Meta-analyses of the efficacy of pharmacotherapies and sublingual allergy immunotherapy tablets for allergic rhinitis in adults and children.

BACKGROUND: Treatment options for seasonal and perennial allergic rhinitis (SAR/PAR) include pharmacotherapies and allergy immunotherapy. These meta-analyses evaluated the efficacy of pharmacotherapies and sublingual immunotherapy tablets (SLIT-tablets) versus placebo on nasal symptoms associated with SAR and PAR. METHODS: Randomized, double-blind, placebo-controlled trials were identified from systematic PubMED/EMBASE searches through 7/18/2019 (PROSPERO protocol CRD42018105632). The primary outcome was mean numerical difference in total nasal symptom score (TNSS; 0-12) between active treatment and placebo at the end of the assessment period. Random-effects meta-analyses estimated the mean difference for each medication group weighted by the inverse of the trial variance. Publication bias assessments and sensitivity analyses were conducted. RESULTS: Rescue symptom-relieving pharmacotherapy was prohibited in most pharmacotherapy trials but was allowed in all SLIT-tablet trials. For adult/adolescent SAR, the mean numerical difference (95% CI) in TNSS versus placebo was: intranasal corticosteroids (INCS)=1.38 (1.18, 1.58; 39 trials); combination intranasal antihistamine/INCS=1.34 (1.15, 1.54; 4 trials); intranasal antihistamines=0.72 (0.56, 0.89; 13 trials); oral antihistamine=0.62 (0.35, 0.90; 18 trials); SLIT-tablets=0.57 (0.41, 0.73; 4 trials); and montelukast=0.48 (0.36, 0.60; 10 trials). For adult/adolescent PAR, mean difference in TNSS versus placebo (95% CI) was: INCS=0.82 (0.66, 0.97; 14 trials); SLIT-tablets=0.65 (0.42, 0.88; 3 trials); and oral antihistamine=0.27 (0.11, 0.42; 3 trials). The number of eligible trials limited meta-analyses for pediatric SAR/PAR. CONCLUSIONS: All treatments significantly improved nasal symptoms versus placebo. SLIT-tablets provided improvement in TNSS despite access to rescue symptom-relieving pharmacotherapy. Extensive trial heterogeneity and strong indications of publication bias preclude the comparison of treatment effects among treatment classes.

Altered brain structure with preserved cortical motor activity after exertional hypohydration: a MRI study.

Hypohydration exceeding 2% body mass can impair endurance capacity. It is postulated that the brain could be perturbed by hypohydration, leading to impaired motor performance. We investigated the neural effects of hypohydration with magnetic resonance imaging (MRI). Ten men were dehydrated to approximately -3% body mass by running on a treadmill at 65% maximal oxygen consumption (V̇o2max) before drinking to replace either 100% [euhydration (EU)] or 0% [hypohydration (HH)] of fluid losses. MRI was performed before start of trial (baseline) and after rehydration phase (post) to evaluate brain structure, cerebral perfusion, and functional activity. Endurance capacity assessed with a time-to-exhaustion run at 75% V̇o2max was reduced with hypohydration (EU: 45.2 ± 9.3 min, HH: 38.4 ± 10.7 min; P = 0.033). Mean heart rates were comparable between trials (EU: 162 ± 5 beats/min, HH: 162 ± 4 beats/min; P = 0.605), but the rate of rise in rectal temperature was higher in HH trials (EU: 0.06 ± 0.01°C/min, HH: 0.07 ± 0.02°C/min; P < 0.01). In HH trials, a reduction in total brain volume (EU: +0.7 ± 0.6%, HH: -0.7 ± 0.9%) with expansion of ventricles (EU: -2.7 ± 1.6%, HH: +3.7 ± 3.3%) was observed, and vice versa in EU trials. Global and regional cerebral perfusion remained unchanged between conditions. Functional activation in the primary motor cortex in left hemisphere during a plantar-flexion task was similar between conditions (EU: +0.10 ± 1.30%, HH: -0.11 ± 0.31%; P = 0.637). Our findings demonstrate that with exertional hypohydration, brain volumes were altered but the motor-related functional activity was unperturbed. NEW & NOTEWORTHY Dehydration occurs rapidly during prolonged or intensive physical activity, leading to hypohydration if fluid replenishment is insufficient to replace sweat losses. Altered hydration status poses an osmotic challenge for the brain, leading to transient fluctuations in brain tissue and ventricle volumes. Therefore, the amount of fluid ingestion during exercise plays a critical role in preserving the integrity of brain architecture. These structural changes, however, did not translate directly to motor functional deficits in a simple motor task.

Deubiquitinase USP10 regulates Notch signaling in the endothelium.

Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs. In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.

Sugammadex hypersensitivity and underlying mechanisms: a randomised study of healthy non-anaesthetised volunteers.

