Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy - CONTROL study.

INTRODUCTION: Extrafine formulation of beclomethasone/formoterol fixed combination (BDP/F pMDI HFA) is approved for both fixed maintenance and maintenance and reliever therapy (MART) of asthma, and recent data has proven that BDP/F pMDI HFA maintenance and reliever therapy is an effective alternative to other regimens. OBJECTIVE: This study aimed to assess the level of asthma control in a real-life setting in adult patients using extrafine BDP/F pMDI HFA fixed combination in a pressurized metered-dose inhaler (pMDI) as fixed maintenance dosing as well as maintenance and maintenance and reliever therapy. Additionally, we examined patients' satisfaction with the inhaler device and compliance with therapy as essential factors determining asthma control. METHODS: This multicenter prospective non-interventional observational study lasted 4 months with 3 patient visits. We used the Asthma Control Questionnaire 7 (ACQ-7) to evaluate the degree of asthma control and Morisky Medication Adherence Scale (MMAS-4) to assess compliance. A self-developed questionnaire was used to assess satisfaction with the inhaler device. RESULTS: 2179 patients using BDP/F pMDI HFA fixed combination as maintenance and reliever therapy or BDP/F pMDI HFA as maintenance therapy and SABA (short-acting beta2-agonist) as a reliever for at least 2 months were included. During the prospective follow-up, we observed an upward trend in the FEV1% (forced expiratory volume in 1 s) predicted values, improvement in the control of symptoms as indicated by a decline in the mean ACQ-7 score was noted (1.62 at Visit 1 vs. 1.21 at Visit 2 vs. 0.94 at Visit 3, p < 0.001) and increase in patients' compliance (the number of patients that reported forgetting at times to take their medication was reduced from 49.7 % to 27.1 %, p < 0.001). At the same time, we noted a reduction in the number of as-needed doses used for symptom relief (p < 0.001). Most patients were satisfied with the pMDI, considered it easy and convenient to use, and preferred it to a dry powder inhaler (p < 0.001). CONCLUSIONS: The use of extrafine BDP/F pMDI HFA as maintenance as well as reliever therapy seems to be associated with increased asthma control and better compliance to therapy.

Upper-airway dysbiosis related to frequent sweets consumption increases the risk of asthma in children with chronic rhinosinusitis.

BACKGROUND: Innate immunity response to local dysbiosis seems to be one of the most important immunologic backgrounds of chronic rhinosinusitis (CRS) and concomitant asthma. We aimed to assess clinical determinants of upper-airway dysbiosis and its effect on nasal inflammatory profile and asthma risk in young children with CRS. METHODS: We recruited one hundred and thirty-three children, aged 4-8 years with doctor-diagnosed CRS with or without asthma. The following procedures were performed in all participants: face-to-face standardized Sinus and Nasal Quality of Life questionnaire, skin prick test, taste perception testing, nasopharynx swab, and sampling of the nasal mucosa. Upper-airway dysbiosis was defined separately by asthma-specific microbiome composition and reduced biodiversity. Multivariate methods were used to define the risk factors for asthma and upper-airway dysbiosis and their specific inflammatory profile of nasal mucosa. RESULTS: The asthma-specific upper-airway microbiome composition reflected by the decreased ratio of Patescibacteria/Actinobacteria independently of atopy increased the risk of asthma (OR:8.32; 95%CI: 2.93-23.6). This asthma-specific microbiome composition was associated with ≥ 7/week sweet consumption (OR:2.64; 95%C:1.11-6.28), reduced biodiversity (OR:3.83; 95%CI:1.65-8.87), the presence of Staphylococcus strains in the nasopharynx (OR:4.25; 95%CI:1.12-16.1), and lower expression of beta-defensin 2, IL-5, and IL-13 in the nasal mucosa. The reduced biodiversity was associated with frequent antibiotic use and with a higher nasal expression of IL-17 and T1R3 (sweet taste receptor). In asthmatic children, reduced sweet taste perception was observed. CONCLUSIONS: Specific upper-airway dysbiosis related to frequent sweet consumption, frequent antibiotic courses, and altered nasal immune function increases the risk of asthma in young children with CRS.

