Allergic Rhinitis and House Dust Mite Sensitization Determine Persistence of Asthma in Children.

OBJECTIVE: To specify clinical and immunological parameters of the mechanisms, which may lead to development of persistent asthma, or regression of the disease symptoms. METHODS: Eighty children with childhood asthma, diagnosed in the past by using the modified Asthma Predicted Index (mAPI), were divided into two groups: remission group and persistent group. There were 3 study visits (baseline, at 6 mo, and at 12 mo). Clinical remission of asthma was defined as the absence of asthma symptoms for at least 12 mo without treatment. The patients could switch from one group to another during the 12 mo of follow-up. Clinical, inflammatory, and immunoregulatory predictors of asthma remission/persistence were analyzed. RESULTS: The presence of mAPI criteria as well as house dust mite (HDM) allergy and allergic rhinitis at 7-10 y, were associated with a reduced prevalence of asthma remission. The increased eosinophil blood count in mAPI criteria was associated with a lower expression of CD25 positive cells. HDM allergy was associated with a higher fractional exhaled nitric oxide (FeNO) level (p = 0.0061) and higher expression of CD25CD71 (p = 0.0232). Allergic rhinitis was associated with a higher expression of PPAR (p = 0.0493) and CD25CD71 (p = 0.0198), and lower expression of glycoprotein A repetitions predominant (GARP). CONCLUSIONS: Persistence of childhood asthma was largely determined by the presence of allergic rhinitis and sensitization to HDM. Additionally, API criteria but not immunoregulation processes, were related to asthma persistence.

Effectiveness of ongoing face-to-face anti-tobacco intervention in children with asthma.

Background: Interventions to help parents quit smoking may yield important benefits for children with asthma. Children's exposure to environmental tobacco smoke can be measured by reporting of an adult in the household and testing the child's biomarker, e.g., cotinine. Objective: The aim of the study was to assess the effectiveness of "face-to-face" intervention carried out since 2016 in families with children diagnosed with asthma 3 years after beginning the anti-tobacco intervention. Methods: This study was a follow-up to an interventional study that assessed the effectiveness of direct patient education versus educational leaflets alone about parental tobacco smoking. The patients with asthma (ages 4-17 years) enrolled in our original intervention study conducted in 2016 were under the care of the allergy outpatient clinic. The active group was individually educated about the harmful effects of environmental tobacco smoke on their children. The control group included patients and parents, among whom only leaflets were distributed. After 3 years of ongoing intervention, in patients from both groups, exposure to tobacco smoking was evaluated with a questionnaire addressed to parents and/or caregivers and measurement of cotinine in children's urine. The forced expiratory volume in the first second of expiration and fractional exhaled nitric oxide levels were measured. Results: Seventy participants completed the study: 37 in the active group and 33 in the control group. In the active group, 27% of the parents quit smoking entirely compared with 9.4% of parents in the control group. In the group of active intervention, a significant decrease in the cotinine level (p < 0 .001) and the number of cigarettes smoked daily were observed (p < 0.001) 3 years after the active intervention compared with values right after the intervention. In the control group, there were no significant changes in the above-mentioned parameters. Conclusion: "Face-to-face" intervention among families with smokers were effective and lowered cotinine levels in children with asthma and the number of cigarettes smoked assessed 3 years after the intervention.

IL-33 is associated with allergy in children sensitized to the cat

BACKGROUND: Several studies suggest that early-life exposure to animal allergens constitutes a relevant risk factor for the development of allergic sensitization. OBJECTIVES: The aim of the present study was to determine the role of interleukin-33 in children sensitive to cat allergen with allergic rhinitis and/or asthma. METHODS: The study included 51 children aged 5-18 years, both sexes, allergic to cats. Sensitization to cat allergen was confirmed by skin prick tests or specific IgE. Children were evaluated for the presence of bronchial asthma, atopic dermatitis, allergic rhinitis. A questionnaire evaluating the occurrence of allergic symptoms in children after contact with the cat and dog was performed. Mothers completed a questionnaire regarding cat exposure: during pregnancy and having a cat at home. A blood sample was taken from all children to measure the level of IL-33 in the serum. RESULTS: Keeping a cat in the home, once in the past, or having a cat in the home during the mother's pregnancy, revealed a statistically significant relationship with IL-33 levels in the studied patients. Also, daily contact with a cat during pregnancy affected the level of IL-33. Higher levels of IL-33 were shown in people with hypersensitivity to cat and pollen allergens and cat and other animals. In patients with bronchial asthma higher levels of IL-33 were found than in patients without bronchial asthma. CONCLUSIONS: Increased serum levels of IL-33 is related with keeping cats during pregnancy and in early childhood and can be associated with the development of asthma in children

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IL-33 is associated with allergy in children sensitized to the cat.

