Effects Of Beta-agonists Research Articles

Beta2-agonist impairs muscle insulin sensitivity in persons with insulin resistance.

Given the promising effects of prolonged treatment with beta2-agonist on insulin sensitivity in animals and non-diabetic individuals, the beta2-adrenergic receptor has been proposed as a target to counter peripheral insulin resistance. On the other hand, rodent studies also reveal that beta2-agonists acutely impair insulin action, posing a potential caveat for their use in treating insulin resistance. To assess the impact of beta2-agonist on muscle insulin action and glucose metabolism and identify the underlying mechanism(s) in 10 insulin-resistant subjects. In a cross-over design, we assessed the effect of beta2-agonist on insulin-stimulated muscle glucose uptake during a 3-h hyperinsulinemic isoglycemic clamp with and without intralipid infusion in 10 insulin-resistant overweight subjects. Two hours into the clamp, we infused beta2-agonist. We collected muscle biopsies before, two hours into and by the end of the clamp and analyzed them using metabolomic and lipidomic techniques. We establish that beta2-agonist, independently from and additively to intralipid, impairs insulin-stimulated muscle glucose uptake via different mechanisms. In combination, beta2-agonist and intralipid nearly eliminates insulin-dependent muscle glucose uptake. While both beta2-agonist and intralipid elevated muscle glucose-6-phosphate, only intralipid caused accumulation of downstream muscle glycolytic intermediates, whereas beta2-agonist attenuated incorporation of glucose into glycogen. Our findings suggest that beta2-agonist inhibits glycogenesis while intralipid inhibits glycolysis in skeletal muscle of insulin-resistant individuals. These results should be addressed in future treatment of insulin resistance with beta2-agonist.

Acute Effects of Albuterol on Ventilatory Capacity in Children with Asthma.

Children with asthma may have a reduced ventilatory capacity, which could lead to symptoms and early termination of a cardiopulmonary exercise test (CPET). The purpose of this study was to examine the effects of short-acting beta agonist (albuterol) administration on estimated ventilatory capacity in children with asthma. Fifteen children (eleven boys, 10.6 ± 0.9 years) completed spirometry at baseline, after 180 µg of albuterol, and after the CPET in this cross-sectional study. Ventilatory capacity was calculated from forced vital capacity (FVC) and isovolume forced expiratory time from 25 to 75% of FVC (isoFET25-75) as follows: FVC/2 × [60/(2 × isoFET25-75)]. Differences in outcome variables between baseline, after albuterol administration, and after the CPET were detected with repeated measures mixed models with Bonferroni post hoc corrections. Estimated ventilatory capacity was higher after albuterol (68.7 ± 21.2 L/min) and after the CPET (75.8 ± 25.6 L/min) when compared with baseline (60.9 ± 22.0 L/min; P = 0.003). Because forced vital capacity did not change, the increased ventilatory capacity was primarily due to a decrease in isoFET25-75 (i.e., an increase in mid-flows or isoFEF25-75). Albuterol administration could be considered prior to CPET for children with asthma with relatively well-preserved FEV1 values to increase ventilatory capacity pre-exercise and potentially avoid symptom-limited early termination of testing.

The Wiser Strategy of Using Beta-Agonists in Asthma: Mechanisms and Rationales.

Concerns regarding the safety of beta-2 agonists have led to revisions of the major asthma guidelines to better address these issues. Although these updates allow for a combination of previous and current strategies, they may confuse clinical practitioners. Beta-2 agonists are vital for alleviating asthma symptoms by relaxing smooth muscles; however, they also pose significant risks by inducing pro-inflammatory mediators both in vitro and in vivo. In addition to the risks of overuse and symptom masking, the use of beta-agonists alone at therapeutic doses can worsen airway inflammation and enhance virus-induced inflammation during asthma exacerbation. Inhaled corticosteroids (ICS) can effectively prevent these adverse effects. With new insights into the mechanisms of these adverse events, reserving short-acting beta-agonists for acute symptom relief during exacerbations and only for those who are already on ICS or oral steroids represents a careful approach to using beta-agonists with least adverse effects in patients with asthma. However, a major drawback of this approach is the potential non-compliance with ICS, leading to beta-agonist use without the necessary counteraction by ICS. An optimal strategy, both during and outside exacerbations, would integrate beta-agonists into an anti-inflammatory regimen that includes ICS, ideally combined with the same inhaler to ensure their concurrent use where finances allow. This would maintain the beneficial effects of beta-agonists, such as bronchodilation, while preventing the adverse effects from the induction of inflammatory mediators. This method is aligned with diverse clinical settings, maximizes the safe use of beta-agonists, and supports a comprehensive guideline-compliant management strategy.

