Interpretation of exhaled NO in asthma

a simpler method has been proposed in the American Thoracic Society Clinical Practice Guideline for interpretation of FeNO:

  • A FeNO less than 25 ppb in adults and less than 20 ppb in children younger than12 years of age implies the absence of eosinophilic airway inflammation.
  •  A FeNO greater than 50 ppb in adults or greater than 35 ppb in children suggests eosinophilic airway inflammation.
  •  Values of FeNO between 25 and 50 ppb in adults (20 to 35 ppb in children) should be interpreted cautiously with reference to the clinical situation.
  • A rising FeNO with a greater than 20 percent change and more than 25 ppb (20 ppb in children) from a previously stable level suggests increasing eosinophilic airway inflammation, but there are wide inter-individual differences.
  • A decrease in FeNO greater than 20 percent for values over 50 ppb or more than 10 ppb for values less than 50 ppb may be clinically important.

Diagnosis and characterization of asthma

The Global Initiative for Asthma advises against the use of FeNO for the diagnosis of asthma, as it may not be elevated in noneosinophilic asthma and may be elevated in diseases other than asthma, such as eosinophilic bronchitis or allergic rhinitis.

As a guide to therapy

International guidelines suggest using FeNO levels, in addition to other assessments (e.g., clinical care, questionnaires) to guide initiation and adjustment of asthma controller therapy.

Use in clinical research

Exhaled nitric oxide has an important role in clinical research and will likely help in expanding our understanding of asthma, such as the factors responsible for asthma exacerbations and the sites and mechanisms of action of medications for asthma.


Bronchiectasis and cystic fibrosis

Children with cystic fibrosis (CF) have lower FeNO levels than appropriately matched controls. In contrast, one study found that patients with non-CF bronchiectasis had elevated levels of FeNO, and these levels were correlated with the degree of abnormality apparent on chest CT.

Interstitial lung disease and sarcoidosis

In a study of patients with scleroderma, a higher exhaled NO was noted among patients with interstitial lung disease (ILD) compared with those without ILD, while the opposite was found in another study. In a study of 52 patients with sarcoidosis, the mean FeNO value was 6.8 ppb, which is substantially less than the cut-point of 25 ppb used to denote asthma inflammation.

Chronic obstructive pulmonary disease

FENO levels are minimally elevated in stable COPD, but may increase with more severe disease and during exacerbations. Current smokers have approximately 70 percent lower levels of FeNO. In patients with COPD, FeNO levels may be useful in establishing the presence of reversible airflow obstruction and determining glucocorticoid responsiveness, although this has not been assessed in large randomized trials.

Cough variant asthma

FENO has moderate diagnostic accuracy in predicting a diagnosis of cough variant asthma (CVA) in patients with chronic cough. In a systematic review of 13 studies (2019 patients), the optimal cut-off range for FENO was 30 to 40 ppb (although lower values were noted in two studies), and the summary area under the curve was 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity.

Nonasthmatic eosinophilic bronchitis

In patients with nonasthmatic eosinophilic bronchitis (NAEB), sputum eosinophils and FENO are increased in a range similar to patients with asthma. In a systematic review of four studies (390 patients) in patients with chronic cough due to NAEB, optimal FENO cut-off levels were 22.5 to 31.7 ppb. The estimated sensitivity was 0.72 (95% CI 0.62-0.80) and estimated specificity was 0.83 (95% CI 0.73-0.90). Thus, FENO is more useful to confirm NAEB, than to exclude it.

Upper respiratory infections

In one study of patients without underlying pulmonary disease, viral upper respiratory infections resulted in increased FENO.

Pulmonary hypertension

NO is well-recognized as a pathophysiologic mediator in pulmonary arterial hypertension (PAH). In addition to vasodilation, NO regulates endothelial cell proliferation and angiogenesis, and maintains overall vascular health. Interestingly, patients with PAH have low FENO values.

FENO seems to also have a prognostic significance, with improved survival in patients who have a rise in FENO level with therapy (calcium channel blockers, epoprostenol, treprostinil) compared to those who do not. Thus, the low FENO levels in patients with PAH and the improvement with effective therapies suggest it may be a promising biomarker for this disease.

Primary ciliary dysfunction

Nasal NO is very low or absent in patients with primary ciliary dysfunction (PCD). The use of nasal NO to screen for PCD in patients with a clinical suspicion of PCD is discussed separately.

Other conditions

In addition to pulmonary hypertension, other conditions associated with low FENO levels include hypothermia, and bronchopulmonary dysplasia, as well as the use of alcohol, tobacco, caffeine, and other drugs.

Post time: Apr-08-2022