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Predictors of response to tiotropium versus salmeterol in asthmatic adults.

J Allergy Clin Immunol. 2013 Sep 28;

Authors: Peters SP, Bleecker ER, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, Boushey HA, Calhoun WJ, Castro M, Cherniack RM, Craig T, Denlinger LC, Engle LL, Dimango EA, Israel E, Kraft M, Lazarus SC, Lemanske RF, Lugogo N, Martin RJ, Meyers DA, Ramsdell J, Sorkness CA, Sutherland ER, Wasserman SI, Walter MJ, Wechsler ME, Chinchilli VM, Szefler SJ, for the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network

Abstract
BACKGROUND: Tiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described.
OBJECTIVE: We sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response.
METHODS: Data from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for individual and differential treatment responses to salmeterol and tiotropium and predictors of a positive response to the end points FEV1, morning peak expiratory flow (PEF), and asthma control days (ACDs).
RESULTS: Although approximately equal numbers of patients showed a differential response to salmeterol and tiotropium in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53, respectively), more showed a differential response to tiotropium for FEV1 (n = 104) than salmeterol (n = 62). An acute response to a short-acting bronchodilator, especially albuterol, predicted a positive clinical response to tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P < .001) and morning PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil count, fraction of exhaled nitric oxide, asthma duration, and body mass index were not.
CONCLUSION: Although these results require confirmation, predictors of a positive clinical response to tiotropium include a positive response to albuterol and airway obstruction, factors that could help identify appropriate patients for this therapy.

PMID: 24084072 [PubMed - as supplied by publisher]

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Does BCG vaccination protect against childhood asthma? Final results from the Manchester Community Asthma Study retrospective cohort study and updated systematic review and meta-analysis.

J Allergy Clin Immunol. 2013 Sep 28;

Authors: Linehan MF, Nurmatov U, Frank TL, Niven RM, Baxter DN, Sheikh A

Abstract
BACKGROUND: The Manchester Community Asthma Study (MANCAS) found a protective effect against the risk of wheeze at age 6 to 11 years for children given neonatal BCG vaccination. Our subsequent systematic review and meta-analysis suggested that BCG vaccination did not protect against allergic sensitization but might have exerted a protective effect against nonatopic asthma.
OBJECTIVES: We sought to assess whether the protective effect of BCG vaccination on wheeze observed in the MANCAS cohort was maintained at age 13 to 17 years and to incorporate the findings from this final MANCAS analysis into an updated systematic review and meta-analysis.
METHODS: BCG vaccination status was determined from health records and respiratory outcomes from questionnaire responses. We updated the systematic review and used fixed-effects and random-effects modeling to undertake meta-analyses.
RESULTS: There were 1608 participants in the final MANCAS analysis. The 12-month prevalence of wheeze was 15.1%. There was no difference in prevalence between those who were and were not BCG vaccinated (15.8% vs 14.3%; relative risk, 1.05; 95% CI, 0.94-1.19). The updated meta-analysis incorporated 4 new studies: this showed that the protective effect of BCG vaccination against the development of asthma identified in our previous meta-analysis was attenuated (odds ratio, 0.95; 95% CI, 0.89-1.00). No protective effect of BCG was seen for sensitization, eczema/atopic dermatitis, rhinoconjunctivitis, or allergy in general.
CONCLUSIONS: Taken together, the final results of the MANCAS cohort and the updated systematic review and meta-analysis provide clearer evidence that any protective effect of BCG vaccination on childhood asthma is likely to be transient.

PMID: 24084077 [PubMed - as supplied by publisher]

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Breathing exercises for adults with asthma.

