Respiratory and Cardiovascular Effects in COPD (KOLIN)
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Bronchoscopy
Sponsored by
About this trial
This is an interventional basic science trial for Pulmonary Disease, Chronic Obstructive focused on measuring Aging, Oxidative stress, Proteases, Bronchoscopy
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of COPD, GOLD stage 2-3.
- Smoking history of at least 10 packyears.
Exclusion Criteria:
- Severe ischemic heart disease.
- Other severe disease.
- Respiratory infection within four weeks.
Sites / Locations
- Department of Public Health and Clinical Medicine, Division of medicine, Pulmonary medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Other
Other
Other
Other
Arm Label
Healthy controls
Smokers
COPD rapid decline
COPD slow decline
Arm Description
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Outcomes
Primary Outcome Measures
Cellular senescence marker - Ki67
Endobronchial mucosal biopsies collected by bronchoscopy. Immunohistochemistry for the cellular senescence markers Ki67 will be performed.
Matrix metalloproteinase 12 (MMP12) and the inhibitor TIMP1
Airway lavages collected by bronchoscopy and serum will be analysed for MMP and TIMP using ELISAs.
Levels of oxidized proteins, 4 HNE
The accumulation of oxidized proteins, 4-Hydroxynonenal, will be assessed in bronchial biopsies.
Antioxidant-related transcription factor Nrf2
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor known to be induced by oxidative stress and related to cytoprotection.
Secondary Outcome Measures
Metals in airway lavages
Airway lavages collected by bronchoscopy will be analysed for metals using mass spectrometry
Lymphocyte subsets in bronchoalveolar lavage
Airway lavages collected by bronchoscopy will be analysed for lymphocyte subsets using flow cytometry.
Arterial stiffness
Non-invasive measurement of arterial stiffness
Full Information
NCT ID
NCT02729220
First Posted
February 24, 2016
Last Updated
April 5, 2016
Sponsor
Dr Annelie F Behndig, MD PhD
1. Study Identification
Unique Protocol Identification Number
NCT02729220
Brief Title
Respiratory and Cardiovascular Effects in COPD
Acronym
KOLIN
Official Title
Respiratory and Cardiovascular Effects in COPD - Report From a Bronchoscopy Investigation Based on the Obstructive Lung Disease In the Northern Sweden (OLIN) Studies
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr Annelie F Behndig, MD PhD
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to find out if subjects with chronic obstructive pulmonary disease have signs of accelerated ageing in their airways.
Detailed Description
The age-related impairment of innate immunity and antioxidant defenses likely impacts on development and disease progression of chronic obstructive pulmonary disease, COPD. It has been suggested that aging-related declines in function are accelerated in COPD due to recurrent cycles of inflammation, tissue injury and repair, associated with long-term exposure to cigarette smoke or other airway irritants. Here, the investigators aim to follow up on previous observations of impaired antioxidant responses in the lung of COPD patients, to establish the extent to which this reflects an accelerated aging phenotype, to characterize the molecular mechanisms resulting in this functional deficiency. The proposed studies will employ well-characterized patients with COPD of varying severity and smoking habits, as well as carefully age and smoking history-matched controls. Accelerated aging within the COPD lung will be assessed in endobronchial mucosal biopsies and airway macrophages by assessment of established senescence markers using immunohistochemical, biochemical and PCR-based methods. These markers of tissue age will then be related to the functional activation of transcription factors, known to be induced by oxidative stress and related to cytoprotection such as Nrf2 and AP1. The investigators will also examine whether COPD is associated with an enhanced secretion of inflammatory mediators from senescent cells, consistent with the accelerated aging paradigm and establish how this influences cell function. Deficiencies in metal handling, antioxidant defenses and diminished airway innate immune defenses at the air-lung interface will be assessed. The aim is to identify biomarkers for the risk of rapid lung function deterioration in COPD patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
Aging, Oxidative stress, Proteases, Bronchoscopy
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Healthy controls
Arm Type
Other
Arm Description
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Arm Title
Smokers
Arm Type
Other
Arm Description
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Arm Title
COPD rapid decline
Arm Type
Other
Arm Description
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Arm Title
COPD slow decline
Arm Type
Other
Arm Description
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Intervention Type
Other
Intervention Name(s)
Bronchoscopy
Intervention Description
Sampling of airways
Primary Outcome Measure Information:
Title
Cellular senescence marker - Ki67
Description
Endobronchial mucosal biopsies collected by bronchoscopy. Immunohistochemistry for the cellular senescence markers Ki67 will be performed.
Time Frame
Baseline
Title
Matrix metalloproteinase 12 (MMP12) and the inhibitor TIMP1
Description
Airway lavages collected by bronchoscopy and serum will be analysed for MMP and TIMP using ELISAs.
Time Frame
Baseline
Title
Levels of oxidized proteins, 4 HNE
Description
The accumulation of oxidized proteins, 4-Hydroxynonenal, will be assessed in bronchial biopsies.
Time Frame
Baseline
Title
Antioxidant-related transcription factor Nrf2
Description
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor known to be induced by oxidative stress and related to cytoprotection.
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
Metals in airway lavages
Description
Airway lavages collected by bronchoscopy will be analysed for metals using mass spectrometry
Time Frame
Baseline
Title
Lymphocyte subsets in bronchoalveolar lavage
Description
Airway lavages collected by bronchoscopy will be analysed for lymphocyte subsets using flow cytometry.
Time Frame
Baseline
Title
Arterial stiffness
Description
Non-invasive measurement of arterial stiffness
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of COPD, GOLD stage 2-3.
Smoking history of at least 10 packyears.
Exclusion Criteria:
Severe ischemic heart disease.
Other severe disease.
Respiratory infection within four weeks.
Facility Information:
Facility Name
Department of Public Health and Clinical Medicine, Division of medicine, Pulmonary medicine
City
Umeå
State/Province
Sverige
ZIP/Postal Code
SE-90185
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
33317530
Citation
Eriksson Strom J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Airway regulatory T cells are decreased in COPD with a rapid decline in lung function. Respir Res. 2020 Dec 14;21(1):330. doi: 10.1186/s12931-020-01593-9.
Results Reference
derived
PubMed Identifier
30526599
Citation
Eriksson Strom J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking. Respir Res. 2018 Dec 7;19(1):244. doi: 10.1186/s12931-018-0940-7.
Results Reference
derived
Learn more about this trial
Respiratory and Cardiovascular Effects in COPD
We'll reach out to this number within 24 hrs