BACKGROUND: Several studies suggest that early-life exposure to animal allergens constitutes a relevant risk factor for the development of allergic sensitization. OBJECTIVES: The aim of the present study was to determine the role of interleukin-33 in children sensitive to cat allergen with allergic rhinitis and/or asthma. METHODS: The study included 51 children aged 5-18 years, both sexes, allergic to cats. Sensitization to cat allergen was confirmed by skin prick tests or specific IgE. Children were evaluated for the presence of bronchial asthma, atopic dermatitis, allergic rhinitis. A questionnaire evaluating the occurrence of allergic symptoms in children after contact with the cat and dog was performed. Mothers completed a questionnaire regarding cat exposure: during pregnancy and having a cat at home. A blood sample was taken from all children to measure the level of IL-33 in the serum. RESULTS: Keeping a cat in the home, once in the past, or having a cat in the home during the mother's pregnancy, revealed a statistically significant relationship with IL-33 levels in the studied patients. Also, daily contact with a cat during pregnancy affected the level of IL-33. Higher levels of IL-33 were shown in people with hypersensitivity to cat and pollen allergens and cat and other animals. In patients with bronchial asthma higher levels of IL-33 were found than in patients without bronchial asthma. CONCLUSIONS: Increased serum levels of IL-33 is related with keeping cats during pregnancy and in early childhood and can be associated with the development of asthma in children.

Early life environmental exposure in relation to new onset and remission of allergic diseases in school children: Polish Mother and Child Cohort Study.

Background: This study was based on data from the Polish Mother and Child Cohort Study. Objective: The aim was to study associations between home environment factors and allergic diseases at 1 year of life and new onset and remission of children's allergy diagnosis at ages 7-9 years. Methods: Children's health status was assessed at ∼12 months of age and then at ages between 7-9 years by using a questionnaire administered to the mothers. Children were assessed by pediatrician/allergists. The patients, who were 7-9 years old, underwent skin-prick tests. Exposure to tobacco smoke was evaluated with a questionnaire addressed to parents and/or caregivers and cotinine measurements were taken of mother's saliva during pregnancy and in children's urine at ages 7-9 years. Incidence and remission were calculated by comparing symptoms in the first year of life with symptoms at 7-9 years. We studied the associations among demographic data, home environment, and new onset and remission of food allergy, atopic dermatitis, and asthma and allergic rhinitis in logistic regression analysis. All associations were adjusted for independent risk factors of dependent variables. Results: Data from 211 participants were included in the analysis. During the first year of life, food allergy was the most common symptom (39%), followed by atopic dermatitis (35%) and asthma (12%). When comparing diagnoses at ages 7-9 years with the first year of life, food allergy had decreased by as much as 18.6%, atopic dermatitis decreased by as much as 23.8%, and asthma decreased by as much as 8%, whereas asthma and allergic rhinitis had increased from 6% to 14.8%. More frequent house cleaning negatively correlated with the new onset of atopic dermatitis and of asthma and allergic rhinitis. Hypersensitivity to seasonal allergens and mites and to any other allergen positively correlated with new onset of food allergy, atopic dermatitis, and asthma and allergic rhinitis. Parental atopy positively correlated with the new onset of asthma and negatively correlated with asthma remission. Conclusion: Analysis of our findings indicated that new onset and/or remission of allergic diseases was linked with hypersensitivity to house-dust mites in children who were polysensitized and with parental atopy. In addition, children who had food allergy, allergic rhinitis, or atopic dermatitis at the age of 1 year had more of a chance developing other atopic disease (except asthma) at ages 7-9 years and less of a chance of having a remission of the disease.

Vitamin D inhibits pro-inflammatory cytokines in the airways of cystic fibrosis patients infected by Pseudomonas aeruginosa- pilot study.

