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1.
Purpose of Review
MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs that are increasingly being recognized as important epigenetic regulators. They have been implicated in the pathogenesis of many diseases including cancer, cardiovascular diseases, connective tissue diseases, and neuromuscular disorders.Recent Findings
A few miRNAs have already been recognized as a core set of miRNAs important in allergic inflammation. These include let-7, miR-21, miR-142, and miR-146.Summary
This review aims to bring together some of the recent findings on how miRNAs regulate allergic inflammation with special focus on asthma, atopic dermatitis, allergic rhinitis, and eosinophilic esophagitis. We will also touch upon extracellular miRNAs and future perspective of this field of study.2.
Purpose of Review
Biologics and small molecules are key therapeutic options in the treatment of chronic immunologic and allergic skin conditions. By directly targeting innate and inflammatory responses within the skin, including pro-inflammatory cytokines and cellular signaling pathways, these new agents have the potential to counteract the inflammatory cascade responsible for various conditions, including psoriasis and atopic dermatitis. Over the past decade, groundbreaking research identifying key cytokines and receptors involved in the pathogenesis of these diseases has allowed for the development of highly efficacious biologics and small molecules that are associated with unprecedented rates of skin clearance and favorable adverse event profiles.Recent Findings
This narrative review evaluates new and upcoming biologic and small molecule agents for the treatment of two allergic/immunologic skin diseases—atopic dermatitis and psoriasis. Numerous small molecules and biologics targeting TNF-α, IL-12/23, IL-17 and IL-17R, and IL-23 are commercially available for the treatment of psoriasis, and newer agents are in various stages of development. Currently, dupilumab, a monoclonal antibody that blocks IL-4R∝, is the only approved biologic for atopic dermatitis. Antibodies targeting IL-13 and IL-31 and small molecules that inhibit Janus kinase and pruritus-mediating receptors are currently being studied in clinical trials. Further investigations into the pathophysiology of atopic dermatitis will likely yield additional therapeutic options in the future.Summary
This article reviews recent literature on small molecules and biologics for the treatment of atopic dermatitis and psoriasis.3.
4.
Wirach Chitsuthipakorn Kachorn Seresirikachorn Doron D. Sommer Tobial McHugh Kornkiat Snidvongs 《Current allergy and asthma reports》2018,18(9):46
Purpose of Review
Preliminary studies have suggested differences in endotypes of chronic rhinosinusitis (CRS) across ancestry/ethnic groups. Eosinophilic CRS (ECRS) is the predominant subtype for Western/European ancestry CRS patients and non-eosinophilic CRS (nECRS) for Asian patients. This review aims to re-analyze CRS endotypes across ancestry populations using one consistent criteria to existing data.Recent Findings
Although tissue eosinophilia is the most commonly used criterion for ECRS, various cut-off points are suggested. Surrogate markers have been extensively studied. Sixty-six cohorts with study criteria were included with a total of 8557 patients. Raw data from 11 studies 544 patients were re-analyzed using number of tissue eosinophils. At lower cut-off values of ≥?5 and ≥?10 cells/HPF, most patients of Asian and Western/European ancestry were classified as ECRS without difference. In contrast, at cut-off points of ≥?70 and ≥?120 cells/HPF, the majority of both groups became reclassified as nECRS.Summary
After applying one consistent criteria to existing data, differences across ancestry and geographic populations in endotypes of CRS were no longer evident.5.
