***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: Sublingual immunotherapy is widely recognized as a viable treatment for allergic rhinitis and asthma , but the optimal dosage is still under debate , expecially with modified allergens . We assessed the clinical effects of a monomeric allergoid across 3 different maintenance doses in mite-monosensitized patients with rhinitis and intermittent asthma . Eighty-nine patients allergic to HDM were r and omized to 3 maintenance doses of monomeric allergoid ( Lais ® , Lofarma ) or medications only . All the patients recorded their symptoms and rescue drug consumption in a diary card from November to February . Additionally , nasal eosinophil count , spirometry and methacholine bronchial challenge were performed at the beginning of the study and after 3 years . The symptom scores showed a clear improvement in all the three active arms versus baseline and versus the controls , irrespective of the dose . Likewise , a similar improvement versus baseline was seen for nasal inflammation and bronchial hyperreactivity . The SLIT with monomeric allergoids produces clinical ly significant results across a wide range of doses . The absence of significant side effects , even at high doses , is probably due to their low level of allergenicity IMPORTANCE The house dust mite ( HDM ) sublingual allergen immunotherapy ( SLIT ) tablet is a potential novel treatment option for HDM allergy-related asthma . OBJECTIVES To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid ( ICS ) reduction period . DESIGN , SETTING S , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled  trial conducted between August 2011 and April 2013 in 109 European trial sites . The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products , and with HDM allergy-related rhinitis . Key exclusion criteria were FEV1 less than 70 % of predicted value or hospitalization due to asthma within 3 months before r and omization .  Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50 % for 3 months and then completely withdrawn for 3 months . INTERVENTIONS 1:1:1 r and omization to once-daily treatment with placebo ( n = 277 ) or HDM SLIT tablet ( dosage groups : 6 SQ-HDM [ n = 275 ] or 12 SQ-HDM [ n = 282 ] ) in addition to ICS and the short-acting β2-agonist salbutamol . MAIN OUTCOMES AND MEASURES Primary outcome was time to first moderate or severe asthma exacerbation during the ICS reduction period . Secondary outcomes were deterioration in asthma symptoms , change in allergen-specific immunoglobulin G4 ( IgG4 ) , change in asthma control or asthma quality -of-life question naires , and adverse events . RESULTS Among 834 r and omized patients ( mean age , 33 years [ range , 17 - 83 ] ; women , 48 % ) , 693 completed the study . The 6 SQ-HDM and 12 SQ-HDM doses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo ( hazard ratio [ HR ] : 0.72 [ 95 % CI , 0.52 - 0.99 ] for the 6 SQ-HDM group , P = .045 , and 0.69 [ 95 % CI , 0.50 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) . The absolute risk differences based on the observed data ( full analysis set ) in the active groups vs the placebo group were 0.09 ( 95 % CI , 0.01 - 0.15 ) for the 6 SQ-HDM group and 0.10 ( 95 % CI , 0.02 - 0.16 ) for the 12 SQ-HDM group . There was no significant difference between the 2 active groups . Compared with placebo , there was a reduced risk of an exacerbation with deterioration in asthma symptoms ( HR , 0.72 [ 95 % CI , 0.49 - 1.02 ] for the 6 SQ-HDM group , P = .11 , and 0.64 [ 95 % CI , 0.42 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) and a significant increase in allergen-specific IgG4 . However , there was no significant difference for change in asthma control question naire or asthma quality -of-life question naire for either dose . There were no reports of severe systemic allergic reactions . The most frequent adverse events were mild to moderate oral pruritus ( 13 % for the 6 SQ-HDM group , 20 % for the 12 SQ-HDM group , and 3 % for the placebo group ) , mouth edema , and throat irritation . CONCLUSIONS AND RELEVANCE Among adults with HDM allergy-related asthma not well controlled by ICS , the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction , with an estimated absolute reduction at 6 months of 9 to 10 percentage points ; the reduction was primarily due to an effect on moderate exacerbations . Treatment-related adverse events were common at both active doses . Further studies are needed to assess long-term efficacy and safety . TRIAL REGISTRATION clinical trialsregister.eu Identifier : 2010 - 018621 - 19 Sublingual immunotherapy ( SLIT ) with monomeric carbamylated allergoid administered in accordance with the st and ard regimen has proven to be effective and safe . Achieving clinical benefit , however , requires a lengthy period of time so it is not very suitable for short-lasting allergies . We thus performed this study to compare an administration protocol starting in the coseasonal period ( with a 4-day build-up phase ) with a precoseasonal scheme to verify if the former regimen provides the same benefit in a shorter period of time . The prospect i ve , r and omized , drug therapy-controlled study was conducted in 33 rhinitic patients monosensitized to Olea with or without asthma . Ten patients were assigned to the coseasonal therapy with 5000 allergic units (AU)/week for 6 weeks , 11 to the precoseasonal therapy with 3000 AU/week for 10 weeks , and 12 to drug therapy . They were treated from April or May to June 2008 . A visual analog scale ( VAS ) was performed at baseline and after treatment to assess the well being of the patients . Drug consumption was evaluated by means of a monthly diary . There was greater VAS improvement in both the SLIT groups versus the controls , but it was statistically significant only in the coseasonal group ( p < 0.01 ) . Furthermore , there was a reduction in the rescue medication only in the coseasonal SLIT ( p < 0.05 versus drug therapy ) . One mild adverse event was observed . The allergoid SLIT was shown to be effective and safe in Olea allergy in particular when a coseasonal regimen was used Sublingual immunotherapy with monomeric allergoid ( allergoid SLIT ) , given according to the st and ard scheme , has proved effective and safe in