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Background: Diagnosing sarcoidosis can be challenging, and a noninvasive diagnostic method is lacking. The electronic nose (eNose) technology profiles volatile organic compounds in exhaled breath and has potential as a point-of-care diagnostic tool.Research Question: Can eNose technology be used to distinguish accurately between sarcoidosis, interstitial lung disease (ILD), and healthy control subjects, and between sarcoidosis subgroups?Study Design and Methods: In this cross-sectional study, exhaled breath of patients with sarcoidosis and ILD and healthy control subjects was analyzed by using an eNose (SpiroNose). Clinical characteristics were collected from medical files. Partial least squares discriminant and receiver-operating characteristic analyses were applied to a training and independent validation cohort.Results: The study included 252 patients with sarcoidosis, 317 with ILD, and 48 healthy control subjects. In the validation cohorts, eNose distinguished sarcoidosis from control subjects with an area under the curve (AUC) of 1.00 and pulmonary sarcoidosis from other ILD (AUC, 0.87; 95% CI, 0.82-0.93) and hypersensitivity pneumonitis (AUC, 0.88; 95% CI, 0.75-1.00). Exhaled breath of sarcoidosis patients with and without pulmonary involvement, pulmonary fibrosis, multiple organ involvement, pathology-supported diagnosis, and immunosuppressive treatment revealed no distinctive differences. Breath profiles differed between patients with a slightly and highly elevated soluble IL-2 receptor level (median cutoff, 772.0 U/mL; AUC, 0.78; 95% CI, 0.64-0.92).Interpretation: Patients with sarcoidosis can be distinguished from ILD and healthy control subjects by using eNose technology, indicating that this method may facilitate accurate diagnosis in the future. Further research is warranted to understand the value of eNose in monitoring sarcoidosis activity. [ABSTRACT FROM AUTHOR]