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Respirology (Carlton, Vic.) Mar 2018Severe asthma is defined by the high treatment requirements to partly or fully control the clinical manifestations of disease. It remains a problem worldwide with a... (Review)
Review
Severe asthma is defined by the high treatment requirements to partly or fully control the clinical manifestations of disease. It remains a problem worldwide with a large burden for individuals and health services. The key to improving targeted treatments, reducing disease burden and improving patient outcomes is a better understanding of the pathophysiology and mechanisms of severe disease. The heterogeneity, complexity and difficulties in undertaking clinical studies in severe asthma remain challenges to achieving better understanding and better outcomes. In this review, we focus on the structural, mechanical and inflammatory abnormalities that are relevant in severe asthma.
Topics: Airway Remodeling; Asthma; Bronchoconstriction; Forced Expiratory Flow Rates; Humans; Severity of Illness Index
PubMed: 29316003
DOI: 10.1111/resp.13251 -
The European Respiratory Journal Oct 2018Acetylcholine binds to muscarinic receptors to play a key role in the pathophysiology of asthma, leading to bronchoconstriction, increased mucus secretion, inflammation... (Review)
Review
Acetylcholine binds to muscarinic receptors to play a key role in the pathophysiology of asthma, leading to bronchoconstriction, increased mucus secretion, inflammation and airway remodelling. Anticholinergics are muscarinic receptor antagonists that are used in the treatment of chronic obstructive pulmonary disease and asthma. Recent and data have increased our understanding of how acetylcholine contributes to the disease manifestations of asthma, as well as elucidating the mechanism of action of anticholinergics. This review assesses the latest literature on acetylcholine in asthma pathophysiology, with a closer look at its role in airway inflammation and remodelling. New insights into the mechanism of action of anticholinergics, their effects on airway remodelling, and a review of the efficacy and safety of long-acting anticholinergics in asthma treatment will also be covered, including a summary of the latest clinical trial data.
Topics: Acetylcholine; Airway Remodeling; Asthma; Bronchoconstriction; Cholinergic Antagonists; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic
PubMed: 30115613
DOI: 10.1183/13993003.01247-2017 -
Pneumonologia I Alergologia Polska 2011Terms exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB) are used to describe transient bronchoconstriction occurring during or immediately... (Review)
Review
Terms exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB) are used to describe transient bronchoconstriction occurring during or immediately after vigorous exercise in some subjects. For the diagnosis of EIB it is necessary to show at least 10% decrease in FEV1 from baseline following physical exercise. The prevalence of EIB has been reported to be 12-15% in general population, 10-20% in summer olympic athletes, affecting up to 50-70% of winter athletes (particularly ski runners and skaters). There are two key theories explaining EIB: thermal and osmotic. Differential diagnosis of EIB should include chronic cardio-pulmonary diseases, vocal cord dysfunction, hyperventilation syndrome and poor physical fitness or overtraining. According to the ATS guidelines from 1999 for the diagnosis of EIB a standardized exercise on a treadmill or cycle ergometer test with stable environmental conditions regarding temperature and humidity of inhaled air, should be employed. Other laboratory tests assessing bronchial hyperresponsiveness to indirect stimuli including eucapnic voluntary hyperpnea (EVH), mannitol, hypertonic saline, AMP or measurement of exhaled nitric oxide (FENO) are also successfully used. In the prevention of EIB include both pharmacologic and non-pharmacologic treatment. In patients with poorly controlled asthma intensification of anti-inflammatory treatment can decrease the frequency and severity of EIB. Short and long acting beta2-agonists, antileukotriene drugs can be used prior to exercise to prevent EIB.
Topics: Asthma, Exercise-Induced; Bronchial Provocation Tests; Bronchoconstriction; Exercise; Exercise Test; Humans; Prevalence; Respiratory Function Tests
PubMed: 21190152
DOI: No ID Found -
Lung Dec 2023Airway nerves regulate vital airway functions including bronchoconstriction, cough, and control of respiration. Dysregulation of airway nerves underlies the development... (Review)
Review
Airway nerves regulate vital airway functions including bronchoconstriction, cough, and control of respiration. Dysregulation of airway nerves underlies the development and manifestations of airway diseases such as chronic cough, where sensitization of neural pathways leads to excessive cough triggering. Nerves are heterogeneous in both expression and function. Recent advances in confocal imaging and in targeted genetic manipulation of airway nerves have expanded our ability to visualize neural organization, study neuro-immune interactions, and selectively modulate nerve activation. As a result, we have an unprecedented ability to quantitatively assess neural remodeling and its role in the development of airway disease. This review highlights our existing understanding of neural heterogeneity and how advances in methodology have illuminated airway nerve morphology and function in health and disease.
