Chronic Obstructive Pulmonary DiseaseNCT05743582
Innate Immunity in COPD
An observational study of Chronic Obstructive Pulmonary Disease, run by University of Edinburgh at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 77 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Bronchoscopy for sample collection and Blood donation
- Type of treatment
- Surgery or procedure
- How many people
- 189 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 11 May 2023to 10 Feb 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 77 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 189 participants split evenly into: COPD patients, healthy smokers, healthy non-smokers (63 each)
Who may be able to join
- 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
Show all 9Show fewer
- Healthy volunteers:
- Any healthy volunteer aged 18-77 years
- Ability to provide informed consent
Who cannot join
- 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.
Show all 23Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sarah Walmsley, MD contact
United Kingdom2 sites, 2 recruiting
- Not yet recruiting
University of Edinburgh
Edinburgh, EH16 4TJ
David H Dockrell, MD, David.Dockrell@ed.ac.uk
- Recruiting
Royal Infirmary of Edinburgh
Edinburgh, EH16 5SA
David H Dockrell, MD, +441312426213, David.Dockrell@ed.ac.uk
About this study
Official title: Analysis of Innate Immune Competence in People With Chronic Obstructive Pulmonary Disease (COPD)
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.
Read the detailed description
COPD has become one of the major causes of ill health throughout the world. COPD has major economic impact being the second commonest causes of hospital admission and days lost to work in the UK where an estimated 10% of the population over 40 are affected. The disease causing mechanisms are not well defined but a central feature is development of a chronic inflammatory process. Inflammation in COPD is progressive and persists after inciting factors, such as cigarette smoke, are removed. The stimuli to persistent inflammation and the failure of normal cues to resolve this inflammation are poorly characterised. Lung inflammation in COPD is largely resistant to the antiinflammatory actions of corticosteroids, currently used as treatment, which fail to modify disease progression or mortality. Existing therapeutic approaches for COPD are therefore flawed and do not alter the central chronic inflammatory process.
Better understanding of COPD pathogenesis is essential if new therapeutic strategies are to be developed that will alter the course of the disease. A sub-set of COPD patients have more frequent exacerbations, which are associated with more rapid decline in pulmonary function tests and increased mortality. Bacterial infection is a frequent cause of these exacerbations. In addition some of the high-risk patients with COPD are more susceptible to bacterial pneumonia. In COPD, the lower respiratory tract is colonised with a higher density of bacteria (including Haemophilus influenzae or Streptococcus pneumoniae), whereas in non-smoking subjects and smokers with normal lung function the density of bacteria is much lower. This suggests there may be a defect in immune responses to bacteria in patients with COPD, in particular involving the part of the immune response which is termed 'innate', which provides the most rapid and generic response to bacteria.
Lung host defence against bacteria requires the co-ordinated action of both immune cells and factors released into the airway termed humoral factors. Alveolar macrophage (AM) competence is essential to maintain sterility in the lower airway and bacterial phagocytosis and killing is complemented by a delayed programme of cell death termed apoptosis, which provides a significant increment to bacterial killing and shuts off the inflammatory response. When this component of host defence is over-whelmed recruited cells that ingest bacteria termed phagocytes (i.e. neutrophils and macrophages) become key effectors of the host response. Research suggests that monocyte-derived macrophages (MDM) isolated from patients with COPD have impaired capacity for phagocytosis of bacteria as compared to healthy donors or smokers without COPD. That this defect is apparent in cells isolated from the blood suggests it may reflect a systemic defect in bacterial clearance. In addition there is a marked defect in AM isolated from the lung, suggesting additional defects imposed by the lung environment, that impacts uptake of bacteria coated with antibody. The investigators have also shown that macrophages are impaired in their ability to kill the bacteria they ingest. The molecular basis of the decreased clearance of bacteria is unclear but research by the investigators has found that macrophages fail to produce an increment in a factor that kills bacteria that is produced by mitochondria, termed mitochondrial reactive oxygen species (mROS) and this may contribute to both impaired ingestion and killing of bacteria.
