Overview
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.
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.
Eligibility
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).