scholarly journals Neuroimmune Pathophysiology in Asthma

2021 ◽  
Vol 9 ◽  
Author(s):  
Gandhi F. Pavón-Romero ◽  
Nancy Haydée Serrano-Pérez ◽  
Lizbeth García-Sánchez ◽  
Fernando Ramírez-Jiménez ◽  
Luis M. Terán
Keyword(s):  
Inhaled Corticosteroids ◽  
Bronchial Hyperresponsiveness ◽  
Airway Disease ◽  
Neuroendocrine Cells ◽  
Lower Airway ◽  
Neurokinin A ◽  
Type I ◽  
Matrix Deposition ◽  
Novel Approach ◽  
Anti Inflammatory

Asthma is a chronic inflammation of lower airway disease, characterized by bronchial hyperresponsiveness. Type I hypersensitivity underlies all atopic diseases including allergic asthma. However, the role of neurotransmitters (NT) and neuropeptides (NP) in this disease has been less explored in comparison with inflammatory mechanisms. Indeed, the airway epithelium contains pulmonary neuroendocrine cells filled with neurotransmitters (serotonin and GABA) and neuropeptides (substance P[SP], neurokinin A [NKA], vasoactive intestinal peptide [VIP], Calcitonin-gene related peptide [CGRP], and orphanins-[N/OFQ]), which are released after allergen exposure. Likewise, the autonomic airway fibers produce acetylcholine (ACh) and the neuropeptide Y(NPY). These NT/NP differ in their effects; SP, NKA, and serotonin exert pro-inflammatory effects, whereas VIP, N/OFQ, and GABA show anti-inflammatory activity. However, CGPR and ACh have dual effects. For example, the ACh-M3 axis induces goblet cell metaplasia, extracellular matrix deposition, and bronchoconstriction; the CGRP-RAMP1 axis enhances Th2 and Th9 responses; and the SP-NK1R axis promotes the synthesis of chemokines in eosinophils, mast cells, and neutrophils. In contrast, the ACh-α7nAChR axis in ILC2 diminishes the synthesis of TNF-α, IL-1, and IL-6, attenuating lung inflammation whereas, VIP-VPAC1, N/OFQ-NOP axes cause bronchodilation and anti-inflammatory effects. Some NT/NP as 5-HT and NKA could be used as biomarkers to monitor asthma patients. In fact, the asthma treatment based on inhaled corticosteroids and anticholinergics blocks M3 and TRPV1 receptors. Moreover, the administration of experimental agents such as NK1R/NK2R antagonists and exogenous VIP decrease inflammatory mediators, suggesting that regulating the effects of NT/NP represents a potential novel approach for the treatment of asthma.

scholarly journals Potential of Immunoglobulin A to Prevent Allergic Asthma

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Anouk K. Gloudemans ◽  
Bart N. Lambrecht ◽  
Hermelijn H. Smits
Keyword(s):  
Allergic Asthma ◽  
Immunoglobulin A ◽  
Bronchial Hyperresponsiveness ◽  
Airway Disease ◽  
Epidemiological Studies ◽  
Allergic Airway Disease ◽  
Secretory Iga ◽  
Th2 Cells ◽  
Lower Airway

Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies.

scholarly journals Regulation of Interaction between the Upper and Lower Airways in United Airway Disease

2019 ◽  
Vol 7 (2) ◽  
pp. 27 ◽  
Author(s):  
Akira Kanda ◽  
Yoshiki Kobayashi ◽  
Mikiya Asako ◽  
Koichi Tomoda ◽  
Hideyuki Kawauchi ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inhaled Corticosteroids ◽  
Upper Airway ◽  
Airway Disease ◽  
Comprehensive Approach ◽  
Lower Airway ◽  
T Helper 2 ◽  
Neural Modulation ◽  
Lower Airways ◽  
Novel Therapeutic

The concept of united airway disease comprises allergic rhinitis (AR) with asthma, and eosinophilic chronic rhinosinusitis (ECRS) with asthma. It embodies a comprehensive approach to the treatment of upper and lower airway inflammation. The treatment of upper airway inflammation reduces asthma symptoms and decreases the dose of inhaled corticosteroids (ICS) necessary to treat asthma. However, little is known about the mechanisms of interaction between upper and lower airway inflammation. Here we review these mechanisms, focusing on neural modulation and introduce a novel therapeutic approach to united airway disease using a fine-particle ICS. Our understanding of the relationship between the upper and lower airways and its contribution to T helper 2 (Th2)-skewed disease, such as AR and/or ECRS with asthma, has led us to this novel therapeutic strategy for a comprehensive approach to the treatment of upper airway inflammation with asthma.

