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Can FeNO testing replace induced sputum and blood eosinophils to support asthma diagnosis?

To date, there is no single test available to diagnose asthma. Alongside traditional methods, such as spirometry and peak expiratory flow rate (PEFR), clinicians can directly check airway inflammation by measuring induced sputum, blood eosinophils, and FeNO (fractional exhaled nitric oxide). In this article, we look into whether FeNO testing can be used as an alternative to sputum and blood eosinophils to support a diagnosis.

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How is asthma diagnosed?

Asthma is a complex condition with several subtypes. Symptoms often overlap with other conditions such as COPD, and studies have shown that asthma diagnosis may be incorrect in a third of adults and half of children.1,2 Along with clinical history, several methods are used to arrive at a diagnosis. Some of the most common techniques are discussed below.

Traditional asthma tests: spirometry and peak expiratory flow rate

Two common methods used to diagnose asthma are spirometry and peak expiratory flow rate (PEFR). These tests involve strongly blowing into a hand-held device to measure airway obstruction and lung capacity. They are easy to carry out and readily available in most places.

However, neither of these tests directly indicates the level of airway inflammation, which is one of the characteristics of asthma. There are also cases of mild asthma where the airways are not always obstructed.4

Newer methods: induced sputum, blood eosinophils, and FeNO

Airway inflammation can be measured with several methods. Bronchial biopsy and bronchoalveolar lavage are quite invasive procedures. Less invasive techniques can be employed to measure inflammation, such as induced sputum eosinophils, blood eosinophils and FeNO testing. Those are inflammatory biomarkers that can be used alongside traditional methods.

Nurse FeNO testing female patient with NIOX VERO

A patient performing a FeNO test with NIOX VERO®

Induced sputum and blood eosinophils both measure the presence of eosinophils, a type of white blood cell. A normal level of eosinophils helps to fight infection, but high numbers are associated with inflammation and asthma symptoms.4

According to several studies, induced sputum eosinophils is the most accurate of the less invasive methods for detecting Type 2 inflammation. However, sputum analysis is not widely available as it requires lab facilities and specialist knowledge. Some patients also experience discomfort during the test and are unable to produce an adequate sample.4

A blood eosinophil count is considerably easier to carry out as it only requires a blood test. However, the easiest and least invasive technique is FeNO testing, which is done by breathing steadily into a hand-held device.

How reliable is a FeNO test?

Studies have shown that FeNO correlates well with induced sputum and blood eosinophilia.4

A study in 2004 found that FeNO was the most effective indicator to support a diagnosis of asthma, compared to conventional tests such as spirometry and peak flow. FeNO was shown to have high sensitivity (88%) and specificity (79%) and to correlate well with sputum eosinophils (p<0.001).3 In a 2017 study, the authors concluded that FeNO had the potential of making bronchial challenge tests superfluous.5 Bronchial challenge tests measure how a patient's airways respond to common asthma triggers. It is important to be aware that many factors may affect a patient’s FeNO levels, including age, gender, smoking habits, and food. These factors must be taken into account when interpreting the test results.

Eosinophilic asthma and the use of biologics

Not all types of asthma are associated with Type 2 airway inflammation. Therefore, it is generally considered that induced sputum, blood eosinophils and FeNO are especially useful to manage Type 2 or eosinophilic asthma.

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Some patients are unable to control their asthma despite high doses of corticosteroids, which make them more susceptible to asthma exacerbations. They may, however, respond well to a new type of treatment called biologics, also known as monoclonal antibodies.6 Blood eosinophils and FeNO testing can be used to monitor the patient's response to those biologics.6,7

Conclusion: FeNO is useful to detect airway inflammation, especially in eosinophilic asthma

While induced sputum is considered the most accurate way to measure airway inflammation, several studies have shown that FeNO and blood eosinophils can be used as valid alternatives. These three methods are especially useful to support a diagnosis of asthma associated with Type 2 inflammation.

As a low effort procedure, FeNO testing is the easiest and least invasive technique for measuring airway inflammation.

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1.Looijmang-van den Akker I et al. Overdiagnosis of asthma in children in primary care: a retrospective analysis. Br J Gen Pract. 2016 66 (644): e152-e157
2.Aaron SD et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017 317(3): 269-279
3.Smith AD et al. Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Respir Crit Care Med. 2004 169: 473-478.
4.Wagener AH et al. External validation of blood eosinophils, FeNO and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015 70: 115-120.
5.Karrasch S et al. Accuracy of FeNO for diagnosing asthma: a systematic review. Thorax. 2017 72: 109-116
6.GINA. Diagnosis and Management of Difficult-to-treat and Severe Asthma in adolescent and adult patients, a pocket guide. 2020.
7. Corren J et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma. J Allergy Clin Immunol Pract. 2020 8(2): 516-526.