Biomarkers in Chronic Obstructive Pulmonary Disease (COPD)
Biomarkers in Chronic Obstructive Pulmonary Disease (COPD)
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.
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.
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).