Hyperpolarized Xenon-129 MRI: a New Multi-dimensional Biomarker to Determine Pulmonary Physiologic Responses to COPD Therapeutics

• Anoro Ellipta (Drug), also known as umeclidinium + vilanterol: inhaler approved by FDA (strength umeclidinium 65 microgram + vilanterol 25 microgram) One puff once a day for 30 days
• Arnuity Ellipta (Drug), also known as fluticasone: inhaler approved by FDA (strength 250 microgram) One puff twice a day for 30 days

Primary outcomes

• Changes in the hyper polarized MRI xenon-129 MRI (HXe MRI) assessment pre-post 30-day treatment of umeclidinium+vilanterol or Flovent [Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: In vivo lung physiology measurement obtained by HXe MRI pre and post drug intervention. In vivo lung physiology is measured by % of the lung that does not ventilate (dead space ventilation), among of the dissolved xenon-129 gas location among airways, interstitial tissues, or circulating red blood cells. These measures will be reported as continuous variables for data analyses.

Secondary outcomes

• High resolution CT of lung [First baseline only=day 0]: Quantification of emphysematous lung tissues and abnormally thickened airways in correlation with changed detectable by HXe MRI. % of lung tissues with emphysema will be quantified by measuring tissue density using Hounsfield Unit (HU). Based on COPDgene and other studies, we will use HU < -950 as emphysematous lung tissue. The lung CT scan will then be processed to yield % of lung tissue with emphysema. The airway thickness will be measured by standardized imaging algorithm developed by VIDA imaging.
• Changes in pulmonary Function Test (PFT) from pre to post-umeclidinium+vilanterol or Flovent [Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: Measurement of in vivo lung physiology using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. The gas exchange capacity will be assessed by diffusion capacity of carbon monoxide represented as percent DLCO. This is a standard clinical measure being used routinely in pulmonary clinics.
• Changes in Baseline Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent [Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.
• Changes in Transient Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent [Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.
• Changes in Saint George's Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent [Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.
• Changes in Chronic Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent [Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention. Quality of life survey will be administered to obtain numeric number as a results.
• Changes in BODE score from pre to post-umeclidinium+vilanterol or flovent [Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. BODE score is calculated by the results from the pulmonary function test, modified medical research council score, and body mass index. This will yield a score ranging from 0 to 10 with higher scores predicting higher chance of mortality.
• Changes in GOLD Stage from pre to post-umeclidinium+vilanterol or flovent [Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67]: Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. GOLD stage is calculated by a combination of pulmonary function test result, modified medical research council score, and history of frequency of COPD exacerbation previous 12 months. This score will yield GOLD stages A (mild) to , B, C, D (most severe).

Sex: All, ages: 18 Years to 85 Years

Inclusion Criteria:

* post bronchodilator PFT spirometry FEV1/FVC < 70% predicted
* History of diagnosis of COPD
* History of alpha 1 anti-trypsin deficiency

Exclusion Criteria:

* previous diagnosis of asthma, interstitial lung disease, pulmonary vascular disease, inability to complete MRI or any of the assessment testings.

• Results publication: Qing K, Ruppert K, Jiang Y, Mata JF, Miller GW, Shim YM, Wang C, Ruset IC, Hersman FW, Altes TA, Mugler JP 3rd. Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI. J Magn Reson Imaging. 2014 Feb;39(2):346-59. doi: 10.1002/jmri.24181. Epub 2013 May 16. PMID 23681559
• Results publication: Qing K, Mugler JP 3rd, Altes TA, Jiang Y, Mata JF, Miller GW, Ruset IC, Hersman FW, Ruppert K. Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI. NMR Biomed. 2014 Dec;27(12):1490-501. doi: 10.1002/nbm.3179. Epub 2014 Aug 22. PMID 25146558

• Yun M Shim, MD, Principal investigator, University of Virginia
• Kun Qing, PhD, Principal investigator, University of Virginia