Mitochondria are structures in cell that generate energy but how they burn fuels in the form of molecules adapts to aid immune function. The investigators believe that in COPD mitochondria in macrophages fail to adapt during bacterial challenge and this underpins the immune defect observed for bacteria. Similarly, the investigators have shown that peripheral blood neutrophils have impaired killing of bacteria in COPD and that this is associated with impaired gluconeogenesis, a process that stores glucose in the form of glycogen. This glycogen is normally used by neutrophils as a source of glucose to help prime responses to bacteria and this defect in COPD neutrophils impairs their capacity to kill bacteria This has not been previously addressed and the investigators will focus on four main aspects: i) the molecules myeloid cells burn as fuel sources during metabolism in COPD in at rest and in response to bacteria and other inflammatory stimuli, ii) alterations in mitochondrial function in myeloid cells in COPD, iii) whether alterations are confined to myeloid cells in the lung or expressed at sites removed from the lung and the mechanisms of these effects and iv) methods to recalibrate altered responses determined by the investigators in myeloid cells in COPD. The cells and materials that will be generated will allow additional research and will be used to help test other hypotheses and identify additional mechanism underlying immune dysfunction and promotion of inflammation in COPD that emerge as work by the investigators and the field progresses during the lifetime of this research.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Bronchoscopy for sample collection, Blood donation
- Keywords
- Alveolar macrophages, Peripheral blood mononuclear cells, Neutrophils, Bactericidal mechanisms, Immune cell metabolism, Epigenetics
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchoscopy for sample collectionProcedure or surgery
Participants will undergo a single bronchoscopy and bronchoalveolar lavage to obtain immune cells.
Blood donationProcedure or surgery
Participants will donate a single blood sample for isolation of immune cells from peripheral blood.
| Study group | Role | What they receive |
|---|---|---|
| COPD patients | Bronchoscopy to retrieve bronchoalveolar lavage fluid for isolation of immune cells, and phlebotomy for blood sample collection. Receives: Procedure: Bronchoscopy for sample collection; Procedure: Blood donation | |
| Healthy controls - smokers | Bronchoscopy to retrieve bronchoalveolar lavage fluid for isolation of immune cells, and phlebotomy for blood sample collection. Receives: Procedure: Bronchoscopy for sample collection; Procedure: Blood donation | |
| Healthy controls - non-smokers | Bronchoscopy to retrieve bronchoalveolar lavage fluid for isolation of immune cells, and phlebotomy for blood sample collection. Receives: Procedure: Bronchoscopy for sample collection; Procedure: Blood donation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of immunometabolic responses in immune cells required for microbicidal activity.
This programme will identify core features of the immunometabolic response and of mitochondrial function that are required for optimal macrophage responses to bacteria and establish how these core responses are perturbed in COPD. Outcomes will be related back to clinical phenotypes of the patients enrolled in the study. The investigators will also develop models and therapeutic approaches with which to translate this programme and suggest approaches for future clinical trials that may include use of repurposed agents.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2023
- Study start11 May 2023
- Primary completion1 Dec 2027 (estimated)
- Study completion10 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 189 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David H Dockrell, MD, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05743582
- Sponsor's protocol ID
- AC23003
- Status last verified
- Jun 2026
- First submitted
- 14 Feb 2023
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication will be shared, in anonymised form only, upon request. No identifiable personal information will be used when publishing results.
Publications
Dockrell DH, Marriott HM, Prince LR, Ridger VC, Ince PG, Hellewell PG, Whyte MK. Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection. J Immunol. 2003 Nov 15;171(10):5380-8. doi: 10.4049/jimmunol.171.10.5380.
PubMed 14607941Taylor AE, Finney-Hayward TK, Quint JK, Thomas CM, Tudhope SJ, Wedzicha JA, Barnes PJ, Donnelly LE. Defective macrophage phagocytosis of bacteria in COPD. Eur Respir J. 2010 May;35(5):1039-47. doi: 10.1183/09031936.00036709. Epub 2009 Nov 6.
