Exhaled nitric oxide, usually abbreviated FeNO, is a gas your lungs produce naturally that has become one of the most useful breath-based biomarkers in respiratory medicine. Measured in parts per billion, it reflects the level of a specific type of inflammation in your airways and is most commonly used to help diagnose and manage asthma. But the story of this simple breath test reaches well beyond asthma, touching on everything from how smoking changes your lungs to what happens after you drink beetroot juice.
Where the Gas Comes From
Nitric oxide is a signaling molecule your body uses in dozens of ways, from dilating blood vessels to fighting infections. In the lungs, the cells lining your airways continuously produce it using an enzyme called inducible nitric oxide synthase, or iNOS. What makes this interesting is that iNOS was originally thought to switch on only in response to infection or injury. In airway lining cells, though, it runs all the time. Early molecular work showed that iNOS is abundantly expressed across all airway epithelial cell types but is not detected in other lung cell types, making the airway lining the dominant source of the nitric oxide you breathe out.1PubMed. Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo
When those airway cells become inflamed, particularly through a pathway driven by certain immune cells and signaling proteins associated with allergies, iNOS ramps up dramatically, and nitric oxide production soars. That is why FeNO has become a practical window into what is happening inside the airways: the more this type of inflammation is present, the more nitric oxide you exhale.2PubMed Central. Understanding the Cellular Sources of the Fractional Exhaled Nitric Oxide (FeNO) and Its Role as a Biomarker of Type 2 Inflammation in Asthma
What FeNO Tells Doctors About Asthma
Asthma is not one disease. Some people’s asthma is driven by eosinophils, a type of white blood cell that congregates in the airways and triggers the inflammation pattern known as type 2 (or “T2”) inflammation. Others have asthma driven primarily by neutrophils, or by structural changes in the airways that have little to do with eosinophils at all. The distinction matters because the most common asthma treatments, inhaled corticosteroids, work best against T2 inflammation and may do very little for other forms.
FeNO has become a key way to tell these patterns apart. It is considered an indicator of T2 inflammation and, by extension, a useful predictor of whether someone will respond to inhaled steroids.3PubMed Central. What is the added value of FeNO as T2 biomarker? A normal FeNO value in a healthy adult is typically below about 25 parts per billion (ppb). Levels above that threshold suggest T2 airway inflammation is present. But the number itself is a spectrum, not a simple pass/fail, and higher values generally signal more inflammation.
Predicting Who Will Benefit From Steroids
Before FeNO testing became available, doctors who suspected a patient might benefit from inhaled steroids often had to run a “trial of steroid,” prescribing the medication for weeks and watching to see if symptoms improved. That approach is slow, and if the patient’s symptoms have nothing to do with eosinophilic inflammation, it wastes time and medication.
A study of patients presenting with persistent respiratory symptoms found that those in the highest FeNO group, above 47 ppb, had a significantly greater response to steroid treatment than those with lower levels. That relationship held regardless of the specific diagnosis. FeNO outperformed almost all other baseline predictors of steroid response, with an optimum cutoff around 47 ppb.4PubMed. Exhaled nitric oxide: a predictor of steroid response In practice, this means a single breath test can help doctors skip the trial-and-error stage and move toward the right treatment faster.
Higher FeNO levels have also been linked to worse lung function and a greater risk of future asthma flare-ups. The predictive value gets stronger when FeNO is combined with other standard asthma assessments rather than used alone.5PubMed Central. Update on the Role of FeNO in Asthma Management
What FeNO Cannot Do
For all its usefulness, FeNO has real blind spots. It is essentially a T2 inflammation detector. If someone’s asthma is driven by neutrophilic inflammation rather than eosinophilic, their FeNO may be perfectly normal even while their disease is active and uncontrolled. Research comparing FeNO levels against sputum samples from patients with uncontrolled asthma found that while sputum neutrophil counts showed some correlation with FeNO, the test was not useful for distinguishing neutrophilic patterns.6PubMed Central. Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma A low or normal FeNO, in other words, does not rule out asthma. It rules out one particular type of airway inflammation.