Topics: Humans; Cough; Asthma; Respiratory System; Bronchoconstriction; Chronic Disease
PubMed: 37985513
DOI: 10.1007/s00408-023-00659-x -
Experimental Biology and Medicine... Jun 2021Asthma is a chronic inflammatory lung disease affecting approximately 7.7% of the US population. Sex differences in the prevalence, incidence, and severity of asthma... (Review)
Review
Asthma is a chronic inflammatory lung disease affecting approximately 7.7% of the US population. Sex differences in the prevalence, incidence, and severity of asthma have been widely described throughout the lifespan, showing higher rates in boys than girls before puberty, but a reversed pattern in adults. Asthma is often associated with atopy, i.e. the tendency to develop allergic diseases, and can be worsened by environmental stimuli and/or exercise. While not exclusive to patients with asthma, exercise-induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. Currently, there is limited research on sex differences in EIB and its relationship with atopy and asthma in men and women. In this minireview, we summarize the available literature on this topic. Overall, the collective knowledge supports the notion that physiological changes triggered during exercise affect males and females differently, suggesting an interaction among sex, exercise, sex hormones, and atopic status in the course of EIB pathophysiology. Understanding these differences is important to provide personalized management plans to men and women who exercise regularly and suffer from underlying asthma and/or atopy.
Topics: Animals; Asthma; Athletes; Bronchoconstriction; Exercise; Humans; Prevalence; Sex Characteristics
PubMed: 33794694
DOI: 10.1177/15353702211003858 -
Respirology (Carlton, Vic.) Jun 2019
Topics: Body Mass Index; Bronchoconstriction; Humans; Lung; Obesity
PubMed: 30897266
DOI: 10.1111/resp.13532 -
Journal of Veterinary Internal Medicine Jul 2021Electrical impedance tomography (EIT) generates images of the lungs based on impedance change and was able to detect changes in airflow after histamine challenge in...
BACKGROUND
Electrical impedance tomography (EIT) generates images of the lungs based on impedance change and was able to detect changes in airflow after histamine challenge in horses.
OBJECTIVES
To confirm that EIT can detect histamine-provoked changes in airflow and subsequent drug-induced bronchodilatation. Novel EIT flow variables were developed and examined for changes in airflow.
METHODS
Bronchoconstriction was induced using stepwise histamine bronchoprovocation in 17 healthy sedated horses. The EIT variables were recorded at baseline, after saline nebulization (control), at the histamine concentration causing bronchoconstriction (C ) and 2 and 10 minutes after albuterol (salbutamol) administration. Peak global inspiratory (PIF ) and peak expiratory EIT (PEF ) flow, slope of the global expiratory flow-volume curve (FV ), steepest FV over all pixels in the lung field, total impedance change (surrogate for tidal volume; VT ) and intercept on the expiratory FV curve normalized to VT (FV /VT ) were indexed to baseline and analyzed for a difference from the control, at C , 2 and 10 minutes after albuterol. Multiple linear regression explored the explanation of the variance of Δflow, a validated variable to evaluate bronchoconstriction using all EIT variables.
RESULTS
At C , PIF , PEF , and FV significantly increased whereas FV /VT decreased. All variables returned to baseline 10 minutes after albuterol. The VT did not change. Multivariable investigation suggested 51% of Δflow variance was explained by a combination of PIF and PEF .
CONCLUSIONS AND CLINICAL IMPORTANCE
Changes in airflow during histamine challenge and subsequent albuterol administration could be detected by various EIT flow volume variables.
Topics: Animals; Bronchoconstriction; Electric Impedance; Horses; Lung; Tidal Volume; Tomography, X-Ray Computed
PubMed: 33977584
DOI: 10.1111/jvim.16152 -
Current Opinion in Allergy and Clinical... Feb 2016To provide an overview on the present understanding of roles of oxidative DNA damage repair in cell signaling underlying bronchoconstriction common to, but not... (Review)
Review
PURPOSE OF REVIEW
To provide an overview on the present understanding of roles of oxidative DNA damage repair in cell signaling underlying bronchoconstriction common to, but not restricted to various forms of asthma and chronic obstructive pulmonary disease.
RECENT FINDINGS
Bronchoconstriction is a tightening of smooth muscle surrounding the bronchi and bronchioles with consequent wheezing and shortness of breath. Key stimuli include air pollutants, viral infections, allergens, thermal and osmotic changes, and shear stress of mucosal epithelium, triggering a wide range of cellular, vascular, and neural events. Although activation of nerve fibers, the role of G-proteins, protein kinases and Ca++, and molecular interaction within contracting filaments of muscle are well defined, the overarching mechanisms by which a wide range of stimuli initiate these events are not fully understood. Many, if not all, stimuli increase levels of reactive oxygen species, which are signaling and oxidatively modifying macromolecules, including DNA. The primary reactive oxygen species target in DNA is guanine, and 8-oxoguanine is one of the most abundant base lesions. It is repaired by 8-oxoguanine DNA glycosylase1 during base excision repair processes. The product, free 8-oxo-7,8-dihydro-2'-deoxyguanosine base, is bound by 8-oxoguanine DNA glycosylase1 with high affinity, and the complex then functions as an activator of small guanosine triphosphatases, triggering pathways for inducing gene expression and contraction of intracellular filaments in mast and smooth muscle cells.
