Utility of microRNAs in Exhaled Breath Condensate as Diagnostic Biomarkers to Differentiate Pulmonary Sarcoidosis from Pulmonary Tuberculosis

Divyanjali Rai; Adwika PP; Jaya Tak; Sunil Bangaru; Bijay Pattnaik; Sunita  Yadav; Seetu Kumari; Jyoti Kumari; Umashankar verma; Geetika Yadav; RS Dhaliwal; Naveen Bhatraju; Saurabh Mittal; Pawan Tiwari; Vijay Hadda; Karan Madan; Anurag Agrawal; Randeep Guleria; Rohit Vadala; Sachin Kumar; Anant Mohan

doi:10.36141/svdld.v42i4.16920

Authors

Divyanjali Rai Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Adwika PP Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA https://orcid.org/0009-0001-1131-1328
Jaya Tak Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI,INDIA
Sunil Bangaru Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Bijay Pattnaik Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Sunita Yadav Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Seetu Kumari Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Jyoti Kumari Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Umashankar verma Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Geetika Yadav INDIAN COUNCIL OF MEDICAL RESEARCH, NEW DELHI, INDIA
RS Dhaliwal INDIAN COUNCIL OF MEDICAL RESEARCH, NEW DELHI, INDIA
Naveen Bhatraju TRIVEDI SCHOOL OF BIOSCIENCES, ASHOKA UNIVERSITY, SONIPAT, HARYANA, INDIA
Saurabh Mittal Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Pawan Tiwari Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Vijay Hadda Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Karan Madan Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Anurag Agrawal TRIVEDI SCHOOL OF BIOSCIENCES, ASHOKA UNIVERSITY, SONIPAT, HARYANA, INDIA
Randeep Guleria Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Rohit Vadala Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Sachin Kumar DEPARTMENT OF MEDICAL ONCOLOGY, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Anant Mohan Department of Pulmonary, Critical Care & Sleep Medicine, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA

Keywords:

exhaled breath, microRNAs, Biomarkers, Sarcoidosis

Abstract

Background and aim: Pulmonary sarcoidosis and pulmonary tuberculosis (PTB) are two granulomatous diseases with similar clinical presentations. This study explored the potential of microRNAs (miRNAs) in exhaled breath condensate (EBC) as non-invasive diagnostic biomarkers to distinguish between pulmonary sarcoidosis and PTB.

Methods: EBC samples were collected from 46 participants (20 with PTB, 26 with pulmonary sarcoidosis) and 20 healthy controls and miRNA profiling was done. Differentially expressed miRNAs were further validated using qRT-PCR in independent cohorts in EBC (17 PTB, 18 sarcoidosis, and 25 controls) and blood (10 PTB, 10 sarcoidosis, and 10 controls).

Results: Initial profiling identified 19 miRNAs differentially expressed between pulmonary sarcoidosis and PTB, one between sarcoidosis and controls, and 22 between PTB and controls. The top five upregulated miRNAs (miR-132, miR-362-5p, miR-181c, miR-181a, and miR-512-3p) and two downregulated miRNAs (miR-454 and miR-139-5p) in sarcoidosis compared to PTB were selected for validation. Validation showed significant downregulation (p value <0.05) of only miR-454 in EBC of sarcoidosis patients compared to PTB patients with an optimal AUC of 0.663. miR-150* discriminated sarcoidosis patients from healthy controls with an AUC of 0.982. When PTB were compared to healthy controls, miR-454 and miR-139-5p were discriminating both groups with AUCs of 0.991 and 0.994 respectively in EBC.

Conclusions: These findings suggest that while miR-454 differentiated pulmonary sarcoidosis from pulmonary tuberculosis, their clinical utility in EBC is limited. Further investigation is needed to explore their diagnostic potential, and to improve diagnostic accuracy in EBC.

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