FeNO Measurement

FeNO measurement (FeNO or FENO is the abbreviation for “fractional exhaled nitric oxide (NO)”; synonyms: Determination of Nitric Oxide Concentration (FENO) in Exhaled Air; Multiple Breath Draw Method, FENO Test) is a diagnostic procedure to determine the level of FeNO (nitric oxide) in exhaled air for the detection of existing inflammatory processes and chronic pulmonary diseases. The determination of this marker for the detection of bronchial inflammation (eosinophilic inflammation) represents a noninvasive procedure that can be used in patients of all ages.

Indications (areas of application)

  • Bronchial asthma – the indications for performing FeNO measurement in bronchial asthma represent the prediction of exacerbations (worsening) and, further, the monitoring of the effect of therapy. From this, it can be concluded to what extent additional drug administration of steroids (anti-inflammatory drugs) is necessary to combat the inflammatory process. An assessment of patient compliance (adherence to therapy measures) in difficult-to-treat asthma is facilitated with the help of FeNO measurement. The use of FeNO measurement in bronchial asthma is also known as inflammometry.
  • Chronic obstructive pulmonary disease (COPD) – as in bronchial asthma, chronic inflammatory response is an important basis of the pathological process in COPD. With the help of FeNO measurement, exacerbations (worsening episodes) can be detected at an early stage, so that the administration of corticosteroids (in this case: glucocorticoids: main representative cortisol) can be carried out in time to optimize the therapeutic measure. The correlation of the eosinophilic inflammatory reaction with the concentration of exhaled nitric oxide is of decisive importance for the significance of the method. The eosinophilic inflammatory reaction describes an inflammatory process in which eosinophilic granulocytes (phagocytes) are the predominant cell type. However, it is problematic that smokers achieve lower levels of NO when measured than nonsmokers, although smoking is considered a crucial trigger for the development of COPD.
  • Chronic bronchitis – since chronic bronchitis can progress to COPD, it is indicated to evaluate the inflammatory processes in chronic bronchitis using FeNO measurement.
  • Bacterial infections of the paranasal sinuses ((lat. Sinus paranasales) – in the paranasal sinuses, the concentration of nitric oxide is physiologically much higher than in the bronchial system. The synthesis (production) of nitric oxide seems to play a role in the defense against infections. Thus, conclusions can be made about chronic inflammation of this section of the upper respiratory tract.

Contraindications

  • There are no known contraindications.

Before the examination

  • FeNO measurement is performed with modern medical devices that do not require any preparation. However, nicotine consumption should be avoided on the day of measurement to prevent altered readings. Likewise, the patient should not eat or drink anything about 1 hour before the measurement, as this may possibly lead to a change in the NO concentration.

The procedures

The basic principle of FeNO measurement is based on the exhalation of nitric oxide. Nitric oxide is produced by nitric oxide synthases (enzyme) found on epithelial cells in the respiratory tract. In bronchial asthma and COPD, the activity of this enzyme is increased, so more nitric oxide is released through the air we breathe. For FeNO readings to be comparable and meaningful, conditions must be very similar for each measurement. Of critical importance is the flow dependence of the FeNO measurement, as NO concentration is directly dependent on exhalation rate. During fast breathing, the NO concentration is significantly lower than during slow breathing. Nevertheless, it should be kept in mind that the measurement can be relatively influenced by food intake. Furthermore, it was found that in some patients with significant nocturnal asthma symptoms, NO levels were reduced at night. Despite these problems, clinical studies have shown that use of FeNO measurement has positive effects on therapeutic measures. Conventional FeNO measurement

  • This procedure describes the method in which directly in the exhaled air the nitric oxide content can be determined using the NO analyzer. After exhalation, the NO concentration is displayed after a few seconds.

External FeNO measurement

  • In infants and young children, conventional FeNO measurement cannot be implemented because a constant flow rate cannot be achieved. By using external FeNO measurement, it is possible to analyze any sample gas. To do this, the infant or child must exhale into a collection bag.

Interpretation

FeNO reading Interpretation
<25 ppb (children: <20 ppb), Initial diagnosis/eosinophilic inflammation is not confirmed (→ seek alternative diagnosis).
25-50 ppb (children: 20-35 ppb) Values must be interpreted individually or in knowledge of previous findings
> 50 ppb (children: > 35 ppb) Suspected diagnosis/eosinophilic inflammation is supported.

After the examination

  • After the determination of the FeNO value, the patient’s therapy must be evaluated (analyzed and assessed) by the treating physician.

Possible complications

  • Since this is a non-invasive measurement method, no complications are expected. Only allergic reactions to the material of the measuring unit may occur.

Further notes

  • A meta-analysis showed that FeNO measurement is probably not an appropriate method to detect severe exacerbations early. The measurement data are also unlikely to guide decisions to intensify or de-escalate therapy.
  • A meta-analysis of the diagnostic accuracy of FENO in breath-derived air in suspected asthma and unclear spiroergometry (a method in which statements about cardiac and pulmonary performance can be made by measuring respiratory gases, at rest and on exertion) showed an intermediate sensitivity (percentage of diseased patients in whom the disease is detected by use of the procedure, ie. FENO had a mean sensitivity (percentage of patients with the disease detected by the test, i.e., a positive result) of 65% and a specificity (probability that healthy individuals who do not have the disease in question are detected as healthy by the test) of 82%. The diagnostic odds ratio was 9.23, meaning that patients with an elevated FENO have about 9 times the risk of having asthma as patients with unremarkable values.

FENO measurements in asthma: thresholds and possible indications.

Reason for FENO measurement FENO < 25 ppb(for children FENO < 20 ppb). FENO > 50 ppb(in children FENO > 35 ppb).
Diagnosis of asthma
  • Check alternative diagnoses
  • Steroid sensitivity less likely
  • Supports the suspected diagnosis
  • Steroid sensitivity/type II inflammation likely.
Symptoms and therapy
  • Consider alternative diagnoses
  • Steroid dose increase less useful
  • Check therapy adherence/allergen exposure.
  • In case of adherence: steroid dose increase useful
Symptom freedom and therapy
  • Consider reduction of steroid dose
  • Avoid reduction of steroid dose