Nilufer Galip

Multiallergen-specific immunotherapy in polysensitized patients: where are we?

Allergen-specific immunotherapy administered by the subcutaneous route was introduced a century ago and has been shown to be effective in the management of allergic rhinitis and asthma. More recently, the sublingual administration of allergen extracts has become popular, especially in European countries, and has also demonstrated efficacy in respiratory allergic diseases. Both modes of allergen administration during immunotherapy have been shown not only to reduce symptoms and the need for medication, but also to prevent the development of additional sensitivities in monosensitized patients, as well as asthma development in patients with allergic rhinitis, with a long-lasting effect after the completion of several years of treatment. Almost all of the well-designed and double-blinded, placebo-controlled studies evaluated treatment with single-allergen extracts. Therefore, most meta-analyses published to date evaluated immunotherapy with single allergen or extracts containing several cross-reactive allergens. As a result, in general, multiallergen immunotherapy in polysensitized patients (mixture of noncross-reactive allergens) is not recommended owing to lack of evidence. Although some guidelines have recommended against the use of multiallergen mixtures, allergists commonly use mixtures to which the patient is sensitive with the rationale that effective immunotherapy should include all major sensitivities. Literature on this subject is scarce in spite of the widespread use worldwide. Here, this issue will be extensively discussed based on currently available literature and future perspectives will also be explored.

A milestone in house dust-mite-allergen immunotherapy: the new sublingual tablet S-524101 (actair)

Subcutaneous allergen-specific immunotherapy has long been used in the treatment of allergic rhinitis and/or asthma and its efficacy has been confirmed. However, due to the discomfort of injections and the risk of severe adverse reactions, alternative routes of allergen administration have emerged. Delivery of allergens through the mucosal route had been proposed and investigated thoroughly, confirming the sublingual route to be the most efficacious. Later, the efficacy and safety of this route have been documented by numerous controlled trials both for house dust mite (HDM) and pollens. Recently, sublingual orodispersable grass pollen allergen tablets were in use followed by the newly developed HDM allergen tablets with satisfactory clinical results: Moreover, very recently 1 year of HDM tablet treatment was demonstrated to exert its clinical efficacy 1 year after discontinuation of tablet IT. The persistence of efficacy after only 1 year of treatment is a new and promising era. Currently, Sublingual Immunotherapy is the most easily administered and safe treatment option until more immunogenic, less allergenic and more efficient allergen extracts are developed.

Comparing subcutaneous and sublingual ımmunotherapy: what do we know?

Purpose of reviewAlthough allergen-specific sublingual (SLIT) and subcutaneous immunotherapy (SCIT) have been demonstrated to be clinically effective with similar immunological responses, head-to-head studies comparing those two modes of allergen administration in terms of onset of clinical improvement along with simultaneous immunological responses and underlying mechanisms of preventive effect are scarce. The present review will update current data on this issue. Recent findingsCompared with SLIT, SCIT provides a rapid onset of clinical improvement by eliciting a simultaneous surge in production of T helper 1 (Th1) and T regulatory cell (Treg) cytokines and blocking antibodies. Similar immunological and clinical responses are evoked quite later, with no effect on Immunoglobulin G (IgG)4 levels during SLIT. Increases in TGF&bgr; secretion due to nonrelevant allergens during SLIT may explain the preventive effect on new sensitizations. SummarySLIT and SCIT are both clinically effective in the treatment of respiratory allergic diseases with slight differences in the early phase in terms of onset of clinical efficacy and simultaneous immunological responses. Both SLIT and SCIT induce similar T-cell responses in time, but specific IgG4-blocking antibody responses are more prevalent following SCIT. Further head-to-head studies addressing the preventive effect of monotherapy and the efficacy and immunological responses of nonrelated multiallergen immunotherapy in polysensitized patients are warranted.

