For years, the Fractional Exhaled Nitric Oxide (FeNO) test has served as a valuable companion in the asthma clinician's toolkit, primarily guiding management decisions. The 2025 update to the Global Initiative for Asthma (GINA) guidelines marks a significant evolution, formally expanding the role of FeNO beyond assessment and management to now actively support the diagnosis of Type 2 (T2) inflammatory asthma. This refinement acknowledges the central role of phenotyping in modern asthma care and provides a more precise, biologically-grounded approach to initial diagnosis.
FeNO: A Window into Airway Inflammation
FeNO measures the concentration of nitric oxide in exhaled breath, which serves as a direct, non-invasive biomarker for eosinophilic, or T2, airway inflammation. This inflammation, driven by cytokines like interleukin-4, -5, and -13, is characterized by elevated IgE, eosinophils in blood and sputum, and responsiveness to corticosteroids. Traditionally, FeNO has been used to:
Predict response to inhaled corticosteroids (ICS): High FeNO levels reliably indicate a greater likelihood of benefit from ICS therapy.
Monitor adherence and inflammation control: Serial measurements can objectively assess patient adherence to anti-inflammatory therapy and the suppression of underlying T2 inflammation.
Guide treatment adjustment: FeNO trends can inform decisions on stepping up or stepping down ICS dosage.
The 2025 Shift: FeNO in the Diagnostic Pathway
The key advancement in the 2025 GINA report is the strengthened endorsement of FeNO as a diagnostic aid for identifying T2-high asthma at the point of presentation. This is particularly crucial in the context of heterogeneous asthma presentations.
Differentiating Asthma Phenotypes: Not all wheeze or breathlessness is classic T2 asthma. Patients with non-T2 or pauci-granulocytic inflammation may present with similar symptoms but have low FeNO levels. A consistently elevated FeNO level (e.g., >35-40 ppb in adults) in a patient with suggestive symptoms (cough, wheeze, variable airflow limitation) now provides compelling positive evidence for a T2-high endotype, even before a trial of treatment.
Supporting Diagnosis in Challenging Scenarios: For patients with atypical symptoms or where spirometry results are ambiguous or normal at the time of testing, an elevated FeNO can be the critical piece of objective evidence pointing toward an underlying T2 inflammatory process. It helps move the diagnosis from one based solely on variable symptomatology to one incorporating a biological signature.
Informing Initial Treatment Strategy: By incorporating FeNO at the diagnostic stage, clinicians can stratify therapy more rationally from the outset. A high FeNO level not only supports an asthma diagnosis but also strongly predicts a favorable response to first-line ICS therapy. This facilitates a more personalized, "right-first-time" treatment approach, potentially improving early control and outcomes.
Clinical Implications and Integration
The 2025 guidelines recommend integrating FeNO testing into the initial diagnostic workup when suspicion of asthma exists and access to the test is available. The interpretation follows a stratified model:
High FeNO (>50 ppb in adults): Strongly supports a diagnosis of T2-high asthma and predicts ICS responsiveness.
Intermediate FeNO (25-50 ppb in adults): Should be interpreted in clinical context; may suggest T2 inflammation but can be influenced by atopy, recent allergen exposure, or other factors.
Low FeNO (<25 ppb in adults): Makes T2-high inflammation less likely, prompting consideration of alternative diagnoses (e.g., vocal cord dysfunction, non-T2 asthma phenotypes, COPD) or non-inflammatory causes of symptoms.
This update does not make FeNO a standalone diagnostic test but positions it as a powerful complement to clinical history, symptom patterns, and spirometry/reversibility testing. It adds a layer of objectivity that refines diagnostic confidence.
Conclusion
The 2025 GINA guidelines represent a paradigm shift, solidifying the status of FeNO testing from a management adjunct to a integral diagnostic supporter for Type 2 asthma. By providing an immediate, objective measure of underlying T2 inflammation, FeNO empowers clinicians to make more accurate phenotypic diagnoses at the first encounter. This leads to more targeted and effective initial treatment, aligning perfectly with the modern ambition of precision medicine in asthma care. As access to FeNO technology widens, its role in both diagnosing and directing therapy for T2-high asthma is set to become a standard of care, ultimately aiming for better patient outcomes through earlier and more accurate intervention.
UBREATH Breath Gas Analysis System (BA200) is a medical device designed & manufactured by e-LinkCare Meditech to associate with both FeNO and FeCO testing to provide rapid, precise, quantitative measurement in order to assist with clinical diagnosis and management such as asthma and other chronic airway inflammations.
Post time: Jan-23-2026