Effects of Short-Acting Beta-Agonist (SABA) Alone and SABA with Inhaled Corticosteroids in the Management of Asthma among Children

Introduction: However, the comparative efficacy of SABA alone vs SABA in conjunction with ICS in the treatment of childhood asthma remains an important topic of research. Understanding the comparative efficacy of SABA alone versus SABA in conjunction with ICS in the treatment of childhood asthma is critical for evidence-based decision-making. Methodology: This randomized controlled study (RCT) included 80 children aged 6 to 12 years who were diagnosed with mild chronic asthma. The participants were separated into two groups: SABA alone and SABA plus ICS. For symptom alleviation, the SABA alone group got as-needed treatment with a short-acting beta-agonist (SABA). The SABA with ICS group got SABA therapy on a regular basis for symptom alleviation, as well as daily inhaled corticosteroid (ICS) therapy for maintenance. To compare the outcomes of the two groups, statistical analysis was done using an independent t-test. A statistically significant p-value of less than 0.05 was evaluated. Results: Spirometry measures were taken to quantify vital capacity (VC), forced expiratory volume at one second (FEV1), and the FEV1/VC ratio. Both groups had lower baseline values for these measures, indicating decreased lung function. However, both groups' lung function improved significantly following the intervention (p<0.05). Practical Implication: The findings of this study can not only educate clinical practice, but also assist healthcare practitioners in making informed treatment decisions in order to enhance asthma management and outcomes for patients. Conclusion: According to the data, combining these drugs can enhance symptom management and lung function in children with moderate chronic asthma. Keywords: Asthma, Lung Function test, Forced expiratory volume, Short Acting Beta Agonist, Inhaled Corticosteroids, Children.

Dietary higenamine from Annonaceae family fruits as a possible source of unintentional doping

Members of the genus Aconitum have been used for millennia, both as poisons and medicines, in Eastern culture. Higenamine has non-selective beta-agonist effects, activating both β1 and β2 adrenoreceptors, and is present in a variety of plants. The World Anti-Doping Agency has banned Higenamine both in competition and out of competition. Due to the common uses of higenamine in Brazilian culture, both as medicine and food, we studied the urinary concentrations of higenamine after the consumption of fruits of the Annona genus. We evaluated whether the ingestion of these fruits has the potential to cause anti-doping code violations. We measured higenamine concentrations for a 72 h period in the urine of ten healthy, physically active males (age 20–30; weight 70–80 kg; not consuming supplements or medications) after eating a unique meal containing fruits. Fruit consumption ranges were: Carica papaya (control) 348 ± 98 g; A. muricata 450 ± 282 g; and A. squamosa 314 ± 60 g. (all mean± SD). Higenamine was measured using ultra-performance liquid chromatography coupled with electrospray-tandem mass spectrometry. The appearance of urinary higenamine occurred within the first 12 h after eating A. muricata (n = 3), and the maximum concentration found was 1.9 ng/mL. The ingestion of A. squamosa has also been shown to cause higenamine urinary excretion. The elimination kinetics of the subjects who ingested A. squamosa (n = 4) were different from each other. After ingestion of the control fruit, C. papaya, we detected no higenamine in the urine of any participants (n = 3). Although the kinetics varied by individuals and fruits, A. muricata ingestion produced higher higenamine excretion; however, the A. squamosa portion weighed ∼66 % of the A. muricata portion. We conclude that eating Annonaceae family fruits cause detectable higenamine excretion. Conversely, single ingestion did not reach the WADA’s threshold to cause adverse analytical findings.

