Beta-agonist Drugs Research Articles

Industrial meat in Canada, growth promoters and the struggle over international food standards

This article focuses on differing national regulations and standards regarding how meat for human consumption is produced and what is permissible in that production process. Attempts to harmonize these regulations at the global level to facilitate international trade have proven to be challenging. Such harmonization of regulations is especially important to countries exporting meat, such as Canada. The conflict at the global level reflects a range of differing trade interests and values about what meat is and how it should be produced. One area of disagreement is over the extent to which methods of growth promotion in animals using technology, particularly drugs, is acceptable and safe in terms of human consumption. Canada has taken the position that they are acceptable and safe. Using two case studies of regulations related to the most recent set of beta agonist drugs, ractopamine and zilpatrol, fed to livestock to promote growth, I examine the underlying sources of these conflicts and the extent to which they reflect the interests of various actors and the forms of power they may employ to try to shape global standards at the Codex Alimentarius and the view of what is acceptable meat.

Beta-agonist drugs modulate the proliferation and differentiation of skeletal muscle cells in vitro

Essentially employed for the treatment of airway obstructions in humans, β-agonists are also known to have an anabolic effect in animals’ skeletal muscle. In vivo and in vitro studies have attested the increase in animal body mass and the hypertrophy of muscle cells following the administration of specific β-agonists. However, the contribution of β-agonists to C2C12 myoblasts growth remains obscure. We therefore aimed to investigate the impact of β1-and β2-agonist drugs on the proliferation and differentiation of skeletal muscle cells. Direct observations and cytotoxicity assay showed that clenbuterol, salbutamol, cimaterol and ractopamine enhanced muscle cell growth and viability during the proliferation stage. Structural examinations coupled to Western blot analysis indicated that salbutamol and cimaterol triggered a decrease in myotube formation. A better comprehension of the effect of β-agonists on myogenic regulatory genes in the muscle cells is crucial to establish a specific role of β-agonists in muscle development, growth, and regeneration.

The Association between anti-hypertensive and beta-agonist drugs and risk of Parkinson's Disease: a large meta-analysis study

Background: Growing evidence showed the association between beta-2 adrenoreceptor modulation, calcium regulation, renin-angiotensin system, and pathophysiology of Parkinson's disease (PD). However, the relationship between drugs targeting these systems and PD remains inconclusive.

Preservation of renal function in cardiac surgery patients with low cardiac output syndrome: levosimendan vs beta agonists

BackgroundSome studies have been performed to assess the effects of levosimendan on cardiac function when administered to cardiac surgery patients with low cardiac output syndrome (LCOS) in the immediate postoperative period. Levosimendan is an inotropic agent for the treatment of low cardiac output syndrome that seems to have a protective effect on renal function.MethodsIt is a quasi-experimental study. A total of 100 patients with LCOS received either beta-agonists or levosimendan. We assessed the incidence of postoperative kidney failure in cardiac surgery patients. In patients who had kidney failure at diagnosis of LCOS, we examined whether differences existed in the evolution of kidney failure based on the treatment administered for LCOS. The parameters measured included haemodynamics, oxygen supply, and renal function as assessed by the AKI scale. ANOVA, Student’s t-test and Wilcoxon or Friedman tests were used.ResultsUp to 30% of cardiac surgery patients had kidney failure at diagnosis of LCOS. Kidney failure at discharge from the ICU was more frequent in patients who received beta-agonist drugs as compared to those who received levosimendan (p < 0.05).ConclusionThe incidence of kidney failure decreased with the postoperative administration of levosimendan to cardiac surgery patients with LCOS, as compared to beta-agonists.Trial registrationCurrent Controlled Trials ISRCTN 46058317. Date of registration: 7/10/2019.Retrospectively registered.

