Title: The utility of gas transfer measurement to identify low total lung capacity

<bold>Introduction:</bold> Static lung volumes can be measured using gas dilution or plethysmography techniques. <bold>Aim:</bold> To explore the agreement of alveolar volume (VA) assessed by single breath gas transfer in detecting low total lung capacity (TLC) by plethysmography in different diseases. <bold>Methods:</bold> A retrospective analysis of lung function data between 2016 and 2023. Patients underwent single breath gas transfer and body plethysmography on the same visit according to ATS/ERS standards. Low VA defined as VA<LLN and low TLC defined as TLC<LLN. The GLI reference equations were used to calculate the LLN. Receiver operator characteristic analyses (ROC) assessed the agreement between VA and TLC, including sensitivity, specificity, and area under the curve (AUC) calculations. Analyses were 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%) showed a low TLC. Among those, 1585 (94%) had a low VA. Sensitivity, specificity and AUC were 94%, 89%, and 0.91 (95% CI; 0.90-0.92), respectively. There were significant differences in accuracy (p<0.0001) of low VA to detect low TLC with the AUC ranging from 0.87 (0.86-0.90) in COPD to 0.95 (0.92-0.97) in connective tissue disease. <bold>Conclusion:</bold> VA can be used as a surrogate for TLC, particularly in restrictive associated lung disease. Variation in comparisons is primarily driven by obstructive conditions overestimating the number of patients with low TLC.