Clinical and Radiological Characteristics of Symptomatic Emphysema Patients with PRISm and Pre-COPD Phenotypes:...

Background: Pre-Chronic Obstructive Pulmonary Disease (pre-COPD) and Preserved Ratio Impaired Spirometry (PRISm) phenotypes represent important components of the early obstructive lung disease spectrum, characterized by respiratory symptoms and structural lung abnormalities prior to the development of overt airflow limitation. Emphysema is considered one of the major structural phenotypes underlying airway disease and the COPD spectrum. Although cigarette smoking is the best recognized risk factor for these conditions, non-tobacco exposures may also contribute to early structural lung changes. In this study, we evaluated the radiological features, pulmonary function parameters, and dyspnea severity of CT-detected emphysema in symptomatic patients classified as having pre-COPD or PRISm, with particular attention paid to the potential influence of smoking status on disease characteristics. Methods: In this retrospective, single-center study, symptomatic patients aged 20-50 years classified as having pre-COPD or PRISm and in whom emphysema was detected on high-resolution computed tomography (HRCT) were evaluated. Only symptomatic patients who underwent HRCT for clinical indications and in whom emphysema was identified were included. Demographic characteristics, emphysema type and quantitative emphysema severity, pulmonary function parameters, and Modified Medical Research Council (mMRC) dyspnea scores were analyzed. The PRISm and pre-COPD groups were compared in terms of clinical and symptomatic characteristics. In addition, smoking-related clinical and radiological characteristics were also evaluated. Results: A total of 232 patients were included in the study. The median age was 43 years (38-48), and 84.1% of the participants were male. Among the study population, 68.5% were classified in the pre-COPD group and 31.5% in the PRISm group. The most frequently identified emphysema patterns were paraseptal (44.4%) and centrilobular (40.5%). The median total lung emphysema area was 18% (13-22). A weak negative correlation was observed between the degree of emphysema and FEV₁ (r = -0.185; p = 0.005), whereas a weak positive correlation was found between emphysema extent and the mMRC dyspnea score (r = 0.214; p = 0.001). Dyspnea severity was significantly higher in the PRISm group compared with the pre-COPD group (p < 0.001). In the smoking-status subgroup analysis, ever-smokers demonstrated significantly greater dyspnea severity and lower FEV₁ values, whereas never-smokers had a significantly higher proportion of emphysema extent > 18% (all p < 0.05). Conclusions: Radiologically detected emphysema in symptomatic patients without airflow limitation was associated with statistically significant but weak alterations in pulmonary function and dyspnea burden. Dyspnea severity was significantly higher in the PRISm phenotype. In a smoking-status subgroup analysis, ever-smokers had significantly greater dyspnea severity, whereas never-smokers showed a significantly higher proportion of extensive emphysema (>18%), despite similar functional impairment across groups. These findings underscore the importance of non-tobacco exposures in the development of emphysema within pre-obstructive spirometric phenotypes. Multicenter prospective studies incorporating healthy controls and systematic exposure documentation are needed to confirm these observations.