FeNO is also not reliable as a standalone measure of medication adherence. Doctors sometimes hope that a rising FeNO in a patient on inhaled steroids might flag that the patient has stopped taking their medicine. But research in children managed in primary care found that a single high FeNO value did not reliably predict whether a patient was actually taking their inhaled corticosteroids.7npj Primary Care Respiratory Medicine. Asthma medication adherence and exacerbations and lung function in children managed in Leicester primary care The relationship between FeNO and adherence is real over time and across populations, but a single snapshot is not enough to catch someone skipping doses.
Things That Change Your FeNO Besides Disease
One of the most important things to understand about FeNO is that plenty of factors besides airway disease move the number around. If you are not aware of these, a test result can be genuinely misleading.
Smoking is the most dramatic confounder. Smokers have significantly lower exhaled nitric oxide than nonsmokers. One early study measured peak exhaled NO concentrations of roughly 42 ppb in smokers compared with about 88 ppb in nonsmokers, with a strong relationship between the number of cigarettes smoked and the degree of suppression.8PubMed. Acute and chronic effects of cigarette smoking on exhaled nitric oxide Even a single cigarette temporarily drops the reading. The mechanism appears to involve cigarette smoke interfering with the nitric oxide synthase enzyme itself.9PubMed. Effect of cigarette smoke extract on nitric oxide synthase in pulmonary artery endothelial cells This matters clinically because a smoker with T2 inflammation might show a deceptively low FeNO.
E-cigarettes have a similar though smaller acute effect. A study comparing exhaled NO after smoking conventional cigarettes, vaping with nicotine, and vaping without nicotine found that all three produced a significant short-term drop in exhaled NO compared to a control session with no smoking or vaping at all.10PubMed. Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide
Diet can push FeNO in the opposite direction. Foods rich in nitrate, particularly leafy greens and beetroot, can raise exhaled nitric oxide markedly within an hour or two. In healthy volunteers, drinking beetroot juice increased FeNO by about 21% within 45 minutes, an effect that persisted at the 90-minute mark.11PLoS ONE. Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals In COPD patients given dietary nitrate supplements, exhaled nitric oxide levels rose by more than 200%.12PubMed. Influence of dietary nitrate supplementation on lung function and exercise gas exchange in COPD patients Most clinical guidelines recommend avoiding nitrate-rich meals for several hours before a FeNO test, but not every patient hears that instruction, and the resulting spike can easily be misread as worsening inflammation.
Air pollution is another factor. A systematic review of personal exposure studies found that nine out of twelve studies reported significant FeNO increases with higher exposure to fine particulate matter (PM2.5). Increases of up to about 11.5% per interquartile-range rise in exposure were also reported for gaseous pollutants like ozone and nitrogen dioxide.13PubMed Central. The Association Between Personal Air Pollution Exposures and Fractional Exhaled Nitric Oxide (FeNO): A Systematic Review The effect was stronger in people who already had respiratory disease or allergies. Studies in children with asthma similarly linked short-term personal exposure to PM2.5, soot, and nitrogen dioxide with higher FeNO readings over the following one to two days.14PubMed Central. Personal and ambient air pollution is associated with increased exhaled nitric oxide in children with asthma This is worth knowing because a child tested on a smoggy day might look like their asthma is flaring when the real trigger is the air outside the clinic.
FeNO Beyond Asthma
While asthma is where FeNO testing found its clinical home, the biomarker has increasingly been studied in other respiratory conditions.
