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| Name | Class |
|---|---|
| Foresee Pharmaceuticals Co., Ltd. | INDUSTRY |
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The hypothesis is that in patients with emphysema, a high MMP12 sputum and/or blood level correlates with airspace enlargement and with increased sputum Th2 immune biomarkers.
Since MMP-12 apparently has a preponderant role in the genesis of emphysema and probably in airspace enlargement, its inhibition may result in an interesting targeting point in view to find specific therapies in obstructive diseases. There is abundant evidence in animal models that shows how MMP-12 blockade inhibits the development of emphysema and airway remodeling. Unfortunately, the results have not been conclusive in human models.
In the last years, pulmonary imaging biomarkers that measure airspace enlargement have been developed. In particular, the apparent diffusion coefficient (ADC), quantified by inhaled hyperpolarized gas MRI, reflects alveolar airspace size. ADC provides information consistent with histopathological findings that may be used to estimate lung disease progression and treatment response.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with emphysema and eosinophilia in blood and sputum | blood eosinophils ≥300 cells/μL and sputum eosinophils >3% |
| |
| Patients with emphysema and paucicellular inflammation | sputum neutrophils <65% and eosinophils <3% |
| |
| Patients with emphysema and sputum neutrophilia | sputum neutrophils >65% and sputum eosinophils < 3% |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI | Procedure | Participants will inhale a one litre gas mixture containing hyperpolarized 129Xe mixed with nitrogen (N2) or helium (4He) from a one litre dose bag. Breath-hold will be up to 16 seconds |
| Measure | Description | Time Frame |
|---|---|---|
| Blood and sputum matrix metalloproteinase-12 (MMP12) levels | Measure sputum and blood MMP12 levels | Baseline |
| Quantify their alveolar destruction using Computed Tomography (CT) and magnetic resonance imaging (MRI) | The relative area of the Computed Tomography (CT) attenuation histogram with attenuation of 950 HU or less (RA950) and the 15th percentile of the CT attenuation histogram (HU15) will be generated to quantify emphysema. For analysis of 129Xe diffusion-weighted MR images we will employ the same approach as described by Kirby and colleagues to quantify the apparent diffusion coefficient (ADC) and generate ADC maps12 to assess airspace size. | Baseline |
| Measure other T2 activity biomarkers in sputum | Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many | Baseline |
| Measure other T2 activity biomarkers in sputum supernatant | Sputum supernatant: Levels of (interleukin) IL-4, IL-5 and IL-13, eosinophil peroxidase, transforming growth factor (TGF)-beta, Phospho-Smad2 and Phospho-Smad3 (SMAD=Small Mothers Against Decapentaplegic gene) | Baseline |
| Measure other T2 activity biomarkers in blood | Ferritin in microgram per litre (ug/L) | Baseline |
| Measure other T2 activity biomarkers in blood | C reactive protein (CRP) in milligram/litre (mg/L) | Baseline |
| Compare type-2 (T2) activity biomarkers with healthy individuals in sputum |
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Inclusion Criteria (COPD):
Inclusion criteria for normal controls:
Exclusion Criteria:
Any potential subject who meets any of the following criteria will be excluded from participating in the study:
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This is a cross-sectional study in healthy controls and patients with pulmonary emphysema.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sarah Svenningsen, PhD | Contact | 905-522-1155 | 33024 | svennins@mcmaster.ca |
| Melanie Kjarsgaard | Contact | 905-522-1155 | 33024 | mkjarsga@stjoes.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Firestone Institute for Respiratory Health, St. Joseph's Healthcare | Recruiting | Hamilton | Ontario | L8N 4A6 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22591724 | Background | Shukla Y, Wheatley A, Kirby M, Svenningsen S, Farag A, Santyr GE, Paterson NA, McCormack DG, Parraga G. Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. Acad Radiol. 2012 Aug;19(8):941-51. doi: 10.1016/j.acra.2012.03.018. Epub 2012 May 15. | |
| 26645414 | Background |
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| ID | Term |
|---|---|
| D004646 | Emphysema |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D014978 | Xenon |
| ID | Term |
|---|---|
| D005741 | Noble Gases |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D005740 | Gases |
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Sputum
Sputum: enumeration of Free eosinophils granules (FEG) as few, moderate and many. |
| Baseline |
| Compare type-2 (T2) activity biomarkers with healthy individuals in blood | Ferritin in microgram per litre (ug/L) | Baseline |
| Compare type-2 (T2) activity biomarkers with healthy individuals in blood | C reactive protein (CRP) in milligram/litre (mg/L) | Baseline |
| Compare type-2 (T2) activity biomarkers with healthy individuals in sputum supernatant | Sputum supernatant: Levels of IL-4, IL-5 and IL-13, eosinophil peroxidase, TGF-beta, Phospho-Smad2 and Phospho-Smad3. | Baseline |
| Ostridge K, Williams N, Kim V, Bennett M, Harden S, Welch L, Bourne S, Coombs NA, Elkington PT, Staples KJ, Wilkinson TM. Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD. Thorax. 2016 Feb;71(2):126-32. doi: 10.1136/thoraxjnl-2015-207428. Epub 2015 Dec 8. |
| 23931643 | Background | Nair P, Ochkur SI, Protheroe C, Radford K, Efthimiadis A, Lee NA, Lee JJ. Eosinophil peroxidase in sputum represents a unique biomarker of airway eosinophilia. Allergy. 2013 Sep;68(9):1177-84. doi: 10.1111/all.12206. Epub 2013 Aug 9. |