Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Zhiyu Lu, Weina Huang, Linfeng Wang, Ning Xu, Qunli Ding, Chao Cao, Zhiyu Lu, Weina Huang, Linfeng Wang, Ning Xu, Qunli Ding, Chao Cao

Abstract

Background: Fractional exhaled nitric oxide (FENO) is a useful and noninvasive biomarker for eosinophilic airway inflammation, particularly in asthma. However, its utility in chronic obstructive pulmonary disease (COPD) remains controversial. In this study, we performed a systematic review and meta-analysis to evaluate FENO levels in COPD.

Methods: A search of PubMed, Embase, Cochrane Library, and clinical trial registry was conducted from inception to January 2018. Studies were included if they reported FENO levels in patients with COPD and healthy controls. We then extracted relevant information and analyzed data. Standard mean difference (SMD) with 95% confidence interval (CI) was applied in this meta-analysis.

Results: A total of 2,073 studies were reviewed for eligibility, with 24 studies pooled for analysis. The FENO levels in patients with COPD were elevated mildly compared with healthy controls (SMD 1.28, 95% CI 0.60-1.96). A similar result was also observed in stable COPD, with an SMD of 1.21 (95% CI 0.47-1.96). On the other hand, we found no association between FENO levels and exacerbated COPD. Additionally, for patients with COPD, ex-smokers had higher levels of FENO than current smokers (SMD 2.05, 95% CI 1.13-2.97).

Conclusion: Our studies demonstrated a mild elevation of FENO in COPD, and the association between exacerbated COPD and FENO levels needs to be further explored. The potential mechanism is still unknown and conflicting.

Keywords: biomarker; chronic obstructive pulmonary disease; fractional exhaled nitric oxide; meta-analysis.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flow diagram of literature search and study selection. Abbreviation: COPD, chronic obstructive pulmonary disease.
Figure 2
Figure 2
Comparison of FENO levels between COPD patients and controls in the included studies. Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FENO, fractional exhaled nitric oxide; IV, inverse variance; SMD, standard mean deviation; SD, standard deviation.
Figure 3
Figure 3
Comparison of fractional exhaled nitric oxide levels between stable/exacerbated COPD patients and controls. Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FENO, fractional exhaled nitric oxide; IV, inverse variance; SMD, standard mean deviation; SD, standard deviation.
Figure 4
Figure 4
Comparison of FENO levels between ex-smokers and current smokers. Abbreviations: CI, confidence interval; FENO, fractional exhaled nitric oxide; IV, inverse variance; SMD, standard mean deviation; SD, standard deviation.

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