Quantification of smooth muscle in human airways by polarization-sensitive optical coherence tomography requires correction for perichondrium.

Quantifying airway smooth muscle (ASM) in patients with asthma raises the possibility of improved and personalized disease management. Endobronchial polarization-sensitive optical coherence tomography (PS-OCT) is a promising quantitative imaging approach that is in the early stages of clinical translation. To date, only animal tissues have been used to assess the accuracy of PS-OCT to quantify absolute (rather than relative) ASM in cross sections with directly matched histological cross sections as validation.

From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma-Obesity.

This article provides a contemporary report on the role of adipose tissue in respiratory dysfunction. Adipose tissue is distributed throughout the body, accumulating beneath the skin (subcutaneous), around organs (visceral), and importantly in the context of respiratory disease, has recently been shown to accumulate within the airway wall: "airway-associated adipose tissue." Excessive adipose tissue deposition compromises respiratory function and increases the severity of diseases such as asthma.

Distribution, composition, and activity of airway-associated adipose tissue in the porcine lung.

Patients with comorbid asthma-obesity experience greater disease severity and are less responsive to therapy. We have previously reported adipose tissue within the airway wall that positively correlated with body mass index. Accumulation of biologically active adipose tissue may result in the local release of adipokines and disrupt large and small airway function depending on its anatomical distribution.

Heterogeneity of Airway Smooth Muscle Remodeling in Asthma.

Ventilatory defects in asthma are heterogeneous and may represent the distribution of airway smooth muscle (ASM) remodeling. To determine the distribution of ASM remodeling in mild-severe asthma. The ASM area was measured in nine airway levels in three bronchial pathways in cases of nonfatal ( = 30) and fatal asthma ( = 20) and compared with control cases without asthma ( = 30).

Requirements and limitations of imaging airway smooth muscle throughout the lung in vivo.

Clinical visualization and quantification of the amount and distribution of airway smooth muscle (ASM) in the lungs of individuals with asthma has major implications for our understanding of airway wall remodeling as well as treatments targeted at the ASM. This paper theoretically investigates the feasibility of quantifying airway wall thickness (focusing on the ASM) throughout the lung in vivo by means of bronchoscopic polarization-sensitive optical coherence tomography (PS-OCT). Using extensive human biobank data from subjects with and without asthma in conjunction with a mathematical model of airway compliance, we define constraints that airways of various sizes pose to any endoscopic imaging technique and how this is impacted by physiologically relevant processes such as constriction, inflation and deflation.

Growth of the airway smooth muscle layer from late gestation to childhood is mediated initially by hypertrophy and subsequently hyperplasia.

Background And Objective: The airway smooth muscle (ASM) layer thickens during development. Identifying the mechanism(s) for normal structural maturation of the ASM reveals pathways susceptible to disease processes. This study characterized thickening of the ASM layer from foetal life to childhood and elucidated the underlying mechanism in terms of hypertrophy, hyperplasia and extracellular matrix (ECM) deposition.

Angiogenic regulatory influence of extracellular matrix deposited by resting state asthmatic and non-asthmatic airway smooth muscle cells is similar.

The extracellular matrix (ECM) is the tissue microenvironment that regulates the characteristics of stromal and systemic cells to control processes such as inflammation and angiogenesis. Despite ongoing anti-inflammatory treatment, low levels of inflammation exist in the airways in asthma, which alters ECM deposition by airway smooth muscle (ASM) cells. The altered ECM causes aberrant behaviour of cells, such as endothelial cells, in the airway tissue.

Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3.

Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [ extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process.

A Web Resource for Exploring the CORD-19 Dataset Using Root- and Rule-Based Phrases.

This short paper describes a web resource-the NIST CORD-19 Web Resource-for community explorations of the COVID-19 Open Research Dataset (CORD-19). The tools for exploration in the web resource make use of the NIST-developed Root- and Rule-based method, which exploits underlying linguistic structures to create terms that represent phrases in a corpus. The method allows for auto-suggesting-related terms to discover terms to refine the search of a COVID-19 heterogenous document base.

Airway remodelling with spatial correlations: Implications for asthma pathogenesis.

Airway remodelling is a cardinal feature of asthma in which airways undergo structural changes - in particular, increased airway smooth muscle mass and total airway wall area. Remodelling has long been thought to have functional consequences in asthma due to geometric effects that can increase airway narrowing and luminal occlusion. Prior studies have examined the distribution of remodelling between and within patients, but none have yet considered the possibility for spatial correlations in airway remodelling.

Airway narrowing and response to simulated deep inspiration in bronchial segments from subjects with fixed airflow obstruction.

The volume fraction of extracellular matrix (ECM) within the layer of airway smooth muscle (ASM) is increased in subjects with fixed airflow obstruction. We postulated that changes in ECM within the ASM layer will impact force transmission during induced contraction and/or in response to externally applied stresses like a deep inspiration (DI). Subjects were patients undergoing lung resection surgery who were categorized as unobstructed ( = 12) or "fixed" obstructed ( = 6) on the basis of preoperative spirometry.

Fatty airways: implications for obstructive disease.

Epidemiological studies report that overweight or obese asthmatic subjects have more severe disease than those of a healthy weight. We postulated that accumulation of adipose tissue within the airway wall may occur in overweight patients and contribute to airway pathology. Our aim was to determine the relationship between adipose tissue within the airway wall and body mass index (BMI) in individuals with and without asthma.

Patient-specific targeted bronchial thermoplasty: predictions of improved outcomes with structure-guided treatment.

Bronchial thermoplasty is a recent treatment for asthma in which ablative thermal energy is delivered to specific large airways according to clinical guidelines. Therefore, current practice is effectively "blind," as it is not informed by patient-specific data. The present study seeks to establish whether a patient-specific approach based on structural or functional patient data can improve outcomes and/or reduce the number of procedures required for clinical efficacy.

Airway smooth muscle proliferation and inflammation in asthma.

In asthma, it is unclear if the airway smooth muscle cells proliferate more or are increased at the onset of asthma and remain stable. This study aimed to compare smooth muscle cell proliferation in individuals with and without asthma and correlate proliferation rates with cell size and number and with granulocytic airway inflammation. Postmortem airway sections were labeled with proliferating cell nuclear antigen (PCNA) and percent positive muscle cells calculated.

Inflammation-dependent and independent airway remodelling in asthma.

Background And Objective: The pathology of asthma is characterized by airway inflammation (granulocytic (GA) or paucigranulocytic (PGA)) and remodelling of airway structures. However, the relationship between inflammatory phenotypes and remodelling is unclear. We hypothesized that some features of airway remodelling are dependent on granulocytic airway inflammation while others are not.

Unraveling a Clinical Paradox: Why Does Bronchial Thermoplasty Work in Asthma?

Bronchial thermoplasty is a relatively new but seemingly effective treatment in subjects with asthma who do not respond to conventional therapy. Although the favored mechanism is ablation of the airway smooth muscle layer, because bronchial thermoplasty treats only a small number of central airways, there is ongoing debate regarding its precise method of action. Our aim in the present study was to elucidate the underlying method of action behind bronchial thermoplasty.

Unique mechanisms of connective tissue growth factor regulation in airway smooth muscle in asthma: Relationship with airway remodelling.

Neovascularization, increased basal membrane thickness and increased airway smooth muscle (ASM) bulk are hallmarks of airway remodelling in asthma. In this study, we examined connective tissue growth factor (CTGF) dysregulation in human lung tissue and animal models of allergic airway disease. Immunohistochemistry revealed that ASM cells from patients with severe asthma (A) exhibited high expression of CTGF, compared to mild and non-asthmatic (NA) tissues.

Generating Domain Terminologies using Root- and Rule-Based Terms.

Motivated by the need for flexible, intuitive, reusable, and normalized terminology for guiding search and building ontologies, we present a general approach for generating sets of such terminologies from natural language documents. The terms that this approach generates are root- and rule-based terms, generated by a series of rules designed to be flexible, to evolve, and, perhaps most important, to protect against ambiguity and standardize semantically similar but syntactically distinct phrases to a normal form. This approach combines several linguistic and computational methods that can be automated with the help of training sets to quickly and consistently extract normalized terms.

Independent and combined effects of airway remodelling and allergy on airway responsiveness.

Airway remodelling and allergic inflammation are key features of airway hyperresponsiveness (AHR) in asthma; however, their interrelationships are unclear. The present study investigated the separate and combined effects of increased airway smooth muscle (ASM) layer thickness and allergy on AHR. We integrated a protocol of ovalbumin (OVA)-induced allergy into a non-inflammatory mouse model of ASM remodelling induced by conditional and airway-specific expression of transforming growth factor-α (TGF-α) in early growth response-1 (Egr-1)-deficient transgenic mice, which produced thickening of the ASM layer following ingestion of doxycycline.