Embracing the Cascade part 3: clinical decision making in equine asthma

UK-Vet Equine ◽  
2020 ◽  
Vol 4 (1) ◽  
pp. 19-29
Author(s):  
James Bailey ◽  
Mark Bowen
Keyword(s):  
Severe Asthma ◽  
Clinical Decision Making ◽  
Inhaled Corticosteroids ◽  
Rescue Therapy ◽  
Clinical Decision ◽  
Airway Disease ◽  
Evidence Base ◽  
Lower Airway ◽  
Mucus Production ◽  
Equine Asthma

Equine asthma is the current terminology that covers chronic non-infectious lower airway disorders in the horse. Mild and moderate equine asthma reflect the syndrome previously referred to as inflammatory airway disease, while severe asthma reflects both recurrent airway obstruction and summer pasture-associated obstructive airway disease. Corticosteroids are the most important therapeutic agents for the management of horses with all severities of equine asthma. Prednisolone and dexamethasone products are authorised for use in horses and can be used for the management of asthma. Inhaled corticosteroids have the potential advantages of reduced systemic effects and reduced detection times in competition animals. ‘Special’ (extemporaneous) formulations of oral dexamethasone may be valuable in horses with severe asthma. A range of bronchodilator therapies can be used for the management of severe asthma; although the clinical efficacy of systemic bronchodilators still lacks a robust evidence base, they may have a particular role in ‘rescue-therapy’ and in acute exacerbations. The evidence for the use of mucolytic agents is limited and excessive mucus production should resolve with improvements in airway inflammation. Inhaled saline and inhaled acetylcysteine may provide useful improvements in mucus secretion without any effects on competition horses. Mast cell stabilisers may have a role in the management of mild equine asthma, although they have a limited evidence base for their use. The use of the prescribing cascade provides access to a range of medications that are useful in the management of equine asthma.

scholarly journals Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design

2020 ◽  
Vol 6 (2) ◽  
pp. 00333-2019
Author(s):  
Tim Harrison ◽  
Ian D. Pavord ◽  
James D. Chalmers ◽  
Glenn Whelan ◽  
Malin Fagerås ◽  
...  
Keyword(s):  
Lung Function ◽  
Maintenance Therapy ◽  
Airway Inflammation ◽  
Temporal Dynamics ◽  
Inhaled Corticosteroids ◽  
Dry Powder Inhaler ◽  
Airway Disease ◽  
Open Label ◽  
Asthma Symptoms ◽  
Anti Inflammatory

Asthma is a chronic inflammatory airway disease. Increase in airway inflammation is hypothesised to contribute to worsening of asthma symptoms and deterioration in lung function, resulting in the use of reliever medication. Short-acting β2-agonists only treat the symptoms, whereas an anti-inflammatory reliever is believed to treat both symptoms and the underlying inflammation, thereby arresting the progression to an exacerbation. As-needed budesonide/formoterol as an anti-inflammatory reliever reduces the risk of severe exacerbations. However, supporting mechanistic evidence has not yet been described, specifically the temporal dynamics of parameters including airway inflammation, over time and during asthma worsening.The STIFLE study aims to characterise daily variability in airway inflammation, symptoms, lung function and reliever use in people with asthma. This phase IV, open-label, parallel-group, multicentre, exploratory study will enrol 60–80 adult patients with asthma receiving low- or medium-dose inhaled corticosteroids/long-acting β2-agonists (EudraCT identifier number 2018-003467-64). Participants will be randomised 1:1 to either as-needed budesonide/formoterol dry-powder inhaler or salbutamol reliever for 24 weeks, in addition to their maintenance therapy. Daily data will be captured for fractional exhaled nitric oxide, spirometry, asthma symptoms and medication use using devices connected to a smartphone via the STIFLE application. STIFLE will thereby enable not only characterisation of the variability of airway inflammation and clinical outcomes in relation to asthma worsening, but also elucidate the effect of as-needed budesonide/formoterol on airway inflammation against a background of daily maintenance therapy.

CLINICAL AND SPIROGRAPHIC FEATURES OF BRONCHIAL ASTHMA IN SCHOOLCHILDREN DEPENDING ON THE DIFFERENT REGIMENS OF BASIC ANTI-INFLAMMATORY THERAPY

2020 ◽  
Vol 73 (1) ◽  
Author(s):  
Olena Koloskova ◽  
Tetiana Bilous ◽  
Galyna Bilyk ◽  
Kristina Buryniuk-Glovyak ◽  
Olena Korotun ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Inhaled Corticosteroids ◽  
Persistent Asthma ◽  
High Specificity ◽  
Clinical Feature ◽  
Clinical Group ◽  
Comparison Groups ◽  
Anti Inflammatory ◽  
High Doses ◽  
Persistent Bronchial Asthma

