Unveiling Eosinophilic Airways: FeNO in Non-Asthmatic Diagnostic Practice

Eosinophilic airway disorders often present with asthma-like features, presenting unique challenges to clinical diagnostics. Emerging evidence positions fractional exhaled nitric oxide (FeNO) as an increasingly valuable tool in untangling these non-asthmatic complexities.

FeNO is an adjunctive, non-invasive biomarker that supports assessment of eosinophilic (type 2) airway inflammation and can inform differential diagnosis when integrated with clinical context and other tests. Interpretation should follow established ATS/ERS guidance, which highlights typical cut-points and caveats such as effects of inhaled corticosteroids and smoking; clinicians should apply these thresholds within the broader clinical context.

The mechanism that allows FeNO to identify eosinophilic inflammation also provides insights into non-asthmatic airway pathology, suggesting potential links between detection and intervention. Because FeNO reflects type 2 inflammation seen across multiple conditions, it supports—rather than determines—differentiation from asthma when integrated with complementary measures such as induced sputum eosinophils and observed response to inhaled corticosteroids.

Addressing eosinophilic disorders without obvious asthma symptoms remains particularly challenging. These disorders require enhanced diagnostic sensitivity as traditional asthma markers often fail to capture their complexity.

Clinical challenges necessitate advanced diagnostic tools like FeNO and sputum analysis to accurately identify non-asthmatic eosinophilic airway disorders, as recommended in consensus reviews. Specialized diagnostics can lead to improved patient management and targeted therapies. Signals of macrophage activation from transcriptomic studies are exploratory and may inform future diagnostics, whereas current clinical decisions rely more heavily on established measures such as FeNO and sputum eosinophils.

Taken together, a tiered protocol that pairs FeNO with induced sputum eosinophil counts and insights from sputum transcriptomics can guide stepwise evaluation before broader conclusions are drawn. Integrating more robust diagnostic protocols is essential to improve patient outcomes across eosinophilic spectrums. Novel biomarkers and innovative techniques (e.g., FeNO thresholds and induced sputum eosinophil counts) expand potential treatment landscapes, supporting clinicians in their quest for precise medical interventions.

Key Takeaways:

• FeNO offers a critical, non-invasive method for assessing eosinophilic airway inflammation beyond asthma.
• Differentiating eosinophilic airway disorders requires advanced metrics beyond standard asthma diagnostics.
• Diagnosis remains challenging in the absence of typical symptoms, necessitating nuanced clinical approaches.
• Innovations in biomarker utilization are reshaping the diagnostic landscape for these respiratory conditions.