Bossé Ynuk

Laval University | ULAVAL · Faculty of Medicine

Force adaptation, a process whereby sustained spasmogenic activation (viz., tone) of airway smooth muscle (ASM) increases its contractile capacity, has been reported in isolated ASM tissues in vitro, as well as in mice in vivo. The objective of the present study was to assess the effect of tone on airway responsiveness in humans. Ten healthy volunt...

Asthma is a lung disorder triggered by various airborne factors in susceptible individuals. Although generally controlled, asthma can be severe and difficult to treat. Presently, increasing numbers of pharmaceuticals capable of blocking or mimicking specific endogenous molecules are undergoing clinical trials in asthmatic individuals whose symptoms...

Studying airway smooth muscle (ASM) in conditions that emulate the in vivo environment within which the bronchi normally operate may provide important clues regarding its elusive physiological function. The present study examines the effect of lengthening and shortening of ASM on tension development in human bronchial segments. ASM from each bronch...

Airway hyperresponsiveness to a spasmogenic challenge, such as methacholine, and an increased baseline tone, measured by the reversibility of airway obstruction with a bronchodilator, are two common features of asthma. However, whether the increased tone influences the degree of airway responsiveness to a spasmogen is unclear. Herein, we hypothesiz...

Rationale: Airway narrowing is maintained for a prolonged period after acute bronchoconstriction in humans in the absence of deep inspirations (DIs). Objectives: To determine whether maintenance of airway smooth muscle (ASM) shortening is responsible for the persistence of airway narrowing in healthy subjects following transient methacholine (MC...

Background and objective: The effect of serial incremental concentrations of methacholine is only slightly cumulative when assessed by spirometry. This limited cumulative effect may be attributed to the bronchodilator effect of deep inspirations that are required between concentrations to measure lung function. Using oscillometry, the response to...

Metrics used in spirometry caught on in respiratory medicine not only because they provide information of clinical importance but also because of a keen understanding of what is being measured. The forced expiratory volume in 1 s (FEV1), for example, is the maximal volume of air that can be expelled during the first second of a forced expiratory ma...

Hypoxia is common in lung diseases and a potent stimulator of the long non-coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 ( MALAT1 ). Herein, we investigated the impact of Malat1 on hypoxia-induced lung dysfunction in mice. Malat1 -deficient mice and their wild-type littermates were tested after 8 days of normoxia or hypoxia (10%...

Despite decades of research, studies investigating the physiological alterations caused by an acute bout of inflammation induced by exposing the lung to lipopolysaccharide have yielded inconsistent results. This can be attributed to small effects and/or a lack of fitted physiological testing. Herein, a comprehensive investigation of lung mechanics...

BALB/c mice from both sexes underwent one of two nebulized methacholine challenges that were preceded by a period of 20 min either with or without tone induced by repeated contractions of the airway smooth muscle. Impedance was monitored throughout and the constant phase model was used to dissociate the impact of tone on conducting airways (RN - Ne...

Objectif Nous avons testé l’hypothèse que la testostérone module les réponses pulmonaires à l’hypoxie intermittente (IH – modèle d’apnée du sommeil) chez des souris mâles. Méthodes Nous avons utilisé des souris intactes (SHAM) ou orchiectomisées (ORX) exposées à l’IH pendant 14 jours (12 h/jour, 10 cycles/h, 6 % O2 nadir) ou en normoxie (Nx). Nous...

There are renewed interests in using the parameter K of Salazar-Knowles' equation to assess lung tissue compliance. K either decreases or increases when the lung's parenchyma stiffens or loosens, respectively. However, whether K is affected by other common features of respiratory diseases, such as inflammation and airway smooth muscle (ASM) contrac...

New findings: What is the central question of this study? Does endogenous testosterone modulate the consequences of intermittent hypoxia (IH) in the lungs of male mice? What is the main finding and its importance? Orchiectomized mice exposed to IH develop a pattern that is similar to emphysema or obstructive lung disease with elevated lung volumes...

Aim of the study The current gold standard to assess respiratory mechanics in mice is oscillometry, a technique from which several readouts of the respiratory system can be deduced, such as resistance and elastance. However, these readouts are often not altered in mouse models of asthma. This is in stark contrast with humans, where asthma is genera...

