Function Exhaled Nitric Oxide Research Articles

Predictors of asthma control differ from predictors of asthma attacks in children: The Swiss Paediatric Airway Cohort.

It is unclear if predictors of asthma attacks are the same as those of asthma symptom control in children. We evaluated predictors for these two outcomes in a clinical cohort study. The Swiss Paediatric Airway Cohort (SPAC) is a multicentre prospective clinical cohort of children referred to paediatric pulmonologists. This analysis included 516 children (5-16 years old) diagnosed with asthma. At baseline, we collected sociodemographic information, symptoms, personal and family history and environmental exposures from a parental baseline questionnaire, and treatment and test results from hospital records. Outcomes were assessed 1 year later by parental questionnaire: asthma control in the last 4 weeks as defined by GINA guidelines, and asthma attacks defined as any unscheduled visit for asthma in the past year. We used logistic regression to identify and compare predictors for suboptimal asthma control and asthma attacks. At follow-up, 114/516 children (22%), reported suboptimal asthma control, and 114 (22%) an incident asthma attack. Only 37 (7%) reported both. Suboptimal asthma control was associated with poor symptom control at baseline (e.g. ≥1 night wheeze/week OR: 3.2; 95% CI: 1.7-6), wheeze triggered by allergens (2.2; 1.4-3.3), colds (2.3; 1.4-3.6) and exercise (3.2; 2-5), a more intense treatment at baseline (2.4; 1.3-4.4 for Step 3 vs. 1), history of preschool (2.6; 1.5-4.4) and persistent wheeze (2; 1.4-3.2), and exposure to tobacco smoke (1.7; 1-2.6). Incident asthma attacks were associated with previous episodes of severe wheeze (2; 1.2-3.3) and asthma attacks (2.8; 1.6-5 for emergency care visits), younger age (0.8; 0.8-0.9 per 1 year) and non-Swiss origin (0.3; 0.2-0.5 for Swiss origin). Lung function, exhaled nitric oxide (FeNO) and allergic sensitization at baseline were not associated with control or attacks. Children at risk of long-term suboptimal asthma control differ from those at risk of attacks. Prediction tools and preventive efforts should differentiate these two asthma outcomes.

Exploring the role of basophil activation test in diagnosis of Dermatophagoides farinae sensitization and evaluation of therapeutic efficacy of subcutaneous immunotherapy in children

It aims to detect basophil activation ratio (%CD63+ ) in peripheral blood of children with allergic asthma and rhinitis by using flow cytometry (FCM), so as to analyse the application values and clinical relevance of the basophil activation test (BAT) in diagnosis of Dermatophagoides farinae (Derf) sensitization and monitoring therapeutic efficacy of subcutaneous immunotherapy (SCIT). It was a prospective study. From the newly diagnosed children with asthma and rhinitis in our paediatric clinic, 39 patients diagnosed Derf sensitization and 15 patients not allergic to Derf were enrolled; another 4 healthy children were taken as control group. Using Derf extracts in concentration of 1, 10μg/mL and 100μg/mL as the stimulus, BAT results were expressed as %CD63+ in diagnosis of Derf sensitization and its correlation with skin prick tests (SPT), serum total IgE (tIgE), specific IgE (sIgE), sIgE/tIgE, specific IgG4 (sIgG4), FEV1%pred in pulmonary ventilation function, exhaled nitric oxide (FeNO), children asthma control test (C-ACT) and visual analogue scale (VAS) were observed. In sensitization group, %CD63+ , sIgG4 and clinical indicators were detected again from patients who had received SCIT to analyse their internal connections. The average levels of %CD63+ in 3 concentrations showed an increasing concentration-dependent trend overall. %CD63+ in sensitization group was significantly higher than that in the other 2 groups. The analysis of ROC for Derf sensitization showed the area under the curve (AUC) for BAT in 3 concentrations was higher than that for sIgE whose AUC is 0.893. %CD63+ was positively correlated with SPT grade, sIgE, sIgE/tIgE and VAS, and negatively correlated with C-ACT. In patients receiving SCIT, %CD63+ became lower and sIgG4 level became higher than pretreatment. There was no obvious change in sIgG4 in those who had not received SCIT. BAT is a reliable and non-invasive tool for diagnosis of Derf sensitization in children with asthma and rhinitis. CD63-based BAT has clinical value to monitor outcome of SCIT, and the change in basophil activation is inherently related to induction of sIgG4.

Effects of exposure to ambient ultrafine particles on respiratory health and systemic inflammation in children