many clinical trials . However , its build-up phase requires a long time ranging from 16 days to 14 weeks . This study therefore investigated whether , with a four-day up-dosing , the same benefit could be achieved in a shorter time . Thirty rhinitic and /or asthmatic patients ( 16 M and 14 F , mean age 36±8.2 years ) allergic to house dust mites ( HDM ) with or without other sensitizations were r and omized to allergoid SLIT or st and ard drug therapy . The build-up phase lasted four days . The first day the patients took a 300 AU tablet , the second day two 300 AU tablets , the third day three 300 AU tablets and the fourth day four 300 AU tablets . The total amount taken during the up-dosing was 3000 AU . Patients were then treated for 12 months at the dosage of 2000 AU/week ( total amount of allergen : 104,000 AU/year ) . The symptom score and drug consumption were recorded from November to February on monthly diary cards . At baseline and after 12 months a Visual Analogue Scale ( VAS ) was used to rate the patients ' well-being . Skin prick test reactivity was evaluated before and after the 12-month treatment in both groups using 10 mg/mL histamine as reference . VAS scores rose significantly ( about 45 % ) in both groups in comparison to baseline ( p=0.001 ) . In addition , there was a significantly greater reduction of the global symptoms score ( about 52 % ) - but not in drug consumption - in the SLIT group in comparison to controls ( p=0.0004 ) . The SLIT group showed a highly significant reduction ( about 39 % ) in skin prick test reactivity ( p=0.000003 ) while the control group remained unchanged ( p=0.5226 ) . No severe adverse events were observed . Even with this short four-day up-dosing , the allergoid SLIT proves to be safe . In addition , it is already effective in patients allergic to HDM after 12 months , and significantly reduces allergen-specific skin reactivity BACKGROUND Few studies have compared the effects of immunotherapy and inhaled steroids . The main limitation of such studies is the long duration required to fully appreciate the effects of immunotherapy . OBJECTIVE To compare the effects of inhaled budesonide and sublingual immunotherapy ( SLIT ) in mild persistent asthma for up to 5 years . METHODS Patients with mild persistent asthma and rhinitis due to grass pollen were enrolled in an open r and omized controlled trial . After a run-in season , they were r and omized to either budesonide , 800 microg/d , in the pollen season or continuous grass SLIT for 5 years . All patients received rescue medications . Symptoms were evaluated by diary cards filled out from May to July at baseline and after 3 and 5 years . In-season nasal eosinophils and bronchial hyperresponsiveness were also assessed . RESULTS Fifty-one patients were enrolled and 46 completed the study . The bronchial symptom scores and the use of bronchodilators decreased significantly in both groups , but the improvement was greater in the SLIT patients at 3 and 5 years . The nasal symptom score and the intake of nasal steroids decreased only in the SLIT group , and the difference vs the budesonide group was always significant . In the SLIT group vs the budesonide group , a statistically significant decrease of nasal eosinophils was found at 3 and 5 years ( P < .01 ) . The bronchial hyperresponsiveness improved significantly only in the SLIT group . CONCLUSION In patients with grass pollen-induced asthma , in the long term SLIT was equally effective as inhaled budesonide in treating bronchial symptoms and provided an additional benefit in treating rhinitis symptoms and bronchial hyperresponsiveness RATIONALE Heterogeneity in asthma expression is multidimensional , including variability in clinical , physiologic , and pathologic parameters . Classification requires consideration of these disparate domains in a unified model . OBJECTIVES To explore the application of a multivariate mathematical technique , k-means cluster analysis , for identifying distinct phenotypic groups . METHODS We performed k-means cluster analysis in three independent asthma population s. Clusters of a population managed in primary care ( n = 184 ) with predominantly mild to moderate disease , were compared with a refractory asthma population managed in secondary care ( n = 187 ) . We then compared differences in asthma outcomes ( exacerbation frequency and change in corticosteroid dose at 12 mo ) between clusters in a third population of 68 subjects with predominantly refractory asthma , clustered at entry into a r and omized trial comparing a strategy of minimizing eosinophilic inflammation ( inflammation-guided strategy ) with st and ard care . MEASUREMENTS AND MAIN RESULTS Two clusters ( early-onset atopic and obese , noneosinophilic ) were common to both asthma population s. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation ( early-onset symptom predominant and late-onset inflammation predominant ) were specific to refractory asthma . Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster ( 3.53 [ SD , 1.18 ] vs. 0.38 [ SD , 0.13 ] exacerbation/patient/yr , P = 0.002 ) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster ( mean difference , 1,829 mug beclomethasone equivalent/d [ 95 % confidence interval , 307 - 3,349 mug ] ; P = 0.02 ) . CONCLUSIONS Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms BACKGROUND No studies have directly compared the effects of immunotherapy and antileukotrienes due to the long time required to appreciate the clinical effects of immunotherapy . We compared the effect of montelukast ( MK ) and 
    Output:
    
Compared with traditional therapy , SLIT add-on therapy was associated with significant improvements in lower and upper airway scores , a higher forced expiratory volume in 1 second , and maximal expiratory flow at 25 % of forced vital capacity , and improved bronchial reactivity .
Drug consumptions were significantly decreased as well .
Airway inflammatory parameters , such as nasal eosinophil infiltration , were markedly improved .
The findings of this study suggested that long-term SLIT add-on therapy is a complementary treatment for adults with asthma in addition to conventional medicine .
It not only reduces symptom scores but also improves lung function and airway inflammation