***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 : Allergen-specific immunotherapy ( SIT ) is a highly effective treatment for allergic diseases , but the underlying mechanisms are unclear . In this study , we investigated the effects of cluster SIT with Dermatophagoides pteronyssinus ( Der p ) on IL-10-secreting type I T regulatory ( Tr1 ) cells in Der p-sensitized patients with allergic rhinitis . Methods : This was a prospect i ve r and omized study involving 68 participants ( aged 18–60 years ) of whom 38 were patients with allergic rhinitis and received Der p-SIT for 1 year and 30 were nonallergic controls .  IL-10+IL-4–CD4 + T cells were measured by flow cytometry for the patient group at baseline and at the end of 1 year of SIT , and for nonallergic controls . Similarly , IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell ( P BMC ) cultures were measured by ELISA , and the suppressive effect of Tr1 cells on cell proliferation and cytokine release ( IFN-γ and IL-4 ) in P BMC s was estimated in cultures from both groups . Allergen-specific serum IgE and IgG4 were also assessed by RAST and ELISA for the SIT group . Results : The levels of IL-10-secreting Tr1 cells , IgG4 and allergen-induced IL-10 synthesis from P BMC cultures were significantly increased and the function of Tr1 cells was enhanced after 1 year of SIT compared to baseline levels . In contrast , the level of IgE was not significantly changed . Conclusion : These data suggest that the cluster Der p-SIT may enhance the frequency and function of IL-10-secreting Tr1 cells BACKGROUND Data on the long-term effects of sublingual immunotherapy ( SLIT ) are sparse , and the optimal duration of treatment is a matter of debate . OBJECTIVE We sought to prospect ively evaluate the long-term effect of SLIT given for 3 , 4 , or 5 years and to compare the effect of those different duration s. METHODS In this prospect i ve open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years . The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3 , 4 , or 5 years . Clinical scores , skin sensitizations , methacholine reactivity , and nasal eosinophil counts were evaluated every year during the winter months . The clinical effect was considered to persist until clinical scores remained at less than 50 % of the baseline value , and then patients underwent another course of SLIT . RESULTS Seventy-eight patients were enrolled , and 59 completed the study . In the 12 control subjects no relevant change in clinical scores was seen throughout the study . In the patients receiving SLIT for 3 years , the clinical benefit persisted for 7 years . In those receiving immunotherapy for 4 or 5 years , the clinical benefit persisted for 8 years . New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT ( 21 % , 12 % , and 11 % , respectively ) . The second course of vaccination induced a benefit more rapidly than the first course . The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score . CONCLUSION Under the present conditions , it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination BACKGROUND Subcutaneous allergen-specific immunotherapy ( SIT ) has an early onset of action , whereas repeated injections and safety concerns have limited its use in the pediatric age group . Meanwhile , the improved safety profile of the sublingual route has been accepted as an alternative despite its relatively late onset of action . OBJECTIVE We sought to improve the efficacy and safety of SIT with a combination of the subcutaneous route in the build-up phase and sublingual maintenance in comparison with the sublingual or subcutaneous routes alone . METHODS Fifty-one house dust mite-sensitized children with mild-to-moderate asthma were r and omized into one of 4 groups to receive either ( 1 ) subcutaneous immunotherapy ( SCIT ) , ( 2 ) sublingual immunotherapy ( SLIT ) , ( 3 ) SCIT plus SLIT , or ( 4 ) pharmacotherapy . Clinical parameters were evaluated at baseline and months 1 , 4 , 12 , and 18 . Allergen-specific immunoglobulin levels and allergen-induced IL-5 , IL-10 , IL-13 , IL-17 , TGF-β , and IFN-γ levels were evaluated as well . RESULTS In the SCIT and SCIT plus SLIT groups , the number of asthma attacks and inhaled corticosteroid dosage decreased compared with baseline values at the months 4 , 12 , and 18 but only at month 12 in the SLIT group . The improvement in visual analog scores for rhinitis was significant only in the SCIT plus SLIT group . Increases in the levels of regulatory and T(H)1 cytokines were observed both in the SCIT and SLIT groups , with some differences in dynamics . Antigen-specific IgG(4 ) levels increased in the SCIT and SCIT plus SLIT groups but not in the SLIT group . Clinical symptom scores were correlated positively with IL-5 levels and negatively with antigen-specific IgG(4 ) , IFN-γ , and TGF-β levels . CONCLUSION Our novel regimen of immunotherapy , SCIT plus SLIT , appeared promising in that it successfully combined the advantages of the 2 alternatives : rapid onset and potency in SCIT and safety and avoidance of injections in SLIT BACKGROUND Icatibant , a bradykinin B(2 ) receptor antagonist , inhibits the reduction in nasal patency after challenge with house dust mite antigen in sensitive subjects and abolishes the nasal hyperresponsiveness induced by platelet-activating factor in nonatopic subjects . OBJECTIVE We sought to investigate the effect of icatibant on the response to nasal antigen challenge in subjects with seasonal allergic rhinitis . METHODS Patients allergic to grass pollen antigen ( n = 9 - 13 ) were included in a double-blind , r and omized-block , placebo-controlled , crossover study outside the pollen season . Subjects first received an intranasal spray of icatibant ( 200 microg per nostril ) or a saline control . Subjects were then challenged with antigen or diluent ( control ) , and their responses were monitored by using acoustic rhinometry . Six hours later , nasal lavage fluid was collected and quantified for inflammatory cells and various inflammatory mediators ( kinin , eosinophil cationic protein , IL-5 , and IL-8 ) . At 24 hours , the response of the nasal airways to 200 microg of histamine was assessed , and a further nasal lavage was carried out . RESULTS Antigen challenge caused a significant increase in nasal obstruction and albumin extravasation , which was not affected by icatibant .  