BlueCross BlueShield of Tennessee Medical Policy Manual

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 exhaled nitric oxide (ENO) (e.g., NIOX®, NIOX MINO®, NIOX VERO®) is being investigated as a noninvasive marker of airway inflammation. Exhaled nitric oxide is typically measured during single breath exhalations. First, the individual inspires nitric oxide-free air via a mouthpiece until total lung capacity is achieved. This is 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

IMPORTANT REMINDERS

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

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 Academy of Allergy Asthma & Immunology/American Academy of Allergy, Asthma and Immunology. (2012). AAAAI/ACAAI joint statement of support of the ATS clinical practice guideline: interpretation of exhaled nitric oxide for clinical applications. Retrieved May 6, 2016 from http://www.aaaai.org/my-membership/constituency-groups/joint-efforts-of-the-AAAAI-ACAAI.

American Thoracic Society. (2014, February). International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.  Retrieved January 11, 2018 from National Guideline Clearinghouse (#010509).

BlueCross BlueShield Association. Medical Policy Reference Manual. (9:2017). Measurement of exhaled nitric oxide and exhaled breath condensate in the diagnosis and management of respiratory disorders (2.01.61). Retrieved January 11, 2018 from BlueWeb. (60 articles and/or guidelines reviewed)

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)

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.

Kozij, N., Granton, J., Silkoff, P., Thenganatt, J., Chakravorty, S., and Johnson, S. (2017, February) Exhaled nitric oxide in systemic sclerosis lung disease. Canadian Respiratory Journal, article ID 6736239. (Level 2 evidence)

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. Abstract retrieved February 3, 2017 from PubMed database.

National Institute for Health and Care Excellence. (2017, November). NICE guideline: Asthma: diagnosis, monitoring and chronic asthma management Retrieved January 11, 2018 from www.nice.org.uk.

Petsky, H., Kew, K., & Chang, A. (2016). Exhaled nitric oxide levels to guide treatment for children with asthma (review). Cochrane Library, 2016, 11 (CD011439). (Level 2 evidence)

Petsky, H., Kew, K., Turner, C., & Chang, A. (2016). Exhaled nitric oxide levels to guide treatment for adults with asthma (review). Cochrane Library, 2016, 9 (CD011440). (Level 2 evidence)

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, 2017 Jan 11. (Epub ahead of print). Abstract retrieved February 3, 2017 from PubMed database.

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.

U. S. Food and Drug Administration. (2009, January). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K083617. Retrieved September 27, 2013 from http://www.accessdata.fda.gov.

U. S. Food and Drug Administration. (2012, December). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K123683. Retrieved September 27, 2013 from http://www.accessdata.fda.gov.

U. S. Food and Drug Administration. (2014, December). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K133898. Retrieved May 4, 2016 from http://www.accessdata.fda.gov.

Van Horck, M., Alonso, A., Wesseling, G., de Winter-de Groot, K., van Aalderen, W., Hendricks, H., et al. (2016). Biomarkers in exhaled breath condensate are not predictive for pulmonary exacerbations in children with cystic fibrosis: results of a one-year observational study. PLoS One, 11 (4), e0152156. (Level 2 evidence)

Winifred S. Hayes, Inc., Medical Technology Directory. (2016, October; last update search September 2017). Nitric oxide breath analysis for the diagnosis of asthma. Retrieved January 11, 2018 from https://www.hayesinc.com . (56 articles and/or guidelines reviewed)

Winifred S. Hayes, Inc., Medical Technology Directory. (2016,September; last update search September 2017). Nitric oxide breath analysis for the management of asthma. Retrieved February 3, 2017 from https://www.hayesinc.com . (67 articles and/or guidelines reviewed)

Zhang, D.,  Luo, J., Qiao, Y., Xiao, Y., Huang, R., and Zhong, X. (2017, February) Measurement of exhaled nitric oxide concentration in patients with obstructive sleep apnea. Medicine (2017), 96(12), e-published. (Level 1 evidence)

ORIGINAL EFFECTIVE DATE:  11/11/2006

MOST RECENT REVIEW DATE:  2/8/2018

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