***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 
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    ***EXAMPLES*** 
    Input: Asthma is an increasing health problem worldwide , but the long-term temporal pattern of clinical symptoms is not understood and predicting asthma episodes is not generally possible . We analyse the time series of peak expiratory flows , a st and ard measurement of airway function that has been assessed twice daily in a large asthmatic population during a long-term crossover clinical trial . Here we introduce an approach to predict the risk of worsening airflow obstruction by calculating the conditional probability that , given the current airway condition , a severe obstruction will occur within 30 days . We find that , compared with a placebo , a regular long-acting bronchodilator ( salmeterol ) that is widely used to improve asthma control decreases the risk of airway obstruction . Unexpectedly , however , a regular short-acting β2-agonist bronchodilator ( albuterol ) increases this risk . Furthermore , we find that the time series of peak expiratory flows show long-range correlations that change significantly with disease severity , approaching a r and om process with increased variability in the most severe cases . Using a nonlinear stochastic model , we show that both the increased variability and the loss of correlations augment the risk of unstable airway function . The characterization of fluctuations in airway function provides a quantitative basis for objective risk prediction of asthma episodes and for evaluating the effectiveness of therapy CRTH2 is a G‐protein‐coupled receptor on T helper2 cells that mediates pro‐inflammatory effects of prostagl and in D2 in allergic responses . Background Chemoattractant receptor-homologous molecule expressed on T helper type 2 ( Th2 ) cell ( CRTh2 ) receptor antagonists is being investigated for asthma . Objectives The aim of this study was to assess the effects of the CRTh2 receptor antagonist , AZD1981 ( with/without inhaled corticosteroids [ ICSs ] ) , on lung function and asthma control . Patients and methods Adults aged 18–60 years were enrolled in two r and omized , placebo-controlled , parallel-group trials ( protocol number : D9830C00003 [ study 1 , n=209 ] and protocol number : D9830C00004 [ study 2 , n=510 ] ) . In study 1 , patients with stable asthma ( forced expiratory volume in 1 second [ FEV1 ] : 65%−110 % ) were withdrawn from ICS ( < 400 µg/d ) and r and omized to AZD1981 1,000 mg twice daily ( bid ) or placebo . In study 2 , patients with uncontrolled asthma ( FEV1 : 40%−85 % ) despite ICS therapy ( ≥500 µg/d ) were r and omized to 50 mg , 400 mg , or 1,000 mg bid AZD1981 or placebo . The primary efficacy variable for both trials was the change in morning peak expiratory flow after 4 weeks of treatment . Secondary variables included Asthma Control Question naire ( ACQ-5 ) scores , FEV1 assessment s , safety , and tolerability . In study 2 , efficacy was also assessed according to atopic status . Results Following 4 weeks of treatment , there was a nonsignificant increase in morning peak expiratory flow on AZD1981 1,000 mg bid ( 9.5 L/min vs placebo , P=0.086 [ study 1 ] and 12 L/min vs placebo , P=0.16 [ study 2 ] ) . In study 2 , all doses of AZD1981 provided significant improvements in ACQ-5 scores ( 0.26–0.3 units vs placebo , P=0.010–0.022 ) ; however , there was no dose – response relationship . Improved ACQ-5 scores and FEV1 were observed in the majority of atopic patients treated with AZD1981 . AZD1981 was well tolerated across treatment groups . Conclusion Further research may be warranted in atopic patients to fully evaluate the clinical efficacy of AZD1981 BACKGROUND There is an unmet medical need for allergic asthma patients who are uncontrolled on conventional therapies . The aim of this study was to collect efficacy and safety data for QAW039 , an oral chemoattractant receptor-homologous molecule expressed on Th2 cells ( CRTh2 ) receptor antagonist , for the treatment of asthma . METHODS This was an exploratory phase II , double-blind , r and omized , placebo-controlled multi-center study . Patients with mild-to-moderate uncontrolled allergic asthma ( N = 170 ) were either without or weaned off inhaled corticosteroids ( ICS ) and long-acting β-agonists ( LABA ) and r and omized ( 1:1 ) to QAW039 ( 500 mg once daily ) or to placebo for 28 days . RESULTS Overall , 157 patients completed the study . There were no significant differences between QAW039 and placebo for trough forced expiratory volume in 1 s ( FEV1 ) or Asthma control question naire ( ACQ ) in the total population . Subgroup analyses demonstrated that patients with a FEV1 < 70 % of predicted at baseline treated with QAW039 had significant improvement compared with placebo in trough FEV1 ( QAW039- Placebo [ Δ ] = 207 mL ; 90 % confidence interval [ CI ] : 96 , 319 ; P = 0.002 ) and ACQ7 ( Δ = -0.41 ; 90%CI : -0.69 , -0.13 ; P = 0.009 ) . QAW039 reached a mean maximum concentration ( Cmax ) of 3440 ng/mL on day 28 at a median Tmax of 1 h ( range 0.5 - 4 h ) . Most adverse events ( AEs ) were mild/moderate and balanced between both groups , with no serious AEs . CONCLUSIONS In the general study population , no improvement in lung function was observed with QAW039 . However , a subgroup analysis revealed that patients with greater severity of airflow limitation ( FEV1 < 70 % ) had improved lung function and asthma control when treated with QAW039 . QAW039 also demonstrated a favorable safety profile . TRIALS REGISTRATION Clinical Trials.govNCT01253603 BACKGROUND Asthma is characterized by a complex interaction of inflammatory mediators . The prostagl and in D2 receptor , chemoattractant receptor-homologous molecule on Th2 cells ( CRTH2 ) , plays a pivotal role in the pathogenesis of allergic airway inflammation . OBJECTIVE To ealuate the efficacy , safety , and pharmacokinetics of BI 671800 , a CRTH2 antagonist , when added to inhaled corticosteroid therapy in adult patients with symptomatic asthma . METHODS In this phase IIa , 12-week , r and omized , double-blind , three-period , four-treatment , incomplete block crossover trial , BI 671800 was administered either as a single 400-mg dose in the morning ( A.M. ) or evening ( P.M. ) , or 200 mg twice daily ( A.M. and P.M. ) versus placebo , together with fluticasone propionate ( 44 μg , two inhalations twice daily ) . The primary end point was the change from baseline in trough forced expiratory volume in 1 second percentage predicted after 4 weeks . The secondary end point was the change in Asthma Control Question naire score from baseline . RESULTS A total of 108 patients were r and omized and treated . After 4 weeks , the adjusted mean ( ± SE ) treatment differences for the primary end point versus placebo were 0.08 ± 0.62 % , 0.28 ± 0.61 % , and 0.67 ± 0.63 % for BI 671800 at 200 mg twice daily , 400 mg A.M. , and 400 mg P.M. , respectively ( not statistically significant ) . No statistically significant or clinical ly meaningful differences in the Asthma Control Question naire score were observed versus placebo . Each treatment was well tolerated . CONCLUSION BI 671800 at a dose of 400 mg administered for 4 weeks with fluticasone propionate did not provide clinical improvement in patients with asthma ; reasons for this are unclear , but it may be due to insufficient inhibition of the CRTH2 receptor at the doses used CRTH2 ( chemoattractant receptor expressed on T-helper ( Th ) type 2 cells ) is a G-protein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostagl and in (PG)D2-driven chemotaxis . We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients . A r and omised , double-blind , placebo-controlled , two-way crossover study of 16 days ’ treatment with OC000459 ( 200 mg twice daily ) on the late ( LAR ) and early ( EAR ) asthmatic responses to bronchial allergen challenge was conducted , with 16 subjects completing the study . There was a 25.4 % ( 95 % CI 5.1–45.6 % ) reduction in the LAR area under the curve ( AUC ) for change in forced expiratory volume in 1 s with OC000459 compared with placebo ( p=0.018 ) but no effect on the EAR . Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment ( p=0.002 ) . PGD2-induced blood eosinophil shape change ex vivo was assessed at day 7 ( n=7 ) . The AUC of eosinophil shift for OC000459 was lower than placebo ; the mean difference was -33.6 % ( 95 % CI -66.8– -0.4 % ; p=0.048 ) . OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils . This CRTH2 antagonist appears to inhibit allergic inflammation in asthma The Asthma Control Question naire ( ACQ ) measures the adequacy of asthma treatment as identified by international guidelines . It consists of seven items ( 5 x symptoms , rescue bronchodilator use and FEV1 % of predicted normal ) . A validation study suggested that in clinical studies measurement of FEV1 and bronchodilator use may not be needed but this has never formally been tested in a clinical trial . The aims of this analysis were ( 1 ) to examine the measurement properties of three shortened versions of the ACQ ( symptoms alone , symptoms plus FEV1 and symptoms plus short-acting beta2-agonist )  and ( 2 ) to determine whether using the shortened versions would alter the results of a clinical trial . In the r and omised trial , 552 adults completed the ACQ at baseline and after 13 and 26 weeks of treatment . The analysis showed that the measurement properties of all four versions of the ACQ are very similar . Agreement between the original ACQ and the reduced versions was high ( intraclass correlation coefficients : 0.94 - 0.99 ) . Mean differences between the ACQ and the shortened versions were less than 0.04 ( on the 7-point scale ) . Clinical trial results using the four versions were almost identical with the mean treatment difference ranging from -0.09 ( P=0.17 ) , to -0.13 ( P=0.07 ) . For interpretability , the minimal important difference for all four versions was close to 0.5 . In conclusion , these three shortened versions of the ACQ can be used in large clinical trials without loss of validity or change in interpretation Objectives To evaluate the efficacy and safety of AZD1981 , a potent , specific antagonist of the CRTh2 receptor , as add-on therapy to inhaled corticosteroids ( ICS ) and long-acting β2-agonists ( LABA ) , in patients with persistent asthma with an allergic component . Patients and methods In this placebo-controlled , parallel-group Phase IIb study , patients with persistent atopic asthma on ICS and LABA were r and omized to receive 12 weeks of treatment with placebo or AZD1981 ( 80 mg daily , 200 mg daily , and 10 mg , 40 mg , 100 mg , or 400 mg twice daily [ BID ] ) . The primary end point was the mean change from baseline in predose , prebronchodilator forced expiratory volume in 1 second ( FEV1 ) averaged over weeks 2 , 4 , 8 , and 12 in the AZD1981-treatment group vs the placebo group . Secondary end points included other measures of lung function , symptoms , and asthma control , as well as st and ard measures of safety . Results In total , 1,140 patients ( 99.7 % ) received study treatment . There were improvements in the primary end point across all treatment groups over 12 weeks of treatment . However , the improvement for the highest AZD1981 dose ( 400 mg BID ) vs placebo was not statistically significant ( 0.02 L , P=0.58 ) , preventing interpretation of statistical testing for the lower doses . AZD1981 was well tolerated , and the incidence of adverse events was comparable 
    Output:
    
Conclusions CRTH2 antagonist monotherapy can safely improve lung function and quality of life , and reduce asthma exacerbations and SABA use in asthmatics