Showing papers in "Current Opinion in Allergy and Clinical Immunology in 2014"
TL;DR: This review summarizes the current understanding of the molecular mechanism behind iDILI, and suggests that reactive metabolite formations, oxidative stress and signalling pathway inductions, with the mitochondria taking centre stage, are believed to be orchestrated by multiple events.
Abstract: Purpose of reviewIdiosyncratic drug-induced liver injury (iDILI) is a relatively rare condition, but can have serious consequences for the individual patient, public health, regulatory agencies and the pharmaceutical industry. Despite increased awareness of iDILI, its underlying mechanism is still n
160 citations
TL;DR: How I LC2 traits, discovered in mouse models, have informed research in humans and how newly identified human ILC2 pathways might provide potential therapeutic benefits in the future are discussed.
Abstract: Purpose of reviewRecent decades have seen allergic diseases become endemic in a number of developed countries. Understanding the inflammatory processes that dictate these allergic responses is therefore important.Recent findingsCritical to many allergic responses is the inappropriate release of the
91 citations
TL;DR: Susceptibility to asthma and allergic diseases is complex and involves genetic variants and environmental exposures, alteration of the microbiome and potentially large-scale manipulation of the environment over the past century.
Abstract: Purpose of reviewUnderstanding the mechanisms involved in the development of asthma and allergic diseases is expanding, due in part to sequencing advances that have led to the identification of new viral strains such as human rhinovirus strain C (HRV-C) and the human microbiome project.Recent findin
85 citations
TL;DR: Recent findings related to conjunctival goblet cells provide the basis for novel therapeutic approaches, involving modulation ofGoblet cell mucin production, to improve treatment of ocular allergies.
Abstract: Purpose of review Although conjunctival goblet cells are a major cell type in ocular mucosa, their responses during ocular allergy are largely unexplored. This review summarizes the recent findings that provide key insights into the mechanisms by which their function and survival are altered during chronic inflammatory responses, including ocular allergy. Recent findings Conjunctiva represents a major component of the ocular mucosa that harbors specialized lymphoid tissue. Exposure of mucin-secreting goblet cells to allergic and inflammatory mediators released by the local innate and adaptive immune cells modulates proliferation, secretory function, and cell survival. Allergic mediators like histamine, leukotrienes, and prostaglandins directly stimulate goblet cell mucin secretion and consistently increase goblet cell proliferation. Goblet cell mucin secretion is also detectable in a murine model of allergic conjunctivitis. Additionally, primary goblet cell cultures allow evaluation of various inflammatory cytokines with respect to changes in goblet cell mucin secretion, proliferation, and apoptosis. These findings in combination with the preclinical mouse models help understand the goblet cell responses and their modulation during chronic inflammatory diseases, including ocular allergy. Summary Recent findings related to conjunctival goblet cells provide the basis for novel therapeutic approaches, involving modulation of goblet cell mucin production, to improve treatment of ocular allergies.
70 citations
TL;DR: In this paper, the authors describe mechanism(s) that may explain the association between obesity and asthma and the two conditions also appear to be linked with an increased risk of asthma in people who are obese.
Abstract: Purpose of reviewObesity and asthma are chronic conditions affecting millions of people worldwide. The two conditions also appear to be linked with an increased risk of asthma in people who are obese. The purpose of this review is to describe mechanism(s) that may explain the association between ast
64 citations
TL;DR: A critical update of the evidence for AIT-related cost savings for both subcutaneous immunotherapy (SCIT) and SLIT is reviewed, spanning research from Southern Europe, Scandinavia, Northern Europe, North America, and the Czech Republic.
Abstract: Purpose of reviewGiven the widespread prevalence of allergic disease, its substantially associated clinical and economic burden, the unique disease-modifying benefits of allergy immunotherapy (AIT), and increased availability of sublingual immunotherapy (SLIT), a critical update of the evidence for
58 citations
TL;DR: This review summarizes the current knowledge of biomarkers for the determination of asthma phenotypes and indicates the discordance between treatment response or adjustment and FeNO levels and serum periostin is a strong serum biomarker for eosinophilic airway inflammation.
Abstract: Purpose of reviewA variety of novel asthma treatments have been developed based on phenotypes, and the clinical trial results show promising responses. This review summarizes the current knowledge of biomarkers for the determination of asthma phenotypes.Recent findingsEosinophilic inflammation is th
58 citations
TL;DR: FPIES is not as rare as once thought, but how common it is, what factors predispose to its development, and why there is regional variation needs to be addressed by future well designed population-based studies.
