***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To demonstrate the presence of functional cardiac β2-adrenoceptors in man , we studied the responses to intracoronary injections of salbutamol in three groups of six patients . We injected salbutamol , a selective β2-adrenoceptor agonist , into the right coronary artery to avoid peripheral vasodilator action and to stimulate the sinoatrial node directly . Salbutamol injections caused a sinus tachycardia . The same doses of salbutamol injected into the aortic root caused no change in heart rate , ruling out a systemic effect . The mean dose required to cause an increase in heart rate of 30 beats/min ( IHR30 ) was 2.6 μg in the first group of six patients . In 12 other patients salbutamol was given after β-blockade to confirm the β2-selectivity of the responses . Doses of practolol ( β1,-selective blockade ) and of propranolol ( β1- and β2-blockade ) that had equal β1-blocking activity were used . In six patients who were given practolol  , the mean IHR30 dose was 2.1 μg . In six patients who were given propranolol , the mean IHR30 dose was significantly greater at 64 μg ( p < 0.001 , practolol vs. propranolol ) . This study demonstrates that direct cardiac β2-adrenoceptor stimulation in man has a positive chronotropic effect The aim of this study was to determine the influence of single nucleotide polymorphisms in the β2-adrenoceptor gene , on the response to inhaled β2-agonists  in children with acute asthma . We hypothesised that children with polymorphisms that generate enhanced receptor downregulation in vitro , Gly16 and Gln27 , would have a slower response to β2-agonist therapy during acute asthma . One hundred and forty-eight children with acute asthma were recruited and genotyped for β2Arg16Gly and β2Gln27Glu . For Gln27Glu , individuals Gln27Gln took longest to stretch out to 1 , 2 and 4 hourly β2-agonists , followed by heterozygotes who were intermediate and Glu27Glu who responded most rapidly ( 1hourly : 2.6hr vs. 2.0 vs. 1.4 , p = 0.02 ; 2 hourly : 10.6hr vs. 10.7 vs. 6.8 , p = 0.07 ; 4 hourly : 29.8hr vs. 28.5 vs. 24.3 , p = 0.30 ) . The ability to prospect ively identify children who respond less effectively to β 2-agonists  during an acute asthma attack has the potential to allow the generation of genotype-specific treatment pathways Asthmatic patients receiving ICSs ( inhaled corticosteroids )  may take frequent add-on therapy with salbutamol despite on-dem and prescription . Frequent salbutamol use can be detrimental in asthma . The isomeric formulation of salbutamol and the B2ADR ( β2 adrenoceptor ) 16 genotype may also influence this phenomenon . We performed a r and omized , double-blind , placebo-controlled , triple crossover , proof of concept trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol [ 200 μg q.i.d . ( four times daily ) ] , levosalbutamol ( 100 μg q.i.d . ) or placebo on trough methacholine PC20 [ provocative concentration causing 20 % fall in FEV1 ( forced expiratory volume in 1 s ) ] 6 h post-dose ( the primary outcome ) in 30 persistent asthmatic patients ( 15 who were Arg16 homozygous and 15 who were Gly16 homozygous ) all receiving ICSs . There was no worsening of AHR ( airway hyper-responsiveness ) at trough to methacholine after 2 weeks regular exposure to either racemic ( P=0.53 ) or levosalbutamol ( P=0.84 ) compared with placebo , nor between genotypes-as dd ( doubling dilution ) difference in methacholine PC20 from placebo [ salbutamol/Arg16=0.36 dd [ 95 % CI ( confidence interval ) , -0.43 , 1.15 ] ; salbutamol/Gly16=0.01 dd ( 95 % CI , -0.47 , 0.49 ) ; levosalbutamol/Arg16=-0.01 dd ( 95 % CI , -0.89 , 0.87 ) ; and levosalbutamol/Gly16=0.28 dd ( 95 % CI , -0.22 , 0.77 ) ] . Both active treatments improved morning PEF ( peak expiratory flow ) in Gly16 ( P=0.04 overall ) but not Arg16 ( P=0.50 overall ) patients , whereas evening PEF improved in both Gly16 ( P<0.001 overall ) and Arg16 ( P=0.006 overall ) patients . In conclusion , the regular exposure to either racemic or levosalbutamol for 2 weeks added to ICSs did not cause worsening of AHR at trough compared with placebo ; with no difference seen between B2ADR 16 genotypes BACKGROUND Beta2-adrenergic receptor ( B2AR ) polymorphisms have been associated with a variety of asthma-related phenotypes , but association results have been inconsistent across different studies . OBJECTIVE We sought to apply family-based association methods to individual single nucleotide polymorphisms ( SNPs ) and haplotypes of SNPs in B2AR to define the relationship of these genetic variants to asthma-related phenotypes . METHODS DNA sample s were obtained from 707 Childhood Asthma Management Program participants , representing 650 sibships , as well as their parents .  