Biomarkers in Chronic Obstructive Pulmonary Disease (COPD)

• 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.
  
  

• 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.
  
  

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.