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.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Other: scleroderma health assessment questionnaire (SHAQ), BHT, and 6MWT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Other: scleroderma health assessment questionnaire (SHAQ), BHT, and 6MWT; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of breath-holding test with Borg Dyspnea Index	Borg Scale on a 0-10 point	Day 1 at inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of breath-holding time with 6 minute walk test (6MWT) distance	6MWT distance measured in meters according to American Thoracic Society guidelines	Day 1 at inclusion
Correlation of breath-holding time with oxygen saturation during 6MWT	Oxygen saturation monitored by wearable pulse oximeter (Radius PPG™ Tetherless Pulse Oximetry, Masimo Corp., Irvine, CA, USA)	Day 1 at inclusion
Correlation of breath-holding time with pulmonary function indices	Pulmonary function indices including FVC (%) and DLCO (%)	Day 1 at inclusion
Correlation of breath-holding time with data on the echocardiography	Echocardiography including left ventricular ejection fraction and pulmonary arterial systolic pressure (mmHg)	Day 1 at inclusion
Correlation of breath-holding time with scleroderma health assessment questionnaire (SHAQ)	SHAQ ranging from 0 to 3	Day 1 at inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of oxygen saturation during breath-holding test	Oxygen saturation monitored by radius or forehead pulse oximeter (Masimo Corp., Irvine, CA, USA)	Day 1 at inclusion
Changes of oxygen saturation during of 6MWT	Oxygen saturation monitored by wearable pulse oximeter (Radius PPG™ Tetherless Pulse Oximetry, Masimo Corp., Irvine, CA, USA)	Day 1 at inclusion
Responsiveness of breath-holding test	Correlation of Δbreath-holding test and ΔPulmonary function indices after 6months	Month 6 at inclusion
Reliability of breath-holding test	Additional 30 patients collection for test-retest reliability	Day 1, and Day 7~Day14 at inclusion
Development of the machine learning model to predict pulmonary parameters	Developing two cohorts: Cohort 1 for training a ML model and internal validation; and Cohort 2 for external validation	Year 2 at inclusion

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Study Director: Jina Yeo, MD, Seoul National University College of Medicine; Principal Investigator: Eun Bong Lee, MD PhD, Seoul National University College of Medicine

Publications and helpful links

General Publications

• ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available. Erratum In: Am J Respir Crit Care Med. 2016 May 15;193(10):1185.
• Hachulla E, Launay D. Diagnosis and classification of systemic sclerosis. Clin Rev Allergy Immunol. 2011 Apr;40(2):78-83. doi: 10.1007/s12016-010-8198-y.
• Morelli S, Ferrante L, Sgreccia A, Eleuteri ML, Perrone C, De Marzio P, Balsano F. Pulmonary hypertension is associated with impaired exercise performance in patients with systemic sclerosis. Scand J Rheumatol. 2000;29(4):236-42. doi: 10.1080/030097400750041389.
• Vandecasteele E, De Pauw M, De Keyser F, Decuman S, Deschepper E, Piette Y, Brusselle G, Smith V. Six-minute walk test in systemic sclerosis: A systematic review and meta-analysis. Int J Cardiol. 2016 Jun 1;212:265-73. doi: 10.1016/j.ijcard.2016.03.084. Epub 2016 Mar 25.
• Impens AJ, Wangkaew S, Seibold JR. The 6-minute walk test in scleroderma--how measuring everything measures nothing. Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v68-9. doi: 10.1093/rheumatology/ken273.
• Yeo J, Kim JY, Kim MH, Park JW, Park JK, Lee EB. Utility of the breath-holding test in patients with systemic sclerosis. Rheumatology (Oxford). 2022 Oct 6;61(10):4113-4118. doi: 10.1093/rheumatology/keac020.

Helpful Links

• Azza Slim, Abir Hedhli, Sana Cheikh Rouhou, et al. Maximal voluntary inspiratory breath holding time test in patients with chronic obstructive pulmonary disease. European Respiratory Journal 2018 52:PA4053

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2020
• Primary Completion (Actual): January 29, 2021
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Systemic sclerosis; Breath-holding test; Six minute walk test
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: H-2006-054-1131

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No