Title: The utility of spirometry in the detection of low total lung capacity in clinical populations

<bold>Introduction:</bold> Low total lung capacity (TLC) detected by plethysmography, as a marker of restrictive lung disease, requires expensive specialist equipment. <bold>Aim:</bold> To determine the diagnostic role of spirometry in the detection of low TLC in different clinical populations. <bold>Methods:</bold> A retrospective analysis of lung function data obtained from consecutive patients between 2016 and 2023. Patients underwent spirometry and body plethysmography on the same visit according to ATS/ERS standards. Spirometric restriction was defined as FEV1/FVC≥LLN and FVC<LLN and low TLC as TLC<LLN. The Global Lung Initiative reference equations were used to calculate the LLN. Receiver operator characteristic analyses (ROC) were performed to assess the ability of spirometric restriction to accurately discriminate low TLC, including calculation of sensitivity, specificity, and area under the curve (AUC). Analyses were further stratified by diagnosis. Analyses performed using STATA version 17. <bold>Results:</bold> Out of 13,166 patients (50% male, age: 58±15 years, BMI: 28±6), 1,688 (13%) had low TLC and only 480 (28%) had an accompanying low FVC, showing that 72% of patients with low TLC were missed when spirometry was performed alone. Spirometry had a sensitivity of 27% and specificity of 99% for detecting low TLC, with an AUC of 0.63 (95% CI; 0.62-0.64). There were significant differences in diagnostic accuracy across diagnoses with the AUC ranging from 0.52 (0.47-0.57) in bronchiectasis to 0.69 (0.51-0.87) in graft-versus-host disease. <bold>Conclusion:</bold> Due to low sensitivity, spirometry is a poor predictor of true low TLC. Predictive ability varied depending on diagnosis.