Are High FeNO Levels Linked to Risk of Frequent Asthma Exacerbations?

Woman suffering with respiratory issues, chest pain
Woman suffering with respiratory issues, chest pain
How do FeNO levels in asthma affect disease burden, quality of life, and the need for OCS maintenance therapy?

High levels of the biomarker fraction of exhaled nitric oxide (FeNO) are associated with a heavy disease burden in patients with severe asthma and are also correlated with chronic rhinosinusitis with nasal polyposis (CRSWNP), later asthma onset, poor lung function and asthma control, low quality of life, frequent exacerbations, and the need for maintenance oral corticosteroid (OCS) therapy. These were among findings of a German study published in the European Respiratory Journal.

The current study was based on cross-sectional data taken from the Severe Asthma Registry of the German Asthma Net. Of 1689 patients on the registry with severe asthma, 1007 had available FeNO data, permitting the correlation of FeNO with epidemiologic, laboratory, clinical, lung function, or quality of life parameters and the need for OCS maintenance therapy. In the selected cohort, 64% had high FeNO measurements (≥25 ppb), 58% were female, and 72% had uncontrolled asthma. The average age was 50.3 years, BMI was 27 kg/m², forced expiratory volume in 1 second (FEV1) was 2.04 L (67% predicted), and median FeNO (interquartile range) was 34 (18 – 66) parts per billion (ppb).

Patients with FeNO levels 25 ppb or above had a significantly higher rate of asthma exacerbations than patients with low FeNO levels. They also had significantly lower partial pressure of oxygen (pO2), FEV1 (both absolute and % predicted), and FEV1/FVC ratio and were considerably older than those with low FeNO. A FeNO level of 25 ppb or higher had a sensitivity of 65% to predict the occurrence of 2 or more exacerbations per year, with a positive predictive value of 61% and an area under curve (AUC) of 0.53 (95% CI, 0.50-0.56).

After patients were separated into categories, significantly higher FeNO levels were found to be linked to the following factors: BMI <30 kg/m2, the presence of CRSWNP, age 12 years or older at asthma onset, pO2 <72 mm Hg, lower lung function values (FEV1/FVC <70% or FVC/inspiratory vital capacity (IVC) <0.93 [the lower limit of normal]), poor asthma control on the Asthma Control Questionnaire 5 (ACQ-5 ≥1.5) or Asthma Control Test (ACT <20), worse asthma quality of life on the mini Asthma Quality of Life Questionnaire (mAQLQ <5.4), frequent exacerbations (≥2/year), immunoglobulin E ≥75 U/mL, and maintenance OCS use.

The researchers validated their results through linear regression analysis and included the results in a multiple regression analysis, in which, age, CRSWNP, BMI, FEV1/FVC, and exacerbations per year were independently and significantly associated with FeNO levels. Maintenance OCS therapy displayed a borderline significance.

The authors stated that the strengths of their study lie in the careful selection of patients with severe asthma and the large cohort size, noting that discrepant results seen in previous studies primarily resulted from smaller sample sizes.

The study reinforces the role of FeNO in pinpointing patients with a high risk of frequent asthma exacerbations, wrote the authors. “Translating these results into clinical practice, we suggest that FeNO can act as a marker of disease burden, and could be a useful parameter in the identification and management of patients with increased risk of complications associated with severe asthma, and those who may require intensified therapy,” said the authors.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industries. Please refer to the original article for a full list of disclosures.


Bal C, Idzko M, Škrgat S, et al. FeNO is associated with disease burden in the German Asthma Net severe asthma cohort. Eur Respir J. Published online March 10, 2022. doi:10.1183/13993003.01233-2021