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What is known and objective Calciphylaxis is a rare and potentially life-threatening cause of skin necrosis and is poorly recognized by clinicians in non-uraemic patients. Case description We report five cases of warfarin-induced calciphylaxis in patients with normal renal function. In four cases, sodium thiosulphate was successfully used as a treatment. No other predisposing factors besides obesity and warfarin were found in these patients. What is new and conclusion Previously only few cases of solely warfarin-induced calciphylaxis have been described. Treatment with sodium thiosulphate has shown promising results, and there is thus a need to improve the recognition of calciphylaxis. [ABSTRACT FROM AUTHOR]

Although clinical drug trials are indispensable in providing an appropriate background for dosage recommendations, they can provide mechanistic pharmacokinetic information only indirectly with the help of certain biomarkers for pathological, physiological and pharmacological determinants. Thus, to provide such mechanistic information of clinical value, various in vitro and in silico tests and approaches are increasingly employed in drug discovery and development. Integration of the results of these primarily preclinical studies has been made possible by various computational models, such as in vitro-in vivo extrapolation of hepatic clearance or physiologically based pharmacokinetic modelling. In this article, the current status of these modelling approaches is surveyed and some examples are given, highlighting advantages and disadvantages in applying them at various phases of drug development. A new paradigm of model-based drug development is briefly described, and the importance of the approach of integrating all of the information coming from different investigations at all levels--be it in vivo, in vitro or in silico--is emphasized. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and INTERVENTIONS: 176 children aged 5-10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 microg twice daily for 1 month, 200 microg twice daily for months 2-6, 100 microg twice daily for months 7-18); (2) budesonide, identical treatment to group 1 during months 1-6, then budesonide for exacerbations as needed for months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1-18. Exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. MAIN OUTCOME MEASURES: Lung function, the number of exacerbations and growth. RESULTS: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7-18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. CONCLUSIONS: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and interventions: 176 children aged 5-10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 μg twice daily for 1 month, 200 μg twice daily for months 2-6, 100 μg twice daily for months 7-18); (2) budesonide, identical treatment to group 1 during months 1-6, then budesonide for exacerbations as needed for months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1-18. Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks. Main outcome measures: Lung function, the number of exacerbations and growth. Results: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7-18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. Conclusions: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment. [ABSTRACT FROM AUTHOR]

One major challenge in drug development is defining of the optimal animal species to serve as a model of metabolism in man. The study compared the hepatic drug metabolism characteristics of humans and six widely used experimental animal species. Classical in vitro model enzyme assays with known human cytochrome P450 (CYP) enzyme selectivity were employed and optimized to target human hepatic CYP forms. The profile of CYP activities best resembling the human was seen in mouse followed by monkey, minipig, and dog liver microsomes, with rats displaying the most divergent. The widest interindividual variability was found in CYP3A-mediated midazolam α-hydroxylase, and omeprazole sulphoxidase activities in human and monkey liver microsomes. These data demonstrate that if hepatic xenobiotic-metabolizing characteristics were to be the sole reason for the selection of animal species for toxicity studies, then the rat might not be the most appropriate model to mimic human CYP activity patterns. [ABSTRACT FROM AUTHOR]

Although the measurement of metabolite formation or substrate depletion in in vitro systems, from recombinant enzymes to tissue slices, is a relatively routine task, there are a number of more or less unresolved issues in the extrapolation of the enzymatic intrinsic clearance into hepatic metabolic clearance. Nominal concentrations of the drug added to the incubation system are not necessarily the concentration the transporter or the metabolizing enzyme sees. In addition, peculiarities of incubation set-ups should be assessed. Unbound drug fractions (concentrations) in the in vitro system itself should be measured or estimated for the appropriate assessment of enzymatic intrinsic clearance. In addition, blood and/or plasma concentrations to be encountered in the in vivo situation should be measured or estimated for the extrapolation. Extrapolation always means making a number of assumptions and the most important of these, such as scaling factors from recombinant enzymes, microsomes or hepatocytes to the mass unit of the liver, liver weight, blood flow, and distribution volume amongst others, and so on, should be explicitly stated and included in the extrapolation process. Despite all the above-mentioned reservations the in vitro-in vivo extrapolation of metabolic clearance seems to be a useful and mostly fairly precise tool for predicting the important pharmacokinetic processes of a drug. [ABSTRACT FROM AUTHOR]