R. S. van Onkelen M. P. Gosselink M. van Meurs M. J. Melief W. R. Schouten J. D. Laman 《Techniques in coloproctology》2016,20(9):619-625
Background
Sphincter-preserving procedures for the treatment of transsphincteric fistulas fail in at least one out of every three patients. It has been suggested that failure is due to ongoing disease in the remaining fistula tract. Cytokines play an important role in inflammation. At present, biologicals targeting cytokines are available. Therefore, detection and identification of cytokines in anal fistulas might have implications for future treatment modalities. The objective of the present study was to assess local production of a selected panel of cytokines in anal fistulas, including pro-inflammatory interleukin (IL)-1β and tumor necrosis factor α (TNF-α).Methods
Fistula tract tissue was obtained from 27 patients with a transsphincteric fistula of cryptoglandular origin who underwent flap repair, ligation of the intersphincteric fistula tract or a combination of both procedures. Patients with a rectovaginal fistula or a fistula due to Crohn’s disease were excluded. Frozen tissue samples were sectioned and stained using advanced immuno-enzyme staining methods for detection of selected cytokines, IL-1β, IL-8, IL-10, IL-12p40, IL-17A, IL-18, IL-36 and TNF-α. The presence and frequencies of cytokine-producing cells in samples were quantitated.Results
The key finding was abundant expression of IL-1β in 93 % of the anal fistulas. Frequencies of IL-1β-producing cells were highest (>50 positive stained cells) in 7 % of the anal fistulas. Also, cytokines IL-8, IL-12p40 and TNF-α were present in respectively 70, 33 and 30 % of the anal fistulas.Conclusions
IL-1β is expressed in the large majority of cryptoglandular anal fistulas, as well as several other pro-inflammatory cytokines.6.
7.
Carmen Rondón Ibon Eguíluz-Gracia Mohamed H. Shamji Janice A. Layhadi María Salas María José Torres Paloma Campo 《Current allergy and asthma reports》2018,18(12):67
Purpose of Review
IgE is a key player in multiple inflammatory airway diseases. Ample literature demonstrates its presence in mucosa of patients with allergic rhinitis (AR), local allergic rhinitis (LAR), asthma, or chronic rhinosinusitis with nasal polyposis (CRSwNP).Recent Findings
Current evidence shows that high-affinity IgE in blood stream of allergic individuals derives mainly from the mucosae. Also, mucosal synthesis of IgE can occur in the absence of systemic atopy, and may be relevant in atopic and non-atopic phenotypes of rhinitis as demonstrated in LAR. Specific IgE (sIgE) detection varies depending on technique used for sample collection and its measurement. sIgE detection is highly specific for diagnosis of LAR. Moreover, measurement of sIgE in secretions could be useful in monitoring response to allergen-specific immunotherapy in both AR and LAR phenotypes.Summary
This review will focus on recent developments in the role of IgE in respiratory diseases, and the clinical implications of its measurement in secretions.8.
Kathryn R. Michels Nicholas W. Lukacs Wendy Fonseca 《Current allergy and asthma reports》2018,18(11):61
Purpose of Review
Allergy and asthma are growing problems in the developed world. The accelerated increase of these diseases may be related to microbiome modification that leads to aberrant activation of Toll-like receptors (TLRs). Current research supports the concept that changes in microbial communities in early life impact TLR activation, resulting in an altered risk for the development of asthma and allergies.Recent Findings
Prenatal and early childhood events that generate microbiome modification are closely related with TLR activation. Early childhood exposure to a rich array of TLR agonists, particularly lipopolysaccharide, strongly predicts protection against allergic disease later in life even when other lifestyle factors are accounted for. Genetic deletion of TLR signaling components in mice results in reduced function of tolerogenic cell populations in the gut. In contrast, weak TLR signaling can promote allergic sensitization later in life.Summary
This review summarizes the role of TLR signaling in microbiome-mediated protection against allergy.9.
Purpose of review
The purpose of this review is to evaluate the most recent findings on indoor allergens and their impact on allergic diseases.Recent findings
Indoor allergens are present inside buildings (home, work environment, school), and given the chronic nature of the exposures, indoor allergies tend to be associated with the development of asthma. The most common indoor allergens are derived from dust mites, cockroaches, mammals (including wild rodents and pets), and fungi. The advent of molecular biology and proteomics has led to the identification, cloning, and expression of new indoor allergens, which have facilitated research to elucidate their role in allergic diseases. This review is an update on new allergens and their molecular features, together with the most recent reports on their avoidance for allergy prevention and their use for diagnosis and treatment.Summary
Research progress on indoor allergens will result in the development of new diagnostic tools and design of coherent strategies for immunotherapy.10.
