Quantitative assessment of airway remodelling and response to allergen in asthma

Abstract

Background and objective: In vivo evaluation of the microstructural differences between asthmatic and nonasthmatic airways and their functional consequences is relevant to understanding and, potentially, treating asthma. In this study, we use endobronchial optical coherence tomography to investigate how allergic airways with asthma differ from allergic non-asthmatic airways in baseline microstructure and in response to allergen challenge. Methods: A total of 45 subjects completed the study, including 20 allergic, mildly asthmatic individuals, 22 non-asthmatic allergic controls and 3 healthy controls. A 3-cm airway segment in the right middle and right upper lobe were imaged in each subject immediately before and 24 h following segmental allergen challenge to the right middle lobe. Relationships between optical airway measurements (epithelial and mucosal thicknesses, mucosal buckling and mucus) and airway obstruction (FEV 1 /FVC (forced expiratory volume in 1 s/forced vital capacity) and FEV 1 % (FEV 1 as a percentage of predictive value)) were investigated. Results: Significant increases at baseline and in response to allergen were observed for all four of our imaging metrics in the asthmatic airways compared to the non-asthmatic airways. Epithelial thickness and mucosal buckling exhibited a significant relationship to FEV 1 /FVC in the asthmatic group. Conclusion: Simultaneous assessments of airway microstructure, buckling and mucus revealed both structural and functional differences between the mildly asthmatic and control groups, with airway buckling seeming to be the most relevant factor. The results of this study demonstrate that a comprehensive, microstructural approach to assessing the airways may be important in future asthma studies as well as in the monitoring and treatment of asthma. † P < 0.05 for post hoc comparison with AC. ‡ P < 0.05 for post hoc comparison with HC. § HC group excluded and Mann-Whitney test was used for statistical analysis. AA, allergic asthmatic; AC, allergic control; BAU, bioequivalent allergen unit; FEV 1 , forced expiratory volume in 1 s; FVC, forced vital capacity; HC, healthy control; PC20, concentration of methacholine needed to produce a 20% fall of FEV 1 from baseline.

In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition

“…To induce UJT we exposed the cell layer to apical-to-basal mechanical compression of 2.9 kPa (30 cm H 2 O) for 3 h. This level of compression was chosen for three reasons. First, this level of compressive stress mimics that experienced by the epithelial layer during asthmatic bronchoconstriction 66,[68][69][70][71][72][73] . Second, based upon simple physical arguments this level of compressive stress is readily generalizable to other situations For example, the bulk compressive stiffness modulus of the cell is quite large-on the order of 10 7 -10 8 Pa-whereas traction stresses are typically on the order of 100 Pa, intercellular stresses are on the order of 1000 Pa, cellular Young's moduli vary from 100 Pa to 10 kPa depending on cell type 74 , and the cortical shear stiffness is on the order of 1000 Pa 37,[75][76][77] .…”

Peering deeper into asthmatic lungs

“…The degree of baseline mucosal buckling strongly correlated with airway obstruction as measured by forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC) ratio. Segmental allergen challenge resulted in an increase in mucosal and epithelial thickness, as well as inducing more mucosal buckling; this increase was still detectable 24 h after allergen challenge . This is the first directly observed mucosal buckling in human airways at baseline or following allergen challenge.…”

“…In a recent publication in Respirology , Adams et al . demonstrate mucosal buckling in the airways of allergic asthmatic patients following segmental allergen challenge using optical coherence tomography (OCT) via a bronchoscope OCT is routine in retinal imaging and uses light to image a few millimetres into living tissue without causing damage. The investigating team performed endobronchial OCT on a 3‐cm length of the airway in the right middle and upper lobes of the study subjects, before and following segmental allergen challenge.…”

Assessing the progression of systemic sclerosis by monitoring the tissue optic axis using PS-OCT

“…We believe that this approach could replace current subjective clinical approaches for assessing fibrosis by offering the ability to provide large-scale quantitative assessments. Fiber optic PS-OCT has been performed in intracoronary 35 , gastrointestinal 36 and other endoscopic applications 37 . Though our study focused on the assessment of dermal fibrosis, PS-OCT imaging and OA entropy analysis could open the opportunity to objectively follow and compare disease progression, treatment and management of other organs within the body.…”