Beyond blue inhaler: Doctor explains how FeNO testing could unlock biologic treatment for severe Asthma
New Delhi: For millions living with asthma, the familiar blue reliever inhaler can feel like a lifeline. But when breathlessness, wheezing and repeated asthma attacks continue despite intensive inhaled treatment, simply reaching for another inhaler may no longer be the answer. Talking to News9 Live, Dr Rajiv Kovil, Diabetes and Obesity Specialist at Zandra Healthcare, Mumbai, highlights the growing role of biomarker-driven care in identifying the biology behind difficult-to-control asthma. One of the tools increasingly used in this assessment is Fractional Exhaled Nitric Oxide, or FeNO, a quick, non-invasive breath test that can provide clues about Type 2 airway inflammation.
“The future of asthma care lies not merely in relieving symptoms but in understanding the biology behind them.” explains Dr Rajiv Kovil
The shift matters because asthma is not one uniform disease. Modern respiratory medicine increasingly recognises different inflammatory patterns, or phenotypes, that can sit behind apparently similar symptoms. In some patients, Type 2 inflammation – involving pathways associated with cytokines such as IL-4, IL-5 and IL-13 – plays a major role. These patients may be candidates for targeted biological therapies when asthma remains uncontrolled despite optimised standard treatment.
What exactly does a FeNO test measure
FeNO measures the concentration of nitric oxide in a person’s exhaled breath. Nitric oxide is produced in the airways, and elevated FeNO can be associated with Type 2 airway inflammation, particularly inflammation involving IL-13 signalling.
The test is remarkably straightforward: the patient breathes into a specialised analyser according to the device’s instructions, allowing the machine to measure exhaled nitric oxide, usually reported in parts per billion (ppb). Unlike spirometry, which primarily assesses airflow and lung function, FeNO provides information about an inflammatory component of airway disease.
That distinction can be clinically useful. A patient can have relatively preserved lung function at the time of testing and still have evidence of airway inflammation. Conversely, a low FeNO does not rule out asthma.
When is a FeNO reading considered high
The American Thoracic Society’s clinical guidance provides useful reference points for interpreting FeNO in adults.
A FeNO level below 25 ppb generally makes eosinophilic airway inflammation and corticosteroid responsiveness less likely, while a level above 50 ppb makes eosinophilic inflammation and likely corticosteroid responsiveness more probable in a symptomatic patient. Results between 25 and 50 ppb require greater clinical context.
But the number should never be interpreted in isolation.
Smoking, allergen exposure, age, treatment with corticosteroids and other factors can affect FeNO. An elevated result can also occur in some patients who do not have asthma. This is why physicians consider the FeNO result alongside symptoms, lung-function testing, blood eosinophils, allergy history, exacerbation history, medication adherence and inhaler technique.
Severe asthma is not simply “bad asthma”
The distinction between difficult-to-treat and severe asthma is important.
According to the latest GINA guidance, severe asthma is asthma that remains uncontrolled despite optimised treatment with high-dose inhaled corticosteroid plus a long-acting bronchodilator, or that requires such intensive treatment — including biologic therapy — to prevent the disease from becoming uncontrolled. Before labelling asthma as severe, doctors need to check the diagnosis, inhaler technique, adherence, environmental exposures and other conditions that can mimic or worsen asthma.
This matters because repeatedly escalating medication without identifying why asthma remains uncontrolled can miss potentially correctable problems.
Where do biologics fit in
Biologics are not simply “stronger inhalers”. They are targeted medicines designed to interfere with specific immune pathways involved in asthma inflammation.
Current biologic options for severe asthma include therapies directed against:
- IgE, such as omalizumab
- IL-5 or the IL-5 receptor, including mepolizumab, reslizumab and benralizumab, with newer agents expanding this class
- IL-4 receptor alpha, such as dupilumab, which affects IL-4 and IL-13 signalling
- TSLP, an epithelial-derived inflammatory signal targeted by tezepelumab
So, can FeNO actually “unlock” a biologic
It can help — but the picture is more nuanced than that.
Higher FeNO can identify patients with Type 2 inflammation and is associated with an increased likelihood of response to some biologic therapies, particularly those targeting IL-4/IL-13 signalling and, in certain populations, TSLP. Recent evidence also suggests that FeNO above about 40 ppb, particularly when combined with elevated blood eosinophils, can help predict response to several biologic classes.
But FeNO is not a universal eligibility test.
For example, blood eosinophil levels are particularly important when considering anti-IL-5 or anti-IL-5 receptor therapies, while allergic sensitisation and total IgE are central to assessing eligibility for omalizumab. Tezepelumab has demonstrated benefit across a broader range of severe asthma phenotypes, including patients without elevated Type 2 biomarkers, although responses may be greater in some biomarker-high groups.
FeNO can also help beyond severe asthma
The potential usefulness of FeNO extends beyond deciding whether a patient might be considered for biologic treatment.
It can support assessment of Type 2 airway inflammation, help evaluate the likelihood of corticosteroid responsiveness and can be used in monitoring airway inflammation in people with established asthma. Changes over time can sometimes provide additional information about treatment response or adherence.
FeNO may also have a role in patients presenting with chronic cough, particularly where asthma or eosinophilic airway inflammation is suspected. But here too, the evidence is more limited: European Respiratory Society guidance notes that there is currently insufficient high-quality evidence to establish FeNO as a definitive treatment-response predictor in chronic cough, and optimal cut-offs have not been established for this population.
Asthma remains a major global health problem. The World Health Organization estimates that 363 million people were living with asthma in 2023 and that asthma caused about 442,000 deaths that year. Most asthma-related deaths occur in low- and lower-middle-income countries, where under-diagnosis and under-treatment remain significant challenges.
Against that backdrop, the significance of FeNO is not that it can diagnose every case of asthma or determine every patient’s treatment. Its value lies in adding another layer of biological information to a disease that has historically been managed largely through symptoms and lung function.