***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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    Input: 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 Abstract Background The occurrence of  allergic multimorbidity  ( coexistence of asthma , allergic rhinitis and eczema ) has not been evaluated longitudinally from early childhood up to adulthood in a population ‐based study sample . We aim ed to determine the prevalence of  allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospect i ve follow‐up data from two decades of a birth cohort study . Methods In 1990 , we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population ‐based MAS birth cohort study . The sample was purpose ly risk‐enriched by increasing the proportion of children at high allergy risk ( i.e. at least 2 allergic family members among parents and siblings ) from 19 % in the source population to 38 % in the final sample . The remaining 62 % of all MAS children had a low or no allergy risk . Symptoms , medication and doctor 's diagnoses of allergic diseases have been assessed using st and ardized question naires including vali date d ISAAC questions in 19 follow‐up assessment s up to age 20 . Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant : asthma , allergic rhinitis and eczema . Results Response at age 20 was 72 % ( n = 942 ) of all recruited participants . At age 20 , 18.5 % ( 95 % CI , 15.0–22.5 % ) of all participants with allergic parents  had 2 or 3 concurrent allergies as compared to only 6.3 % ( 95 % CI , 4.3–9.0 % ) of those with non‐allergic parents . At this age , allergic multimorbidity was similar in women and men ( 12.7 % ( 95 % CI , 9.7–16.2 % ) vs. 11.6 % ( 95 % CI , 8.9–14.8 % ) ) , whereas single allergic diseases were slightly more common in women than men ( 24.2 % ( 95 % CI , 20.2–28.5 % ) vs. 20.1 % ( 95 % CI , 16.6–24.0 % ) ) . Asthma occurred more frequently with coexisting allergic rhinitis and /or eczema than as a single entity from pre‐puberty to adulthood . Conclusion Having parents with allergies is not only a strong predictor to develop any allergy , but it strongly increases the risk of developing allergic multimorbidity . In males and females alike , coexisting allergies were increasingly common throughout adolescence up to adulthood . Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity BACKGROUND Although several studies support the efficacy of specific immunotherapy in allergic asthma , its benefit compared with that of st and ardized pharmacologic intervention remains unknown . OBJECTIVE A double-blind , placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite ( HDM ; Dermatophagoides species ) was conducted to assess the effects of specific immunotherapy added to guideline -adjusted pharmacologic treatment and allergen avoidance . METHODS After 1 observational year of pharmacologic treatment and st and ard measures of HDM avoidance , 2 groups of asthmatic subjects were r and omly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine ( n=41 ) or placebo ( n=31 ) for 3 years . Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines . RESULTS The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects . The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators , an increase in morning and evening peak expiratory flow , and a reduced skin sensitivity to HDM extracts . The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids , asthma symptoms , lung volumes , or bronchial responsiveness to methacholine . CONCLUSION These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits , possibly by reducing the allergic response of asthmatic patients sensitized to HDM BACKGROUND Allergen specific immunotherapy and allergen reduction are the only therapies in perennial allergic diseases to reduce symptoms in the long term . Specific immunotherapy has the potential to reduce symptoms and the need for medication significantly and furthermore to prevent progression into more severe disease e. g. asthma . METHODS The clinical value of specific immunotherapy has been studied for the last 30 years . We undertook an analysis of clinical trials of subcutaneous specific immunotherapy with Der p or Der f in adults to assess the efficacy of this controversial form of allergy treatment . RESULTS A computerized bibliographic search revealed 13 r and omised double-blind , placebo-controlled trials of specific immunotherapy with Der p/Der f for rhinitis and /or asthma in adults since 1970 . The results extracted included patients  symptoms , medication requirements , lung function , specific challenge-tests as titrated nasal , conjunctival or bronchial challenge test and side effects . For studies with continuous outcomes as symptom score and medication score the effect size was obtained by the difference in the scores between the active therapy and the placebo groups . For studies with categorical outcomes as increase or decrease in challenge-tests the results were expressed as odds ratios for improvement against no change and 95 % confidence intervals were calculated . DISCUSSION Focused on the studies after 1980 there was a significant improvement on symptom score and medication score in the actively treated group compared to the placebo group , while the lung