Background and purpose:The cytochrome P450 2B6 (CYP2B6) enzyme metabolises a number of clinically important drugs. Drug-drug interactions resulting from inhibition or induction of CYP2B6 activity may cause serious adverse effects. The aims of this study were to construct a three-dimensional structure-activity relationship (3D-QSAR) model of the CYP2B6 protein and to identify novel potent and selective inhibitors of CYP2B6 for in vitro research purposes.Experimental approach:The inhibition potencies (IC50 values) of structurally diverse chemicals were determined with recombinant human CYP2B6 enzyme. Two successive models were constructed using Comparative Molecular Field Analysis (CoMFA).Key results:Three compounds proved to be very potent and selective competitive inhibitors of CYP2B6 in vitro (IC50<1 μM): 4-(4-chlorobenzyl)pyridine (CBP), 4-(4-nitrobenzyl)pyridine (NBP), and 4-benzylpyridine (BP). A complete inhibition of CYP2B6 activity was achieved with 0.1 μM CBP, whereas other CYP-related activities were not affected. Forty-one compounds were selected for further testing and construction of the final CoMFA model. The created CoMFA model was of high quality and predicted accurately the inhibition potency of a test set (n=7) of structurally diverse compounds.Conclusions and implications:Two CoMFA models were created which revealed the key molecular characteristics of inhibitors of the CYP2B6 enzyme. The final model accurately predicted the inhibitory potencies of several structurally unrelated compounds. CBP, BP and NBP were identified as novel potent and selective inhibitors of CYP2B6 and CBP especially is a suitable inhibitor for in vitro screening studies.British Journal of Pharmacology (2007) 150, 932–942. doi:10.1038/sj.bjp.0707173; published online 26 February 2007 [ABSTRACT FROM AUTHOR]

Background there is increasing consensus about the significance of food allergens in the pathogenesis of atopic dermatitis (AD) in infancy and childhood, with cow's milk and egg accounting for most of the reactions. Previous studies have indicated that multiple food sensitization, such as cereals, is very common in patients with cow's milk allergy (CMA). Evidence is lacking, however, as to its clinical relevance. Objective The purpose of this study was to determine the concurrent occurrence of cereal allergy among children with challenge-proven CMA who have residual symptoms, such as AD and/or gastrointestinal symptoms, during cow's milk elimination diet. Further, we sought to evaluate the utility of patch testing in prescreening foods other than cow's milk behind allergic symptoms in children. Methods the study population comprised 90 children, aged from 2.5 to 36 months (mean 1.1 years), with challenge-proven CMA. As a result of residual symptoms during meticulous cow's milk elimination diet (AD: n = 80, and gastrointestinal: n = 10), the children were put on a cereal elimination diet (oats, wheat, rye, and barley) and skin prick tests (SPT) and patch testing with cereals were performed. Open cereal challenge was performed to confirm cereal allergy. Results Cereal challenge was positive in 66 (73%) of the children with CMA. Of them, 17% reacted with immediate reactions and delayed-onset reactions were seen in 83% of the children. SPT was positive in 23%, patch test in 67%, and either SPT or patch test was positive in 73% of the children with cereal allergy. SPT gave the best positive predictive value, whereas SPT together with patch test gave the best negative predictive value. Conclusions Residual symptoms, such as eczema or gastrointestinal symptoms in CMA children may be a sign of undetected allergy to other food antigens. SPT with cereals aids in diagnosing cereal allergy in small children, especially when used together with patch testing. [ABSTRACT FROM AUTHOR]

