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Respiratory and Cardiovascular Effects in COPD (KOLIN)

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ClinicalTrials.gov Identifier: NCT02729220
Recruitment Status : Completed
First Posted : April 6, 2016
Last Update Posted : April 6, 2016
Sponsor:
Information provided by (Responsible Party):
Dr Annelie F Behndig, MD PhD, University Hospital, Umeå

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.

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Other: Bronchoscopy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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 Start Date : January 2012
Actual Primary Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Arm Intervention/treatment
Healthy controls
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Other: Bronchoscopy
Sampling of airways

Smokers
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Other: Bronchoscopy
Sampling of airways

COPD rapid decline
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Other: Bronchoscopy
Sampling of airways

COPD slow decline
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
Other: Bronchoscopy
Sampling of airways




Primary Outcome Measures :
  1. Cellular senescence marker - Ki67 [ Time Frame: Baseline ]
    Endobronchial mucosal biopsies collected by bronchoscopy. Immunohistochemistry for the cellular senescence markers Ki67 will be performed.

  2. Matrix metalloproteinase 12 (MMP12) and the inhibitor TIMP1 [ Time Frame: Baseline ]
    Airway lavages collected by bronchoscopy and serum will be analysed for MMP and TIMP using ELISAs.

  3. Levels of oxidized proteins, 4 HNE [ Time Frame: Baseline ]
    The accumulation of oxidized proteins, 4-Hydroxynonenal, will be assessed in bronchial biopsies.

  4. Antioxidant-related transcription factor Nrf2 [ Time Frame: Baseline ]
    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 :
  1. Metals in airway lavages [ Time Frame: Baseline ]
    Airway lavages collected by bronchoscopy will be analysed for metals using mass spectrometry

  2. Lymphocyte subsets in bronchoalveolar lavage [ Time Frame: Baseline ]
    Airway lavages collected by bronchoscopy will be analysed for lymphocyte subsets using flow cytometry.

  3. Arterial stiffness [ Time Frame: Baseline ]
    Non-invasive measurement of arterial stiffness



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Ages Eligible for Study:   45 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02729220


Locations
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Sweden
Department of Public Health and Clinical Medicine, Division of medicine, Pulmonary medicine
Umeå, Sverige, Sweden, SE-90185
Sponsors and Collaborators
Dr Annelie F Behndig, MD PhD

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr Annelie F Behndig, MD PhD, Investigator, University Hospital, Umeå
ClinicalTrials.gov Identifier: NCT02729220     History of Changes
Other Study ID Numbers: 2011-147_31M
First Posted: April 6, 2016    Key Record Dates
Last Update Posted: April 6, 2016
Last Verified: March 2016

Keywords provided by Dr Annelie F Behndig, MD PhD, University Hospital, Umeå:
Aging
Oxidative stress
Proteases
Bronchoscopy

Additional relevant MeSH terms:
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Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive