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 allerg… Show more
“…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] .…”
The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. After triggering pEMT these and other metrics of UJT versus pEMT diverge. A computational model attributes effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, those tissues that are subject to development, injury, or disease become endowed with rich mechanisms for cellular migration, plasticity, self-repair, and regeneration.
“…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] .…”
The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. After triggering pEMT these and other metrics of UJT versus pEMT diverge. A computational model attributes effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, those tissues that are subject to development, injury, or disease become endowed with rich mechanisms for cellular migration, plasticity, self-repair, and regeneration.
“…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.…”
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confidence: 59%
“…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.…”
“…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.…”
The clinical assessment of fibrosis is critical to the diagnosis and management of patients with systemic sclerosis. Current clinical standards for patient assessment is to use skin fibrosis as an indicator of organ involvement, though this approach is highly subjective and relies on manual palpation. The development of a new method for accurately quantifying collagen content may therefore significantly improve the accuracy of the traditional skin score in patients with systemic sclerosis and may additionally aid in the monitoring of anti-fibrotic therapies in clinical practice. Polarization-sensitive optical coherence tomography (pS-oct) is a high-speed volumetric imaging modality that can be used to assess birefringent tissues including collagen. In this work we demonstrate a novel computational approach using PS-OCT for the assessment of fibrosis. This approach, based on the measured distribution of optic axis values associated with a given volume of collagen orientation, characterizes fibrotic changes independently from the depth of the region of interest in the tissue. This approach has the potential to accurately quantify collagen content and orientation faster and more robustly compared to traditional pS-oct metrics. We investigate the viability of this approach for assessing the development of fibrosis in a bleomycin induced skin fibrosis mouse model.
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