Biomarkers in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yvonne Nussbaumer-Ochsner, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01145300
First received: June 14, 2010
Last updated: January 25, 2012
Last verified: January 2012
  Purpose

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and is characterized by fixed airflow obstruction. The cornerstone of the disease is chronic inflammation leading to narrowing of the small airways and thus impairment of lung function. Compared to spirometry, the single breath N2-washout-test is more sensitive to identify the regional heterogeneity of bronchial airflow obstruction in the small airways.

The aim of this study is to evaluate whether there is a correlation between the sbN2-test, markers in exhaled air and the inflammatory cells in the small airways.


Condition
Chronic Obstructive Pulmonary Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Relationship Between Exhaled Markers and Airway Pathology in Smokers With and Without Airflow Obstruction

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • 1. Slope of the sbN2-test (phase III/IV) 2. Inflammatory markers in exhaled breath (NO, EBC, eNose, DMS) 3. Inflammation: localisation, numbers and profile of inflammatory cells in the large/small airways (neutrophils, macrophages, mastcells) [ Time Frame: 1 week before surgery ] [ Designated as safety issue: No ]
    To demonstrate that the change in slope of the sbN2-test (phase III/IV) is correlated to an influx of inflammatory cells in the small airways (histology, morphology, immunopathology) and to inflammatory markers in exhaled breath in patients with normal and abnormal small airways function.


Secondary Outcome Measures:
  • Expression of the 1,25(OH)2D3 degrading enzyme CYP24A1 and antimicrobial peptides in small and large airways [ Time Frame: within 1 week after surgery ] [ Designated as safety issue: No ]
    To assess whether there is a relationship between the expression of the 1,25(OH)2D3 degrading enzyme CYP24A1 and antimicrobial peptides in small and large airways in COPD patients and whether there is a correlation with local inflammation and lung function.

  • Markers in exhaled breath [ Time Frame: 1 week before and 3 months after surgery ] [ Designated as safety issue: No ]
    To demonstrate that the presence of lung cancer per se is a condition leading to a change in the breath pattern. Exhaled breath patterns will be assessed by the eNose and the differential mobility spectrometry before and after lung cancer surgery.

  • Expression of macrophage markers (Mf1 and Mf2) and chymase/tryptase in mast cell subsets [ Time Frame: within 1 week after surgery ] [ Designated as safety issue: No ]
    To assess whether there is a difference in expression of macrophage Mf1 and Mf2 markers, and in mast cell subsets (chymase/tryptase positive vs. tryptase positive) in small and large airways from patients with COPD at lung tissue level.


Biospecimen Retention:   Samples With DNA

blood


Enrollment: 32
Study Start Date: June 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Detailed Description:

The cornerstone of COPD is a chronic inflammation leading to narrowing of the small airways and thus impairment of lung function. Spirometry, the most frequently used pulmonary function test for diagnosing and monitoring disease, mostly reflects obstruction of the larger airways. The single breath N2-test, however, is more sensitive to identify the regional heterogeneity of bronchial airflow obstruction in the small airways, a main site of injury in COPD.

The aim of this study is to evaluate whether there is a correlation between the sbN2-test, markers in exhaled air and the inflammatory cells in the small airways.

This protocol describes a cross-sectional, explorative trial in at least 16 patients with COPD (up to GOLD III) and 8 patients without COPD who are scheduled for surgical resection for primary lung cancer. Immunohistological methods will be used to characterize the airways (large and small) inflammation pattern in macroscopically normal tissue containing small and large airways collected from sites distant from the tumor. Inflammatory markers will be measured in exhaled breath (exhaled breath condensate, exhaled NO) and be correlated to the sbN2 test. Breath patterns before and after lung cancer surgery will be assessed by the electronic nose and differential mobility spectrometry.

We hypothesize that the sbN2-test and inflammatory markers in exhaled breath reflect changes at peripheral tissue level. Therefore the results of the present study would lead to validation of these non-invasive tools for studies into the pathogenesis of obstructive lung disease, to increased knowledge about the relationship between airway inflammation and small airways obstruction, and may provide further support for the small airways as a specific target for inhaled drug delivery.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with and without COPD scheduled for lung resection for lung cancer.

Criteria

Inclusion Criteria:

  • Male or female subject, age > 40 years, current or ex-smokers.
  • Planned lung resection for primary lung cancer of any size.
  • Patients with COPD: irreversible airflow limitation (postbronchodilator FEV1/FVC < 70% according to GOLD guidelines). Patients already receiving inhalative therapy can continue their medication. Patients showing a partial reversibility after bronchodilation (postbronchodilator FEV1 increase > 150 ml but < 200ml) and complaining respiratory symptoms (e.g. dyspnea at exertion) will be treated preoperatively with a short-acting beta-agonist to achieve optimal perioperative conditions.
  • Patients without COPD: postbronchodilator FEV1/FVC > 70%.
  • Patients have to be in clinical stable condition (no symptoms of respiratory tract infection for at least 2 weeks prior to the study).
  • Written informed consent.

Exclusion Criteria:

  • Patients with a history of asthma or other active lung disease.
  • Lung resection for other reasons than lung cancer (e.g. infective diseases like bronchiectasis).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01145300

Locations
Netherlands
Department of Pulmonology, Leiden University Medical Center
Leiden, Netherlands, 2333 ZA
Sponsors and Collaborators
Leiden University Medical Center
Investigators
Principal Investigator: Klaus F. Rabe, MD, PhD Leiden University Medical Center
  More Information

No publications provided

Responsible Party: Yvonne Nussbaumer-Ochsner, MD, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01145300     History of Changes
Other Study ID Numbers: P10.045
Study First Received: June 14, 2010
Last Updated: January 25, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
COPD
Inflammation
Small airways

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 22, 2014