Abstract: Purpose of reviewTo summarize the epidemiology of food protein-induced enterocolitis syndrome (FPIES).Recent findingsFPIES is regarded as a rare non-IgE-mediated gastrointestinal allergic disorder. Older nonpopulation-based studies reported an average of 1–15 cases presenting to allergy clinics a ye
58 citations
TL;DR: Important developments have been made in the understanding of histone deacetylase expression in normal and diseased airways and pulmonary tissue as well as effects of hist one de acetylase inhibitors on structural and inflammatory cells in the lung, including cell proliferation, differentiation and apoptosis and senescence.
Abstract: Purpose of reviewThe importance of the role of histone deacetylase enzymes in the pathogenesis of asthma and chronic respiratory diseases is increasingly being recognized. Similarly, the potential clinical utility of histone deacetylase enzymes in the treatment of disease is emerging. In this review
57 citations
TL;DR: Over the past several years, there has been an increasing awareness of FPIES and this knowledge should lead to a more timely diagnosis and should reassure parents and practitioners alike regarding its favorable course.
Abstract: Purpose of reviewBecause of the paucity of reports and variability in the diagnostic criteria utilized, little is known regarding the natural outcome of patients with food protein-induced enterocolitis syndrome (FPIES) Data extracted from referenced manuscripts, as well as allergists’ unpublished o
54 citations
TL;DR: Formation of hapten–protein complexes, their processing and antigen presentation have been implicated in the development of drug allergy to p-phenylenediamine, sulfonamides and &bgr;-lactams, but evidence also supports the pi mechanism of immune activation wherein drugs interact directly with immune receptors.
Abstract: Purpose of reviewDrug allergy is an adverse drug reaction that is immune-mediated. Immune activation can occur when drugs or haptens bind covalently to proteins and then act as antigens. The purpose of this review is to summarize the recent data on the formation of hapten–protein complexes and to as
TL;DR: Many of the mechanisms proposed for the immune-modulating effects of IVIG demonstrate the complexity of immune effector functions in disease processes and the potential role of the prostaglandin E pathway may offer alternative treatments.
Abstract: Purpose of review In the past few years there have been many advances in our understanding of the mechanisms by which intravenous immune globulin (IVIG) modulates immune function in autoimmune disorders. Recent findings Previous investigations have focused on the Fc domain of the IgG molecule, and the role of the FcγRIIB receptor and the sialylated Fc domain that have been show to mediate the anti-inflammatory effects in certain murine models of autoantibody-mediated diseases. More recent findings have implicated the F(ab')₂ domain in IVIG-induced immune modulation in T-cell-mediated autoimmune disease models in which upregulation of T-regulatory cells and downregulation of the Th17 pathways are important components of this mechanism. The prostaglandin E pathway may be playing a role in the IVIG-induced changes in the T-regulatory pathway. Summary Many of the mechanisms proposed for the immune-modulating effects of IVIG demonstrate the complexity of immune effector functions in disease processes. Although controversy exists on the role of the FcγRIIB receptor and the importance of the sialylated Fc domain in human autoimmune disorders, probably no one single mechanism is responsible for the effects of IVIG in autoimmune and inflammatory diseases. The potential role of the prostaglandin E pathway may offer alternative treatments.
TL;DR: Anti-IL-4/13 therapies, guided by knowledge of an individual's underlying pathophysiology, are a promising class of therapies for treatment of asthma.
Abstract: Purpose of reviewTo summarize recent advances in IL-4 and IL-13 blockade in the treatment of asthma.Recent findingsHistorically, anticytokine therapies have historically been unsuccessful in the treatment of asthma because of the heterogeneity of its pathogenesis. Recent advances in our understandin
TL;DR: This review describes recent findings and trends in prevalence and treatment of allergic ocular diseases and places a significant emphasis on immunotherapy as an alternative treatment modality, particularly in the USA.
Abstract: Purpose of review This review describes recent findings and trends in prevalence and treatment of allergic ocular diseases. Although the major focus is on seasonal and perennial allergic conjunctivitis, related disorders will also be considered. Recent findings Published reports from countries around the world suggest that the spectrum of atopic diseases, including seasonal and perennial allergic conjunctivitis, is continuing its pattern of increasing prevalence, which has been well documented over the past few decades. In addition, although treatment modalities have focused on topical formulations including antihistamines and corticosteroids, there is a significant emphasis on immunotherapy as an alternative treatment modality, particularly in the USA. Summary Allergic conjunctivitis is a key component in the spectrum of allergic diseases that is sometimes collectively referred to as rhinoconjunctivitis. Because of its high prevalence worldwide, it exacts an increasing toll in terms of patient discomfort, morbidity, and loss of productivity. Current estimates suggest that at least 20% of the overall population suffers from some form of allergic conjunctivitis, many without ever seeking treatments. In addition, a significant proportion of patients experience chronic forms of allergy that are less responsive to existing therapies. Recent approval of immunotherapy-based treatments may address this therapeutic gap.
