Asthma and atopy are associated with chromosome 17q21 markers in Chinese children

Background:  Single-nucleotide polymorphism (SNP)-based genome-wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest signal being detected for the SNP rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children.
Methods:  Asthmatic children and non-allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen-specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshot™, and their genotype associations with asthma traits analyzed using multivariate regression.
Results:  315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 ( P  =   0.019–0.034), whereas atopy was associated only with rs11650680 ( P  =   0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 ( P  =   0.008–0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09–0.52 ( P  =   0.0002) and 0.41 and 0.18–0.90 ( P  =   0.025).
Conclusion:  Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than ORMDL3 in this region.     

‘25‐Hydroxyvitamin D,Autoantigenic and Total Antibody Concentrations: Results from a Danish Case–control Study of Newly Diagnosed Patients with Childhood Type 1 Diabetes and their Healthy Siblings’

B cells have recently entered the stage as an important accessory player in type 1 diabetes (T1D) etiopathogenesis. Experimental studies suggest regulatory functions of vitamin D on B cells. However, only a few human studies, with considerable methodological limitations, have been conducted within this field. Our objective was to investigate whether higher 25‐hydroxyvitamin D (25(OH )D) concentrations were inversely associated with β‐cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA ) and insulinoma‐associated antigen‐2A (IA ‐2A). Further, we also wanted to examine the relationship between 25(OH )D and total antibody concentrations. We randomly selected 500 patients with newly diagnosed T1D and 500 siblings for 25(OH )D, antibody and genetic analysis from the population‐based Danish Registry of Childhood and Adolescent Diabetes. The relative change (RC ) in the mean concentration of GADA , IA ‐2A and antibody isotypes by a 10 nmol/l increase in 25(OH )D concentration was modelled by a robust log‐normal regression model. We found no association between 25(OH )D and GADA [adjusted RC per 10 nmol/l increase: 1.00; 95% confidence interval (CI ): 0.98–1.02] and IA ‐2A [adjusted RC per 10 nmol/l increase: 0.92; CI : 0.76–1.12]. Further, 25(OH )D was not associated with the total concentration of antibody isotypes [immunoglobulin (Ig)A, IgE, IgG and IgM]. All null findings were unaltered after adjustment for genetic variation in the vitamin D pathway. Physiological concentrations of 25(OH )D are unlikely to have a clinically important effect on antibody concentrations in a paediatric population of newly diagnosed patients with T1D and their healthy siblings.

     

Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children

Background Vitamin D is known to have a number of immunological effects and it may play a role in preventing allergic diseases.
Objectives To study the effect of maternal intake of vitamin D during pregnancy on the emergence of asthma, allergic rhinitis (AR), and atopic eczema by the age of 5 years in children with HLA-DQB1-conferred susceptibility for type 1 diabetes.
Methods Children (1669) participating in the population-based birth cohort study were followed for asthma, AR, and atopic eczema assessed by validated questionnaire at 5 years. Maternal diet was assessed by a food-frequency questionnaire.
Results The mean maternal intake of vitamin D was 5.1 (SD 2.6) μg from food and 1.4 (2.6) μg from supplements. Only 32% of the women were taking vitamin D supplements. When adjusted for potential confounders, maternal intake of vitamin D from food was negatively related to risk of asthma [hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.64–0.99] and AR [HR 0.85; 95% CI 0.75–0.97]. Vitamin D supplements alone were not associated with any outcome. Adjustment for maternal intake of other dietary factors did not change the results.
Conclusion Maternal vitamin D intake from foods during pregnancy may be negatively associated with risk of asthma and AR in childhood.     