SUMMARY
Oxidative DNA damage repair-mediated cell activation signaling result in gene expression that 'primes' the mucosal epithelium and submucosal tissues to generate mediators of airway smooth muscle contractions.
Topics: Animals; Bronchoconstriction; DNA Damage; DNA Repair; Humans; Muscle Contraction; Muscle, Smooth; Oxidation-Reduction
PubMed: 26694039
DOI: 10.1097/ACI.0000000000000232 -
Annals of Physical and Rehabilitation... Jun 2022Healthy trained athletes generally have an "overbuilt" respiratory system in order to face the huge ventilation and gas-exchange demand imposed by strenuous exercise.... (Review)
Review
BACKGROUND
Healthy trained athletes generally have an "overbuilt" respiratory system in order to face the huge ventilation and gas-exchange demand imposed by strenuous exercise. Athletes frequently complain of respiratory symptoms regardless of whether they have a diagnosed respiratory disease, therefore evoking a kind of respiratory limitation during exercise. Some respiratory pathologies athletes present are closely linked to exercise and include asthma, exercise-induced bronchoconstriction (EIB) or exercise-induced laryngeal obstruction. Management of asthma and EIB are mainly based on pharmacological treatments. However, many athletes still complain of respiratory symptoms despite optimal pharmacological treatments, which highlights the need for non-pharmacological approaches including breathing retraining, inspiratory muscle training and/or laryngeal exercise performed under the guidance of a physiotherapist in this specific population.
OBJECTIVES
With this literature overview, we aimed to report evidence supporting the interest of rehabilitation for athletes with respiratory disorders and discuss whether inspiratory muscle training programs can improve performance in healthy athletes.
METHODS
We searched MEDLINE and Cochrane databases for trials, reviews and meta-analyses assessing respiratory rehabilitation and muscle training programs in athletes by using the MesH terms "athletes", "asthma", "dyspnea", "rehabilitation" and "education" published from January 2010 to March 2020. The selection of articles was based on the author's expertise to elaborate this review of the literature.
RESULTS
Major findings suggest that breathing retraining may help asthmatic athletes better control their respiratory symptoms and that inspiratory muscle training may improve respiratory symptoms of exercise-induced laryngeal obstruction in athletes. Improvement of performance by respiratory muscle training still remains controversial.
CONCLUSIONS
Respiratory rehabilitation could be of interest in the specific population of athletes but should be further evaluated to improve the level of evidence of such strategies.
Topics: Asthma; Asthma, Exercise-Induced; Athletes; Bronchoconstriction; Dyspnea; Humans; Respiratory Tract Diseases
PubMed: 33271343
DOI: 10.1016/j.rehab.2020.101461 -
JCI Insight Oct 2022Obesity-induced asthma responds poorly to all current pharmacological interventions, including steroids, suggesting that classic, eosinophilic inflammation is not a...
Obesity-induced asthma responds poorly to all current pharmacological interventions, including steroids, suggesting that classic, eosinophilic inflammation is not a mechanism. Since insulin resistance and hyperinsulinemia are common in obese individuals and associated with increased risk of asthma, we used diet-induced obese mice to study how insulin induces airway hyperreactivity. Inhaled 5-HT or methacholine induced dose-dependent bronchoconstriction that was significantly potentiated in obese mice. Cutting the vagus nerves eliminated bronchoconstriction in both obese and nonobese animals, indicating that it was mediated by a neural reflex. There was significantly greater density of airway sensory nerves in obese compared with nonobese mice. Deleting insulin receptors on sensory nerves prevented the increase in sensory nerve density and prevented airway hyperreactivity in obese mice with hyperinsulinemia. Our data demonstrate that high levels of insulin drives obesity-induced airway hyperreactivity by increasing sensory innervation of the airways. Therefore, pharmacological interventions to control metabolic syndrome and limit reflex-mediated bronchoconstriction may be a more effective approach to reduce asthma exacerbations in obese and patients with asthma.
Topics: Mice; Animals; Bronchoconstriction; Mice, Obese; Methacholine Chloride; Insulin; Receptor, Insulin; Serotonin; Asthma; Reflex; Hyperinsulinism; Obesity
PubMed: 36107629
DOI: 10.1172/jci.insight.161898