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Asthma
\"Describes what it is like to live with asthma, what its symptoms are, and how it is treated\"-- Provided by publisher.
Book
Potential mechanisms and effects of AFB.sub.1-induced asthma: A comprehensive analysis based on network toxicology and molecular docking
The aim of this study was to systematically explore the potential molecular mechanisms by which aflatoxin B1 (AFB.sub.1) may trigger asthma using network toxicology and molecular docking. Potential targets related to asthma caused by AFB.sub.1 were obtained from databases, such as PubChem, ProTox, ADMETab, and GeneCards. The targets most significantly related to asthma were further screened using STRING and Cytoscape and analyzed using GO and KEGG enrichment. Finally, molecular docking and visualization were performed using AutodockVina 1.2.2 and PyMOL 2.5 to further determine the affinity between AFB.sub.1 and the core targets. We identified 31 potential targets associated with AFB.sub.1 exposure and asthma, including PTGS2, ADRB2, CysLTR1, PTGS1, and others. The enrichment analysis revealed that the core targets of AFB.sub.1 -induced asthma were neuroactive ligand-receptor interactions, the calcium signaling pathway, and the adipocyte catabolism-related signaling pathway. Molecular docking results revealed that AFB.sub.1 exhibited good affinity for the core targets. In the present study, the potential mechanisms involved in AFB.sub.1 -induced asthma were elucidated, new insights into how environmental toxins trigger asthma were provided, and a theoretical foundation for asthma prevention and treatment was established.
Journal Article
Handy health guide to asthma
\"An overview of asthma for children in grades 5 and up. Find out what asthma is, what causes it, how it is diagnosed, and some treatment options\"-- Provided by publisher.
Book
T-helper Type 2-driven Inflammation Defines Major Subphenotypes of Asthma
T-helper type 2 (Th2) inflammation, mediated by IL-4, IL-5, and IL-13, is considered the central molecular mechanism underlying asthma, and Th2 cytokines are emerging therapeutic targets. However, clinical studies increasingly suggest that asthma is heterogeneous.
To determine whether this clinical heterogeneity reflects heterogeneity in underlying molecular mechanisms related to Th2 inflammation.
Using microarray and polymerase chain reaction analyses of airway epithelial brushings from 42 patients with mild-to-moderate asthma and 28 healthy control subjects, we classified subjects with asthma based on high or low expression of IL-13-inducible genes. We then validated this classification and investigated its clinical implications through analyses of cytokine expression in bronchial biopsies, markers of inflammation and remodeling, responsiveness to inhaled corticosteroids, and reproducibility on repeat examination.
Gene expression analyses identified two evenly sized and distinct subgroups, \"Th2-high\" and \"Th2-low\" asthma (the latter indistinguishable from control subjects). These subgroups differed significantly in expression of IL-5 and IL-13 in bronchial biopsies and in airway hyperresponsiveness, serum IgE, blood and airway eosinophilia, subepithelial fibrosis, and airway mucin gene expression (all P < 0.03). The lung function improvements expected with inhaled corticosteroids were restricted to Th2-high asthma, and Th2 markers were reproducible on repeat evaluation.
Asthma can be divided into at least two distinct molecular phenotypes defined by degree of Th2 inflammation. Th2 cytokines are likely to be a relevant therapeutic target in only a subset of patients with asthma. Furthermore, current models do not adequately explain non-Th2-driven asthma, which represents a significant proportion of patients and responds poorly to current therapies.
Journal Article
P69 Peak flow variability in asthma diagnosis – which is the best threshold to use in practice?
IntroductionAlthough peak flow variability (PEFv) is one of the diagnostic tests in the NICE guidance for asthma (NG80), instructions on how to calculate PEFv are brief; PEFv can be expressed as amplitude% mean (A%M) or amplitude% highest (A%H, a simpler calculation). A positive test can be recorded if the average daily amplitude ≥20% (A%M20, advised in NG80), ≥15% (A%M15) or ≥10% (A%M10). We investigated the effect of changing the way a positive PEFv test is defined on the classification of adults and children with symptoms in keeping with asthma.MethodsAdults and children with symptoms in keeping with asthma were referred by primary care for a thorough evaluation. Participants were asked to record PEF at least twice per day for two weeks with an electronic PEF meter. Participants completed a detailed panel of lung function tests and were treated with ICS for 8 weeks. All tests and response to treatment were evaluated by a panel of consultant respiratory physicians and participants were diagnosed with asthma or not asthma (or insufficient evidence). We calculated sensitivity and specificity of different PEFv thresholds in diagnosing asthmaResultsOf the 117 symptomatic participants recruited into the study, 91 (50 adults) completed PEF measurements for ≥4 days (median 10 days [IQR 8–12 days]). A significant correlation (R=0.927) was found between PEFv for patients who collected ≥10 days PEF and their first 5 days of PEF data. Of 47 adults with sufficient data, 31 were diagnosed with asthma. Of 31 children with sufficient data, 23 had asthma. Sensitivity and specificity of different thresholds of PEFv are shown in table 1. Only 3 adults with asthma had PEFv A%M20, indicating this threshold is too high. Expressing results as A%M or A%H made little difference in sensitivity or specificity, as did using the first 5 days of data rather than all data collected.Abstract P69 Table 1Sensitivity = TP/(TP+FN) Specificity = TN/(TN+FP) Sensitivity All available readings Specificity All available readings Sensitivity using 1st 5 days only Specificity using 1st 5 days only Adults A%M20 9.7% 100% 12.9% 100% Adults A%H20 6.4% 100% 3.2% 100% Adults A%M15 16.1% 100% 22.6% 100% Adults A%H15 16.1% 100% 19.4% 100% Adults A%M10 54.8% 75% 45.2% 81.3% Adults A%H10 54.8% 81.3% 41.9% 93.4% Children A%M20 43.4% 100% 34.8% 100% Children A%H20 17.4% 100% 30.4% 100% Children A%M15 56.5% 87.5% 60.7% 87.5% Children A%H15 47.8% 87.5% 52.2% 100% Children A%M10 78.2% 87.5% 82.6% 87.5% Children A%H10 73.9% 87.5% 69.6% 87.5% ConclusionPEFv could be calculated as A%H10 for 5 days as part of the NICE CG80 diagnostic algorithm, as this is simpler to collect and to calculate, is more sensitive, and has little loss in specificity compared to A%M20 for 2 weeks.
Journal Article
Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma
In patients with asthma who had elevated blood eosinophil levels and marginal asthma control despite treatment with high-dose inhaled or oral glucocorticoids, asthma exacerbations were reduced in those receiving a monoclonal antibody that binds to and inactivates interleukin-5.
Severe asthma affects less than 10% of patients with asthma and is associated with substantial morbidity and mortality and a large fraction of the health care costs among patients with asthma.
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Despite available care, recurrent asthma exacerbations are a major issue in a subgroup of patients with eosinophilic airway inflammation.
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Mepolizumab, a humanized monoclonal antibody against interleukin-5, selectively inhibits eosinophilic inflammation
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and reduces the number of eosinophils in both sputum and blood, resulting in a reduction in exacerbations and in the need for treatment with systemic glucocorticoids.
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In the Dose Ranging Efficacy and Safety with Mepolizumab . . .
Journal Article
Mighty Monty
Monty, a quiet first-grader, continues to come into his own--playing the part of a tree in a miscued school play, sharing his enthusiasm for ants at an outdoor birthday party, and even signing up for karate class despite his asthma.
Book
Tezepelumab for severe asthma: elevating current practice to recognize epithelial driven profiles
Background
An increasing amount of evidence supports the relevance of epithelium across the wide spectrum of asthma pathobiology. On a clinical ground tezepelumab, selectively binding TSLP, a major epithelial cytokine, has demonstrated to be effective in asthma patients regardless their specific phenotype. In order to avoid the risk of considering tezepelumab as a not-specific option, the present perspective aims to sketch the tezepelumab best eligible patient profile and to propose some hallmarks of epithelial-driven disease by reviewing the published evidence on the drug mechanism of action and efficacy data.
Main body
Although it cannot rely on standardised or exclusive “markers”, the relationship between environment and poor asthma control might suggest a major relevance of the epithelial barrier dysfunction. In that light, allergy and asthma exacerbations concomitant with specific exposures (pathogens, pollutants, chemicals), as well as increased susceptibility to infections can be considered as the hallmark of an impaired epithelial immune response. Tezepelumab is effective in allergic patients, being able to reduce asthma exacerbations precipitated by the exposure to seasonal or perennial aeroallergens, including fungi. In addition, tezepelumab reduced the incidence of co-occurring respiratory illness and asthma exacerbations. In terms of inflammation, epithelial immune response has been related to an impaired mucus hypersecretion and plugging. A placebo-controlled trial demonstrated a significant reduction of mucus plugging in treated patient. Airways hyperreactivity (AHR), airways obstruction and remodelling have been described as an expression of epithelial orchestrated immunological activation. Of note, a significantly higher incidence of mannitol negative test in patients treated with tezepelumab when compared to placebo group has been observed. In addition, A 130 mL improvement in pre-BD FEV1 has been described in patients assuming Tezepelumab. The above-mentioned data suggest that bronchial reversibility and AHR can be considered “functional biomarkers” supporting patients’ phenotyping and the identification of tezepelumab best responders.
Conclusion
Integrating “functional biomarkers” to the inflammatory ones and a better characterization of asthma exacerbations might pave the way to a different and more transversal phenotyping, which overcomes the “restrictive” labels including T2 high, allergic/atopic or T2 low asthma. Precisely defining the disease characteristics and potential targets for a better control even in tezepelumab eligible subjects is essential to avoid the block buster temptation and optimize the personalized medicine approach according to each patient’s individuality.
Journal Article