The association of asthma, atopy and lung function with hormone replacement therapy and surgical cessation of menstruation in a population-based sample of English women

Background:  Gynaecological surgery that may lead to cessation of menstruation is a major indication for the use of hormone replacement therapy (HRT) which in turn has been associated with asthma.
Methods:  Information on asthma-like symptoms, lung function and immunoglobulin E (IgE) sensitization to house dust mite (HDM) and on menstrual status and use of HRT was collected from 3724 women aged between 35 and 64 years living in England. Association of health outcomes with use of HRT and with surgery resulting in cessation of menstruation was examined in multivariable models.
Results:  Over a third of women who had ever used HRT had undergone surgery resulting in cessation of menstruation. Current use of HRT was associated with frequent wheeze, particularly in lean women [body mass index (BMI) < 25; odds ratio (OR) 1.90; 95% confidence interval (CI) 1.17–3.05; BMI 25+; OR 1.02; 95% CI 0.69–1.51]. Wheeze was associated with the reporting of menstrual cessation that was due to surgery even if women denied ever using HRT (OR 1.55; 95% CI 1.09–2.20). There was some evidence that HRT use was associated with airway obstruction in leaner women but little evidence that it was associated with IgE sensitization to HDM.
Conclusions:  In this cross-sectional study use of HRT was associated with asthma-like symptoms, particularly in those who have lower BMI. A substantial proportion of women whose periods have stopped because of surgery use HRT but this does not fully explain their increased morbidity.     

Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults

Background:  Filaggrin ( FLG ) null mutations are important genetic predisposing factors for atopic asthma and have recently been shown to influence controller and reliever medication needs in asthmatic children. Our objective was to study the role of FLG null alleles in asthma exacerbations.
Methods:  FLG mutations R501X and 2282del4 were assayed in 1135 individuals ranging from 3 to 22 years old with asthma from Tayside and Dumfries, Scotland. Asthma exacerbations over the previous 6 months were also studied.
Results:  The FLG mutations were significantly associated with greater risk of exacerbations in children with asthma. Exacerbations were significant for the R501X but not the 2282del4 mutation and the combined genotype compared to the wild-type with odds ratios of 1.97 (95% CI, 1.19–3.22; P  = 0.009) and 1.61 (95% CI, 1.08–2.40; P  = 0.021), respectively. Individuals with FLG null alleles were more likely to require oral steroids (31.4% vs 19.5%; OR = 1.89; P  =   0.021) for their exacerbations. There was also a 1.71-fold increased risk (42.6% vs 30%; P  =   0.041) of school absence owing to asthma exacerbations in asthmatic individuals with FLG null mutation. On sub-group analysis, the effect of FLG mutations on asthma exacerbations is significant ( P  =   0.045) only for participants with relatively mild asthma controlled on inhaled steroids, with inhaled albuterol according to need.
Conclusion:  In addition to their effect on asthma medication requirements reported previously, there is an association between the presence of FLG null mutations and the risk of asthma exacerbations in asthmatic children and young adults.     

Predictivity of allergic sensitization (RAST) for the onset of allergic diseases in adults

Background:  Specific IgE antibodies are often detected without any clinical manifestation of allergies. We aimed to analyse the predictivity of allergic sensitization for incident symptoms of allergic diseases in adults during a 10-year follow-up .
Methods:  In 1994/95 specific IgE antibodies against five common inhalant allergens (grass pollen, birch pollen, house dust mite, cat dander and Cladosporium ) were diagnosed by radioallergosorbent test in 4178 adults aged 25–74 years. A subset of 2656 participants could be re-evaluated in 2004/05. Information on socio-economic factors and medical history, including data on atopic diseases, was assessed by a combination of a personal interview and a self-administered questionnaire. Logistic regression models were applied to study associations between allergic sensitization and incident allergic diseases.
Results:  Allergic sensitization was an important predictor for incident hay fever (OR 7.95, CI 95% 4.64–13.62) and asthma (OR 1.82, CI 95% 1.29–2.57). Specific IgE antibodies were mainly related to outdoor allergens (grass and birch pollen) for hay fever and indoor allergens (mite and cat dander) for asthma, while for atopic dermatitis no specific IgE antibodies were identified as major predictors.
Conclusions:  Allergic sensitization not only covers clinically apparent allergies, but indicates a prognostic factor for later allergies, even in adulthood.     

