Glycoprotein A (GARP) in children who outgrow food allergy.

BACKGROUND: There is little understanding of the mechanisms by which food allergy (FA) develops into persistent disease, or by which symptoms it regresses. Food allergy is a major health problem in developed countries, where the prevalence reaches up to 6% in children and 3% in the adult population. OBJECTIVE: Children with food allergy remission (FAR) and those without FAR below five years of age, were compared 7-10 years with respect to clinical data and expression of glycoprotein A repetitions predominant (GARP) on peripheral blood mononuclear cells. METHODS: Forty children with FAR and 40 children without FAR at age 7-10, in whom FA was previously diagnosed at age below five years were evaluated. In this prospective study, demographic and clinical data were taken, patients were classified as atopic based on history and serum specific IgE (sIgE) for a specific allergen. Blood samples were obtained from all patients to assess expression of GARP. RESULTS: We observed higher expression of GARP in children with FAR compared to children without FA (p=0.005); optimal cut-off for GARP prediction of the remission was 20.1%. Children with FAR and food-specific IgE in serum had higher expression of GARP compared to children with low food specific IgE (<0.35kU/L). Keeping pets at home decreased, and presence of allergic rhinitis increased ORs for high expression of GARP (hGARP) in our patients. CONCLUSION: hGARP (>20.1%) is related with FAR in school children. Allergic rhinitis, and pets at home modify this effect of GARP. Children with allergic rhinitis have less chance of developing remission despite maintaining immune tolerance (hGARP); quite the opposite case with pets at home.

A 2-year-old girl with chronic crackles after respiratory syncytial virus infection: a case report.

BACKGROUND: Respiratory syncytial virus is the most common cause of lower respiratory tract infections in infants and young children. While the majority of infants display only mild upper respiratory tract infection or occasionally otitis media, around one-third will develop an infection of the lower respiratory tract, usually bronchiolitis. There is now convincing evidence from a number of cohorts that respiratory syncytial virus is a significant, independent risk factor for later wheezing, at least within the first decade of life. The wide variation in response to respiratory syncytial virus infection suggests that susceptibility and disease are influenced by multiple host-intrinsic factors. CASE PRESENTATION: A 2-year-old white girl presented to our Pediatric Allergy Clinic with recurrent crackles in addition to cough, fevers, and labored breathing since her first respiratory syncytial virus infection at the age of 7 months. She had been under the care of pulmonologists, who suspected childhood interstitial lung disease. She was hospitalized eight times due to exacerbation of symptoms and prescribed systemic and inhaled steroids, short-acting ß2-mimetics, and antileukotriene. There was no short-term clinical improvement at that time between hospitalizations. During her hospital stay at the Pneumonology and Cystic Fibrosis Department in Rabka a bronchoscopy with bronchoalveolar lavage was performed. Laboratory bacteriological tests found high colony count of Moraxella catarrhalis (ß-lactamase positive), sensitive to amoxicillin-clavulanate, in bronchial secretions and swabs from her nose. After this, infections were treated with antibiotics; she remained in good condition without symptoms. Crackles and wheezing recurred only during symptoms of infections. Therefore, we hypothesize that respiratory syncytial virus infection at an early age might cause severe damage of the lung epithelium and prolonged clinical symptoms, mainly crackles and wheezing, each time the child has a respiratory infection. CONCLUSIONS: This case illustrates the importance of respiratory syncytial virus infection in an immunocompetent child. Pediatricians need to have a high index of suspicion and knowledge of recurrent symptoms associated with severe damage of the lung epithelium to establish the correct diagnosis.

Clinical and immunological effects of vitamin D supplementation during the pollen season in children with allergic rhinitis.

INTRODUCTION: Vitamin D deficiency has been proposed as a potential contributing factor in patients with allergic diseases. We compared the clinical and immunological effects of vitamin D supplementation to placebo during the pollen season in children with allergic rhinitis. MATERIAL AND METHODS: Thirty-eight children aged 5-12, sensitive to grass pollen, participated in a prospective, randomized, double-blind, placebo-controlled trial. Children received either vitamin D 1000 IU daily supplementation or placebo. We studied symptoms/medication score, lung function, exhaled nitric oxide concentration (FENO), methacholine bronchial provocation test and serum level of 25(OH)D, as well as; CD4+CD25+Foxp3+ cells, TLR4, IL-1, IL-6, TNF and the IL-10 and transforming growth factor ß1 (TGF-ß1) levels in cell culture supernatants. RESULTS: Vitamin D therapy was effective in reduction of the symptoms/medication score (p = 0.0371). In vitamin D group an increase in the CD4+CD25+Foxp3+ cells (7.06 vs. 10.5%; p = 0.0013) and serum 25(OH)D concentration (49.6 vs. 96.6 ng/ml; p = 0.0001) and in control group an increase in FENO (15.6 vs. 21 ppb; p = 0.0331) and serum 25(OH)D level were observed (82.9 vs. 100.3 ng/ml; p = 0.0003).We revealed a higher increase from baseline in the percentage of CD4+CD25+Foxp3+ cells in the vitamin D group compared to the control group (p = 0.0058). A significant correlation between CD4+CD25+Foxp3+ cell induction and FENO reduction in the vitamin D group was observed (p = 0.0217). CONCLUSIONS: Vitamin D 1000 IU as a supplementary treatment of grass pollen allergy in children with allergic rhinitis during the pollen season significantly reduced the symptoms/medication score. The study revealed an immunological effect of vitamin D.

