PURPOSE OF REVIEW: Several population-based studies have replicated the finding that exposure to a farm environment is protective against the development of atopic diseases. From these studies, novel insights into potential allergy-protective mechanisms were retrieved. This review focuses on consistent and novel findings of immune mechanisms involved in the ‘farm effect’. RECENT FINDINGS: The most recent studies suggest that the ‘farm effect’ mediated by microbial exposure may be attributed to both microbial diversity and species specificity. There is convincing evidence that farm milk components and grass arabinogalactan, commonly found in cowshed, may be important. Furthermore, early exposure to a farming environment, in particular in utero, showed stronger effects than exposure later in life, potentially through modulation of the immature immune system by microbes, also involving epigenetic changes. This protective ‘farm effect’ remains in later adulthood. Regarding gene-environment interactions, polymorphisms in GRM1 interacted with farming in a genome-wide interaction scan for asthma. SUMMARY: The novel studies strengthen the role of microbial exposure and farm milk and grass components, especially early in life, in the modulation of the immune system towards a Th1/Treg predominance. This may subsequently lead to a long-lasting lower risk of developing atopic diseases.
PMID: 22306551 [PubMed - as supplied by publisher]
The role of lymphocyte proliferation tests in assessing occupational sensitization and disease.
Curr Opin Allergy Clin Immunol. 2012 Feb 2;
Authors: Hines SE, Pacheco K, Maier LA
Abstract
PURPOSE OF REVIEW: Lymphocyte proliferation testing (LPT) is used in diagnosing occupationally acquired delayed-type hypersensitivity. It has been used in beryllium-health effects, and its role is expanding in metal allergy. It may find application in diagnosis of other sensitizers. RECENT FINDINGS: Use of the beryllium LPT (BeLPT) in medical surveillance identifies beryllium sensitization at low exposure with chronic beryllium disease (CBD) that leads to physiologic impairment and need for immunosuppressive medications. New studies indicate that both beryllium exposure and genetic variation are associated with increased risk of CBD. Borderline positive BeLPTs warrant inclusion into diagnostic algorithms. Furthermore, use of LPTs to diagnose metal allergy is being proposed in diagnosis of chromium allergy and hypersensitivity to surgical implants. New occupational sensitizers continue to be identified including metalworking fluids, the sterilizing agent ortho-phthalaldehyde and the solvent para-chlorobenzotrifluoride. Use of LPT in occupational surveillance to these agents and other known sensitizers may play expanding roles. SUMMARY: Lymphocyte proliferation testing serves a valuable role in diagnosing occupational sensitization, as demonstrated with beryllium-health effects, as cases continue to be found at low exposure levels. The use of LPTs in diagnosing contact allergy is expanding, and new applications may be identified in human and animal studies.
PMID: 22306552 [PubMed - as supplied by publisher]
The effect of environmental oxidative stress on airway inflammation.
Curr Opin Allergy Clin Immunol. 2012 Feb 2;
Authors: Auerbach A, Hernandez ML
Abstract
PURPOSE OF REVIEW: Asthma is an inflammatory respiratory condition with significantly associated morbidity and mortality that is increasing in prevalence. Air pollution is an important factor in both the development of asthma and in asthma exacerbations. Oxidative stress as a result of exposure to air pollution and underlying genetic polymorphisms that may play a role in susceptibility to this oxidative stress are the subject of current investigation. This article reviews the data regarding the effects of air pollution on the innate immune response and potential clinical and treatment implications of how genetic polymorphisms affect this response. RECENT FINDINGS: Recent investigation reveals how pollutant-induced oxidative stress impacts airway inflammatory responses. Work by our study group demonstrates that asthmatic patients have an exaggerated inflammatory response to air pollution-induced oxidative stress. New trials investigating antioxidants as potential therapeutic interventions may target this specific issue. SUMMARY: Air pollution plays a critical role in asthma and may affect certain patients more than others. Further investigation into the genetic polymorphisms that affect inflammatory responses may help target patient populations at greatest risk for air pollution-induced asthma and may provide new therapeutic options for these patient populations.
