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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 METHODS    The 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 L1, L2, and L3-5. Selected remodeling (matrix metalloproteinase 9 [MMP-9], tissue inhibitor of metalloproteinase 1, transforming growth factor β1 [TGF-β1]) 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 L1 and L2, which histologically correspond to the mucosa, submucosa, and smooth muscle, demonstrated a positive correlation with TGF-β1 levels in BALF (r = 0.366, P = 0.046 and r = 0.425, P = 0.02) and the thickness of L1 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-β1 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.

Introduction: While spirometry plays a key role in diagnosing chronic obstructive pulmonary disease (COPD), imaging methods including endobronchial ultrasound (EBUS) and chest computed tomography (CT) appear to be useful for investigating structural changes in the lungs., Objectives: The aim of this study was to evaluate remodeling in COPD patients using EBUS and chest CT., Patients and Methods: The study included 33 patients with COPD, 15 patients with severe asthma, and 15 control subjects. All subjects underwent pulmonary function tests and bronchoscopy with EBUS to measure the total thickness of the bronchial wall and its layers. Additionally, in COPD patients, a chest CT was performed to measure total bronchial wall thickness., Results: The total bronchial wall thickness measured by EBUS in patients with COPD (1.192 ±0.079 mm) was significantly smaller than that in asthmatic patients (1.433 ±0.230 mm, P = 0.001) and significantly greater than in control subjects (1.099 ±0.095 mm, P = 0.04), and was positively correlated with residual volume (RV) / total lung capacity (r = 0.5, P = 0.02), RV (r = 0.6, P = 0.007), and RV (%) (r = 0.5, P = 0.05). The thickness of the bronchial wall layers in patients with COPD were as follows: L1 = 0.135 ±0.018 mm, L2 = 0.151 ±0.026 mm, and L3-5 = 0.906 ±0.065 mm. There was no correlation between the thickness of the bronchial wall layers and forced expiratory volume in 1 second., Conclusions: The results of this study show that EBUS is a useful method for evaluating bronchial wall layers not only in asthma but also in COPD, and suggest that the pattern of remodeling differs in each of these diseases.

Jerzy Soja,1,2 Karolina Górka,1,2 Iwona Gross-Sondej,1,2 Bogdan Jakieła,2 Sławomir Mikrut,3 Krzysztof Okoń,4 Adam Ćmiel,5 Piotr Sadowski,4 Wojciech Szczeklik,6 Anna Andrychiewicz,7 Tomasz Stachura,1,2 Grażyna Bochenek,1,2 Stanisława Bazan-Socha,2 Krzysztof Sładek1,2 1Department of Pulmonology and Allergology, University Hospital, Kraków, Poland; 2 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland; 3Faculty of Mining, Surveying and Environmental Engineering, AGH University of Science and Technology, Kraków, Poland; 4Department of Pathology, Jagiellonian University Medical College, Kraków, Poland; 5Department of Applied Mathematics, AGH University of Science and Technology, Kraków, Poland; 6Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Kraków, Poland; 7Department of Endoscopy, University Hospital, Kraków, PolandCorrespondence: Jerzy Soja, Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, Krakow, 30-688, Poland, Email jerzy.soja@uj.edu.plBackground: Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe asthma leading to the clinical improvement, but morphologic changes of bronchial wall related to the procedure and predictors of a favorable response to BT remain uncertain. The aim of the study was to validate an endobronchial ultrasound (EBUS) in assessing the effectiveness of BT treatment.Methods: Patients with severe asthma who met the clinical criteria for BT were included. In all patients clinical data, ACT and AQLQ questionnaires, laboratory tests, pulmonary function tests and bronchoscopy with radial probe EBUS and bronchial biopsies were collected. BT was performed in patients with the thickest bronchial wall L2 layer representing ASM. These patients were evaluated before and after 12 months of follow-up. The relationship between baseline parameters and clinical response was explored.Results: Forty patients with severe asthma were enrolled to the study. All 11 patients qualified to BT successfully completed the 3 sessions of bronchoscopy. BT improved asthma control (P=0.006), quality of life (P=0.028) and decreased exacerbation rate (P=0.005). Eight of the 11 patients (72.7%) showed a clinically meaningful improvement. BT also led to a significant decrease in the thicknesses of bronchial wall layers in EBUS (L1 decreased from 0.183 to 0.173 mm, P=0.003; L2 from 0.207 to 0.185 mm, P = 0.003; and L3– 5 from 0.969 to 0.886 mm, P=0.003). Median ASM mass decreased by 61.8% (P=0.002). However, there was no association between baseline patient characteristics and the magnitude of clinical improvement after BT.Conclusion: BT was associated with a significant decrease in the thickness of the bronchial wall layers measured by EBUS including L2 layer representing ASM and ASM mass reduction in bronchial biopsy. EBUS can assess bronchial structural changes related to BT; however, it did not predict the favorable clinical response to therapy.Keywords: airway remodeling, airway smooth muscle, bronchial thermoplasty, bronchial wall layers, endobronchial ultrasound

