Didem Yazi

Efficacy of long-term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mite-allergic children with asthma

Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific‐allergen immunotherapy, the efficacy of long‐term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel‐group, controlled study. Children with asthma aged 4–16 yr, sensitive to house dust mite (HDM) were followed up for a run‐in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom‐medication scores and lung function tests every 3 months, as well as skin‐prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within‐group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM‐allergic children with asthma.

Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model

Background Chitin, a natural polysaccharide extracted from shrimp, is a potent T and B cell adjuvant when delivered in the form of chitin microparticles and can shift a polarized T‐helper type 2 (Th2) immune response towards a Th1 response.

Comparison of Der p1-specific antibody levels in children with allergic airway disease and healthy controls

Although children, with allergic airway disease, who are sensitized to house‐dust mite (HDM) are known to have increased levels of allergen‐specific IgE and IgG, the association between the quantity of those immunoglobulins and the clinical features of disease is not yet well established. The purpose of this study was (i) to evaluate Der p1‐specific IgA, IgG1, IgG4, and IgE levels of children with HDM‐allergic asthma and allergic rhinitis and to compare it with that of healthy controls (ii) to assess the association with disease duration. A total of 73 patients were included. Of those, 58 had asthma (M/F: 27/31, mean age 7.9 ± 2.7 yr) and 15 were diagnosed as allergic rhinitis (M/F: 8/7, mean age 10.1 ± 4.0 yr) without asthma. Twenty‐five (M/F: 13/12, mean age 9.5 ± 4.2 yr) non‐allergic children were included as healthy controls. Data on age at onset and duration of disease were recorded. Then, Der p1‐specific IgA, IgG1, IgG4, IgE levels were measured in all of the 98 subjects by ELISA. Comparison of Der p1‐specific antibody levels of patients and controls revealed that Der p1‐specific IgG1, IgG4 and IgE levels of patients with asthma (p = 0.012, p = 0.021, p = 0.004, respectively) were significantly higher than healthy controls. Also, the ratio of Der p1‐specific IgA/IgE was significantly lower in asthmatic children when compared with children with allergic rhinitis and controls (p = 0.029, p < 0.001, respectively). Der p1‐specific IgG1, IgG4, IgE and IgA levels of asthmatic children with duration of disease of ≥4 yr were significantly higher than those with disease duration of <4 yr. IgA/IgE ratio was not significantly different in those two groups of asthmatics. We concluded that although all of the specific antibody levels increased with longer duration of asthma, IgA/IgE ratio remains to be low in asthmatic children allergic to HDM.

Mycobacterium vaccae Immunization to OVA Sensitized Pregnant BALB/c Mice Suppressed Placental and Postnatal IL-5 and Inducing IFN-γ Secretion

Although the development of atopy in the newborn is determined by a multitude of factors, an intense Th1 stimulus early in life could be protective by facilitating a switch away from Th2. Aimed to determine the effect of single Mycobacterium vaccae (M. vaccae) immunization to OVA-sensitized pregnant mice on IL-5 and IFN-γ secretion from placental lymphocytes and splenocytes of offspring. Pregnant BALB/c mice were divided into 4 groups, OVA-sensitized + M. vaccae immunized, OVA-sensitized, M. vaccae immunized and controls. Sensitization with OVA was initiated before mating, and aerosol OVA challenge were performed during pregnancy. M. vaccae immunization was performed on the 12th day of pregnancy. IL-5 and IFN-γ levels of placental lymphocytes were analyzed on the 18th day of pregnancy and splenocytes of offspring on the 2nd and 28th days during postnatal period. A single administration of M. vaccae to OVA-sensitized pregnant mice downregulated IL-5 secretion and induced IFN-γ secretion from placental lymphocytes. On the other hand, after M. vaccae immunization downregulation of IL-5 levels and upregulation of IFN-γ secretion persisted in offspring when determined on 2nd and 28th days of life. Vaccination with M. Vaccae to OVA-sensitized pregnant BALB/c mice prevented Th2 immune responses by enhancing secretion of IFN-γ and lowering IL-5 levels during pregnancy and the effect persisted during the postnatal period in offspring.

Prevalence of immediate hypersensitivity reactions to cow's milk in infants based on skin prick test and questionnaire

OBJECTIVE Cows milk (CM) hypersensitivity is one of the most frequent hypersensitivities in infants. The objective of our study was to investigate the prevalence of immediate hypersensitivity to CM based on skin prick test results and to evaluate associated allergic conditions ascertained by questionnaire in infants living in Istanbul. METHODS All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on cows milk hypersensitivity and other allergic diseases was completed during this interview. A cows milk skin prick test (SPT) was applied to all infants. An open CM challenge test was then carried out on infants with a positive SPT to CM. RESULTS Among the 1015 infants who underwent SPT, six (0.59 %) demonstrated immediate hyper-sensitivity to the CM allergen and three (0.29 %) developed a positive response to the CM challenge test. The results of the questionnaire revealed that 112 (11.0 %) of the infants had family history of allergic diseases, 96 infants (9.5 %) had a positive history of recurrent wheezing, and 166 (16.4 %) had a history of skin rash resembling atopic dermatitis. CONCLUSIONS Our results suggest that CM hyper-sensitivity, with its low prevalence, might not be a serious health concern in Turkish infants.

