Physiology of severe vs. mild-moderate U-BIOPRED cohorts interpreted using a computational model

Background: FEV1 correlates with symptoms and exacerbation risk in asthma. Although considered an index of airway resistance (R), FEV1 also varies with vital capacity (VC) as a function of airway recruitment. Aims: Quantify the contributions of airway narrowing vs. closure by analyzing airflow limitation and bronchodilator reversibility in U-BIOPRED patients with severe (S) vs. mild-moderate (MM) disease. Methods: Patients with S (n=305) and MM (n=95) underwent spirometry and plethysmography (PFTs) in a cross-sectional design. Employing a single compartment lung model, FEV1 = (TLC-RV){1-exp[-1/(RC)]}1. PFT values were entered into the model to assess airway narrowing and closure in each cohort. Results: Baseline % predicted FEV1 (67.4 vs. 88.4%; p Conclusion: Modeling of PFT data from U-BIOPRED reveals distinct patterns of baseline physiology and bronchodilator responsiveness in S and MM cohorts. S display lower FEV1 with airway collapse and gas trapping, partly reversible with bronchodilators. MM display minimal gas trapping, less bronchodilator %ΔFEV1, but larger changes in R suggesting greater b-agonist effect on airway tone in milder disease.