BACKGROUND: We investigated potential for hypersensitivity reactions after repeated sugammadex administration and explored the mechanism of hypersensitivity. METHODS: In this double-blind, placebo-controlled study (NCT00988065), 448 healthy volunteers were randomised to one of three arms to receive three repeat i.v. administrations of either sugammadex 4 mg kg-1, 16 mg kg-1, or placebo. Primary endpoint was percentage of subjects with hypersensitivity (assessed by an independent adjudication committee). Secondary endpoint of anaphylaxis was classified per Sampson and Brighton criteria. Exploratory endpoints included skin testing, serum tryptase, anti-sugammadex antibodies [immunoglobulin (Ig) E/IgG], and other immunologic parameters. RESULTS: Hypersensitivity was adjudicated for 1/148 (0.7%), 7/150 (4.7%), and 0/150 (0.0%) subjects after sugammadex 4 mg kg-1, 16 mg kg-1, and placebo, respectively. After sugammadex 16 mg kg-1, one subject met Sampson criterion 1 and Brighton level 1 (highest certainty) anaphylaxis criteria; two met Brighton level 2 criteria. After database lock it was determined that certain protocol deviations could have introduced bias in the reporting of hypersensitivity signs/symptoms in a subject subset. Objective laboratory investigations indicated that potential underlying hypersensitivity mechanisms were unlikely to have been activated; the results suggest that most of the observed hypersensitivity reactions were unlikely IgE/IgG-mediated. CONCLUSION: Dose-dependent hypersensitivity or anaphylaxis reactions to sugammadex were observed when administered without prior neuromuscular blocking agent. Laboratory investigations do not suggest prevalent allergen-specific IgE/IgG-mediated immunologic hypersensitivity. Because it could not be fully excluded that estimates of hypersensitivity/anaphylaxis incidence were unbiased, an additional study was conducted to characterise the potential for hypersensitivity reactions and is described in a companion report. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00988065; Protocol number P06042.

Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper.

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma.

BACKGROUND: Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT-tablet) treatment, such as severe systemic reactions and asthma-related events. Using data from eight trials of grass SLIT-tablet in subjects with allergic rhinitis with/without conjunctivitis (AR/C), AE frequencies were determined in adults and children with and without reported asthma. METHODS: Data from randomized, double-blind, placebo-controlled trials of Timothy grass SLIT-tablet MK-7243 (2800 BAU/75 000 SQ-T, Merck/ALK-Abelló) were pooled for post hoc analyses. Subjects with uncontrolled and severe asthma were excluded from the trials. Frequencies for treatment-emergent AEs (TEAEs), local allergic swelling (mouth or throat), systemic allergic reactions, and asthma-related treatment-related AEs (TRAEs) were calculated. RESULTS: Among adults (n = 3314) and children (n = 881), 24% and 31%, respectively, had reported asthma. No serious local allergic swellings or serious systemic allergic reactions occurred in subjects with asthma treated with SLIT-tablet. There was no evidence of increased TEAEs, systemic allergic reactions, or severe local allergic swellings in adults or children with asthma treated with grass SLIT-tablet versus subjects without asthma in or outside of pollen season. There were 6/120 asthma-related TRAEs assessed as severe with grass SLIT-tablet and 2/60 with placebo, without a consistent trend among subjects with and without asthma (5 and 3 events, respectively). CONCLUSIONS: In the AR/C subjects with reported well-controlled mild asthma included in these studies, grass SLIT-tablet did not increase TEAE frequency, severe local allergic swelling, or systemic allergic reactions versus subjects without asthma. There was no indication that treatment led to acute asthma worsening.

[Electroconvulsive therapy in depression: insights from fMRI, PET and SPECT studies]. / Elektrokonvulsive Therapie bei Depression: Welche Erkenntnisse erbringen fMRT-, PET- und SPECT-Untersuchungen?

Electroconvulsive therapy (ECT) is the most potent and rapidly acting of all antidepressant treatments in major depressive disorder (MDD). Nuclear and functional magnetic (fMRI) brain imaging studies of ECT have substantially contributed to the neurobiological understanding of this treatment modality. Neuroimaging methods may also validate potential mechanisms of antidepressant action. Models of neural dysfunction in MDD suggest impaired modulation of activity within a cortico-limbic circuitry, along with alterations in the functional organisation of multiple brain networks implicated in emotional processes. Nuclear imaging techniques have demonstrated consistent patterns of ECT-induced ictal changes in brain activity that appear to be linked to efficacy and side effects of ECT. Interictally, widespread alterations of brain function have been reported, however, results remain inconclusive. FMRI studies of ECT have demonstrated longer-lasting, interictal changes of neural activity in multiple cerebral regions that are in accordance with functional neuroanatomical models of mood disorders. Future research detailing ECT interactions with brain pathophysiology in MDD could potentially provide a clinically useful framework to better predict ECT treatment response and/or side effects, and may also facilitate the development of more focused brain stimulation techniques.

A comparative analysis of symptom and medication scoring methods used in clinical trials of sublingual immunotherapy for seasonal allergic rhinitis.

