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.

Hyperinflation of bronchi in vitro impairs bronchodilation to simulated breathing and increases sensitivity to contractile activation.

Background And Objective: Lung hyperinflation and reduced bronchodilation to deep inspiration (DI) are features of chronic obstructive pulmonary disease (COPD). Hyperinflation might impair the ability of a DI to stretch airway smooth muscle (ASM), as the bronchi operate at a stiff region of the pressure-volume curve.

Methods: Bronchial segments from pig lungs were mounted in an organ bath and equilibrated at either 5 cm H O (control) or 20 cm H O (hyperinflated) transmural pressure (P ).

Investigating the role of MRGPRC11 and capsaicin-sensitive afferent nerves in the anti-influenza effects exerted by SLIGRL-amide in murine airways.

Background: The hexapeptide SLIGRL-amide activates protease-activated receptor-2 (PAR-2) and mas-related G protein-coupled receptor C11 (MRGPRC11), both of which are known to be expressed on populations of sensory nerves. SLIGRL-amide has recently been reported to inhibit influenza A (IAV) infection in mice independently of PAR-2 activation, however the explicit roles of MRGPRC11 and sensory nerves in this process are unknown. Thus, the principal aim of this study was to determine whether SLIGRL-amide-induced inhibition of influenza infection is mediated by MRGPRC11 and/or by capsaicin-sensitive sensory nerves.

TNF and IL-1β exposure increases airway narrowing but does not alter the bronchodilatory response to deep inspiration in airway segments.

Background And Objective: While chronic inflammation of the airway wall and the failure of deep inspiration (DI) to produce bronchodilation are both common to asthma, whether pro-inflammatory cytokines modulate the airway smooth muscle response to strain during DI is unknown. The primary aim of the study was to determine how an inflammatory environment (simulated by the use of pro-inflammatory cytokines) alters the bronchodilatory response to DI.

Methods: We used whole porcine bronchial segments in vitro that were cultured in medium containing tumour necrosis factor and interleukin-1β for 2 days.

Does smooth muscle in an intact airway undergo length adaptation during a sustained change in transmural pressure?

In isolated airway smooth muscle (ASM) strips, an increase or decrease in ASM length away from its current optimum length causes an immediate reduction in force production followed by a gradual time-dependent recovery in force, a phenomenon termed length adaptation. In situ, length adaptation may be initiated by a change in transmural pressure (Ptm), which is a primary physiological determinant of ASM length. The present study sought to determine the effect of sustained changes in Ptm and therefore, ASM perimeter, on airway function.

Bronchodilatory response to deep inspiration in bronchial segments: the effects of stress vs. strain.

During deep inspirations (DI), a distending force is applied to airway smooth muscle (ASM; i.e., stress) and the muscle is lengthened (i.

Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma.

The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma (n = 5) or had no history of asthma (n = 8).

Airway Smooth Muscle Dynamics and Hyperresponsiveness: In and outside the Clinic.

The primary functional abnormality in asthma is airway hyperresponsiveness (AHR)-excessive airway narrowing to bronchoconstrictor stimuli. Our understanding of the underlying mechanism(s) producing AHR is incomplete. While structure-function relationships have been evoked to explain AHR (e.

Airways dilate to simulated inspiratory but not expiratory manoeuvres.

In a healthy human, deep inspirations produce bronchodilation of contracted airways, which probably occurs due to the transient distension of the airway smooth muscle (ASM). We hypothesised that deep expiratory manoeuvres also produce bronchodilation due to transient airway wall and ASM compression. We used porcine bronchial segments to assess the effects of deep inspirations, and maximal and partial expiration (submaximal) on airway calibre.

Responsiveness of the human airway in vitro during deep inspiration and tidal oscillation.

In healthy individuals, deep inspiration produces bronchodilation and reduced airway responsiveness, which may be a response of the airway wall to mechanical stretch. The aim of this study was to examine the in vitro response of isolated human airways to the dynamic mechanical stretch associated with normal breathing. Human bronchial segments (n = 6) were acquired from patients without airflow obstruction undergoing lung resection for pulmonary neoplasms.

Distribution of airway narrowing responses across generations and at branching points, assessed in vitro by anatomical optical coherence tomography.

Background: Previous histological and imaging studies have shown the presence of variability in the degree of bronchoconstriction of airways sampled at different locations in the lung (i.e., heterogeneity).

Airway narrowing assessed by anatomical optical coherence tomography in vitro: dynamic airway wall morphology and function.

Regulation of airway caliber by lung volume or bronchoconstrictor stimulation is dependent on physiological, structural, and mechanical events within the airway wall, including airway smooth muscle (ASM) contraction, deformation of the mucosa and cartilage, and tensioning of elastic matrices linking wall components. Despite close association between events in the airway wall and the resulting airway caliber, these have typically been studied separately: the former primarily using histological approaches, the latter with a range of imaging modalities. We describe a new optical technique, anatomical optical coherence tomography (aOCT), which allows changes at the luminal surface (airway caliber) to be temporally related to corresponding dynamic movements within the airway wall.

Effects of simulated tidal and deep breathing on immature airway contraction to acetylcholine and nerve stimulation.

Background And Objective: In adults, respiratory movements, such as tidal and deep breaths, reduce airway smooth muscle force and cause bronchodilation. Evidence suggests that these beneficial effects of oscillatory strain do not occur in children, possibly because of reduced coupling of the airways to lung tissue or maturational differences in the intrinsic response of the airways to oscillatory strain.

Methods: The bronchodilator effects of oscillatory strain were compared in isolated airway segments from immature (3-4 weeks and 8-10 weeks old) and mature (18-20 weeks old) pigs.

Responsiveness of the isolated airway during simulated deep inspirations: effect of airway smooth muscle stiffness and strain.

In vivo, breathing movements, including tidal and deep inspirations (DIs), exert a number of beneficial effects on respiratory system responsiveness in healthy humans that are diminished or lost in asthma, possibly as a result of reduced distension (strain) of airway smooth muscle (ASM). We used bronchial segments from pigs to assess airway responsiveness under static conditions and during simulated tidal volume oscillations with and without DI and to determine the roles of airway stiffness and ASM strain on responsiveness. To simulate airway dilations during breathing, we cycled the luminal volume of liquid-filled segments.