Longitudinal changes in sputum and blood inflammatory mediators during FeNO suppression testing

Area of Science:

• Respiratory Medicine
• Immunology
• Pharmacology

Background:

• Asthma management often relies on corticosteroids, but some patients exhibit resistance.
• Fractional exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation.
• Identifying corticosteroid resistance is crucial for optimizing asthma treatment.

Purpose of the Study:

• To investigate if non-suppression of FeNO during a suppression test identifies corticosteroid resistance.
• To analyze inflammatory mediator changes in response to high-intensity corticosteroid therapy based on FeNO suppression.
• To correlate FeNO suppression with clinical and biological markers of treatment response.

Main Methods:

• A FeNO suppression test was conducted with monitored high-intensity corticosteroid therapy.
• Asthma Control Questionnaire scores and sputum eosinophil counts were assessed.
• Levels of sputum inflammatory mediators, including prostaglandin D2 and type-2 cytokines, were measured.
• Linear mixed-effects models were used to analyze changes over time.

Main Results:

• Patients with FeNO non-suppression (≥42% FeNO suppression) showed persistent sputum eosinophilia despite therapy.
• FeNO suppressors normalized Asthma Control Questionnaire scores and sputum eosinophils.
• Non-suppressors had significantly higher end-test inflammatory mediator levels compared to suppressors.
• FeNO non-suppression was associated with biological corticosteroid resistance.

Conclusions:

• Non-suppression of FeNO during a monitored suppression test is a marker for corticosteroid resistance in asthma.
• This test can help differentiate between steroid-sensitive and steroid-resistant asthma.
• Findings support personalized treatment strategies based on FeNO response to therapy.