Karolina Górka,1,2 Iwona Gross-Sondej,1,2 Jacek Górka,3 Tomasz Stachura,1,2 Kamil Polok,1,3 Natalia Celejewska-Wójcik,1,2 Sławomir Mikrut,4 Anna Andrychiewicz,5 Krzysztof Sładek,1,2,* Jerzy Soja1,2,* 1Department of Pulmonology and Allergology, University Hospital, Kraków, Poland; 2 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland; 3Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Kraków, Poland; 4Faculty of Mining Surveying and Environmental Engineering, AGH University of Science and Technology, Kraków, Poland; 5Department of Endoscopy, University Hospital, Kraków, Poland*These authors contributed equally to this workCorrespondence: Jerzy Soja 2nd Department of Internal Medicine, Jagiellonian University Medical College, ul Jakubowskiego 2, Kraków, 30-688, PolandTel +48 12 400 30 53Fax +48 12 400 30 67Email jerzy.soja@uj.edu.plPurpose: The aim of this study was to evaluate the structural changes of the airways using the endobronchial ultrasound (EBUS) in ACO patients compared to severe asthma and COPD patients.Patients and Methods: The study included 17 patients with ACO, 17 patients with COPD and 33 patients with severe asthma. Detailed clinical data were obtained from all participants. Basic laboratory tests were performed, including measurement of eosinophil counts in blood and serum immunoglobulin E (IgE) concentrations. All patients underwent spirometry and bronchoscopy with EBUS (a 20‑MHz ultrasound probe) to measure the total thicknesses of the bronchial walls and their particular layers in segmental bronchi of the right lower lobe. EBUS allows to distinguish five layers of the bronchial wall. Layer 1 (L1) and layer 2 (L2) were analyzed separately, while the outer layers (layers 3– 5 [L3– 5]) that correspond to cartilage were assessed together.Results: In patients with ACO the thicknesses of the L1 and L2 layers, which are mainly responsible for remodeling, were significantly greater than in patients with COPD and significantly smaller than in patients with severe asthma (median L1= 0.17 mm vs 0.16 mm vs 0.18 mm, p< 0.001; median L2= 0.18 mm vs 0.17 mm vs 0.20 mm, p< 0.001, respectively). The thicknesses of the total bronchial walls (L1+L2+L3– 5) and L3– 5 were significantly smaller in ACO and COPD patients compared to asthma patients (median L1+L2+L3– 5= 1.2 mm vs 1.14 mm vs 1.31 mm, p< 0.001; median L3– 5= 0.85 mm vs, 0.81 mm vs 0.92 mm, p=0.001, respectively).Conclusion: The process of structural changes in the airways assessed by EBUS is more advanced in individuals with ACO compared to patients with COPD, and less pronounced compared to patients with severe asthma. It seems that EBUS may provide useful information about differences in airway remodeling between ACO, COPD and severe asthma.Keywords: asthma-COPD overlap, airway remodeling, total bronchial wall, bronchial wall layers, endobronchial ultrasound