{"title":"How Airway Caliber Affects FeNO Thresholds Used to Identify Type 2 Inflammation in Asthma","authors":"Alain Michils PhD , Amaryllis Haccuria PhD , Myrna Virreira PhD , Nathalie Grimaldi BS , Nathalie Demaeyer MD , Silvia Perez-Bogerd MD , Andreï Malinovschi PhD , Alain Van Muylem PhD","doi":"10.1016/j.jaip.2025.05.049","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div><span>Fractional exhaled nitric oxide<span> (FeNO) has emerged as a biomarker of type 2 (T2) airway inflammation (AI), primarily reflecting IL-13 activity. Reducing airway caliber reduces FeNO levels, suggesting an impact of </span></span>airway obstruction.</div></div><div><h3>Objective</h3><div>This study compared the relative contributions of airway IL-13 and airway caliber to FeNO values in patients with asthma. We also investigated how airway caliber reduction affects FeNO thresholds for detecting active T2 AI.</div></div><div><h3>Methods</h3><div><span>FeNO and forced expiratory volume in 1 second (FEV</span><sub>1</sub><span><span>) measurements as well as sputum<span> induction were performed in 120 patients with asthma and 13 controls. Elevated sputum IL-13, IL-5, or </span></span>eosinophils identified 100 patients with active T2 AI. The contributions of IL-13 and FEV</span><sub>1</sub> to FeNO were assessed in asthmatics with clear evidence of T2 AI by multivariable linear models. Receiver operating characteristic (ROC) curve analysis was used to identify FeNO thresholds marking the presence of active T2 AI according to FEV<sub>1</sub>.</div></div><div><h3>Results</h3><div>In T2 patients<em>,</em> IL-13 and FEV<sub>1</sub> contribute significantly (<em>P</em> = .005 and <em>P</em> = .008, respectively) to FeNO based on multivariable analysis. From the ROC curve analysis, the FeNO threshold corresponding to a specificity >85% was 45 parts per billion (ppb) in the whole population and dropped to 22 ppb in patients with FEV<sub>1</sub> <70%.</div></div><div><h3>Conclusions</h3><div>Airway caliber is a major determinant of FeNO values in asthma, as crucial as concomitant T2 AI. As a result, the optimal thresholds for FeNO to signal the presence of active T2 AI in asthmatics decrease significantly as FEV<sub>1</sub> decreases. New thresholds considering the impact of lung function should be established in larger cohorts.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 9","pages":"Pages 2397-2404"},"PeriodicalIF":6.6000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology-In Practice","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213219825005264","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Fractional exhaled nitric oxide (FeNO) has emerged as a biomarker of type 2 (T2) airway inflammation (AI), primarily reflecting IL-13 activity. Reducing airway caliber reduces FeNO levels, suggesting an impact of airway obstruction.
Objective
This study compared the relative contributions of airway IL-13 and airway caliber to FeNO values in patients with asthma. We also investigated how airway caliber reduction affects FeNO thresholds for detecting active T2 AI.
Methods
FeNO and forced expiratory volume in 1 second (FEV1) measurements as well as sputum induction were performed in 120 patients with asthma and 13 controls. Elevated sputum IL-13, IL-5, or eosinophils identified 100 patients with active T2 AI. The contributions of IL-13 and FEV1 to FeNO were assessed in asthmatics with clear evidence of T2 AI by multivariable linear models. Receiver operating characteristic (ROC) curve analysis was used to identify FeNO thresholds marking the presence of active T2 AI according to FEV1.
Results
In T2 patients, IL-13 and FEV1 contribute significantly (P = .005 and P = .008, respectively) to FeNO based on multivariable analysis. From the ROC curve analysis, the FeNO threshold corresponding to a specificity >85% was 45 parts per billion (ppb) in the whole population and dropped to 22 ppb in patients with FEV1 <70%.
Conclusions
Airway caliber is a major determinant of FeNO values in asthma, as crucial as concomitant T2 AI. As a result, the optimal thresholds for FeNO to signal the presence of active T2 AI in asthmatics decrease significantly as FEV1 decreases. New thresholds considering the impact of lung function should be established in larger cohorts.
期刊介绍:
JACI: In Practice is an official publication of the American Academy of Allergy, Asthma & Immunology (AAAAI). It is a companion title to The Journal of Allergy and Clinical Immunology, and it aims to provide timely clinical papers, case reports, and management recommendations to clinical allergists and other physicians dealing with allergic and immunologic diseases in their practice. The mission of JACI: In Practice is to offer valid and impactful information that supports evidence-based clinical decisions in the diagnosis and management of asthma, allergies, immunologic conditions, and related diseases.
This journal publishes articles on various conditions treated by allergist-immunologists, including food allergy, respiratory disorders (such as asthma, rhinitis, nasal polyps, sinusitis, cough, ABPA, and hypersensitivity pneumonitis), drug allergy, insect sting allergy, anaphylaxis, dermatologic disorders (such as atopic dermatitis, contact dermatitis, urticaria, angioedema, and HAE), immunodeficiency, autoinflammatory syndromes, eosinophilic disorders, and mast cell disorders.
The focus of the journal is on providing cutting-edge clinical information that practitioners can use in their everyday practice or to acquire new knowledge and skills for the benefit of their patients. However, mechanistic or translational studies without immediate or near future clinical relevance, as well as animal studies, are not within the scope of the journal.