Childhood asthma treatment based on indirect hyperresponsiveness test: Randomized controlled trial.

PURPOSE: The purpose of this study was to assess the usefulness of indirect airway hyperresponsiveness (AHR) test using hypertonic saline in determining the dose of inhaled corticosteroids (ICS) to maintain asthma control in children. METHODS: A group of 104 patients (7-15 years) with mild-moderate atopic asthma were monitored for their asthma control and treatment for 1 year. Patients were randomly assigned to a symptom-only monitored group and a group with therapy changes based on the symptoms and severity of AHR. Spirometry, exhaled nitric oxide, and blood eosinophils (BEos) were assessed on enrollment and every 3 months thereafter. RESULTS: During the study period, the number of mild exacerbations was lower in the AHR group (44 vs. 85; the absolute rate per patient 0.83 vs. 1.67; relative rate 0.49, 95% confidence interval: 0.346-0.717 (p < 0.001)]. Mean changes from baseline in clinical (except asthma control test), inflammatory, and lung function parameters were similar between groups. Baseline BEos correlated with AHR and was a risk factor for recurrent exacerbation in all patients. There was no significant difference in the final ICS dose between AHR and symptoms group: 287 (SD 255) vs. 243 (158) p = 0.092. CONCLUSIONS: Adding an indirect AHR test to clinical monitoring of childhood asthma reduced the number of mild exacerbations, with similar current clinical control and final ICS dose as in the symptom-monitored group. The hypertonic saline test appears to be a simple, cheap, and safe tool for monitoring the treatment of mild-to-moderate asthma in children.

Eosinophilic airway inflammation is a main feature of unstable asthma in adolescents.

BACKGROUND: Stability of asthma is a clinical phenotype of the disease based on long-term evaluation of control of asthma symptoms and its exacerbations. A relationship between airway inflammation and clinical classification of asthma based on stability criterion has not been well studied. OBJECTIVES: The purpose of our study was to analyze the inflammation profile of stable and unstable asthma in adolescents treated with moderate and high doses of inhaled corticosteroids. METHODS: 139 young asthmatics of 16.8 (3.25) years were classified in the stable group (N = 72) and unstable group (N = 67) after a 3-month prospective observation. Inflammatory markers including cytogram of the induced sputum (IS), fractional exhaled nitric oxide (FeNO) and bronchial hyperresponsiveness (BHR) following provocation with hypertonic saline and exercises, as well as clinical and spirometric parameters in both groups were compared. RESULTS: 75% of patients with unstable asthma revealed elevated percentage of eosinophils in the induced sputum (>2.5%), and mean values were significantly higher in comparison with stable asthma: 2.0 (0,5-4,2) vs 5,5 (2,6-11,3), p < 0,001. Bronchial hyperresponsiveness was markedly higher in unstable asthma, especially in asthma with eosinophilic profile; statistically significant differences also related to functional pulmonary tests. In multivariate analysis, asthma instability was significantly associated with sEos (p = 0.005), BHR (p = 0.001) but not FeNO (p = 0.24). CONCLUSION (AND CLINICAL RELEVANCE): Eosinophilic inflammation, relatively resistant to high doses of inhaled corticosteroids, is a dominant type of inflammation in unstable asthma in adolescents. Asthma instability is also associated with higher bronchial hyperresponsiveness and lower spirometric parameters. In the light of the new studies and progress in biological methods of therapy of eosinophilic inflammation, unstable asthma, especially in case of severe course, requires extended diagnostics with determination of inflammatory phenotype.

Inflammatory markers as exacerbation risk factors after asthma therapy switch from inhaled steroids to montelukast.

BACKGROUND: Asthma guidelines allow anti-leukotriene medications to be used as an alternative to inhaled corticosteroids (ICS) in second-step intensity therapy. The aim of the study was to analyze the risk factors of exacerbations, particularly inflammatory markers, during the 12-month period following therapy reduction from an ICS to montelukast in young patients with mild asthma. METHODS: A total of 84 patients (aged 7-18 years old) with mild asthma controlled by low-dose ICS, had their treatment switched to montelukast. Exhaled nitric oxide (eNO), sputum eosinophils (sEos), and bronchial hyperreactivity (BHR) were assessed at the beginning and then every three months throughout the one-year period. The patients with asthma exacerbations (first severe or third mild) were discontinued from the study. RESULTS: Over the study period, 22 patients (26%) discontinued montelukast due to asthma exacerbations. An increased risk of exacerbations was noted among patients with initial sEos above 2.5% (relative risk, RR 36.6; 95% CI: 7.1-189.3; p < 0.001), as well as those with augmented BHR (RR 9.5; 2.8-31.6; p < 0.001), or eNO greater than 20 ppb (RR 3.7; 95% CI: 1.3-10.7; p = 0.013). An increase in BHR and eNO was observed during the last visit before exclusion. CONCLUSIONS: After switching treatment from a low-dose ICS, montelukast maintained control of asthma symptoms in 75% of patients. High sEos before the treatment change was the strongest exacerbation risk factor. In patients with asthma controlled by low-dose ICS and low inflammatory markers, treatment could be safely switched to montelukast.