Purpose: Although medication-related adverse events (MRAEs) in health care are vastly studied, high heterogeneity in study results complicates the interpretations of the current situation. The main objective of this study was to form an up-to-date overview of the current knowledge of the prevalence, risk factors, and surveillance of MRAEs in health care. Methods: Electronic databases (PubMed, MEDLINE, Web of Science, and Scopus) were searched with applicable search terms to collect information on medication-related adverse events. In order to obtain an up-to-date view of MRAEs, only studies published after 2000 were accepted. Results: The prevalence rates of different MRAEs vary greatly between individual studies and meta-analyses. Study setting, patient population, and detection methods play an important role in determining detection rates, which should be regarded while interpreting the results. Medication-related adverse events are more common in elderly patients and patients with lowered liver or kidney function, polypharmacy, and a large number of additional comorbidities. However, the risk of MRAEs is also significantly increased by the use of high-risk medicines but also in certain care situations. Preventing MRAEs is important as it will decrease patient mortality and morbidity but also reduce costs and functional challenges related to them. Conclusions: Medication-related adverse events are highly common and have both immediate and long-term effects to patients and healthcare systems worldwide. Conclusive solutions for prevention of all medication-related harm are impossible to create. In the future, however, the development of efficient real-time detection methods can provide significant improvements for event prevention and forecasting. [ABSTRACT FROM AUTHOR]

The article focuses on the unaffected peak inspiratory flow (PIF) through the turbuhaler (TBH) in a histamine inhalation challenge test. It states that the multidose dry powder inhaler turbuhaler is used for the release of asthma medications. It mentions that conformity with proper use of the inhaler is significant in controlled situations that resulted in clinically relevant PIF during the use of turbuhaler. It adds that the test was suspended when the highest histamine dose has been inhaled.

An abstract of the study "True adherence with the Turbuhaler in young children with asthma," by K. Nikander et al, published in the November 19, 2010 online issue of the journal "Archives of Disease in Childhood" is presented.

Objective To investigate true adherence with a dry powder inhaler, the Turbuhaler (TBH), in children with asthma. True adherence was calculated by multiplying adherence to treatment with inhaler competence, that is correct use of the inhaler. Patients and design In an 18-month study, children aged 5-10 years with asthma received twice daily budesonide via a TBH. Parents and children were trained in the correct use of the inhaler before the study started. For each inhalation, peak inspiratory flow through the TBH (PIFTBH) was recorded with an electronic pneumotachograph. The PIFTBH recordings were used to calculate true adherence for the first and last 45-day periods in the study by multiplying adherence in using the device (percentage of days with PIFTBH recordings) with inhaler competence (correct use of inhaler defined as PIFTBH values >40 l/min). Main outcome measures True adherence, adherence, inhaler competence and PIFTBH. Results 115 children were treated. The mean (morning and evening) true adherence during the first 45 days was 81.6% (range 78.1-86.4%) and during the last 45 days 57.4% (44.0-66.9%). Mean adherence was 86.0% and 59.3%, whereas mean inhaler competence was 94.7% and 96.2%, respectively. Thus the decline in true adherence was due to the decline in adherence. The largest decline in true adherence occurred in older children. Conclusions True adherence with budesonide TBH treatment decreased significantly during the 18-month study due to a decrease in adherence. Inhaler competence with the correct use of the budesonide TBH was high and unchanged over the study period. [ABSTRACT FROM AUTHOR]

Background: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma.Methods: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS).Results: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted.Conclusions: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children. [ABSTRACT FROM AUTHOR]

Purpose: Adverse drug events (ADEs) have been internationally recognized as a major threat to patient safety. The purpose of this study was to conduct a meta-analysis focusing on inpatient ADEs in the Western World to provide better estimate of the current state of medication safety in these countries. Methods: The studies for meta-analysis were identified through electronic search in Cochrane, Scopus, Medline, and Web of science databases. Included articles focused on adult inpatient ADEs, had commonly accepted definition for ADE, and were conducted between 2000 and 2016. Disease or ADE-specific studies were excluded. Meta-analysis was conducted on the prevalence of inpatient ADEs and fatal adverse drug reactions (FADRs). Results: The pooled estimate of the prevalence of inpatient ADEs was formed by 46,626 patient records included in 9 articles. Inpatient ADE prevalence was 19 and 32.3% of these ADEs were assessed preventable (MD 28.6%, SD 22.6%). Three articles including 3385 patients focused on inpatient FADRs, but the pooled estimate of this was disregarded due to low number and high heterogeneity of the included studies. Conclusions: ADEs are estimated to affect 19% of inpatients during hospitalization. Most of the ADEs are moderate in severity causing no permanent harm to the patient. Only a small amount of ADEs cause inpatient deaths, but in this meta-analysis, however, we were unable to give direct estimate of the prevalence. [ABSTRACT FROM AUTHOR]

Background: Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years.Methods: 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children's hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit.Results: 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and β agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively).Conclusions: Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children. [ABSTRACT FROM AUTHOR]

Background: The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue are poorly characterized in vivo. Methods: We compared MMP-8 and TIMP-1 levels in induced sputum and their expression in airway inflammatory cells of healthy children (n = 27) and of children with newly diagnosed asthma with mild (n = 20) or moderate symptoms (n = 19), before and after 6 months of treatment with inhaled budesonide. Results: At baseline, MMP-8 was higher in asthmatic children with moderate symptoms, TIMP-1 was lower and the MMP-8/TIMP-1 ratio was higher in both groups of asthmatic children compared with controls. Inhaled budesonide increased TIMP-1 levels in both groups of asthmatic children and normalized the MMP-8/TIMP-1 ratio, and this paralleled the improvement in forced expiratory volume in 1 s in children with mild symptoms. At baseline, asthmatic children had significantly more MMP-8-positive macrophages than control children, whereas the number of TIMP-1-positive macrophages was almost the same. Budesonide decreased the percentage of MMP-8-positive macrophages and increased that of TIMP-1-positive macrophages; these changes were significant in asthmatic children with mild symptoms. Conclusions: Inhaled budesonide normalized the MMP-8/TIMP-1 ratio in asthmatic children by upregulation of TIMP-1 production and downregulation of MMP-8 production by airway macrophages. This change may be a biochemical marker of an effect on airway inflammation and possibly of an ongoing remodeling process that should be further investigated using biopsy specimens. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The compulsive nature of tobacco use is attributable to nicotine addiction. Nicotine is eliminated by metabolism through the cytochrome P450 2A6 (CYP2A6) enzyme in liver. Inhibition of CYP2A6 by chemical compounds may represent a potential supplement to anti-smoking therapy. The purpose of this study was to rationally design potent inhibitors of CYP2A6. 3D-QSAR models were constructed to find out which structural characteristics are important for inhibition potency. Specifically located hydrophobic and hydrogen donor features were found to affect inhibition potency. These features were used in virtual screening of over 60 000 compounds in the Maybridge chemical database. A total of 22 candidate molecules were selected and tested for inhibition potency. Four of these were potent and selective CYP2A6 inhibitors with IC50 values lower than 1 μM. They represent novel structures of CYP2A6 inhibitors, especially N1-(4-fluorophenyl)cyclopropane-1-carboxamide. This compound can be used as a lead in the design of CYP2A6 inhibitor drugs to combat nicotine addiction.The Pharmacogenomics Journal (2008) 8, 328–338; doi:10.1038/sj.tpj.6500481; published online 9 October 2007 [ABSTRACT FROM AUTHOR]