In COPD, the picture is more complicated. Most COPD is driven by neutrophilic inflammation, so FeNO is often low or normal. But a subset of COPD patients have eosinophilic inflammation and elevated FeNO, and this group may behave more like asthma patients in their response to steroids. A study of former smokers with eosinophilic COPD found that elevated FeNO, defined as 25 ppb or above, was linked to greater odds of having been diagnosed with asthma in the past and to a recent severe COPD exacerbation, though the confidence intervals were wide.15PubMed Central. Fractional Exhaled Nitric Oxide in Eosinophilic COPD FeNO may help identify which COPD patients could benefit from inhaled corticosteroids, a group sometimes described as having asthma-COPD overlap.16Breathe. Clinical utility of exhaled nitric oxide fraction in the management of asthma and COPD
Nasal nitric oxide (not the same as standard exhaled FeNO, which comes from the lower airways) has a distinct clinical role in diagnosing primary ciliary dyskinesia (PCD), a genetic condition in which the tiny hair-like structures lining the airways do not beat properly, leading to chronic infections and bronchiectasis. In PCD, nasal nitric oxide concentrations are extremely low, and measuring nasal NO is recommended as a diagnostic test in cooperative patients aged five and older.17PubMed Central. Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia The European Respiratory Society has endorsed nasal NO measurement as part of the diagnostic workup for PCD in children.18PubMed. Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia This is a case where abnormally low nitric oxide, rather than high, is the clinically important signal.
Nasal nitric oxide also tends to be low in people with chronic rhinosinusitis with nasal polyps. One study found nasal NO levels in this group were roughly a third of those in healthy controls, though levels were somewhat higher when patients also had allergic rhinitis.19PubMed. Nasal and exhaled nitric oxide in chronic rhinosinusitis with polyps
FeNO in Children
Diagnosing asthma in young children is notoriously difficult because they often cannot perform the standard breathing maneuvers used in lung-function testing. FeNO offers a simpler alternative: exhale slowly and steadily into a device for a few seconds. Even children as young as five or six can manage this with coaching.
Establishing what counts as “normal” in children has required dedicated research. An early reference study of healthy children aged 6 to 15 found a mean exhaled NO of about 9 ppb, with no meaningful differences between boys and girls and no significant correlation with age, height, or lung-function measurements.20PubMed. Reference values of exhaled nitric oxide for healthy children 6-15 years old A much larger recent study of nearly 6,000 Chinese children and adolescents aged 6 to 18 found a somewhat higher mean FeNO of about 14 ppb and identified some correlations between FeNO, age, height, and sex that differed between younger and older age groups.21PubMed Central. Reference values for exhaled nitric oxide in healthy children aged 6-18 years in China The difference between these studies hints at an important caveat: normal FeNO ranges vary across populations, and using a one-size-fits-all cutoff risks misclassifying children who are perfectly healthy.
When researchers tested age- and sex-specific cutoffs (the 90th percentile for each child’s demographic group) in symptomatic children who had not yet been treated, a FeNO reading above that personalized threshold gave 96% specificity and a positive predictive value of 97% for an eventual asthma diagnosis. That approach correctly identified about 59% of the children who were later confirmed to have asthma after extensive testing.22ERJ Open Research. Defining the normal range of fractional exhaled nitric oxide in children: one size does not fit all In plain terms, when the test flagged a child, it was almost always right, but it missed a substantial number of children who did have asthma. It is a high-confidence positive test rather than a sensitive screen.
How the Test Works in Practice
The gold-standard technology for measuring FeNO is a bench-top chemiluminescence analyzer, which detects nitric oxide by its chemical reaction with ozone. These machines are accurate but expensive, bulky, and mostly found in specialist clinics and research labs. Over the past two decades, portable handheld devices using electrochemical sensors have made FeNO testing accessible in general practice offices and even at home.
A comparison of multiple handheld analyzers against a chemiluminescence reference device found good clinical agreement across the board, with mean differences between the portable devices and the reference ranging from less than 1 ppb to about 7.5 ppb.23PubMed Central. Comparison of usability and user-friendliness of three FeNO analyzers in a general population cohort of the LEAD study The portable devices were considered clinically equivalent for practical purposes, though the agreement got somewhat looser at higher FeNO values. For a patient with a FeNO of 15 ppb, a couple of ppb of device-related variation does not change the clinical interpretation. For someone with a FeNO of 90 ppb, a wider spread matters less because the clinical message (“elevated T2 inflammation”) is clear either way.
