Ayumi Shimizu, Mitsunori Hino, Kaoru Kubota, Akiko Yoshikawa, Koichiro Kamio, Yosuke Tanaka, Masahiro Seike Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, JapanCorrespondence: Ayumi Shimizu, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1– 1-5 Sendagi, Bunkyo-ku, Tokyo, 113– 8602, Japan, 113– 8602, Email s7034@nms.ac.jpPurpose: Preserved ratio impaired spirometry (PRISm) is heterogeneous, and its physiological relationship to early COPD remains unclear. We compared respiratory-mechanical patterns between non-restrictive PRISm (NrP) and GOLD stage 1 COPD (GOLD 1) using impulse oscillometry (IOS) and spirometry and explored longitudinal changes in a trackable subset.Patients and Methods: We retrospectively analyzed 1,139 adults who underwent post-bronchodilator spirometry in 2013; IOS was available for a subset. PRISm was defined by FEV1/FVC ≥ LLN with %FEV1 10 pack-years, IgE < 170 U/L, eosinophils < 300/μL, and ≥ 2 examinations to minimize Th2-high asthma confounding.Results: Among PRISm cases, 18 met NrP criteria, and 127 met GOLD 1 criteria; IOS was available for all 18 NrP and for 39 GOLD 1 participants cross-sectionally. IOS indicated greater peripheral airway dysfunction in NrP than in GOLD 1, with higher R5–R20 and Fres and more negative X5, despite relatively preserved spirometric indices. In the longitudinal subset (39 GOLD 1; 8 NrP), annual changes in spirometry and IOS exhibited wide variability and did not differ meaningfully between groups. These analyses were limited by small NrP sample size and incomplete IOS availability.Conclusion: PRISm and GOLD 1 demonstrated distinct respiratory-mechanical patterns despite partially overlapping spirometric profiles. IOS identified peripheral airway abnormalities in PRISm that were not evident on spirometry, suggesting potential value for characterizing early or atypical airway dysfunction. However, sample-size limitations and major confounding factors—including age, smoking status, and bronchodilator exposure—preclude causal inference. Findings should be considered descriptive and hypothesis-generating. Larger prospective studies with balanced treatment exposure and comprehensive imaging and lung-volume assessment are needed to clarify the clinical relevance of IOS patterns in PRISm.Plain Language Summary: Some people have breathing problems that do not fit neatly into common categories such as asthma or chronic obstructive pulmonary disease (COPD). One such pattern is called preserved ratio impaired spirometry (PRISm). People with PRISm have reduced overall lung performance, even though a standard breathing test may still appear relatively normal.In this study of patients attending a respiratory clinic, we used a gentle, non-invasive test that measures how air moves through the small airways during quiet breathing. Compared with people who had very mild COPD, individuals with PRISm showed differences in these measurements, suggesting altered airway mechanics, even when standard lung tests appeared less impaired.These findings suggest that PRISm may involve different airway characteristics rather than simply representing an early stage of COPD. Tests that assess breathing during normal, relaxed breathing may provide additional information alongside standard lung tests and help doctors better understand and monitor this heterogeneous condition.Keywords: small airway disease, peripheral airway mechanics, airway resistance, early detection, lung function decline, phenotypic heterogeneity
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