The Diagnostic Accuracy of Fractional Exhaled Nitric Oxide Testing in Asthma: A Systematic Review and Meta-analyses

Zhen Wang, PhD

, 

Paolo T. Pianosi, MD

, 

Karina A. Keogh, MD

, 

Feras Zaiem, MD

, 

Mouaz Alsawas, MD, MSc

, 

Fares Alahdab, MD

, 

Jehad Almasri, MD

, 

Khaled Mohammed, MBBCh

, 

Laura Larrea-Mantilla, MD

, 

Wigdan Farah, MBBS

, 

Lubna Daraz, PhD

, 

Patricia Barrionuevo, MD

, 

Allison S. Morrow, BA

, 

Larry J. Prokop, MLS

, 

Mohammad Hassan Murad, MD, MPHCorrespondence information about the author MD, MPH Mohammad Hassan MuradEmail the author MD, MPH Mohammad Hassan Murad

DOI: http://dx.doi.org/10.1016/j.mayocp.2017.11.012

                                                         Article Info

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Article Outline

1. Methods
   1. Data Sources and Searches
   2. Study Selection
   3. Data Extraction and Quality Assessment
   4. Main Outcome Measures
   5. Data Synthesis and Analysis
   6. Grading the Quality of Evidence (ie, Certainty in Estimates)
2. Results
   1. Description of the Evidence
   2. Diagnostic Accuracy of FeNO Testing
   3. Subgroup and Sensitivity Analyses
3. Discussion
4. Conclusion
5. Acknowledgments
6. Supplemental Online Material
7. References

Jump to SectionMethods  Data Sources and Searches  Study Selection  Data Extraction and Quality Assessment  Main Outcome Measures  Data Synthesis and Analysis  Grading the Quality of Evidence (ie, Certainty in Estimates)Results  Description of the Evidence  Diagnostic Accuracy of FeNO Testing  Subgroup and Sensitivity AnalysesDiscussionConclusionAcknowledgmentsSupplemental Online MaterialReferences

Abstract

Objective

To evaluate the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) measurement in individuals with suspected asthma.

Methods

We searched MEDLINE, EMBASE, PsycINFO, Cochrane databases, and SciVerse Scopus from the databases' inception through April 4, 2017, for studies that enrolled patients aged 5 years and older with suspected asthma and evaluated FeNO diagnostic accuracy. Independent reviewers selected studies and extracted data. We used the symmetric hierarchical summary receiver operating characteristic models to estimate test performance.

Results

We included 43 studies with a total of 13,747 patients. In adults, using FeNO cutoffs of less than 20, 20 to 29, 30 to 39, and 40 or more parts per billion, FeNO testing had sensitivities of 0.80, 0.69, 0.53, and 0.41, respectively, and specificities of 0.64, 0.78, 0.85, and 0.93, respectively. In children, using FeNO cutoffs of less than 20 and 20 to 29 parts per billion, FeNO testing had sensitivities of 0.78 and 0.61, respectively, and specificities of 0.79 and 0.89, respectively. Depending on the FeNO cutoff, the posttest odds of having asthma with a positive FeNO test result increased by 2.80- to 7.00-fold. Diagnostic accuracy was modestly better in corticosteroid-naive asthmatics, children, and nonsmokers than in the overall population.

Conclusion

Fractional exhaled nitric oxide measurement has moderate accuracy to diagnose asthma in individuals aged 5 years and older. Test performance may be modestly better in corticosteroid-naive asthmatics, children, and nonsmokers than in the general population with suspected asthma.

Trial Registration

International Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42016047887

Abbreviations and Acronyms:

DOR (diagnostic odds ratio), FeNO (fractional exhaled nitric oxide), HSROC (hierarchical summary receiver operating characteristic), ICS (inhaled corticosteroids), ppb (parts per billion)