The test itself takes about 10 to 15 seconds of steady exhalation. Standard protocols ask for a flow rate of 50 milliliters per second, because the concentration of nitric oxide in your breath changes depending on how fast you breathe out. Blowing too fast dilutes the signal; blowing too slowly concentrates it. Most modern devices provide real-time coaching on a screen, often a visual cue like an animated balloon or a bar graph, to help you hold a steady flow.
Research into flow-rate design has shown that low flow rates are better for estimating nitric oxide production in the airways themselves, while high flow rates give more information about what is happening deeper in the alveoli.24PubMed Central. Optimal flow rate sampling designs for studies with extended exhaled nitric oxide analysis The standard clinical test uses a single moderate flow rate and focuses on the airway signal, which is the one most relevant to asthma. Extended protocols that use multiple flow rates can estimate alveolar nitric oxide as well, which is of interest in research settings and in diseases that affect the deep lung.
The Cost Question
Adding a test to clinical practice always raises the question of whether the added information justifies the expense. For FeNO in pediatric asthma management, one economic modeling study compared FeNO-guided treatment adjustments against standard care without FeNO monitoring. The model found that FeNO-guided management was associated with a lower average cost per patient (roughly $1,333 versus $1,452) and a slightly higher quality of life. The probability that FeNO monitoring was the more cost-effective approach exceeded 99% across all willingness-to-pay thresholds tested.25PubMed Central. Cost utility of fractional exhaled nitric oxide monitoring for the management of children asthma The savings come largely from avoiding unnecessary steroid dose increases in children whose inflammation is already controlled, and from reducing exacerbations by catching rising inflammation before symptoms spiral.
That said, economic models depend heavily on their assumptions, and real-world cost savings depend on how consistently clinicians actually act on the FeNO result. A test that changes the number on a chart but not the prescription pad does not save money.
Lung Transplantation and Nitric Oxide
Outside the outpatient clinic, nitric oxide in the lungs plays a role in a very different setting: organ transplantation. Transplanted lungs are vulnerable to injury during harvesting, preservation, and the moment blood flow is restored. The lung’s capacity to generate nitric oxide contributes to matching airflow with blood flow, fighting infection, and regulating inflammatory processes. Inhaled nitric oxide has been given to lung transplant recipients with reports of improved blood flow through the lungs, better gas exchange, shorter time on a ventilator, and lower mortality.26The Lancet. Endogenous nitric oxide in lung transplantation This is not a FeNO measurement application but rather a therapeutic use of the same molecule, illustrating how central nitric oxide is to normal lung function.
Getting an Accurate Reading
If you are scheduled for a FeNO test, or you track your levels at home, a few practical considerations help ensure the number you get reflects your actual airway inflammation rather than something you ate or breathed in that morning.
- Avoid nitrate-rich food: Beetroot, spinach, lettuce, and other high-nitrate foods can spike your reading for hours. Most guidelines suggest fasting or at least avoiding these foods for a few hours before the test.
- Do not smoke or vape beforehand: Smoking suppresses the reading, potentially masking real inflammation. Even a single session can temporarily lower your FeNO.
- Test before spirometry: If you are also getting lung-function testing on the same visit, FeNO should be measured first. The deep forced breaths required for spirometry can temporarily alter your exhaled NO level.
- Note recent pollution exposure: If you walked along a busy road or spent time near a pollution source, mention it to your doctor. Elevated background exposure can nudge the number up by several ppb.
- Consider timing with meals: Even foods that are not particularly high in nitrate can cause minor fluctuations. Testing at a consistent time of day relative to meals helps with longitudinal tracking.
These factors matter more when your FeNO is in the borderline range, say between 20 and 35 ppb, where a shift of five or ten parts per billion could change the clinical interpretation. At very low or very high levels, confounders are less likely to flip the answer.