PMID: 22306553 [PubMed - as supplied by publisher]
Immunological and inflammatory responses to organic dust in agriculture.
Curr Opin Allergy Clin Immunol. 2012 Feb 2;
Authors: Poole JA, Romberger DJ
Abstract
PURPOSE OF REVIEW: Agriculture represents a major industry worldwide, and despite protection against the development of IgE-mediated diseases, chronic exposure to agriculture-related organic dusts is associated with an increased risk of developing respiratory disease. This article will review the literature regarding new knowledge of important etiologic agents in the dusts and focus on the immunologic responses following acute and repetitive organic dust exposures. RECENT FINDINGS: Although endotoxin remains important, there is an emerging role of nonendotoxin components such as peptidoglycans from Gram-positive bacteria. Pattern recognition receptors including Toll-like receptor 4 (TLR4), TLR2 and intracellular nucleotide oligomerization domain-like receptors are partially responsible for mediating the inflammatory consequences. Repeated organic dust exposures modulate innate and adaptive immune function with a resultant adaptation-like response. However, repetitive exposures cause lung parenchymal inflammation, chronic disease, and lung function decline over time. SUMMARY: The immunological consequences of organic dust exposure in the farming industry are likely explained by the diversity of microbial motifs in dust that can elicit differing innate immune receptor signaling pathways. Whereas initial activation results in a robust inflammatory response, repetitive dust exposures modulate immunity. This can result in low-grade, chronic inflammation, and/or protection against allergic disease.
PMID: 22306554 [PubMed - as supplied by publisher]
Epigenetics mediate environment : gene effects on occupational sensitization.
Curr Opin Allergy Clin Immunol. 2012 Feb 2;
Authors: Pacheco KA
Abstract
PURPOSE OF REVIEW: Epigenetics is the study of stable modifications of fixed genomes that direct which genes are expressed and which are silenced. Epigenetic changes are modulated by environmental exposures, making epigenetics the interface between genes and environment. This has particular relevance in understanding the effect of occupational exposures on the expression of allergic disease. The goal of this review is to describe how epigenetic changes affect transcription potential, and to examine more closely the effect of specific environmental and occupational exposures on epigenetic variations that alter allergy gene transcripts and the inflammatory milieu. RECENT FINDINGS: Gene transcription is activated when specific CpG sites are demethylated and histones are acetylated, and, conversely, silenced when sites are methylated and histones deacetylated. The development of Th1 and Th2 phenotypes, and expression of Treg cells, are now known to be modulated by epigenetic mechanisms. Workplace exposures such as tobacco smoke, particulates, diesel exhaust, polyaromatic hydrocarbons, ozone, and endotoxin, among others, suppress Treg development, and enhance expression of inflammatory cytokines and allergic phenotypes by epigenetic means. SUMMARY: Epigenetic manipulation to open and close transcription sites provides flexibility of gene expression in response to changing environmental cues. It may also be the window whereby allergic disease in the workplace can be reduced by targeted environmental interventions.
PMID: 22306555 [PubMed - as supplied by publisher]
Vitamin D deficiency as a risk factor for childhood allergic disease and asthma.
Curr Opin Allergy Clin Immunol. 2012 Jan 19;
Authors: Litonjua AA
Abstract
PURPOSE OF REVIEW: Over the past 2 years, the number of studies relating vitamin D deficiency and asthma and allergies has increased significantly. The purpose of this review is to update the last review in this journal and examine the evidence of the relationship between vitamin D deficiency and childhood asthma and allergies. RECENT FINDINGS: In the past 2 years since the last review, there have been many studies, both cross-sectional and prospective, that have investigated the effects of vitamin D on the inception and severity of asthma and allergies. Most, but not all, studies have shown that low vitamin D levels increase the risk for asthma and allergies, but a few suggest an increased risk with high levels. Results from small trials of short duration suggest that vitamin D supplementation decreases severity of eczema and decreases the risk for asthma exacerbations. SUMMARY: Data that vitamin D deficiency results in increased risks for asthma and allergies continues to accumulate. However, the optimal level of vitamin D that decreases both the risk for development and severity of these disorders remains elusive. Results of ongoing clinical trials of vitamin D supplementation will be needed before recommendations can be firmly established.