CTLA4 gene polymorphisms and soluble CTLA4 protein in Behcet's disease

Cytotoxic T lymphocyte antigen 4 (CTLA4; CD152) is a costimulatory molecule expressed on activated T cells that plays a key inhibitory role during T lymphocyte activation. The gene encoding for CTLA4 has been suggested as a candidate for conferring susceptibility to autoinflammatory diseases. We investigated the polymorphisms of the CTLA4 gene [promoter region (−1722 T/C, −1661 A/G and −318 C/T) and exon 1 (+49 G/A)] and the differences of serum soluble sCTLA4 levels in 285 patients with Behcet's disease (BD) and 287 controls. The frequency of the CTLA4 −1661 GG genotype was significantly higher in BD patients than in controls [ P  = 0.019, odds ratio (OR) = 5.2, 95% confidence interval (CI) = 1.13–23.86]. Also, the genotype frequency for CTLA4 −1722 TC was significantly higher ( P  = 0.014, OR = 1.8, 95% CI = 1.13–2.99), while CTLA4 −1722 CC was significantly lower ( P  = 0.018, OR = 0.4, 95% CI = 0.20–0.87) in BD patients with ocular lesions compared with patients without this symptom. Serum sCTLA4 levels in BD patients were significantly lower, especially in BD patients with the CTLA4 +49 G allele, than those in healthy controls ( P  < 0.05). Although our understanding of the role of the CTLA4 gene and its protein product in BD is incomplete, these results suggest that single nucleotide polymorphisms of the promoter and exon regions in the CTLA4 gene are candidates that predispose to BD and that sCTLA4 may be related to the immunological abnormalities and disease expressions associated with BD.     

Maternal vitamin D status and infant anthropometry in a US multi-centre cohort study

Background: Maternal vitamin D status in pregnancy is linked to foetal growth and may impact infant growth.

Aim: This study examined the association between maternal vitamin D status and infant anthropometry.

Subjects and methods: Data came from n?=?2473 mother–child pairs from the 12-site US Collaborative Perinatal Project (1959–1965). Maternal serum 25-hydroxyvitamin D (25(OH)D) was measured at?≤?26 weeks gestation. Multivariate-adjusted linear mixed models were used to relate maternal vitamin D status to infant z-scores for length (LAZ), head circumference (HCZ), weight (WAZ) and BMI (BMIZ), measured at birth and 4, 8 and 12 months.

Results: Infants with maternal 25(OH)D ≥30?nmol/L vs <30?nmol/L had LAZ and HCZ measures 0.13 (95% CI?=?0.03–0.23) and 0.20 (95% CI?=?0.11–0.28) units higher, respectively, across the first year of life. Similar differences in WAZ and BMIZ at birth were resolved by 12 months of age due to interactions indicating steeper age slopes in infants with maternal 25(OH)D <30?nmol/L.

Conclusion: Low maternal vitamin D status was associated with deficits at birth in infant weight and BMI that were recouped across the first year of life; associations with reduced measures of linear and skeletal growth were sustained from birth to 12 months.     

25-hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal women

Introduction

Low 25-hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms.

Study design

Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial.

Main Outcome Measures

25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling.

Results

The 25(OH) D levels were commonly low with 53% having deficient (<50 nmol/L) and only 17% having sufficient (>72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R = 0.29, p < 0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P = 0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile.

Conclusions

Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials.     

