0000000000023738

AUTHOR

Alkis Togias

Deep inspiration-induced changes in lung volume decrease with severity of asthma

Summary We have previously reported that the magnitude of deep inspiration (DI)-induced bronchodilation is only slightly reduced in mild asthmatics, compared to healthy subjects. The aim of this study was to evaluate whether increased severity of asthma is associated with impairment in the ability of DI to induce changes in lung volume. Thirty-six consecutive asthmatics recruited from the Pulmonary and the Allergy Outpatient Clinics of the Institute of Respiratory Diseases of the University of Palermo were divided into 3 groups: Intermittent (I), Mild Persistent (MP) and Moderate–Severe (MS), based on GINA guidelines. Single dose methacholine (Mch) bronchoprovocations were performed in the …

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The role of lung inflation in airway hyperresponsiveness and in asthma

Airway hyperresponsiveness (AHR) is a fundamental phenomenon in asthma that can explain many aspects of the clinical manifestations of the disease. Several theories on the mechanisms of AHR have been proposed, but the true nature of this problem is yet to be defined. During the past decade, the role of lung inflation in airway physiology and its relationship to AHR have attracted major attention. Deep inspirations are known to exert strong beneficial effects on the airways of healthy humans. These effects appear to be of dual nature: bronchoprotective and bronchodilatory. The bronchoprotective effect of deep inspiration is lost in asthma, even in mild disease. It is also lost in individuals…

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Reduced airway responsiveness in non elite runners

Med Sci Sports Exerc. 2005 Dec;37(12):2019-25. Reduced airway responsiveness in nonelite runners. Scichilone N, Morici G, Marchese R, Bonanno A, Profita M, Togias A, Bonsignore MR. SourceInstitute of Medicine and Pneumology, Respiratory Unit; University of Palermo, Italy. n.scichilone@libero.it Abstract PURPOSE: The effects of endurance training on airway responsiveness in nonasthmatic subjects are poorly defined. We hypothesized that airway responsiveness may differ between none-lite endurance athletes and sedentary subjects, and studied healthy, nonelite runners and sedentary controls by single-dose methacholine challenges carried out in the absence of deep inspirations, in that deep insp…

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Should atopy be assessed in elderly patients with respiratory symptoms suggestive of asthma?

Aging is associated with modifications of the immune system and this could contribute to a reduced prevalence of allergic disease in the elderly. Atopy has rarely been considered in the clinical assessment of the geriatric respiratory patient. This article is a review of the available literature assessing the impact of age on atopy in the asthmatic patient. In the majority of papers, we found a lower prevalence of atopy in the most advanced ages, both in healthy subjects and in individuals affected by allergic respiratory diseases. No large, longitudinal studies performed in the general population have been conducted to confirm this observation. Although available data seem to favor the dec…

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The Lack of the Bronchoprotective and Not the Bronchodilatory Ability of Deep Inspiration Is Associated with Airway Hyperresponsiveness

In healthy subjects, deep inspiration (DI) acts both as a bronchodilator and a bronchoprotector. The latter is impaired in asthmatics. We have now evaluated whether the lack of bronchoprotection is related to bronchial hyperresponsiveness (BHR), and whether the bronchodilatory effect is also lost in asthmatics. Ten healthy subjects (PC20 > 75 mg/ml), 12 asthmatics with moderate to severe BHR (PC20 < 1 mg/ml), 14 asthmatics with mild to borderline BHR (1 < PC20 < 25 mg/ml), and 10 rhinitics with mild to borderline BHR (1 < PC20 < 25 mg/ml) underwent single-dose methacholine provocations inducing at least 20% reduction in FEV1 after 20 min of DI inhibition. To measure the bronchodilatory effe…

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Deep inspiration-induced bronchoprotection is stronger than bronchodilation

We have previously shown that in healthy subjects, deep inspiration (DI) has not only a bronchodilatory but also a bronchoprotective effect that is absent in asthmatic subjects. We conducted the study reported here to test the hypothesis that the bronchoprotective effect is stronger than the bronchodilatory effect, and to determine the extent to which these two effects are related. Ten healthy subjects underwent provocations in which single doses of methacholine, previously shown to reduce FEV(1) by 10% to 20% (Dose 1) and by 20% to 40% (Dose 2) were administered after a 20-min period devoid of DI. To measure the bronchodilator effect, DIs were performed immediately after the first spiromet…

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Airways Hyperresponsiveness and the Effects of Lung Inflation

Lung inflation has a beneficial effect on the airways of healthy subjects. It acts as a bronchoprotector, that is to prevent bronchoconstriction, and as a bronchodilator, in that it reverses bronchial obstruction. The bronchoprotective effect of deep inspiration is more potent than the bronchodilatory one, and the two phenomena appear to advocte different mechanisms. Asthmatics and rhinitics with airways hyperresponsiveness show an impairment in bronchoprotection induced by deep breaths, whereas the bronchodilatory effect, although reduced, is still effective. The lack of the bronchoprotective effect of deep inspiration may contribute to the development of airways hyperresponsiveness. The m…

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Alterations of the beneficial effect of deep inspiration in scleroderma: relationships between lung function and imaging.

