Rafał Stelmach

Fractional exhaled nitric oxide (FeNO) may predict exercise-induced bronchoconstriction (EIB) in schoolchildren with atopic asthma.

BACKGROUND There is a need for the performance of exercise-induced bronchoconstriction (EIB) tests in the monitoring of childhood asthma control. We aimed to evaluate whether in children with atopic asthma, EIB can be predicted by one or more of the following parameters or by their combination: fractional exhaled nitric-oxide (FeNO), allergy profile, asthma treatment, total IgE serum concentration and eosinophil blood count (EBC). METHODS It was a retrospective, cross-sectional study. We evaluated data from medical documentation of children with atopic asthma who had performed standardized spirometric exercise challenge test. RESULTS One hundred and twenty six patients with atopic asthma, aged 5-18, were included in the analysis. There were two groups of patients: the EIB group (n=54) and the no-EIB group (n=72). The median FeNO level prior to exercise in the EIB group was 27.6 vs. 16.3 ppb in the no-EIB group (p=0.002). FeNO level higher than 16 ppb had the highest diagnostic value to confirm EIB. When using the FeNO level of >16 ppb, the sensitivity, specificity, negative predictive and positive predictive values for EIB were 83%, 46.9%, 74.2%, and 60%, respectively. In the EIB group, the degree of FeNO elevation did correlate positively with the absolute fall in FEV(1) (p=0.002; r=0.45). The FeNO value of >16 ppb, EBC value of >350 cell/mm(3) and allergy to house dust mites presented the highest odds ratios of EIB. However, the FeNO value of >16 ppb was the only independent odds ratio of EIB. CONCLUSIONS Elevated FeNO level increased the odds of EIB in asthmatic schoolchildren, independently of other asthma severity markers and the intensity of anti-asthma therapy. It seems likely that FeNO measurement may act as a screening tool and help to prevent under-diagnosis and under-treatment of exercise-induced bronchoconstriction in schoolchildren with atopic asthma.

Diagnostic value of lung function parameters and FeNO for asthma in schoolchildren in large, real‐life population

To establish a diagnostic value of fractional exhaled nitric oxide (FeNO), interrupter resistance measurement (Rint), specific resistance of the airways (sRaw), spirometric parameters in asthma diagnosis in schoolchildren.

Validity of the Pediatric Asthma Quality of Life Questionnaire in Polish children

To cite this article: Stelmach I, Podlecka D, Majak P, Jerzyńska J, Stelmach R, Janas A, Krakowiak J, Stelmach W. Validity of the Pediatric Asthma Quality of Life Questionnaire in Polish children. Pediatric Allergy Immunology 2011; 22: 660–666.

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.

Spirometry-Adjusted Fraction of Exhaled Nitric Oxide Allows Asthma Diagnosis in Children, Adolescents, and Young Adults.

BACKGROUND: Recently, it has been proved that fractional exhaled nitric oxide (FENO) results are in disagreement with other measurements of asthma control. The objective of this work is to present and validate new lung function/lung inflammation ratios. METHODS: This is a retrospective, cross-sectional study in which we evaluated data from medical documentation of 1,529 pediatric and adolescent subjects and a small number (2% of the studied population) of young adults, who presented symptoms suggestive of asthma (age range 4–24 y). We are the first to analyze results obtained in this manner (before the introduction of controlled medication): FENO, spirometry, specific resistance of the airways, diagnosis of allergic diseases, and allergen sensitization (specific immunoglobulin E results). RESULTS: Cut-off points for the new indicators allowed us to diagnose asthma in the study participants: for FVC/FENO ratio, 0.17 L/ppb; for FEV1/FENO ratio, 0.15 L/ppb; for forced expiratory flow during the middle half of the FVC maneuver (FEF25–75%)/FENO ratio, 0.16 L/s/ppb; for FENO/FVC ratio, 11.00 ppb/L; for FENO/FEV1 ratio, 12.53 ppb/L; and for FENO/FEF25–75% ratio, 11.81 ppb/L/s. Only the ratios described above were closely correlated with the diagnosis of asthma and with one another. They significantly differed between subjects with asthma and healthy subjects as well as between females and males. Only FEF25–75%/FENO and FENO/FEF25–75% values were significant predictors of any sensitization in the studied subjects. We found higher sensitivity than specificity and higher positive predictive value than negative predictive value for FVC/FENO, FEV1/FENO, and FEF25–75%/FENO and found a mirror image for reverse parameters. However, the positive predictive values and negative predictive values were not clearly convincing with respect to diagnostic accuracy in the case of the new parameters proposed. CONCLUSIONS: We propose new lung function/lung inflammation ratios by which it may become possible to diagnose asthma in children and adolescents on the basis of a subjects spirometry and FENO measurements. We believe that our ratios are only supportive of the universally used parameters in the process of diagnosing asthma. (ClinicalTrials.gov registration NCT01805635.)

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.

Cytokine profiling in exhaled breath condensate after exercise challenge in asthmatic children with post-exercise symptoms

Introduction Markers of exhaled breath condensate (EBC) correlate with lung function impairment, airway remodeling and different aspects of the disease such as exercise-induced bronchoconstriction (EIB). Aim of the study was to determine the cytokine profile in EBC of children with asthma after an exercise treadmill challenge in order to obtain clinically useful information about mechanisms of EIB; also, to assess correlations between cytokine concentrations in EBC and clinical characteristics of the patients. Material and methods The study population consisted of 25 randomly selected children, aged 8 to 19 years, with asthma and EIB symptoms despite the use of control medications. Patients on the day of the study visit underwent fractional exhaled nitric oxide measurement (FeNO) and baseline spirometry, performed an exercise treadmill challenge (ETC), and EBC samples were obtained at the end of the ETC. Results In asthmatic children with positive ETC, monocyte hemotactic protein-1 (MCP-1) and IL-16 adjusted to pre-EBC forced expiratory volume in 1 s (FEV1) were significantly higher compared to children with negative ETC (p = 0.022 and p = 0.017 respectively). After adjustment to pre-EBC FEV1 other cytokines (IL-4, IL-5, IL-6, IL-8, MIG, TNF-α) were not related to post-exercise changes in FEV1. Conclusions We observed a specific inflammatory profile in the airways of asthmatic children with bronchoconstriction induced by exercise. The concentration of cytokines in EBC depended on the post-exercise decrease in FEV1, which was measured by the area under the curve (AUC). MCP-1 and IL-16, adjusted to pre-EBC FEV1, were significantly higher in children with a positive exercise challenge compared to those with a negative one.