A severity grading system of food-induced acute allergic reactions to avoid the delay of epinephrine administration.

BACKGROUND: Substantial discrepancies among anaphylaxis severity scores may delay epinephrine administration. OBJECTIVE: The study aims to develop a transparent severity grading system of food-induced acute allergic reactions with a decision model for epinephrine use. METHODS: The natural course of 315 acute food-induced allergic reactions in children hospitalized at the Allergology department between May 2016 and July 2019 owing to follow-up treatment and allergy diagnostics was evaluated. The severity of episodes was classified according to the 5 most accepted grading systems. The interrater reliability of classification between anaphylaxis severity scores was assessed. All symptoms were grouped into a heat map according to their real-life incidence and clinical relevance. Based on the heat map analysis, a severity grading system of food-induced acute allergic reactions in children with the epinephrine administration decision model was created. RESULTS: Data from 259 food-induced anaphylaxis episodes in 157 children were included in the analysis. Comparing the grading systems, we observed a 24.7% to 70.2% disagreement between severity scores. The heat map illustrated a strong association between 29 symptoms and their categorization. A new severity grading system was developed and a 2-stage decision model was proposed: "epinephrine yes" (any rapidly progressing symptoms, even mild ones or from 1 organ system; any symptoms from more than 1 organ system; or every grade of anaphylaxis), and "epinephrine available and prepared to use" (nonprogressing mild systemic allergic reaction from 1 system area only; no anaphylaxis). CONCLUSION: A new severity grading system of food-induced acute allergic reactions in children could serve as a clinical tool for health care professionals to avoid epinephrine administration delay.

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.

Dog keeping at home before and during pregnancy decreased the risk of food allergy in 1-year-old children.

INTRODUCTION: The relationship between allergen exposure to animals in pregnancy and the development of allergic symptoms is not clear. AIM: To evaluate the association between prenatal and postnatal exposure to pet ownership and development of atopic dermatitis, food allergy and wheezing in children at the age of 1 and 2. MATERIAL AND METHODS: The mother-child pairs included in this study were part of the Polish Mother and Child Cohort. Mothers in each trimester of pregnancy and 1 year after childbirth have completed a questionnaire on animal exposure. Children's health status was assessed at around one year and two years of age. RESULTS: Keeping a dog at home before and during pregnancy (every trimester) decreased the risk of food allergy in the first year of life. On the other hand, keeping any animal other than a dog (cat, hamster, guinea pig, rabbit) before pregnancy and during each trimester separately increased the risk of food allergy in the first year of life of children. Keeping a guinea pig in the first trimester of pregnancy increased the risk of wheezing in the first year of life. The analysis did not show any significant associations between keeping animals at home before and during pregnancy and the occurrence of atopic dermatitis in the second year of life. CONCLUSIONS: Keeping a dog at home before and during pregnancy decreased the risk of food allergy in 1-year-old children. This effect was eliminated in case of having a cat, hamster, guinea pig, or rabbit.

Food allergy endotype with high risk of severe anaphylaxis in children-Monosensitization to cashew 2S albumin Ana o 3.

BACKGROUND: Food allergy in children can be life-threatening. Component-resolved diagnostics approach to food anaphylaxis is rarely assessed in children. The aim of the study was to identify the food allergen components as the triggers responsible for severe anaphylaxis, with regard to characteristics and associated risks, among children in a large, population-based setting. METHODS: Two hundred and seventy-one children who were hospitalized due to systemic allergic reaction (SAR) and food anaphylaxis were recruited. Medical history was assessed, and culprit allergen source and anaphylaxis severity grade were established. Specific IgE to 112 allergen components using multiplex ImmunoCAP ISAC immunoassay and specific IgE to hazelnut, Cor a 14, and cashew, Ana o 3, using singleplex ImmunoCAP immunoassay were determined. RESULTS: We analyzed data from 237 SAR/anaphylaxis in 237 children. Trigger at allergen component level was defined for every episode. The most common triggers of SAR/anaphylaxis were seeds (50.6%), among them, the storage proteins. Anaphylaxis triggered by Ana o 3, 2S albumin from cashews (aOR = 15.0; 95% CI: 3.27 to 73.47); Tri a 19 from wheat (aOR = 9.93; 95% CI: 1.73 to 56.97); and Cor a 9 from hazelnut (aOR = 6.53; 95% CI: 1.16 to 36.72) had the worst clinical presentation including cardiovascular and severe respiratory symptoms (grade IV-V vs I-III in Cox scale). Thirteen out of 237 (5.5%) SAR/anaphylaxis patients were triggered by Ana o 3. Almost 82% of patients with severe Ana o 3 anaphylaxis were sensitized only to this component and had no concomitant food sensitization. CONCLUSION: Monosensitization to Ana o 3 is, irrespective of other parameters, connected with high risk of severe anaphylaxis.

