***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: BACKGROUND The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial . Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine ( Arg/Arg ) , rather than glycine ( Gly/Gly ) , at aminoacid residue 16 of the beta2-adrenergic receptor . However , the existence of any genotype-dependent difference has not been tested in a prospect i ve clinical trial . METHODS Patients with mild asthma , not using a controller medication , were enrolled in pairs matched for forced expiratory volume in 1 s ( FEV1 ) according to whether they had the Arg/Arg ( n=37 ; four of 41 matches withdrew before r and omisation ) or Gly/Gly ( n=41 ) genotype . Regularly scheduled treatment with albuterol or placebo was given in a masked , cross-over design , for 16-week periods . During the study , as-needed albuterol use was discontinued and ipratropium bromide was used as needed . Morning peak expiratory flow rate ( PEFR ) was the primary outcome variable . The primary comparisons were between treatment period for each genotype ; the secondary outcome was a treatment by genotype effect . Analyses were by intention to treat . FINDINGS During the run-in period , when albuterol use was kept to a minimum , patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min ( p=0.0162 ) ; the change in patients with the Gly/Gly genotype was not significant ( 2 L/min ; p=0.8399 ) . During r and omised treatment , patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo ( 14 L/min [ 95 % CI 3 to 25 ] ; p=0.0175 ) . By contrast , patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period , when albuterol use was limited ( -10 L/min [ -19 to -2 ] ; p=0.0209 ) . The genotype-attributable treatment difference was therefore -24 L/min ( -37 to -12 ; p=0.0003 ) . There were similar genotype-specific effects in FEV1 , symptoms , and use of supplementary reliever medication . INTERPRETATION Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use . Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions BACKGROUND The study of determinants of asthma is a subject of much interest currently , especially the pharmacogenetic aspects of asthma management . Genetic polymorphisms affecting amino-acids at positions 16 and 27 within beta(2)-adrenoceptor ( beta(2)AR ) gene have been implicated in the asthma phenotypes and influence on the variability observed in response to use of bronchodilator agents used in the treatment of asthma . Whether these polymorphisms alter the bronchoprotection response to beta(2)-agonist treatment in Spanish asthmatic population is unknown . The aim of this study was to investigate whether genetic polymorphisms within beta(2)AR gene modulate the clinical outcomes of the individual response to beta(2)-agonist therapy and the development of desensitization in Spanish asthmatic patients . METHODS In a prospect i ve , case-control study were included 80 asthmatic patients . Based on the st and ard criteria , patients were classified into two groups : patients with tachyphylaxis and good responders to beta(2)-agonist therapy .  DNA sample s were genotyped for the Arg(16)Gly and Glu(27)Gln alleles within the beta(2)AR gene as well as in 64 control sample s from blood donors . RESULTS Arg(16 ) allele was slightly more frequent within the group with tachyphylaxis ( P=0.039 ) , whereas Gly(16 ) allele carriers were overrepresented within the group of good responders ( 59.7 % , P=0.028 ) . On the other h and , the allele frequency of Gln(27 ) and the proportion of Gln(27 ) carriers was higher within the group with tachyphylaxis ( P=0.010 and 0.049 , respectively ) and Glu(27 ) allele carriers were overrepresented within the group of good responders ( P=0.026 ) . The Arg(16 ) and Gln(27 ) alleles were in strong linkage disequilibrium across this locus , result ing in the occurrence of disease haplotype . CONCLUSIONS The predisposition to develop tachyphylaxis in our population seems to be linked to the Arg(16 ) and Gln(27 ) alleles and to the Arg(16)/Gln(27 ) risk haplotype ( positive association between the presence of the Arg(16 ) and Gln(27 ) alleles and tachyphylaxis ) . The Arg(16 ) allele is perhaps overrepresented due to the strong linkage disequilibrium between both polymorphisms . The presence of the Glu(27 ) allele seems to be a protective factor against tachyphylaxis in this cohort study Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients . Polymorphisms of the beta(2)-adrenergic receptor ( beta(2)-AR ) can affect regulation of the receptor . Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results . We examined whether polymorphisms at codon 16 ( beta(2)-AR-16 ) and codon 27 ( beta(2)-AR-27 ) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use . During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 ( Arg/Arg ) who used albuterol regularly . This effect was magnified during a 4-wk run out period , during which all patients returned to using as-needed albuterol , so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30 . 5 + /- 12.1 L/min lower ( p = 0.012 ) than Arg/Arg patients who had used albuterol on an as needed basis . There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16 . Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis . No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR . No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms . Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment The prevalence of asthma in children has doubled over the past 25 years.1 Two common polymorphisms exist in the β adrenoceptor at amino acids 16 ( glycine for arginine ) and 27 ( glutamic acid for glutamine ) . Both are functionally relevant in cultured cells , with the glycine 16 form of the receptor showing enhanced downregulation and the glutamic acid 27 form showing attenuated downregulation after exposure to β agonists.2 The glutamine 27 polymorphism is associated with raised IgE concentrations in families with a history of asthma , and with increased reactivity of the airways in people with asthma . 3 4 We measured the prevalence of these polymorphisms in a r and om population of children to identify their importance in the expression of reported asthma . We approached children between the ages of 5 and 15 years ( mean 10.5 years ) and an accompanying parent who were attending the accident and To examine the roles of genetic polymorphism of the β2-adrenergic receptor ( β2AR ) in the relationship between eosinophil ( EOS ) counts and eosinophil cationic protein ( ECP ) counts and lung function , we recruited a r and om sample from the 1996 nationwide survey of asthma prevalence in middle school children . A total of 149 subjects—42 asthmatic children , 38 asthmatics in remission ( no reported attack for more than 12 months ) , and 69 nonasthmatics — completed a physical evaluation , pulmonary function test , and determination of EOS , ECP , and β2AR genotypes at amino acids 16 and 27 . Asthmatic children had higher EOS and ECP than did nonasthmatics . No association was found between asthma and β2AR genotypes . Lung function was significantly and inversely correlated with EOS but not with ECP in asthmatic children . By genotype , an inverse correlation between lung function and EOS was found in asthmatic children with Arg16Arg or Gln27Glu . A nonsignificant but similar inverse correlation was found in asthmatic children with Arg16Gly or Gln27Gln . However , a nonsignificant but positive correlation was found in asthmatic children with Gly16Gly . In conclusion , we suggest that EOS is a better clinical indicator of airway inflammation than ECP when children are not having an asthma attack . The association between an increase of EOS and lower lung function can be differentiated by β2AR genotypes at amino acid 16 To determine the association between the β2‐adrenoceptor polymorphisms at amino acids 16 and 27 and markers of allergic disease and asthma per se in a r and om adult population , and to determine the degree of linkage disequilibrium existing between polymorphisms at amino acid positions 16 , 27 , 164 and nucleic acid residue 523 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:
    
Conclusion The meta- analysis suggests that the ADRB2 rs1042714 polymorphism has a protective association with asthma in the overall population and the pediatric subgroup