***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: Cluster immunotherapy represents an interesting alternative to conventional up‐dosing schedules because it allows achieving the maintenance dose within a shorter time interval . In this study , the efficacy and safety of  cluster immunotherapy with a high polymerized allergen extract of a grass/rye pollen mixture have been evaluated in a r and omized , double‐blind , placebo‐controlled , multicenter study Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one pollen allergen , and mixed pollen extracts are widely used for allergen immunotherapy in practice , there are few published trials Background and Objectives : Allergy to house dust mite is one of the most common causes of allergic rhinitis ( AR ) in China . We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR . Methods : The trial was a prospect i ve and r and omized study involving 96 patients with persistent AR , aged 14–60 years , who were allergic to Dermatophagoides pteronyssinus . While 48 patients were r and omly assigned to the cluster schedule reaching the maintenance dose within 6 weeks , the other 48 were r and omly assigned to the conventional schedule reaching the maintenance dose within 14 weeks . Eighty-nine patients completed a 1-year treatment course . While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment , quality of life , cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment . Results : The cluster schedule reduced the time to reach the maintenance dose by 57 % and caused mild systemic adverse reactions after 1.0 % of injections ( 6.7 % of patients ) , with no differences in comparison with the conventional schedule . Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule . Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year . Conclusions : The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner BACKGROUND Few studies have investigated the use of specific immunotherapy ( SIT ) for childhood seasonal allergic asthma . OBJECTIVE We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen ( Phleum pratense Alutard SQ ; ALK-Abelló , Hørsholm , Denmark ) in children with seasonal allergic asthma . METHODS A r and omized , double-blind , placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed . Children ( 3 - 16 years ) with a history of seasonal allergic asthma sensitized to grass pollen ( P pratense ) and requiring at least 200 microg of inhaled beclomethasone equivalent per day were enrolled . Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded . The primary outcome measure was a combined asthma symptom-medication score during the second pollen season . Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen , sputum eosinophilia , exhaled nitric oxide , and adverse events . RESULTS Thirty-nine subjects were enrolled . Thirty-five subjects provided data for analysis . The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo ( P = .04 ) . There were also significant reductions in cutaneous ( P = .002 ) , conjunctival ( P = .02 ) , and bronchial ( P = .01 ) reactivity to allergen after SIT compared with that after placebo . The 2 groups had similar levels of airway inflammation , despite a trend toward less inhaled steroid use in the active group . No serious adverse events were reported , and no subjects withdrew because of adverse events . CONCLUSION The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen BACKGROUND The clinical efficacy of allergen immunotherapy using therapeutic vaccines containing modified allergen extracts has been previously shown . OBJECTIVE To evaluate the clinical efficacy of a vaccine containing depigmented , polymerized extract of Dermatophagoides pteronyssinus in asthmatic children , monosensitized to mites , after 4 months of treatment . MATERIAL AND METHODS A total of 30 mite-allergic , asthmatic children ( age range , 8 - 16 years ) were entered in the study ; 15 were treated with the modified allergen extract ( active group ) and 15 received only pharmacologic treatment ( control group ) . The study was open , controlled and parallel with r and om allocation of the patients to each of the groups . Efficacy was evaluated using allergen-specific bronchial challenge tests , dose-response skin-prick tests , and symptom and medication scores . The results of the bronchial challenges and dose-response skin-prick tests were compared at baseline and after 4 months of treatment . The build up phase consisted of 4 injections in 2 days , followed by 4 injections of the maintenance dose . RESULTS All patients of the active group concluded the study , whereas 2 of the control group did not . In the active group , there was a significant difference in the PC20FEV1 ( P < .01 ) after 4 months . The mean allergen quantity needed was 26 microg at baseline vs. 309 microg after 4 months ( a 12.8-fold increase ) . There was no difference in the control group ( 5 tg at baseline vs 8 microg at the end ) . A significant reduction in the number of cases with dual bronchial response