Efficacy analysis of three-year subcutaneous SQ-standardized specific immunotherapy in house dust mite-allergic children with asthma e-Monitoring of Asthma Therapy to Improve Compliance in children using a real-time medication monitoring system (RTMM): the e-MATIC study protocol Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis. Allergic rhinitis is associated with poor asthma control in children with asthma A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes. A controlled trial of hyposensitization with adsorbed tyrosine Dermatophagoides pteronyssinus antigen in childhood asthma: in vivo aspects Efficacy of immunotherapy for treatment of allergic asthma in children. CONTROLLED TRIAL OF HYPOSENSITISATION TO DERMATOPHAGOIDES PTERONYSSINUS IN CHILDREN WITH ASTHMA Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D.pt.) in children. A prospective, randomized, double‐blind, placebo‐controlled multi‐centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen Sublingual immunotherapy and influence on urinary leukotrienes in seasonal pediatric allergy. Failure hyposensitisation in treatment of children with grass-pollen asthma. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: a randomized controlled trial. Comparison between the use of adsorbed and aqueous immunotherapy material in Dermatophagoides pteronyssinus sensitive asthmatic children. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children. Efficacy of sublingual immunotherapy with high-dose mite extracts in asthma: a multi-center, double-blind, randomized, and placebo-controlled study in Taiwan. [Sublingual immunotherapy with allergenic extract of Dermatophagoides pteronyssinus in asthmatic children]. Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. The Dutch Chronic Non-specific Lung Disease Study Group. Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double-blind, placebo-controlled study. Immunotherapy in allergy to dog: a double-blind clinical study. A Double‐Blind, Multicenter Immunotherapy Trial in Children, Using a Purified and Standardized Cladosporium herbarum Preparation I. Clinical Results Prevalence and severity of asthma, rhinitis, and atopic eczema in 13- to 14-year-old schoolchildren from the northeast of England. Efficacy of sublingual immunotherapy in patients with rhinitis and asthma due to house dust mite. A double-blind study. Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria‐induced respiratory allergy: a randomized controlled trial † Double‐blind, placebo‐controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization Allergen immunotherapy for the treatment of allergic rhinitis and/or asthma: an umbrella review. Clinical efficacy of house dust mite-specific immunotherapy in asthmatic children. Immunomodulation during sublingual therapy in allergic children. Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures. A controlled trial of immunotherapy for asthma in allergic children. Clinical and immunologic effects of long‐term sublingual immunotherapy in asthmatic children sensitized to mites:a double‐blind, placebo‐controlled study Preseasonal local allergoid immunotherapy to grass pollen in children: a double‐blind, placebo‐controlled, randomized trial
The present study aim ed to evaluate the efficacy of three-year subcutaneous SQ-st and ardized specific immunotherapy ( SCIT ) in house dust mite (HDM)-allergic children with asthma . Ninety children with allergic asthma to HDMs , with or without allergic rhinitis , were r and omly divided into two groups , the treatment group and the control group . The treatment group received SCIT combined with st and ardized glucocorticoid management and the control group received st and ardized glucocorticoid management alone for a period of three years . The mean daily dose of inhaled corticosteroids ( ICSs ) , a four-week diary recording the symptom scores of asthma , peak expiratory flow ( PEF ) measurements , skin prick test results and serum immunoglobulin E ( IgE ) levels were assessed prior to treatment and following one , two and three years of treatment . The median dose of ICS  was reduced in the treatment group after two and three years of treatment compared with that of the control group . After three years of treatment , the discontinuation percentage of ICS in the treatment group was higher than that in the control group . The treatment group demonstrated significantly reduced daytime and night-time asthmatic symptom scores , increased PEF values and reduced serum IgE levels after two and three years of treatment compared with those in the control group ( P<0.05 ) . In conclusion , three-year SCIT treatment combined with ICS is an effective immunotherapy for children with allergic asthma and result ed in a reduction of the required ICS dose Background Many children with asthma do not have sufficient asthma control , which leads to increased healthcare costs and productivity loss of parents . One of the causative factors are adherence problems . Effective interventions improving medication adherence may therefore improve asthma control and reduce costs . A promising solution is sending real time text-messages via the mobile phone network , when a medicine is about to be forgotten . As the effect of real time text-messages in children with asthma is unknown , the primary aim of this study is to determine the effect of a Real Time Medication Monitoring system ( RTMM ) with text-messages on adherence to inhaled corticosteroids ( ICS ) . The secondary objective is to study the effects of RTMM on asthma control , quality of life and cost-effectiveness of treatment . Methods A multicenter , r and omized controlled trial involving 220 children ( 4–11 years ) using ICS for asthma . All children receive an RTMM-device for one year , which registers time and date of ICS doses . Children in the intervention group also receive tailored text-messages , sent only when a dose is at risk of omission . Primary outcome measure is the proportion of ICS dosages taken within the individually predefined time-interval . Secondary outcome measures include asthma control ( monthly