&lt;i&gt;Background:&lt;/i&gt; It has been postulated that the beneficial effects of deep inspiration are dependent on the magnitude of airway distension by virtue of airway to parenchyma interdependence. &lt;i&gt;Objective:&lt;/i&gt; This study was designed to examine whether the changes that occur in pulmonary fibrosis affect the beneficial effect of deep inspiration. &lt;i&gt;Methods:&lt;/i&gt; Thirty-one subjects with scleroderma underwent lung volume and diffusion capacity assessment as well as high-resolution computed tomography. To assess the effect of deep inspiration, each subject underwent methacholine provocations in the absence of deep breaths. When the targeted change in lung f…

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Technical standards in allergen exposure chambers worldwide - an EAACI Task Force Report

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. A…

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High-Resolution Computed Tomographic Evaluation of Airway Distensibility and the Effects of Lung Inflation on Airway Caliber in Healthy Subjects and Individuals with Asthma

The effects of a deep inspiration (DI) in individuals with asthma differ from those observed in healthy subjects. It has been postulated that the beneficial effect of lung inflation is mediated by airway stretch. One hypothesis to explain the defects in the function of lung inflation in asthma is that a DI may be unable to stretch the airways. This may result from attenuation of the tethering forces between the airways and the surrounding parenchyma. In the current study, we used high-resolution computed tomography (HRCT) to examine the ability of a DI to distend the airways of subjects with asthma (n = 10) compared with healthy subjects (n = 9) at baseline and after increasing airway tone …

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The hidden burden of severe asthma: from patient perspective to new opportunities for clinicians

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a conse…

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The bronchodilatory effect of deep inspiration diminishes with aging

AbstractDeep inspirations have the ability to dilate constricted airways. The impairment of this function has been associated with the occurrence of asthmatic symptoms. We evaluated whether the bronchodilatory effect of deep inspiration (DI) is affected by aging. We tested 25 healthy subjects (median age: 54 yrs, range: 25–83 yrs). Single dose methacholine (Mch) provocations were performed in the absence of DI, which induced at least 15% reduction in inspiratory vital capacity (IVC) from baseline. The post-Mch IVC measurement was followed by 4 DIs and by another IVC (post-DI IVC). The fractional difference between post-DI IVC and post-Mch IVC represented the % bronchodilation by DI. The % b…

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Inspiration through the nose increases the bronchoprotective effect of lung inflation

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Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA&lt;sup&gt;2&lt;/sup&gt;LEN – ARIA Position Paper

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in …

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Effects of exercise training on airway responsiveness and airway cells in healthy subjects.

J Appl Physiol. 2010 Aug;109(2):288-94. Epub 2010 Jun 10. Effects of exercise training on airway responsiveness and airway cells in healthy subjects. Scichilone N, Morici G, Zangla D, Chimenti L, Davì E, Reitano S, Paternò A, Santagata R, Togias A, Bellia V, Bonsignore MR. SourceDept. of Internal Medicine, Div. of Pulmonology (DIBIMIS Univ. of Palermo, "Villa Sofia-Cervello" Hospital, Via Trabucco 180, 90146 Palermo, Italy. n.scichilone@libero.it Abstract Airway responsiveness to methacholine (Mch) in the absence of deep inspirations (DIs) is lower in athletes compared with sedentary individuals. In this prospective study, we tested the hypothesis that a training exercise program reduces th…

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Inhaled Corticosteroids and the Beneficial Effect of Deep Inspiration in Asthma

Deep inspiration-induced bronchoprotection and bronchodilation are impaired in asthma. We evaluated the effect of inhaled glucocorticosteroids on these phenomena. Two groups of subjects with asthma, 9 with moderate/severe hyperresponsiveness to methacholine, and 12 with mild/borderline hyperresponsiveness to methacholine, received inhaled fluticasone (880 microg daily) for 12 weeks. Serial bronchoprovocations were performed at Weeks 0, 6, and 12. The impact of deep inspirations on the airway response to methacholine was evaluated on the basis of inspiratory vital capacity and FEV(1). Fluticasone produced a wide spectrum of changes in the beneficial effects of deep inspiration, but the mean …