The contractility of airway smooth muscle (ASM) is labile. Although this feature can greatly modulate the degree of airway responsiveness in vivo, the extent by which ASM’s contractility is affected by pulmonary allergic inflammation has never been compared between strains of mice exhibiting a different susceptibility to develop airway hyperrespons...

The airway smooth muscle undergoes an elastic transition during a sustained contraction, characterized by a gradual decrease in hysteresivity caused by a relatively greater rate of increase in elastance than resistance. We recently demonstrated that these mechanical changes are more likely to persist after a large strain when they are acquired in d...

Due to frequent and often severe lung affections caused by COVID-19, murine models of acute respiratory distress syndrome (ARDS) are increasingly used in experimental lung research. The one induced by a single lipopolysaccharide (LPS) exposure is practical. However, whether it is preferable to administer LPS intranasally or intratracheally remains...

The degree of airway responsiveness is generally measured by directly activating the airway smooth muscle (ASM) with incremental doses of inhaled methacholine. In this context, airway hyperresponsiveness (AHR) is defined as an excessive decline in lung function in response to methacholine. Innate or acquired defects in ASM size and/or contractile c...

Résumé Introduction Une portion importante des symptômes de certaines pathologies pulmonaires découle d’une constriction excessive des voies respiratoires due à la contraction du muscle lisse et à l’hyperréactivité bronchique. Une meilleure compréhension de l’ensemble des molécules extracellulaires qui contrôlent la contractilité du muscle lisse e...

Airway smooth muscle (ASM) is continuously strained during breathing at tidal volume. Whether this tidal strain influences the magnitude of the bronchodilator response to a deep inspiration (DI) is not clearly defined. The present in vitro study examines the effect of tidal strain on the bronchodilator effect of DIs. ASM strips from sheep tracheas...

Force adaptation of airway smooth muscle (ASM) is a process whereby the presence of tone (i.e., a sustained contraction) increases the contractile capacity. For example, tone has been shown to increase airway responsiveness in both healthy mice and humans. The goal of the present study is to elucidate the underlying molecular mechanisms. The maxima...

The shortening of airway smooth muscle (ASM) is greatly affected by time. This is because stimuli affecting ASM shortening, such as bronchoactive molecules or the strain inflicted by breathing maneuvers, not only alter quick biochemical processes regulating contraction but also slower processes that allow ASM to adapt to an ever changing length. Li...

Chronic obstructive pulmonary disease (COPD) can sometimes be associated with skeletal muscle atrophy. Hypoxemic episodes, which occur during disease exacerbation and daily physical activity, are frequent in COPD patients. However, the link between hypoxemia and muscle atrophy remains unclear, along with mechanisms of muscle hypoxic stress response...

The deep inspiration (DI) maneuver entices a great deal of interest because of its ability to temporarily ease the flow of air into the lungs. This salutary effect of a DI is proposed to be mediated, at least partially, by momentarily increasing the operating length of airway smooth muscle (ASM). Concerningly, this premise is largely derived from a...

A certain amount of time is required to achieve a maximal contraction from airway smooth muscle (ASM) and stretches of substantial magnitude, such as the ones imparted by deep inspirations (DIs), interfere with contraction. The duration of ASM contraction without interference may thus affect its shortening, its mechanical response to DIs and the ov...

Neutrophils and eosinophils are important sources of bioactive lipids from the 5- and the 15-lipoxygenase (LO) pathways. Herein, we compared the effectiveness of humans eosinophils and eosinophil-depleted neutrophils to synthesize 15-LO metabolites using a cocktail of different 15-LO substrates as well as their sensitivities to eight documented 15-...

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Air volume changes created by a conscious subject breathing spontaneously within a body box are at the basis of plethysmography, a technique used to non-invasively assess some features of the respiratory function in humans as well as in laboratory animals. The present article focuses on the application of the double-chamber plethysmography (DCP) in...

Background: Cigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associated with smoking and lipid homeostasis disruption. Severa...

