Lower Airway Dysfunction in Patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): Associations with Asthma, ACQ5, and Inflammatory Markers

OBJECTIVE: CRSwNP is typically a type 2 inflammatory condition of the upper airways often associated with asthma. However, emerging evidence suggests that lower airway dysfunction may also occur in CRSwNP patients without a formal asthma diagnosis. This study aimed to explore the associations between lower airway symptoms (ACQ5), lung function, airway hyperresponsiveness (AHR), and inflammatory markers in patients with CRSwNP.

METHODS: In this cross-sectional study, 72 patients with CRSwNP were systematically evaluated using spirometry, impulse oscillometry (IOS), methacholine and mannitol challenge tests, fractional exhaled nitric oxide (FeNO), blood and polyp eosinophil counts, and symptom scores (SNOT-22, ACQ5). Associations between ACQ5 scores and lower airway parameters were assessed using correlation and multivariable regression analyses, adjusting for asthma diagnosis and markers of type 2 inflammation.

RESULTS: Patients with higher ACQ5 scores (>1.5) demonstrated significantly lower FEV 1% predicted, FEV 1/FVC, and MFEF 75- 25, and higher small airway resistance and AHR ( p  < 0.01 for all). These associations remained significant after adjustment for asthma status, FeNO, blood eosinophils, and polyp eosinophils. Inflammatory markers showed weak or no significant associations with lung function, suggesting that ACQ5 captures aspects of lower airway dysfunction in patients with CRSwNP not explained solely by type 2 inflammation.

CONCLUSIONS: Higher ACQ5 scores in CRSwNP patients, even in the absence of asthma, are independently associated with impaired lung function, small airway dysfunction, and increased AHR. These findings support the global airway concept and highlight the potential value of ACQ5 in identifying subclinical lower airway involvement in CRSwNP.