Effect of pulmonary rehabilitation in an allergen safe outdoor environment on children and adolescents with mild to moderate persistent allergic asthma.

BACKGROUND: Environmental interactions are very complex in childhood asthma, and we hypothesized that even a short-term exposure to an allergy safe outdoor environment (AllSOE) combined with pulmonary rehabilitation program (PRP) could exert significant beneficial effects. Our aim was to test the effects of 2-week PRP provided in an AllSOE in children with mild to moderate asthma. METHODS: 110 children (aged 7.5-17 years, 46% girls), with partially or totally controlled asthma, attended the PRP at the Island of Losinj (Croatia) supervised by a multidisciplinary team (pediatric pulmonologist, sports medicine specialist, physiotherapist and kinesiologist). Each child had an adjusted intensity of physical activity with at least 2 h of exercise per day. Body height and weight, spirometry, fraction of exhaled nitric oxide (FeNO), running distance during free running test (FRT) and the decline in lung function after FRT (exercise-induced bronchoconstriction- EIB) were measured at baseline and after PRP. RESULTS: A significant improvement in running distance (from 903 ± 272 m to 968 ± 289 m; p < 0.001), a decrease of FeNO (from 37 ± 32 ppb to 25 ± 17 ppb; p < 0.001) were determined after PRP. There were no significant changes in lung function and EIB, except EIB in the fourth quartile (significant EIB at baseline) where EIB significantly decreased (p < 0.001) after PRP. CONCLUSION: Two weeks of PRP in an AllSOE significantly improved exercise capacity and reduced airway inflammation and airway hyperreactivity showing that even a short-term PRP within a proper environment could be effective and affordable management strategy for children and adolescents with mild to moderate asthma.

Eight weeks of omeprazole 20 mg significantly reduces both laryngopharyngeal reflux and comorbid chronic rhinosinusitis signs and symptoms: Randomised, double-blind, placebo-controlled trial.

OBJECTIVES: Gastroesophageal reflux recommended treatment (dose and duration) with proton-pump inhibitor (PPI) compared to placebo significantly reduces the signs and symptoms of laryngopharyngeal reflux (LPR) and comorbid chronic rhinosinusitis (CRS). DESIGN: Double-blind randomised placebo-controlled trial. SETTING: Eight weeks of treatment with omeprazole 20 mg once daily (OD). PARTICIPANTS: Sixty patients (28 women, aged 19-87 years) with diagnosed LPR and comorbid CRS. MAIN OUTCOME MEASURES: Significant reduction in signs and symptoms (reflux symptom index (RSI) score as subjective, and reflux finding score (RFS) as objective measure) of LPR after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo. Secondary objectives were significant reduction in signs and symptoms of comorbid CRS after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo and the association of the severity of signs and symptoms of LPR with the ones of CRS. RESULTS: RSI and RFS decreased significantly more in the active treatment group after 8 weeks compared to placebo (P < .001 for both). CRS and endoscopy scoring decreased both significantly more in the active group after 8 weeks compared to placebo (P < .001 for both). CRS scoring significantly correlated with RSI (R = 0.312, P = .015) but not with RFS (R = 0.199, P = .127). CONCLUSIONS: The results of our trial suggest that omeprazole 20 mg OD for 8 weeks was effective in reducing signs and symptoms of both LPR and CRS, although in most patients still present at the end of the trial.

Diagnostic value of a pattern of exhaled breath condensate biomarkers in asthmatic children

BACKGROUND: Diagnosing asthma in children is a challenge and using a single biomarker from exhaled breath condensate (EBC) showed the lack of improvement in it. OBJECTIVE: The aim of this study was to assess the diagnostic potential of a pattern of simple chemical biomarkers from EBC in diagnosing asthma in children in a real-life setting, its association with lung function and gastroesophageal reflux disease (GERD). METHODS: In 75 consecutive children aged 5-7 years with asthma-like symptoms the following tests were performed: skin prick tests, spirometry, impulse oscillometry (IOS), exhaled NO (FENO), 24-hour oesophageal pH monitoring and EBC collection with subsequent analysis of pH, carbon dioxide tension, oxygen tension, and concentrations of magnesium, calcium, iron and urates. RESULTS: No significant differences were found for individual EBC biomarkers between asthmatics and non-asthmatics (p > 0.05 for all). A pattern of six EBC biomarkers showed a statistically significant (p = 0.046) predictive model for asthma (AUC = 0.698, PPV = 84.2%, NPV = 38.9%). None to moderate association (R2 up to 0.43) between EBC biomarkers and lung function measures and FENO was found, with IOS parameters showing the best association with EBC biomarkers. A significantly higher EBC Fe was found in children with asthma and GERD compared to asthmatics without GERD (p = 0.049). CONCLUSIONS: An approach that involves a pattern of EBC biomarkers had a better diagnostic accuracy for asthma in children in real-life settings compared to a single one. Poor to moderate association of EBC biomarkers with lung function suggests a complementary value of EBC analysis for asthma diagnosis in children

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Diagnostic value of a pattern of exhaled breath condensate biomarkers in asthmatic children.