Prevalensi dan Pola Peresepan Obat Asma Eksaserbasi pada Salah Satu Rumah Sakit Di Klaten

&#x0D; &#x0D; &#x0D; &#x0D; Exacerbation of asthma is a condition of worsening asthma symptoms that result in disruption of one's activities. Treatment efforts that are not in accordance with the guidline actually worsen and have side effects. This study aims to determine the prevalence and characteristics of exacerbation of asthma drugs given by doctors. The study design used retrospective data on 82 exacerbated asthma patients in the outpatient pharmacy Dr. Soeradji Tirtonegoro Klaten in 2018. The results showed the prevalence of asthma exacerbations of 461 cases. The drug groups obtained included beta-2 agonists (41.4%), corticosteroid groups (30.4%), antihistamines (16%), mucolytic groups (6.1%), analgesic groups (6.1%) . The types of drugs that are often used are salbutamol (39.0%), methylprednisolone (17.1%), seretide (10.9%), cetirizine (10.9%), ambroxol (6.1%), paracetamol (6, 1%), ranitidine (4.9%), simbicort (2.5%), dexametasone (2.5%). The results showed that the drugs most prescribed by doctors were the Beta-2 Agonist drugs with salbutamol.&#x0D; &#x0D; &#x0D; &#x0D;

Emakumezkoaren gernu-inkontinentzia

Emakumezkoetan gernu-inkontinentzia (GI) sarritan agertzen den osasun-arazo bat da, haien bizikalitatea sendo asaldatzen duena; halere, lotsa edota informazio faltagatik ia erdiek ez dute kontsultatzen. Gernu-inkontinentzia mota ezberdinak daude eta horien artean bi dira nagusiak: premiazko gernu-inkontinentzia (PGI) eta estresagatiko gernu-inkontinentzia (EGI). Bai ginekologoak bai urologoak azter dezake arazo hau eta beharrezko ikerketa burutu ondoren tratamendu egokiena ezarri; hasteko teknika kontserbatzaileak erabiltzen dira, zeinak zoru pelbikoko muskuluen indartzean, gernu-maskuriaren heziketan edota eguneroko bizi-ohiturak aldatzean oinarritzen diren. Horiek porrot egiten badute, inkontinentzia motaren arabera tratamendu ezberdinak daude. PGIan tratamendu farmakologikoa erabil dezakegu, antimuskarinikoak edota beta 3 agonista adrenergikoak hain zuzen. EGIaren kasuan, ostera, kirurgiara joko dugu; badaude horretarako hainbat teknika, urteetan zehar hobetuz joan direnak, gaur egun erabiliena uretra azpiko xingolak direlarik, polipropilenozkoak. Xingolen eraginkortasun-tasa altua da, mota ezberdinak daude bakoitza bere berezitasunekin eta horiek ezagutzea ezinbestekoa da pazienteari aholku egokiena emateko. Beraz funtsezkoa da emakumeek jakin dezaten gernu-inkontinentzia ez dela zahartzearen ondorio normal bat eta badaudela horretarako konponbideak.

Effect of CArbocisteine in Prevention of exaceRbation of chronic obstructive pulmonary disease (CAPRI study): An observational study

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a chronic and progressive lung disease characterized by irreversible airflow obstruction, airway inflammation, oxidative stress and, often, mucus hypersecretion. The aim of this study is to determine if carbocisteine, a mucolytic and antioxidant agent, administered daily for 12 months, can reduce exacerbation frequency in COPD patients. MethodsThis observational study was conducted in Naples (population approximately 1000,000), Italy. It included 85 out-patients (mean age of 67.8 ± 8.6 years) followed by Clinic of Respiratory Diseases of the University Federico II. Every patient underwent spirometry demonstrating airflow obstruction not fully reversible according to ERS/ATS criteria for COPD diagnosis (Tiffenau index less than 70% after administration of salbutamol, a beta2 agonist drug). Patients enrolled had diagnosed COPD since 2 years and suffered at least one exacerbation in the previous year. None of the patients had been treated with carbocisteine or other mucolytic agent for a longer period of time than 7 days and no more than 4 times in the previous year to the enrollment. All of them assumed daily 2.7 g of carbocisteine lysine salt for a year in addition to their basic therapy. ResultsThe comparison of exacerbation frequency between the previous year (T0) and the end of study treatment (T12), documents a statistically significant reduction of exacerbations(number of exacerbations at T0: 2 [1,3] vs number of exacerbations at T12: 1 [1,2]; p < 0.001).Quality of life was also reported and showed a statistically significant improvement at the end of the study (p < 0.001).We did not find correlation between reducing exacerbation frequency and exposure to cigarette smoking, passive smoking exposure in childhood, the use of inhaled steroids, the level of education of our patients and the GOLD stadium. InterpretationDaily administration of a mucolytic drug such as carbocisteine for prolonged periods in addition to the bronchodilator therapy can be considered a good strategy for reducing exacerbation frequency in COPD.