TL;DR: Multicenter studies are necessary to reevaluate and modify the oral food challenge criteria and research on the pathophysiology of FPIES reactions is necessary to provide insight into the evidence-based approach to diagnosis and management ofFPIES.
Abstract: Purpose of reviewFood protein-induced enterocolitis syndrome (FPIES) is a poorly understood non-IgE-mediated food hypersensitivity, primarily affecting infants and toddlers. There are few data regarding pathophysiology of FPIES that suggest local intestinal imbalance between TNF-α and TGF-β. Patient
TL;DR: Data from children with severe asthma have shown that findings from adults cannot be translated to children, and that steroid-resistant eosinophilic inflammation appears central to the pathogenesis of paediatric disease.
Abstract: Purpose of review The importance and functional contribution of eosinophils to the pathogenesis of severe asthma was questioned when adult studies reported neutrophilic inflammation and Th17 cells were central to disease. Recent findings Eosinophilic inflammation, atopic sensitization and airway remodelling are the hallmark features of severe asthma in children. Contrary to adult reports, neutrophils, Th17 and Th2 cytokines are rarely detected in children with severe disease who are prescribed high-dose steroids. Type 2 innate lymphoid cells (ILCs), which are induced by the epithelial cytokine interleukin (IL)-33, and also release the Th2 cytokines IL-5 and IL-13, have been shown to be important in mediating asthma, and specifically, ILCs have a role in mediating eosinophil homeostasis. A direct link between IL-33, airway remodelling and steroid resistance in paediatric severe asthma suggests the steroid-resistant eosinophilia may be mediated by ILCs rather than classical Th2 lymphocytes. Summary Data from children with severe asthma have shown that findings from adults cannot be translated to children, and that steroid-resistant eosinophilic inflammation appears central to the pathogenesis of paediatric disease. Age-appropriate experimental models and use of airway samples from children are critical to understanding the underlying mechanisms and identifying novel therapeutic targets.
TL;DR: Significant pathologic findings in nasal polyp tissues include intense eosinophilic inflammation, which is caused by elevated production of eOSinophil-related cytokines and chemokines, specific immunoglobulin E responses to staphylococcal enterotoxins, and altered arachidonic acid metabolism.
Abstract: Purpose of reviewThe key features of aspirin-exacerbated respiratory diseases (AERDs) include chronic, severe asthma and a high prevalence (60–80%) of chronic rhinosinusitis with nasal polyps, all of which are exacerbated by exposure to aspirin and other NSAIDs. Although the pathogenic mechanisms of
TL;DR: In this paper, the authors present the current perspectives regarding the role of microbial exposure and airway bacterial colonization on the development and the activity of asthma and discuss the potential role of early life microbial exposure in health and disease.
Abstract: Purpose of this review
Recent application of advanced culture-independent molecular techniques for identification of microorganisms has contributed to our knowledge on the role of early life microbial exposure and colonization in health and disease. The purpose of this review is to present the current perspectives regarding the role of microbial exposure and airway bacterial colonization on the development and the activity of asthma.
TL;DR: All the possible differential diagnosis of food protein-induced enterocolitis syndrome (FPIES), both in acute and chronic presentation, are assessed, reviewing the data reported in published studies.
Abstract: Purpose of review
To assess all the possible differential diagnosis of food protein-induced enterocolitis syndrome (FPIES), both in acute and chronic presentation, reviewing the data reported in published studies.
TL;DR: An overview on recent developments in the field of asthma and allergy epigenetics is given with a special focus on the role of DNA methylation in these diseases, where it seems that methylation is affected by environmental stimuli such as prenatal smoke exposure and farming environments, whereas asthma status is associated with change inmethylation in early childhood.
Abstract: Purpose of reviewEpigenetic mechanisms such as DNA methylation, histone modification and microRNA control the accessibility of the genome and manage gene transcription in response to the environment in a heritable fashion. Recent evidence suggests that these mechanisms play a role in allergy and ast
TL;DR: A better understanding of the mechanisms leading to cardiac mast cell activation and the effects of mast cell mediators on cardiovascular system can help improve the prevention and treatment of anaphylaxis.
Abstract: Purpose of reviewAnaphylaxis is a life-threatening event in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. This review summarizes the most recent clinical and experimental data on cardiovascular involvement during anaphylaxis.R
TL;DR: Prospective cohort studies and two recently published meta-analyses found an association between overweight (and especially obesity) and asthma in the appropriate temporal sequence and in a dose–response manner.