Purpose of Review
This review summarizes recent findings on mast cell biology with a focus on IgE-independent roles of mast cells in regulating allergic responses.Recent Findings
Recent studies have described novel mast cell-derived molecules, both secreted and membrane-bound, that facilitate cross-talk with a variety of immune effector cells to mediate type 2 inflammatory responses.Summary
Mast cells are complex and dynamic cells that are persistent in allergy and are capable of providing signals that lead to the initiation and persistence of allergic mechanisms.11.
Purpose of Review
The review provides insight into recent findings on bedroom allergen exposures, primarily focusing on pet, pest, and fungal exposures.Recent Findings
Large-scale studies and improved exposure assessment technologies, including measurement of airborne allergens and of multiple allergens simultaneously, have extended our understanding of indoor allergen exposures and their impact on allergic disease. Practical, streamlined methods for exposure reduction have shown promise in some settings, and potential protective effects of early-life exposures have been further elucidated through the investigation of specific bacterial taxa. Advances in molecular allergology have yielded novel data on sensitization profiles and cross-reactivity.Summary
The role of indoor allergen exposures in allergic disease is complex and remains incompletely understood. Advancing our knowledge of various co-exposures, including the environmental and host microbiome, that interact with allergens in early life will be crucial for the development of efficacious interventions to reduce the substantial economic and social burden of allergic diseases including asthma.12.
Purpose of Review
Chronic rhinosinusitis is a disease with high prevalence, significant impact on health-related quality of life (HRQoL) and it is associated with substantial healthcare and productivity costs. We face an urgent need to improve the level of disease control and achieve higher patient satisfaction and disease prevention. Precision medicine is increasingly recognized as the way forward in optimal patient care. The combination of personalized care, prevention of disease, prediction of success of treatment, and participation of the patient in the elaboration of the treatment plan is expected to guarantee the best possible therapeutic approach for individuals suffering from a chronic disabling condition.Recent Findings
This is a narrative review on the current state of endotypes, biomarkers, and targeted treatments in chronic inflammatory conditions of the nose and paranasal sinuses. Different phenotypes of rhinitis and chronic rhinosinusitis (CRS) have been described based on symptom severity and duration, atopy status, level of control, comorbidities, and presence or absence of nasal polyps in CRS. The underlying pathophysiological mechanisms are diverse, with different endotypes being recognized. Novel emerging therapies are targeting specific pathophysiological pathways or endotypes. This endotype-driven treatment approach requires careful selection of the patient population who might benefit from a specific treatment.Summary
This review provides a comprehensive overview of the current state of endotypes, biomarkers and targeted treatments in chronic inflammatory conditions of the nose and paranasal sinuses.13.
Wei-jie Guan Yang Peng Xiao-xue Zi Kai Sen Tan Ting-ting He Nan-shan Zhong De Yun Wang 《Current allergy and asthma reports》2018,18(9):48
Purpose of Review
Impaired mucociliary clearance has been implicated in chronic upper and lower airway inflammatory diseases (i.e., allergic and non-allergic rhinitis, chronic rhinosinusitis with or without nasal polyps and asthma). How motile ciliary disorders (impaired ciliogenesis, ciliary beating and ultrastructural defects) are implicated in chronic airway inflammatory diseases is not fully understood. Elaboration of the role of motile ciliary disorders may serve as therapeutic targets for improving mucociliary clearance, thereby complementing contemporary disease management.Recent Findings
We have summarized the manifestations of motile ciliary disorders and addressed the underlying associations with chronic airway inflammatory diseases. A panel of established and novel diagnostic tests and therapeutic interventions are outlined. Physicians should be vigilant in screening for motile ciliary disorders, particularly in patients with co-existing upper and lower airway inflammatory diseases.Summary
Proper assessment and treatment of motile ciliary disorders may have added value to the management and prevention of chronic airway inflammatory diseases.14.