Background: In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen presenting cells (APC) and regulatory T cells (Treg) are important modifiers of T cell immunity but little is known about their distribution in bronchial mucosa at this age. Here the subset distribution of APC and the appearance of Foxp3+ Treg and bronchus associated lymphoid tissue (BALT) were examined immunohistochemically in children less than 2 years of age with chronic asthma-like symptoms of the lower airways. Methods: mmunophenotyping was performed in situ on bronchial biopsy specimens obtained from 45 infants, 4-23 months of age, under investigation for airway disease. Results: A well developed HLA-DR+ network of APC was present in all samples, approximately 50% of the cells being CD68+ macrophages and the remainder various subsets of dendritic cells. The density of HLA-DR+ cells increased significantly with age but was not related to atopy, clinical symptoms or lung function. Comparing the density of APC subsets and clinical parameters, only the number of intraepithelial CD1a+ dendritic cells was significantly increased in infants who had recently suffered a respiratory infection. BALT structures were identified in 22 children, with no relation to lung function, atopic status or human rhinovirus positivity. Plasmacytoid dendritic cells and Foxp3+ Treg were located primarily within these isolated lymphoid follicles. Conclusion: A bronchial network of dendritic cells and macrophages develops quite rapidly after birth, apparently independent of clinical symptoms or atopy. The high frequency of BALT structures containing putative tolerogenic dendritic cells and Treg suggests that these lymphoid follicles play an important role in bronchial immune homeostasis during infancy. [ABSTRACT FROM AUTHOR]

The forced oscillation technique makes it possible to evaluate the mechanical properties of the respiratory system with a minimum of cooperation. The method is therefore especially useful in children. Impulse oscillometry (IOS) is a commercially available version of this technique. There is, as yet, limited information on reference values for IOS in children. The aim of this study was to extend the reference values for IOS variables and to study their correlation with height, weight and age in healthy children. A sample ( n = 360) of children (age 2·1–11·1 years) was measured by using impulse oscillometry (IOS; Jaeger, Würzburg, Germany). The sample was based on children attending kindergarten in Finland and children attending primary school in Sweden. Measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs) and the resonance frequency (Fr) were made. All variables were related to body height. Most of them were also weakly related to weight. Reference equations for children (height 90–160 cm) are presented. [ABSTRACT FROM AUTHOR]

There are few controlled studies on the effects of anti-inflammatory treatment on airway inflammation in newly diagnosed childhood asthma. Sixty children with newly diagnosed mild persistent asthma, 5–10 years of age, and 17 healthy control subjects were studied. Asthmatic children were randomized into an open study with two treatment groups: (1) budesonide 400 μg twice daily for 1 month, 200 μg twice daily for 5 months and (2) disodium cromoglycate (DSCG) 10 mg three-times daily for 6 months. All exacerbations were treated with budesonide 400 μg twice daily for 2 weeks. Symptoms and lung function were recorded throughout the study. Sputum induction was safe and the overall success rate was 71%. This improved with age and decreased after treatment. At baseline, the asthmatic children had more eosinophils in blood (0.26 vs 0.18 × 109/l, P = 0.03) and sputum (1.1 vs 0.0 %, P = 0.0001) than the control subjects. The numbers of sputum eosinophils correlated with bronchial responsiveness ( R = −0.58, P = 0.0002). Eosinophils were higher in children with atopic asthma than with nonatopic asthma ( P < 0.0001), and in children with a history wheezing than in children without wheezing ( P = 0.02). Six months of budesonide treatment, but not of DSCG, improved lung function ( P = 0.007), decreased symptoms ( P = 0.007) and sputum eosinophils ( P = 0.003). The effects of budesonide were pronounced in children with intense sputum eosinophilia (>3%). Sputum eosinophilia is present in children with newly diagnosed mild persistent asthma. Treatment with inhaled budesonide, but not with DSCG, decreases sputum eosinophils along with clinical and functional improvement. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the long-term effects of postnatal dexamethasone treatment in high-risk infants of very low birthweight. Methods: The study included 16 children aged 7.8 to 9.2 y who had been born very prematurely at gestational ages of 24-29 wk and with birthweights of <1500 g and who had participated in a randomized study of dexamethasone or placebo treatment in ventilator-dependent infants at 10 d of age. Flow-volume spirometry, impulse oscillometry, skin-prick tests and Doppler echocardiography were carried out at school age, and respiratory morbidity and overall neurological outcome evaluated. Controls were 18 non-atopic children born at term, tested for lung function. Results: No significant differences were found in respiratory morbidity at school age between the dexamethasone ( n = 8) and placebo ( n = 8) groups. Six of the 16 children had moderate to severe neurosensory impairments, but all were able to walk without support and attended primary school. In prematurely born children, standardized height was significantly less than that in controls, but between the two study groups, no significant differences existed in somatic growth. Atopy was uncommon: skin-prick tests were positive in only one child in the placebo group. In the dexamethasone group, forced vital capacity adjusted to height was significantly higher than that in the placebo group, but impairment of basic lung function and bronchial obstruction was evident in both study groups. No hypertrophic cardiomyopathy was apparent, and non-invasive measurements of pulmonary arterial pressure did not reveal any significant difference between the study groups. Conclusion: In very low-birthweight children, high respiratory morbidity and neurological impairment continued until school age. Neonatal dexamethasone treatment at school age was not associated with any detectable adverse effects on somatic growth, or pulmonary or cardiac function. [ABSTRACT FROM AUTHOR]