PubMed 19897561Bewley MA, Preston JA, Mohasin M, Marriott HM, Budd RC, Swales J, Collini P, Greaves DR, Craig RW, Brightling CE, Donnelly LE, Barnes PJ, Singh D, Shapiro SD, Whyte MKB, Dockrell DH. Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages. Am J Respir Crit Care Med. 2017 Oct 1;196(7):845-855. doi: 10.1164/rccm.201608-1714OC.
PubMed 28557543Bewley MA, Budd RC, Ryan E, Cole J, Collini P, Marshall J, Kolsum U, Beech G, Emes RD, Tcherniaeva I, Berbers GAM, Walmsley SR, Donaldson G, Wedzicha JA, Kilty I, Rumsey W, Sanchez Y, Brightling CE, Donnelly LE, Barnes PJ, Singh D, Whyte MKB, Dockrell DH; COPDMAP. Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists. Am J Respir Crit Care Med. 2018 Sep 15;198(6):739-750. doi: 10.1164/rccm.201705-0903OC.
PubMed 29547002Belchamber KBR, Singh R, Batista CM, Whyte MK, Dockrell DH, Kilty I, Robinson MJ, Wedzicha JA, Barnes PJ, Donnelly LE; COPD-MAP consortium. Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages. Eur Respir J. 2019 Oct 10;54(4):1802244. doi: 10.1183/13993003.02244-2018. Print 2019 Oct.
PubMed 31320451Mills EL, Kelly B, O'Neill LAJ. Mitochondria are the powerhouses of immunity. Nat Immunol. 2017 Apr 18;18(5):488-498. doi: 10.1038/ni.3704.
PubMed 28418387Sadiku P, Willson JA, Ryan EM, Sammut D, Coelho P, Watts ER, Grecian R, Young JM, Bewley M, Arienti S, Mirchandani AS, Sanchez Garcia MA, Morrison T, Zhang A, Reyes L, Griessler T, Jheeta P, Paterson GG, Graham CJ, Thomson JP, Baillie K, Thompson AAR, Morgan JM, Acosta-Sanchez A, Darde VM, Duran J, Guinovart JJ, Rodriguez-Blanco G, Von Kriegsheim A, Meehan RR, Mazzone M, Dockrell DH, Ghesquiere B, Carmeliet P, Whyte MKB, Walmsley SR. Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis. Cell Metab. 2021 Feb 2;33(2):411-423.e4. doi: 10.1016/j.cmet.2020.11.016. Epub 2020 Dec 10.
PubMed 33306983
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Innate Immune Competence in People With Chronic Obstructive Pulmonary Disease (COPD)
- ClinicalTrials.gov ID
- NCT05743582
- Acronym / sponsor ID
- AC23003
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- Alveolar macrophages, Peripheral blood mononuclear cells, Neutrophils, Bactericidal mechanisms, Immune cell metabolism, Epigenetics
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 189 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Study start
- 11 May 2023 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 10 Feb 2028 (estimated)
- First posted
- 24 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
COPD has become one of the major causes of ill health throughout the world. COPD has major economic impact being the second commonest causes of hospital admission and days lost to work in the UK where an estimated 10% of the population over 40 are affected. The disease causing mechanisms are not well defined but a central feature is development of a chronic inflammatory process. Inflammation in COPD is progressive and persists after inciting factors, such as cigarette smoke, are removed. The stimuli to persistent inflammation and the failure of normal cues to resolve this inflammation are poorly characterised. Lung inflammation in COPD is largely resistant to the antiinflammatory actions of corticosteroids, currently used as treatment, which fail to modify disease progression or mortality. Existing therapeutic approaches for COPD are therefore flawed and do not alter the central chronic inflammatory process.
Better understanding of COPD pathogenesis is essential if new therapeutic strategies are to be developed that will alter the course of the disease. A sub-set of COPD patients have more frequent exacerbations, which are associated with more rapid decline in pulmonary function tests and increased mortality. Bacterial infection is a frequent cause of these exacerbations. In addition some of the high-risk patients with COPD are more susceptible to bacterial pneumonia. In COPD, the lower respiratory tract is colonised with a higher density of bacteria (including Haemophilus influenzae or Streptococcus pneumoniae), whereas in non-smoking subjects and smokers with normal lung function the density of bacteria is much lower. This suggests there may be a defect in immune responses to bacteria in patients with COPD, in particular involving the part of the immune response which is termed 'innate', which provides the most rapid and generic response to bacteria.