BACKGROUND: Diagnosing asthma in children is a challenge and using a single biomarker from exhaled breath condensate (EBC) showed the lack of improvement in it. OBJECTIVE: The aim of this study was to assess the diagnostic potential of a pattern of simple chemical biomarkers from EBC in diagnosing asthma in children in a real-life setting, its association with lung function and gastroesophageal reflux disease (GERD). METHODS: In 75 consecutive children aged 5-7 years with asthma-like symptoms the following tests were performed: skin prick tests, spirometry, impulse oscillometry (IOS), exhaled NO (FENO), 24-hour oesophageal pH monitoring and EBC collection with subsequent analysis of pH, carbon dioxide tension, oxygen tension, and concentrations of magnesium, calcium, iron and urates. RESULTS: No significant differences were found for individual EBC biomarkers between asthmatics and non-asthmatics (p>0.05 for all). A pattern of six EBC biomarkers showed a statistically significant (p=0.046) predictive model for asthma (AUC=0.698, PPV=84.2%, NPV=38.9%). None to moderate association (R2 up to 0.43) between EBC biomarkers and lung function measures and FENO was found, with IOS parameters showing the best association with EBC biomarkers. A significantly higher EBC Fe was found in children with asthma and GERD compared to asthmatics without GERD (p=0.049). CONCLUSIONS: An approach that involves a pattern of EBC biomarkers had a better diagnostic accuracy for asthma in children in real-life settings compared to a single one. Poor to moderate association of EBC biomarkers with lung function suggests a complementary value of EBC analysis for asthma diagnosis in children.

Prevalence of and risk factors for the development of atopic dermatitis in schoolchildren aged 12-14 in northwest Croatia

BACKGROUND: Atopic dermatitis is a common allergic disorder. A multifactorial background for atopic dermatitis has been suggested, with genetic as well as environmental factors influencing disease development. Our aim was to estimate the prevalence rate and associated factors for atopic dermatitis in northern Croatia using the methods of the internationally standardised ISAAC protocol. METHODS: The study was undertaken among 12-14-year-old schoolchildren. Data were collected using standardised ISAAC written questionnaire Phase One and some selected questions from the ISAAC supplementary questionnaire completed by parents. RESULTS: A total of 2887 children participated in the study. Estimated lifetime (ever) prevalence rate of atopic dermatitis symptoms was 7.55% and estimated 12-month prevalence rate was 5.75%. The factors found to be associated to the symptoms of atopic dermatitis ever were: positive family atopy, female gender, sleeping on feather pillow and contact with pets after age of seven, and to the symptoms in the past 12 months were: positive family atopy, female gender, sleeping on feather pillow, parasite infestation, and contact with pets in the first year of life. CONCLUSIONS: The results of our study show that northern Croatia is a region with moderate prevalence rates of atopic dermatitis. Following risk factors were family atopy, female gender and sleeping on feather pillow. Because of controversial results of previous studies conducted on the same topic further investigations should be made

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Prevalence of and risk factors for the development of atopic dermatitis in schoolchildren aged 12-14 in northwest Croatia.

BACKGROUND: Atopic dermatitis is a common allergic disorder. A multifactorial background for atopic dermatitis has been suggested, with genetic as well as environmental factors influencing disease development. Our aim was to estimate the prevalence rate and associated factors for atopic dermatitis in northern Croatia using the methods of the internationally standardised ISAAC protocol. METHODS: The study was undertaken among 12-14-year-old schoolchildren. Data were collected using standardised ISAAC written questionnaire Phase One and some selected questions from the ISAAC supplementary questionnaire completed by parents. RESULTS: A total of 2887 children participated in the study. Estimated lifetime (ever) prevalence rate of atopic dermatitis symptoms was 7.55% and estimated 12-month prevalence rate was 5.75%. The factors found to be associated to the symptoms of atopic dermatitis ever were: positive family atopy, female gender, sleeping on feather pillow and contact with pets after age of seven, and to the symptoms in the past 12 months were: positive family atopy, female gender, sleeping on feather pillow, parasite infestation, and contact with pets in the first year of life. CONCLUSIONS: The results of our study show that northern Croatia is a region with moderate prevalence rates of atopic dermatitis. Following risk factors were family atopy, female gender and sleeping on feather pillow. Because of controversial results of previous studies conducted on the same topic further investigations should be made.

Markers of systemic and lung inflammation in childhood asthma.

