Systemic Sclerosis: Can Breathomics help clinicians for ILD management? 

Authors: Thibault Massenet (1*), Judith Potjewijd (2), Rachid Tobal (2), Fanny Gester (3), Delphine Zanella (1), Monique Henket (3), Makon-Sébastien Njock (3), Thibaut Dejong (1), Gregory Gridelet (1), Laurie Giltay3, Françoise Guissard (3), Béatrice André (4), Clio Ribbens (4), Renaud Louis (3), Pieter Van Paassen (2), Julien Guiot (3), Pierre-Hugues Stefanuto (1)

Affiliations: 1 Molecular System, Organic & Biological Analytical Chemistry Group, University of Liege, Belgium. 2 Department of Internal Medicine, Division of Clinical and Experimental Immunology, Maastricht University Medical Center, Maastricht, The Netherlands. 3 Respiratory Medicine, CHU Liege, Belgium. 4 Rheumatology department, CHU Liège, Belgium. °co-last authors, they contributed equally to the research

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Abstract

Systemic sclerosis (SSc) is an autoimmune disease causing inflammation, blood vessel damage, and collagen deposition. Interstitial lung disease (ILD) is common in SSc, leading to significant mortality. Early detection of SSc-ILD is crucial, but current biomarkers are limited. Our previous research identified distinct volatile organic compound (VOC) patterns in SSc patients' breath (N=64)1. This study aims to establish standardized breath analysis procedures, and assess VOCs' potential in predicting SSc-ILD2. Two expert medical centers, the University Hospital of Liège (CHU), Belgium, and Maastricht University Medical Center (MUMC+), the Netherlands, collaborated in studying and recruiting 21 SSc patients and 21 SSc-ILD patients. Breath samples were collected at both centers in 5L Tedlar® bags. Volatiles were then transferred onto thermal desorption tubes and finally released and separated into a Pegasus GC-HRT 4D (GC×GC-MS). Nine VOCs were identified as discriminatory between SSc and SSc-ILD. The statistical model based on these markers achieved an AUC of 0.82, accuracy of 85%, sensitivity of 77% and a specificity of 100% for indentifying ILD phenotype, comparable to traditional lung function tests. A correlation was also observed between the functional respiratory parameters (i.e., DLco value) and the VOCs. Additionally, our study confirmed the potential of four terpenes in distinguishing SSc patients. Methodological SOPs for multi-center studies were developed. This study demonstrates the potential of breath analysis and in particular markers discovery in understanding SSc metabolic changes and could aid prompt ILD treatment. This study paves the way for improved diagnosis and management of SSc-ILD.

1. Zanella D, et al. Anal Bioanal Chem. doi:10.1007/S00216-021-03333-4 2. Massenet T, et al. ERJ Open Res. Breathomics to monitor interstitial lung disease associated with systemic sclerosis. doi:10.1183/23120541.00175-2024