Nazan Cobanoglu

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.

Subcutaneous versus sublingual immunotherapy for allergic rhinitis and/or asthma.

Subcutaneous allergen-specific immunotherapy has long been used in allergic rhinitis and/or asthma and has been recognized to be efficacious. However, owing to the inconvenience of injection and the risk of serious side effects, alternative concepts inspiring the search for effective noninjective routes, namely sublingual administration of allergens, have emerged. Sublingual immunotherapy (SLIT) appears to be associated with a lower incidence of systemic reactions. The clinical efficacy of subcutaneous immunotherapy (SCIT) is well established for both rhinitis and asthma. Meta-analyses relating to its efficacy on asthma and rhinitis are available. SLIT has also been validated in this respect. Comparative clinical studies of SLIT versus SCIT are scarce demonstrating both routes to be clinically efficient. Knowledge of the exact mechanism of action of SLIT has been increasing in the last decade. In addition, recent studies have proved similarities of the immunological changes with the treatment of both routes. Further comparative clinical and immunological studies of SLIT versus SCIT are needed to confirm the long-term efficacy and to complete the knowledge of immunological mechanisms of both routes. Moreover, better understanding of the interaction of allergen and oral mucosal dendritic cells during SLIT may allow improved targeting of SLIT vaccines.

Relation of bone mineral density with clinical and laboratory parameters in pre‐pubertal children with cystic fibrosis

To study bone mineral density (BMD) of pre‐pubertal cystic fibrosis (CF) children, and its relation with clinical and laboratory parameters, we enrolled 16 CF (8 girls) (4–8 years), and 16 control children (8 girls) (4–8 years). After anthropometric measurements, BMD, serum calcium, phosphorus, total alkaline phosphatase (ALP), 25‐hydroxy vitamin D (25‐OHD), parathyroid hormone, osteocalcin, tumor necrosis factor (TNF)‐α, soluble TNF‐α receptor 2 (sTNFR2), and soluble IL‐2 receptor (sIL‐2R) levels, and urinary calcium and hydroxyproline excretions were assessed. Disease severity of CF patients was determined with Shwachman–Kulczycki clinical and Brasfield radiological scoring systems.

An epidemic of pseudo-Bartter syndrome in cystic fibrosis patients

A total of 57 episodes of PBS were found in 43 CF patients between January 1989 and November 2005 in our center [4, 6]; of these, nine occurred between August 15 and August 31, 2006. The demographic features and laboratory characteristics of these nine CF-PBS patients are given in Table 1. All patients, with the exception of patient no. 8, who was newly diagnosed, had been admitted prior to these dates with PBS. Eight patients were using oral salts, as recommended. A 23-month-old-boy died 6 h after admission despite intensive therapy. While between 1975–2005 the mean air temperature in August in the Ankara region was 22.9°C (range: 7.2– 37.2°C), in August 2006, it was 27.2°C (range: 14.6°C– 38°C). August 2006 was the hottest August since 1975 (http://www.meteor.gov.tr).

TAP1 and TAP2 gene polymorphisms in childhood cystic echinococcosis.

The incidence of cystic echinococcosis (CE) due to Echinococcus granulosus is as high as 2000-2500 patients per year in Turkey. Whether genetic characteristics of the Turkish population cause a tendency to the disease is currently unknown. We aimed at studying the role of TAP gene polymorphisms in Turkish children with cystic echinococcosis. For an overview of allelic distribution of TAP1 and TAP2 genes, genotypes of 85 patients with CE and 100 controls were studied. To determine the genotype-phenotype correlation, 81 of the patients whose clinical data were available were analyzed. For TAP1-637, Asp/Gly heterozygosity was significantly more prevalent in CE patients than in controls (20 vs. 4%, odds ratio 6.0), while Gly/Gly homozygosity was less frequent (5 vs. 14%). For TAP2-379, Ile/Val heterozygosity was significantly more prevalent in CE patients than in controls (14 vs. 1%, odds ratio 16.27), while Ile/Ile homozygosity was less frequent (13 vs. 25%). TAP1-637 and TAP2-379 polymorphisms may have a role in causing genetic tendency for CE in children. The data may reflect the genetic properties of the Turkish population or may reveal the minor role of TAP gene polymorphisms in CE.

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.

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.

A 4-month-old boy with acrodermatitis enteropathica-like symptoms

A 4-month-old boy was admitted for having diffuse eruption in the perianal region, legs, trunk hands, and face with failure to thrive, edema, hypoalbuminemia, and anemia. The patient was thought to have acrodermatitis enteropathica-like eruption due to malabsorption. The eruption completely resolved with enzyme supplement and proper nutrition and skin care.

Does Defective Apoptosis Play A Role in Cystic Fibrosis Lung Disease

BACKGROUND AND AIMS Although apoptotic dysfunction has recently been suggested in cystic fibrosis (CF), there are few studies reported concerning apoptosis in CF with controversial results. The aim of this study was to investigate apoptosis in CF human lung tissues and compare with non-CF bronchiectatic and normal healthy lung tissues. We also investigated the relation between apoptosis and histopathological features of tissues and microbiological factors influencing apoptosis. METHODS Lung tissue samples from CF (n=30), non-CF bronchiectasis (n=28, BE group) and normal control cases (n=24, C group) were included in the study. Histological examination of H & E-stained archived slides was performed and TUNEL method was used to detect DNA fragmentation. RESULTS Apoptotic alveolar epithelial cells were significantly increased in the CF group compared to BE and C groups (p=0.046). Bronchopneumonia (BP) was present in 15 CF cases (50%), whereas none of the cases in C group had BP (p=0.0001). Apoptosis was significantly increased in cases with BP (n=17) compared to cases without BP (n=65) (p=0.04). CONCLUSIONS Apoptotic epithelial cells and BP were significantly increased in the CF group and excess level of apoptosis may be the result of enhanced occurrence of BP. Apoptotic cells were alveolar epithelial cells in the great majority of the patients and were not detected in other locations where CFTR expression is much more prominent than alveolar cells. We may postulate that increased apoptotic findings in the alveolar epithelium were related with the presence of chronic infections rather than CFTR dysfunction.

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.