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

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

Impaired small airway function in non‐asthmatic chronic rhinosinusitis with nasal polyps

“…Some evidence suggests that the degree of type‐2 inflammation in the lower airway and circulation is related to lower airway dysfunction. Kozlik et al 34 found that patients with airflow limitations had greater degrees of eosinophilia in blood and bronchoalveolar lavage samples, and Mauro et al 35 reported that asthma patients with impaired lung function had increased blood Eos numbers and values for fractional exhaled NO (FeNO). Asthma patients with nasal polyps show a more severe type‐2 response than asthma patients without nasal polyps 35 .…”

ERS International Congress, Madrid, 2019: highlights from the Airway Diseases, Asthma and COPD Assembly

“…BAZAN-SOCHA et al [99] found that fixed airflow limitation and histological signs of airway remodelling correlated better with computed tomography changes in distal than proximal airways in asthmatic patients. Interestingly, those patients had eosinophilia and higher circulating periostin, but also higher blood neutrophils and circulating ADAM33 [100]. Of note, ADAM33 gene polymorphism has already been associated with asthma [101].…”

Developments allergy in 2019 through the eyes of Clinical and Experimental Allergy, Part II clinical allergy

“…Kozlik and colleagues have reported a detailed and complex study of airway structure in ~100 asthmatics linking structure, cytokines, biomarkers and lung function in asthma 62 . The findings broadly suggest that remodelling is most closely associated with classic Th2 biomarkers together with systemic neutrophilia and a variety of other inflammatory markers.…”