Asthma Control Tests ) , asthma exacerbations , healthcare use ( collected from hospital records , patient reports and pharmacy record data ) , and disease-specific quality of life ( PAQLQ question naire ) . Parental and children ’s acceptance of RTMM is evaluated with online focus groups and patient question naires . An economic evaluation is performed adopting a societal perspective , including relevant healthcare costs and parental productivity loss . Furthermore , a decision-analytic model is developed in which different levels of adherence are associated with clinical and financial outcomes . Also , sensitivity analyses are carried out on different price levels for RTMM . Discussion If RTMM with tailored text-message reminders proves to be effective , this technique can be used in daily practice , which would support children with suboptimal adherence in their asthma (self)management and in achieving better asthma control and better quality of life . Trial registration Netherl and s Trial Register NTR2583 BACKGROUND The efficacy and safety of the 300-index of reactivity ( IR ) dose of 5-grass-pollen sublingual immunotherapy ( SLIT ) tablets ( Stallergènes , Antony , France ) have been demonstrated for the treatment of hay fever in adults . OBJECTIVE We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 278 children ( 5 - 17 years of age ) with grass pollen-related rhinoconjunctivitis ( confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement ) received once-daily SLIT tablets or placebo . Treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was the rhinoconjunctivitis total symptom score ( RTSS ) , a sum of 6 individual symptom scores : sneezing , runny nose , itchy nose , nasal congestion , watery eyes , and itchy eyes . Secondary end points included rescue medication intake , individual scores , and safety . RESULTS The intent-to-treat population included 266 children ( mean age , 10.9 + /- 3.22 years ) . The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001 ) . The 300-IR group showed a mean improvement for the RTSS of 28.0 % over that seen with placebo and a median improvement of 39.3 % . Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146 , respectively ) . Adverse events were generally mild or moderate in intensity and expected . No serious side effects were reported . CONCLUSION Five-grass-pollen SLIT tablets ( 300 IR ) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis Background Asthma and allergic rhinitis are the two most common chronic disorders in childhood and adolescence . To date , no study has examined the impact of comorbid allergic rhinitis on asthma control in children . Objective To examine the prevalence of allergic rhinitis in children with asthma , and the impact of the disease and its treatment on asthma control . Methods A cross-sectional survey in 203 children with asthma ( 5–18 years ) using vali date d question naires on rhinitis symptoms ( stuffy or runny nose outside a cold ) and its treatment , and the  paediatric Asthma Control Question naire  ( ACQ  ) . Fraction of nitric oxide in exhaled air ( FeNO ) was measured with a Niox Mino analyser ;  total and specific IgE levels were assessed by the Immunocap system . Results 157 children ( 76.2 % ) had symptoms of allergic rhinitis but only 88 of these ( 56.1 % ) had been diagnosed with the condition by a physician  . ACQ scores were worse in children with allergic rhinitis than in those without the condition ( p=0.012 ) . An ACQ score ≥1.0 ( incomplete asthma control ) was significantly more likely in children with allergic rhinitis than in those without ( OR 2.74 , 95 % CI 1.28 to 5.91 , p=0.0081 ) , also after adjustment for FeNO levels and total serum IgE. After adjustment for nasal corticosteroid therapy , allergic rhinitis was no longer associated with incomplete asthma control ( OR 0.72 , 95 % CI 0.47 to 1.12 , p=0.150 ) . Conclusion Allergic rhinitis is common in children with asthma , and has a major impact on asthma control . The authors hypothesise that recognition and treatment of this condition with nasal corticosteroids may improve asthma control in children , but r and omised clinical trials are needed to test this hypothesis 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 Continuing study for a second year and further analysis of a double‐blind placebo controlled trial , already briefly reported , of injections of tyrosine‐adsorbed , glutaraldehyde‐modified Dermatophagoides pteronyssinus antigen in fifty‐one children with perennial asthma and positive bronchial challenge to the antigen , confirms that the patients receiving the treatment reduced their symptomatic medication more than controls , without deterioration of symptoms . Some became symptom‐free , when off all treatment Asthma is the most common chronic disease of childhood . Specific immunotherapy is widely used in several countries for managing allergic asthma . Many clinical trials and a meta- analysis of several studies support its efficacy to reduce the symptoms and medical requirements . The purpose of this study was to clarify the efficacy of subcutaneous immunotherapy ( SCIT ) in improving the symptoms and reducing medication requirements in primary school children with asthma in comparison with pharmacotherapy . A single-blind , drug-controlled clinical trial was performed . A total of 242 primary school children with allergic asthma were included in the study . The patients were recruited from subjects attending the Allergic Center in Mosul City . Their age range was 7 - 12 years with mean age of 10 + /- 2 years . From the total only 197 children ( 81 % ) completed the study and were eligible for analysis , of those , 85 children were managed with SCIT and 112 children were managed with pharmacotherapies only . The follow-up after 1 year indicated that the children treated with SCIT show a marked reduction in the clinical symptoms , medication requirements , and the level of serum-specific IgE when compared with children treated with conventional drugs . SCIT was effective treatment and can prevent or decrease the onset of new