Comparison of the effect of 5-grass pollen sublingual immunotherapy tablets and drops in children with rhinoconjunctivitis.

BACKGROUND: One of the most important aspects of sublingual immunotherapy (SLIT) is the regimen of administration. AIM: To find any differences in symptom-medication scores between the two groups of SLIT tablets and drops, given pre-coseasonally (starting 8 weeks before the pollen season) in children with rhinoconjunctivitis allergy to grass pollen. The secondary outcome were the differences in lung function and induction of T-regulatory forkhead box P3 (FOXP3) positive cells. METHODS: This was a retrospective, secondary analysis of pooled data obtained from our two prospective randomized placebo controlled trials that involved children who underwent SLIT. Forty-one children, ages 6-18 years, with allergic rhinitis (AR), sensitive to grass pollen, participated in the study. RESULTS: Treatment with both tablets and drops significantly reduced all symptoms (nasal, asthma, and ocular) within the groups; there was no significant difference between both groups. When compared with the tablet therapy, there was a trend for drops therapy to be more effective in the reduction of combined symptom-medication score, but the difference was not statistically significant (p = 0.1036); there was no significant difference in asthma and nasal scores. We showed a significant decrease in the fractional exhaled nitric oxide level comparable in both immunotherapy groups. There were no differences between the groups in the induction of CD4+ CD25+ FOXP3+-positive cells in peripheral blood. CONCLUSIONS: Both protocols showed similar decreases in symptom-medication scores; however, when compared with tablet therapy, there was a trend for drops therapy to be more effective in the reduction of combined symptom-medication score.

Effectiveness of the Polish program for the treatment of severe allergic asthma with omalizumab: a single-center experience.

BACKGROUND: A national program for the treatment of severe allergic (IgE-dependent) asthma with omalizumab (OMA) was implemented in Poland in 2013. This observational study evaluated the effectiveness of the Polish OMA program and monitored asthma control after treatment discontinuation. METHODS: In the first year of the program, 53 patients (23 new/30 continuing treatment) received OMA in the Barlicki Hospital, Poland. Patients were evaluated at baseline and after 16 weeks of OMA treatment by spirometry, mean dose of inhaled corticosteroids (ICS) and oral corticosteroids (OCS), number of asthma exacerbations, the Asthma Control Questionnaire (ACQ), and the Asthma Quality of Life Questionnaire (AQLQ). OMA treatment responses were determined using the global effectiveness of treatment evaluation scale. Fourteen patients ceased OMA treatment following ≥36 months of therapy and entered follow up. RESULTS: All patients treated with OMA de novo for at least 16 weeks had a decrease in asthma exacerbations and showed a good (15/16, 94 %) or an excellent (1/16, 6 %) response to treatment. We observed a reduction in OCS dose (≥5 mg/day) in 14/16 (88 %) patients. ACQ and AQLQ scores improved by ≥0.5 points in 15/16 (94 %) and 14/16 (88 %) patients, respectively. After OMA cessation, 11/14 (79 %) patients showed worsening of asthma control and severe exacerbations. CONCLUSIONS: Patients in the OMA program show significant benefits, including reduced use of OCS, improved asthma control and quality of life. After OMA discontinuation, frequent severe exacerbations were observed primarily in patients whose asthma was previously uncontrolled by high OCS doses.

Serum tryptase level and inflammatory markers in exhaled breath condensate of children with exercise-induced symptoms.

