Using Thoracic Ultrasound to Detect Interstitial Lung Disease in Patients With Rheumatoid Arthritis (AURORA)

Using Thoracic Ultrasound in a Rheumatological Setting to Detect Interstitial Lung Disease in Patients With Rheumatoid Arthritis: Protocol for a Cross-Sectional Diagnostic Test Accuracy Study. AURORA.

Background: Pulmonary diseases are significant contributors to morbidity and mortality in patients with rheumatoid arthritis (RA). One of the most common pulmonary manifestation in RA is interstitial lung disease (RA-ILD). Consequently, RA-ILD may be prevalent in approximately 30% and clinically evident in about 10% of RA patients. Since the median survival for patients with manifest RA-ILD is only 6.6 years, feasible methods of detecting early RA-ILD are warranted.

Objectives: To determine the diagnostic accuracy of thoracic ultrasound (TUS), using a 14-zone protocol, for ILD in RA patients with respiratory symptoms by using chest high-resolution computed tomography (HRCT) as the reference standard. The secondary aim is to evaluate the diagnostic accuracy for the blood biomarkers surfactant protein-D (SP-D) and microfibrillar-associated protein 4 (MFAP4) in the detection of ILD in this group of patients.

Data collection: Participants will be included after signing the informed consent; data will be collected and stored in a REDCap database.

Eligibility criteria for participants and settings where data will be collected: Patients eligible for inclusion are consenting adults (≥18 years) diagnosed with RA (according to the 2010 ACR-criteria for RA) and respiratory symptoms indicating RA-ILD, based on the presence of at least one of the following symptoms: unexplained dyspnoea, unexplained cough and/or a residual pneumonia or a chest X-ray indicating interstitial abnormalities in the lung.

Whether participants form a consecutive, random or convenience series: Participants form a consecutive series of up to 80 individuals in total.

Description of the index test and reference standard: Patients suspected of having RA-ILD will undergo a 14 zone TUS as index test performed by a junior resident in rheumatology, who is certified by the European Respiratory Society in performing TUS assessment. The anonymised images will be stored, and scored by the junior resident and two senior rheumatologists, who have also received training in TUS, as well as a TUS and ILD experienced pulmonologist. Chest HRCT will be the gold standard, i.e. the ILD reference standard.

Estimates of diagnostic accuracy and their precision: The two basic measures for quantifying the diagnostic accuracy of the TUS (index) test are the sensitivity and specificity in comparison to the chest HRCT. Statistical tests will be conducted using the McNemar test for correlated proportions.

Study Overview

• Status: Completed
• Conditions: Lung Diseases, Interstitial; Rheumatoid Arthritis and Associated Conditions
• Intervention / Treatment: Diagnostic test: National guideline treatment

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

• Study Contact: Name: Torkell Ellingsen, MD, PhD; Phone Number: 0045 29177002; Email: torkell.ellingsen@rsyd.dk
• Study Contact Backup: Name: Bjørk K Sofíudóttir, MD; Email: bjork.k.sofiudottir@rsyd.dk

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Rheumatology Research Unit, Dept. of Rheumatology, OUH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Eligible patients will be recruited from the Department of Rheumatology in the Hospital of South West Jutland, Odense University Hospital - Svendborg Hospital, Lillebaelt Hospital and Odense University Hospital (OUH). Patients coming inn for a planned control of their RA disease and management, will be asked if they have respiratory symptoms. If respiratory symptoms are present, the patient will receive oral information about this project and those who are interested in participating, will receive written information as well as a signed consent form (not yet to be signed). Subsequently, the patients will be referred to the highly specialized unit in the Department of Rheumatology at OUH as well as a full clinical evaluation in the PUlmo-REuma (PURE) Clinic located at OUH.

Description

Inclusion Criteria:

• Patients eligible for inclusion are consenting adults (≥18 years) diagnosed with RA, with presence of at least one of the following symptoms: unexplained dyspnoea, unexplained cough, residual pneumonia or a chest X-ray indicating interstitial lung disease. All patients must fulfil the 2010 criteria for RA. A diagnosis of COPD does not exclude the patient from the study.

Exclusion Criteria:

• Patients with other systemic autoimmune diseases than RA (except secondary Sjøgrens syndrome) will be excluded. Other exclusion criteria are; previous or active lung cancer, lung transplant recipients and patients with known ILD or congenital lung disease, as well as patients who have had an HRCT performed within 12 months prior to the inclusion date. Patients who are unwilling or unable to provide written informed consent will also be excluded (i.e. not eligible).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RA-ILD	Estimates of diagnostic accuracy and precision: The diagnostic accuracy of the TUS (index) test for interstitial lung disease in rheumatoid arthritis in comparison to the chest HRCT.	31.01.2024

Collaborators and Investigators

• Sponsor: Torkell Ellingsen
• Investigators: Principal Investigator: Torkell Ellingsen, MD, PhD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Actual): May 15, 2023
• Study Completion (Actual): June 2, 2023

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: May 25, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Lung Diseases; Lung Diseases, Interstitial
• Other Study ID Numbers: S-20210154

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from the AURORA study will be stored in the Danish Data Archive (DDA) when data have been analysed and published. Through an agreement with the Danish Data Protection agency, the DDA preserves data materials containing personal identifiers. Data and the personal identifiers will be stored separately and special permits are required for access to the data. Data will be available on request for academic researchers.
• IPD Sharing Time Frame: 31.01.2024 - 31.01.2034
• IPD Sharing Access Criteria: Data will be available on request for academic researchers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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