Respiratory and Cardiovascular Effects in COPD

NCT ID: NCT02729220

Last Updated: 2016-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy controls

Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness

Group Type: OTHER

Bronchoscopy

Intervention Type: OTHER

Sampling of airways

Smokers

Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness

Group Type: OTHER

Bronchoscopy

Intervention Type: OTHER

Sampling of airways

COPD rapid decline

Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness

Group Type: OTHER

Bronchoscopy

Intervention Type: OTHER

Sampling of airways

COPD slow decline

Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness

Group Type: OTHER

Bronchoscopy

Intervention Type: OTHER

Sampling of airways

Interventions

Bronchoscopy

Sampling of airways

Intervention Type: OTHER

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dr Annelie F Behndig, MD PhD

OTHER

Sponsor Role: lead

Responsible Party

Dr Annelie F Behndig, MD PhD

Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Department of Public Health and Clinical Medicine, Division of medicine, Pulmonary medicine

Umeå, Sverige, Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 33317530 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30526599 (View on PubMed)

Other Identifiers

2011-147_31M

Identifier Type: -

Identifier Source: org_study_id