Contemporary treatment of children with critical and near-fatal asthma.

Asthma is the most common chronic illness in childhood. Although the vast majority of children with acute asthma exacerbations do not require critical care, some fail to respond to standard treatment and require escalation of support. Children with critical or near-fatal asthma require close monitoring for deterioration and may require aggressive treatment strategies. This review examines the available evidence supporting therapies for critical and near-fatal asthma and summarizes the contemporary clinical care of these children. Typical treatment includes parenteral corticosteroids and inhaled or intravenous beta-agonist drugs. For children with an inadequate response to standard therapy, inhaled ipratropium bromide, intravenous magnesium sulfate, methylxanthines, helium-oxygen mixtures, and non-invasive mechanical support can be used. Patients with progressive respiratory failure benefit from mechanical ventilation with a strategy that employs large tidal volumes and low ventilator rates to minimize dynamic hyperinflation, barotrauma, and hypotension. Sedatives, analgesics and a neuromuscular blocker are often necessary in the early phase of treatment to facilitate a state of controlled hypoventilation and permissive hypercapnia. Patients who fail to improve with mechanical ventilation may be considered for less common approaches, such as inhaled anesthetics, bronchoscopy, and extracorporeal life support. This contemporary approach has resulted in extremely low mortality rates, even in children requiring mechanical support.

To: Contemporary treatment of children with critical and near-fatal asthma.

Asthma is the most common chronic illness in childhood. Although the vast majority of children with acute asthma exacerbations do not require critical care, some fail to respond to standard treatment and require escalation of support. Children with critical or near-fatal asthma require close monitoring for deterioration and may require aggressive treatment strategies. This review examines the available evidence supporting therapies for critical and near-fatal asthma and summarizes the contemporary clinical care of these children. Typical treatment includes parenteral corticosteroids and inhaled or intravenous beta-agonist drugs. For children with an inadequate response to standard therapy, inhaled ipratropium bromide, intravenous magnesium sulfate, methylxanthines, helium-oxygen mixtures, and non-invasive mechanical support can be used. Patients with progressive respiratory failure benefit from mechanical ventilation with a strategy that employs large tidal volumes and low ventilator rates to minimize dynamic hyperinflation, barotrauma, and hypotension. Sedatives, analgesics and a neuromuscular blocker are often necessary in the early phase of treatment to facilitate a state of controlled hypoventilation and permissive hypercapnia. Patients who fail to improve with mechanical ventilation may be considered for less common approaches, such as inhaled anesthetics, bronchoscopy, and extracorporeal life support. This contemporary approach has resulted in extremely low mortality rates, even in children requiring mechanical support.

COPD: maximization of bronchodilation

&#x0D; &#x0D; &#x0D; &#x0D; The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient’s functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.&#x0D; &#x0D; &#x0D; &#x0D;

COPD: maximization of bronchodilation.

The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient’s functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.

