-analysis

BACKGROUND: The fractional exhaled nitric oxide (FeNO) level significantly correlates with eosinophilic airway inflammation and is considered a useful biomarker to guide inhaled corticosteroid (ICS) treatment in chronic obstructive pulmonary disease (COPD). This study investigated the FeNO response to ICS therapy in patients with COPD. METHODS: Pubmed, Embase, and Cochrane Central Register were searched for relevant trials. The primary outcome measure was the change in FeNO after ICS treatment in COPD. Subgroup analysis was performed to identify factors affecting FeNO responsiveness. Also, we investigated the association between FeNO reduction and improvements in lung function. RESULTS: A total of 6 clinical trials comprising 9 study arms and 258 patients were included in the analysis. The pooled estimates demonstrated a significant reduction in FeNO levels following ICS treatment (mean difference -6.30 parts per billion [ppb]; 95% confidence interval [CI], -10.46 to -2.14). This reduction was more enhanced in the high baseline FeNO group (≥25 ppb), with a mean difference of -14.59 ppb (95% CI, -20.38 to -8.80). Meta-regression analysis identified baseline FeNO level as the only significant moderator of treatment response. Furthermore, in the high baseline FeNO group, ICS therapy led to a significant improvement in trough forced expiratory volume in 1 second at 12 weeks (mean difference 0.13 L; 95% CI, 0.06-0.20). CONCLUSION: These findings suggest that ICS therapy significantly reduces FeNO levels in COPD patients. High baseline FeNO may serve as a useful predictor of treatment response, as ICS tended to improve forced expiratory volume in 1 second in this subgroup.