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

医学 中性粒细胞 支气管肺泡灌洗 病理 哮喘 嗜酸性粒细胞增多症 骨膜炎 嗜酸性粒细胞 内科学 细胞外基质 生物 细胞生物学
作者
Paweł Koźlik,Joanna Żuk,Sylwia Bartyzel,Jacek Zarychta,Krzysztof Okoń,Lech Zaręba,Jan G. Bazan,Joanna Kosałka,Jerzy Soja,Jacek Musiał,Stanisława Bazan‐Socha
出处
期刊:Clinical & Experimental Allergy [Wiley]
卷期号:50 (1): 15-28 被引量:26
标识
DOI:10.1111/cea.13501
摘要

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 Th 2 profile, higher circulating ADAM33, and blood neutrophilia. Lung function abnormalities and RBM thickening correlate better with CT‐metrics of distal than proximal airways.
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