A novel solid phase extraction column combined with ultra performance liquid chromatography/tandem mass spectrometry for selective enrichment and determination of clenbuterol in pork

A simple and efficient method based on a novel solid phase extraction (SPE) cartridge and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) was developed for the determination of clenbuterol residue in pork. The minced pork sample was ultrasonically extracted by 5% (v/v) perchloric acid and centrifuged at 10 000 r/min for 15 min, then the supernatant was purified by an SMCX cartridge, which is a novel SPE column based on homemade silica matrix with two mixed modes of reversed-phase and strong cation exchange, for the selective enrichment and purification of the analyte. The linear range of the method was 0.25 - 50 microg/kg with a correlation coefficient of 0.998 2. The average recoveries ranged from 62.2% to 72.0% at the three spiked levels of 1.25, 12.5 and 50 microg/kg with the relative standard deviations (RSDs) between 4.2% and 6.1%. The limit of detection (S/N = 3) was 0.05 microg/kg. The method is simple, fast and can be extended to enrich and determine beta-agonist drugs.

GSNO reductase and β2-adrenergic receptor gene–gene interaction: bronchodilator responsiveness to albuterol

Short-acting inhaled beta2-agonists such as albuterol are used for bronchodilation and are the mainstay of asthma treatment worldwide. There is significant variation in bronchodilator responsiveness to albuterol not only between individuals but also across racial/ethnic groups. The beta2-adrenergic receptor (beta2AR) is the target for beta2-agonist drugs. The enzyme, S-nitrosoglutathione reductase (GSNOR), which regulates levels of the endogenous bronchodilator S-nitrosoglutathione, has been shown to modulate the response to beta2-agonists. We hypothesized that there are pharmacogenetic interactions between GSNOR and beta2AR gene variants that are associated with variable response to albuterol. We performed family-based analyses to test for association between GSNOR gene variants and asthma and related phenotypes in 609 Puerto Rican and Mexican families with asthma. In addition, we tested these individuals for pharmacogenetic interaction between GSNOR and beta2AR gene variants and responsiveness to albuterol using linear regression. Cell transfection experiments were performed to test the potential effect of the GSNOR gene variants. Among Puerto Ricans, several GSNOR SNPs and a haplotype in the 3'UTR were significantly associated with increased risk for asthma and lower bronchodilator responsiveness (P=0.04-0.007). The GSNOR risk haplotype affects expression of GSNOR mRNA and protein, suggesting a gain of function. Furthermore, gene-gene interaction analysis provided evidence of pharmacogenetic interaction between GSNOR and beta2AR gene variants and the response to albuterol in Puerto Rican (P=0.03), Mexican (P=0.15) and combined Puerto Rican and Mexican asthmatics (P=0.003). Specifically, GSNOR+17059*beta2AR+46 genotype combinations (TG+GG*AG and TG+GG*GG) were associated with lower bronchodilator response. Genotyping of GSNOR and beta2AR genes may be useful in identifying Latino individuals, who might benefit from adjuvant therapy for refractory asthma.

Long-Acting Beta-Agonists and Asthma Death: How Useful Are Different Study Designs to Evaluate the Potential Association?

Background and Objective. There is uncertainty whether long-acting beta-agonist (LABA) drugs may increase the risk of asthma mortality. This uncertainty is partly due to the difficulty in estimating the risk of rare adverse outcomes. The aim of this paper is to consider the utility of three approaches to determine the magnitude and statistical significance of this potential association. Methods. Using a death rate of 9 per 10,000 subjects with asthma, derived from a meta-analysis of randomized controlled trials (RCTs) of formoterol, power calculations for a single RCT, a case-control study, and a meta-analysis of RCTs were determined. Results. For each study design, the number of subjects and events required to have adequate statistical power to detect a 1.5- and 2.0-fold increased risk of death were calculated. For a single RCT, or meta-analyses of RCTs, very large sample sizes are required. In contrast, case-control methodology represents a realistic method of estimating the risk of rare serious adverse events. Conclusions. Major practical limitations exist in the use of RCTs to determine the potential risk of death with LABAs in the treatment of asthma. Case-control methodology may be more effective in establishing causation; however, if selection bias occurs, estimates of risk may be inaccurate.

