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.

Impaired GH secretion in patients with SHOX deficiency and efficacy of recombinant human GH therapy.

BACKGROUND/AIMS: Mutations of the short stature homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency. PATIENTS AND DESIGN: We studied 16 patients (10 females; 9.7 ± 2.9 years old; height -2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 ± 0.053 mg/kg/week). RESULTS: Impaired GH secretion was present in 37.5% of the studied subjects. Comparing baseline data with those at the last visit, we found that rhGH treatment improved growth velocity SDS (from -1.03 ± 1.44 to 2.77 ± 1.95; p = 0.001), height SDS (from -2.41 ± 0.71 to -1.81 ± 0.87; p < 0.001), and IGF-1 values (from -0.57 ± 1.23 to 0.63 ± 1.63 SDS, p = 0.010) without affecting body mass index SDS. Height SDS measured at the last visit was significantly correlated with chronological age (r = -0.618, p = 0.032), bone age (r = -0.582, p = 0.047) and height SDS (r = 0.938, p < 0.001) at the beginning of treatment. No adverse events were reported on rhGH therapy which was never discontinued. CONCLUSION: These data showed that impaired GH secretion is not uncommon in SHOX deficiency subjects, and that rhGH therapy may be effective in increasing height in most of these patients independent of their GH secretory status, without causing any adverse events of concern.

[Control of asthma symptoms and cellular markers of inflammation in induced sputum in children and adolescents with chronic asthma]. / Ocena klinicznej kontroli astmy oraz komórkowych markerów zapalenia w plwocinie indukowanej u dzieci i mlodziezy chorych na przewlektla astme.

UNLABELLED: After the GINA 2006 publication, asthma therapy is based on control of symptoms. However there are suggestions of monitoring of airway inflammation. Aim of the study was to compare clinical criteria of asthma control with cellular markers of lower airway inflammation in induced sputum in a group of young asthmatics. To assess relationship between sputum eosinophilia, asthma severity and spirometry. MATERIAL AND METHODS: A group of 154 young patients with chronic asthma (8-21 years) underwent sputum induction by inhalation of 4,5% saline solution. Sputum induction was effective in 121 patients (78%), and in this group control of clinical symptoms was assessed according to GINA 2006 criteria. RESULTS: Asthma was controlled in 82 subjects (67.8%) and uncontrolled in 39 (32.2%). Patients with controlled asthma had higher FEV1/FVC (79.8 +/- 7.1% vs 74.2 +/- 9.9%; p = 0.004) and MMEF (80.7 +/- 23.0% vs 65.3 +/- 21.8%; p < 0.001) than those with uncontrolled disease, but the average FEV1 (as percent predicted) did not differ between the two groups. Patients with controlled asthma had lower sputum eosinophil count than those with uncontrolled asthma (3.5 +/- 6.3% vs 7.2 +/- 8.7%; p = 0.01), but difference in neutrophil count was borderline (27.3 +/- 15.5% vs 34.5 +/- 21.0%; p = 0.05). High sputum eosinophil count (> 3%) was observed in 24.4% of patients with controlled asthma and in 61.5% with uncontrolled asthma (p < 0.001). Increased sputum neutrophil count was more frequent in a group of uncontrolled asthma (2.4 vs 15.4%; p = 0.022). Mean sputum eosinophil count was lower in patients with mild astma than in patients with moderate-severe disease (3.1 +/- 5.7% vs 7.1% +/- 8.8; p = 0.006). Patients with high sputum eosinophil count had lower FEV1 (89.4 +/- 14.9% vs 94.9 +/- 13.9%; p = 0.047), FEV1/FVC (74.5 +/- 10.1% vs 79.2 +/- 9.3%; p = 0.01) and MMEF (68.7 +/- 23.3% vs 81.7 +/- 23.1%; p = 0.004). CONCLUSIONS: In this study of young asthmatics, control of asthma symptoms was observed in 67.8% of patients. However, cellular markers of lower airway inflammation were present in 1/4 of patients with controlled asthma and in 3/4 with uncontrolled disease. Sputum eosinophilia was related to asthma severity. FEV1/FVC and MMEF were more important that FEV1 for estimating control of asthma. Improvement of asthma control scoring is needed as well as availability of simple methods of inflammation monitoring.