The Potential Synergistic Risk of Albuterol and Vasoactives in Acute Lung Injury Trials.

Critically ill patients are often prescribed both inhaled beta-agonists and intravenous vasoactive; however, the interaction of the additive beta-agonist effects of these 2 agents remains largely uncharacterized. The purpose of this study was to evaluate how concomitant use of albuterol and vasoactive or inotropes affected ventilator-free days (VFDs) by re-analyzing the data from the Albuterol to Treat Acute Lung Injury (ALTA) trial. In this study, subjects were grouped to albuterol-vasoactive (n = 84) versus (vs) placebo-vasoactive (n = 62). Ventilator-free days, intensive care unit (ICU)-free days, organ failure-free days, cardiovascular adverse events, and 90-day mortality were compared. The primary outcome was VFDs. Patients in the albuterol-vasoactive group had significantly fewer VFDs than patients in the placebo-vasoactive group (11 vs 19, P = 0.05). Patients in the albuterol-vasoactive group also had significantly fewer ICU-free days (9.5 vs 18.5, P = .006). The 90-day mortality was similar between groups (36.9% vs 27.4%, P = .20). Similarly, no significant difference in cardiac adverse events between the groups (14.3% vs 11.3%, P = 0.59). This study has shown fewer VFDs for patients who received both vasoactive and albuterol. There were also fewer ICU-free days when compared to those on vasoactive only. Given the common use of both agents, a prospective evaluation of the additive adverse effects of beta-agonism is warranted.

Beta-Agonist, Ractopamine Hydrochloride, Improves Growth, Alters Body Composition, and Suppresses Gonadal Maturation in All-Female Giant Freshwater Prawn, Macrobrachium rosenbergii

All-female giant freshwater prawn Macrobrachium rosenbergii has a significant growth limitation due to its early sexual maturity. A 60-day trial was carried out to determine the effect of beta-agonist, ractopamine hydrochloride (RAC), on the growth performance, body composition, and gonadal maturation of all-female prawns. Prawn juveniles ( 4.39 ± 0.40 g initial weight) were stocked at 10 prawns/m2 in 15 plastic tanks (1000 liters each) in a completely randomized design with four treatments and a control (0, 5, 10, 15, and 20 mg/kg) in triplicate. The significantly ( p < 0.05 ) highest values of final weight, weight gain, daily weight gain, and specific growth rate (SGR) were observed in the female prawns fed with the diet containing 10 mg/kg RAC, while the lowest values were found in the control tank. Similarly, survival rate, feed conversion rate (FCR), and condition factors were observed among all treatments, which were significantly better than the control (0 mg/kg). Significantly greater yield and lower gonadosomatic index (GSI) values were obtained in prawns fed with a 10 mg/kg RAC-containing diet than in all other treatments, except for the diet containing 15 mg/kg RAC, while the lowest yield was produced by the control tank. A diet containing 10 mg/kg RAC had significantly improved the whole-body protein content in prawns, while diets containing 10 and 15 mg/kg RAC exhibited lower lipid content in prawns than in the other treatments. A significant increase in the number of Stage 1 (virgin) females (up to 54% at 10 mg/kg RAC diet) was found in all RAC treatments, while the control had a significantly higher number of females at various maturity stages, indicating that RAC administration effectively suppresses gonadal maturity. Residue analysis of whole prawn samples at the end of the trial indicated no trace of ractopamine. The quadratic regression analysis of weight gain, SGR, FCR, and yield revealed that the optimum dietary ractopamine level for all-female prawn culture should be between 10 and 15 mg/kg.

Improving skeletal muscle insulin sensitivity via beta2 -agonist administration: a promising strategy to counteract metabolic disease and muscle loss.

Improving skeletal muscle insulin sensitivity via beta2 -agonist administration: a promising strategy to counteract metabolic disease and muscle loss.