Risk of mortality associated with formoterol: a systematic review and meta-analysis

There is concern long-acting beta-agonist (LABA) drugs may increase the risk of asthma mortality. We undertook a systematic review which included the AstraZeneca Formoterol Clinical Trial Safety Database and Novartis Food and Drug Administration Formoterol Briefing Document. Randomised controlled clinical trials of duration > or = 4 weeks that compared formoterol with a non-LABA comparator treatment in asthma were included in a meta-analysis of the risk of all-cause mortality and asthma death. Simple contingency tables, Peto's one-step method and a Bayesian analysis were used. There were 42 deaths (nine from asthma) recorded in 62 studies with 49,327 subjects. The simple contingency table odds ratio for risk of all-cause mortality with formoterol was 1.1 (95% CI 0.6-2.2) and for asthma death was 2.7 (95% CI 0.5-26.7). Analyses by the other methods using both "as randomised" and "as exposed" classifications of treatment gave similar risk estimates with wide confidence and credible intervals. We conclude that there was insufficient power to determine whether formoterol increases the risk of mortality. However, the point estimates of a 2.0- to 3.2-fold increased risk of asthma death are not reassuring and add weight to evidence that LABA use in certain circumstances may increase the risk of asthma mortality.

Alterações ecocardiográficas em doentes asmáticos

Introduction: Asthma is a chronic inflammatory disease which has increased during the last 20 years, putting a strain on medical resources, particularly severe forms of the disease. Treatment in such cases is inhaled corticosteroids and beta agonist drugs that can produce a range of side effects. The aim of this study is to identify echocardiograph abnormalities and correlate them with severity of disease.Methodology: Eight-seven outpatients were selected at the asthma unit of the Gaffrée Guinle University Hospital (HUGG). Each patient underwent spirometry, electrocardiogram (ECG) and echocardiogram (ECO) during the trial within a month maximum. Echocardiograph abnormalities found related to degree of asthma. Statistical analysis was made by non-parametric tests.Results: We found significant differences (p≤0.05) for age, disease duration and haemoglobin saturation (SaO2) between the moderate and severe groups. In the sample a high prevalence of tricuspid insufficiency (41.4%) was identified.Conclusions: ECO identified a series of abnormalities that were not always dependent on severity of disease. ECO can identify pulmonary hypertension through calculation of mean pressure of the pulmonary artery.Rev Port Pneumol 2008; XIV (3): 363-377

Echocardiograph alterations in asthma patients

IntroductionAsthma is a chronic inflammatory disease which has increased during the last 20 years, putting a strain on medical resources, particularly severe forms of the disease. Treatment in such cases is inhaled corticosteroids and beta agonist drugs that can produce a range of side effects. The aim of this study is to identify echocardiograph abnormalities and correlate them with severity of disease. MethodologyEight-seven outpatients were selected at the asthma unit of the Gaffree Guinle University Hospital (HUGG). Each patient underwent spirometry, electrocardiogram (ECG) and echocardiogram (ECO) during the trial within a month maximum. Echocardiograph abnormalities found related to degree of asthma. Statistical analysis was made by nonparametric tests. ResultsWe found significant differences (p≤0.05) for age, disease duration and haemoglobin saturation (SaO2) between the moderate and severe groups. In the sample a high prevalence of tricuspid insufficiency (41.4%) was identified. ConclusionsECO identified a series of abnormalities that were not always dependent on severity of disease. ECO can identify pulmonary hypertension through calculation of mean pressure of the pulmonary artery.

International trends in asthma mortality.

