B102-19 Measurements of Mid-Flow Impairment (FEF25-75%) Associated With Airway Dominant Phenotype and Future Obstruction in Preserved Ratio Impaired Spirometry (PRISm)

Abstract Rationale Spirometry with a restrictive pattern characterized in the COPDGene cohort and recognized by GOLD as Preserved Ratio Impaired Spirometry (PRISm) is likely a physiologically heterogenous condition ranging from traditional chest wall and parenchymal restrictive processes vs. airways disease associated with widely heterogeneous expiratory time constants. We assessed whether forced expiratory flow 25-75% (FEF25-75%), a measure of mid-flow impairment (MFI) could better identify symptom burden, quantitative radiographic findings, and negative long term events including exacerbations and future obstruction as expected from an airway dominant phenotype. Methods Deidentified data were collected by the COPDGene study and included 1419 patients categorized as PRISm (defined FEV1/FVC ≥ 0.7 and FEV1 80% predicted by GLI global equations). Patients were dichotomized by FEF25-75%, where patients with FEF25-75% less than 60% predicted by Hankinson-White was considered to have MFI. We analyzed demographics, symptoms, spirometry, and quantitative computed tomography as well as longitudinal changes in lung function and radiography, and exacerbation rates with median follow-up of 10.5 years. Comparative statistics used included Students’ t-test, Chi-Squared, Kaplan-Meier analysis with log-rank, least squares regression, and negative binominal regression. Results PRISm with MFI (n = 511) were more commonly male with higher BMI, and with a higher St. George’s Respiratory Questionnaire (SGRQ) compared to their PRISm counterparts without MFI (n = 908) supporting greater symptom burden (see Table). MFI individuals had significantly lower baseline FEV1 and FEV1/FVC ratios, greater Pi10 and wall-area % measures of airway wall thickening, higher FRC/TLC by computed tomography supporting radiographic air trapping, and greater prevalence of bronchodilator reversibility. The MFI PRISm group also had a higher use of bronchodilators and inhaled corticosteroids despite not meeting traditional criteria for airflow obstruction. MFI was associated with a greater longitudinal increase in airway thickening and trend toward FEV1 decline. Finally, MFI individuals were nearly 3X more likely to develop FEV1/FVC of 0.7 at subsequent follow-up and had a greater risk of exacerbation or COPD related hospitalization (annualized rate of 0.32±0.70 vs. 0.24±0.56). Notably individuals without MFI have a decreased TLC % predicted by computed tomography supportive of traditional restrictive processes. Conclusions Mid-flow impairment measured by FEF25-75% 60% defines a subclass of PRISm with an airway dominant radiographic and imaging phenotype that is associated with greater symptoms and is more likely to be treated with bronchodilators, have exacerbations, and progress to physiological obstruction. This abstract is funded by: None