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International Journal of Molecular... Feb 2021Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms... (Review)
Review
Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood. As technology in genome sequencing progressed, scientific efforts were made to explain and predict asthma's complexity and heterogeneity, and genome-wide association studies (GWAS) quickly became the preferred study method. Several gene markers and loci associated with asthma susceptibility, atopic and childhood-onset asthma were identified during the last few decades. Markers near the genes were associated with childhood-onset asthma, interleukin (IL)33 and SNPs were associated with atopic asthma, and the gene was identified as protective against the risk to TH2-asthma. The latest efforts and advances in identifying and decoding asthma susceptibility are focused on epigenetics, heritable characteristics that affect gene expression without altering DNA sequence, with DNA methylation being the most described mechanism. Other less studied epigenetic mechanisms include histone modifications and alterations of miR expression. Recent findings suggest that the DNA methylation pattern is tissue and cell-specific. Several studies attempt to describe DNA methylation of different types of cells and tissues of asthmatic patients that regulate airway remodeling, phagocytosis, and other lung functions in asthma. In this review, we attempt to briefly present the latest advancements in the field of genetics and mainly epigenetics concerning asthma susceptibility.
Topics: Animals; Asthma; Epigenomics; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Immunity, Innate
PubMed: 33673725
DOI: 10.3390/ijms22052412 -
Allergy Nov 2021Last year brought a significant advance in asthma management, unyielding to the pressure of the pandemics. Novel key findings in asthma pathogenesis focus on the... (Review)
Review
Last year brought a significant advance in asthma management, unyielding to the pressure of the pandemics. Novel key findings in asthma pathogenesis focus on the resident cell compartment, epigenetics and the innate immune system. The precision immunology unbiased approach was supplemented with novel tools and greatly facilitated by the use of artificial intelligence. Several randomised clinical trials and good quality real-world evidence shed new light on asthma treatment and supported the revision of several asthma guidelines (GINA, Expert Panel Report 3, ERS/ATS guidelines on severe asthma) and the conception of new ones (EAACI Guidelines for the use of biologicals in severe asthma). Integrating asthma management within the broader context of Planetary Health has been put forward. In this review, recently published articles and clinical trials are summarised and discussed with the goal to provide clinicians and researchers with a concise update on asthma research from a translational perspective.
Topics: Artificial Intelligence; Asthma; Biological Products; Humans
PubMed: 34392546
DOI: 10.1111/all.15054 -
Cell Mar 2021In many asthmatics, chronic airway inflammation is driven by IL-4-, IL-5-, and IL-13-producing Th2 cells or ILC2s. Type 2 cytokines promote hallmark features of the... (Review)
Review
In many asthmatics, chronic airway inflammation is driven by IL-4-, IL-5-, and IL-13-producing Th2 cells or ILC2s. Type 2 cytokines promote hallmark features of the disease such as eosinophilia, mucus hypersecretion, bronchial hyperresponsiveness (BHR), IgE production, and susceptibility to exacerbations. However, only half the asthmatics have this "type 2-high" signature, and "type 2-low" asthma is more associated with obesity, presence of neutrophils, and unresponsiveness to corticosteroids, the mainstay asthma therapy. Here, we review the underlying immunological basis of various asthma endotypes by discussing results obtained from animal studies as well as results generated in clinical studies targeting specific immune pathways.
Topics: Adaptive Immunity; Alveolar Epithelial Cells; Animals; Asthma; B-Lymphocytes; Biological Therapy; Humans; Immunoglobulin E
PubMed: 33711259
DOI: 10.1016/j.cell.2021.02.016 -
Chest Mar 2020This review focuses on recent clinical and translational discoveries in severe and uncontrolled asthma that now enable phenotyping and personalized therapies in these... (Review)
Review
This review focuses on recent clinical and translational discoveries in severe and uncontrolled asthma that now enable phenotyping and personalized therapies in these patients. Although asthma is common in both children and adults and typically responds to standard therapies, a subset of individuals with asthma experience severe and/or persistent symptoms despite appropriate therapies. Airflow obstruction leading to frequent symptoms requiring higher levels of controller therapy is the cardinal feature of severe asthma, but the underlying molecular mechanisms, or endotypes, are diverse and variable between individuals. Two major risk factors that contribute to severe asthma are genetics and environmental exposures that modulate immune responses, and although these often interact in complex manners that are not fully understood, certain endotypes converge in severe asthma. A number of studies have evaluated various features of patients with severe asthma and classified patients into phenotypes with clinical relevance. This phenotyping is now incorporated into clinical practice and can be used to guide advanced biological therapies that target specific molecules and inflammatory pathways that contribute to asthma pathogenesis.
Topics: Anti-Asthmatic Agents; Asthma; Biological Products; Bronchial Thermoplasty; Environmental Exposure; Genetic Predisposition to Disease; Humans; Phenotype; Precision Medicine; Risk Factors; Severity of Illness Index
PubMed: 31678077
DOI: 10.1016/j.chest.2019.10.009 -
Nutrition Reviews Nov 2020Asthma is a chronic respiratory condition characterized by airway inflammation and hyperreactivity. Prevalence has continued to rise in recent decades as Western dietary... (Review)
Review
Asthma is a chronic respiratory condition characterized by airway inflammation and hyperreactivity. Prevalence has continued to rise in recent decades as Western dietary patterns have become more pervasive. Evidence suggests that diets emphasizing the consumption of plant-based foods might protect against asthma development and improve asthma symptoms through their effects on systemic inflammation, oxidation, and microbial composition. Additionally, increased fruit and vegetable intake, reduced animal product consumption, and weight management might mediate cytokine release, free radical damage, and immune responses involved in the development and course of asthma. The specific aim of this review paper is to examine the current literature on the associations between dietary factors and asthma risk and control in children and adults. Clinical trials examining the mechanism(s) by which dietary factors influence asthma outcomes are necessary to identify the potential use of nutritional therapy in the prevention and management of asthma.
Topics: Adult; Asthma; Child; Diet; Humans; Nutritional Status
PubMed: 32167552
DOI: 10.1093/nutrit/nuaa005 -
Minerva Medica Feb 2022Asthma is a very heterogeneous disease and since early childhood many classifications have been proposed according to phenotype and endotype. The phenotype includes the... (Review)
Review
Asthma is a very heterogeneous disease and since early childhood many classifications have been proposed according to phenotype and endotype. The phenotype includes the clinical features of asthma such as age of onset, triggers, comorbidities, response to treatment and evolution over time. The endotype is more difficult to define, includes the underlying immunopathological mechanisms of the disease and requires reliable biomarkers. A deep knowledge of phenotype and endotype of the patient may guide a tailored therapeutic approach. In this review the main phenotypes and endotypes of asthma acknowledged in children will be discussed.
Topics: Asthma; Biomarkers; Child, Preschool; Comorbidity; Humans; Phenotype
PubMed: 33576199
DOI: 10.23736/S0026-4806.21.07332-8 -
The European Respiratory Journal Nov 2022Asthma treatment goals currently focus on symptom and exacerbation control rather than remission. Remission is not identical to cure, but is a step closer. This review... (Review)
Review
Asthma treatment goals currently focus on symptom and exacerbation control rather than remission. Remission is not identical to cure, but is a step closer. This review considers the current definitions of remission in asthma, the prevalence and predictors, the pathophysiology of remission, the possibility of achieving it using the available treatment options, and the future research directions. Asthma remission is characterised by a high level of disease control, including the absence of symptoms and exacerbations, and normalisation or optimisation of lung function with or without ongoing treatment. Even in those who develop a symptomatic remission of asthma, persistent pathological abnormalities are common, leading to a risk of subsequent relapse at any time. Complete remission requires normalisation or stabilisation of any underlying pathology in addition to symptomatic remission. Remission is possible as part of the natural history of asthma, and the prevalence of remission in the adult asthma population varies between 2% and 52%. The factors associated with remission include mild asthma, better lung function, better asthma control, younger age, early-onset asthma, shorter duration of asthma, milder bronchial hyperresponsiveness, fewer comorbidities and smoking cessation or never smoking. Although previous studies have not targeted treatment-induced remission, there is some evidence to show that the current long-term add-on therapies such as biologics and azithromycin can achieve some criteria for asthma remission on treatment, at least in a subgroup of patients. However, more research is required. Long-term remission could be included as a therapeutic goal in studies of asthma treatments.
Topics: Adult; Humans; Asthma; Bronchial Hyperreactivity; Chronic Disease; Remission Induction; Time Factors
PubMed: 35361633
DOI: 10.1183/13993003.02583-2021 -
European Respiratory Review : An... Dec 2021Asthma is a heterogenous disease, and its prevalence and severity are different in males females through various ages. As children, boys have an increased prevalence of... (Review)
Review
Asthma is a heterogenous disease, and its prevalence and severity are different in males females through various ages. As children, boys have an increased prevalence of asthma. As adults, women have an increased prevalence and severity of asthma. Sex hormones, genetic and epigenetic variations, social and environmental factors, and responses to asthma therapeutics are important factors in the sex differences observed in asthma incidence, prevalence and severity. For women, fluctuations in sex hormone levels during puberty, the menstrual cycle and pregnancy are associated with asthma pathogenesis. Further, sex differences in gene expression and epigenetic modifications and responses to environmental factors, including SARS-CoV-2 infections, are associated with differences in asthma incidence, prevalence and symptoms. We review the role of sex hormones, genetics and epigenetics, and their interactions with the environment in the clinical manifestations and therapeutic response of asthma.
Topics: Adult; Asthma; COVID-19; Child; Female; Gonadal Steroid Hormones; Humans; Male; Pregnancy; Prevalence; SARS-CoV-2; Sex Factors
PubMed: 34789462
DOI: 10.1183/16000617.0067-2021 -
Current Opinion in Pulmonary Medicine Jan 2020The purpose of this review is to discuss the most recent studies on lifestyle interventions in pediatric asthma. We include studies on physical activity and exercise,... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to discuss the most recent studies on lifestyle interventions in pediatric asthma. We include studies on physical activity and exercise, sedentary time, nutrition, behavioral therapy and the role of schools.
RECENT FINDINGS
Several small studies in children with asthma suggest that exercise interventions can improve aerobic fitness, asthma symptoms or control and quality of life. Existing evidence supports recommending higher intake of fruits and vegetables for asthma risk and control. In contrast, the 'Western diet' - high in refined grains, highly processed foods, red meats and fried foods with low intake of fruits and vegetables - has a proinflammatory effect and may alter microbiota composition leading to worse asthma outcomes. Finally, there are opportunities to utilize schools to promote physical activity, though standardization of asthma management in the schools is needed.
SUMMARY
Assessing physical activity/fitness levels, sedentary time and nutritional status is important in the management of children with asthma, as they are modifiable factors. Larger rigorous studies evaluating lifestyle interventions are needed to better inform current asthma guidelines as well as to understand the underlying mechanism(s) related to physical activity and diet in asthma.
Topics: Asthma; Child; Diet Therapy; Exercise; Humans; Physical Fitness; Risk Reduction Behavior; School Health Services
PubMed: 31652153
DOI: 10.1097/MCP.0000000000000636 -
Polish Archives of Internal Medicine Apr 2022Asthma is usually associated with pulmonary and extrapulmonary comorbidities that are more common in patients with severe asthma than in those with mild‑to‑moderate... (Review)
Review
Asthma is usually associated with pulmonary and extrapulmonary comorbidities that are more common in patients with severe asthma than in those with mild‑to‑moderate illness or in the general population. These comorbidities may affect the clinical intensity and severity of asthma and, as a result, increase health care costs related to its therapy. On the other hand, their recognition and appropriate treatment appear to improve asthma outcomes while optimizing therapy by preventing overtreatment. Comorbid conditions such as gastroesophageal reflux disease, allergic rhinitis, obesity, depression, diabetes mellitus, and cardiovascular disease are commonly known, though their prevalence varies significantly between studies; however, many more comorbidities may remain undiagnosed and only be discovered in an experienced specialized environment. Unfortunately, the pathogenetic pathways linking asthma and many comorbidities are still unknown, which explains why they may often be misdiagnosed as diseases related to asthma treatment. Nevertheless, asthma and comorbid conditions often have common risk factors, and some evidence suggests that they share inflammatory pathways which exacerbate asthma. Inflammation was shown to play an essential role in the onset and development of various comorbidities. The role of systemic inflammation in asthma, on the other hand, remains unknown. Understanding the mechanism(s) that link(s) asthma and its concomitant disorders is critical for developing an effective treatment strategy. This review examines the epidemiology, pathophysiology, treatment suggestions, and significant knowledge gaps of these comorbidities.
Topics: Asthma; Comorbidity; Gastroesophageal Reflux; Humans; Inflammation; Rhinitis, Allergic
PubMed: 35485651
DOI: 10.20452/pamw.16250