BACKGROUND: The pathogenesis of exercise-induced bronchoconstriction (EIB) is poorly understood. OBJECTIVE: To evaluate the biomarkers concentration in exhaled breath condensate (EBC) in schoolchildren with postexercise symptoms. We also evaluated changes in fractional exhaled nitric oxide (FeNO) value and the serum tryptase level after exercise. METHODS: One hundred children with postexercise symptoms were included. Methacholine challenge testing (MCT) was performed at visit 2, and exercise challenge testing (ECT) was performed at visit 3. Before and after ECT serum tryptase levels and FeNO values were measured. EBC was collected after ECT from 10 randomly selected children from each group. The children were assigned to the following groups: ECT(+) MCT(+), ECT(+) MCT(-), ECT(-) MCT(+), ECT(-) MC(-). We measured the following molecules: eotaxin, interleukin (IL) 8, IL-1ra, IL-1 beta, IL-6, IL-1 alpha, IL-12(p40), IL-5, granulocyte-macrophage colony-stimulating factor, IL-7, IL-15, IL-4, IL-2, IL-10, tumor necrosis factor alpha, interferon gamma, IL-13, tumor necrosis factor beta, monocyte chemoattractant protein-1, IL-17A, macrophage inflammatory proteins-1 alpha, macrophage inflammatory proteins-1 beta, IL-12(p70), and regulated on activation, normal T-cell expressed and secreted by using a multiplex immunoassay. Prostaglandin E2 (PGE2), leukotriene B4, and cysteinyl leukotriene were analyzed by using separate enzyme-linked immunosorbent assay kits. RESULTS: In the MCT(+) group, a detectable level of IL4 in EBC and detectible levels of eicosanoids were seen in the ECT(+) group. We observed the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations in patients with detectable compared with patients without detectable levels of cytokines in EBC. We showed ECT-induced reduction in the tryptase level in patients with a nondetectable PGE2 level in EBC and an increase in tryptase levels in patients who had detectable levels of PGE2 in EBC. CONCLUSIONS: EBC was a useful method to estimate inflammation but only in children with symptoms and with EIB shown by a positive ECT. Children with a positive ECT had detectable levels of eicosanoids in EBC; the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations was observed. The results of above study confirm the role of mast cells and eicosanoids in the pathogenesis of EIB in children.

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.

Prognostic value of thymidine kinase activity in patients with chronic lymphocytic leukemia.

Thymidine kinase (TK) activity is a marker of biological activity that allows the indolent and aggressive forms of chronic lymphocytic leukemia (CLL) to be distinguished. The aims of the study were to determine the relationship between TK activity and clinical status and prognosis, as well as to compare its activity with that of other prognostic and predictive factors. TK activity was measured in patient sera at the time of diagnosis using the DiviTum method, with the mean value being 439 Du/L. A correlation was found between TK activity and risk of disease progression (p=0.045). The optimal discriminative value of TK activity in the prediction of CLL progression was found to be 600 Du/L. TK activity significantly differed between the patients who achieved complete remission and those who only partially responded to therapy. In 93% of patients without any response to treatment and 18 out of 20 patients with progressive disease, TK activity over 600 Du/L was noted. In addition, all of the 10 patients with 17p13 deletion displayed TK activity of over 600 Du/L (p=0.0004). High TK activity also correlated with elevated levels of LDH (p=0.001) and ß2­microglobulin (p=0.03) in the study group. The results of the study indicated the importance of TK activity as a prognostic factor in patients with CLL.

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.

Do children with stable asthma benefit from addition of montelukast to inhaled corticosteroids: randomized, placebo controlled trial.