Abstract: Purpose of reviewWhen evaluating the causal link between obesity and the development of asthma in children, prospective cohort studies are essential. The results of the most recently published birth cohort studies from Sweden, Germany, Brazil, Belarus, and California, USA, as well as from a joint an
TL;DR: The latest information on the nutritional management of food protein-induced enterocolitis syndrome is summarized, focusing on the foods implicated and how to avoid these whilst maintaining a nutritionally sound diet.
Abstract: Purpose of reviewTo summarize the latest information on the nutritional management of food protein-induced enterocolitis syndrome (FPIES), focusing on the foods implicated and how to avoid these whilst maintaining a nutritionally sound diet.Recent findingsA number of foods are implicated in FPIES su
TL;DR: Viral respiratory infections in early life are a major source of morbidity and are critical in the development of asthma, and mechanisms by which these infections lead to asthma inception in susceptible individuals are emerging.
Abstract: Purpose of reviewTo discuss the recent insights into the relationships between viral respiratory infections and asthma inception in the context of a long-term goal of moving toward prevention strategies for childhood asthma.Recent findingsThere is strong evidence for respiratory syncytial virus and
TL;DR: FPIES is a non-IgE-mediated reaction that usually presents with acute severe repetitive vomiting and diarrhea associated with lethargy, pallor, dehydration, and even hypovolemic shock and resolve usually within 24–48 h of elimination of the causative food.
Abstract: Purpose of review To raise awareness among healthcare providers about the clinical and laboratory findings in acute and chronic food protein-induced enterocolitis syndrome (FPIES). Recent findings FPIES can be caused by trivial exposure or rare foods. Summary FPIES is a non-IgE-mediated reaction that usually presents with acute severe repetitive vomiting and diarrhea associated with lethargy, pallor, dehydration, and even hypovolemic shock. Manifestations resolve usually within 24-48 h of elimination of the causative food. In chronic cases, symptoms may include persistent diarrhea, poor weight gain, failure to thrive, and improvement may take several days after the food elimination. In the acute cases, laboratory evaluation may reveal thrombocytosis and neutrophilia, peaking about 6 h postingestion. Depending on the severity, metabolic acidosis and methemoglobinemia may occur. In chronic cases, anemia, hypoalbuminemia and eosinophilia may be seen. Radiologic evaluation or other procedures, such as endoscopy and gastric juice analysis may show nonspecific abnormal findings. The diagnosis is based on clinical manifestations. Further studies looking at the phenotypes of FPIES are needed to identify clinical subtypes, and to understand the predisposing factors for developing FPIES compared with immediate-type, IgE-mediated gastroenteropathies.
TL;DR: Advances in transplant outcomes for Wiskott–Aldrich syndrome and chronic granulomatous disease support the strategy of early transplantation before the onset of severe complications; additional multicenter studies are needed to fully define optimal approaches.
Abstract: Purpose of the Review
This review describes recent studies on outcomes after allogeneic hematopoietic cell transplantation (HCT) for primary immunodeficiency (PID) in North America including severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD).
TL;DR: Cyclosporine A and tacrolimus are currently available for the treatment of severe allergic conjunctivitis and these agents have led to improved therapeutic results for patients with severe and chronic allergic eye diseases.
Abstract: Purpose of reviewAllergic eye diseases comprise a spectrum of diseases, with each condition being characterized by a complex immunopathology. The more severe and chronic conditions, such as vernal keratoconjunctivitis and atopic keratoconjunctivitis, involve predominantly mast cells and eosinophils,
TL;DR: Clinical management of patients affected by food protein-induced enterocolitis syndrome must take into account, among other factors, improved understanding of pathogenesis, possible detection of different phenotypes, and the introduction of more effective therapies for acute episodes.
Abstract: Purpose of reviewThe article discusses the clinical management of patients affected by food protein-induced enterocolitis syndrome (FPIES), focusing on established therapeutic choices and future options.Recent findingsAfter FPIES has been diagnosed and avoidance of the culprit food prescribed, the m
TL;DR: Better knowledge of atopic dermatitis pathways will form the basis for the development of rationale-based therapeutic approaches in the future.
Abstract: Purpose of reviewResearch on atopic dermatitis is actively growing and continuously completing our knowledge on the pathophysiology of this complex disease.Recent findingsGenome-wide association studies revealed new susceptibility loci for atopic dermatitis. In addition, different tissue-specific pa
TL;DR: The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure that can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.
Abstract: PURPOSE OF REVIEW: Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies.
RECENT FINDINGS: The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration.
SUMMARY: The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.