sensitization to the offending allergen and maintain its beneficial effect for years after discontinuation Hyposensitisation with Dermatophagoides pteronyssinus tyrosine absorbate in asthmatic children with bronchial sensitivity to D. pteronyssinus  was effective in a 12-month double-blind controlled clinical trial . Compared with controls , treated children used a smaller quantity of drugs while maintaining clinical and lung function improvements . In most children who improved there was no change in immediate response to D. pteronyssinus on bronchial provocation test , but the late reaction was lost in half the patients and these showed the greatest improvement in symptoms UNLABELLED SAFETY and efficacy of sublingual ( sublingual-swallow ) immunotherapy ( IT ) with house dust mite extract were evaluated in 30 children ( 6 - 15 2/3 years of age ) over the first 12 months of an ongoing study . The cumulative dose was 570 micrograms Der p I ( five times that administered with subcutaneous therapy ) . SAFETY One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness , question ably induced by the therapy . Five patients on active therapy and one patient on placebo reported minor local side effects . EFFICACY Pulmonary symptoms were reduced after 12 months in actively treated asthmatics , but this was not consistent with the lack of improvement in bronchial reactivity , skin sensitivity and specific IgG and IgG4 against D.pt . in this group . In patients with rhinitis  nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score . Specific IgE ( D.pt . and D.f . ) increased significantly more in the active treatment group after 3 and 12 months . We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated , but there was no consistent clinical or immunological benefit compared to placebo Background : Especially in childhood , sublingual immunotherapy ( SLIT ) could offer advantages over subcutaneous therapy . However , limited data on its efficacy is available Sublingual immunotherapy has been suggested for the treatment of respiratory allergies . Many controversial studies have been reported on the efficacy of sublingual immunotherapy . The aim of this prospect i ve study was to evaluate whether sublingual immunotherapy was effective according to clinical and laboratory results in pediatric allergies . Thirty-nine allergic , grass pollen sensitive children were admitted into the study .  Sublingual immunotherapy was given over a 12-month period to 21 children ( mean age 10.5 + /- 3.3 years ) , 10 of whom had seasonal allergic rhinitis and 11 seasonal allergic asthma . During the same period , 18 children ( mean age 11.1 + /- 2.5 years ) , 10 with seasonal allergic rhinitis and eight with seasonal allergic asthma , received placebo .  Symptom scores and drug requirements were recorded and urine sample s were collected to detect urinary levels of leukotrienes ( Uc-LTB4 and Uc-LTE4 ) . In patients who received sublingual immunotherapy , the symptom scores of seasonal allergic rhinitis significantly decreased , but no statistically significant changes were observed in terms of symptoms of seasonal allergic asthma . Uc-LTE4 and Uc-LTB4 levels of seasonal allergic rhinitis , with a geometric mean and 95 % confidence interval ( CI ) , were significantly decreased from 216 ( 103 - 464 ) and 61 ( 22 - 198 ) pmol/mmol creatinine to 78 ( 29 - 159 ) and 35 ( 12 - 118 ) pmol/mmol creatinine , respectively ( p < 0.05 and p < 0.05 ) . On the other h and , Uc-LTE4 and Uc-LTB4 levels for seasonal allergic asthma were 180 ( 92 - 355 ) and 78 ( 44 - 258 ) pmol/mmol creatinine and decreased to 156 ( 72 - 402 ) and 69 ( 32 - 254 ) pmol/mmol creatinine , respectively . These changes were not statistically significant ( p > 0.05 ) . According to our clinical results and urinary levels of leukotrienes , which are mediators showing the severity of allergic inflammation , it can be suggested that sublingual immunotherapy may be useful in the treatment of seasonal allergic rhinitis but not of seasonal allergic asthma Twenty asthmatic children with laboratory proved bronchial reactivity to rye-grass pollen were studied over two consecutive grass-pollen seasons . In the first year 11 patients received preseasonal hyposensitisation treatment with an aqueous rye extract  and nine received placebo injections . No treatment was given in the second year . Patients in both the active-treatment and placebo groups showed a pronounced clinical deterioration in their asthma during both pollen seasons . Serum concentrations of IgG-specific antibodies to the rye allergen before treatment were similar in both groups , but after immunotherapy and before the pollen season in the first year these antibody concentrations were raised significantly in the treated group ( p less than 0.005 ) : by the middle of the pollen seasons the difference was no longer significant . IgE-specific antibodies showed a similar but nonsignificant pattern of response . We found no evidence that limited hyposensitisation with a pollen extract is of any clinical benefit in seasonal asthma despite evidence of an immunological response BACKGROUND Immunotherapy with the SQ-st and ardized grass tablet Grazax is efficacious and well-tolerated in adult patients with rhinoconjunctivitis . Allergic asthma and rhinoconjunctivitis are closely linked , and a strategy combining treatment of the upper and lower airways is recommended . OBJECTIVE To investigate the efficacy of treatment with the grass tablet on grass pollen-induced rhinoconjunctivitis and asthma as well as the immunologic response and the safety profile in children . METHODS A total of 253 children age 5 to 16 years , with grass pollen-induced rhinoconjunctivitis with/without asthma , were r and omized 1:1 to active treatment or placebo . Treatment was initiated 8 to 23 weeks before the start of the grass pollen season 2007 and continued throughout the entire season . Symptomatic medication was provided as relief medication to both groups in a stepwise fashion . Primary endpoints were rhinoconjunctivitis symptom and medication scores . RESULTS