Quality of life in asthmatic children and their caregivers after two-year treatment with omalizumab, a real-life study.

INTRODUCTION: Omalizumab, a monoclonal anti-immunoglobulin E antibody, has been successfully used as a supplementary therapy to improve asthma control in children aged ≥ 6 years with severe persistent allergic asthma. AIM: To demonstrate the quality of life in children with severe asthma and their caregivers, and changes from baseline in forced expiratory volume in 1 s (FEV1) and daily inhaled corticosteroids (ICS) dose after 2-year treatment with omalizumab. MATERIAL AND METHODS: Participants were seen in the clinic at enrollment (visit 1), after 16 weeks (visit 2), after 52 weeks (visit 3) and after 104 weeks (visit 4) of treatment with omalizumab. We evaluated lung function, ICS use and the quality of life with the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ). RESULTS: Nineteen children and caregivers were enrolled. Significant improvement was observed in PAQLQ and PACQLQ scores, both in all domains and in total scores. Significant differences were found between the first and the other visits. A positive correlation between PAQLQ and PACQLQ at the first and at the second visit was found, 63.3% of patients achieved reduction in ICS doses. We did not notice any significant improvement in FEV1. CONCLUSIONS: The improvement in quality of life in asthmatic children and adolescents observed after omalizumab correlates with the improvement of quality of life in caregivers, reduction in ICS use but not with FEV1.

Effect of Lactobacillus rhamnosus GG and vitamin D supplementation on the immunologic effectiveness of grass-specific sublingual immunotherapy in children with allergy.

BACKGROUND: An important issue in sublingual immunotherapy (SLIT) is how to improve efficacy. OBJECTIVE: To compare the clinical and immunologic efficacy of SLIT given alone and, to enhance clinical efficacy, given with probiotic or vitamin D supplementation. METHODS: One hundred children, ages 5-12 years, sensitive to grass pollen, with allergic rhinitis participated in a 5-month prospective, randomized, double-blind, placebo-controlled trial. Children received 5-grass SLIT 300 IR tablets with either vitamin D 1000 IU daily supplementation, probiotic, or placebo. The control group included children with allergy who did not qualify for immunotherapy. Primary end points included a symptom-medication score, lung function, and exhaled nitric oxide concentration. The secondary end point was the immunologic efficacy measured by the following: CD4(+)CD25(+)Foxp3(+) (forkhead box P3) cells, Toll-like receptor (TLR) 4, interleukin (IL) 1, IL-6, tumor necrosis factor, IL-10, and transforming growth factor ß-1 levels in cell culture supernatants. RESULTS: Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group. In the SLIT-probiotic group, between-group analysis showed significantly higher CD4(+)CD25(+)Foxp3(+) induction compared with the SLIT group and higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group (Fig. 1). An increase in CD4(+)CD25(+)Foxp3(+) induction, reduction in TLR-positive cells recruitment and an increase in transforming growth factor ß-1 production were independently associated with a better clinical effect of SLIT in children. CONCLUSIONS: We demonstrated the clinical and immunologic effect of probiotic and vitamin D supplementation on SLIT. Probiotic supplementation showed better clinical and immunologic response in children with allergic rhinitis.

Food allergy is associated with recurrent respiratory tract infections during childhood.

INTRODUCTION: To find out whether children with food allergy have an increased risk of recurrent upper and lower respiratory tract infections and of asthma. AIM: To describe the clinical profile of children diagnosed with food allergy referred to the Allergy Clinic. MATERIAL AND METHODS: We conducted a retrospective study to assess the patients' demographic, anthropometric and clinical data. The analysis included data of all children by the age of 10 years (registered with the Allergy Clinic between 2012 and 2013) in whom IgE mediated food allergy had been diagnosed during 18 months of observation. RESULTS: We included 280 children into the analysis. Recurrent respiratory tract infections (rRTI), asthma and gastrointestinal (GI) symptoms were observed in 153 (54.6%), 96 (34.3%), 39 (13.9%), respectively, with a significant increasing trend across age-subgroups. In children from 1 to 2 years old, sensitization to ß-lactoglobulin increased the risk of rRTI (OR = 3.91; 95% CI: 1.03-14.87). In older children sensitization to allergens other than milk or egg decreases the risk of rRTI (OR = 0.25; 95% CI: 0.10-0.62); sensitization to egg decreased the risk of asthma diagnosis (OR = 0.09; 95% CI: 0.01-0.75). We did not identify food allergens which change the risk of GI symptoms in children. This finding was consistent throughout all age-subgroups. CONCLUSIONS: Sensitization to ß-lactoglobulin increased the risk of rRTI in children under 2 years of age nearly four times. The presence of sensitization to food allergens above 3 years of age did not increase the risk of developing clinical presentation of food allergy other than atopic dermatitis.