Jaymin B. Morjaria Massimo Caruso Rosalia Emma Cristina Russo Riccardo Polosa 《Current allergy and asthma reports》2018,18(4):23
Purpose of Review
To evaluate the impact of allergic rhinitis (AR) on the development of asthma and to update readers on recent literature suggesting that early treatment of allergic subjects with immunotherapy may prevent asthma onset.Recent Findings
AR is frequently associated with asthma, leading to the concept that these two conditions are different aspects of the same disease. There is increasing evidence that AR precedes the onset of asthmatic symptoms and current treatment strategies are beneficial in symptom control with no impact prevention. There is limited knowledge about the risk factors responsible for the progression of AR to asthma, though recent data supports the notion that it is possible to prevent asthma onset by allergen immunotherapy.Summary
Despite significant advances in specific immunotherapy (SIT) therapy strengthening its efficacy in AR and possible prevention of progression to asthma, the adoption of this therapeutic strategy is still restricted in comparison to therapies directed towards treatment of AR symptoms. Unlike corticosteroids and other symptomatic therapies, the benefit of SIT treatment in allergic individuals has been shown to prevent the development of allergic conditions. Hence, large well-conducted randomized clinical trials with long-term efficacy of SIT are required to confirm or refute the concept that SIT may abrogate the progression of AR to asthma in patients.15.
Masaya Iwamuro Sakiko Hiraoka Hiroyuki Okada Yoshinari Kawai Yoshio Miyabe Katsuyoshi Takata Seiji Kawano Kazuhide Yamamoto 《International journal of colorectal disease》2016,31(2):313-317
Purpose
The purpose of this study was to determine the prevalence of lymphoid hyperplasia in the lower gastrointestinal tract and its role in patients undergoing colonoscopic examinations, particularly focusing on any allergic predisposition.Methods
A database search performed at the Department of Gastroenterology at Onomichi Municipal Hospital identified seven patients with lymphoid hyperplasia in the large intestine (i.e., cecum, colon, and/or rectum). Data regarding the endoscopic, biological, and pathological examinations performed and the allergic histories for each patient were retrospectively reviewed from the clinical records.Results
Median age of the patients (four males, three females) was 50 years. Lymphoid hyperplasia was seen in the cecum (n?=?5), ascending colon (n?=?2), and transverse colon (n?=?1). Six patients (85.7 %) had one of the allergic airway diseases: allergic rhinoconjunctivitis for pollen (n?=?3), bronchial asthma (n?=?1), infantile asthma (n?=?1), or allergic bronchitis (n?=?1). Drug allergy (n?=?3) and urticaria (n?=?2) were also found. All seven patients had one or more allergic diseases; however, none had a history of food allergy. Blood tests for allergens revealed that six patients (85.7 %) had positive reactions to inherent allergens, whereas only one patient had a positive reaction to food allergens.Conclusions
Our results indicate that lymphoid hyperplasia in the large intestine may be associated with allergic airway diseases rather than with food allergies; thus, its presence may be useful to detect patients with underlying airway hyperreactivity.16.
Yoon Seok Roh Surim Park Chae Woong Lim Bumseok Kim 《Digestive diseases and sciences》2015,60(7):2009-2018
Background
Accumulating evidence suggests that Foxp3+ regulatory T (Treg) cells act as inhibitory mediators of inflammation; however, the in vivo mechanism underlying this protection remains elusive in liver diseases.Aims
To clarify the in vivo role of Foxp3+ Treg cells in liver fibrosis, we used the DEREG mouse, which expresses the diphtheria toxin receptor under control of the Foxp3 promoter, allowing for specific deletion of Foxp3+ Treg cells.Methods
Bile duct ligation-induced liver injury and fibrosis were assessed by histopathology, fibrogenic gene expression, and measurement of cytokine and chemokine levels.Results
Depletion of Foxp3+ Treg cells enhanced Th17 cell response as demonstrated by the increase of IL-17+ cells and related gene expressions including Il17f, Il17ra, and Rorgt in the fibrotic livers of DEREG mice. Of note, infiltration of CD8+ T cells and Cd8 gene expression was significantly increased in the livers of DEREG mice. Consistent with increased IL-17+ and CD8+ T cell responses, DEREG mice generated higher levels of inflammatory cytokines (TNF-α, IL-6, and IL-12p70) and chemokines (MCP-1, MIP-1α, and RANTES). These results were concordant with severity of liver fibrosis and hepatic enzyme levels (ALT and ALP).Conclusions
The present findings demonstrate that Foxp3+ Treg cells inhibit the profibrogenic inflammatory milieu through suppression of pro-fibrogenic CD8+ and IL-17+ T cells.17.
