Relationship between the thickness of bronchial wall layers, emphysema score, and markers of remodeling in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease

Abstract

KEY WORDSchronic obstructive pulmonary disease, computed tomography, emphysema score, endobronchial ultrasound, markers of remodelling ABSTRACT INTRODUCTION Airway remodeling plays an important role in the development of chronic obstructive pulmonary disease (COPD). Imaging methods, such as computed tomography (CT) and endobronchial ultrasound (EBUS), may be useful in the assessment of structural alterations in the lungs.OBJECTIVES The aim of this study was to evaluate a relationship between the severity of emphysema assessed by chest CT, the thickness of bronchial wall layers measured by EBUS, and the markers of remodeling in bronchoalveolar lavage fluid (BALF) in patients with COPD. PATIENTS AND METHODSThe study included 33 patients with COPD who underwent pulmonary function tests, emphysema score assessment by chest CT, as well as bronchofiberoscopy with EBUS in order to measure the total bronchial wall thickness and, separately, layers L 1 , L 2 , and L 3-5 . Selected remodeling (matrix metalloproteinase 9 [MMP-9], tissue inhibitor of metalloproteinase 1, transforming growth factor β 1 [TGF-β 1 ]) and inflammatory markers (neutrophil elastase, eosinophil cationic protein) were measured in BALF samples using an enzyme-linked immunosorbent assay.RESULTS MMP-9 levels in BALF were significantly higher in patients with very severe bronchial obstruction than in those with moderate and mild bronchial obstruction (P = 0.02), and showed a negative correlation with forced expiratory volume in 1 second (r = -0.538, P = 0.002). The thickness of L 1 and L 2 , which histologically correspond to the mucosa, submucosa, and smooth muscle, demonstrated a positive correlation with TGF-β 1 levels in BALF (r = 0.366, P = 0.046 and r = 0.425, P = 0.02) and the thickness of L 1 showed a negative association with neutrophil elastase levels (r = -0.508, P = 0.004). There was no significant correlation between the analyzed markers in BALF and the emphysema score. CONCLUSIONS Significant correlations of TGF-β 1 and elastase with the thickness of bronchial wall layers, and of MMP-9 with the severity of obstruction, may suggest the involvement of these markers in airway remodeling in patients with COPD.

The relationship of airway structural changes to blood and bronchoalveolar lavage biomarkers, and lung function abnormalities in asthma

“…We compared CT‐derived dimensions of proximal and distal airways, and measured low‐attenuation lung area (LAA%) by the conventional threshold level of −950 Hounsfield units, to show which of those indices correlate best with lung function, histology, and asthma biomarkers. The LAA% determines the percentile quantity of voxels showing a value lower than preset attenuation from all voxels within lung tissue and is usually employed for evaluation of emphysema . In asthma, however, it might be also related to the excessive narrowing of large and small airways with subsequent air trapping and hyperinflation .…”

AFM‐based nanomechanical characterization of bronchoscopic samples in asthma patients

“…Chronic inflammation and bronchial wall remodeling can alter the anatomy and mechanical properties of the airways. In routine diagnosis, an assessment of tissue remodeling is commonly performed by morphometry and histopathological analysis of biopsies and/or high‐resolution computed tomography, endobronchial ultrasound,, or optical coherence tomography . However, new emerging approaches are strongly needed to help diagnosis of asthma.…”

Seeking for the links between biochemical markers of remodeling and structural changes in chronic obstructive pulmonary disease: where are we?

“…10 The authors used both EBUS and HRCT to correlate the airway wall structural parameters as well as the so called emphysema score with the levels of selected biomarkers in the bronchoalveolar lavage fluid (BALF) and pulmonary function assessed in spirometry and body plethysmography. The evaluated biomarkers included matrix Although numerous antitobacco campaigns resulted in a decreased prevalence of some smoking--related diseases, chronic obstructive pulmonary disease (COPD), for which smoking remains the main risk factor, is still a major health problem worldwide.…”

“…In addition, EBUS seems to be more accurate than HRCT in the assessment of the airway wall, allowing even to discriminate its particular layers. 9,10 Indeed, a very recent study showed that EBUS may be more precise than HRCT in the measurement of BWT. 13 However, it must be emphasized that the evaluation of the features of the airway wall by EBUS is usually limited to a single segmental bronchus.…”

“…In the study by Górka et al, 10 the analysis of BALF provided mainly data from peripheral airways, while BWT was measured by EBUS in proximal airways. Therefore, it cannot be excluded that the lack of correlations between BWT and some investigated BALF biomarkers was, at least to some extent, associated with the different sites evaluated.…”