What are the effects of as-required fixed-dose combination beta agonist plus steroid inhaler for adults with mild asthma?

What are the effects of as-required fixed-dose combination beta agonist plus steroid inhaler for adults with mild asthma?

The ELSA trial: single versus combinatory effects of non-prohibited beta-2 agonists on skeletal muscle metabolism, cardio-pulmonary function and endurance performance\u2014study protocol for a randomized 4-way balanced cross-over trial

BackgroundAsthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor (beta-2) agonists use. Nevertheless, there are data on dose-dependent ergogenic effects of beta-2 agonists suggesting increased muscle strength, endurance and neuromuscular performance. Therefore, most beta-2 agonists belong to the World Anti Doping Agency (WADA) list of prohibited substances and it is tempting to speculate that illegitimate use of beta-2 agonists might be a common practice to boost performance in competitive sports. It is currently unknown whether or not inhaled beta-2 agonists enhance performance by stimulatory effects in skeletal and cardiac muscle.MethodsThe ELSA trial is a double-blinded, placebo-controlled, randomized, balanced, four-way cross-over study. Study participants (n=24, 12 ♀, 12 ♂) complete four study arms (i.e. periods with treatment A, placebo; B, salbutamol; C, formoterol; D, formoterol + salbutamol) in random order after an initial preliminary testing session. Participants inhale the study medication 20 min before the 10-min time trial (TT; exercise performance test), where participants cycle 10 min at the highest possible workload. Cardiac output is measured continuously. A skeletal muscle biopsy is collected 3 h after the TT. Study endpoints include measures of skeletal muscle expression of nuclear receptors, hormones and cytokine levels, urinary and plasma concentrations of salbutamol and formoterol, circulating cardiac markers, cardiopulmonary function and exercise performance (average power and peak power during the TT). Blood and urine are collected and respiratory testing is performed 24 h post TT.Summary/conclusionsThis clinical trial evaluates the potential performance-enhancing effects of non-prohibited, not medically indicated inhaled short- and long-acting beta-2 agonists on skeletal muscle gene expression, endocrine regulation, cardiac biomarkers, cardiopulmonary function and acute endurance exercise performance. These data will be used by WADA to adapt the annually published list of prohibited substances (WADA 2021) and will be published in scientific journals.Trial registrationThe trial is registered at the European Clinical Trials Database (Eudra CT) with the number: 2015-005598-19 as well as at the German register for clinical studies (DRKS number 00010574).

Salbutamol Increases Leg Glucose Uptake and Metabolic Rate but not Muscle Glycogen Resynthesis in Recovery From Exercise.

Exercise blunts the effect of beta2-agonists on peripheral glucose uptake and energy expenditure. Whether such attenuation extends into recovery is unknown. To examine the effect of a beta2-agonist on leg glucose uptake and metabolic rate in recovery from exercise. Using leg arteriovenous balance technique and analyses of thigh muscle biopsies, we investigated the effect of a beta2-agonist (24 mg of oral salbutamol) vs placebo on leg glucose, lactate, and oxygen exchange before and during quadriceps exercise, and 0.5 to 5 hours in recovery from quadriceps exercise, as well as on muscle glycogen resynthesis and activity in recovery. Twelve healthy, lean, young men participated. Before exercise, leg glucose uptake was 0.42 ± 0.12 and 0.20 ± 0.02 mmol × min-1 (mean ± SD) for salbutamol and placebo (P = .06), respectively, while leg oxygen consumption was around 2-fold higher (P < .01) for salbutamol than for placebo (25 ± 3 vs 14 ± 1 mL × min-1). No treatment differences were observed in leg glucose uptake, lactate release, and oxygen consumption during exercise. But in recovery, cumulated leg glucose uptake, lactate release, and oxygen consumption was 21 mmol (95% CI 18-24, P = .018), 19 mmol (95% CI 16-23, P < .01), and 1.8 L (95% CI 1.6-2.0, P < .01) higher for salbutamol than for placebo, respectively. Muscle glycogen content was around 30% lower (P < .01) for salbutamol than for placebo in recovery, whereas no treatment differences were observed in muscle glycogen resynthesis or glycogen synthase activity. Exercise blunts the effect of beta2-agonist salbutamol on leg glucose uptake, but this attenuation diminishes in recovery. Salbutamol increases leg lactate release in recovery, which may relate to glycolytic trafficking due to excessive myocellular glucose uptake.