BACKGROUND: Vitamin D plays an important role in inflammatory responses after antigen exposure. Interleukin-23 (Il-23) promotes Il-17-dependent inflammation during Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection. We aimed to compare the ability of calcitriol and cholecalciferol to modulate the inflammatory response of the CF airways infected with P. aeruginosa. METHODS: This was a randomized, placebo-controlled, double-blind, cross-over trial. Twenty-three patients with CF (aged 6-19), chronically infected by P. aeruginosa were randomly assigned to: calcitriol group receiving 1,25(OH)2D 0,5 mcg daily or cholecalciferol group receiving cholecalciferol 1000 IU daily for three months. The levels of Il-23 and Il-17A in the exhaled breath concentrate (EBC) were measured. Calcium-phosphorus balance was also evaluated (serum concentration of calcium, phosphorus, 25OHD, parathormone (PTH) and calcium/creatinine ratio in urine). Data were analyzed using means of Stata/Special Edition, release 14.2. A level of P < 0.05 was considered statistically significant. RESULTS: The level of Il-17A in EBC significantly decreased in calcitriol group from 0,475 pg/mL (± SD 0,515 pg/mL) to 0,384 pg/mL (± SD 0,429 pg/mL) (p = 0,008); there was no change in cholecalciferol group (p = 0,074). The level of Il-23 in EBC did not significantly change in calcitriol group (p = 0,086); there was significant decrease in cholecalciferol group from 8,90 pg/mL (± SD 4,07 pg/mL) to 7,33 pg/mL (± SD 3,88 pg/mL) (p = 0,001). In calcitriol group serum phosphorus and PTH significantly decreased (p = 0,021 and p = 0,019 respectively), the concentration of calcium significantly increased (p = 0,001); there were no changes in cholecalciferol group. CONCLUSIONS: Both analogs of vitamin D revealed their anti-inflammatory effect and reduced the level of Il-17A and Il-23 in the airway of CF patients with chronic P. aeruginosa infection. We observed improvement in calcium-phosphorus metabolism after supplementation with calcitriol, without adverse effects. It is recommended to use vitamin D in CF patients.

The effect of passive smoking on exhaled nitric oxide in asthmatic children.

To date, some studies suggest that passive smoking (PS) may be an important determinant of FeNO levels in children but sill there is a need of investigations using objective methods of PS exposure. The aim of our study was to examine the effect of PS, measured by urine cotinine levels, on FeNO and lung function (FEV1) in allergic and non-allergic asthmatic children. METHODS: It was a prospective, non-interventional study. 140 children, aged 4-17, newly diagnosed with asthma were recruited into two study groups (exposed group, unexposed group), according to smoking exposure/unexposure based on the questionnaire. There was one study visit. Subjects underwent a medical history (including history of atopy), physical examination, spirometry, FeNO and urinary cotinine measurement. RESULTS: 70 individuals had been exposed to tobacco smoke. The patients exposed to tobacco smoke were characterized by statistically significantly higher urine concentration of cotinine, 10,80 ng/mL, than their counterparts who had not been exposed to tobacco smoke, 1,56 ng/mL (P = 0,019). In the group of individuals unexposed to tobacco smoke the mean value of FeNO was 34,99 ppb, while in the group of patient who had been exposed to tobacco smoke, the corresponding mean value was significantly lower, it amounted to 22,41 ppb (P = 0,001) (Table 1). As regards to FEV1 measurements, there were not any statistically significant differences by study groups unexposed/exposed to tobacco smoke (P = 0,179 and P = 0,074, respectively). FeNO levels (ppb) in the studied patients allergic to cat, grass or trees, exposed to tobacco smoke were significantly lower than in those children unexposed to tobacco smoke. Our results suggest a clinically important issue, that FeNO results should be interpreted in the context of environmental tobacco smoke exposure. Additionally allergy to cat dander, grass or tree may be potential confounding factor, which should be taken into consideration.

Association between environmental exposure and CD4+CD25+ regulatory T cells

Background: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. Aim: To compare CD4+/CD25+ T-regulatory cells and forkhead transcription factor Foxp3 expression in asthmatic children allergic to house dust mites (HDM) living in rural and farm areas. Materials and Methods: This was a prospective analysis of 35 children living in farm areas (n = 19) and rural areas (n = 16), aged 8-16, with allergic rhinitis (allergic to dust mites) and newly diagnosed asthma. Surface molecule CD4+CD25+Foxp3+ expression on cultured PBMCs was estimated by flow cytometry using fluorophore-conjugated monoclonal antibodies in each patient. Results: Thirty-five children were included into the analysis: 19 children living in farm areas and 16 in rural areas. Within and between-groups (farm area vs. rural area) differences in CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression did not reach the level of significance. Conclusion: The current analysis showed that CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression was not associated with place of living in asthmatic children sensitive to HDM

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Association between environmental exposure and CD4+CD25+ regulatory T cells.

