Changes in Inflammatory Markers During Pulmonary Rehabilitation Based on Exacerbation States in COPD

NCT02740686 | Completed

• 1 other identifier: 16/LO/0865
• Study Type: observational
• Target: 85
• Locations: 1 country
• Sites: 6

Brief Summary

This study will examine the inflammatory response to exercise encompassed as part of a standard pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease (COPD). Patients will be split into two groups, frequent exacerbators or infrequent exacerbators, dependent upon exacerbation history to compare responses to pulmonary rehabilitation amongst phenotypes.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Exercise; Immunity; Inflammation; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Concentration of inflammatory markers in plasma and sputum (C-reactive protein, Fibrinogen, Interleukin(IL)-6, IL-8

  July 2016 - August 2018

Secondary Outcomes (8)

• Changes in the expression of anti-inflammatory genes

  July 2016 - August 2018

• Total and differential blood leukocyte count

  July 2016 - August 2018

• Pre-activation and activation of blood neutrophils using flow cytometry

  July 2016 - August 2018

• Pro-coagulant and pro-inflammatory microparticle signatures in plasma

  July 2016 - August 2018

• Severe, moderate and mild exacerbations (number of /days to defined events, severity, recovery)

  July 2016 - August 2018

Study Arms (4)

Frequent exacerbators

Exacerbations will be defined as "a respiratory event which led to a hospitalisation or the prescription of antibiotics and/or oral corticosteroids". Clinicians will ask patients to retrospectively recall how many exacerbations they have had in the past 12 months. Patients will be allocated to the frequent exacerbators group based on whether they have had 2 or more hospitalisations for exacerbations or have taken 2 or more courses on steroids/antibiotics within the past 12 months. Blood sample collection at the following pulmonary rehabilitation sessions: 1st (pre-exercise), 2nd (pre and post-exercise), 8th (pre-exercise), last session (pre and post exercise). Sputum samples collected pre-exercise at the following pulmonary rehabilitation sessions: 1st, 8th, and last session.

Other: Sample collection

Infrequent exacerbators

Exacerbations will be defined as "a respiratory event which led to a hospitalisation or the prescription of antibiotics and/or oral corticosteroids". Clinicians will ask patients to retrospectively recall how many exacerbations they have had in the past 12 months. Patients will be allocated to the infrequent exacerbators group based on whether they have had no more than 1 hospitalisation for exacerbations or have not taken more than 1 course of steroids/antibiotics within the past 12 months. Blood sample collection at the following pulmonary rehabilitation sessions: 1st (pre-exercise), 2nd (pre and post-exercise), 8th (pre-exercise), last session (pre and post exercise). Sputum samples collected pre-exercise at the following pulmonary rehabilitation sessions: 1st, 8th, and last session.

Other: Sample collection

Healthy smokers

Recruited in accordance with inclusion/exclusion criteria with no medical history of COPD diagnosis and currently smoke.This group will be recruited by a nurse using medical records to assess smoking status and age-matching to the COPD groups. A resting blood sample will be taken from these patients and used to compare baseline measurements with the COPD groups.

Other: Sample collection

Healthy never smokers

Recruited in accordance with inclusion/exclusion criteria with no medical history of COPD diagnosis and have never smoked.This group will be recruited by a nurse using medical records to assess smoking status and age-matching to the COPD groups. Resting blood samples will be taken from these patients and used to compare baseline measurements with the COPD groups.

Other: Sample collection

Interventions

Sample collection OTHER

Frequent exacerbators and infrequent exacerbators will have blood and sputum samples obtained around pulmonary rehabilitation. No other intervention will be administered. Healthy controls will have resting blood samples taken.

Frequent exacerbators; Healthy never smokers; Healthy smokers; Infrequent exacerbators

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

116 COPD patients, confirmed by diagnosis, will be recruited (58 frequent and 58 infrequent exacerbators in accordance with criteria listed above) to the study who have been referred to, and are about to enrol, on pulmonary rehabilitation. 20 healthy smokers and 20 healthy never smokers will be recruited for baseline measurements to compare with COPD patients.

You may qualify if:

• frequent exacerbators and 58 infrequent exacerbators (116 in total) who have been diagnosed with any severity of COPD (according to BTS criteria, i.e. \>10 pack year smoking history and post bronchodilator spirometry FEV1/FVC ratio \<0.70 and FEV\<80%).

You may not qualify if:

• Inability or unwillingness to sign informed consent
• Any unstable ongoing cardiovascular events which may be exacerbated by exercise
• Inability to complete walk tests due to physical or mental impairment
• Other active inflammatory conditions e.g. rheumatoid arthritis, cancer.
• Known asthma, allergic rhinitis or other respiratory disease (bronchiectasis, pulmonary fibrosis)
• Healthy control group - Patients who have not been diagnosed with COPD or any other respiratory condition and are characteristically (age (between 45-85 years old) \& smoking status) matched to recruited COPD patients.

Sponsors & Collaborators

• University of Lincoln: lead
• National Health Service, United Kingdom: collaborator

Study Sites (6)

Lindum Medical Practice

Lincoln, Lincolnshire, LN2 2JP, United Kingdom

Location

Nettleham Medical Practice

Lincoln, Lincolnshire, LN2 2RS, United Kingdom

Location

Welton Surgery

Lincoln, Lincolnshire, LN2 3JH, United Kingdom

Location

Birchwood Medical Practice

Lincoln, Lincolnshire, LN6 0QQ, United Kingdom

Location

Sudbrooke Drive Community Centre

Lincoln, LN2 2EF, United Kingdom

Location

Bracebridge Community Centre

Lincoln, LN5 8QS, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood samples will be used on the day of collection and analysed before being appropriately disposed of on the same day. Blood samples will be centrifuged with separated plasma to be frozen at -80c for later analysis of cellular content. Sputum samples will also be centrifuged with supernatant extracted and frozen -80c for later analysis.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Motor Activity; Inflammation

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Alex R Jenkins, MPhil

  PhD student

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mr Alex Jenkins

Study Record Dates

• First Submitted: April 8, 2016
• First Posted: April 15, 2016
• Study Start: July 1, 2016
• Primary Completion: August 28, 2018
• Study Completion: August 28, 2018
• Last Updated: October 19, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)