Utility of Breath-holding Test in Systemic Sclerosis

Utility of Breath-holding Test for Assessment of Pulmonary Disease Severity in Patients With Systemic Sclerosis

This study aims to evaluate the utility of breath-holding test as a marker of pulmonary disease severity in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease of unknown etiology with high morbidity and mortality. SSc manifests by fibrosis of skin and internal organs. Although the underlying mechanisms are still subject to investigation, endothelial dysfunction and abnormal immune response are thought to contribute to vascular dysfunction and fibrosis in SSc. Pulmonary involvement, such as pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) is a major cause of death in SSc. Although the 6MWT is generally used for evaluating PAH and ILD, the utility in SSc is undetermined. Several investigators have found weak or moderate correlations of 6MWT in pulmonary involvement in SSc. The 6MWT is influenced by the status of all organ systems involved in exercise (pulmonary, cardiac, peripheral vascular, neuromuscular unit and muscle metabolism) as well as by specifics of test conditions. There is a pressing need for new, practical method which corroborates the current 6MWT for the evaluation of pulmonary disease severity in SSc. Breath-holding test (BHT) is one of the most useful methods for assessing the sensitivity of peripheral chemoreflex. Recent studies have demonstrated that BHT was correlated to pulmonary function test. BHT can be safely conducted and doctors handle a medical emergency during test easily as well. Therefore, this study evaluates the utility of BHT as surrogate marker of pulmonary involvement in patients with SSc.

Systemic sclerosis diagnosis according to 2013 American College of Rheumatology(ACR)/European League Against Rheumatism(EULAR) classification criteria

Participants will perform the SHAQ. BHT and 6MWT will be performed in the randomized way for each participant. For BHT, the participants will be told to sit comfortably on a chair, and breath normally. After 1 minute, they were required to make a maximum expiration followed by a maximum inspiration and to hold the breath as long as possible at maximum inspiratory level. This procedure was repeated three times, with 5-minute intervals between the tests. 6MWT will be performed according to the ATS guidelines. Information on CXR, TTE, and PFT (FVC%, DLCO%) will be obtained from the medical record if the data was obtained within 3 months. If not, the tests will be performed. BHT and PFT will be followed by six months after the first breath-holding test to confirm the responsiveness. Additional 30 patients with systemic sclerosis will be collected to perform the test-retest reliability of BHT.

Oxygen saturation monitored by wearable pulse oximeter (Radius PPG™ Tetherless Pulse Oximetry, Masimo Corp., Irvine, CA, USA)

Echocardiography including left ventricular ejection fraction and pulmonary arterial systolic pressure (mmHg)

Oxygen saturation monitored by wearable pulse oximeter (Radius PPG™ Tetherless Pulse Oximetry, Masimo Corp., Irvine, CA, USA)

Developing two cohorts: Cohort 1 for training a ML model and internal validation; and Cohort 2 for external validation

Inclusion Criteria: A diagnosis of systemic sclerosis according to 2013 ACR/EULAR criteria Must understand and voluntarily sign an informed consent form including writing consent for data protection Exclusion Criteria: The resting oxygen saturation by pulse oximetry < 90% in room air Unstable angina or myocardial infarction during the previous month Patients considered unable to the breath-holding test or 6 minute walk test

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