Pawel Kozlik1, Joanna Zuk1, Sylwia Bartyzel1, Jacek Zarychta1,2, Krzysztof Okon3, Lech Zareba4, Jan G Bazan5, Joanna Kosalka1, Jerzy Soja1, Jacek Musial1, Stanislawa Bazan-Socha1. 1. Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. 2. Pulmonary Hospital, Zakopane, Poland. 3. Department of Pathology, Jagiellonian University Medical College, Krakow, Poland. 4. Faculty of Mathematics and Natural Sciences, University of Rzeszow, Rzeszow, Poland. 5. Interdisciplinary Centre for Computational Modelling, University of Rzeszow, Rzeszow, Poland.
Abstract
BACKGROUND: Airway structural changes are important in asthma pathology and require further investigations. OBJECTIVE: We sought to evaluate which computed tomography (CT) indices, bronchial histological traits, or blood and bronchoalveolar lavage (BAL) biomarkers correlate best with lung function abnormalities in asthma. METHODS: In 105 white adult asthmatics (53 with a component of fixed airflow obstruction), we determined airway cross-sectional geometry of two proximal (the right upper lobe apical segmental and the left apicoposterior) and two distal (the right and the left basal posterior) bronchi, quantified the low-attenuation lung area (LAA%), and analysed clusters based on airway CT-metrics. We also performed bronchofiberoscopy with BAL and endobronchial biopsy, assessed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, IL-23, interferon (INF)γ and periostin, together with circulating a disintegrin and metalloproteinase domain-containing protein (ADAM)33, and investigated interplays between analysed variables. RESULTS: Patients with fixed airflow limitation were characterized by lower lumen area and increased wall area and wall thickness ratios in distal airways, accompanied by raised LAA%. They had also higher blood neutrophilia, blood and BAL eosinophilia, increased circulating fibrinogen, periostin, and ADAM33. Blood neutrophilia, serum high density lipoproteins, thyroid-stimulating hormone, and shortened activated partial thromboplastin time were determinants of thicker reticular basement membrane (RBM). BAL eosinophilia was the only positive predictor of collagen I accumulation. Surprisingly, we observed a negative correlation between RBM thickening and collagen I deposit. Cluster analysis based on CT-metrics of the right lower lobe basal posterior bronchus revealed three well-separated clusters similar in age, asthma duration, and BMI, but different in RBM thickness, collagen I accumulation, and inflammatory markers. CONCLUSIONS AND CLINICAL RELEVANCE: Airway remodelling traits are mainly related to the Th2 profile, higher circulating ADAM33, and blood neutrophilia. Lung function abnormalities and RBM thickening correlate better with CT-metrics of distal than proximal airways.
BACKGROUND: Airway structural changes are important in asthma pathology and require further investigations. OBJECTIVE: We sought to evaluate which computed tomography (CT) indices, bronchial histological traits, or blood and bronchoalveolar lavage (BAL) biomarkers correlate best with lung function abnormalities in asthma. METHODS: In 105 white adult asthmatics (53 with a component of fixed airflow obstruction), we determined airway cross-sectional geometry of two proximal (the right upper lobe apical segmental and the left apicoposterior) and two distal (the right and the left basal posterior) bronchi, quantified the low-attenuation lung area (LAA%), and analysed clusters based on airway CT-metrics. We also performed bronchofiberoscopy with BAL and endobronchial biopsy, assessed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, IL-23, interferon (INF)γ and periostin, together with circulating a disintegrin and metalloproteinase domain-containing protein (ADAM)33, and investigated interplays between analysed variables. RESULTS:Patients with fixed airflow limitation were characterized by lower lumen area and increased wall area and wall thickness ratios in distal airways, accompanied by raised LAA%. They had also higher blood neutrophilia, blood and BAL eosinophilia, increased circulating fibrinogen, periostin, and ADAM33. Blood neutrophilia, serum high density lipoproteins, thyroid-stimulating hormone, and shortened activated partial thromboplastin time were determinants of thicker reticular basement membrane (RBM). BAL eosinophilia was the only positive predictor of collagen I accumulation. Surprisingly, we observed a negative correlation between RBM thickening and collagen I deposit. Cluster analysis based on CT-metrics of the right lower lobe basal posterior bronchus revealed three well-separated clusters similar in age, asthma duration, and BMI, but different in RBM thickness, collagen I accumulation, and inflammatory markers. CONCLUSIONS AND CLINICAL RELEVANCE: Airway remodelling traits are mainly related to the Th2 profile, higher circulating ADAM33, and blood neutrophilia. Lung function abnormalities and RBM thickening correlate better with CT-metrics of distal than proximal airways.
Authors: Alberto Papi; Dave Singh; J Christian Virchow; G Walter Canonica; Andrea Vele; George Georges Journal: Clin Transl Allergy Date: 2022-04-17 Impact factor: 5.657
Authors: Stanislawa Bazan-Socha; Sylwia Buregwa-Czuma; Bogdan Jakiela; Lech Zareba; Izabela Zawlik; Aleksander Myszka; Jerzy Soja; Krzysztof Okon; Jacek Zarychta; Paweł Kozlik; Sylwia Dziedzina; Agnieszka Padjas; Krzysztof Wojcik; Michal Kepski; Jan G Bazan Journal: Int J Mol Sci Date: 2021-01-20 Impact factor: 5.923
Authors: Andrew Menzies-Gow; Flavia L Hoyte; David B Price; David Cohen; Peter Barker; James Kreindler; Maria Jison; Christopher L Brooks; Peggy Papeleu; Rohit Katial Journal: Adv Ther Date: 2022-03-14 Impact factor: 4.070
Authors: Stanisława Bazan-Socha; Krzysztof Wójcik; Magdalena Olchawa; Tadeusz Sarna; Jakub Pięta; Bogdan Jakieła; Jerzy Soja; Krzysztof Okoń; Jacek Zarychta; Lech Zaręba; Michał Stojak; Daniel P Potaczek; Jan G Bazan; Magdalena Celińska-Lowenhoff Journal: Biomedicines Date: 2022-06-24
Authors: Stanislawa Bazan-Socha; Bogdan Jakiela; Joanna Zuk; Jacek Zarychta; Jerzy Soja; Krzysztof Okon; Sylwia Dziedzina; Lech Zareba; Jerzy Dropinski; Krzysztof Wojcik; Agnieszka Padjas; Cezary Marcinkiewicz; Jan G Bazan Journal: Int J Mol Sci Date: 2021-06-12 Impact factor: 5.923
Authors: Lies Lahousse; Thomas Bahmer; Sara Cuevas-Ocaña; Pauline Flajolet; Alexander G Mathioudakis; Melissa McDonnell; Lena Uller; Florence Schleich; Sergio Dortas Junior; Marco Idzko; Dave Singh; Fabio L M Ricciardolo; Ian M Adcock; Omar Usmani; Antonio Spanevello; Sara J Bonvini Journal: ERJ Open Res Date: 2020-02-17