The aim: To study the clinical and spirographic features persistence of the bronchial asthma in schoolchildren against the background of the alternative daily doses of inhaled corticosteroids to increase the effectiveness of anti-inflammatory therapy for this disease. Materials and methods: A complete comprehensive clinical-paraclinical examination of 65 schoolchildren with persistent asthma was conducted. According to the average daily dose of inhaled corticosteroids (ICS) the patients were divided into two clinical groups. The first (I) group consisted of 46 children who received ICS in the regimen of low-to-medium equipotent doses (253.95±9.98 μg per day), and the second (II) comparison group was formed of 19 patients who controlled the pBA using high doses of ICS (494.74±5.56 μg per day). Results: The patients of the І clinical group compared to patients of the ІІ group have a higher risk of the mild bronchial obstructive syndrome during asthma attacks. In assessing the level of control of persistent bronchial asthma using the CIA-scale, it was found that in II group cases of the controlled course of the disease were observed almost two times less than in children of the I group of comparison. In conducting spirography in children of comparison groups, it was shown that the ratio of indices of bronchospasm (FEV1/ FVC) was worse in patients receiving high doses of ICS. Conclusions: So, сharacteristic clinical feature of asthma controlled by high doses of ICS is more severe nature of bronchial obstructive syndrome during the period of exacerbation (OR=1.9-3.0). In the management of persistent bronchial asthma, the Gensler index which has high specificity (94.4%) and accuracy (92.2%) should be used for disease control verification.

scholarly journals Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1615
Author(s):  
Zhongwei Zhang ◽  
Yosuke Kurashima
Keyword(s):  
Mast Cells ◽  
Chronic Inflammation ◽  
Regulatory Function ◽  
Type I ◽  
Allergic Reactions ◽  
Novel Approach ◽  
Molecular Patterns ◽  
Regulatory Functions ◽  
Damage Associated Molecular Patterns ◽  
Two Sides

It is well known that mast cells (MCs) initiate type I allergic reactions and inflammation in a quick response to the various stimulants, including—but not limited to—allergens, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). MCs highly express receptors of these ligands and proteases (e.g., tryptase, chymase) and cytokines (TNF), and other granular components (e.g., histamine and serotonin) and aggravate the allergic reaction and inflammation. On the other hand, accumulated evidence has revealed that MCs also possess immune-regulatory functions, suppressing chronic inflammation and allergic reactions on some occasions. IL-2 and IL-10 released from MCs inhibit excessive immune responses. Recently, it has been revealed that allergen immunotherapy modulates the function of MCs from their allergic function to their regulatory function to suppress allergic reactions. This evidence suggests the possibility that manipulation of MCs functions will result in a novel approach to the treatment of various MCs-mediated diseases.

scholarly journals Asthma in elderly is characterized by increased sputum neutrophils, lower airway caliber variability and air trapping

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
F. Schleich ◽  
S. Graff ◽  
F. Guissard ◽  
M. Henket ◽  
V. Paulus ◽  
...  
Keyword(s):  
Bronchial Hyperresponsiveness ◽  
Forced Expiratory Volume ◽  
Lower Airway ◽  
Low Grade ◽  
Sputum Induction ◽  
Air Trapping ◽  
Cell Counts ◽  
Airway Caliber ◽  
Significant Difference ◽  
Long Acting

Abstract Background Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. Methods We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. Results Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV1) and FEV1/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. Conclusion Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.

scholarly journals Higher Omega-3 Index Is Associated with Better Asthma Control and Lower Medication Dose: A Cross-Sectional Study

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 74 ◽  
Author(s):  
Isobel Stoodley ◽  
Manohar Garg ◽  
Hayley Scott ◽  
Lesley Macdonald-Wicks ◽  
Bronwyn Berthon ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Asthma Control ◽  
Inhaled Corticosteroids ◽  
Asthma Management ◽  
Airway Disease ◽  
Cross Sectional Study ◽  
Erythrocyte Membranes ◽  
Omega 3 ◽  
Asthma Control Questionnaire ◽  
Cross Sectional

Asthma is a chronic inflammatory airway disease, associated with systemic inflammation. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have established anti-inflammatory effects, thus having potential as an adjunct therapy in asthma. This study aimed to compare erythrocyte n-3 PUFA in adults with (n = 255) and without (n = 137) asthma and determine the relationship between erythrocyte n-3 PUFA and clinical asthma outcomes. Subjects had blood collected, lung function measured and Juniper Asthma Control Questionnaire (ACQ) score calculated. Fatty acids were measured in erythrocyte membranes by gas chromatography, and the omega-3 index (O3I) was calculated (% eicosapentaenoic acid + % docosahexaenoic acid). O3I was similar in subjects with and without asthma (p = 0.089). A higher O3I was observed in subjects with controlled or partially controlled asthma (ACQ < 1.5) compared to subjects with uncontrolled asthma (ACQ ≥ 1.5) (6.0% (5.4–7.2) versus 5.6% (4.6–6.4) p = 0.033). Subjects with a high O3I (≥8%) had a lower maintenance dose of inhaled corticosteroids (ICS) compared to those with a low O3I (<8%) (1000 μg (400–1000) versus 1000 μg (500–2000) p = 0.019). This study demonstrates that a higher O3I is associated with better asthma control and with lower ICS dose, suggesting that a higher erythrocyte n-3 PUFA level may have a role in asthma management.

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