Overcoming beta-agonist tolerance: high dose salbutamol and ipratropium bromide. Two randomised controlled trials

BACKGROUND: Asthmatics treated with long-acting beta-agonists have a reduced bronchodilator response to moderate doses of inhaled short acting beta-agonists during acute bronchoconstriction. It is not known if the response to higher doses of nebulised beta-agonists or other bronchodilators is impaired. We assessed the effect of long-acting beta-agonist treatment on the response to 5 mg nebulised salbutamol and to ipratropium bromide. METHODS: Two double-blind, placebo-controlled, crossover studies of inhaled formoterol 12 μg twice daily in patients with asthma. High-dose salbutamol: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled methacholine to produce a 20% fall in FEV(1). Salbutamol 5 mg was then administered via nebuliser and the FEV(1 )was monitored for 20 minutes. Ipratropium: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled 4.5% saline to produce a 20% fall in FEV(1). Salbutamol 200 μg or ipratropium bromide 40 μg was then inhaled and the FEV(1 )was monitored for 30 minutes. Four study arms compared the response to each bronchodilator after formoterol and placebo. Analyses compared the area under the bronchodilator response curves, adjusting for changes in pre-challenge FEV(1), dose of provocational agent and FEV(1 )fall during the challenge procedure. RESULTS: The response to nebulised salbutamol was 15% lower after formoterol therapy compared to placebo (95% confidence 5 to 25%, p = 0.008). The response to ipratropium was unchanged. CONCLUSION: Long-acting beta-agonist treatment induces tolerance to the bronchodilator effect of beta-agonists, which is not overcome by higher dose nebulised salbutamol. However, the bronchodilator response to ipratropium bromide is unaffected

Vitamin D, innate immunity and outcomes in community acquired pneumonia

We investigated the associations between vitamin D status, the antimicrobial peptides cathelicidin and beta defensin-2 and outcomes in community acquired pneumonia. In hospitalised patients with community acquired pneumonia, vitamin D deficiency but not antimicrobial peptide levels were associated with increased 30-day mortality. Vitamin D was not associated with levels of the antimicrobial peptide cathelicidin or beta defensin-2

Maternal post-natal tobacco use and current parental tobacco use is associated with higher body mass index in children and adolescents: an international cross-sectional study

Background: We investigated whether maternal smoking in the first year of life or any current parental smoking is associated with childhood or adolescent body mass index (BMI). Methods: Secondary analysis of data from a multi-centre, multi-country, cross-sectional study (ISAAC Phase Three). Parents/guardians of children aged 6-7 years completed questionnaires about their children's current height and weight, whether their mother smoked in the first year of the child's life and current smoking habits of both parents. Adolescents aged 13-14 years completed questionnaires about their height, weight and current parental smoking habits. A general linear mixed model was used to determine the association between BMI and parental smoking. Results: 77,192 children (18 countries) and 194 727 adolescents (35 countries) were included. The BMI of children exposed to maternal smoking during their first year of life was 0.11 kg/m2 greater than those who were not (P = 0.0033). The BMI of children of currently smoking parents was greater than those with non-smoking parents(maternal smoking: +0.08 kg/m2 (P = 0.0131), paternal smoking: +0.10 kg/m2 (P < 0.0001)). The BMI of female adolescents exposed to maternal or paternal smoking was 0.23 kg/m2 and 0.09 kg/m2 greater respectively than those who were not exposed (P < 0.0001). The BMI of male adolescents was greater with maternal smoking exposure, but not paternal smoking (0.19 kg/m2, P < 0.0001 and 0.03 kg/m2, P = 0.14 respectively). Conclusion: Parental smoking is associated with higher BMI values in children and adolescents. Whether this is due to a direct effect of parental smoking or to confounding cannot be established from this observational study

Imperfections in a two-dimensional hierarchical structure

Hierarchical and fractal designs have been shown to yield high mechanical efficiency under a variety of loading conditions. Here a fractal frame is optimized for compressive loading in a two-dimensional space. We obtain the dependence of volume required for stability against loading for which the structure is optimized and a set of scaling relationships is found. We evaluate the dependence of the Hausdorff dimension of the optimal structure on the applied loading and establish the limit to which it tends under gentle loading. We then investigate the effect of a single imperfection in the structure through both analytical and simulational techniques. We find that a single asymmetric perturbation of beam thickness, increasing or decreasing the failure load of the individual beam, causes the same decrease in overall stability of the structure. A scaling relationship between imperfection magnitude and decrease in failure loading is obtained. We calculate theoretically the limit to which the single perturbation can effect the overall stability of higher generation frames

The use of β2-agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis

Background: Patterns of inhaled β2-agonist therapy use during severe asthma exacerbations before hospital attendance are poorly understood. Aims: To assess β2-agonist use prior to hospital attendance. Methods: We undertook an exploratory post hoc analysis of data from a 6-month clinical trial of 303 patients randomised to combination budesonide/formoterol inhaler according to a Single combination inhaler as Maintenance And Reliever Therapy regimen (‘SMART’) or fixed-dose budesonide/formoterol with salbutamol as reliever (‘Standard’). Patterns of β2-agonist use for 14 days before hospital attendance with a severe asthma exacerbation were determined by electronic monitoring of inhaler use. Results: There were 22 hospital attendances in 16 patients during the study. Seven and nine hospital attendances were eligible for analysis in the SMART and Standard groups, respectively. In both regimens, β2-agonist use increased before hospital attendance, with a median (range) maximum daily number of actuations of 14 (9 to 63) budesonide/formoterol in SMART and 46 (6 to 95) salbutamol in Standard with 4 (0 to 10) budesonide/formoterol actuations on the day of maximal salbutamol use. There was delay in obtaining medical review despite high β2-agonist use, in 9/16 patients. Different patterns of use were observed, including repeated days of no inhaled corticosteroid despite marked salbutamol use, which occurred in 3/9 patients in the Standard group. Conclusions: Delay in obtaining medical review in association with high β2-agonist use is common in patients before hospital presentation with severe exacerbations of asthma. The SMART regimen reduced nonadherence with inhaled corticosteroid therapy during severe exacerbations

