Measurement of Exhaled Nitric Oxide and Exhaled Breath Condensate in the Diagnosis and Management of Asthma and Other Respiratory Disorders
DESCRIPTION
Evaluation of exhaled nitric oxide and exhaled breath condensate are proposed as techniques to diagnose and monitor asthma and/or other respiratory conditions. Asthma is characterized by airway inflammation that leads to airway obstruction and hyperresponsiveness, which in turn lead to characteristic clinical symptoms including wheezing, shortness of breath, cough, and chest tightness.
Measurement of fractional exhaled nitric oxide (FeNO) (e.g., NIOX®, NIOX MINO®, NIOX VERO®, Fenom Pro™ Nitric Oxide Test, NObreath®) is being investigated as a noninvasive marker of airway inflammation. The individual inspires nitric oxide-free air via a mouthpiece until total lung capacity is achieved followed immediately by exhalation through the mouthpiece into the measuring device. Researchers have raised concerns regarding the lack of a standardized protocol for monitoring ENO, which creates difficulties for use of ENO levels for monitoring.
Measurement of exhaled breath condensate (EBC) is being investigated as a noninvasive method for studying the composition/inflammation of the fluid lining the airway. There are a variety of laboratory techniques (e.g., RTube™ Exhaled Breath Condensate collection system, ECoScreen™ EBC collection system) to measure EBC. These techniques include pH measurement, gas chromatography/mass spectrometry and high-performance liquid chromatography. It is not known if EBC pH measurements provide accurate estimates of airway pH. Researchers have raised concerns regarding the standardization of EBC collection and measurement methods.
POLICY
Measurement of exhaled nitric oxide for the diagnosis and management of respiratory disorders, including, but not limited to the following: asthma, chronic cough, cystic fibrosis, and primary ciliary dyskinesia is considered investigational.
Measurement of exhaled breath condensate for the diagnosis and management of respiratory disorders, including, but not limited to the following: asthma, chronic cough, cystic fibrosis, and primary ciliary dyskinesia is considered investigational.
IMPORTANT REMINDERS
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ADDITIONAL INFORMATION
There is a lack of well-designed, long-term studies in peer-reviewed journals that evaluate whether the addition of exhaled nitric oxide and/or exhaled breath condensate measurements to clinical and lung function assessment results in improved control of respiratory disorders or improved health outcomes.
SOURCES
Agency for Healthcare Research and Quality. (2017, December). Comparative effectiveness review number 197: The clinical utility of fractional exhaled nitric oxide (FeNO) in asthma management. Retrieved November 19, 2020 from PubMed database.
Aldakheel, F., Thomas, P., Bourke, J., Matheson, M., Dharmage, S., & Lowe, A. (2016). Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review. Allergy, 2016, DOI: 10.000/all.12865. (Level 1 evidence)
American Thoracic Society. (2021). Use of fractional exhaled nitric oxide to guide the treatment of asthma an official american thoracic society clinical practice guideline. Retrieved August 24, 2022 from https://www.atsjournals.org/.
BlueCross BlueShield Association. Evidence Positioning System. (7:2023). Measurement of exhaled nitric oxide and exhaled breath condensate in the diagnosis and management of respiratory disorders (2.01.61). Retrieved September 27, 2023 from https://www.evidencepositioningsystem.com/. (83 articles and/or guidelines reviewed)
Boer, S., Honkoop, P.J., Loijmans, R.J.B., Assendelft, W.J.J., Schermer, T.R.J., & Sont, J.K. (2020). Personalised exhaled nitric oxygen fraction (FENO)-driven asthma management in primary care: a FENO subgroup analysis of the ACCURATE trial. European Respiratory Journal Open Research, 6 (3), doi:10.1183/23120541.00351-2019. (Level 2 evidence)
Buhl, R., Korn, S., Menzies-Gow, A., Aubier, M., Chapman, K.R., Canonica, G.W., et al. (2020). Prospective, single-arm, longitudinal study of biomarkers in real-world patients with severe asthma. The Journal of Allergy and Clinical Immunology. In Practice, 8 (8), 2630-2639. (Level 3 evidence)
Dinakar, C. & Chipps, B. (2017). Clinical tools to assess asthma control in children. Pediatrics, 139 (1), e20163438. (Level 2 evidence)
Essat, M., Harnan, S., Gomersall, T., Tappenden, P., Wong, R., Pavord, I., et al. (2016). Fractional exhaled nitric oxide for the management of asthma in adults: a systematic review. European Respiratory Journal, 47 (3), 751-768. (Level 1 evidence)
European Respiratory Society (ERS). American Thoracic Society (ATS). (2020).Management of severe asthma: a european respiratory society/american thoracic society guideline. Retrieved August 24, 2022 from https://erj.ersjournals.com/content/erj/55/1/1900588.full.pdf.
Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier, M.M., Baptist, A.P., Blake, K.V., Brooks, E.G., Bryant-Stephens, T., DiMango,. E, et al. (2020). 2020 Focused updates to the asthma management guidelines. Retrieved June 10, 2021 from https://www.nhlbi.nih.gov/health-topics/asthma-for-health-professionals.
Global Initiative for Asthma. (2023). Global strategy for asthma management and prevention. Retrieved September 29, 2023 from https://ginasthma.org/wp-content/uploads/2023/07/GINA-2023-Full-report-23-07-06-WMS.pdf.
Gomersal, T., Harnan, S., Essat, M., Tappenden, P., Wong, R., Lawson, R., et al. (2016). A systematic review of fractional exhaled nitric oxide in the routine management of childhood asthma. Pediatric Pulmonology, 51 (3), 316-328. Abstract retrieved May 5, 2016 from PubMed database.
Guo, Z., Wang, Y., Xing, G., & Wang, X. (2016). Diagnostic accuracy of fractional exhaled nitric oxide in asthma: a systematic review and meta-analysis of prospective studies. The Journal of Asthma, 53 (4), 404-412. Abstract retrieved May 5, 2016 from PubMed database.
Lehtimäki, L., Csonka, P., Mäkinen, E., Isojärvi, J., Hovi, S., Ahovuo-Saloranta, A. (2016). Predictive value of exhaled nitric oxide in the management of asthma: a systematic review. European Respiratory Journal, 48 (3), 706-714. (Level 1 evidence)
National Institute for Health and Care Excellence. (2014, April; last update search May 2019). Measuring fractional exhaled nitric oxide concentration in asthma: NIOX MINO, NIOX VERO and NObreath. Retrieved August 24, 2022 from www.nice.org.uk.
National Institute for Health and Care Excellence. (2017, November; last updated search March 2021). Asthma: diagnosis, monitoring and chronic asthma management. Retrieved August 24, 2022 from www.nice.org.uk.
Song, W., Kim, H., Shim, J., Won, H., Kang, S., Sohn, K., et al. (2017). Diagnostic accuracy of fractional exhaled nitric oxide in predicting cough variant asthma and eosinophilic bronchitis in adult patients with chronic cough: a systematic review and meta-analysis. The Journal of Allergy and Clinical Immunology, 140 (3), 701 – 709. (Level 1 evidence)
Sutherland, L., Shaw, K., Parrish, C., Singleton, N., McKeever, T.M., et al. (2021). A low exhaled nitric oxide level excludes a short-term benefit from inhaled corticosteroids in suspected asthma: A randomized placebo-controlled trial. Respirology, 26 (7), 666 – 672. (Level 2 evidence)
Tang, S., Xie, Y., Yuan, C., Sun, X., & Cui, Y. (2016). Fractional exhaled nitric oxide for the diagnosis of childhood asthma: a systematic review and meta-analysis. Clinical Reviews in Allergy and Immunology, 2016 Jul 21 (Epub ahead of print). Abstract retrieved February 3, 2017 from PubMed database.
Turner, S., Cotton, S., Wood, J., Bell, V., Raja, E. A., Scott, N. W., et al. (2022). Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial. The Lancet. Respiratory Medicine, 10 (6), 584–592. Abstract retrieved September 29, 2023 from PubMed database.
Wang, K., Verbakel, J.Y., Oke, J., Fleming-Nouri, A., Brewin, J., Roberts, N., et al. (2020). Using fractional exhaled nitric oxide to guide step-down treatment decisions in patients with asthma: a systematic review and individual patient data meta-analysis. European Respiratory Journal, 55 (5), 1902150. (Level 1 evidence)
ORIGINAL EFFECTIVE DATE: 11/11/2006
MOST RECENT REVIEW DATE: 11/9/2023
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