Nasal hyperresponsiveness to histamine was present 24 hours after antigen and was abolished by pretreatment with icatibant . Icatibant also reduced the antigen-induced increase in eosinophils , eosinophil cationic protein , kinin , and IL-8 in nasal lavage fluid . CONCLUSION Pretreatment with icatibant does not affect the acute inflammatory response in seasonal allergic rhinitis . However , our results imply the involvement of kinins and the bradykinin B(2 ) receptor in the development of antigen-induced hyperresponsiveness and the associated eosinophilia in the human nasal airway Live Lactobacillus paracasi 33 ( LP33 ) may effectively improve the quality of life for patients with perennial allergic rhinitis . It has been demonstrated that heat-killed lactic acid bacteria ( LAB ) suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals . The aim of this study was , therefore , to evaluate the efficacy of heat-killed LP33 in the treatment of allergic rhinitis induced by house-dust-mite in human subjects . A total of 90 patients were enrolled in a r and omized , double blind , placebo-controlled trial and assigned to three treatment groups . Patients in groups A and B received two capsules per day of live or heat-killed LAB ( 5 x 10(9 ) colony-forming units/capsule ) , respectively , over a period of 30 days while those in Group C received placebo capsules . A modified question naire on pediatric rhinoconjunctivitis-related quality of life was administered to all subjects or their parents during each clinical visit . The overall quality of life score decreased for groups A and B , as compared with the placebo group , in terms of both frequency ( 9.47 + /- 2.89 , 6.30 + /- 2.19 , vs. -3.47 + /- 1.53 , respectively ; p < 0.0001 ) and level of bother ( 5.91 + /- 3.21 , 6.04 + /- 2.44 , vs. -2.80 + /- 1.64 , respectively ; p = 0.004 ) after the 30-day treatment . The efficacy of the heat-killed LP33 was not inferior to the live variant . No obvious side effects were reported for either active treatment group during the study period . Our results suggest that heat-killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis , and that it may be efficacious as an alternative treatment BACKGROUND House dust mite ( HDM ) allergy is associated with persistent allergic rhinitis ( AR ) and allergic asthma . OBJECTIVE To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease and report the AR results . METHODS Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were r and omized 1:1:1:1 to double-blinded daily treatment with 1 , 3 , 6 SQ-HDM or placebo . End-of-treatment rhinoconjunctivitis symptoms and medication score were predefined extrapulmonary end points . A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score ( TCRS ) > 0 ( ie , with AR symptoms and /or AR medication use during the 4-week baseline period ) . The subgroup was comprised of 498 subjects ( 82 % ) . RESULTS In the subgroup , the absolute difference in end-of-treatment TCRS between 6 SQ-HDM and placebo was -0.78 ( 95 % confidence interval -1.47 to -0.07 , relative difference 28.8 % , P = .0357 ) . Furthermore , a significant difference was found for the total score of the Rhinitis Quality of Life Question naire with St and ardized Activities RQLQ(S ) and for the individual domains : activities , sleep , non-nose and non-eye symptoms , and nasal symptoms . For the TCRS and Rhinitis Quality of Life Question naire score , a dose response was seen , with numerically lower , nonsignificant differences for 1 and 3 SQ-HDM . The predefined analysis for the entire trial population showed no statistically significant difference between the placebo and actively treated groups . No safety concerns were observed . CONCLUSION Efficacy in mild to severe AR of 6 SQ-HDM compared with placebo was demonstrated by statistically significant improvements in TCRS and Rhinitis Quality of Life Question naire score in subjects with AR present at baseline . The treatment was well tolerated . TRIAL REGISTRATION EudraCT , no 2006 - 001795 - 20 ; Clinical Trials.gov , identifier NCT00389363 BACKGROUND Both SCIT ( subcutaneous immunotherapy ) and SLIT ( sublingual immunotherapy ) have clinical and immunologic efficacy in children with rhinitis and asthma but comparative studies are scarce . OBJECTIVE To investigate the clinical and immunological efficacy of mite-specific SLIT and SCIT in children with rhinitis and asthma . METHOD Thirty children monosensitized to house dust mite were r and omized to receive either active SCIT or SLIT or placebo for 1 yr in a double-blind double-dummy placebo controlled design ( Yukselen A et al. , Int Arch Allergy Immunol 2012 ; 157:288 - 298 ) . Thereafter , the placebo group was r and omized to receive SCIT or SLIT , and for 1 yr all patients received active treatment with SCIT or SLIT .  Symptom scores , drug usage , titrated skin prick tests , nasal and bronchial allergen provocation doses , serum house dust mite-specific immunglobulin E , sIgG4 , IL-10 and IFN- g levels were evaluated . RESULTS The reduction of clinical scores with SLIT was more evident after 2 years of treatment in comparison to both the baseline and DBPC phase of the study . The change in titrated skin prick tests and nasal provocative doses was more prominent with both SCIT and SLIT at the end of the open phase . Although the increase inbronchial provocative doses was not significant at the end of the first year of treatment with SLIT , it reached a statistically significant difference after two years of treatment . CONCLUSION The clinical efficacy of SLIT is more prominent at the end of the second year , although this improvement is 
    Output:
    
Conclusions : SLIT tablets effectively relieve rhinitis symptoms in adults with allergic rhinitis .