Vacuum-assisted delivery is associated with late-onset asthma

Background:  Perinatal factors during delivery might modulate fetal immunological development and thereby be associated with the development of allergic diseases and asthma later.
Methods:  Perinatal data was recorded during pregnancy and at the time of delivery in regard to 5823 children who were born in Northern Finland in 1985–1986. Data from self-administered questionnaires were available at the ages of 7 and 15–16 years and skin prick tests for four main allergens were carried out at the age of 15–16 years. Only singletons delivered by the vaginal route were analyzed.
Results:  There was a higher prevalence of doctor-diagnosed asthma at any time of life among children who were delivered by vacuum extraction (RR 1.80, 95% CI 1.27–2.56; P  < 0.001) in comparison with spontaneously delivered children. In particular, this risk was increased as regards late-onset asthma (RR 2.41, 95% CI 1.52–3.81; P  < 0.001). Perinatal effects had less impact on the development of other asthma, atopy or hay fever.
Conclusions:  The delivery by vacuum extraction had significant impact on the development of late-onset asthma compared with spontaneously delivered children.     

Pre-Eclampsia, Placental Abruption and Increased Risk of Atopic Sensitization in Male Adolescent Offspring

Problem  The aim of this study was to investigate maternal pre-eclampsia (PE), placental abruption (PA) and atopy among offspring.
Method of study  Obstetric data was recorded from 378 women who were included into the Caesarean delivery birth cohort during 1990–1992. When their children were 15–17 years old skin prick tests (SPTs) and inhalant allergen-specific (IAS) immunoglobulin E (IgE) were determined among offspring.
Results  Adolescents whose mothers had either PE or PA at the time of delivery had more atopy and especially more severe atopy as measured by the incidence of SPTs positive for ≥5 allergens (RR: 4.28, 95% CI: 1.54–11.92; P  < 0.005) and elevated IAS IgE levels (≥1.0 kU/L) (RR: 4.27, 95% CI: 1.08–16.99; P  < 0.039). This increased risk was particularly observed in male adolescents.
Conclusion  Maternal PE and PA were associated with an increased risk of severe atopy, especially in male adolescent offspring.     

The socio-economic burden of asthma is substantial in Europe

Background:  Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe.
Methods:  In 1999–2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed.
Results:  The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4–15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1–16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18–4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52–5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63–4.61) and sixfold (RRR = 5.76; 95% CI: 3.25–10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16–3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9–27.1%).
Conclusions:  The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.     

中国北方地区老年人冬季维生素D缺乏与骨量丢失

背景：中国北方地区老年人维生素D营养状态存在季节变化,冬春季维生素D缺乏严重。 目的：分析沈阳市老年人冬季维生素D缺乏对骨量丢失的影响。 方法：随机选择沈阳市60岁以上汉族健康老年人100名,于2000-03检测受试者血浆中25羟维生素D、甲状旁腺激素、钙和磷,清晨空腹2 h尿中脱氧吡啶、钙、磷、肌酐,2000-03/2005-03两次检测髋部骨密度。 结果与结论：基线时,血浆25羟维生素D浓度为(31.0±12.30) nmol/L,40%受试者低于25 nmol/L;血浆甲状旁腺激素水平为(29.4±11.5) ng/L,血浆25羟维生素D浓度低于25 nmol/L者甲状旁腺激素水平为(34.6±13.5) ng/L,血浆25羟维生素D浓度与甲状旁腺激素呈负相关(r=-0.479,P < 0.000 1)。5年后股骨颈骨丢失率为(3.05±4.07)%,大转子为(1.46±5.02)%,经体质量和身高变化率校正后,股骨颈骨丢失率与基线血浆25羟维生素D浓度呈负相关(r=-2.3,P=0.02),股骨颈骨丢失率基线血浆25羟维生素D浓度≤ 25 nmol/L者高于浓度>25 nmol/L者103%( F=7.206 2,P=0.008 5)。其他检测指标与骨丢失无显著相关性。说明老年人群冬季维生素D缺乏严重,维生素D缺乏促进骨量丢失,影响骨健康。      

The association between serum 25-hydroxyvitamin D concentrations and serum lipids in the Southern Thai population