Fast-food consumption and body mass index in children and adolescents: an international cross-sectional study

OBJECTIVE: To investigate whether reported fast-food consumption over the previous year is associated with higher childhood or adolescent body mass index (BMI). DESIGN: Secondary analysis from a multicentre, multicountry cross-sectional study (International Study of Asthma and Allergies in Children (ISAAC) Phase Three). SUBJECTS AND METHODS: Parents/guardians of children aged 6-7 completed questionnaires which included questions about their children's asthma and allergies, fast-food consumption, height and weight. Adolescents aged 13-14 completed the same questionnaire. The questionnaire asked 'In the past 12 months, how often on average did you (your child) eat fast-food/burgers?' The responses were infrequent (never/only occasionally), frequent (once/twice a week) or very frequent (three or more times per week). A general linear mixed model was used to determine the association between BMI and fast-food consumption, adjusting for Gross National Income per capita by country, measurement type (whether heights/weights were reported or measured), age and sex. RESULTS: 72,900 children (17 countries) and 199,135 adolescents (36 countries) provided data. Frequent and very frequent fast-food consumption was reported in 23% and 4% of children, and 39% and 13% of adolescents, respectively. Children in the frequent and very frequent groups had a BMI that was 0.15 and 0.22 kg/m(2) higher than those in the infrequent group (p<0.001). Male adolescents in the frequent and very frequent groups had a BMI that was 0.14 and 0.28 kg/m(2) lower than those in the infrequent group (p<0.001). Female adolescents in the frequent and very frequent groups had a BMI that was 0.19 kg/m(2) lower than those in the infrequent group (p<0.001). CONCLUSIONS: Reported fast-food consumption is high in childhood and increases in adolescence. Compared with infrequent fast-food consumption, frequent and very frequent consumption is associated with a higher BMI in children. Owing to residual confounding, reverse causation and likely misreporting, the reverse association observed in adolescents should be interpreted with caution

Association between Frequency of Consumption of Fruit, Vegetables, Nuts and Pulses and BMI: Analyses of the International Study of Asthma and Allergies in Childhood (ISAAC).

Diets which emphasize intakes of plant-based foods are recommended to reduce disease risk and for promoting healthy weight. The aim of this study was to examine the association between fruit, vegetables, pulses and nut intake and body mass index (BMI) across countries in adolescents (13-14 years) and children (6-7 years). Data from the International Study of Asthma and Allergies in Childhood; 77,243 children's parents and 201,871 adolescents was used to examine the association between dietary intake (Food Frequency Questionnaire) and BMI using general linear models, adjusting for country gross national index. Adolescents who consumed fruit, vegetables, pulses and nuts three or more times a week had a lower BMI than the never or occasional group; eating nuts three or more times a week, was associated with a BMI value of 0.274 kg/m² lower than the never group (p < 0.001). Compared to children who never or occasionally reported eating vegetables, those reporting that they ate vegetables three or more times per week had a lower BMI of -0.079 kg/m². In this large global study, an inverse association was observed between BMI and the reported increasing intake of vegetables in 6-7 years old and fruit, vegetables, pulses and nuts in adolescents. This study supports current dietary recommendations which emphasize the consumption of vegetables, nut and pulses, although the effect sizes were small.Acknowledgments: This work was supported by Cure Kids New Zealand through a grant to E.A. Mitchell and I. Braithwaite. Cure Kids New Zealand had no role or influence in design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.Revisión por pare

Correlation between measures of insulin resistance in fasting and non-fasting blood

<p>Abstract</p> <p>Background</p> <p>Epidemiological investigation of insulin resistance is difficult. Standard measures of insulin resistance require invasive investigations, which are impractical for large-scale studies. Surrogate measures using fasting blood samples have been developed, but even these are difficult to obtain in population-based studies. Measures of insulin resistance have not been validated in non-fasting blood samples. Our objective was to assess the correlations between fasting and non-fasting measures of insulin resistance/sensitivity.</p> <p>Methods</p> <p>Fasting and non-fasting measurements of metabolic function were compared in 30 volunteers (15 male) aged 28 to 48 years. Participants provided a morning blood sample after an overnight fast and a second sample approximately 4 hours after lunch on the same day.</p> <p>Results</p> <p>Non-fasting levels of the adipokines leptin, adiponectin, and leptin:adiponectin ratios were not significantly different and highly correlated with fasting values (r values 0.95, 0.96, and 0.95 respectively, P values < 0.001). There were moderate correlations between fasting and non-fasting estimates of insulin sensitivity using the McAuley (r = 0.60, P = 0.001) and QUICKI formulae (r = 0.39, P = 0.037). The HOMA-IR estimate of insulin resistance was also moderately correlated (r = 0.45, P = 0.016).</p> <p>Conclusions</p> <p>Semi-fasting measures of leptin, adiponectin, and leptin:adiponectin ratios correlate closely with fasting values and are likely to be sufficient for population-based research. Other measures of insulin resistance or sensitivity in semi-fasted blood samples are moderately correlated with values obtained after an overnight fast. These estimates of insulin resistance/sensitivity may also be adequate for many epidemiological studies and would avoid the difficulties of obtaining fasting blood samples.</p