Is calprotectin a marker of tobacco smoke related inflammation?: a pilot study in children

Context: Environmental tobacco smoke (ETS) related inflammation has an anorexigenic effect through affecting the release of appetite-modulating mediators, leptin and ghrelin. Elevated serum calprotectin levels are found in a variety of inflammatory conditions. Objective: To study the relation between ETS and body mass index (BMI), as well as serum levels of leptin, ghrelin and calprotectin. Materials and methods: A cross-sectional study was performed by searching the smoking status of parents. After filling in the questionnaires, parents were phoned and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to calculate their BMIs. Participant children were divided into Group 1 (n = 51), those who are not exposed to and Group 2 (n = 46), exposed to indoor ETS. Results: There were no statistical difference in BMI, leptin and ghrelin levels between Group 1 and Group 2 (p values are 0.85, 0.87 and 0.42, respectively), but serum calprotectin levels were statistically higher in Group 2 (p = 0.003). Discussion and conclusion: In this study serum levels of calprotectin were found to be higher in children with indoor ETS exposure where no relation was detected with BMI and serum levels of leptin and ghrelin. Increased serum levels of calprotectin might be an indicator of inflammation related to ETS exposure.

Rare adverse events due to house dust mite sublingual immunotherapy in pediatric practice: two case reports

Sublingual route, a noninjective way of allergen administration appears to be associated with a lower incidence of severe systemic reactions compared with the subcutaneous route. Local adverse reactions are reported which resolve spontaneously within a few days without need for discontinuation of treatment. Hereby, we report two pediatric cases, one with persistent asthma and the other one with persistent allergic rhinitis. Both were treated by house dust mite sublingual immunotherapy, one of whom developed severe wheezing (grade 2 systemic reaction based on World Allergy Organization subcutaneous systemic reaction grading system) and the other intractable vomiting (grade 3 local reaction based on World Allergy Organization sublingual immunotherapy local adverse events grading system) at the end of the build-up phase which repeated on re-administration of the same dose. Both of those two cases completed their 3-year immunotherapy successfully by patient-based adjustment of the highest tolerated dose of the maintenance.

Leptin, ghrelin and calprotectin: inflammatory markers in childhood asthma?

BackgroundAppetite-modulating hormones ghrelin and leptin might be relevant to asthma with their pro-inflammatory effects, and calprotectin has been recognized as a promising marker of inflammation. The purpose of this study was to explore whether asthma, atopy and lung functions has a relation with serum levels of leptin, ghrelin and calprotectin as inflammatory markers in children.MethodsA cross-sectional study was performed by searching the doctor diagnosed asthma through questionnaires filled in by parents who were phoned, and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to perform skin prick test and spirometry. Participants were divided into Group 1, children with previous diagnosis of asthma, and Group 2, children without previous diagnosis of asthma.ResultsOne thousand and two hundred questionnaires were distributed and 589 of them were returned filled in. Out of 74 children whose parents accepted to participate in the study, 23 were in Group 1 and 51 were in Group 2. There was no statistical difference in serum levels of leptin, ghrelin, calprotectin, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) , forced expiratory flow between 25 and 75% of vital capacity (FEF25-75) values , and skin prick test results between the two groups (p values are 0.39, 0.72, 0.5, 0.17, 0.5, 0.27, 0.18, and 0.81 respectively).ConclusionIn this study the inflammation in asthmatic children could not be shown by using serum leptin, ghrelin and calprotectin levels and this is possibly due to the low number of children with ever asthma and equal skin prick test positivity in both groups. This study is the first study aimed to show the relation between serum calprotectin levels and inflammation in asthma. As this study was a cross-sectional study, further prospectively designed randomized controlled studies are necessary to show the association of these markers and inflammation in asthma.

High prevalence of allergy in North Cypriot children.