The rhinoconjunctivitis symptom and medication scores and the asthma symptom score were all statistically significantly different between the 2 treatment groups . The differences in medians relative to placebo were 24 % , 34 % , and 64 % in favor of active treatment . The immunologic response was similar to that observed in adults . The most common adverse reaction was oral pruritus , reported by 40 subjects ( 32 % ) in the active and 3 ( 2 % ) in the placebo group . Six subjects withdrew because of adverse events . No serious adverse events were assessed as treatment-related . CONCLUSION Immunotherapy with the grass tablet reduced grass pollen-induced rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced an immunomodulatory response , consistent with treatment of the underlying allergic disease . The treatment was well tolerated BACKGROUND Asthma control is now recognized as the main goal of asthma therapy . Guidelines recommend finding the lowest effective dose of inhaled corticosteroids in children with persistent asthma . OBJECTIVE The aim of this study was to investigate the efficacy of an allergen-specific immunotherapy with a high-dose hypoallergenic mite preparation ( allergoid ) as steroid-sparing agent in children with allergic asthma . METHODS Sixty-five children with asthma ( Global Initiative for Asthma treatment levels II and III ; 6 - 17 years old ) , after reaching asthma control with inhaled steroids during a 5-month baseline period , were r and omized for subcutaneous mite allergoid immunotherapy ( SCIT ) plus fluticasone propionate ( FP ) or FP therapy alone for 2 years . During 2 subsequent 5-month winter periods , steroid therapy was adjusted according to predefined dose steps , determining and comparing the changes in FP dosages and the lowest FP dose sufficient to maintain asthma control . Immunologic and functional investigations were also carried out . RESULTS Children treated with house dust mite SCIT plus FP were able to significantly reduce the FP dose by more steps ( P < .05 ) , compared with the control group on FP alone . The mean daily dose in the immunotherapy group decreased from 330.3 μg in the baseline period to 151.5 μg after 2 treatment years , whereas in the control group the dose decreased from 290.6 μg to 206.3 μg . Compared with the control group , significant improvement was also observed in morning peak expiratory flow ( P = .0315 ) . Significantly increased levels of specific IgG(1 ) ( P = .0001 ) and IgG(4 ) ( P < .0001 ) were also observed . CONCLUSION Adding a mite allergoid SCIT to pharmacologic treatment is an effective and safe strategy to reduce corticosteroid doses while maintaining disease control in children with mite-induced allergic asthma BACKGROUND dermatophagoides pteronyssinus ( Der PI ) is the major allergen which causes allergic asthma and perennial rhinitis . The extracts of Der PI may be used in treatment of patients who are unresponsive to pharmacological treatment and avoidance of allergens . The success of immunotherapy ( IT ) depends on the selection of appropriate patients and allergens as well as a regular follow up . OBJECTIVE three different groups of IT material s and a placebo were tested on 34 patients with Der PI sensitive asthma . Clinical evaluations of allergen challenge and in vitro immunologic tests were made on the patients before , on the 6th month and at the end of the second year of IT . The results were compared to the placebo treated group . RESULTS there were no significant differences among the groups in regard to age , sex and duration of illness . The time required for reaching the maintenance dose for group I ( Alutard ) , II ( APSI retard Ca ) and III ( Greer ) was 15.40 + /- 0.69 , 18.2 + /- 4.0 and 108 + /- 33 weeks , respectively . Even though there was some significant difference between those receiving aqueous IT and the placebo ( p < 0.05 ) , there was a greater significant difference between those receiving adsorbed IT and placebo ( p < 0.00001 ) . Also there was a significant difference between the I and II groups receiving adsorbed IT . There was no significant difference in the maximum tolerated doses between group I and II ( p > 0.05 ) , but significant differences was found between group III and the other two groups ( p < 0.05 ) . Specific IgE levels were not changed by IT . There were no differences in the side effects scores among the groups ( p < 0.05 ) . The maximum tolerated dose of the diluted skin prick test ( DSPT ) solution increased significantly after 6 months and two years treatment as compared to the dose before specific immunotheraphy ( SIT ) . Significant differences were found between group III and group I or group II as well as between the groups under treatment and that group given a placebo ( p < 0.05 ) . The maximum tolerated dose with the bronchial provocation test ( BPT ) increased significantly after IT ( p < 0.05 ) . The differences between the groups under treatment and that given a placebo were significant ( p < 0.05 ) . A significant increase was detected in the levels of the Der PI specific IgG4 after IT ( p < 0.01 ) . The difference between the treatment groups and the placebo group was significant . There was a significant difference between group I and the other groups ( p < 0 . 05 ) but differences between group II and III was not significant ( p > 0.05 ) . No significant correlation was found between ( 1 ) spIgE and the symptom medication score ( SMS ) ( 2 ) sp IgE and spIgG4 ( 3 ) , DSPT and BPT .  