Lung host defence against bacteria requires the co-ordinated action of both immune cells and factors released into the airway termed humoral factors. Alveolar macrophage (AM) competence is essential to maintain sterility in the lower airway and bacterial phagocytosis and killing is complemented by a delayed programme of cell death termed apoptosis, which provides a significant increment to bacterial killing and shuts off the inflammatory response. When this component of host defence is over-whelmed recruited cells that ingest bacteria termed phagocytes (i.e. neutrophils and macrophages) become key effectors of the host response. Research suggests that monocyte-derived macrophages (MDM) isolated from patients with COPD have impaired capacity for phagocytosis of bacteria as compared to healthy donors or smokers without COPD. That this defect is apparent in cells isolated from the blood suggests it may reflect a systemic defect in bacterial clearance. In addition there is a marked defect in AM isolated from the lung, suggesting additional defects imposed by the lung environment, that impacts uptake of bacteria coated with antibody. The investigators have also shown that macrophages are impaired in their ability to kill the bacteria they ingest. The molecular basis of the decreased clearance of bacteria is unclear but research by the investigators has found that macrophages fail to produce an increment in a factor that kills bacteria that is produced by mitochondria, termed mitochondrial reactive oxygen species (mROS) and this may contribute to both impaired ingestion and killing of bacteria.
Mitochondria are structures in cell that generate energy but how they burn fuels in the form of molecules adapts to aid immune function. The investigators believe that in COPD mitochondria in macrophages fail to adapt during bacterial challenge and this underpins the immune defect observed for bacteria. Similarly, the investigators have shown that peripheral blood neutrophils have impaired killing of bacteria in COPD and that this is associated with impaired gluconeogenesis, a process that stores glucose in the form of glycogen. This glycogen is normally used by neutrophils as a source of glucose to help prime responses to bacteria and this defect in COPD neutrophils impairs their capacity to kill bacteria This has not been previously addressed and the investigators will focus on four main aspects: i) the molecules myeloid cells burn as fuel sources during metabolism in COPD in at rest and in response to bacteria and other inflammatory stimuli, ii) alterations in mitochondrial function in myeloid cells in COPD, iii) whether alterations are confined to myeloid cells in the lung or expressed at sites removed from the lung and the mechanisms of these effects and iv) methods to recalibrate altered responses determined by the investigators in myeloid cells in COPD. The cells and materials that will be generated will allow additional research and will be used to help test other hypotheses and identify additional mechanism underlying immune dysfunction and promotion of inflammation in COPD that emerge as work by the investigators and the field progresses during the lifetime of this research.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| COPD patients | – | Procedure: Bronchoscopy for sample collection, Procedure: Blood donationBronchoscopy to retrieve bronchoalveolar lavage fluid for isolation of immune cells, and phlebotomy for blood sample collection. |
| Healthy controls - smokers | – | Procedure: Bronchoscopy for sample collection, Procedure: Blood donationBronchoscopy to retrieve bronchoalveolar lavage fluid for isolation of immune cells, and phlebotomy for blood sample collection. |
| Healthy controls - non-smokers | – | Procedure: Bronchoscopy for sample collection, Procedure: Blood donationBronchoscopy to retrieve bronchoalveolar lavage fluid for isolation of immune cells, and phlebotomy for blood sample collection. |
Who may qualify
- Ages
- 18 to 77 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 189 participants split evenly into: COPD patients, healthy smokers, healthy non-smokers (63 each)
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bronchoscopy for sample collectionParticipants will undergo a single bronchoscopy and bronchoalveolar lavage to obtain immune cells. | Procedure or surgery | COPD patients, Healthy controls - non-smokers, Healthy controls - smokers |
| Blood donationParticipants will donate a single blood sample for isolation of immune cells from peripheral blood. | Procedure or surgery | COPD patients, Healthy controls - non-smokers, Healthy controls - smokers |
Primary outcome
Identification of immunometabolic responses in immune cells required for microbicidal activity.
