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

Completed
Conditions
Chronic Obstructive Pulmonary Disease
Interventions
Other: Sample collection
Registration Number
NCT02740686
Lead Sponsor
University of Lincoln
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.

Detailed Description

Pulmonary rehabilitation has been proven to benefit COPD patients in terms of quality of life and functional capabilities. The effects of pulmonary rehabilitation (exercise) on immune function are unclear despite clear benefits of exercise on immune function in healthy individuals being identified. Moderate-intensity and frequency of exercise has been shown to decrease the risk of upper respiratory tract infections in healthy individuals in comparison to sedentary individuals. Respiratory infections, also known as exacerbations, in COPD are the main cause of hospitalisation and mortality. Therefore, if exercise can modulate immune function in COPD, it can be encouraged further in COPD to reduce hospitalisation risk. However, it is important to compare the effects of exercise amongst different phenotypes as frequent exacerbators are known to have elevated inflammatory markers, and may consequently respond to exercise differently to infrequent exacerbators, paving a rationale for a different approach to this subset of patients.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
85
Inclusion Criteria
  • 58 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%).
Exclusion Criteria
  • 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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Infrequent exacerbatorsSample collectionExacerbations 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.
Healthy smokersSample collectionRecruited 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.
Healthy never smokersSample collectionRecruited 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.
Frequent exacerbatorsSample collectionExacerbations 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.
Primary Outcome Measures
NameTimeMethod
Concentration of inflammatory markers in plasma and sputum (C-reactive protein, Fibrinogen, Interleukin(IL)-6, IL-8July 2016 - August 2018
Secondary Outcome Measures
NameTimeMethod
Routine clinical outcome measures following pulmonary rehabilitation (completion rates and clinically important differences - ISWT, ESWT, 6MWD, CRQ)July 2016 - August 2018
Respiratory Symptoms™ (RS-Total score; RS-Breathlessness; RS-Cough and Sputum, and RS-Chest Symptoms)July 2016 - August 2018
Total and differential blood leukocyte countJuly 2016 - August 2018
Pre-activation and activation of blood neutrophils using flow cytometryJuly 2016 - August 2018
Severe, moderate and mild exacerbations (number of /days to defined events, severity, recovery)July 2016 - August 2018
Changes in the expression of anti-inflammatory genesJuly 2016 - August 2018
Pro-coagulant and pro-inflammatory microparticle signatures in plasmaJuly 2016 - August 2018
Differences in basal levels of inflammation between frequent and infrequent exacerbators in comparison to healthy controlsJuly 2016 - August 2018

Trial Locations

Locations (6)

Nettleham Medical Practice

🇬🇧

Lincoln, Lincolnshire, United Kingdom

Welton Surgery

🇬🇧

Lincoln, Lincolnshire, United Kingdom

Birchwood Medical Practice

🇬🇧

Lincoln, Lincolnshire, United Kingdom

Sudbrooke Drive Community Centre

🇬🇧

Lincoln, United Kingdom

Bracebridge Community Centre

🇬🇧

Lincoln, United Kingdom

Lindum Medical Practice

🇬🇧

Lincoln, Lincolnshire, United Kingdom

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