Methacholine challenge testing is superior to the exercise challenge for detecting asthma in children.

BACKGROUND: Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma. OBJECTIVE: To compare the predictive value of methacholine challenge testing (MCCT) and the exercise treadmill challenge (ETC) for detecting asthma in children with postexercise symptoms. METHODS: This was a prospective study of children 10 to 18 years old with postexercise symptoms. During asthma diagnosis, they underwent MCCT and ETC. There were 2 study visits. All subjects underwent ECT at visit 1 and MCCT 1 week later at visit 2. RESULTS: One hundred one children were included; 62.9% had a history of atopy, and asthma was confirmed in 43.6%. MCCT showed 90.9% sensitivity, 82.5% specificity, 80.0% positive predictive value, and 92.2% negative predictive value; the respective values for ECT were 77.3%, 68.4%, 65.4%, and 79.6%. Positive MCCT results showed significantly higher sensitivity and higher positive predicative value in the diagnosis of asthma in children with postexercise symptoms compared with a 10% decrease in forced expiratory volume in 1 second for ECT (P = 0.034). Conducting MCCT during asthma diagnosis confirmed asthma in an additional 24.3% of children with exercise-induced symptoms. With a cutoff level at 17% of forced expiratory volume in 1 second for ECT, the discrepancy was decreased and reasonable values for sensitivity, specificity, positive predictive value, and negative predictive value were attained (61.0%, 77.1%, 69.4%, and 69.8%, respectively). CONCLUSION: A large number of school children with asthma and postexercise symptoms could have positive MCCT and negative ECT findings. Untreated asthma in children with exercise-induced bronchoconstriction could cause them to be discharged from physical education classes. TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT01798823.

Total specific airway resistance vs spirometry in asthma evaluation in children in a large real-life population.

BACKGROUND: Total specific airway resistance (sRtot) has been introduced as an alternative technique to assess lung function with a particular application to younger children with asthma. OBJECTIVE: To establish a diagnostic value of the body plethysmographic parameter (sRtot) in asthma diagnosis in young children. METHODS: This was a prospective, noninterventional study. Children 4 to 18 year old with symptoms suggestive of asthma were included (n = 885). Subjects underwent body plethysmography and spirometry (when capable) with reversibility tests. Of 788 subjects who could perform spirometry in addition to body plethysmography, 578 were diagnosed with asthma. Subjects with asthma were treated for minimum of 6 months and then their asthma was confirmed or refuted. RESULTS: In 471 patients, asthma diagnosis was confirmed after 6 months of antiasthmatic treatment; 142 patients were 4 to 6 years old and 329 were 7 to 18 years old. Change in response to bronchodilator in children with asthma was significant for sRtot (P = .02) but not for forced expiration volume in 1 second (P = .21); sRtot was more sensitive and specific in identifying children with reversible obstruction than spirometry. There was a significant association between sRtot and asthma diagnosis in patients 4 to 6 years old (odds ratio 1.02, 95% confidence interval 1.01-1.03, P = .001); to differentiate subjects with asthma from those without asthma, the optimal cutoff point for sRtot was 174.5%. A sRtot value higher than 174.5% was associated with a positive prediction of an asthma diagnosis in patients 4 to 6 years old. A ratio of forced expiration volume in 1 second to forced vital capacity below 80% was not significantly associated with asthma. CONCLUSION: These data support the recommendation of performing sRtot rather than spirometry in young children as a fairly sensitive marker of asthma. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT01805635).

Omalizumab in the prevention of anaphylaxis during immunotherapy: a case report.

Omalizumab is approved for the treatment of chronic severe persistent asthma. As a trigger for anaphylaxis, the frequency of subcutaneous specific immunotherapy (SCIT) is high. We report the case of a 11-year-old boy with severe allergic asthma. During the initial phase of immunotherapy he experienced anaphylaxis and SCIT was discontinued. Because of uncontrolled asthma, despite the inhaled steroids and ß-agonists were taken into consideration, omalizumab 300 mg once every 4 weeks was initiated. Currently, the maintenance dose has been reached and SCIT is continued without any side effects. The clinical implication of the above case report is that children with severe allergic asthma who are pre-treated with omalizumab might also benefit in the future from SIT as a causal treatment option.

Omalizumab as a new therapeutic approach for children with severe asthma.

Omalizumab has been shown to improve asthma control when added to a regimen of guideline-based therapy for inner-city children and adolescents, nearly eliminating seasonal peaks in exacerbation and reducing the need for other medications to control asthma. Below, we describe a case of a 17-year-old non-smoker with a history of severe asthma admitted to our clinic after unsuccessful 10-year immunotherapy. The patient fulfilled the criteria for anti-IgE therapy, he was prescribed omalizumab 600 mg every 2 weeks. During therapy he was able to reduce his use of ICS and did not require any oral corticosteroids. He experienced an increase in his ability to exercise and noted no exacerbation of asthma symptoms. It is possible that in our patient, specific immunotherapy could be successfully continued after the initiation of omalizumab therapy.