function was not significantly altered . Allergen provocation tests reflect the sensitivity of the shock organ . As the documentation of the clinical effects measured by challenge tests shows a highly significant improvement in the actively treated group , we recommend allergen provocation tests as a useful and sensitive parameter during specific immunotherapy . The risk of life-threatening side effects is low , although severe anaphylactic reactions may be induced . Specific immunotherapy using a st and ardized house-dust mite extract is effective and safe in adults when administered under optimal conditions To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts , we performed a double‐blind , placebo‐controlled immunotherapy study in 30 patients with proven allergy to mite allergens . The specific immunotherapy with st and ardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated . After 1 year of treatment , the actively treated group showed a significant improvement compared to their starting value as well as to the placebo‐treated patients with regard to skin prick test , conjunctival provocation test , and subjective rhinitis score . The subjective asthma score and bronchial hyperreactivity , measured by the methacholine provocation test , was improved in comparison to the starting value , but not to the placebo group , after 12 months . However , a further , open comparison of the placebo‐ and verum‐treated groups at 18 months revealed a significant reduction . The drug intake was not increased in the verum‐treated group . Exposure to mite levels was constant throughout this time period , as revealed by antigen measurement . We conclude that specific immunotherapy in perennial , mite‐allergen‐induced asthma may reduce not only immediate , IgE‐mediated symptoms but , after a rather long time period of 12–18 months , also the inflammatory component of bronchial asthma , thus leading to a reduction of unspecific hyperreactivity The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol . Nine active-treatment subjects who received a mean cumulative dose of cat allergen , 1 of 10.9 units , and eight placebo-treatment subjects completed the study . Active treatment result ed in significant reductions in bronchial sensitivity ( p less than 0.05 ) and prick test titer ( p less than 0.01 ) . In addition , active treatment result ed in a significant delay in the onset of ocular ( p less than 0.05 ) and pulmonary ( p less than 0.02 ) symptoms on exposure to living cats . Significant increases in IgG antibody to cat allergen 1 ( p less than 0.001 ) and cat albumin ( p less than 0.01 ) also occurred with active treatment . There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils . These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings . We studied the role of IL-10 in the induction of clinical , cellular , and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis . Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen ( Phleum pratense , Phl P ) immunotherapy . We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy , but only during the pollen season . IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA+ cells . These changes were not observed in placebo-treated subjects or in healthy controls . Fifteen and 35 % of IL-10 mRNA signals were colocalized to CD3 + T cells and CD68 + macrophages , respectively , whereas only 1–2 % of total CD3 + cells and 4 % of macrophages expressed IL-10 . Following immunotherapy , peripheral T cells cultured in the presence of grass pollen extract also produced IL-10 . Immunotherapy result ed in blunting of seasonal increases in serum allergen Phl p 5-specific IgE , 60- to 80-fold increases in Phl p 5-specific IgG , and 100-fold increases in Phl p 5-specific IgG4 . Post-immunotherapy serum exhibited inhibitory activity , which coeluted with IgG4 , and blocked IgE-facilitated binding of allergen-IgE complexes to B cells . Both the increases in IgG and the IgG “ blocking ” activity correlated with the patients ’ overall assessment of improvement . Thus , grass pollen immunotherapy may induce allergen-specific , IL-10-dependent “ protective ” IgG4 responses BACKGROUND Both specific immunotherapy ( SIT ) and nasal steroid ( NS ) have been shown to effectively reduce symptoms of  allergic rhinitis .  Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies , few comparative studies have been performed . OBJECTIVE The purpose of this study was to compare the effects of preseason SIT with a st and ardized allergen extract and NS in seasonal allergic disease ( rhinoconjunctivitis and asthma ) . METHODS We examined 41 patients allergic to birch pollen , 21 with rhinoconjunctivitis and 20 with both rh 
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This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity .
The impact on measures of lung function or asthma control was however less clear .
We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT .
SLIT had a favorable safety profile when compared to SCIT , particularly in relation to the risk of systemic reactions .
Conclusions AIT has the potential to achieve reductions in symptom and medication scores , but there is no clear or consistent evidence that measures of lung function can be improved .