Asthma and lower airway disease
Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis

https://doi.org/10.1016/j.jaci.2016.11.037Get rights and content

Background

Individual studies have suggested the utility of fractional exhaled nitric oxide (Feno) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients with chronic cough.

Objective

We sought to obtain summary estimates of diagnostic test accuracy of Feno measurement in predicting CVA, EB, or both in adults with chronic cough.

Methods

Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of Feno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of Feno measurement.

Results

A total of 15 studies involving 2187 adults with chronic cough were identified. Feno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 [95% CI, 0.81-0.88] and 0.72 [95% CI, 0.61-0.81], respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 [95% CI, 0.77-0.84]), and specificity was inconsistent.

Conclusions

The present meta-analyses indicated the diagnostic potential of Feno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, Feno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of Feno measurement in clinical practice of patients with chronic cough.

Section snippets

Search strategy

We conducted a systematic literature search to identify studies that had relevant information for the following 3 research questions (RQs):

“What is the diagnostic accuracy of Feno (index test) for CVA and/or EB (reference standard) in patients with chronic cough (target condition)?”

  • RQ1: Feno for CVA in patients with chronic cough;

  • RQ2: Feno measurement for either CVA or EB in patients with chronic cough; and

  • RQ3: Feno measurement for EB in nonasthmatic patients with chronic cough.

We searched the

Study characteristics and methodological quality

In total, 15 studies involving 2187 adult patients with chronic cough were identified to respond to one of the 3 RQs (Fig 1). Baseline characteristics of the 15 included studies are summarized in Table E1 and the Results section in this article's Online Repository at www.jacionline.org. Fourteen studies were published as full articles,14, 15, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 and 1 was a conference abstract.35 Most of the studies were conducted in Asia (10/15; 8 in China, 1 in

Discussion

Feno values can reflect TH2 airway inflammation, which might help define the TH2 endotype of chronic cough. Here we identified the diagnostic potential of Feno measurement in predicting 2 major TH2 inflammatory conditions underlying chronic cough: CVA and EB. We found that Feno measurements had moderate diagnostic accuracy in predicting CVA in adult patients with chronic cough. The estimated summary AUCs ranged from 0.81 to 0.89, according to the RQ, or in subgroup analyses. Sensitivities were

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    Supported by grant no. 23-2015-0200 from the SNUH Research Fund.

    Disclosure of potential conflict of interest: W.-J. Song receives grant support from Seoul National University Hospital. The rest of the authors declare that they have no relevant conflicts of interest.

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