Emphysema
Conditions
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREHyperpolarized 129Xe (Xenon) diffusion-weighted MRI
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
Sponsors
Foresee Pharmaceuticals Co., Ltd.
McMaster University
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Inclusion criteria
(COPD): * ≥40 years of age * Current or ex-smokers with a \>10 pack year smoking history * Have a post-bronchodilator forced expired volume in 1 second (FEV1)/forced expired vital capacity (FVC) ratio of \<70% and a post-bronchodilator FEV1 value from ≥30% predicted (GOLD 1, 2 and 3), (Global Initiative for Obstructive Lung disease) * Have a radiologist confirmed pulmonary emphysema diagnosis based on CT Inclusion criteria for normal controls: * No clinically significant medical condition or a history of asthma, COPD, cystic fibrosis, or other significant respiratory disorder including significant occupational or environmental exposures with ongoing respiratory symptoms. * No current or past smoking history * Have a post-bronchodilator FEV1/FVC ratio of \>70%
Exclusion criteria
Any potential subject who meets any of the following criteria will be excluded from participating in the study: * Patients with other non-COPD airway diseases * Patients with very severe COPD (FEV1\<30% predicted) * Patients with an intercurrent exacerbation * Patients with life expectancy less than 3 months * Pregnant or breastfeeding * Undergoing immunomodulatory or biologic treatment * Use of systemic steroids in the last month * Hospitalization in the last 12 months due to exacerbation * Known cardiovascular comorbidity under treatment or with hospitalizations of this cause in the last year * That they cannot perform spirometry * Active malignancy * Realization of lung surgery during the study period * History of alcohol and drug abuse that prevents compliance with follow-up * History of bronchial thermoplasty * Participating in another study concomitantly * MRI Related: patients who have implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, artificial limb, metallic fragments of foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood and sputum matrix metalloproteinase-12 (MMP12) levels | Baseline | Measure sputum and blood MMP12 levels |
| Quantify their alveolar destruction using Computed Tomography (CT) and magnetic resonance imaging (MRI) | Baseline | 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. |
| Measure other T2 activity biomarkers in sputum | Baseline | Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many |
| Measure other T2 activity biomarkers in sputum supernatant | Baseline | 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) |
| Measure other T2 activity biomarkers in blood | Baseline | Ferritin in microgram per litre (ug/L) |
| Compare type-2 (T2) activity biomarkers with healthy individuals in sputum | Baseline | Sputum: enumeration of Free eosinophils granules (FEG) as few, moderate and many. |
| Compare type-2 (T2) activity biomarkers with healthy individuals in blood | Baseline | Ferritin in microgram per litre (ug/L) |
| Compare type-2 (T2) activity biomarkers with healthy individuals in sputum supernatant | Baseline | Sputum supernatant: Levels of IL-4, IL-5 and IL-13, eosinophil peroxidase, TGF-beta, Phospho-Smad2 and Phospho-Smad3. |
Countries
Canada
Contacts
Primary ContactSarah Svenningsen, PhD
Backup ContactMelanie Kjarsgaard
Outcome results
None listed