Influenza Vaccination and COPD Phenotypes

Study Overview
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Brief Summary
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The aim of this study is to determine responses of the immune system to the annual flu vaccination in people with COPD who experience frequent or infrequent exacerbations and healthy participants. We will collect blood and saliva immediately before and one month after flu vaccination at GP surgeries in the Autumn/Winter period. By measuring how quickly antibodies (that provide protection against infection) develop in the blood after vaccination we can provide important new information to help confirm whether those prone to COPD flare ups have weaker immune systems.

Official Title
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Responses of the Immune System to Influenza Vaccination in Phenotypes of Chronic Obstructive Pulmonary Disease

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Other: Influenza Vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 65-85 years with a diagnosis of COPD (according to Global Initiative for Chronic Obstructive Lung Disease criteria: post bronchodilator FEV1/FVC ratio <0.70) and moderate to severe airflow limitation (FEV1 30-80% predicted) who opt to receive the annual influenza vaccine. We will also include healthy participants aged 65-85 years without symptoms of lung disease who opt to receive the annual influenza vaccine. Exclusion Criteria: Unable/unwilling to provide informed consent Any history of allergies, suspected hypersensitivity and/or contraindication to vaccines (e.g egg protein allergy) Participation in another clinical trial (use of investigational product or device) Not on optimal treatment (COPD patients only) Current smokers, exhaled CO >10 parts per million Clinical instability, defined as experiencing a COPD exacerbation less than 4 weeks prior to baseline visit, as indicated by treatment with systemic glucocorticosteroids and/or antibiotics and/or hospitalization (COPD only) An upper/lower respiratory tract infection e.g. common cold, sinus symptoms, pneumonia, which has not resolved four weeks prior to baseline visit Diagnosis of asthma and/or other relevant lung disease (e.g. history of primary or clinically significant bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], active tuberculosis) Known alpha-1-antitrypsin deficiency Immunological diseases or known infection with Human Immunodeficiency Virus (HIV) Any diagnosis of a malignant disease (other than basal or squamous cell carcinoma) in the last 5 years Currently taking immunosuppressive medications Diagnosis of diabetes mellitus Severe renal failure (calculated eGFR less than 60 ml/min) Liver impairment Child-Pugh B/C and/or active viral hepatitis Severe psychiatric or neurological disorders (Parkinson's disease or motor neurone disease) Planned donation of human tissue (blood, organs or bone marrow) during the course of the trial

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COPD frequent exacerbators<br>Aged 65-85 years with a diagnosis of COPD according to Global Initiative for Chronic Obstructive Lung Disease criteria (post bronchodilator FEV1/FVC ratio <0.70). Moderate to severe airflow limitation (FEV1 30-80% predicted). Patients have experienced 2 or more exacerbations requiring oral steroids/antibiotics treatment and/or hospitalisation in the previous 12 months. | Other: Influenza Vaccination<br> <br> |
| COPD infrequent exacerbators<br>Aged 65-85 years with a diagnosis of COPD according to Global Initiative for Chronic Obstructive Lung Disease criteria (post bronchodilator FEV1/FVC ratio <0.70). Moderate to severe airflow limitation (FEV1 30-80% predicted). Patients have experienced no more than 1 course of oral steroids/antibiotics and none exacerbations requiring hospital admission in the previous 12 months. | Other: Influenza Vaccination<br> <br> |
| Healthy controls<br>Aged 65-85 years and do not have any symptoms of lung disease and have normal spirometry. | Other: Influenza Vaccination<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination inhibition (HI) antibody titres |  | October 2016 - August 2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pseudotype-based neutralization antibody titres |  | October 2016 - August 2017 | 
| Serum and saliva concentrations of total (and sub-classes of) IgA, IgG and IgM |  | October 2016 - August 2017 | 
| Concentrations of inflammatory mediators in RNA extracted from unstimulated and in vitro stimulated peripheral blood mononuclear cells. |  | October 2016 - August 2017 | 
| Plasma concentrations of markers of B and T cell activation |  | October 2016 - August 2017 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Exacerbations