Respiratory and Cardiovascular Effects in COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02729220
• Other study ID #: 2011-147_31M
• Status: Completed
• Phase: N/A
• First received: February 24, 2016
• Last updated: April 5, 2016
• Start date: January 2012

Study information

• Verified date: March 2016
• Source: University Hospital, Umeå
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review BoardSweden: Central Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 45 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chronic Disease
• Pulmonary Disease, Chronic Obstructive

Intervention

Other:
• Bronchoscopy
Sampling of airways

Locations

Country	Name	City	State
Sweden	Department of Public Health and Clinical Medicine, Division of medicine, Pulmonary medicine	Umeå	Sverige

Sponsors (1)

Lead Sponsor	Collaborator
Dr Annelie F Behndig, MD PhD

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cellular senescence marker - Ki67	Endobronchial mucosal biopsies collected by bronchoscopy. Immunohistochemistry for the cellular senescence markers Ki67 will be performed.	Baseline	No
Primary	Matrix metalloproteinase 12 (MMP12) and the inhibitor TIMP1	Airway lavages collected by bronchoscopy and serum will be analysed for MMP and TIMP using ELISAs.	Baseline	No
Primary	Levels of oxidized proteins, 4 HNE	The accumulation of oxidized proteins, 4-Hydroxynonenal, will be assessed in bronchial biopsies.	Baseline	No
Primary	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.	Baseline	No
Secondary	Metals in airway lavages	Airway lavages collected by bronchoscopy will be analysed for metals using mass spectrometry	Baseline	No
Secondary	Lymphocyte subsets in bronchoalveolar lavage	Airway lavages collected by bronchoscopy will be analysed for lymphocyte subsets using flow cytometry.	Baseline	No
Secondary	Arterial stiffness	Non-invasive measurement of arterial stiffness	Baseline	No