BACKGROUND: To determine the effects of montelukast added to maintenance inhaled steroids (ICS) therapy during the school year in children with stable asthma on the ICS use, frequency of exacerbations, lung function, asthma symptoms, fractional exhaled nitric oxide (FeNO) level and exercise-induced bronchoconstriction (EIB). METHODS: Seventy six asthmatic children aged 6-14 years, allergic to house dust mites were randomized to a double-blinded trial comparing montelukast therapy to a matching placebo. We studied following end-points: the reduction in the ICS dose, the frequency of exacerbations, lung function, asthma control test score, and the change from baseline in FEV1 during a standardized exercise treadmill challenge. ICS dose was adjusted in a stepwise fashion to determine the lowest dose necessary to control asthma symptoms. RESULTS: We showed that children with baseline value of FeNO above 31 ppb and well controlled asthma symptoms on low doses of ICS, benefit the most from additive therapy with montelukast; their cumulative ICS dose is lower than in children treated with ICS only. Also, the addition of montelukast to regular treatment in asthmatic children resulted in a significant reduction in the frequency of exacerbations and EIB protection. CONCLUSION: It is reasonable to add montelukast to ICS therapy in asthmatic children during the school year, to lower cumulative ICS dose in children with well controlled asthma symptoms, as well as to reduce number of exacerbations, and to achieve better control of EIB. TRIAL REGISTRATION: NCT01266772.

The effect of prenatal exposure to phthalates on food allergy and early eczema in inner-city children.

BACKGROUND AND OBJECTIVE: We hypothesized that maternal prenatal and children urine metabolite concentration of phthalates would be associated with food allergy and early eczema among inner-city children. The study was based on data from the Polish Mother and Child Cohort. METHODS: Prenatal and postnatal exposure to the following phthalates: diethyl phthalate, diisobutyl phthalate, di-n-butyl phthalate, butyl-benzyl phthalate, di(2-ethylhexyl) phthalate, diisononyl phthalate, and di-n-octyl phthalate were determined by measuring phthalate metabolites in the urine collected from the mothers during the third trimester of pregnancy and from their children at age 2 years. Pre- and postnatal observations limited the response rate and final sample size; data from 147 participants were included in the analysis. Children's health status was assessed at 24 months of age by using a questionnaire administered to the mothers. We studied associations between the urine level of phthalates and the presence of food allergy and atopic dermatitis in logistic regression analysis. All associations were adjusted for independent risk factors of dependent variables. Associations with atopic dermatitis were adjusted for the effect of atopy in the family, the father's education, frequency of house cleaning, and breastfeeding; associations with food allergy were adjusted for the presence of pets at home during pregnancy and breastfeeding. RESULTS: The prevalence of the outcomes were as follows: atopic dermatitis, 12.2%, and food allergy, 48.9%. We showed that higher urine concentrations of monobenzyl phthalate in mothers during pregnancy increased the risk of food allergy in children during the first 2 years of life (odds ratio 4.17 [95% confidence interval, 1.17-17.89]). There were no associations with children's urine and allergic symptoms. CONCLUSIONS: Results of our study indicated awareness of environmental factors that may affect children's health because the phthalates were shown to be risk factors for food allergy in children.

Prevalence of exercise-induced cough in schoolchildren: a pilot study.

Association between exercise-induced bronchoconstriction (EIB) and physical activity has not been investigated in a natural school environment in a general pediatric population. Our objective was to determine the prevalence of exercise-induced symptoms (cough, wheeze, chest tightness, dyspnea) and bronchospasm among schoolchildren during physical education (PE). A total of 557 schoolchildren from seven public schools were enrolled. Information regarding demographic characteristic, previously diagnosed asthma was obtained. All children attended 45-minute PE lesson with similar exercise intensity. Pulmonary function tests were performed before and immediately after PE lesson. The diagnosis of EIB was defined as a forced expiratory volume in one second (FEV1) decrease from baseline of more than or equal to 10% with exercise. Cough and dyspnea after exercise were recorded. A total of 557 participants were included into the analysis. After PE lesson, 15.3% children suffered from cough, 0.9% reported dyspnea, and 10.1% had more than 10% fall in FEV1 from baseline. Among all participants, 5.9% had doctors' diagnosed asthma, 4.8% of them were treated with inhaled corticosteroids (ICS). Among children with cough, 21.5% had asthma and 17.6% experienced EIB. Among asthmatics, 48.6% suffered from cough and 18.2% had more than 10% fall in FEV1 from baseline after PE lesson. EIB was not affected by age, gender, body mass index, asthma diagnosis, and ICS use. Only cough (odds ratio: 2.21, 95% confidence interval: 1.16-4.23; p = 0.0161) was independently associated with EIB. This study showed a high prevalence of exercise-induced cough and/or 10% fall in FEV1 during activity lesson in a natural school environment in a large urban population of schoolchildren. Our results call for another studies addressing the impact of environment on exercise-induced symptoms.

