An inflammatory marker in exhaled breath

NO and asthma

Nitric oxide (NO) is an important endogenous regulatory mediator produced by bronchial epithelial cells, among others. The endogenous NO is produced by the enzyme NO synthase (NOS) from L-arginine, which occurs in three isoforms. NO is a gaseous molecule contained in exhaled breath.1 Exhaled NO plays a crucial role in the pathophysiology of asthma. The NO released in the lower respiratory tract – measured as FeNO (fractional exhaled NO) – acts as a direct biomarker for airway inflammation and also reflects inflammatory activity.

Standardized measurement for determining bronchial NO

To obtain a sample of NO produced in the bronchial tubes, the exhaled breath has to be fractionated. The measurement of fractional exhaled NO (FeNO) has been standardized for clinical measurement.2,3 The NO fraction from the bronchoalveolar chamber is measured during slow, controlled exhalation through a mouthpiece. The soft palate (velum) must be closed to prevent contamination with NO from the upper respiratory tract. The closure of the velum is achieved by exhaling against a resistance of between 5 and 20 cm H₂O. A constant flow of 50 ml/s must also be maintained during breathing maneuvers.

FeNO measurement has become a recognized standard diagnostic procedure and is used daily in medical practices and clinics all over the world. It is quick and easy to perform and is non-invasive and stress-free for the patient.

Respiratory system

• Exhalation against resistance (velum closure between 5 and 20 cm H₂O)

• Slow, controlled, and constant rate of exhalation (50 ml/s)

• Measurement after bypassing the respiratory volume of the lower respiratory tract (fractionation)

Importance of FeNO measurement for diagnostics and therapy

  • Numerous studies verify the importance of FeNO measurement in delivering diagnosis confirmation and a prognosis of response to treatment with inhaled corticosteroids (ICS).4,5,6
  • Regular FeNO measurement simplifies the monitoring of airway inflammation and may provide information about patients’ adherence to ICS treatment.7
  • FeNO-based monitoring supports therapy management and can help to prevent exacerbation.8
  • Increased FeNO values indicate a worsening of the course of the disease even before a conspicuous pulmonary function test result and therefore allow early therapeutic countermeasures to be taken.9
FeNO interpretation table
Interpretation table according to recommendation of the American Thoracic Society (ATS)

Importance and use of FeNO testing

FeNO measurement (inflammometry) is usually used in primary diagnostics in addition to the pulmonary function test, and for follow-up monitoring of asthma. The diagnostic value of FeNO testing for asthma diagnosis is comparable to the bronchoprovocation, or bronchial challenge, test.12 According to the new NICE Guideline on Asthma Diagnosis and Monitoring (2017), a conclusive FeNO test and proven reversible bronchodilation can even eliminate the need for a bronchoprovocation test for asthma diagnosis.10

Vivatmo system
inspired by GINA cycle of asthma care

Current recommendations and guidelines

The guidelines of the American Thoracic Society (ATS) recommend FeNO measurement for diagnosis, therapy management, and monitoring of asthma patients.4

The NICE Clinical Guideline on Asthma recommends including FeNO measurement in the diagnosis algorithm in order to improve diagnostic quality, and considers the FeNO result to be an important parameter for long-term asthma management. FeNO measurement can also help to increase cost effectiveness.

Recommendation of the National Institute for Health and Care Excellence (NICE)

“Offer a FeNO test to adults and young people older than 16 if a diagnosis of asthma is being considered.”

“Consider FeNO measurement as an option to support asthma management in people who are symptomatic despite using inhaled corticosteroids.”10

The German Guidelines for Diagnosis and Treatment of Asthma Patients also recommend using the FeNO value as an additional marker for confirming the asthma diagnosis.11

1 Baur et al. Dt. Ärzteblatt, 2007

2 ATS/ERS Am J Respir Crit Care Med 2005;171:912-30

3 Horváth et al. Eur Respir J 2017;49:1600965

4 Dweik et al. Am J Respir Crit Care Med 2011;184:602-15

5 Karrasch et al. Thorax 2017;72:109-16

6 Taylor et al. Thorax 2006;61:817-27

7 Petsky et al. Cochrane Database of Systematic Reviews 2016;9: CD011440

8 Essat et al. Eur Respir J 2016;47:751-68

9 Bodini et al. Chest 2017;132:1520-25

10 NICE: Guideline Asthma - diagnosis and monitoring (November 2017, www.nice.org.uk)

11 NVL Asthma, 3. Auflage, Version 1 (September 2018, https://www.leitlinien.de/mdb/downloads/nvl/asthma/asthma-3aufl-vers1-lang.pdf)

12 Schneider et al. Respir Med. 2014; 108(1):34-40