Abstract
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 738-747 |
| Number of pages | 10 |
| Journal | Chest |
| Volume | 161 |
| Issue number | 3 |
| Early online date | 28 Oct 2021 |
| DOIs | |
| Publication status | Published - 1 Mar 2022 |
Bibliographical note
Funding Information:Author contributions: All authors are responsible for all content of the manuscript. All were involved in acquisition, analysis, and/or interpretation of the data presented in the manuscript, as well as critical revision of the manuscript. All authors approved submission of the final version of the manuscript, and all agreed to be accountable for all aspects of the submitted work. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: I. G. v. d. S. reports grants from Boehringer Ingelheim outside the submitted work and paid to her institution. C. C. M. reports grants and other from Boehringer Ingelheim paid to her institution. A. H. M.-v. d. Z. has received a research grant from Breathomix within the context of the P402 project (as described here); received research grants from GSK, Boehringer Ingelheim, AstraZeneca, and Vertex, all outside the submitted work; is the Principal Investigator of a P4O2 (Precision Medicine for More Oxygen) public private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, ORTEC LogiqCare, Philips, Quantib-U, Roche, Smartfish, SODAQ, Thirona, TopMD, and Novartis); and has served in advisory boards for AstraZeneca, GSK, and Boehringer Ingelheim with money paid to her institution. P. B. reports grants from Amsterdam UMC, Stichting Astma Bestrijding, Boehringer Ingelheim, and Vertex Pharmaceuticals, all outside the submitted work. M. S. W. reports grants and other from Boehringer Ingelheim and Hoffman-La Roche; and other from Respivant, Galapagos, Safara, Novartis, and Bristol Myers Squibb, all outside the submitted work and paid to her institution. None declared (J. C. O. M. L. L. P. L. A. v. D.). Role of the sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Additional information: The e-Appendexes and e-Figures can be found in the Supplemental Materials section of the online article. FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.
Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: I. G. v. d. S. reports grants from Boehringer Ingelheim outside the submitted work and paid to her institution. C. C. M. reports grants and other from Boehringer Ingelheim paid to her institution. A. H. M.-v. d. Z. has received a research grant from Breathomix within the context of the P402 project (as described here); received research grants from GSK , Boehringer Ingelheim , AstraZeneca , and Vertex , all outside the submitted work; is the Principal Investigator of a P4O2 (Precision Medicine for More Oxygen) public private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, ORTEC LogiqCare, Philips, Quantib-U, Roche, Smartfish, SODAQ, Thirona, TopMD, and Novartis); and has served in advisory boards for AstraZeneca, GSK, and Boehringer Ingelheim with money paid to her institution. P. B. reports grants from Amsterdam UMC , Stichting Astma Bestrijding , Boehringer Ingelheim , and Vertex Pharmaceuticals , all outside the submitted work. M. S. W. reports grants and other from Boehringer Ingelheim and Hoffman-La Roche ; and other from Respivant, Galapagos , Safara, Novartis , and Bristol Myers Squibb , all outside the submitted work and paid to her institution. None declared (J. C. O., M. L. L., P. L. A. v. D.).
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© 2021 The Author(s)