Purpose
The purpose of this review was to examine the role of IL-1β in the inflammatory process central to the development of atherosclerosis and to discuss current clinical evidence for treatments targeting IL-1β in coronary artery disease.Recent Findings
IL-1β has been shown to modulate atherosclerotic plaque progression by upregulating the synthesis of adhesion molecules on endothelial cells, as well increasing activation and proliferation of vascular smooth muscle cells. Animal studies have further suggested that alterations in the balance between agonists and antagonists of IL-1β are important in promoting atherosclerosis. In humans, preliminary assessment of therapy targeting IL-1β noted early reductions in serum inflammatory biomarkers among those with systemic inflammatory or coronary artery disease. The CANTOS trial, a large randomized double-blind study found that canakinumab, a monoclonal antibody targeting IL-1β, reduced ischemic events in patients being treated for secondary prevention.Summary
Cellular, animal, and now clinical studies have suggested a role for therapies aimed at IL-1β for treatment of CAD. However, given potential side effects and costs of these medications, further study is required to determine which patients may be most suited for treatment above current standard of care.18.
Daniel Elieh Ali Komi Tohid Kazemi Anton Pieter Bussink 《Current allergy and asthma reports》2016,16(8):57
Purpose of Review
CHI3L1 (also known as YKL-40), a member of “mammalian chitinase-like proteins,” is a serum protein lacking enzymatic activity. Although the protein is highly conserved in mammals, a consensus regarding its role in human pathologies is currently lacking. In an attempt to shed light on the many physiological functions of the protein, specifically with regard to asthma, a comprehensive overview of recent studies is provided.Recent Findings
In asthma, CHI3L1 is secreted from macrophages and airway epithelial cells through an IL-13 related mechanism. Th2-associated inflammatory responses due to allergen exposure, resulting in airway hyper-responsiveness and smooth muscle contraction, play a role in tissue remodeling.Summary
The importance of CHI3L1 in initiation and development of asthma is not limited to its involvement in highly orchestrated events of inflammatory cytokines but further research is needed for further elucidation. Levels of the protein are associated with severity for numerous pathologies, including asthma, suggesting limited specificity as a biomarker.19.
Ana Margarida Pereira Cristina Jácome Rute Almeida João Almeida Fonseca 《Current allergy and asthma reports》2018,18(12):69
Purpose of Review
Evidence-based clinical diagnosis of allergic disorders is increasingly challenging. Clinical decision support systems implemented in mobile applications (apps) are being developed to assist clinicians in diagnostic decisions at the point of care. We reviewed apps for allergic diseases general diagnosis, diagnostic refinement and diagnostic personalisation. Apps designed for specific medical devices are not addressed.Recent Findings
Apps with potential usefulness in the initial diagnosis and diagnostic refinement of respiratory, food, skin and drug allergies are described. Apps to support diagnostic personalisation are not yet available. There is an urgent need to increase the scientific evidence on the real usefulness of these apps, as well as to develop new scientifically grounded apps designed and validated to support all allergic diseases and diagnostic levels.Summary
Apps have the potential to change the diagnosis of allergic diseases becoming part of the routine diagnostics toolset, but its usefulness needs to be established.20.