A significant positive correlation was found between the maximum tolerated dose with DSPT  and increase in spIgG4 ( r = 0.33 , p = 0.046 ) . A negative correlation was found between SMS and spIgG4 ( p = 0.012 , r = -0.42 ) after IT . CONCLUSION SIT with Der PI is an effective and reliable treatment in allergic asthmatic children . Adsorbed extracts may be preferable to in childhood because of effectively , safety , tolerability and , fewer numbers of injection . The best IgG4 response and velocity of maintenance doses achieved was found in group I. Easy , cheap and safe parameters such a SMS and DSPT can be useful for a follow-up of SIT . Further investigation is required to determine which one of the products is the best RATIONALE Allergic rhinitis and exercise induced bronchoconstriction ( EIB ) are common in asthmatic children . The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children . METHODS This was a double-blind , r and omized , placebo-controlled , parallel group study . Subjects aged 12 - 17 years , with mild-to-moderate asthma , intermittent allergic rhinitis and ≥ 10 % fall in FEV(1 ) at a screening exercise challenge were r and omized to 22 ± 3 days treatment with intranasal fluticasone furoate or placebo . The primary outcome was change in exercise induced fall in FEV(1 ) . Secondary outcomes were changes in the area under the curve ( AUC ) , asthma control question naire ( ACQ ) , pediatric asthma quality of life question naire ( PAQLQ ) , and exhaled nitric oxide ( FeNO ) . RESULTS Twenty-five children completed the study . Mean exercise induced fall in FEV(1 ) ( ± SD ) decreased significantly ( 95 % CI : 0.7 - 18.2 % , P = 0.04 ) in the fluticasone furoate group from 28.4 ± 15.8 % to 19.0 ± 13.8 % , compared to the placebo group ( 27.4 ± 16.0 % to 27.4 ± 19.2 % ) . The change in AUC was not significantly different between treatment groups . However , within the fluticasone furoate group the AUC decreased significantly ( P = 0.01 ) . Although total PAQLQ score did not improve , the activity limitation domain score improved significantly within the fluticasone furoate group ( P = 0.03 ) . No significant changes were observed in FeNO and ACQ . CONCLUSION Treatment of allergic rhinitis in asthmatic children with an intranasal corticosteroid reduces EIB and tends to improve quality of life Sublingual immunotherapy ( SLIT ) has been recommended as a viable alternative to subcutaneous injection therapy in the treatment of airway allergies , though more data is needed from well-controlled studies for documenting its efficacy in different ethnic population s. Ninety-seven children ( age range 6 - 12 years ) , mild-to-moderate asthma with a single sensitization to mite allergen , were enrolled from 5 medical centers in Taiwan to evaluate the efficacy and safety of SLIT with st and ardized mite extracts , which contain Dermatophagoides pteronyssinus ( D.p . ) and Dermatophagoides farinae ( D.f . ) . Patients were double blinded and r and omly assigned to either a SLIT or placebo group . Following 24 weeks of study period , symptom and medication scores , lung function tests , skin prick tests , total serum IgE , and specific IgE to D.p . and D.f . were recorded . The results showed that there was statistically significant difference between these two groups in the analysis of daily ( P=0.011 ) , nighttime ( P=0.028 ) , and daytime ( P=0.009 ) asthmatic scores after 24 weeks of treatment . Patients receiving SLIT improved their forced vital capacity ( FVC ) , forced expiratory volume in 1s ( FEV1 ) , and peak expiratory flow ( PEF ) as compared to baseline ( P=0.042 , P=0.048 , and P=0.001 , respectively ) . No differences were found in skin prick test , total serum IgE and specific IgE to D.p . and D.f . Tolerance with high-dose SLIT was good with few minor adverse events reported . Our results indicated that a 24-week SLIT is of clinical benefit to mite-sensitive asthmatic children in Taiwan BACKGROUND Sublingual immunotherapy is based on the treatment of distinct pathologies . It is not exempt from discomfort and hazards ; thus , alternative approaches for therapy are being tested . OBJECTIVE To assess the effectiveness of sublingual immunotherapy , with Dermatophagoides pteronyssinus in asthmatic children . MATERIAL AND METHODS Fifty pediatric patients of both sexes between 5 and 15 years were r and omly divided into two groups . The first group received sublingual immunotherapy with Dermatophagoides pteronyssinus in concentrations of 500 , 1000 , 2000 , 5000 , 8000 and 10,000 biological units . Both groups received conventional therapy , and spirometry and total IgE were measured every 30 days . The use of bronchodilators and steroids  was assessed before and during the test . RESULTS Peak expiratory flow improved in the study group with a remarkable difference ( p < 0.05 ) . There were not significant differences in the control group ( p > 0.05 ) ; however , at the end of the study an increase of 80 % was observed . In urgency services , patients who received immunotherapy had relative risk ( RR ) = 0.36 and confidence interval ( CI ) of 95 % , 0.15 , 0.84 . The use of steroids equally decreased in patients receiving immunotherapy RR = 0.27 , CI 95 % , 0.10 , 0.69 . CONCLUSIONS Sublingual immunotherapy does reduce the risk for asthma episodes in children Background Immunotherapy is a recognized treatment for allergic respiratory diseases In a r and omized double-blind multicenter clinical study , 116 children with asthma were r and omly assigned to treatment with an inhaled beta-2-agonist ( salbutamol 0.2 mg ) plus an inhaled corticosteroid ( budesonide 0.2 mg ) three times a day ( BA+CS ) or to an inhaled beta-2-agonist ( salbutamol 0.2 mg ) plus a placebo three times a day ( BA+PL ) . After a median follow-up time of 22 months , 26 patients receiving BA+PL ( 45 % ) had withdrawn from r and omized treatment , mainly because of asthma symptoms , compared with three withdrawals in the patients receiving BA+CS ( p less than 0.0001 ) . The FEV1 , expressed as a percentage of the predicted value for age , sex , and height , showed an absolute increase of 7.0 % after 2 months of BA+CS compared with a decrease of 4.0 % after 2 months of BA+PL . This 11 % difference in percent predicted FEV1 ( 95 % confidence interval , 7 to 15 % ; p less than 0.0001 ) was then maintained after a median follow-up period of 22 months . Postbronchodilator FEV1 showed an absolute increase of 3.7 % predicted within 2 months in patients receiving BA+CS and an absolute decrease of 1.1 % predicted in children receiving BA+PL ( p = 0.0005 ) . Thereafter , this difference between the two treatment groups was maintained . Average peak expiratory flow rate ( PEFR ) increased from baseline by 36.6 L/min in the BA+CS group compared with 3.7 L/min in the BA+PL group ( p = 0.003 ) . This difference then remained for the median follow-up time of 22 months . ( ABSTRACT TRUNCATED AT 250 WORDS To evaluate the efficacy of specific sublingual immunotherapy ( SLIT ) , we enrolled 15 children with asthma and rhinitis ( 7 girls , 8 boys , mean + /- SD age of 11.7 + /- 3.3 ) allergic to house dust mite ( HDM ) into a double-blind , placebo-controlled study . After a run-in period , patients were r and omized to receive either placebo ( n = 7 ) or SLIT ( n = 8) with a st and ardized Dermatophagoides pteronyssinus ( D. pteronyssinus ) + Dermatophagoides farinea ( D. farinea ) 50/50 extract . They received increasing doses up to 100 index units of reactivity ( IR ) every day for 4 weeks , then 100 IR/day for another 4 weeks , followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months . Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores , serum total IgE levels , results of lung function tests , methacholine provocation tests , and skin prick tests . Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group ( P = 0.05 , P = 0.028 , respectively ) , whereas no such difference was observed in the placebo group . At the end of follow-up , mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group ( P = 0.04 ) . Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups , whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group ( P = 0.026 ) . At the end of 6 months , peak expiratory flow ( PEF ) values in the placebo group was significantly lower than in the SLIT group ( P = 0.049 ) . Throughout the treatment period , the SLIT group was found to have less asthma exacerbations than the placebo group ( P = 0.007 ) . The provocation concentration causing a 20 % drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups . None of the patients reported local or systemic side effects from SLIT . Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM Twenty-seven asthmatic children allergic to dog were included in the study . Their allergy to dog was confirmed by positive results from the skin prick , radioallergosorbent and provocation tests . The subjects were r and omly assigned to active and placebo groups . Fifteen subjects received immunotherapy with a commercial st and ardized aluminum hydroxide-bound dog d and er extract and 12 subjects received placebo injections containing histamine . After one year 's therapy the conjunctival sensitivity to dog d and er extract had decreased significantly ( p less than 0.001 ) in the active treatment group compared to the placebo group . The hyposensitization effect was already observable after six to eight months of treatment . The decrease in bronchial sensitivity was less marked than that in conjunctival sensitivity and statistically not significant . Immunotherapy was observed to be safe and effective . No systemic adverse reactions occurred and local reactions were mild A double‐blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and st and ardized Cladosporium herbarum allergen preparation .  Thirty children with a clinical history suggesting mould‐induced asthma and /or rhinoconjuctivitis were included . The diagnosis was confirmed by positive skin prick test and Phadebas RAST ® as well as positive bronchial and /or conjunctival provocation test to Cladosporium herbarum . Immunotherapy was given for 10 months in a double‐blind manner to r and omized groups with either Pharmalgen ® /Cladosporium herbarum preparation or histamine placebo .  Allergic side effects to injections were common , especially during the peak of the mould season ( July‐September in Sc and inavia ) . In the active group , 13/16 patients experienced general reactions during the first 10 months of treatment . After 6 months of treatment , eye , nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups , maybe because most of the children were also sensitive to many other allergens , including Alternaria alternala . However , medication scores were significantly lower in the treated group ( P < 0.01 ) . Bronchial ( P < 0.01 ) and conjunctival sensitivity ( P= 0.01 ) were significantly reduced in the Cladosporium‐treated group but not in the placebo group after 10 mouths of treatment . This is the first double‐blind clinical trial showing the clinical efficacy of immunotherapy in children with mould‐induced asthma OBJECTIVE To investigate the prevalence and severity of  asthma , rhinitis , and atopic eczema in schoolchildren from the northeast of Engl and . METHODS We r and omly selected 3,000 children from 80 schools . We used the ISAAC ( International Study of Asthma and Allergies in Childhood ) written question naire . RESULTS The lifetime prevalence rates of symptoms were : rhinitis , 32.8 % ; wheezing , 31.3 % ; hay fever , 23.7 % ; and self-reported asthma , 22.3 % . Rhinitis was reported by 53 % and 61 % of boys and girls with asthma , respectively . Girls 13 to 14 years of age had higher prevalence rates of asthma , rhinitis , and eczema symptoms than boys ; a reverse sex ratio has been shown in this age group . Atopic eczema was reported by 32 % of boys with asthma and 37 % of girls with asthma . CONCLUSIONS The prevalence rates of reported asthma , and symptoms suggestive of asthma , were higher than those previously reported in UK children . The present study would be a suitable baseline for monitoring future trends in the prevalence and severity of asthma and allergic disorders among these children , and provides a framework for further etiologic research into the genetics , lifestyle , environmental , and medical care factors affecting these conditions Fifty eight patients under 12 years of age , positive to mites ( Dermatophagoides pteronyssinus and D. farinae ) according to prick , " in vitro " specific IgE and challenge tests , suffering from asthma and rhinitis , were r and omly assigned on a double blind basis to receive per os either a biologically st and ardized extract of mites ( active therapy TA = 30 patients ) or a saline buffered solution ( placebo = 28 patients ) . Patients took sublingually increasing doses of the solution , followed by maintenance therapy consisting of 15 drops 3 times a week . The results of the trial were assessed after 12 an 18 months , according to the following parameters : symptom scores recorded in diary cards , total and specific IgE levels , total IgG level , IgG1 and IgG4 levels , lymphocytes under population s , nasal challenge test , side effects . During the first 18 months , the patients on active therapy had significantly lower scores ( p less than 0.001 ) and clear variations of rhinomanometric parameters ( p less than 0.01 ) ; IgG also significantly increased . After 12 months , bronchial specific and specific challenge tests showed significantly higher threshold values in comparison to initial values ( p less than 0.05 ) . No statistically significative variation was registered in the placebo group Background : The use of immunotherapy in asthmatic children is still controversial . Sublingual immunotherapy ( SLIT ) may represent an advance , due to the good safety profile , but little is known about its effects on lung function and nonspecific bronchial responsiveness For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose , 66 children with seasonal asthma , rhinitis , and conjunctivitis due to sensitization to olive pollen were enrolled in a double‐blind , r and omized , placebo‐controlled  study between October 1994 and October 1996 in Greece . Thirty‐four patients were r and omly allocated to the active group , and 32 received placebo .  Immunotherapy consisted of olive‐allergen extracts ( Stallergenes SA ) administered sublingually pre‐ and coseasonally from January to July for 2 consecutive years . Serial concentrations from 1 to 300 IR were used up to the maintenance dose of 20 drops of 300 IR daily . The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy , and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years . The patients were assessed by clinical parameters ( symptom and medication scores from patients ' daily diaries ) and immunologic measurements ( specific IgE. lgG4 . eosinophil cationic protein [ ECP ] ) were performed . The actively treated patients had a significantly lower score for dyspnea ( P<0.04 during the first season ; P<0.03 during the second season ) . At the poUinic peak during the second year , a lower score of conjunctivitis was recorded ( P<0.05 ) in the actively treated patients . The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo , whereas there was no symptomatic peak for the same period in the group under active treatment . However , the difference between the groups was not significant . The medication score did not differ significantly between the groups . Oral steroids were the only variables with a P value near the significance level ( P=0.06 ) in favor of the actively treated group . A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment . No significant variation in specific IgE and IgG4 was detected . A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season ( P=0.01 ) , but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings . Tolerance was excellent with only a few minor side‐effects reported . In conclusion , high‐dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive‐pollen sensitization BACKGROUND Allergic rhinitis and asthma are important public health concerns , yet there is no consensus about the benefits and harms of allergen-specific immunotherapy to treat these conditions . We performed an umbrella review of systematic review s summarizing the current evidence for the benefits and harms of subcutaneous immunotherapy ( SCIT ) and sublingual immunotherapy ( SLIT ) . METHODS We search ed MEDLINE , Embase , the Cochrane Library and the grey literature from Jan. 1 , 2010 to Nov. 20 , 2016 for systematic review s of r and omized controlled trials or prospect ively controlled studies involving children or adults with allergic rhinitis or asthma . Outcomes were summarized narratively ( benefits : total combined symptom-medication score , symptom score , medication score , disease-specific quality of life , adherence ; harms : anaphylaxis , death , local and systemic reactions ) . RESULTS Twenty-three systematic review s were included . SCIT and SLIT were more effective than placebo for most outcomes . SCIT was better than SLIT at improving medication and symptom scores , with no differences in quality of life ; however , data were limited for this comparison . Anaphylaxis and death were infrequently reported . Few review s assessed benefits or harms among children . INTERPRETATION Allergen immunotherapy appears to be effective among patients with allergic rhinitis and asthma . The safety of allergen immunotherapy is not conclusively established , although death and anaphylaxis appear to be rare . PROSPERO no. : CRD42015024590 BACKGROUND Immunotherapy has been widely used in the treatment of allergic diseases . We evaluated the clinical efficacy of specific immunotherapy with extracts of Dermatophagoides pteronyssinus ( Dp ) and Dermatophagoides farinae ( Df ) in children with asthma . METHODS All 40 children had moderate-to-severe asthma and positive allergen tests for Dp and Df . All required daily medication . They were r and omly assigned to two groups : Half of them received immunotherapy with subcutaneous injections of Dp and Df extracts , while the other half were not given immunotherapy . Participants were followed up for more than 6 months . RESULTS Children in both groups had apparent improvements in medication use and symptoms after 6 months . The mean medication scores declined from 3.6 + /- 1.14 to 1.7 + /- 0.66 in the immunotherapy group ( p < 0.01 ) and from 3.35 + /- 0.87 to 2.4 + /- 1.09 in the control group ( p < 0.01 ) . There was a significant difference between the two groups ( mean difference 0.95 ; p < 0.01 ) . The symptom score improved in the immunotherapy group from 2.65 + /- 0.98 to 1.20 + /- 1.00 ( p < 0.01 ) and in the control group from 2.55 + /- 0.99 to 1.40 + /- 0.88 ( p < 0.01 ) , with a significant difference between the two groups ( mean difference 0.3 ; p < 0.01 ) . The number of office visits in the immunotherapy group was greater than that of the controls , but the frequencies of emergency room visits and hospitalization decreased . CONCLUSION Our study showed that specific immunotherapy with Dp and Df was beneficial for asthmatic children The clinical efficacy of sublingual immunotherapy ( SLIT ) has been demonstrated , but its mechanism of action is still controversial . The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines , such as interleukin-4 ( IL-4 ) , IL-5 and IL-13 , by co-stimulatory molecules , such as CD40 on B cells , and by hormones and neuropeptides . To better underst and whether SLIT affects immune responses we used a double-blind placebo-controlled design . Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus ( 33 of whom also had rhinoconjunctivitis ) were r and omly assigned SLIT ( n = 47 ) or  placebo  ( n = 39 ) . We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP , IL-13 , prolactin ( PRL ) and ACTH at enrolment and after 6 months of therapy . We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group , no variation in CD40 and ACTH , but a significant decrease in ECP , IL-13 and PRL after 6 months of therapy ( p < 0.01 ) . Our results confirm the efficacy and safety of SLIT , and lead us to believe that it could modulate the synthesis of Th2 cytokines , as revealed from the decrease of IL-13 . In addition , the reduction of PRL might be a signal of reduced activation of T lymphocytes Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma , few have shown the same benefit using sublingual immunotherapy ( SLIT ) in asthmatic patients . This study was conducted to assess the efficacy of house dust mite ( HDM ) SLIT in addition to allergen avoidance and st and ard pharmacologic treatment . A double-blind , placebo-controlled trial was performed in 111 children ( aged 5 - 15 yr ) with HDM-induced mild-to-moderate asthma . After a 4-week baseline phase , patients were r and omly assigned to receive SLIT with tablets of HDM extract ( n = 55 ) or placebo ( n = 56 ) for 18 months . Pharmacologic treatment was adjusted every 3 months following a step-down approach . Asthma symptom scores , reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists , rhinitis symptoms , lung function tests , skin sensitivity to HDM , dust mite-specific immunoglobulin ( Ig ) E and IgG(4 ) , and quality of life ( QoL ) were assessed during the study . After 18 months of treatment , diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups . Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups . There were no significant differences in lung function ( forced expiratory volume in 1 s and peak flow rate variations ) between groups . Rhinitis symptom score decreased in both groups , with no difference between the two groups . The severity dimension of QoL was significantly improved in the SLIT group ( age 6 - 12 yr ) . SLIT induced a significant reduction of skin sensitivity to HDM ( p < 0.01 ) and a significant increase in HDM-specific IgE and IgG(4 ) antibodies ( p < 0.001 ) in the SLIT group compared with the placebo group . SLIT was well tolerated with mild/moderate local adverse events . No severe systemic reactions were reported . This study indicates that , when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance , SLIT does not provide additional benefit , despite a significant reduction in allergic response to HDM . Under such conditions , only a complete , but ethically unfeasible , discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT BACKGROUND Injections of allergens are widely prescribed for patients with asthma , but little is known about the effectiveness of immunotherapy . METHODS We conducted a double-blind , placebo-controlled trial of multiple-allergen immunotherapy in 121 allergic children with moderate-to-severe , perennial asthma . The children , who required daily medication for their asthma , were r and omly assigned to receive subcutaneous injections of either a mixture of up to seven aeroallergen extracts or a placebo . Maintenance injections were continued for 18 months or longer . Medications were adjusted every two to three weeks on the basis of peak flow rates and symptoms . The principal outcome was the daily medication score . Bronchial sensitivity to methacholine ( the concentration provoking a 20 percent decrease in the forced expiratory volume in one second [ PC20 ] ) was measured twice yearly . RESULTS The median medication score declined from 5.4 to 4.9 in the immunotherapy group ( P<0.001 ) and from 5.2 to 5.0 in the placebo group ( P<0.001 ) , but there was no significant difference between the groups ( P>0.6 ) . The number of days on which oral corticosteroids were used was similar in the two groups . Partial or complete remission of asthma occurred in 31 percent of the immunotherapy group and in 28 percent of the placebo group ( P>0.5 ) . There was no difference between the groups in the use of medical care , symptoms , or peak flow rates . The median PC20 increased significantly in both groups , but again with no difference between the two groups . CONCLUSIONS Immunotherapy with injections of allergens for over two years was of no discernible benefit in allergic children with perennial asthma who were receiving appropriate medical treatment Background : Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy . We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy ( SLIT ) in asthmatic children with mite‐induced respiratory allergy Background : We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and /or rhinitis and /or rhinoconjunctivitis due to grass pollen
OBJECTIVE Because most children with asthma now use inhaled corticosteroids ( ICS ) , the added benefit of immunotherapy in asthmatic children needs to be examined .
We re-assessed the effectiveness of subcutaneous ( SCIT ) and sublingual immunotherapy ( SLIT ) in childhood asthma treatment focusing on studies with patient-relevant outcome measures and children using ICS .