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Original article
Accuracy of FENO for diagnosing asthma: a systematic review
  1. Stefan Karrasch1,2,3,
  2. Klaus Linde1,
  3. Gerta Rücker4,5,
  4. Harriet Sommer4,5,
  5. Marlies Karsch-Völk1,
  6. Jos Kleijnen6,7,
  7. Rudolf A Jörres3,
  8. Antonius Schneider1
  1. 1Institute of General Practice, University Hospital Klinikum rechts der Isar, Technische Universität München, Munich, Germany
  2. 2Institute of Epidemiology I, Helmholtz Zentrum München—German Research Center for Environmental Health, Munich, Germany
  3. 3Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich, Germany
  4. 4Institute for Medical Biometry and Statistics, Medical Center—University of Freiburg, Freiburg, Germany
  5. 5Faculty of Medicine, University of Freiburg, Freiburg, Germany
  6. 6Kleijnen Systematic Reviews Ltd, Escrick, York, UK
  7. 7School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands
  1. Correspondence to Professor Antonius Schneider, Institute of General Practice, Klinikum rechts der Isar, Technische Universität München, Orleansstraße 47, München 81667, Germany; antonius.schneider{at}


Background Measurement of FENO might substitute bronchial provocation for diagnosing asthma. We aimed to investigate the diagnostic accuracy of FENO measurement compared with established reference standard.

Methods Systematic review and diagnostic meta-analysis. Data sources were Medline, Embase and Scopus up to 29 November 2015. Sensitivity and specificity were estimated using a bivariate model. Additionally, summary receiver-operating characteristic curves were estimated.

Results 26 studies with 4518 participants (median 113) were included. Risk of bias was considered low for six of seven items in five studies and for five items in seven studies. The overall sensitivity in the meta-analysis was 0.65 (95% CI 0.58 to 0.72), the overall specificity 0.82 (0.76 to 0.86), the diagnostic OR 9.23 (6.55 to 13.01) and the area under the curve 0.80 (0.77 to 0.85). In meta-regression analyses, higher cut-off values were associated with increasing specificity (OR 1.46 per 10 ppb increase in cut-off) while there was no association with sensitivity. Sensitivities varied significantly within the different FENO devices, but not specificities. Neither prevalence, age, use of bronchoprovocation in >90% of participants or as exclusive reference standard test, nor risk of bias were significantly associated with diagnostic accuracy.

Conclusions There appears to be a fair accuracy of FENO for making the diagnosis of asthma. The overall specificity was higher than sensitivity, which indicates a higher diagnostic potential for ruling in than for ruling out the diagnosis of asthma.

  • Asthma
  • Exhaled Airway Markers

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  • Contributors AS conceived the study and wrote the review protocol. GR, JK, RAJ, SK and KL contributed to the protocol development. SK, MK-V and KL performed the literature search, selection, data extraction quality assessment and data entry. HS and GR planned and performed statistical analyses. AS, KL and SK drafted the manuscript. All authors contributed to data interpretation and critical revision of the draft manuscript. AS is the guarantor.

  • Funding The project was supported by the German Federal Ministry of Education and Research (BMBF FKZ 01KG1211).

  • Competing interests SK declares that he uses a NIOX Vero testing device provided by Aerocrine without charge within a study outside the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The complete data set for the analyses performed is available as an MS Excel file in the online supplemental material.

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