Genotyping was performed at 8 B2AR SNPs . Qualitative asthma-related phenotypes were analyzed with single SNPs and haplotypes by using TRANSMIT ; quantitative asthma-related phenotypes were analyzed with the Family-Based Association Test . RESULTS Several SNPs , including SNP -654 and SNP + 46 , demonstrated significant associations ( P < .05 ) to postbronchodilator FEV1 as both a qualitative ( < 80 % of predicted value ) and quantitative phenotype . Quantitative phenotypic association analysis demonstrated significant evidence for association of SNP + 523 with bronchodilator responsiveness expressed as a percentage of baseline FEV1 ( P = .012 ) or a percentage of predicted FEV1 ( P = .008 ) . Similar evidence for association between the + 523 SNP and qualitative bronchodilator responsiveness phenotypes was also found . Analysis of haplotypes supported an association of B2AR variants with spirometric values and bronchodilator responsiveness . CONCLUSION B2AR variants are associated with spirometric values and bronchodilator responsiveness , but different regions of the gene provide evidence for association with these phenotypes Six healthy subjects were studied on two occasions . Grade d bolus injections of isoprenaline sulphate were given intravenously and control dose-response curves were drawn for the changes in heart rate and blood pressure . In a r and om order each subject received an intravenous infusion of either propranolol or practolol and further dose-response curves were constructed PRE- and POST-atropine ( 0.04 mg/kg ) . Exercise tachycardia was reduced 26.1 + /- 2.7 % by propranolol and this was not significantly different from the reduction by practolol ( 21.2 + /- 1.9 % ) . Propranolol attenuated the isoprenaline tachycardia ( dose ratio 43.7 ) and after atropinisation the dose ratio was not significantly altered ( 41.1 ) . Practolol also attenuated the isoprenaline tachycardia ( dose ratio 4.4 ) but after atropinisation the dose ratio was significantly increased to 8.8 , though this remained significantly less than the dose ratio for propranolol . At a heart rate increase of 25 beats/min , the isoprenaline-induced control fall in mean blood pressure was 9 - 11 mm Hg . After propranolol administration this fall was converted to a small increase of + 2.3 + /- 1.3 mm Hg . Following practolol , however , the mean blood pressure reduction was 19.7 + /- 2.9 mm Hg . Practolol did not significantly block the isoprenaline-induced fall in diastolic pressure . The difference in potency of propranolol and practolol , demonstrated by their effect on isoprenaline induced tachycardia at doses shown to have equal effects on exercise tachycardia , is contributed to but not fully explained by the reflex withdrawal of cardiac vagal tone which occurs with cardioselective but not non-selective antagonists Abstract Introduction : Genetic mutations in the β2 receptor could alter its functioning and the response to β2 agonists . The study was done to find out the effect of two commonly occurring polymorphisms-Arg16Gly and Gln27Glu , on cause of asthma and on response to nebulized salbutamol in South Indian subjects of asthma . Methods : After baseline measurements of Forced Expiratory Volume in 1st second ( FEV1 ) , Forced Vital Capacity ( FVC ) and Peak Expiratory Flow Rate ( PEFR ) , five mg of nebulized salbutamol was administered and spirometry was repeated . The increase in these parameters was calculated and patients were included for genotyping if the percentage increase in FEV1 was ≥12 % . The frequencies of these polymorphisms in patients were compared with those of healthy volunteers . Results : 112 patients and 127 healthy volunteers were genotyped . The frequencies of the polymorphisms were found to be similar to previously published Dravidian population frequencies . The frequencies of genotypes in asthmatics were similar to healthy volunteers . The increase in FEV1 , FVC and PEFR was similar across various genotypes and haplotypes in both the polymorphisms . The GG-CG haplotype was associated with 3.1 times increased occurrence of asthma ( p value = 0.02 ) . The G allele of the Arg16Gly polymorphism was associated with lower baseline FEV1 , FVC and PEFR values , but these were not statistically significant . Conclusion : The Arg16Gly and Gln27Glu polymorphisms do not determine the occurrence of asthma individually , but the GG-CG haplotype is associated with an increased risk of asthma . There is no effect of the genotypes on the response to nebulized salbutamol 
    Output:
    
If positive correlations are found , this knowledge may be used to improve personalized pharmacotherapy of albuterol use .