Allergy in severe asthma

It is well recognized that atopic sensitisation is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term "Severe Asthma" encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming "uncontrolled", or whose disease remains "uncontrolled" despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The "Allergy and Asthma Severity" EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma. This article is protected by copyright. All rights reserved

Research needs in allergy: an EAACI position paper, in collaboration with EFA

Abstract In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21 st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein

The role of SPINK5 in asthma related physiological events in the airway epithelium

SummaryBackgroundGenetic studies have shown that variants in SPINK5 may be associated with atopic diseases and asthma. However, the functional role of SPINK5 protein in asthma has not been elucidated.ObjectivesTo determine the effects of SPINK5 on asthma related physiological events such as apoptosis, mucus and cytokine production by epithelial cells.MethodsA549 cells were transfected with SPINK5 expression vector and stimulated with increasing doses of hydrogen peroxide and neutrophil elastase (NE) for measurement of cell viability or apoptosis and analysis of mucus production. Cell viability was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide) assay and apoptosis by Annexin V/PI staining. Levels of IL-4, IL-6, IL-8, IL-12, IL-13, IFNγ, IL-1β and RANTES were determined by ELISA in cell culture supernatants. Mucus production was determined by RT-PCR of the MUC5AC gene and PAS staining in NE treated cells.ResultsEpithelial cells transfected with SPINK5 expression vector produced more IL-6, IL-8 and RANTES compared to non-transfected cells (p < 0.001, p = 0.003, p < 0.001, respectively). Even though cells transfected with SPINK5 vector displayed significantly higher cell death, we have not observed any clear effect of SPINK5 on apoptosis. PAS staining showed that SPINK5 slightly decreased the mucin production induced by neutrophil elastase in A549 cells. However, SPINK5 had no effect on MUC5AC transcription.ConclusionSPINK5 is an important molecule in asthma. Its role extends beyond its well known protease inhibitor properties

Co-existing bipolar disease and 17q12 deletion: a rare case report

Background 17q12 microdeletion syndrome is a rare autosomal dominant chromosomal anomaly, caused by the deletion of a 1.4 Mb-spanning DNA sequence on the long arm of chromosome 17. Herein, we report the first bipolar disease (BPD) case with a 1.6-Mb deletion in the 17q11.2-17q12 chromosome region. Materials and methods Physical examination of the case was performed. Karyotype and microarray analyses were performed for the case and the parents. Results Physical examination revealed mild dysmorphic features such as high and forehead, full cheeks, slightly depressed nasal bridge and arched eyebrow. Chromosomal analysis of the patient revealed 46, XX, del(17)(q12) karyotype, and parents' karyotype were normal. In the microarray analysis of patient, 1.6 megabases deletion was detected in the 17q12 region [arr(hg19) 17q12 (34,611,352-36,248,918) x1]. The microarray analysis of the mother was normal. The father's microarray showed 473 kilobases duplication in the 11p11.12 region. Conclusion Although 17q12 deletion syndrome has been associated with bipolar disorder, very few such cases have been described in the literature. Genetic counseling should be considered in patients with remarkable phenotype, complex symptomatology, neurodevelopmental disorder and additional conspicuous medical conditions

Investigation of the Effects of Sevoflurane and Desflurane on Erythrocyte Deformability in Transient Hyperglycemia

Aim: Micro and macrovascular complications due to long-term hyperglycemia are associated with increased mortality and morbidity. Erythrocytes exposed to hyperglycemia for a long time may cause morphological changes in erythrocytes such as decreased deformability and development of aggregation. As a result, complications such as shortening life span of erythrocytes, impairment of oxygen carrying capacity, tissue hypoxia may occur. In our study, we would like to investigate the effects of Sevoflurane and Desflurane on erythrocyte deformability during transient hyperglycemia. Materials and Methods: In this study, 30 male Wistar albino rats were used. The animals were randomly divided into five groups, each contained 6 rats: Diabetic control (group DC), diabetic hyperglycemia group (group DH), diabetic hyperglycemia group with desflurane (group DH-D), and diabetic hyperglycemia group with sevoflurane (group DH-S) groups. Another 6 rats without diabetes were assigned as control group (group C). Streptozotocin-induced diabetic rats were kept 6 weeks, then transient hyperglycemia was created, and the administration of sevoflurane and desflurane were performed. After 24 hours blood samples were obtained and deformability measurements were performed in erythrocyte suspensions containing Htc 5% in a PBS buffer. Results: Diabetes mellitus was found to increase relative resistance in the control group (p < 0.0001). Acute hyperglycemia increased relative resistance in diabetes control, relatively. Group DH, Group DH-D and Group DH-S deformability index were significantly different when compared to Group DC (p=0.007, p=0.025, p=0.016, respectively). It was found that administration of desflurane or sevoflurane did not alter erythrocyte deformability during acute hyperglycemia (p = 0.591, p = 0.739). Conclusion: As a consequence, we think that we can safely use inhalation anesthetics such as Desflurane and Sevoflurane during acute hyperglycemia attacks. But, it needs further investigation as both experimental and clinica

Impact of Rhinitis on Work Productivity: A Systematic Review

Allergic rhinitis (AR) is increasingly acknowledged as having a substantial socioeconomic impact associated with impaired work productivity, although available information remains fragmented.status: accepte

Unanswered questions on the use of biologics in pediatric asthma

The emergence of biologic therapies for the management of asthma has been a revolutionary change in our capacity to manage this disease.Since the launch of omalizumab, several other biologics have been marketed or are close to being marketed, suggesting that a plethora of monoclonal antibodies can be expected in the coming years. This will facilitate the transition to the paradigm of personalized medicine, but on the other hand will decisively further complicate the choice of the most appropriate treatment, in the absence of reliable enough biological markers.For these reasons, along with the relatively short time of use with these treatments, there are recurrently arising questions for which there are not even moderately documented answers, and for which the only solution must be based, with all reservations, on the combination of indirect evidence and expertise. In this paper, we attempt to address such questions, providing relevant commentaries and considering the whole width of the evidence base