It is known that ultrafine particles (UFP, particles smaller than 0.1 μm) can penetrate deep into the lungs and potentially have adverse health effects. However, epidemiological data on the health effects of UFP is limited. Therefore, our objective was to test the hypothesis that exposure to UFPs is associated with respiratory health status and systemic inflammation among children aged 8 to 11 years.We conducted a cross-sectional study among 655 children (43.3% male) attending 25 primary (elementary) schools in the Brisbane Metropolitan Area, Australia. Ultrafine particle number concentration (PNC) was measured at each school and modelled at homes using Land Use Regression to derive exposure estimates. Health outcomes were respiratory symptoms and diagnoses, measured by parent-completed questionnaire, spirometric lung function, exhaled nitric oxide (FeNO), and serum C reactive protein (CRP). Exposure-response models, adjusted for potential personal and environmental confounders measured at the individual, home and school level, were fitted using Bayesian methods.PNC was not independently associated with respiratory symptoms, asthma diagnosis or spirometric lung function. However, PNC was positively associated with an increase in CRP (1.188-fold change per 1000 UFP cm−3 day/day (95% credible interval 1.077 to 1.299)) and an increase in FeNO among atopic participants (1.054 fold change per 1000 UFP cm−3 day/day (95% CrI 1.005 to 1.106)).UFPs do not affect respiratory health outcomes in children but do have systemic effects, detected here in the form of a positive association with a biomarker for systemic inflammation. This is consistent with the known propensity of UFPs to penetrate deep into the lung and circulatory system.

Menopausal asthma–much ado about nothing? An observational study

ABSTRACTObjective: Menopausal asthma is considered a distinct asthma phenotype. Our aim was to identify potential specific features of asthma in postmenopausal women in a cohort of Polish females. Methods: Asthma severity and control, pulmonary function, exhaled nitric oxide (FENO), peripheral blood and induced sputum (IS) differential cell count were compared in three groups: women with premenopausal asthma (group 1), menopausal women with pre-existing asthma (group 2A) and menopausal women with asthma onset in the perimenopausal or menopausal period (group 2B). Results: We enrolled 27 women to group 1, 13 to group 2A and 16 to group 2B. Asthma severity and control, blood eosinophil count and FENO did not differ among the groups. Menopausal women had a higher incidence of irreversible airway obstruction (84.6% in group 2A and 56.2% in group 2B vs. 22.2% in group 1, p < 0.001 and p = 0.03, respectively). The proportion of patients with sputum eosinophilia was highest in menopausal women with pre-existing asthma, although the difference did not reach statistical significance (88.9% in group 2A vs. 66.7% in group 2B and 65.0% in group 1, respectively, p = 0.86). Conclusions: Menopausal women with asthma are characterized by an increased incidence of irreversible airway obstruction regardless of disease duration. This may indicate that age may contribute to pulmonary function impairment in asthmatic women independently of their hormonal status at the time of asthma diagnosis. Our results failed to confirm the presence of specific asthma features which would allow to distinguish the phenotype of menopausal asthma.

Clinical Efficacy and Immunologic Effects of Omalizumab in Allergic Bronchopulmonary Aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. Omalizumab is a humanized anti-IgE monoclonal antibody currently used to treat severe asthma. The aim was to assess the clinical and immunologic effects of omalizumab in ABPA in a randomized, placebo-controlled trial. Patients with chronic ABPA were randomized to 4-month treatment with omalizumab (750 mg monthly) or placebo followed by a 3-month washout period in a cross-over design. The main endpoint was number of exacerbations. Other clinical endpoints included lung function, exhaled nitric oxide (FeNO), quality of life and symptoms. Invitro basophil activation to Aspergillus fumigatus extract and basophil FcεR1 and surface-bound IgE levels were assessed by flow cytometry. Thirteen patients were recruited with mean total IgE 2314 ± 2125 IU/mL. Exacerbations occurred less frequently during the active treatment phase compared with the placebo period (2 vs 12 events, P= .048). Mean FeNO decreased from 30.5 to 17.1 ppb during omalizumab treatment (P= .03). Basophil sensitivity to A.fumigatus and surface-bound IgE and FcεR1 levels decreased significantly after omalizumab but not after placebo. Omalizumab can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to A.fumigatus and FcεR1 and surface-bound IgE levels.

Asthma severity in childhood, untangling clinical phenotypes*

Assessment of childhood asthma severity and asthma control encompasses heterogeneous clinical presentations. The relationship between patterns of asthma symptoms and objective measurements is poorly defined in paediatric asthma. This study includes 115 asthmatic schoolchildren, of which 31 were at inclusion defined as Problematic severe asthma because of inadequate asthma control in the presence of high-dose inhaled corticosteroid (HD-ICS) treatment and at least one other asthma controller drug. Two partially overlapping clinical outcomes were defined irrespective of severity classification (Exacerbations and Chronic persistent asthma) in patients with uncontrolled asthma. The same symptom criteria were used as for Problematic severe asthma, but disregarding current medication. Lung function, exhaled nitric oxide (FE(NO)), bronchial hyperresponsiveness, allergic sensitization and Quality of life (QoL) in the symptom subgroups were compared to children with well-controlled asthma. Multifactor analysis was performed to assess the relative explanatory power of clinical asthma presentations and of HD-ICS treatment on objective measurements. Whereas children included in the Exacerbations subgroup had objective features similar to patients with well-controlled asthma, the Chronic persistent asthma subgroup demonstrated significantly reduced lung function, increased immunoglobin E, allergic poly-sensitization and impaired QoL, similar to that in patients pre-defined as Problematic severe asthma. The presence of chronic asthma symptoms was a significant explanatory factor for reduced lung function, QoL and increased FE(NO) in multifactor analysis. Differences in objective measurements suggest that children with Chronic persistent asthma and those who are symptomatic predominantly during exacerbations may represent distinct phenotypes of childhood asthma with different clinical prognoses.