BACKGROUND: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. AIM: To compare CD4+/CD25+ T-regulatory cells and forkhead transcription factor Foxp3 expression in asthmatic children allergic to house dust mites (HDM) living in rural and farm areas. MATERIALS AND METHODS: This was a prospective analysis of 35 children living in farm areas (n=19) and rural areas (n=16), aged 8-16, with allergic rhinitis (allergic to dust mites) and newly diagnosed asthma. Surface molecule CD4+CD25+Foxp3+ expression on cultured PBMCs was estimated by flow cytometry using fluorophore-conjugated monoclonal antibodies in each patient. RESULTS: Thirty-five children were included into the analysis: 19 children living in farm areas and 16 in rural areas. Within and between-groups (farm area vs. rural area) differences in CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression did not reach the level of significance. CONCLUSION: The current analysis showed that CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression was not associated with place of living in asthmatic children sensitive to HDM.

Associations between sensitization to perennial/seasonal allergens and childhood asthma.

BACKGROUND: Childhood asthma is an important public health problem worldwide. Risk factors for asthma development include allergic sensitization and exposure to animals. OBJECTIVE: To identify which (perennial or seasonal) inhalant allergens are associated with asthma and allergic rhinitis in children. METHODS: This was a cross-sectional, retrospective study. We evaluated data from medical documentation of 6,000 children (aged 6 - 18 years) with diagnosed asthma and/or allergic rhinitis who had attended our allergy outpatient clinic. Into the analyses we included those subjects who had specific IgE test done during diagnostic procedures to confirm allergen sensitization. RESULTS: We included 5,076 children in the analysis. We showed that among seasonal allergens only sensitization to timothy or birch significantly changed the prevalence of allergic rhinitis and asthma diagnosis. Of the perennial allergens, house dust mite or cat were most closely related with both allergic rhinitis and asthma. Results of ROC curve analysis showed that in atopic children the specific IgE level of seasonal allergens did not significantly change the prevalence of asthma diagnosis. Sensitization to more than one perennial allergen significantly increased the prevalence of allergic rhinitis and asthma. CONCLUSION: We showed that sensitization to the seasonal allergens timothy and birch as well as to the perennial allergens house dust mite and cat, is associated with asthma and allergic rhinitis in children. Our study determined the role of multiple perennial indoor allergens in the developement of allergic diseases in children. The identification of the specific allergens makes them potential targets for intervention and prevention strategies.

Effectiveness of immunotherapy in children depends on place of living - A pilot study

BACKGROUND: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. Allergen immunotherapy (AIT) is the only treatment of allergy modifying the immune response with the potential to change the natural history of allergic diseases. It seems that studies evaluating the efficacy of immunotherapy in large cohorts of allergic patients living in farm areas are needed to understand the influence of environment on immune response during AIT. AIM: To compare the clinical effectiveness of immunotherapy between children living in farm versus urban areas. MATERIALS AND METHODS: This was a retrospective analysis of 87 children living in farm area (n=42) and city area (n=45), aged 8-16, who completed three years of subcutaneous immunotherapy due to allergic rhinitis/asthma. An AIT efficacy questionnaire has been designed to be filled in by the allergy specialist during a regular immunotherapy visit before and after AIT. RESULTS: We observed significantly higher improvement in total score among children from farm area compared to children from city area (p < 0.001). Between-group differences in symptoms and drug scores did not reached the level of significance. Multivariate logistic regression analysis (adjustment for the effect of gender and type of allergy) showed that living in farm areas was independently associated with significant improvement in total score after immunotherapy (OR: 10.9; 95%CI: 3.7-32.2). CONCLUSION: The current analysis of the better AIT effectiveness in the farm population has shown the protective influence of environmental exposures on asthma and allergic rhinitis in our children

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Prenatal and postnatal exposure to polycyclic aromatic hydrocarbons and allergy symptoms in city children

