Abstract Rationale Lung dysfunction, a hallmark of COPD, manifests as impaired respiratory mechanics involving some combination of alterations in breathing-related mechanical properties of the diaphragm, rib cage, airways, and parenchyma. Studies suggest that these mechanical changes may precede histologically detectable lung abnormalities. Preserved Ratio Impaired Spirometry (PRISm) represents a distinct pre-COPD pathway characterized by restrictive spirometry associated with a higher mortality risk than mild COPD. Respiratory mechanical impairments in this group remain understudied. We retrospectively examine mechanical impairments in PRISm using multi-volume CT-based measures of respiratory mechanical features. Methods The study cohort included participants in the Genetic Epidemiology of COPD (COPDGene) Iowa cohort at baseline visits after excluding never smokers and BMI outside the range of 20-35 kg/m2. Full inspiratory and expiratory CT-based respiratory mechanical biomarkers were derived: craniocaudal diaphragm displacement (Δdia-CC), transverse-area rib expansion (Δrib-A), and airway radial expansion (Δair-R) and longitudinal stretching (Δair-S). Metric-specific expectation models were developed using linear regression, with age, sex, and BMI as predictors, based on a reference group of smokers with preserved lung function (COPD GOLD stage 0). For each metric, a standardized residual (z-score) was calculated for each participant using their observed value and the expected value derived from the model. Statistical comparisons were performed using two-sample t-tests (significance threshold: p 0.05). Results 481 participants (234 females, age: 62.2±8.5 years) had preserved lung function, while 69 participants (37 females, age: 63.5±8.1 years) had PRISm and 374 participants (164 females, age: 67.1±7.8 years) had COPD. All Δ-metrics, except Δair-R, exhibited lower z-scores in PRISm than in mild COPD, with a significant difference for Δdia-CC (p = 0.002). PRISm exhibited significantly impaired Δrib-A (p = 0.008) compared to smokers with preserved lung function, whereas the impairment was not statistically significant in mild COPD (Figure 1). The moderate COPD group had significantly lower z-scores than PRISm only for Δair-S (p = 0.047), and significantly lower than mild COPD for Δair-R, Δair-S, and Δdia-CC (p = 0.015, 0.001, and 0.001, respectively). Sharp declines in Δair-S and Δdia-CC z-scores were observed between moderate and severe stages (p 0.001), with large effect sizes (1.152 and 1.236). Conclusion The study findings suggest that PRISm differs from other COPD severity groups in its respiratory mechanical impairments, distinct from the conventional interpretation of representing a transitional stage within COPD. Individuals with PRISm demonstrated lower values in key mechanical biomarkers compared to those with mild COPD, further supporting a restrictive respiratory pattern in PRISm. This abstract is funded by: NHLBI grants R21 HL175750, R01 HL142042, U01 HL089897 and U01 HL089856, by NIH shared instrumentation grant S10 OD018526, by NIH contract 75N92023D00011, and by the Bowers Emphysema Research Fund at the University of Iowa.
Liu et al. (Fri,) studied this question.