4DX for the Diagnosis of Constrictive Bronchiolitis
Condition: Constrictive Bronchiolitis
MeSH terms: Bronchiolitis; Bronchiolitis Obliterans; Organizing Pneumonia
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis
Intervention type(s): Diagnostic Test
Intervention description(s): 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.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: 4Dx XV Ventilation Analysis applied to fluoroscopic images
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: fluoroscopy; X-ray velocimetry