Exhaled nitric oxide correlates with IL-2, MCP-1, PDGF-BB and TIMP-2 in exhaled breath condensate of children with refractory asthma.

INTRODUCTION: There is evidence that parameters obtained from exhaled breath condensate (EBC) reflect changes in the level of the airway lining fluid. The telation between exhaled nitric oxide (NO) and EBC inflammatory markers has not been analyzed in the context of the inflammatory profile in the airways in asthmatic children. AIM: To show the cytokine profile in EBC of children with severe/refractory asthma as well as correlations between the fractional exhaled NO (FeNO) level and cytokine concentrations. MATERIAL AND METHODS: The study population consisted of eight children aged 8 to 17 years with IgE-dependent, severe/refractory asthma with a duration of at least 2 years. This was an observational study, the first consecutive eight patients with asthma symptoms on the day of the study visit, when EBC samples were obtained. RESULTS: The inter-subject variability of study cytokines ranged from 8.6 to 54.6. Cytokines with coefficient of variation < 20% were: interferon-γ, interleukins IL-2, IL-7, IL-15, IL-16, monokine induced by interferon γ (MIG) and tumor necrosis factor α. We showed a significant positive correlation between the FeNO level and crucial mediators in asthma development and progression (IL-2, MCP-1), and potent markers of airway remodeling (PDGFBB, TIMP-2). All correlations between two different variables were controlled for the effects of age, forced expiratory volume in 1 s and number of asthma exacerbations during last 12 months. CONCLUSIONS: The profiling of cytokine expression in EBC can be reproducibly performed in children with severe/refractory asthma. When treating asthma in children, the FeNO level should be monitored as a prevention strategy of the progression of the remodeling leading to refractory/severe asthma. Exhaled breath condensate may be a useful tool to phenotype asthma via a non-invasive approach.

Predictive value of fractional nitric oxide in asthma diagnosis-subgroup analyses.

BACKGROUND: There are no studies investigating the benefit of using FeNO measurements in correlation with sensitization to perennial and seasonal allergens in children with asthma. OBJECTIVE: To define the group of children with respiratory symptoms in whose FeNO measurement has predictive value for asthma. We assessed the effect of age, allergy profile, atopy, lung function and the presence of allergic rhinitis on interpretation of FeNO levels for clinical applications. METHODS: It was a retrospective, cross-sectional study. We evaluated data from medical documentation of 1767 children with symptoms of allergic diseases such as asthma and/or allergic rhinitis. We included in the analyses subjects who had the following tests done during diagnostic procedures (single measurement): FeNO, spirometry, specific IgE results. All subjects had undergone a minimum 3-years prospective clinical observation after the first FeNO measurement until the later assignment (or not) of an asthma/allergic rhinitis diagnosis. RESULTS: We included 1767 children into the analysis; asthma diagnosis was confirm in 1054 (59.6%) children. We showed that only atopy (OR: 1.9; 95%CI: 1.5-2.4) and presence of allergic rhinitis (OR: 1.6; 95%CI: 1.4-1.9) were independently associated with increased FeNO level. Only among patients with atopy and allergic rhinitis FeNO level (above 23 ppb) was associated with asthma diagnosis. Sensitivity, specificity, positive predictive value and negative predictive value of FeNO >23 ppb for asthma diagnosis were as follows: 0.9(95%CI: 0.68-0.98), 0.52(95%CI: 0.42-0.61), 0.25(95%CI: 0.16-0.37), 0.97(95%CI: 0.88-0.99). CONCLUSION: We showed that in children with atopy and with allergic rhinitis a negative predictive value for asthma diagnosis was very high with the optimal cut-off point of FeNO 23 ppb. Therefore we showed the utility of FeNO measurements to exclude asthma in the subgroup of patients with atopy and allergic rhinitis.