IntroductionDyslipidaemia is a major risk factor for cardiovascular diseases (CVD). Vitamin D deficiency has been found to be associated with CVD. However, the relationships between vitamin D and lipids are inconsistent. The aim of this study was to investigate the relationship between vitamin D status and serum lipids in Southern Thai subjects.Material and methodsA total of 726 healthy subjects in Southern Thailand were enrolled in the study. Serum 25-hydroxyvitamin D (25(OH)D), lipid profiles, fasting plasma glucose, anthropometric data, blood pressure, and body composition were measured. The relationship between serum 25(OH)D levels and biochemical data was evaluated by partial correlation and multiple linear regression analyses. The association of serum 25(OH)D levels with dyslipidaemia was analysed using multivariate regression analysis.ResultsSerum 25(OH)D levels were negatively correlated with body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and body composition parameters after adjusting for age in women. Multiple linear regression analysis showed that TC and BMI were independent predictors for 25(OH)D concentrations in women. Multivariate logistic regression analysis showed that the odds ratio of hypertriglyceridaemia (OR = 0.51; 95% CI: 0.32–0.80, p = 0.004) and reduced high-density lipoprotein cholesterol (HDL-C) (OR = 0.43; 95% CI: 0.26–0.71, p = 0.001) were significantly lower in vitamin D sufficiency when compared with hypovitaminosis D in women.ConclusionsVitamin D sufficiency could reduce risk of hypertriglyceridaemia and reduced HDL-C, particularly in women, suggesting that vitamin D sufficiency may have beneficial effects on lipids and a decreased risk for CVD in Thai women.     

The influence of the dietary intake of fatty acids and antioxidants on hay fever in adults

Background:  The objective of the investigation was to explore in a prospective study the associations between dietary intake of fatty acids, antioxidants and hay fever manifestation in adulthood.
Methods:  Three hundred and thirty-four hay fever cases with adult onset of clinical symptoms from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort were identified during follow-up and matched with 1336 controls. Dietary intake data were obtained by means of validated food frequency questionnaires. The influence of dietary fatty acid and vitamin intake on hay fever risk was estimated by means of unconditional logistic regression.
Results:  High intake of oleic acid was positively associated with hay fever [odds ratio (OR): 2.86, 95% confidence intervals (95% CI): 1.22–6.70], whereas high intake of eicosapentaenoic acid was inversely related to hay fever (OR: 0.45, 95% CI: 0.22–0.93). Furthermore, high β -carotene intake increased the risk of hay fever (OR: 1.69, 95% CI: 1.09–2.63) while increasing intake of vitamin E was a protective factor (OR: 0.38, 95% CI: 0.17–0.85). In grouped analyses, the effects of β -carotene and vitamin E were mainly observed among women and ex-/current-smokers; in these subgroups, linoleic acid increased the risk of hay fever.
Conclusions:  In conclusion, the present results provide further evidence that dietary factors might affect the risk of clinical manifestation of hay fever. However, the effects in smokers and women may suggest different biological mechanisms for the investigated nutrients, which need further research.     

Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study

Background:  Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment.
Methods:  Patients (7.9–64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG₄ measured.
Results:  Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8−92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between −11.3% and −14.8% for placebo ( P  < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and −1.51% for placebo ( P  < 0.05). Combined score ( P  = 0.0508) and symptom score improvements ( P  = 0.0144) with SLIT continued during follow up. Increases in specific IgG₄ observed in the first season were sustained for SLIT vs placebo throughout treatment ( P  = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported.
Conclusions:  Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.     

Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study

Background:  Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment.
Methods:  Patients (7.9–64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG₄ measured.
Results:  Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8−92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between −11.3% and −14.8% for placebo ( P  < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and −1.51% for placebo ( P  < 0.05). Combined score ( P  = 0.0508) and symptom score improvements ( P  = 0.0144) with SLIT continued during follow up. Increases in specific IgG₄ observed in the first season were sustained for SLIT vs placebo throughout treatment ( P  = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported.
Conclusions:  Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.