Characterizing Mmp12 In Sputum And Its Relationship To Emphysema And Inflammatory Endotypes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Measure other T2 activity biomarkers in sputum
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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).
结局指标
主要结局
Measure other T2 activity biomarkers in sputum
时间窗: Baseline
Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many
Measure other T2 activity biomarkers in sputum supernatant
时间窗: 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
时间窗: Baseline
C reactive protein (CRP) in milligram/litre (mg/L)
Compare type-2 (T2) activity biomarkers with healthy individuals in sputum supernatant
时间窗: Baseline
Sputum supernatant: Levels of IL-4, IL-5 and IL-13, eosinophil peroxidase, TGF-beta, Phospho-Smad2 and Phospho-Smad3.
Quantify their alveolar destruction using Computed Tomography (CT) and magnetic resonance imaging (MRI)
时间窗: 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.
Compare type-2 (T2) activity biomarkers with healthy individuals in sputum
时间窗: Baseline
Sputum: enumeration of Free eosinophils granules (FEG) as few, moderate and many.
Blood and sputum matrix metalloproteinase-12 (MMP12) levels
时间窗: Baseline
Measure sputum and blood MMP12 levels
Compare type-2 (T2) activity biomarkers with healthy individuals in blood
时间窗: Baseline
C reactive protein (CRP) in milligram/litre (mg/L)
次要结局
未报告次要终点