4DX for the Diagnosis of Constrictive Bronchiolitis

Utility of a Novel Imaging Algorithm (4DX) for the Diagnosis of Constrictive Bronchiolitis

Constrictive bronchiolitis is an uncommon lung disease that has been described in Veterans of conflicts in Iraq and Afghanistan. Although these Veterans have evidence of constrictive bronchiolitis on lung biopsies, non-invasive tests such as pulmonary function tests (PFTs) are often normal. This study will determine whether analysis of fluoroscopy images using the 4Dx XV Ventilation Analysis software developed by 4D Medical will be able to detect constrictive bronchiolitis in Veterans better than PFTs.

Study Overview

• Status: Completed
• Conditions: Constrictive Bronchiolitis
• Intervention / Treatment: Diagnostic test: X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis

Detailed Description

Constrictive (or obliterative) bronchiolitis is a rare pulmonary disease characterized by subepithelial inflammatory and fibrotic narrowing of the bronchioles on histologic analysis, which often presents with nonspecific symptoms such as progressive dyspnea on exertion and nonproductive cough over weeks to months. Constrictive bronchiolitis may be triggered by autoimmune disease, chronic allograft rejection in lung transplant recipients, graft versus host disease in stem cell transplant recipients, viral illness, or inhaled toxins. Although pulmonary function tests (PFTs) may be helpful for the diagnosis of constrictive bronchiolitis, a study performed by King and colleagues in 2009 found that many Veterans with biopsy-proven constrictive bronchiolitis had normal PFTs. Thus, for these patients, more sensitive methods of noninvasive testing are needed.

4Dx XV Ventilation Analysis is a new imaging analysis algorithm which utilizes standard fluoroscopy to quantify ventilation with sufficient fidelity to identify regional differences. Fluoroscopic images of a single tidal breath are obtained at 5 distinct angles (direct AP, +/- 36 degrees, and +/- 72 degrees). Readouts from the 4Dx XV Ventilation Analysis include absolute value of total lung ventilation, heterogeneity of lung ventilation, a frequency distribution of lung ventilation as a line plot, and a regional map of lung ventilation. In addition, an expiratory time constant (time to exhale 63% of the tidal volume), heterogeneity of the expiratory time constant, frequency distribution of expiratory time constant as a line plot, and a regional map of expiratory time constant are also calculated. Pilot studies performed by 4D Medical show data generated by the 4Dx XV Ventilation Analysis software applied to fluoroscopy is reproducible in individuals with normal lung function and the heterogeneity index increases in individuals undergoing radiation therapy.

The investigators hypothesize that the 4Dx XV Ventilation Analysis program, when applied to standard fluoroscopic images, is more sensitive for the diagnosis of constrictive bronchiolitis than PFTs in Veterans with constrictive bronchiolitis. Specific metrics that will be evaluated with the software include ventilation heterogeneity and expiratory phase constants, among other metrics. Endpoints will be compared during tidal breathing and a full exhalation to residual volume from functional residual capacity.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Constrictive bronchiolitis arm:

• Biopsy demonstrating constrictive bronchiolitis
• Prior CT Chest
• 18-60 years old
• < 1 pack year history of tobacco use

Control arm:

• 18-60 years old
• Prior CT Chest without evidence chronic lung disease as judged by a Pulmonologist
• No clinically significant dyspnea or functional limitations
• < 1 pack year history of tobacco use

Exclusion Criteria (for both arms)

• Pregnancy (as determined by testing on the morning prior to fluoroscopy)
• Inability to undergo PFTs or fluoroscopy
• Inability to raise arms above a 90-degree angle

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Constrictive Bronchiolitis; Veterans with surgical lung biopsy-proven constrictive bronchiolitis	Diagnostic test: X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis; Fluoroscopy will be performed for a complete tidal breath and full exhalation at 5 angles (AP, +/- 36 degrees from AP, and +/- 72 degrees from AP) while the patient's arms are raised overhead. 4Dx XV Ventilation Analysis software will be used to analyze these images. Both groups will also undergo pulmonary function testing and take a questionnaire regarding respiratory symptoms.
Active Comparator: Controls; Control patients with minimal smoking history and no chronic lung disease or respiratory symptoms	Diagnostic test: X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis; Fluoroscopy will be performed for a complete tidal breath and full exhalation at 5 angles (AP, +/- 36 degrees from AP, and +/- 72 degrees from AP) while the patient's arms are raised overhead. 4Dx XV Ventilation Analysis software will be used to analyze these images. Both groups will also undergo pulmonary function testing and take a questionnaire regarding respiratory symptoms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
X-ray velocimetry results	Heterogeneity of ventilation as detected by X-ray velocimetry	1 month

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: 4DMedical

Publications and helpful links

General Publications

• King MS, Eisenberg R, Newman JH, Tolle JJ, Harrell FE Jr, Nian H, Ninan M, Lambright ES, Sheller JR, Johnson JE, Miller RF. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011 Jul 21;365(3):222-30. doi: 10.1056/NEJMoa1101388. Erratum In: N Engl J Med. 2011 Nov 3;365(18):1749.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2021
• Primary Completion (Actual): May 27, 2022
• Study Completion (Actual): May 27, 2022

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 30, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: fluoroscopy; X-ray velocimetry
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis; Bronchiolitis Obliterans
• Other Study ID Numbers: 200473

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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