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Volume 16
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10.3390/life16071203
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Article

Trajectories in Oxidative Stress and Corticosteroids Insensitivity in Patient with High Risk of Severe Asthma: Use of FeNO as Biomarker of Respiratory Epithelial Barrier Distress

by
Cristiano Caruso
1,†,
Ilaria Baglivo
1,†,
Emanuele Cataldo
2,*,
Ludovica Fabbroni
1,
Maria Antonietta Zavarella
1,
Stefania Colantuono
3,
Gianna Camiciottoli
4,
Giovanna Elisiana Carpagnano
5,
Antonio Di Marco
6,
Loreta Di Michele
7,
Fabiana Furci
8,
Chiara Magni
9,
Laura Martino
10,
Alessandro Mastinu
11,
Corrado Micucci
12,
Nicola Scichilone
13,
Roberto Tazza
14,
Rodolfo Pacilio
15 and
Michele Miraglia Del Giudice
16
1
UOSD Allergy and Clinical Immunology, Fondazione Policlinico A. Gemelli, IRCCS, Catholic University of Sacred Heart, 00168 Rome, Italy
2
UOC Pulmonology, Fondazione Policlinico A. Gemelli, IRCCS, 00168 Rome, Italy
3
UOSD DH Internal Medicine and Digestive Diseases, Fondazione Policlinico A. Gemelli, IRCCS, 00168 Rome, Italy
4
Severe Asthma Unit, Cardio-Thoracic and Vascular Department, Careggi University Hospital, 50134 Florence, Italy
5
Section of Respiratory Diseases, University of Bari, 70121 Bari, Italy
6
Pediatric Pulmonology & Cystic Fibrosis Unit, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Roma, Italy
7
UOSD Pneumology Day Hospital and Pulmonary Interstitial Diseases, San Camillo Forlanini Hospital, 00152 Rome, Italy
8
Provincial Healthcare Unit, Section of Allergology, 89900 Vibo Valentia, Italy
9
SOS Pneumology and Bronchial Endoscopy, San Jacopo Hospital, 51100 Pistoia, Italy
10
UOSD Pneumology, ASL Lanciano-Vasto-Chieti, 66100 Chieti, Italy
11
SSD Pneumology, Asl AT, 14100 Asti, Italy
12
Pneumology Unit, Carlo Urbani Hospital, 60035 Jesi, Italy
13
PROMISE Department, University of Palermo, 90127 Palermo, Italy
14
S.S. Territorial Pneumology, USL Umbria 2, 05100 Terni, Italy
15
UOC Pulmonology Azienda Policlinico Umberto I, DAI Internal Medicine Endocrine Metabolic Sciences and Infectious Diseases, 00161 Rome, Italy
16
Department of Women’s, Children’s, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80130 Naples, Italy
 
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*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Life 2026, 16(7), 1203; https://doi.org/10.3390/life16071203
Submission received: 21 May 2026 / Revised: 26 June 2026 / Accepted: 8 July 2026 / Published: 21 July 2026
(This article belongs to the Special Issue Management of Inflammatory Airway Diseases)
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Abstract

Background: Precision medicine targets clinical remission, but traditional symptom-based frameworks often ignore the biological pathways driving the disease. Adequate T2 biomarker interpretation is crucial to identify phenotypes where FeNO reflects epithelial barrier distress. We investigated the “clinical-biological gap” through the analysis of six groups to distinguish profiles of symptomatic resilience from biological insensitivity to corticosteroids. Methods: Real-world study of 292 patients stratified into six groups based on BEC (≥250 cells/microL), FeNO (≥25 ppb), and IgE (≥100 kU/L). ACT, BMI, FEV1, comorbidities, and therapeutic burden were analyzed. Results: The EoS+ IgE+ group showed “symptomatic resilience”: apparent clinical control (54.5% ACT ≥ 20) supported by a critical pharmacological burden (90% salbutamol, 80% OCS ≥ 7.5 mg). The Triple Positive and EoS+ FeNO+ groups depicted “Maximum Steroid Insensitivity,” characterized by poor control despite maximal ICS/OCS regimens. FeNO could appear like the primary driver of instability, reflecting a trajectory of oxidative stress not altered by steroids. Conclusions: T2 biomarkers provide a unique prognostic value unidentifiable by standard clinical assessment. FeNO monitoring unmasks silent distress in resilient patients and identifies the “therapeutic wall” in refractory profiles. Therefore biological remission could represents the only effective target to modify the natural history of the disease.
Keywords: Type 2 high asthma; severe asthma; FeNO; biomarkers; high risk; resilience; immunology Type 2 high asthma; severe asthma; FeNO; biomarkers; high risk; resilience; immunology

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MDPI and ACS Style

Caruso, C.; Baglivo, I.; Cataldo, E.; Fabbroni, L.; Zavarella, M.A.; Colantuono, S.; Camiciottoli, G.; Carpagnano, G.E.; Di Marco, A.; Di Michele, L.; et al. Trajectories in Oxidative Stress and Corticosteroids Insensitivity in Patient with High Risk of Severe Asthma: Use of FeNO as Biomarker of Respiratory Epithelial Barrier Distress. Life 2026, 16, 1203. https://doi.org/10.3390/life16071203

AMA Style

Caruso C, Baglivo I, Cataldo E, Fabbroni L, Zavarella MA, Colantuono S, Camiciottoli G, Carpagnano GE, Di Marco A, Di Michele L, et al. Trajectories in Oxidative Stress and Corticosteroids Insensitivity in Patient with High Risk of Severe Asthma: Use of FeNO as Biomarker of Respiratory Epithelial Barrier Distress. Life. 2026; 16(7):1203. https://doi.org/10.3390/life16071203

Chicago/Turabian Style

Caruso, Cristiano, Ilaria Baglivo, Emanuele Cataldo, Ludovica Fabbroni, Maria Antonietta Zavarella, Stefania Colantuono, Gianna Camiciottoli, Giovanna Elisiana Carpagnano, Antonio Di Marco, Loreta Di Michele, and et al. 2026. "Trajectories in Oxidative Stress and Corticosteroids Insensitivity in Patient with High Risk of Severe Asthma: Use of FeNO as Biomarker of Respiratory Epithelial Barrier Distress" Life 16, no. 7: 1203. https://doi.org/10.3390/life16071203

APA Style

Caruso, C., Baglivo, I., Cataldo, E., Fabbroni, L., Zavarella, M. A., Colantuono, S., Camiciottoli, G., Carpagnano, G. E., Di Marco, A., Di Michele, L., Furci, F., Magni, C., Martino, L., Mastinu, A., Micucci, C., Scichilone, N., Tazza, R., Pacilio, R., & Miraglia Del Giudice, M. (2026). Trajectories in Oxidative Stress and Corticosteroids Insensitivity in Patient with High Risk of Severe Asthma: Use of FeNO as Biomarker of Respiratory Epithelial Barrier Distress. Life, 16(7), 1203. https://doi.org/10.3390/life16071203

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