Time frame: 5 years
This programme will identify core features of the immunometabolic response and of mitochondrial function that are required for optimal macrophage responses to bacteria and establish how these core responses are perturbed in COPD. Outcomes will be related back to clinical phenotypes of the patients enrolled in the study. The investigators will also develop models and therapeutic approaches with which to translate this programme and suggest approaches for future clinical trials that may include use of repurposed agents.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Background: PubMed 14607941Dockrell DH, Marriott HM, Prince LR, Ridger VC, Ince PG, Hellewell PG, Whyte MK. Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection. J Immunol. 2003 Nov 15;171(10):5380-8. doi: 10.4049/jimmunol.171.10.5380.
- Background: PubMed 19897561Taylor AE, Finney-Hayward TK, Quint JK, Thomas CM, Tudhope SJ, Wedzicha JA, Barnes PJ, Donnelly LE. Defective macrophage phagocytosis of bacteria in COPD. Eur Respir J. 2010 May;35(5):1039-47. doi: 10.1183/09031936.00036709. Epub 2009 Nov 6.
- Background: PubMed 28557543Bewley MA, Preston JA, Mohasin M, Marriott HM, Budd RC, Swales J, Collini P, Greaves DR, Craig RW, Brightling CE, Donnelly LE, Barnes PJ, Singh D, Shapiro SD, Whyte MKB, Dockrell DH. Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages. Am J Respir Crit Care Med. 2017 Oct 1;196(7):845-855. doi: 10.1164/rccm.201608-1714OC.
- Background: PubMed 29547002Bewley MA, Budd RC, Ryan E, Cole J, Collini P, Marshall J, Kolsum U, Beech G, Emes RD, Tcherniaeva I, Berbers GAM, Walmsley SR, Donaldson G, Wedzicha JA, Kilty I, Rumsey W, Sanchez Y, Brightling CE, Donnelly LE, Barnes PJ, Singh D, Whyte MKB, Dockrell DH; COPDMAP. Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists. Am J Respir Crit Care Med. 2018 Sep 15;198(6):739-750. doi: 10.1164/rccm.201705-0903OC.
- Background: PubMed 31320451Belchamber KBR, Singh R, Batista CM, Whyte MK, Dockrell DH, Kilty I, Robinson MJ, Wedzicha JA, Barnes PJ, Donnelly LE; COPD-MAP consortium. Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages. Eur Respir J. 2019 Oct 10;54(4):1802244. doi: 10.1183/13993003.02244-2018. Print 2019 Oct.
- Background: PubMed 28418387Mills EL, Kelly B, O'Neill LAJ. Mitochondria are the powerhouses of immunity. Nat Immunol. 2017 Apr 18;18(5):488-498. doi: 10.1038/ni.3704.
- Background: PubMed 33306983Sadiku P, Willson JA, Ryan EM, Sammut D, Coelho P, Watts ER, Grecian R, Young JM, Bewley M, Arienti S, Mirchandani AS, Sanchez Garcia MA, Morrison T, Zhang A, Reyes L, Griessler T, Jheeta P, Paterson GG, Graham CJ, Thomson JP, Baillie K, Thompson AAR, Morgan JM, Acosta-Sanchez A, Darde VM, Duran J, Guinovart JJ, Rodriguez-Blanco G, Von Kriegsheim A, Meehan RR, Mazzone M, Dockrell DH, Ghesquiere B, Carmeliet P, Whyte MKB, Walmsley SR. Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis. Cell Metab. 2021 Feb 2;33(2):411-423.e4. doi: 10.1016/j.cmet.2020.11.016. Epub 2020 Dec 10.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication will be shared, in anonymised form only, upon request. No identifiable personal information will be used when publishing results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sarah Walmsley, MD contact
David H Dockrell, MD principal investigator
University of Edinburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Obstructive Pulmonary Disease, run by University of Edinburgh at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David H Dockrell, MD (+441312426213, David.Dockrell@ed.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of immunometabolic responses in immune cells required for microbicidal activity. (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05743582, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.