Clinical trial NCT02740686: Changes in Inflammatory Markers During Pulmonary Rehabilitation Based on Exacerbation States in COPD
Official title: Changes in Inflammatory Markers During Pulmonary Rehabilitation Based on Exacerbation States in COPD
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Exercise
Immunity
Inflammation
Biomarkers
Lead sponsor: University of Lincoln
Sponsor class: OTHER
Collaborators: name: National Health Service, United Kingdom
First posted: 2016-04-15
Enrollment: 85
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Concentration of inflammatory markers in plasma and sputum (C-reactive protein, Fibrinogen, Interleukin(IL)-6, IL-8
timeFrame: July 2016 - August 2018
Secondary outcomes:
measure: Changes in the expression of anti-inflammatory genes
timeFrame: July 2016 - August 2018
measure: Total and differential blood leukocyte count
timeFrame: July 2016 - August 2018
measure: Pre-activation and activation of blood neutrophils using flow cytometry
timeFrame: July 2016 - August 2018
measure: Pro-coagulant and pro-inflammatory microparticle signatures in plasma
timeFrame: July 2016 - August 2018
measure: Severe, moderate and mild exacerbations (number of /days to defined events, severity, recovery)
timeFrame: July 2016 - August 2018
measure: Respiratory Symptoms™ (RS-Total score; RS-Breathlessness; RS-Cough and Sputum, and RS-Chest Symptoms)
timeFrame: July 2016 - August 2018
measure: Routine clinical outcome measures following pulmonary rehabilitation (completion rates and clinically important differences - ISWT, ESWT, 6MWD, CRQ)
timeFrame: July 2016 - August 2018
measure: Differences in basal levels of inflammation between frequent and infrequent exacerbators in comparison to healthy controls
timeFrame: July 2016 - August 2018
Other outcomes:
Locations:
city: Lincoln
country: United Kingdom
facility: Lindum Medical Practice
state: Lincolnshire
city: Lincoln
country: United Kingdom
facility: Nettleham Medical Practice
state: Lincolnshire
city: Lincoln
country: United Kingdom
facility: Welton Surgery
state: Lincolnshire
city: Lincoln
country: United Kingdom
facility: Birchwood Medical Practice
state: Lincolnshire
city: Lincoln
country: United Kingdom
facility: Sudbrooke Drive Community Centre
city: Lincoln
country: United Kingdom
facility: Bracebridge Community Centre
Study officials:
affiliation: PhD student
name: Alex R Jenkins, MPhil
role: PRINCIPAL_INVESTIGATOR
References: