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The Journal of Allergy and Clinical... Jul 2017Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective... (Review)
Review
Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children.
Topics: Air Pollution; Allergens; Animals; Environmental Exposure; Humans; Hypersensitivity; Microbiota; Risk Factors
PubMed: 28673399
DOI: 10.1016/j.jaci.2017.05.010 -
American Journal of Rhinology & Allergy May 2018Background Although the cause of adenotonsillar hypertrophy remains unknown, some studies have shown that allergy may be a risk factor. Purpose This study determined the...
Background Although the cause of adenotonsillar hypertrophy remains unknown, some studies have shown that allergy may be a risk factor. Purpose This study determined the levels of allergen-specific immunoglobulin E (sIgE) in the adenotonsillar tissues of children with adenotonsillar hypertrophy and evaluated the clinical significance of local atopy in adenotonsillar tissues. Methods We measured 21 types of specific immunoglobulin E in the serum and adenotonsillar tissues of 102 children with adenotonsillar hypertrophy and compared the sensitization patterns of the serum and local tissues. The patients were divided into three groups-atopy, local atopy, and nonatopy-according to the sensitization of serum and adenotonsillar tissues, and the clinical symptoms among the groups were analyzed. Results Seventy-two (70.6%) children with adenotonsillar hypertrophy were sensitized to more than one allergen in the serum and/or adenotonsillar tissue. Thirty (29.4%) children had no IgE positivity to any allergen in both serum and adenotonsillar tissues. Fifty-five (53.9%) were sensitized to at least one allergen in the serum. Seventy (68.6%) were sensitized to at least one allergen in the adenotonsillar tissue. Seventeen (36.2%) of 47 children with specific immunoglobulin E-negative serum had specific immunoglobulin E-positive adenotonsillar tissues. The rate of specific immunoglobulin E was significantly higher in local tissues than in serum. The rate of inhalant allergen specific immunoglobulin E was significantly higher in the adenoids than in the tonsils. However, the rate of food allergen specific immunoglobulin E was significantly higher in the tonsils than adenoids. The lifetime prevalence of asthma and allergic rhinitis, recent symptoms or treatment of allergic rhinitis, and severity of nasal symptoms (rhinorrhea, sneezing, and nasal itching) were significantly higher in children with local atopy than with nonatopy. Conclusions These results confirm that allergic response may be a risk factor for adenotonsillar hypertrophy. Local allergic inflammation may play an important role in childhood adenotonsillar hypertrophy, and local atopy in adenotonsillar tissues can cause respiratory allergic symptoms in children.
Topics: Adenoids; Allergens; Child; Child, Preschool; Female; Hospitals, University; Humans; Hypersensitivity, Immediate; Hypertrophy; Immunoglobulin E; Male; Organ Specificity; Palatine Tonsil; Republic of Korea; Risk Factors
PubMed: 29649882
DOI: 10.1177/1945892418765003 -
Journal of Clinical Immunology Jan 2018The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder originally described by Dr. Alfred Wiskott in 1937 and Dr. Robert Aldrich in 1954 as a familial disease... (Review)
Review
The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder originally described by Dr. Alfred Wiskott in 1937 and Dr. Robert Aldrich in 1954 as a familial disease characterized by infections, bleeding tendency, and eczema. Today, it is well recognized that the syndrome has a wide clinical spectrum ranging from mild, isolated thrombocytopenia to full-blown presentation that can be complicated by life-threatening hemorrhages, immunodeficiency, atopy, autoimmunity, and cancer. The pathophysiology of classic and emerging features is being elucidated by clinical studies, but remains incompletely defined, which hinders the application of targeted therapies. At the same time, progress of hematopoietic stem cell transplantation and gene therapy offer optimistic prospects for treatment options aimed at the replacement of the defective lymphohematopoietic system that have the potential to provide a cure for this rare and polymorphic disease.
Topics: Autoimmunity; Eczema; Genes, X-Linked; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Humans; Infections; Mutation; Neoplasms; Thrombocytopenia; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 29086100
DOI: 10.1007/s10875-017-0453-z -
Chest Dec 2020Little is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Little is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma overlap and atopy is needed to better target therapies.
RESEARCH QUESTION
What is the overlap between atopy and asthma status among individuals with COPD, and how are categories defined by the presence of atopy and asthma status associated with clinical and radiologic phenotypes and outcomes in the Genetic Epidemiology of COPD Study (COPDGene) and Subpopulation and Intermediate Outcome Measures in COPD Study (SPIROMICS)?
STUDY DESIGN AND METHODS
Four hundred three individuals with COPD from SPIROMICS and 696 individuals from COPDGene with data about specific IgEs to 10 common allergens and mixes (simultaneous assessment of combination of allergens in similar category) were included. Comparison groups were defined by atopic and asthma status (neither, atopy alone, atopic asthma, nonatopic asthma, with atopy defined as any positive specific IgE (≥0.35 KU/L) to any of the 10 allergens or mixes and asthma defined as self-report of doctor-diagnosed current asthma). Multivariable regression analyses (linear, logistic, and zero inflated negative binomial where appropriate) adjusted for age, sex, race, lung function, smoking status, pack-years smoked, and use of inhaled corticosteroids were used to determine characteristics of groups and relationship with outcomes (exacerbations, clinical outcomes, CT metrics) separately in COPDGene and SPIROMICS, and then adjusted results were combined using meta-analysis.
RESULTS
The prevalence of atopy was 35% and 36% in COPD subjects from SPIROMICS and COPDGene, respectively, and less than 50% overlap was seen between atopic status with asthma in both cohorts. In meta-analysis, individuals with nonatopic asthma had the most impaired symptom scores (effect size for St. George's Respiratory Questionnaire total score, 4.2; 95% CI, 0.4-7.9; effect size for COPD Assessment Test score, 2.8; 95% CI, 0.089-5.4), highest risk for exacerbations (incidence rate ratio, 1.41; 95% CI, 1.05-1.88) compared with the group without atopy or asthma. Those with atopy and atopic asthma were not at increased risk for adverse outcomes.
INTERPRETATION
Asthma and atopy had incomplete overlap among former and current smokers with COPD in COPDGene and SPIROMICS. Nonatopic asthma was associated with adverse outcomes and exacerbation risk in COPD, whereas groups having atopy alone and atopic asthma had less risk.
Topics: Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome; Biological Variation, Population; Disease Management; Female; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Male; Middle Aged; Molecular Epidemiology; Prevalence; Pulmonary Disease, Chronic Obstructive; Risk Factors; Smoking; Status Asthmaticus
PubMed: 32450244
DOI: 10.1016/j.chest.2020.04.069 -
Frontiers in Allergy Dec 2020Atopic diseases, particularly atopic dermatitis (AD), asthma, and allergic rhinitis (AR) share a common pathogenesis of inflammation and barrier dysfunction. Epithelial...
Atopic diseases, particularly atopic dermatitis (AD), asthma, and allergic rhinitis (AR) share a common pathogenesis of inflammation and barrier dysfunction. Epithelial to mesenchymal transition (EMT) is a process where epithelial cells take on a migratory mesenchymal phenotype and is essential for normal tissue repair and signal through multiple inflammatory pathways. However, while links between EMT and both asthma and AR have been demonstrated, as we outline in this mini-review, the literature investigating AD and EMT is far less well-elucidated. Furthermore, current studies on EMT and atopy are mostly animal models or studies on cell cultures or tissue biopsies. The literature covered in this mini-review on EMT-related barrier dysfunction as a contributor to AD as well as the related (perhaps resultant) atopic diseases indicates a potential for therapeutic targeting and carry treatment implications for topical steroid use and environmental exposure assessments. Further research, particularly studies, may greatly advance the field and translate into benefit for patients and families.
PubMed: 34308414
DOI: 10.3389/falgy.2020.628381 -
Annals of the American Thoracic Society Mar 2016The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease... (Review)
Review
The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy.
Topics: Animals; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Hypersensitivity; Immunity, Mucosal; Respiratory System
PubMed: 27027953
DOI: 10.1513/AnnalsATS.201507-451MG -
Immunobiology Sep 2023PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed... (Meta-Analysis)
Meta-Analysis
PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed to investigate the association between PDE4D variants (and haplotypes) with asthma and atopy in a Brazilian population. The study comprised 1,246 unrelated participants from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was performed using the Illumina 2.5 Human Omni bead chip. Multivariate logistic regression was used to investigate the association between PDE4D variants and asthma/atopy phenotypes in PLINK 1.09 software. Twenty-four SNVs in PDE4D were associated with atopy or asthma. The rs6898082 (A) variant increased asthma susceptibility (OR 2.76; CI 99% 1.26-6.03) and was also related to a greater PDE4D expression in the GTEx database. Also, the variant rs6870632 was further associated with asthma in meta-analysis with a replication cohort. In addition, the variants rs75699812 (C), rs8007656 (G), and rs958851 (T) were positively associated with atopy. Moreover, these variants formed an atopy risk haplotype (OR 1.82; CI 99% 1.15-2.88). Also, these variants were related to lower levels of IL-10. Functional in silico assessment showed that some PDE4D SNVs may have an impact on gene regulation and expression. Variants in the PDE4D are positively associated with asthma and allergy markers. It is possible that these variants lead to alteration in PDE4D expression and therefore impact immunity and pulmonary function.
Topics: Humans; Child; Haplotypes; Brazil; Genetic Predisposition to Disease; Asthma; Hypersensitivity, Immediate; Hypersensitivity; Polymorphism, Single Nucleotide; Cyclic Nucleotide Phosphodiesterases, Type 4
PubMed: 37549468
DOI: 10.1016/j.imbio.2023.152724 -
Allergy and Asthma Proceedings 2015Atopic diseases are a major public health problem worldwide, and several factors are thought to contribute to this rapid increase. The observed association between mode... (Review)
Review
Atopic diseases are a major public health problem worldwide, and several factors are thought to contribute to this rapid increase. The observed association between mode of delivery and risk of atopy in childhood has had a great deal of interest during the past few decades. In fact, even during delivery, exposure to antigens can index immune system in newborn, which induces the release of biologically active molecules, which are polarizing immune responses toward the T-helper 2 atopic profile. However, to date, studies on the relationship between mode of delivery and atopy have produced conflicting findings. The aim of this review was to summarize what is known about the relationship between mode of delivery and risk of atopic diseases in children. A literature search of electronic databases was undertaken for the major studies published from 1994 to today. The databases searched were PubMed, EMBASE, Medline, and Cochrane Library. The following key words were used: mode of delivery, cesarean section, vaginal delivery, atopy, and atopic diseases.
Topics: Child; Delivery, Obstetric; Female; Humans; Hypersensitivity, Immediate; Immune System; Immunity, Maternally-Acquired; Infant, Newborn; Pregnancy; Risk; Th1-Th2 Balance; Th2 Cells
PubMed: 26314816
DOI: 10.2500/aap.2015.36.3870 -
Epigenetics Jun 2021The increase in the prevalence of allergic diseases is believed to partially depend on environmental changes. DNA methylation is a major epigenetic mechanism, which is...
The increase in the prevalence of allergic diseases is believed to partially depend on environmental changes. DNA methylation is a major epigenetic mechanism, which is known to respond to environmental factors. A number of studies have revealed that patterns of DNA methylation may potentially predict allergic diseases.Here, we examined how maternal atopy is associated with methylation patterns in the cord blood of neonates.We conducted an epigenome-wide association study in a cohort of 96 mother-child pairs. Pregnant women aged not more than 35 years old, not currently smoking or exposed to environmental tobacco smoke, who did not report obesity before conception were considered eligible. They were further tested for atopy. Converted DNA from cord blood was analysed using Infinium MethylationEPIC; for statistical analysis, RnBeads software was applied. Gestational age and sex were included as covariates in the final analysis.83 DM sites were associated with maternal atopy. Within the top DM sites, there were CpG sites which mapped to genes SCD, ITM2C, NT5C3A and NPEPL1. Regional analysis revealed 25 tiling regions, 4 genes, 3 CpG islands and 5 gene promoters, (including PIGCP1, ADAM3A, ZSCAN12P1) associated with maternal atopy. Gene content analysis revealed pointwise enrichments in pathways related to purine-containing compound metabolism, the G1/S transition of the mitotic cell cycle, stem cell division and cellular glucose homoeostasis.These findings suggest that maternal atopy provides a unique intrauterine environment that may constitute the first environment in which exposure is associated with methylation patterns in newborn.
Topics: Adult; CpG Islands; DNA Methylation; Epigenesis, Genetic; Epigenome; Female; Fetal Blood; Genome-Wide Association Study; Humans; Maternal Exposure; Pregnancy
PubMed: 32902349
DOI: 10.1080/15592294.2020.1814504 -
The FEBS Journal Sep 2018A striking feature underlying all atopic disorders, such as asthma, atopic dermatitis, and food allergy, is the presence of pathologic sensory responses, reflexes, and... (Review)
Review
A striking feature underlying all atopic disorders, such as asthma, atopic dermatitis, and food allergy, is the presence of pathologic sensory responses, reflexes, and behaviors. These symptoms, exemplified by chronic airway irritation and cough, chronic itch and scratching, as well as gastrointestinal discomfort and dysfunction, are often cited as the most debilitating aspects of atopic disorders. Emerging studies have highlighted how the immune system shapes the scope and intensity of sensory responses by directly modulating the sensory nervous system. Additionally, factors produced by neurons have demonstrated novel functions in propagating atopic inflammation at barrier surfaces. In this review, we highlight new studies that have changed our understanding of atopy through advances in characterizing the reciprocal interactions between the immune and sensory nervous systems.
Topics: Animals; Asthma; Dermatitis, Atopic; Humans; Hypersensitivity; Immune System; Inflammation; Nervous System; Sensory Receptor Cells
PubMed: 29637705
DOI: 10.1111/febs.14465