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Impaired Bronchodilatory Effect of Deep Inspiration With Increased Asthma Severity

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Bronchodilatory Effect of Deep Inspiration Is Absent in Subjects With Mild COPD

Study objectives To investigate whether the bronchodilatory effect of deep inspiration is impaired in subjects with COPD. Methods We measured deep inspiration-induced bronchodilation in 19 patients with COPD and 17 healthy subjects (mean age, 67.8 ± 7.1 years vs 62.5 ± 9.3 years, respectively [± SEM]). Each subject underwent a series of single-dose methacholine provocations to induce at least a 15% reduction in inspiratory vital capacity (IVC). When this was achieved, subjects were asked to perform four consecutive deep inspirations, after which the IVC measurement was repeated and the percentage of bronchodilation by deep inspiration was calculated. Results The percentage of reduction in I…

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Potent bronchoprotective effect of deep inspiration and its absence in asthma

In the absence of deep inspirations, healthy individuals develop bronchoconstriction with methacholine inhalation. One hypothesis is that deep inspiration results in bronchodilation. In this study, we tested an alternative hypothesis, that deep inspiration acts as a bronchoprotector. Single-dose methacholine bronchoprovocations were performed after 20 min of deep breath inhibition, in nine healthy subjects and in eight asthmatics, to establish the dose that reduces forced expiratory volume in 1 s by &gt;15%. The provocation was repeated with two and five deep inspirations preceding methacholine. Additional studies were carried out to assess optimization and reproducibility of the protocol …

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Association between reduced bronchodilatory effect of deep inspiration and loss of alveolar attachments.

Abstract Background We have previously shown that the bronchodilatory effect of deep inspiration is attenuated in individuals with COPD. This study was designed to investigate whether the impairment in this effect is associated with loss of alveolar attachments. Methods We measured deep inspiration (DI)-induced bronchodilation in 15 individuals with and without COPD (67 ± 2.2 yrs of age, mean ± SEM) undergoing lobar resection for peripheral pulmonary nodule. Prior to surgery, we measured TLCO and determined the bronchodilatory effect of deep inspiration after constricting the airways with methacholine. The number of destroyed alveolar attachments, as well as airway wall area and airway smoo…

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The bronchodilation response to deep inspiration in asthma is dependent on airway distensibility and air trapping

In healthy individuals, deep inspirations (DIs) have a potent bronchodilatory ability against methacholine (MCh)-induced bronchoconstriction. This is variably attenuated in asthma. We hypothesized that inability to bronchodilate with DIs is related to reduced airway distensibility. We examined the relationship between DI-induced bronchodilation and airway distensibility in 15 asthmatic individuals with a wide range of baseline lung function [forced expired volume in 1 s (FEV1) = 60–99% predicted]. After abstaining from DIs for 20 min, subjects received a single-dose MCh challenge and then asked to perform DIs. The effectiveness of DIs was assessed by the ability of the subjects to improve …

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Commentaries on Viewpoint: Airway smooth muscle and airway hyperresponsiveness in human asthma: have we chased the wrong horse?

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Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

International audience; Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance …

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The airway response to deep inspirations decreases with COPD severity and is associated with airway distensibility assessed by computed tomography.

In patients with mild chronic obstructive pulmonary disease (COPD), the effect of deep inspirations (DIs) to reverse methacholine-induced bronchoconstriction is largely attenuated. In this study, we tested the hypothesis that the effectiveness of DI is reduced with increasing disease severity and that this is associated with a reduction in the ability of DI to distend the airways. Fifteen subjects [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I–II: n = 7; GOLD stage III–IV: n = 8] underwent methacholine bronchoprovocation in the absence of DI, followed by DI. The effectiveness of DI was assessed by their ability to improve inspiratory vital capacity and forced expira…

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The impact of age on prevalence of positive skin prick tests and specific IgE tests

SummaryAging is associated with modifications of the immune system, defined as immunosenescence. This could contribute to a reduced prevalence of allergic disease in the elderly population. In this regard, atopy has rarely been considered in the clinical assessment of the geriatric respiratory patient. This article is a review of the available literature assessing the impact of age on atopy. In the majority of papers, we found a lower prevalence of atopy in the most advanced ages, both in healthy subjects and in individuals affected by allergic respiratory diseases. Unfortunately, no large, longitudinal studies performed in the general population have been conducted to further explore this …

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