Cochrane Database Syst Rev. 2013 Oct 1;10:CD001277

Authors: Freitas DA, Holloway EA, Bruno SS, Chaves GS, Fregonezi GA, Mendonça KM

Abstract
BACKGROUND: Breathing exercises have been widely used worldwide as a complementary therapy to the pharmacological treatment of people with asthma.
OBJECTIVES: To evaluate the evidence for the efficacy of breathing exercises in the management of patients with asthma.
SEARCH METHODS: The search for trials led review authors to review the literature available in The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and AMED and to perform handsearching of respiratory journals and meeting abstracts. Trial registers and reference lists of included articles were also consulted.The literature search has been updated to January 2013.
SELECTION CRITERIA: We included randomised controlled trials of breathing exercises in adults with asthma compared with a control group receiving asthma education or, alternatively, with no active control group.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. RevMan software was used for data analysis based on the fixed-effect model. Continuous outcomes were expressed as mean differences (MDs) with confidence intervals (CIs) of 95%. Heterogeneity was assessed by inspecting the forest plots. The Chi(2) test was applied, with a P value of 0.10 indicating statistical significance. The I(2) statistic was implemented, with a value greater than 50% representing a substantial level of heterogeneity.
MAIN RESULTS: A total of 13 studies involving 906 participants are included in the review. The trials were different from one another in terms of type of breathing exercise performed, number of participants enrolled, number and duration of sessions completed, outcomes reported and statistical presentation of data. Asthma severity in participants from the included studies ranged from mild to moderate, and the samples consisted solely of outpatients. The following outcomes were measured: quality of life, asthma symptoms, number of acute exacerbations and lung function. Eleven studies compared breathing exercise with inactive control, and two with asthma education control groups. All eight studies that assessed quality of life reported an improvement in this outcome. An improvement in the number of acute exacerbations was observed by the only study that assessed this outcome. Six of seven included studies showed significant differences favouring breathing exercises for asthma symptoms. Effects on lung function were more variable, with no difference reported in five of the eleven studies that assessed this outcome, while the other six showed a significant difference for this outcome, which favoured breathing exercises. As a result of substantial heterogeneity among the studies, meta-analysis was possible only for asthma symptoms and changes in the Asthma Quality of Life Questionnaire (AQLQ). Each meta-analysis included only two studies and showed a significant difference favouring breathing exercises (MD -3.22, 95% CI -6.31 to -0.13 for asthma symptoms; MD 0.79, 95% CI 0.50 to 1.08 for change in AQLQ). Assessment of risk of bias was impaired by incomplete reporting of methodological aspects of most of the included trials.
AUTHORS' CONCLUSIONS: Even though individual trials reported positive effects of breathing exercises, no reliable conclusions could be drawn concerning the use of breathing exercises for asthma in clinical practice. This was a result of methodological differences among the included studies and poor reporting of methodological aspects in most of the included studies. However, trends for improvement are encouraging, and further studies including full descriptions of treatment methods and outcome measurements are required.

PMID: 24085551 [PubMed - as supplied by publisher]

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Physical training for asthma.

Cochrane Database Syst Rev. 2013 Sep 30;9:CD001116

Authors: Carson KV, Chandratilleke MG, Picot J, Brinn MP, Esterman AJ, Smith BJ

Abstract
BACKGROUND: People with asthma may show less tolerance to exercise due to worsening asthma symptoms during exercise or other reasons such as deconditioning as a consequence of inactivity. Some may restrict activities as per medical advice or family influence and this might result in reduced physical fitness. Physical training programs aim to improve physical fitness, neuromuscular coordination and self confidence. Subjectively, many people with asthma report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. Also, as exercise can induce asthma, the safety of exercise programmes needs to be considered.
OBJECTIVES: To gain a better understanding of the effect of physical training on the respiratory and general health of people with asthma, from randomised trials.
SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials up to January 2013.
SELECTION CRITERIA: We included randomised trials of people over eight years of age with asthma who were randomised to undertake physical training or not. Physical training had to be undertaken for at least 20 minutes, two times a week, over a minimum period of four weeks.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility for inclusion and undertook risk of bias assessment for the included studies.
MAIN RESULTS: Twenty-one studies (772 participants) were included in this review with two additional 2012 studies identified as 'awaiting classification'. Physical training was well tolerated with no adverse effects reported. None of the studies mentioned worsening of asthma symptoms following physical training. Physical training showed marked improvement in cardiopulmonary fitness as measured by a statistically and clinically significant increase in maximum oxygen uptake (mean difference (MD) 4.92 mL/kg/min; 95% confidence interval (CI) 3.98 to 5.87; P < 0.00001; 8 studies on 267 participants); however, no statistically significant effects were observed for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), minute ventilation at maximal exercise (VEmax) or peak expiratory flow rate (PEFR). Meta-analysis of four studies detected a statistically significant increase in maximum heart rate, and following a sensitivity analysis and removal of two studies significance was maintained (MD 3.67 bpm; 95% CI 0.90 to 3.44; P = 0.01). Although there were insufficient data to pool results due to diverse reporting tools, there was some evidence to suggest that physical training may have positive effects on health-related quality of life, with four of five studies producing a statistically and clinically significant benefit.
AUTHORS' CONCLUSIONS: This review demonstrated that physical training showed significant improvement in maximum oxygen uptake, though no effects were observed in other measures of pulmonary function. Physical training was well tolerated among people with asthma in the included studies and, as such, people with stable asthma should be encouraged to participate in regular exercise training, without fear of symptom exacerbation. More research is needed to understand the mechanisms by which physical activity impacts asthma management.

PMID: 24085631 [PubMed - as supplied by publisher]