Initial Liver Copper Status in Finishing Beef Steers Fed Three Dietary Concentrations of Copper Affects Beta Agonist Performance, Carcass Characteristics, Lipolysis Response, and Muscle Inflammation Markers.

Simple SummaryBeta agonists are commonly used in the United States beef industry, offering improved performance in the days leading up to harvest by influencing energy metabolism. Copper has been shown to regulate the biological pathway leading to increased lipid mobilization. However, this connection has not been evaluated in cattle. Therefore, the objective of this study was to determine how Cu influences beta agonist-induced performance, energy metabolism and inflammation in feedlot cattle. Supplementation of Cu resulted in increased liver Cu concentrations, while cattle performance, lipolysis, and some markers of inflammation responded to Cu supplementation differently, depending on whether or not cattle were fed a beta agonist. Therefore, strategic supplementation of Cu may help optimize growth of cattle receiving a beta agonist.Ninety-three Angus-crossbred steers (470 ± 35 kg) were assigned to a 3 × 2 factorial to determine the effects of Cu status and beta agonist (BA) on performance, carcass characteristics, lipolytic rate, and muscle inflammation. Factors included Cu supplementation (mg Cu/kg dry matter (DM)) at: 0 (LO), 10 (MED), or 20 (HI) from Cu amino acid complex (Availa Cu; Zinpro) with no BA (NoRAC) or 300 mg·steer−1·day−1 of ractopamine hydrochloride (RAC; Optaflexx; Elanco) for final 28 days of 88-day trial. Linear and quadratic effects of Cu status within BA treatment were tested. Pre-BA gain was not affected by Cu supplementation (p ≥ 0.57), although day 53 liver Cu quadratically increased (p = 0.01). Average daily gain and muscle IL-8 gene expression quadratically increased (p ≤ 0.01), with MED having greatest gain and gene expression. Ribeye area tended to quadratically increase with Cu supplementation within RAC (p = 0.08). In vitro basal lipolytic rate tended to quadratically increase with Cu supplementation within RAC (p = 0.11), while stimulated lipolytic rate tended to linearly increase within NoRAC (p = 0.10). These data suggest lipolysis and the BA response of steers are influenced by dietary and liver Cu concentrations.

Systematic Review: Guideline-Based Approach for the Management of Asthma and Subtypes via Chinese Medicine

Background Asthma is a chronic condition that results in the inflammation and narrowing of airways, often clinically presenting as wheeze and shortness of breath. Little is known of the mechanisms of action (MOA) of herbs used to treat asthma. The aim of this study is to review existing data regarding known MOA of traditional Chinese medicine which will aid in the understanding of possible interactions between Western drugs and Chinese herbs as well as the standardization of management via a proposed guideline to improve patient safety and possible synergism in the long term. Methods We searched through 5 databases for commonly prescribed herbs and formulas for asthma and narrowed down the search to identify the underlying MOA of individual herbs that could specifically target asthma symptoms. We included studies that stated the MOA of individual herbs when used for treating symptoms of asthma, excluding them if they are described as part of a formula. Results A total of 26 herbs commonly prescribed for asthma with known mechanism of action were identified. Herbs used for asthma were found to have similar MOA as that for drugs. Based on existing GINA guidelines, a guideline is proposed which includes a total of 5 steps depending on the severity of asthma and the herbs' MOA. 16 formulas were subsequently identified for the management of asthma, which consist of 12 “stand-alone” and 4 “add-on” formulas. “Stand-alone” formulas used independently for asthma generally follow the GINA guidelines but do not proceed beyond step 3. These formulas consist mainly of beta-agonist and steroid-like effects. “Add-on” formulas added as adjunct to “stand-alone” formulas, however, mainly act on T helper cells or have steroid-like effects. Conclusion Through the understanding of MOA of herbs and their respective formulas, it will ensue greater patient safety and outcomes.

Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions.

No AccessJournal of UrologyUrological Survey1 Dec 2020Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions Anthony AtalaMD Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001285.02AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions." The Journal of Urology, 204(6), p. 1385 Suggested Reading : Systemic and topical drug administration in the pig ureter: effect of phosphodiesterase inhibitors alpha1, beta and beta2-adrenergic receptor agonists and antagonists on the frequency and amplitude of ureteral contractions. J Urol 2001; 166: 714. Link, Google Scholar © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 204Issue 6December 2020Page: 1385-1385 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Atala More articles by this author Expand All Advertisement PDF DownloadLoading ...

In Vitro Effects of Beta-2 Agonists on Skeletal Muscle Differentiation, Hypertrophy, and Atrophy

Background Beta-2 agonists are widely used in the treatment of asthma and chronic obstructive pulmonary disease for their effect on airway smooth muscle relaxation. They also act on skeletal muscle, although their reported ergogenic effect is controversial.Aim To evaluate the in vitro effects of short-acting and long-acting beta-2 agonists on adrenergic receptor (ADR) expression, hypertrophy, and atrophy markers, in a skeletal muscle cell line.Methods The C2C12 cell line was used as a model of skeletal muscle differentiation. ADR messenger RNA expression was evaluated in proliferating myoblasts, committed cells, and differentiated myotubes, in basal conditions and after treatment with 10-6 M clenbuterol, salbutamol, salmeterol, and formoterol. Effect of beta-2 agonists on gene and protein expression of hypertrophy and atrophy markers was assessed in differentiated myotubes.Results Our study shows that beta-2 ADR messenger RNA was expressed and progressively increased during cell differentiation. Beta-2 agonist treatment did not affect its expression. Skeletal muscle hypertrophy markers (fast and slow myosin, myogenin) were not modulated by any of the beta-2 agonists evaluated. However, clenbuterol induced a significant, dose-dependent downregulation of skeletal muscle atrophy genes (atrogin-1, MuRF-1, and cathepsin L).Conclusions The reported ergogenic effect of beta-2 agonists, if any, should be considered as drug-specific and not class-specific and that of clenbuterol is mediated by the inhibition of the atrophic pathway.

Effect of beta-agonists on LAM progression and treatment

Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2+/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

Long-acting inhaled bronchodilators for cystic fibrosis.