In order to study the determinants of respiratory system impedance and bronchodilator response in preschool children, a sample (n =109) of healthy children (age 2·1–7·0 years) attending kindergarten was measured by using the impulse oscillometry. Their selection was based on a standardized questionnaire, negative skin prick test results and clinical examination, and sufficient cooperation. Triple measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs), the resonance frequency (Fr) and the frequency dependence of resistance (dRrs/df) were performed, to determine individual mean values. Measurements were repeated after inhalation of 300 μg salbutamol (n =89) or placebo (n =19). At the baseline, Zrs and Rrs5-20 showed negative, and Xrs5-20, Fr and dRrs/df positive correlations with age, height and weight. However, logarithmic transformed height was the best independent variable for the regression equations of all the oscillometric variables. After inhalation of placebo, none of the oscillometric variables changed significantly. In the salbutamol group, the mean (SD) change in Rrs5 was -0·187 (0·124) kPa l–1 s–1 and –19·2 (10·2)%, corresponding to a lower reference limit of –36·9%. Both the within-test and between-test repeatabilities for the measurement of respiratory resistance were acceptable, for Rrs5 the coefficients of variation being 6·2 and 6·1%, respectively. As the overall success rate in our sample was high (89%), the forced oscillation technique seems to be a useful method in assessing respiratory function and bronchial lability in preschool children. [ABSTRACT FROM AUTHOR]

Objectives: To compare the acceptability, reproducibility, and sensitivity of spirometric outcome measures of airway caliber during challenge testing in children.Design: FEV(1), forced expiratory volume in 0.75 s, forced expiratory volume in 0.5 s, and peak expiratory flow (PEF) were recorded during stepwise dosimetric histamine challenge tests. The responses were compared, and the reproducibility at baseline and from duplicate measurements at each challenge step was determined.Patients: One hundred five children with newly diagnosed asthma, aged 5 to 10 years.Results: Compared to PEF, FEV(1) showed better baseline reproducibility (p = 0.002) and higher sensitivity (p < 0.0001) during challenge testing, determined as the change normalized to the baseline variation, while the forced expiratory volumes were not significantly different in these respects. During challenge testing in subjects with acceptable flow-volume tracings, paired recordings of FEV(1) agreed within 0.1 L in 85% and within 0.2 L in 93% of measurements. During challenge testing, the reproducibility of FEV(1) measurements was not better than that of the other indexes. Failure to exhale long enough precluded the use of FEV(1) in 16 of the children, particularly the youngest children.Conclusions: The results demonstrated that the recently published guidelines for FEV(1) measurements during challenge tests can be applied to children. During challenge tests in asthmatic children, the advantage of the shorter fractions of forced expiratory volume was that they were more often acceptably recorded than FEV(1), while they showed as good reproducibility and were also equally sensitive in assessing changes in airway obstruction. [ABSTRACT FROM AUTHOR]

Two projects, Silver Stringers and Junior Journalists, are examples of a shift in the role of the news consumer--community members are actively engaged in publishing pursuits previously confined to the traditional media. Their activities range from news gathering and dissemination to asking questions and debating issues of importance, whether local, international, or topical in scope. This paper describes the evolution of these projects, the experiences of the participants, the technologies developed and employed, and the epistemological impact. [ABSTRACT FROM AUTHOR]