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BACKGROUND: Residual volume (RV) is a derived lung compartment that correlates with air trapping in the context of air flow obstruction on spirometry. The significance of an isolated elevation in RV in the absence of other pulmonary function test (PFT) abnormalities is not well defined. We sought to assess the clinical and radiologic findings associated with isolated elevation in RV. METHODS: We searched our out-patient PFT database at Mayo Clinic (Rochester, Minnesota) from 2016-2018 for adult patients with isolated elevation in RV. We defined isolated elevation in RV as RV ≥ upper limit of normal or ≥ 130% predicted with normal total lung capacity (TLC), spirometry, and diffusion capacity of the lung for carbon monoxide (DLCO). We then matched this high-RV group by age and sex to an equal number of individuals with normal RV, TLC, spirometry, and DLCO (normal-RV group). RESULTS: We identified 169 subjects with isolated elevation in RV on PFTs, with a median age of 73 y; 55.6% were female, and median body mass index was 26.8 (vs 29.8 in the normal-RV group). The median RV was 3.08 L (134% predicted, interquartile range [IQR] 130-141) in the high-RV group and 2.26 L (99% predicted, IQR 90-109) in the normal-RV group (P < .001). Subjects with high RV were more likely to have smoked (54% vs 40%, P = .01) and almost twice as likely to have a maximum voluntary ventilation < 30 times the FEV1 (21% vs 12%, P = .02). Clinically, asthma (21% vs 11%, P = .01) and non-tuberculous mycobacterial lung infections (12% vs 2%, P = .001) were more prevalent in the high-RV group. On chest computed tomography, bronchiectasis (31% vs 15%, P = .008), bronchial thickening or mucus plugging (46% vs 22%, P < .001), and emphysema (13% vs 5%, P = .046) were more common in the high-RV group. CONCLUSIONS: Isolated elevation in RV on PFTs is a clinically relevant abnormality associated with airway-centered diseases. [ABSTRACT FROM AUTHOR]