Non‐atopic asthma in children is related to maternal bronchial hyperreactivity

Data on the pathogenic mechanisms underlying the development of non‐atopic asthma in children are scarce. Our aim was to evaluate the association and compare the atopic status, pulmonary functions, bronchial hyperresponsiveness and serum total immunoglobulin E (IgE) levels of parents of atopic and non‐atopic asthmatic children by using objective methods. Fifty‐one asthmatic children aged 4–16 yr and their parents were included into the study. Initially the American Thoracic Society’s Respiratory Disease questionnaire inquiring data on symptoms of asthma, rhinitis and past medical history was filled in. Afterwards, skin prick test with aeroallergens, pulmonary function and methacholine bronchial provocation tests and serum sampling for total IgE level determinations were carried out. Bronchial hyperresponsiveness to methacholine was significantly more common in the mothers of non‐atopic children compared to those of atopic ones, although no significant difference was observed in the skin prick test reactivity, pulmonary function test parameters and serum IgE levels. Questionnaire data revealed that the presence of asthmatic symptoms such as wheezing and phlegm and doctor‐diagnosed asthma were more common in the mothers of non‐atopic children. Meanwhile, asthmatic symptoms were also found to be significantly more common in fathers of non‐atopic children. Logistic regression analyses revealed that maternal PC20 was the only predictive factor for the risk of displaying non‐allergic asthma in children. The results demonstrate that among the risk factors studied, maternal bronchial hyperreactivity was associated with the development of asthma in non‐atopic children.

Prevalence of egg sensitization in Turkish infants based on skin prick test

AIM Egg allergy is one of the most frequent allergies in infants. The aim of this study was to determine the frequency of sensitization to egg in infants based on skin prick test results and to evaluate associated allergic conditions by questionnaire. METHODS All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on food allergy and other allergic diseases was completed during this interview. An egg skin prick test (whole egg) was applied to all infants. RESULTS Positive skin prick test results were recorded in 19 infants (1.87 %). There was no difference between the prick test-positive and -negative groups with respect to any of the demographic characteristics investigated (gender, age, birth weight, egg consumption, age of introduction of egg and other solids, breastfeeding). No significant association was demonstrated between sensitization to egg and family history of allergy. Moreover, there was no association between sensitization to egg and occurrence of atopic dermatitis, recurrent wheezing, gastrointestinal symptoms and doctor diagnosis of asthma. CONCLUSION The prevalence of egg sensitization based on skin prick test results has been found as 1.87 % among Turkish infants in Istanbul. However, no significant relationship was found between allergic sensitization to egg and occurrence of allergic diseases in this study population.

Long-term modulatory effect of Mycobacterium vaccae treatment on histopathologic changes in a murine model of asthma

BACKGROUND Mycobacteria are being investigated for modulation of inflammation in asthma and atopic disorders by eliciting particularly strong protective TH1 immune responses. OBJECTIVE To investigate the long-term effects of intratracheally administered Mycobacterium vaccae on an experimental murine model of asthma. METHODS BALB/c mice were placed in 4 groups: long-term M. vaccae, M. vaccae, asthma, and control groups. All groups but controls were sensitized intraperitoneally and challenged intratracheally with ovalbumin. The long-term M. vaccae and M. vaccae groups were treated with M. vaccae intratracheally simultaneously during challenges. Finally, mice in the long-term M. vaccae group were rechallenged with ovalbumin nebulization 24 days later. Evaluations of lung histopathologic findings and serum cytokine levels were performed. RESULTS Comparison of the long-term M. vaccae group with the asthma model group revealed that the number of hyperplasic goblet cells in small and large airways (small airway: P < .05; large airways: P < .01) and thickness of basement membrane in large airways were significantly less in the long-term M. vaccae group. Furthermore, numbers of hyperplasic goblet cells in small airways (P < .05) and basement membrane in the large airway (P < .05), as well as inflammation in small airways (P < .01), were significantly less in the M. vaccae group when compared with the asthma model group. Interferon-gamma secretion from splenocytes of the M. vaccae group was significantly higher than the asthma model and long-term M. vaccae groups. CONCLUSION Intratracheal administration of M. vaccae exerted a long-lasting ameliorating effect on airway histopathologic features of a murine asthma model.

Treatment with Mycobacterium vaccae ameliorates airway histopathology in a murine model of asthma

The objective of this study was to evaluate the effect of intratracheal (i.t.) or subcutaneous (s.c.) Mycobacterium vaccae treatment on lung histopathology and cytokine responses in a murine model of asthma. BALB/c mice were divided into four groups. To establish an asthma model, Groups I, II and III received intraperitoneal (i.p.) ovalbumin (OVA) and were challenged with i.t. OVA three times (days 41-47). On the same days, mice in Groups I and II were treated with i.t. and s.c. Mycobacterium vaccae, respectively. Mice in Group IV served as controls. On day 49, lungs were taken out for histopathological evaluation. Cytokine levels were determined in splenocyte culture supernatants by ELISA. The thickness of basement membrane and hyperplasic goblet cells in small airways were found to be significantly more in Group III than Group I. Furthermore, smooth muscle and epithelial thickness in small and large airways and hyperplasic goblet cell numbers in all sized airways of this treatment group were not significantly different from controls. Epithelial thickness in medium and large airways, hyperplasic goblet cells in all sized airways, and basement membrane in small and large airways were not significantly different in Group II when compared to controls. OVA-stimulated IL-5 levels was significantly higher in Group I when compared to Group III. OVA-stimulated IL-5 and spontaneous IL-5 levels were significantly higher in Group II than Group III. We demonstrate that subcutaneous and intratracheal Mycobacterium vaccae administered along with allergen has an ameliorating effect in the modulation of airway histopathological changes in OVA sensitized mice.