Throughout the 20th century many different patterns of asthma mortality have been observed. Following relatively stable asthma mortality rates during the first half of this century, there has been a gradual increase in asthma mortality in many countries over the last 50 years. Although a number of possible explanations have been proposed to explain this trend-including increases in asthma prevalence, increases in exposure to factors that trigger asthma attacks and changes in asthma management-their relative contribution in different countries is uncertain. Another pattern is that of sudden marked increases in asthma mortality occurring in at least seven countries in the 1960s and in New Zealand in the 1970s. Available evidence indicates that the cause of these 'epidemics' was the use of high dose preparations of two specific beta-agonist drugs, namely isoprenaline forte and fenoterol. The most recent trend observed in a number of western countries during the last decade has been a gradual reduction in asthma mortality; this may relate to improvements in the management of asthma.

Pharmacogenetics of β&lt;sub&gt;2&lt;/sub&gt;-Agonist Drugs in Asthma

Genetic variation in the structure of the beta2-adrenoceptor (ADRB2) is a potentially important source of variability in the response to beta2-agonist drugs. The relevant polymorphisms are common, with allele frequencies as high as 50% in some cases. "Nonsynonymous" variants result in amino acid substitutions in the receptor structure, of which substitution of Gly for Arg at position 16 and Glu for Gln at position 27 are the most clinically relevant. Other polymorphisms occur in the noncoding flanking regions of the gene and may be important in regulating ADRB2 expression, thus affecting individual drug responses. Linkage disequilibrium involving polymorphisms in both the coding and noncoding regions may explain the diversity of outcomes regarding functional in vitro studies. To date, analysis by haplotype, rather than genotype, has tended to confuse the issues. Functional in vitro studies provide the basis by which these polymorphisms are believed to be relevant in vivo. However, follow-up investigations have not substantiated the conventional wisdom that Gly-16 confers increased propensity to downregulation, whereas Glu-27 confers resistance. The in vivo picture is further complicated by the dynamic status of ADRB2s. Paradoxically, downregulation of receptors with exogenous beta2-agonist drugs may occur more readily in cells that are relatively resistant to downregulation with exposure to endogenous catecholamine. Numerous studies have highlighted that the Arg-16 variant is associated with an enhanced bronchodilator response in vivo, although the picture is not a consistent one. Outcomes during chronic treatment of asthma with beta2-agonists have been more consistent. In patients who are homozygous for Arg-16, reduced lung function and increased frequency of exacerbations occur during chronic treatment with short-acting beta2-agonists. With long-acting beta2-agonists, the overall clinical benefits may be worse for Arg-16 than for the Gly-16 genotype. Therefore, ADRB2 polymorphisms are an important consideration in assessing individual patients with difficult asthma that may be drug-induced for reasons of ADRB2 genotype. They are also relevant in the design of clinical trials involving beta2-agonist therapy.

Bronchodilator Response in Relation to β2-Adrenoceptor Haplotype in Patients with Asthma

Genetic variation of the beta2-adrenoceptor (ADRB2) influences receptor function in vitro. There are reports that, in vivo, bronchodilator response is related to ADRB2 genotype, and that clinical outcomes during chronic therapy with beta2-agonist drugs are also influenced by genotype. Whether these features are related to single nucleotide polymorphisms or to combinations (haplotypes) is unclear. Our aim was to measure bronchodilator response in patients with asthma stratified by ADRB2 haplotype. This was done after eliminating the confounding effect of prior drug treatment with inhaled beta2-agonists and corticosteroids. ADRB2 haplotype was determined in 176 patients with asthma, of whom 161 harbored the six most common combinations. Treatment with inhaled beta2-agonists and inhaled corticosteroids was withheld for appropriate intervals. Spirometric changes 20 minutes after a single dose of albuterol (2.5 mg by nebulizer) were then recorded. There were no significant differences in bronchodilator response (% improvement in FEV(1)) with respect to any of the major ADRB2 haplotypes or genotypes. Genetic variation of the ADRB2 does not influence the immediate response to inhaled beta2-agonist. The confounding effect of tolerance resulting from regular beta2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with beta2-agonists.