Innate Immunity in COPD

Summary

Chronic Obstructive Pulmonary Disease (COPD) causes obstruction to airflow when breathing out. It is a leading cause of chronic lung disease, hospitalization and death. Smoking is the major cause of COPD but why some smokers develop COPD while others do not is poorly understood. A central feature of COPD is accumulation of inflammatory blood cells, macrophages and neutrophils, in the airway, leading to lung injury and airway damage. The small airways of many patients with COPD contain bacteria, which are absent in healthy smokers or non-smokers. These bacteria stimulate recruitment of neutrophils, macrophages and other inflammatory cells, further accelerating airway injury. The investigators and others have shown resident macrophages in the lung and inflammatory cells (neutrophils and macrophages) recruited from the blood, which normally clear bacteria, have reduced anti-bacterial capacity in COPD and that their altered function impairs the resolution of inflammation. The investigators now wish to test why these cells fail to clear bacteria focusing in particular on how they use molecules as food to generate energy, a process termed metabolism, since this is an important determinant of immune cell function. Comparison will be made between lung resident cells (obtained by performing bronchoscopy and washing a segment of lung to flush out immune cells) and those from the blood to determine if the alterations are specific to the lung. The investigators will identify alterations in responses to bacteria in relation to changes in metabolism . A major focus will be on how structures in the cell that normally are key for energy production (i.e. mitochondria) become dysfunctional and how this impacts responses to bacteria. The investigators will relate findings to the clinical features of COPD and to healthy non-smokers and smokers to separate smoking-related changes from COPD. The aim is to develop new approaches with which to treat and manage COPD.

Eligibility

Inclusion Criteria:

COPD patients:

* COPD patients aged 18-77 years who are GOLD Stage 1 or 2 or 3; for patients undergoing bronchoscopy already for a clinical reason.
* COPD patients aged 18-77 years old who are GOLD Stage 1,2 or 3 for patients who are donating blood only.
* COPD patients aged 18-69 years who are GOLD Stage 1 or 2 for patients undergoing bronchoscopy for research purposes.
* COPD- Defined by radiological investigation of chest either chest X-ray or High-resolution CT scan in previous 12 months
* Ability to provide informed consent

Healthy volunteers:

* Any healthy volunteer aged 18-77 years
* Ability to provide informed consent

Exclusion Criteria:

COPD patients:

* Individuals known to have active malignancy, immunosuppression, diabetes mellitus, chronic kidney disease or hepatic failure.
* Individuals with a history of anaemia
* Individuals who have donated \>250 ml of blood for any reason within the last 6 months
* Individuals who are pregnant or breast feeding.
* Current participation in any other clinical trial, except those directly relating to this cohort and study.
* Individuals who have had a febrile illness or other symptoms of acute infectious illness (respiratory, enteric or soft tissue) within the last 2 weeks
* Individuals who have received a vaccine in the past 2 weeks
* Inability to communicate in English or convey willingness to participate.
* For bronchoscopy - Any significant lung condition that would contra-indicate bronchoscopy including:

active acute lung infection (with the exception of asymptomatic pulmonary colonisation) or malignancy, significant coexisting interstitial lung disease or additional pulmonary diagnosis in addition to COPD.

Healthy volunteers:

* Individuals known to have active malignancy, immunosuppression, diabetes mellitus, chronic kidney disease or hepatic failure
* Individuals with anaemia on the screening full blood count (FBC)
* Individuals who donated \>250 ml of blood for any reason within the last 6 months
* Individuals who are pregnant or breast feeding
* Current participation in any other clinical trial
* Individuals who have had a febrile illness or other symptoms of acute infectious illness (respiratory, enteric or soft tissue) within the last 2 weeks.
* Individuals who have received a vaccine in the past 2 weeks
* Chronic or acute respiratory disease.
* Any chronic medical condition or receipt of regular prescription medication other than the oral contraceptive pill.
* Inability to communicate in English or convey willingness to participate
* For bronchoscopy - Any active lung condition including any lung infection or asthma Any significant abnormality on CXR that would contraindicate bronchoscopy FEV1 \<65% predicted (BTS Guidelines, 2001)

Conditions2

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