It is suggested that the frequent strain the airways undergo in asthma, due to repeated airway smooth muscle (ASM)-mediated constrictions, contributes to airway wall remodeling. However, the effects of repeated constrictions on airway remodeling, as well as the ensuing impact of this presumptive remodeling on respiratory mechanics, have never been...

The mechanisms whereby anti-cholinergics improve asthma outcomes, such as lung function, symptoms and rate of exacerbation, can be numerous. The most obvious is by affecting the contraction of airway smooth muscle (ASM). The acetylcholine released from the cholinergic nerves is the most important bronchoconstrictor that sets the baseline degree of...

We designed a crossover and placebo-controlled trial to investigate the impact of a 1-h acute vaping session of nicotine-free and flavour-free e-liquid on the pulmonary functions and respiratory mechanics of healthy and asthmatic individuals. This study shows that a 1-h vaping session of a high-grade and contaminant-free mixture of propylene glycol...

Rationale: Airway hyperresponsiveness (AHR), a major hallmark of asthma, results from alterations of contractile and non-contractile elements of airway reactivity. CD34 is a sialomucin expressed on various cells involved in asthma, such as eosinophils and airway smooth muscle (ASM) precursors, highlighting its potential influence in AHR. Objectiv...

Study of Force adpatation in young healthy humans

Results about molecular mechanisms involved in Force Adaptation

The factors altering the bronchodilatory response to a deep inspiration (DI) in asthma are important to decipher. In this in vitro study, we investigated the effect of changing the duration between DIs on the rate of force recovery post-DI in guinea pig bronchi. The airway smooth muscle (ASM) within the main bronchi were submitted to length oscilla...

A non-invasive index of airway distensibility is required to track airway remodeling over time. The forced oscillation technique (FOT) provides such an index by measuring the change in respiratory system conductance at 5 Hz over the corresponding change in lung volume (ΔGrs5/ΔVL). To become useful clinically, this method has to be reproducible and...

Fibrosis complicates numerous pathologies including interstitial lung diseases. Sphingosine analogs such as FTY720 can alleviate lung injury-induced fibrosis in murine models. Contradictorily, FTY720 also promotes in vitro processes normally leading to fibrosis and high doses in vivo foster lung fibrosis by enhancing vascular leakage into the lung....

In asthma, excessive bronchial narrowing associated with thickening of the airway smooth muscle (ASM) causes respiratory distress. Numerous pharmacological agents prevent experimental airway hyperresponsiveness (AHR) when delivered prophylactically. However, most fail to resolve this feature after disease is instated. Although sphingosine analogs a...

The contractile capacity of airway smooth muscle is not fixed but modulated by an impressive number of extracellular inflammatory mediators. Targeting the transient component of airway hyperresponsiveness ascribed to this contractile lability of ASM is a quest of great promises in order to alleviate asthma symptoms during inflammatory flares. Howev...

Background In vivo phosphorylation of sphingosine analogs with their ensuing binding and activation of their cell-surface sphingosine-1-phosphate receptors is regarded as the main immunomodulatory mechanism of this new class of drugs. Prophylactic treatment with sphingosine analogs interferes with experimental asthma by impeding the migration of de...

In allergic asthma, homeostatic pathways are dysregulated, which leads to an immune response towards normally innocuous antigens. The CD200-CD200R pathway is a central regulator of inflammation and CD200 expression was recently found to be downregulated in circulating leukocytes of asthmatic patients. Given the anti-inflammatory properties of CD200...

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Deep inspirations (DIs) taken prior to an inhaled challenge with a spasmogen limit airway responsiveness in non-asthmatics. This phenomenon is called bronchoprotection and is severely impaired in asthmatics. The ability of DIs to prevent a decrease in FEV1 was initially attributed to inhibition of airway narrowing. However, DIs taken prior to metha...

Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agoni...

Airway inflammation and hyperresponsiveness (AHR) are important features of asthma. Both inflammation and AHR are complex traits that can each originate from a plethora of factors, where every factor can be independent, interconnected and dispensable. This review examines the complexity of the indices that we use to assess airway responsiveness. Th...

Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were: 1-To describe the 'length-dependency of ASM force' in response to different spasmogens; and 2-to predict, based on morphological data and a c...

Asthma is a prevalent and sometimes debilitating lung disorder caused by diverse triggers in susceptible individuals. Based on the salutary effect of drugs relaxing airway smooth muscle (ASM) in the treatment of asthma, there is no doubt that airway narrowing elicited by ASM shortening is involved in the development of symptoms. Asthmatic individua...

Asthma symptoms are triggered or exacerbated by a range of environmental factors, such as allergens, viruses, fungi, exercise, aspirin, pollutants, and occupational irritants and sensitizers. While traditionally considering an intrinsic disease, in more recent years asthma has been viewed by many as a genetically associated environmental lung disor...

The lung is a dynamic organ and the oscillating stress applied to the airway wall during breathing maneuvers can decrease airway smooth muscle (ASM) contractility. However, it is unclear whether it is the stress or the attendant strain that is responsible for the decline of ASM force associated with breathing maneuvers, and whether tone can prevent...

Airways from asthmatics have a propensity to narrow excessively in response to spasmogens (i.e., contractile agonists), a feature called airway hyperresponsiveness (AHR). AHR is an important contributor to asthma symptoms because the degree of responsiveness dictates the amount of airway narrowing that occurs in response to inflammation-derived spa...

Airway inflammation in patients with asthma exposes the airway smooth muscle (ASM) to a variety of spasmogens. These spasmogens increase ASM tone, which can lead to force adaptation. Length oscillations of ASM, which occur in vivo due to breathing maneuvers, can attenuate force adaptation. However, in the presence of tone, the force oscillations re...

Airway smooth muscle (ASM) is the major effector of excessive airway narrowing in asthma. Changes in some of the mechanical properties of ASM could contribute to excessive narrowing and have not been systematically studied in human ASM from nonasthmatic and asthmatic subjects. Human ASM strips (eight asthmatic and six nonasthmatic) were studied at...

Asthma is characterized by airway inflammation, with a consequent increase in spasmogens, and exaggerated airway narrowing in response to stimuli, termed airway hyperresponsiveness (AHR). The nature of any relationship between inflammation and AHR is less clear. Recent ex vivo data has suggested a novel mechanism by which inflammation may lead to A...

Asthma is a respiratory syndrome occurring in individuals who have genetic susceptibility to develop exaggerated airway narrowing to environmental triggers. The symptoms are generally paroxysmal and typically reversible by the use of drugs relaxing airway smooth muscle (ASM). Despite considerable heterogeneity with respect to etiology, age of onset...

Enlargement of airway smooth muscle (ASM) tissue around the bronchi/bronchioles is a histopathological signature of asthmatic airway remodelling and has been suggested to play a critical role in the increased lung resistance and airway hyperresponsiveness seen in asthmatic patients. The pleiotropic cytokine, TGF-β1, is believed to contribute to sev...

To achieve gas exchange, inspired air must pass through an intricate and dynamic tracheobronchial tree. The tree offers resistance to airflow, and increased resistance is the most important functional change in lung disease. Numerous mechanisms contribute to increased resistance by causing airway narrowing, closure, occlusion, and/or obliteration....

Les niveaux d’antioxydants, d’especes oxygenees reactives (ROS) et d’especes azotees reac~tives (RNS) sont les principaux determinants du milieu redox. Les ROS et les RNS produi~tes lors de l’activite physique occasionnent des perturbations redox pouvant moduler la force de contraction des muscles squelettiques et induire la fatigue musculaire. On...

The amplitude of strain in airway smooth muscle (ASM) produced by oscillatory perturbations such as tidal breathing or deep inspiration (DI) influences the force loss in the muscle and is therefore a key determinant of the bronchoprotective and bronchodilatory effects of these breathing maneuvers. The stiffness of unstimulated ASM (passive stiffnes...

Airway smooth muscle (ASM) plays a vital role in the exaggerated airway narrowing seen in asthma. However, whether asthmatic ASM is mechanically different from nonasthmatic ASM is unclear. Much of our current understanding about ASM mechanics comes from measurements made in other species. Limited data on human ASM mechanics prevents proper comparis...