Repeatability and replicability of the Respiratory Symptom Experience Scale (RSES): internal and external validation of smoking-status differences in respiratory symptoms

Background: Respiratory symptoms are common among smokers without COPD, yet symptom instruments are often optimized for established disease and may under-capture early changes relevant to cessation and tobacco harm reduction. We conducted a repeatability and replicability study of the Respiratory Symptom Experience Scale (RSES) in a rigorously phenotyped cohort to confirm both measurement stability and reproducible discrimination by smoking status. Methods: Healthy adults were recruited at a UK hospital and classified as current, former, or never smokers using self-report, exhaled CO, and a comprehensive panel of biomarkers of exposure. RSES was administered at Visit 1 and repeated after 7 ± 3 days at Visit 2 to assess test-retest repeatability. Known-group validity (discriminability by smoking status) was evaluated by comparing RSES scores across biochemically verified groups using non-parametric tests, with ANCOVA for exploratory covariate adjustment. True replicability across independent datasets was not formally tested in the present study. Results: Of 180 enrolled participants, 170 were included (55 current smokers, 60 former smokers, 55 never smokers) after excluding clinical ineligibility and biomarker-inconsistent smoking status. RSES demonstrated high repeatability (Pearson r = 0.87; Spearman ρ = 0.85) with minimal bias (- 0.07) and good agreement. RSES also showed consistent known-group discrimination by smoking status, differing between current and never smokers (p < 0.0001) and across all three groups (p < 0.0001). Current smokers reported higher scores than never (median 2.0 vs. 1.0) and former smokers (2.0 vs. 1.2), whereas former and never smokers did not differ (p = 0.686). Covariate adjustment did not materially alter results. Conclusions: RSES shows strong repeatability and consistent known-group discrimination by smoking status, supporting its use as a patient-relevant endpoint for cessation, and harm-reduction trials, as well as for clinical respiratory and regulatory research.