PMID: 22266772 [PubMed - as supplied by publisher]
PURPOSE OF REVIEW: The objective of this review is to provide an overview and discussion of recent epidemiologic and mechanistic studies of stress in relation to asthma incidence and morbidity. RECENT FINDINGS: Recent findings suggest that stress, whether at the individual (i.e. epigenetics, perceived stress), family (i.e. prenatal maternal stress, early-life exposure, or intimate partner violence) or community (i.e. neighborhood violence; neighborhood disadvantage) level, influences asthma and asthma morbidity. Key recent findings regarding how psychosocial stress may influence asthma through Posttraumatic Stress Disorder, prenatal and postnatal maternal/caregiver stress, and community violence and deprivation are highlighted. SUMMARY: New research illustrates the need to further examine, characterize, and address the influence of social and environmental factors (i.e. psychological stress) on asthma. Further, research and innovative methodologies are needed to characterize the relationship and pathways associated with stress at multiple levels to more fully understand and address asthma morbidity, and to design potential interventions, especially to address persistent disparities in asthma in ethnic minorities and economically disadvantaged communities.
PMID: 22266773 [PubMed - as supplied by publisher]
PURPOSE OF REVIEW: Children with severe asthma have a high degree of respiratory morbidity despite treatment with high doses of inhaled corticosteroids and are therefore very difficult to treat. This review will discuss phenotypic and pathogenic aspects of severe asthma in childhood, as well as remaining knowledge gaps. RECENT FINDINGS: As a group, children with severe asthma have a number of distinct phenotypic features compared with children with mild-to-moderate asthma. Clinically, children with severe asthma are differentiated by greater allergic sensitization, increased exhaled nitric oxide, and significant airflow limitation and air trapping that worsens as a function of age. These findings are accompanied by structural airway changes and increased and dysregulated airway inflammation and oxidant stress which may explain the differential nature of corticosteroid responsiveness in this population. Because children with severe asthma themselves are a heterogeneous group, current efforts are focused on improved definition and sub-phenotyping of the disorder. Whereas the clinical relevance of phenotyping approaches in severe asthma is not yet clear, they may provide important insight into the mechanisms underlying the disorder. SUMMARY: Improved classification of severe asthma through unified definitions, careful phenotypic analyses, and mechanism-focused endotyping approaches may ultimately advance knowledge and personalized treatment.
PMID: 22249197 [PubMed - as supplied by publisher]
PURPOSE OF REVIEW: To discuss the role of vitamin D in chronic rhinitis and chronic rhinosinusitis (CRS).
RECENT FINDINGS: Vitamin D has been shown to have an immunomodulatory effect with a significant impact on immune function. Specifically, vitamin D regulates the mechanisms which suppress the inflammatory response and direct the differentiation fate of immune cells. Vitamin D has been shown to play an important role in asthma, and the concept of the unified airway model allows the extrapolation of vitamin D as a critical player in chronic rhinitis and rhinosinusitis.
SUMMARY: Recent findings on the function of vitamin D may explain aspects of the pathophysiology of chronic rhinitis and CRS, and may help direct future treatment of these diseases.
PURPOSE OF REVIEW: Asthma is a chronic pulmonary inflammatory disease affecting all races, children and adults. The causative or intrinsic development of asthma is diverse, ranging from episodic exposure to environmental insults to physical induction in exercise.
RECENT FINDINGS: Asthma uniquely manifests in affected individuals as episodes of airway hyper-reactivity, chronic airway obstruction, and inflammation. The diversity in asthmatic phenotypes and the mechanisms that lead to initiation and perpetuation of the lung disease continue to make asthma a challenge to treat, classify, and manage therapeutically.
SUMMARY: This review will focus on the newest of mechanistic insights into asthma development, therapeutic innovations, and clinical applications.
PMID: 22193053 [PubMed - in process]
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