was observed in the treated group ( P < .05 ) . Two treated patients of this group experienced a negative bronchial challenge after 4 months of treatment . The group of active patients also experienced significant improvement in skin reactivity and symptom and medication scores . CONCLUSIONS Vaccines containing depigmented polymerized extracts of D pteronyssinus are safe and effective in the treatment of mite allergic asthmatic children , and provide clinical benefit after 4 months of treatment To cite this article : Pfaar O , Urry Z , Robinson DS , Sager A , Richards D , Hawrylowicz CM , Bräutigam M , Klimek L. A r and omized placebo‐controlled trial of  rush preseasonal depigmented  polymerized grass pollen immunotherapy . Allergy 2012 ; 67 : 272–279 BACKGROUND The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America . OBJECTIVE To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali . METHODS The trial was r and omized , double-blind , and placebo-controlled using a rush protocol in the build-up phase . Sixty patients with rhinoconjunctivitis ( 19 also had mild asthma ) were r and omly allocated to receive either active treatment ( polymerized extract ) or placebo . The final distribution was 41 patients in the active and 19 in the placebo group .  Side effects were registered . Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy . A Rhinoconjunctivitis Quality of Life Question naire was completed in the previous pollen season ( before treatment ) and during the pollen season 1 year later ( in the trial ) . Dose-response skin tests were performed at baseline and at the end of the trial . RESULTS There was a significant difference ( P < .05 ) in symptom and medication scores between both groups during the pollen season , with the active group the one that had fewer symptoms and lower intake of medication . The number of days without symptoms was higher in the active group ( P < .05 ) . This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Question naire and a reduction in skin sensitivity . No moderate or severe systemic reactions were registered . CONCLUSION Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinical ly sensitive to this pollen . CLINICAL IMPLICATION S Patients allergic to S kali ( Russian thistle ) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma , reduce medication use , and improve quality of life parameters We investigated the effects of cluster specific immunotherapy ( SIT ) with Dermatophagoides pteronyssinus ( Der p ) on CD4(+ ) CD25(+ ) Foxp3(+ ) Treg cells and IL-10-secreting type I T regulatory ( Tr1 ) cells in Der p-sensitized children with allergic rhinitis ( AR ) . We performed a prospect i ve r and omized study involving 46 children ( aged 8 - 13 yr ) , of whom 25 children received Der p-SIT + pharmacotherapy and 21 received only pharmacotherapy , over a period of 1 yr . Prior to and at end of treatment , CD4(+ ) CD25(+ ) Foxp3(+ ) Treg cells and allergen-specific IL-10(+ ) IL-4(- ) , IFN-γ(+ ) IL-4(- ) , and IL-4(+ ) IFN-γ-CD4(+ ) T cells were measured by flow cytometry . Similarly , IL-4 , IFN-γ , and IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell ( P BMC ) cultures were measured by ELISA , and the suppressive effect of CD4(+ ) CD25(high ) T cells on cell proliferation and cytokine release was estimated from both groups . Allergen-specific serum IgE and IgG4 were also assessed at the beginning and end of treatment by RAST and ELISA , respectively . The levels of allergen-specific Tr1 cells , IgG4 , and allergen-induced IL-10 synthesis from P BMC cultures were significantly increased after SIT for 1 yr compared with baseline levels ( p < 0.001 for all ) , with significant correlation between increased levels of Tr1 cells and improvements in nasal symptoms ( r = 0.48 , p < 0.05 ) . In contrast , the levels of CD4(+ ) CD25(+ ) Foxp3(+ ) T cells , allergen-specific Th1 and Th2 cells , the production of IL-4 and IFN-γ , and the function of CD4(+ ) CD25(high ) T cells were not altered in either group at the end of treatment . These data suggest that the up-regulation of Tr1 cells may play an important role in SIT and be a useful marker of successful SIT in AR patients 
    Output:
    
This review demonstrated that rush and cluster schedules are clinical ly and immunological efficacious , with faster effect than conventional schedules .
No relevant difference with respect to clinical outcomes was noticed between subgroups ( pediatric , adult and mixed population s ) .
Regarding safety , most local adverse reactions were mild and there were neither life-threatening systemic reactions nor fatal events .
No relevant differences in the incidence and severity of either local or systemic reactions between the accelerated schedule group and control group were registered .
Accelerated SCIT build-up schedules are effective in the treatment of respiratory allergy in pediatric patients , representing a safe alternative to the conventional schedules with the advantage of achieving clinical effectiveness sooner