Abstract Background: The ISAAC (the International Study of Asthma and Allergies in Childhood) questionnaire has been used to standardize research on the prevalence of asthma in children since 1991. Aim: In this Phase I study, the prevalence of asthma, other allergic diseases and atopy was evaluated in North Cyprus. Methods: The ISAAC questionnaire was distributed to grades I–V schoolchildren. Data were obtained from parents of 580 schoolchildren aged between 7 and 12 years attending a primary school in Nicosia, the capital of North Cyprus. Of those, a sub-group of 97 (16·7%) randomly selected children were evaluated by skin prick test (SPT) and lung function test (LFT). Results: The prevalence rates of asthma ever, current wheezing and SPT-positivity were 20·8%, 10% and 68%, respectively. The prevalence of atopy was significantly higher in the randomly selected subgroup of 97 (68%) patients subjected to SPT and LFT, and the house dust mite (HDM) was the allergen to which children were most frequently sensitized. Conclusions: In northern Cyprus, the prevalence rates of asthma, allergic diseases and atopic sensitization in 7–12-year-old children are extremely high. Sensitization to HDM is a risk factor for the development of asthma.

Rosai–Dorfman disease presenting as mediastinal lymphadenopathy: case report and review of the literature

Abstract A 6-year-old boy presented with recurrent pneumonia and diarrhoea for 3 years. He had extensive mediastinal lymphadenopathy and atelectasis with low serum levels of IgA, IgG and IgG3. An inguinal lymph node biopsy demonstrated histological and histochemical features of Rosai–Dorfman disease. There was emperipolesis and histiocytes were immune-positive for S100 proteins. He responded to corticosteroids and regular infusions of immunoglobulins.

Prevalence of Mediterranean FeVer Gene Mutations in Turkish Cypriot Population

Objectives This study aims to determine the carrier frequency and the most common mutations of the Mediterranean FeVer (MEFV) gene in healthy Cypriot population of Turkish origin. Patients and methods A total of 296 healthy participants (102 males, 194 females; median age 30 years; range 1 to 81 years) were evaluated. The exon 2, 3, 5 and 10 of MEFV genes were amplified by polymerase chain reaction. Results The participants demonstrated an extremely high carrier rate (12.5%). Most commonly detected mutations were E148Q and A74S, with rates of 7.3% and 2.8%, respectively. Conclusion Mediterranean FeVer gene mutation types and carrier rates in Turkish Cypriot population are different than other Mediterranean populations in the region. MEFV mutation carriage is frequent in North Cyprus and familial Mediterranean fever might be one of the causes for end stage renal disease in Turkish Cypriots.

PO-0672 Cord Blood Osteocalcine, Leptin And Tnf? Levels In Gestational Diabetic Pregnancies

Aim To compare cord blood osteocalcin, leptin and TNF α levels in gestational diabetic and normal pregnancies. Method 191 deliveries were included in this research. 41 (21.5%) of pregnancies were gestational diabetic and 159 (78.5%) of pregnancies were normal. Cord blood osteocalcin, leptin and TNF α levels were compared. Results There was no significant difference among birth weights (p:0.409), heights (p:0.07), head circumferences (p 0.201), gender (p:0.4), gestational weeks (p:0.201), ponderal index (0.564) between groups. There was no significant difference between groups regarding pregnancy complications. However, hypothyroidism was more common in gestational diabetic group (p:< 0.001). In addition, hypoglycemia was more common in gestational diabetic group (p:0.047). Gestational diabetic group’s cord blood osteocalcin levels were higher than in non diabetic group (p:0.037). Cord blood TNF α (p:0.813) and leptin average levels (p: 0,212) were not statistically different. Osteocalcin, leptin and TNF α levels were not statistically different between boys and girls. Discussion Osteocalcin; originating from bones, increases insulin sensitivity in peripheral organs and insulin secretion. Leptin is known to inhibit insulin and osteocalcin secretion. Osteocalcin level increase in gestational diabetic group, may be related to osteocalcin regulation of blood glucose levels. Cord blood leptin and TNF α levels showed no significant difference between groups, probably due to proper regulation of cord blood glucose levels during gestation.