Studying the Airway Microenvironment in Patients Undergoing Surgical and Bronchoscopic Interventions for COPD

NCT ID: NCT03010592

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-02-06
• Study Completion Date: 2023-01-01

Brief Summary

Studying the airway microenvironment in patients undergoing surgical and bronchoscopic interventions for COPD

Detailed Description

Chronic obstructive pulmonary disease (COPD) is an umbrella term encompassing two entities causing progressive and ultimately disabling breathlessness. Emphysema is a process destructive of the airspaces distal to the terminal bronchioles, with loss of gas exchange tissue, of elastic recoil and of circumferential tethering of the small airways leading to their collapse on forced expiration. Chronic bronchitis is a disorder of the bronchi causing excess production and impaired mobilisation of mucus. Increased parasympathetic tone and progressive remodelling of airways impairs response to bronchodilators. Static and dynamic hyperinflation ensue - a persistently expanded chest and flattened diaphragms despite increasing use of accessory respiratory muscles - resulting in a disadvantaged respiratory pump.

Patients with severe emphysema and hyperinflation benefit from lung volume reduction techniques designed to reduce gas trapping and to improve airflow, chest wall and lung mechanics. The best evidence exists for lung volume reduction surgery (LVRS), which however is not without risk and there is increasing interest in the development of bronchoscopic lung volume reduction (BLVR) techniques including emplacement of endobronchial valves and coils and targeted lung denervation (TLD), which have all been shown to improve lung function, exercise capacity, and quality of life.

Endobronchial cryotherapy is a novel investigational treatment in patients with chronic bronchitis. Porcine models have shown ablation of abnormal metaplastic goblet cells and regeneration of healthy ciliated epithelium and submucosa within 48 hours with complete healing by 60 days following treatment. A pilot study evaluated 11 patients undergoing a lobectomy or pneumonectomy for presumed lung cancer. Metered sprays, one to each of two separate locations, were administered 2 weeks prior to surgery, at least 2cm distal to the proposed resection margin (first segmental and lobular bronchi). No adverse events were reported. Histology of the 8 submitted specimens demonstrated localised cryothermic effect extending to but not beyond the submucosa, and minimal inflammation.

Chronic airway infiltration by neutrophils, macrophages, and Th-1 predominant lymphocytes driven by increased expression of inflammatory proteins, cytokines and chemokines, is intensified during exacerbations. It is generally accepted that acute exacerbations accelerate the decline in lung function in COPD. Recent studies have suggested a role for microvesicles (MVs) in the pathogenesis of COPD, driving exacerbations. MVs are fragments of cell membrane ranging from 0.1 to 1µm in diameter shed by almost all eukaryotic cells. They are recognised to be key mediators of intercellular communication, transporting a variety of molecular cargo including proteins and nucleic acids to distant cells, and have been implicated in various inflammatory diseases including COPD. The majority of studies have looked at circulating endothelial-derived MVs, which are elevated in patients with COPD, are significantly higher during an exacerbation, and are predictive of rapid forced expiratory volume in 1 second (FEV1) decline. However, there is a paucity of data on epithelial-derived MVs within the lung. We know from acute lung injury models that alveolar macrophage-derived microvesicles, which carry biologically active tumour necrosis factor, are rapidly released during the early phase and may play a role in initiating the disease process.

Bronchoalveolar lavage and brushings are established techniques to obtain material for respectively, measurement of inflammatory proteins and microvesicles, and for cytology and messenger ribonucleic acid (mRNA) analysis. A novel technique sampling the mucosal lining fluid using a synthetic absorptive matrix ('bronchosorption') has been shown to have greater sensitivity to standard bronchoalveolar lavage (BAL), eliminating the disadvantage of dilution.

A combination of all three techniques to directly harvest lower airway samples at multiples sites of pulmonary inflammation would allow comparison of proteomic, transcriptomic, and histology data from the endobronchial environment before and after intervention. This would be the first study evaluating the lung microenvironment in this context, which may identify predictive biomarkers of response to intervention and future exacerbation risk.

Conditions

Chronic Obstructive Pulmonary Disease; Emphysema; Chronic Bronchitis

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Scheduled for lung volume reduction treatment or endobronchial cryotherapy for the management of severe COPD.

Exclusion Criteria

• Unwilling or unable to sign the informed consent form
• Patients with known Category 3 Organisms as per the Advisory Committee on Dangerous Pathogens (ACDP) for example, Tuberculosis or Human Immunodeficiency Virus.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pallav L Shah, MBBS MD FRCP

Role: PRINCIPAL_INVESTIGATOR

Royal Brompton & Harefields Hospital

Locations

Chelsea & Westminster Hospital

London, Chelsea, United Kingdom

Site Status: RECRUITING

Royal Brompton & Harefields Hospital

London, Fulham, United Kingdom

Site Status: NOT_YET_RECRUITING

Countries

United Kingdom

Central Contacts

Justin L Garner, MBBS MRCP

Role: CONTACT

J.Garner@rbht.nhs.uk

02073518029

Facility Contacts

Nadia Shabbir

Role: primary

Nadia.Shabbir@chelwest.nhs.uk

02033156684

Patrik Patrik Pettersson

Role: primary

p.pettersson@rbht.nhs.uk

02073528121

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Other Identifiers

217587

Identifier Type: -

Identifier Source: org_study_id