Association of Small Airway Functional Indices With Respiratory Symptoms and Comorbidity in Asthmatics: A National Cross-Sectional Study

Background: Small airway dysfunction (SAD) and airway inflammation are vital in asthma exacerbations. Type 2 inflammation (T2), mediated by cytokines from T helper 2 cell (Th2) such as interleukin (IL)-4, IL-5, and IL-13, is a potential mechanism underlying SAD. Research on small airway function in asthma is limited. We aimed to explore the correlation between small airway function and respiratory symptoms and comorbidity in T2 and non-T2 asthma. Methods: Derived from the National Health and Nutrition Examination Survey (NHANES), our study encompassed 2,420 asthma patients aged 6 - 79 years, including pulmonary function (PF) data such as forced expiratory flow between 25% and 75% of forced vital capacity (FEF 25-75 ), forced expiratory volume in 1 second (FEV 1 ), forced expiratory volume in 3 seconds (FEV 3 ), forced expiratory volume in 6 seconds (FEV 6 ), and forced vital capacity (FVC). To evaluate the small airway function, we calculated z-scores for FEF 25-75 , FEF 25-75 /FVC, FEV 1 /FEV 6 , and FEV 3 /FEV 6 . Logistic regression determined the adjusted odds ratios (aORs) for symptoms and comorbidity. Results: FEF 25-75 , FEV 1 /FEV 6 , and FEV 3 /FEV 6 correlated with asthmatic symptoms. FEF 25-75 had the strongest association with wheezing or whistling attacks. An increase of 1 standard deviations (SD) in FEF 25-75 reduced recurrent wheezing (aOR: 0.70; 95% confidence intervals (95% CIs): 0.65 - 0.76) and severe attacks (aOR: 0.67; 95% CI: 0.62 - 0.94). These indices were also linked to dry cough and hay fever, particularly FEV 3 /FEV 6 reducing hay fever risk (aOR: 0.70; 95% CI: 0.55 - 0.91) in non-T2 asthma. FEF 25-75 /FVC related to persistent (aOR: 0.78; 95% CI: 0.72 - 0.84) and severe attacks (aOR: 1.14; 95% CI: 1.08 - 1.22) in non-T2 groups. Lower indices combined with T2 exposure raised severe attack risk. Conclusions: In this nationwide study, small airway function correlated with symptom onset, especially in T2 asthma. Small airway injury differed between T2 and non-T2 asthma. Prospective research is needed to establish reference values. J Clin Med Res. 2024;16(5):220-231 doi: https://doi.org/10.14740/jocmr5158