BACKGROUND: Studies indicate that exposure to polycyclic aromatic hydrocarbons (PAH) is associated with adverse respiratory and allergy outcomes. Exposure to PAH may impair the immune function of the foetus and, subsequently, be responsible for an increased susceptibility of children to allergic diseases. OBJECTIVES: The aim of the present study was to assess the association between mother's exposure to PAH during pregnancy and allergy diseases in their infants. We also assessed the above associations using measured PAH exposure in children's urine during the first two years of life. METHODS: The current analysis was restricted to 455 mothers and their children from Lodz district. The women were interviewed three times during the pregnancy in order to collect demographic, socio-economic and medical history data. Children's health status was assessed at the age of 10-18 months and repeated at two years of age. The associations between dependent dichotomous variables and urine concentrations of 1-hydroxypyrene (1-HP) were analysed using logistic regression. RESULTS: We showed that higher urine concentrations of 1-HP in mothers at 20-24 weeks of pregnancy increased the risk of more frequent respiratory infections (p = 0.02) in children during their first year of life. Higher 1-HP concentrations in children's urine increased the risk of food allergy (p = 0.002) in children during their first two years of life. CONCLUSIONS: This study suggests awareness of environmental factors, which may affect children's health since PAH showed to be a risk factor for airway infections and food allergy in children after adjustment for other risk factors

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Effectiveness of immunotherapy in children depends on place of living - A pilot study.

BACKGROUND: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. Allergen immunotherapy (AIT) is the only treatment of allergy modifying the immune response with the potential to change the natural history of allergic diseases. It seems that studies evaluating the efficacy of immunotherapy in large cohorts of allergic patients living in farm areas are needed to understand the influence of environment on immune response during AIT. AIM: To compare the clinical effectiveness of immunotherapy between children living in farm versus urban areas. MATERIALS AND METHODS: This was a retrospective analysis of 87 children living in farm area (n=42) and city area (n=45), aged 8-16, who completed three years of subcutaneous immunotherapy due to allergic rhinitis/asthma. An AIT efficacy questionnaire has been designed to be filled in by the allergy specialist during a regular immunotherapy visit before and after AIT. RESULTS: We observed significantly higher improvement in total score among children from farm area compared to children from city area (p<0.001). Between-group differences in symptoms and drug scores did not reached the level of significance. Multivariate logistic regression analysis (adjustment for the effect of gender and type of allergy) showed that living in farm areas was independently associated with significant improvement in total score after immunotherapy (OR: 10.9; 95%CI: 3.7-32.2). CONCLUSION: The current analysis of the better AIT effectiveness in the farm population has shown the protective influence of environmental exposures on asthma and allergic rhinitis in our children.

Prenatal and postnatal exposure to polycyclic aromatic hydrocarbons and allergy symptoms in city children.

BACKGROUND: Studies indicate that exposure to polycyclic aromatic hydrocarbons (PAH) is associated with adverse respiratory and allergy outcomes. Exposure to PAH may impair the immune function of the foetus and, subsequently, be responsible for an increased susceptibility of children to allergic diseases. OBJECTIVES: The aim of the present study was to assess the association between mother's exposure to PAH during pregnancy and allergy diseases in their infants. We also assessed the above associations using measured PAH exposure in children's urine during the first two years of life. METHODS: The current analysis was restricted to 455 mothers and their children from Lodz district. The women were interviewed three times during the pregnancy in order to collect demographic, socio-economic and medical history data. Children's health status was assessed at the age of 10-18 months and repeated at two years of age. The associations between dependent dichotomous variables and urine concentrations of 1-hydroxypyrene (1-HP) were analysed using logistic regression. RESULTS: We showed that higher urine concentrations of 1-HP in mothers at 20-24 weeks of pregnancy increased the risk of more frequent respiratory infections (p=0.02) in children during their first year of life. Higher 1-HP concentrations in children's urine increased the risk of food allergy (p=0.002) in children during their first two years of life. CONCLUSIONS: This study suggests awareness of environmental factors, which may affect children's health since PAH showed to be a risk factor for airway infections and food allergy in children after adjustment for other risk factors.

Cord serum 25-hydroxyvitamin D correlates with early childhood viral-induced wheezing.

BACKGROUND: There are investigations concluding that reduced vitamin D status in pregnancy, may be a risk factor for the development of allergic outcomes in offspring. However, studies on the relationship between cord levels of 25-hydroxyvitamin D (25[OH]D) and risk of early childhood wheezing and early-onset atopic dermatitis/food allergy are very limited. OBJECTIVE: To assess the associations between cord blood concentration of 25[OH]D and occurrence of the incidence of wheezing, atopic dermatitis, food allergy, during the first two years of life. METHODS: We evaluated 240 children by the age of 2 years from the Polish Mother and Child Cohort Study. Women were interviewed during pregnancy to collect demographic and socioeconomic data, the medical and reproductive history. At delivery, umbilical cord blood plasma was sampled. The child's health status were examined at approximately 2 years. In the analyses multivariable model was used. RESULTS: Data from 190 participants were included into the analysis. The median value and quartile range of 25[OH]D in cord blood [ng/ml] were as follows: 6.33, 4.16-8.53. 25[OH]D in cord blood below lower quartile increases the risk of multi-triggered wheezing (MTW) in children during first 2 years of life (OR: 2.81; 95% CI: 1.13-7.00). Higher cord serum level of 25[OH]D reduces the risk of viral induced wheezing (VIW). The cord serum level of 25[OH]D below median value (OR: 6.06; 95% CI: 1.3-28.3) or below lower quartile (OR: 5.43; 95% CI: 1.66-17.7) increases the risk of VIW. All above effects of vitamin D level in cord blood were corrected for the effects other independent risk factors of wheezing and VIW in this cohort. CONCLUSIONS: Cord serum 25[OH]D levels were inversely associated with the risk of multi-triggered wheezing, and especially viral-induced wheezing by the age of 2 years, but no association was found with food allergy, atopic dermatitis and frequencies of infections.

Comparative effect of pre-coseasonal and continuous grass sublingual immunotherapy in children.

BACKGROUND: One of the most important aspects of sublingual immunotherapy (SLIT) is the regimen of administration. The aim of the study was to compare the efficacy and the safety of SLIT given pre-coseasonally (starting before the pollen season and continuing until the end of it) and continuously (all year round, independent of the pollen season) in children allergic to grass pollen. METHODS: Sixty children aged 6-18, sensitive only to grass pollen, with rhinitis (20 patients had concomitant asthma) participated in the 2-year prospective, randomized, double-blind, placebo-controlled trial. RESULTS: Both pre-coseasonal and continuous SLIT were associated with a substantial reduction in the combined symptoms/medication score when compared with placebo; there were no significant differences between the regimens (mean difference: 18.1 ± 12.4, P > 0.05). Similar changes were observed in the total symptoms score. Pre-coseasonal therapy, compared with continuous, was more effective in the reduction of nasal symptoms (mean difference: -18.0 ± 2.5, P = 0.006). We did not observe significant differences in medication, ocular, and asthma scores between the regimens. We did not observe changes in morning PEF, FEV1, and PD20 in any of the three groups nor between the groups throughout the study. We showed a significant decrease in FeNO level comparable in both active groups. There were no differences between groups in the induction of CD4CD25Foxp3-positive cells in peripheral blood during the study. CONCLUSION: Both protocols were effective compared with placebo and showed similar decreases for combined symptoms/medication score and all secondary endpoints, with the exception of nasal symptoms that were lower in the pre-coseasonal group.

One-year follow-up of clinical and inflammatory parameters in children allergic to grass pollen receiving high-dose ultrarush sublingual immunotherapy.

BACKGROUND: In a previous double-blind placebo-controlled study, we analyzed a high-dose sublingual immunotherapy (SLIT) ultrarush protocol in asthmatic children monosensitized to grass pollen. In the present open-label study, we assessed the effect of SLIT on symptom score and nonspecific bronchial hyperreactivity in the same cohort followed for 1 subsequent year. METHODS: The study population comprised 35 children who were enrolled in our previous study. Placebo-treated patients were switched to active treatment; therefore, SLIT was administered for a further year to all patients. SLIT was considered effective if it reduced the severity of clinical symptoms and decreased the use of symptomatic medication. The effect of SLIT on nonspecific bronchial hyperreactivity (methacholine challenge test) was also measured. RESULTS: The symptom scores for asthma and rhinitis and medication score remained unchanged in the group who continued SLIT. We also observed further significant improvement in the results of the methacholine challenge test during the third year of treatment. CONCLUSIONS: High-dose ultrarush SLIT reduced the severity of allergic symptoms in the first 2 grass pollen seasons but continuously improved bronchial hyperreactivity in children with asthma, suggesting that SLIT should be continued despite the lack of further improvement in clinical symptoms.