Cystic fibrosis is a life-limiting inherited condition which affects one in 2500 newborns in the UK and 70,000 children and adults worldwide. The condition is multifaceted and affects many systems in the body. The respiratory system is particularly affected due to a build up of thickened secretions and a predisposition to infection. Inhaled bronchodilators are prescribed for 80% of people with cystic fibrosis in order to widen the airways and alleviate symptoms. Both short- and long-acting inhaled bronchodilators are used to improve respiratory symptoms. Short-acting inhaled bronchodilators take effect in minutes and typically last for four to eight hours (muscarinic antagonists). Long-acting inhaled bronchodilators also take effect within minutes but typically last for around 12 hours and sometimes longer. This review is one of two which are replacing a previously published review of both long- and short-acting inhaled bronchodilators. This review aims to evaluate long-acting inhaled bronchodilators in children and adults with cystic fibrosis in terms of clinical outcomes and safety. If possible, we aimed to assess the optimal drug and dosage regimen. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 10 October 2017.We also carried out a separate search of Embase and the reference lists of included trials. We searched clinical trials registries for any ongoing trials and made contact with pharmaceutical companies for any further trials.Date of Embase search: 11 October 2017. Randomised or quasi-randomised parallel trials comparing long-acting inhaled bronchodilators (beta-2 agonists and muscarinic antagonists) with placebo, no treatment or a different long-acting inhaled bronchodilator in adults and children with cystic fibrosis. Both authors independently assessed trials for inclusion (based on title, abstract and full text). The authors independently assessed the included trials for quality and risk of bias and extracted data. Discrepancies were resolved by a third party. The searches identified 195 unique references, of which 155 were excluded on title and abstract. We assessed the full texts of the remaining references, excluded 16 trials (28 references) and included four trials (12 references) in the review with 1082 participants.One trial (n = 16) measuring the effect of beta-2 agonists reported an improvement in forced expiratory volume at one second (FEV1) after treatment (at one month), but the trial was small with an unclear risk of bias so we judged the evidence to be very low quality. The trial did not report on participant-reported outcomes, quality of life or adverse events.Three trials (n = 1066) looked at the effects of the muscarinic antagonist tiotropium at doses of 2.5 µg and 5.0 µg in both the short term (up to 28 days) and the longer term (up to three months). Only one of the trials reported the change in FEV1 (L) after 28 days treatment and showed no significant difference between groups; with 2.5 µg tiotropium, mean difference (MD) -0.02 (95% confidence interval (CI) -0.13 to 0.09), or 5.0 µg tiotropium, MD 0.00 (95% CI -0.10 to 0.10) (moderate-quality evidence). All three trials of muscarinic antagonists provided data on adverse events which were found to differ little from placebo at doses of 2.5 µg, risk ratio (RR) 1.01 (95% CI 0.92 to 1.11) or 5.0 µg, RR 0.98 (95% CI 0.90 to 1.06). Very little participant-reported outcome data or quality of life data were available for analysis. Two of the trials were at low risk of bias overall whilst the remaining trial was at an unclear risk overall. Neither long-acting beta-2 agonists nor long-acting muscarinic antagonist bronchodilators demonstrate improvement in our primary outcome of FEV1. No difference was observed between intervention and placebo in terms of quality of life or adverse events. The quality of evidence for the use of beta-2 agonists was very low. The use of a long-acting inhaled bronchodilator may help to reduce the burden of treatment for people with cystic fibrosis as it is taken less often than a short-acting inhaled bronchodilator, but future trials would benefit from looking at the effects on our primary outcomes (spirometric changes from baseline, quality of life and adverse effects) in the longer term.

The feasibility of using multiple databases to study rare outcomes: the potential effect of long-acting beta agonists with inhaled corticosteroid therapy on asthma mortality.

Long-acting beta agonists (LABAs) when used without concomitant inhaled corticosteroids (ICS) increase the risk of asthma-related deaths, but the effect on asthma-related death of LABA used in combination with ICS therapy is unknown. To address this question, we explored the feasibility of conducting an observational study using multiple US health care data sources. Retrospective cohort study to evaluate the likelihood of getting an upper 95% confidence limit ≤1.4 for the asthma mortality rate ratio and ≤0.40 per 10 000 person-years for the mortality rate difference, assuming no effect of new use of combined LABA + ICS (versus non-LABA maintenance therapy) on asthma mortality. Ten research institutions executed centrally distributed analytic code based on a standard protocol using an extracted (2000-2010) persistent asthma cohort (asthma diagnosis and ≥4 asthma medications in 12 months). Pooled results were analyzed by the coordinating center. Asthma deaths were ascertained by linkage with the National Death Index. In a cohort of 994 627 persistent asthma patients (2.4 million person-years; 278 asthma deaths), probabilities of the upper 95% confidence limit for effect estimates being less than targeted values, assuming a null relation, were about 0.05. Modifications in cohort and exposure definitions increased exposed person-time and outcome events, but study size remained insufficient to attain study goals. Even with 10 data sources and a 10-year study period, the rarity of asthma deaths among patients using certain medications made it infeasible to study the association between combined LABA + ICS and asthma mortality with our targeted level of study precision. Copyright © 2016 John Wiley & Sons, Ltd.

The Effect of Theophyl line Beta Agonist in Laying and Some of Egg Characteristics on Laying Hens

The Effect of Theophyl line Beta Agonist in Laying and Some of Egg Characteristics on Laying Hens

Effects of beta agonists and muscle type on polar lipid fatty acid concentration

Effects of beta agonists and muscle type on polar lipid fatty acid concentration