AIM: To compare different biomarkers of inflammation in children with controlled and uncontrolled asthma and to investigate their relationship with other clinical indices of asthma control (symptoms, lung function, serum IgE, and prn beta-agonist use). MATERIALS AND METHODS: A total of 62 consecutive asthmatic children (age 11 +/- 3.3 years, 32 girls) with controlled ([C], n = 19) and uncontrolled asthma ([NC], n = 43) were studied. Measured lung function and inflammatory biomarkers included: spirometry, exhaled NO (F(E)NO), high-sensitivity C-reactive protein (hs-CRP), peripheral blood white blood cells (WBC) counts, and differentials. RESULTS: Hs-CRP was significantly higher in uncontrolled than in controlled asthma (hs-CRP, median [IQR], mg/L; 0.56 [0.60] vs 0.25 [0.34], p = 0.008). Discriminant analysis (backward stepwise) depicted hs-CRP and lymphocytes (as Z-score for absolute count) as significant discriminative factors for asthma control (F = 8.319, p = 0.0007) with 82.3% diagnostic accuracy. Divided into quartiles hs-CRP showed the significant inverse association with F(E)NO (F = 7.359, p = 0.003, ANOVA) with no significant difference for asthma control (F = 1.032, p = 0.386). Post-hoc analysis revealed that F(E)NO values were significantly lower in the third and the fourth quartile of hs-CRP in comparison to the first and the second one (p < 0.05 for all). CONCLUSION: In asthmatic children with uncontrolled asthma serum hs-CRP was increased compared to children with controlled asthma. Although F(E)NO values were also increased (insignificantly) and inversely correlated with hs-CRP they were probably reflecting different etiology underlying the loss of control. The role of peripheral blood biomarkers in asthmatics is still poorly investigated so new studies are required.

Iron and ferritin concentrations in exhaled breath condensate of children with asthma.

Maintenance of iron homeostasis is of utmost importance for the respiratory system physiology and pathophysiology. Local iron deficiency or accumulation may result in particular respiratory function impairment. The aim of the present study was to find out whether iron and ferritin could be determined in exhaled breath condensate (EBC) of healthy children and children with asthma. Oxidative stress was verified by determination of EBC superoxide dismutase (SOD) activity, and the airway inflammatory process by determination of exhaled nitric oxide (F(E)NO). EBC was collected from 39 children (22 healthy children as a control group and 17 asthmatics) using an EcoScreen condenser. Iron, ferritin, and SOD were determined on optimization and validation for low concentrations. In comparison with a control group, asthma patients had a statistically significantly lower iron concentration (p = 0.0001) and higher SOD catalytic activity (p = 0.0160), with no significant difference in ferritin levels (p = 0.5252), although percentile values indicated elevated ferritin concentration in about half of asthma patients. F(E)NO values were significantly higher in the asthma group (p = 0.0047). This preliminary study demonstrated the possibility of determining iron and ferritin concentrations and SOD activity in EBC, and a significant difference in EBC iron and SOD between asthma patients and healthy children.

Allergen inhalation challenge induces decrease of serum neutral endopeptidase (NEP) in asthmatics.

There is accumulating evidence that tachykinins are implicated in inflammation, including asthma. Therefore, we hypothesized that the neutral endopeptidase (NEP), under challenge conditions, could be affected. Serum from 21 asthmatics and six healthy volunteers was sampled before, 30, and 120 min after allergen challenge. NEP-IR was determined using an ELISA and was found in all subjects. Compared to prechallenge, no difference was seen between asthmatics and controls; however, under challenge conditions, NEP-IR in asthmatics was significantly lower (30 min, P = 0.058; 120 min, P = 0.0017, respectively). This finding supports indirectly the hypothesis that tachykinins are released during allergen exposure, and suggests a regulatory role of NEP.

Decrease in CD23+ B lymphocytes and clinical outcome in asthmatic patients receiving specific rush immunotherapy.

Rush immunotherapy (RIT) has been documented as useful in the treatment of patients with allergic bronchial asthma. To investigate the mechanisms of its action, we studied changes in the serum levels of total IgE, allergen-specific IgE and IgG4, and expression of CD23 on peripheral blood B cells in patients receiving RIT. Twenty patients with perennial bronchial asthma were evaluated before the beginning of RIT, as well as 6 weeks and 6 months later. Compared to pretreatment values, the level of Der-p-specific IgG4 and IgE significantly increased after 6 weeks and 6 months of RIT, while the total serum IgE remained unchanged. Furthermore, after 6 months of RIT, the percentage of CD23+B cells and its CD23 receptor density significantly decreased. Since the symptom score improved and the need for medication decreased, we evaluated RIT as a useful procedure. After 6 months, 30% of patients did not have an asthma attack, with no medication in the last month, while 10% of them were asthma free for the last 3 months. No significant correlation between the clinical improvement, and in vitro changes was found. Furthermore, the observed in vitro changes were not significantly different in patients who responded with clinical improvement, compared to those with unchanged intensity of asthma. In conclusion, during specific RIT we found a significant increase in Der-p-specific IgE and IgG4 antibodies, as well as a moderate decrease in CD23+ B cells and its CD23 receptor density. These findings suggest a change in the lymphokine profile of patients receiving specific immunotherapy, and that the inhibition of IL-4-induced B cell stimulation may be hypothesized as the most important mechanism.