The effect of oral steroids with and without vitamin D3 on early efficacy of immunotherapy in asthmatic children.

BACKGROUND: The possibility of additional strategies to enhance the effectiveness of specific immunotherapy (SIT) is highly attractive. AIM: The aim of our study was to assess the influence of oral corticosteroids and oral corticosteroids combined with vitamin D(3) on the early clinical and immunological effects of SIT. METHODS: It was a randomized, double-blind, placebo-controlled trial conducted in 54 asthmatic children allergic to house dust mites. Intervention was based on receiving a single dose of oral steroid, with or without vitamin D(3), or placebo only on the day of the build-up phase of SIT. RESULTS: After 12 months of SIT, the median daily inhaled corticosteroid (ICS) dose, which controls the symptoms of asthma, was reduced by 25% in the steroid group. However, a 50% reduction of the median daily ICS dose was observed in the control group. The clinical effects of SIT were not affected in the steroid+D(3) group. Concomitantly, we found that intervention with prednisone significantly impaired the induction of T regulatory lymphocytes. Importantly, the clinical and immunological effects of SIT were not affected by intervention with steroids administered with vitamin D(3). CONCLUSIONS: Our study failed to show a beneficial effect of oral corticosteroids on allergen-specific immunotherapy. We observed that the combined administration of a corticosteroid drug and allergen extract suppressed the early clinical and immunological effects of SIT and that vitamin D(3) prevented this 'adverse' influence of steroids.

Early exposure to unhygienic conditions and infections is associated with expression of different Toll-like receptors.

BACKGROUND: We have previously shown a lower prevalence of atopy in children living in foster homes than in children living with their parents. OBJECTIVES: In this study, we explored the associations between atopy and expression of Toll-like receptors (TLRs) 2, 4, 7 and 9 in the same groups of children. MATERIAL AND METHODS: We enrolled all the atopic children living in foster homes in Lodz, Poland and carefully selected, on the basis of age, sex, sensitization profile, clinical manifestation of allergy, and treatment, a similar number of nonatopic children living in foster homes, and a similar number of both atopic and nonatopic children living with their parents. Expression of TLRs 2, 4, 7 and 9 was analyzed in all children. RESULTS: Expression of TLR2 in foster care children was significantly higher in nonatopic children than atopic children (P = .047), while that of TLR7 and TLR9 was significantly higher in atopic children than in nonatopic children. Additionally, expression of TLR9 in nonatopic children in foster care was significantly lower than in nonatopic children living with their parents (P = .003).We also found that both groups of nonatopic children had a greater number of features characteristic of foster home children (poor living conditions in the first year of life) than atopic children. CONCLUSION: Our results may suggest that alternative mechanisms might underlie the in vivo regulation of the expression of different TLRs involved in the development of atopy.

Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen.

BACKGROUND: Although sublingual immunotherapy (SLIT) has been used with increasing frequency, the data on the efficacy of SLIT in pediatric asthma are limited. AIM: The aim of our study was to evaluate the efficacy and the safety of high-dose SLIT given pre-seasonally and co-seasonally in an ultra-rush scheme in children with bronchial asthma allergic to grass pollen. METHODS: Fifty children with asthma, aged 6-17, sensitive to grass pollen, participated in the 2-year prospective, randomized, double-blind, placebo-controlled trial, to investigate the efficacy and safety of SLIT (Staloral 300 IR, Stallergenes SA, 25 microg major allergens) as a standardized extract of five grass pollen with ultra-rush induction. RESULTS: SLIT significantly improved asthma symptom scores (41% vs. placebo group), reduced nasal symptoms (25% vs. placebo group) and the use of rescue medications (10% vs. placebo group), improved forced expiratory volume in 1 s, but had no effect on ocular symptoms, nasal hyper-reactivity, peak expiratory flow and forced expiratory volume between 25% and 75% of vital capacity. Serum levels of immunoglobulin E and IgG4 did not change after SLIT. After the second season of SLIT, an improvement in bronchial hyperresponsiveness was observed; however, compared with placebo, this effect was not significant. Among all subjects in SLIT group, predominantly local reactions have been recorded in 59% of subjects in the first year of treatment and in 35% in the second. CONCLUSIONS: Our study indicated that high-dose ultra-rush, co-seasonal SLIT given for 2 years, was safe and reduced a multiple symptom-medication score.