Symptom and medication use are the key outcomes for assessing the efficacy of subcutaneous (SCIT) and sublingual allergen immunotherapy (SLIT). Our objective was to explore the similarities and differences between existing scoring mechanisms used in clinical trials of SLIT for seasonal allergens and characterize the impact that such differences may have on efficacy reporting. Randomized, double-blind, placebo-controlled clinical trials investigating the efficacy of SLIT for seasonal allergic rhinitis (2009-2013) were selected for review. Simulated and published data were used to demonstrate differences in scoring methods. Symptom and medication scoring methods across trials, although all designed to achieve the same objective, included important differences. The maximum daily symptom score (DSS) can vary widely depending on the number of symptoms assessed, and terminology of symptoms is not consistent. Similarly, daily medication scoring (DMS) methods differ greatly among studies and are dependent on medications allowed and weighting of scores assigned to each medication. When published DSS and DMS scores were used to calculate simulated daily combined scores (DCSs) based on various published methods, changes from placebo ranged from 19% to 29% when assuming all variables other than the DSS and DMS methods were equal. Variations in trial design, analysis, and seasonal characteristics also have effects on symptom and medication scoring outcomes. We identified multiple differences in trial scoring methods and design that make comparison among trials difficult. Symptom, medication, or combined scores cannot be indirectly compared among trials without taking the methods of scoring and other trial differences into account.

Magnitude of efficacy measurements in grass allergy immunotherapy trials is highly dependent on pollen exposure.

BACKGROUND: The objective was to evaluate the association between grass pollen exposure, allergy symptoms and impact on measured treatment effect after grass sublingual immunotherapy (SLIT)-tablet treatment. METHODS: The association between grass pollen counts and total combined rhinoconjunctivitis symptom and medication score (TCS) was based on a post hoc analysis of data collected over six trials and seven grass pollen seasons across North America and Europe, including 2363 subjects treated with grass SLIT-tablet or placebo. Daily pollen counts were obtained from centralized pollen databases. The effect of treatment on the relationship between the TCS and pollen counts was investigated, and the relative difference between grass SLIT-tablet and placebo as a function of average grass pollen counts was modelled by linear regression. RESULTS: The magnitude of treatment effect based on TCS was greater with higher pollen exposure (P < 0.001). The relative treatment effect in terms of TCS for each trial was correlated with the average grass pollen exposure during the first period of the season, with predicted reduction in TCS = 12% + 0.35% × pollen count (slope significantly different from 0, P = 0.003; R(2)  = 0.66). Corresponding correlations to the entire grass pollen season and to the peak season were equally good, whereas there was a poor correlation between difference in measured efficacy and pollen exposure during the last part of the season. CONCLUSIONS: In seasonal allergy trials with grass SLIT-tablet, the observed treatment effect is highly dependent on pollen exposure with the magnitude being greater with higher pollen exposure. This is an important relationship to consider when interpreting individual clinical trial results.

Efficacy and safety of the SQ-standardized grass allergy immunotherapy tablet in mono- and polysensitized subjects.

The efficacy of single-allergen-specific immunotherapy in polysensitized subjects is a matter of debate. We therefore performed a post hoc analysis of pooled data from six randomized, double-blind, placebo-controlled trials (N = 1871) comparing the efficacy and safety of the SQ-standardized grass allergy immunotherapy tablet (AIT), Grazax (Phleum pratense 75 000 SQ-T/2800 BAU, ALK, Denmark), in mono- and polysensitized subjects. A statistically significant reduction in the mean total combined symptom/medication score (TCS) of 27% was demonstrated in actively treated subjects compared with placebo (P < 0.0001). This was not dependent on sensitization status (P = 0.5772), suggesting a similar treatment effect in mono- and polysensitized subjects (i.e. reductions of the TCSs of 28% and 26%, respectively, both P < 0.0001). Finally, a comparable and favourable safety profile of grass AIT was demonstrated in the two subgroups. Thus, no difference in efficacy and safety of single-allergen grass AIT was observed between mono- and polysensitized subjects.

Mometasone furoate/formoterol reduces asthma deteriorations and improves lung function.

This study evaluated the effect of mometasone furoate (MF)/formoterol (F) versus its monocomponents, each administered via metered-dose inhaler, on asthma deteriorations and lung function. This 26-week, multicentre, double-blind, placebo-controlled study included subjects aged ≥12 yrs with not well-controlled asthma on low-dose inhaled corticosteroids. After a 2-3-week open-label run-in (MF 100 µg b.i.d.), 746 subjects were randomised to receive placebo, F 10 µg, MF 100 µg or MF/F 100/10 µg b.i.d. Co-primary end-points were time to first asthma deterioration (MF/F versus F to assess effect of MF) and change in forced expiratory volume in 1 s (FEV(1)) area under the curve of serial spirometry measurements over the 12-h period following the morning dose (AUC(0-12h)) (baseline to week 12; MF/F versus MF to assess effect of F). The therapeutic effect of MF in the combination was demonstrated by a reduction in asthma deterioration incidence with MF/F versus F and a delayed time to first asthma deterioration (p<0.001). Asthma deterioration incidence was also reduced with MF/F versus MF (p=0.006). The therapeutic effect of F in the combination was demonstrated by MF/F versus MF in FEV(1) AUC(0-12h) change (4.00 versus 2.53 L·h, respectively; p=0.001). MF/F treatment also resulted in a marked improvement in health-related quality of life. MF/F 100/10 µg b.i.d. treatment showed greater clinical efficacy than its individual components or placebo; both components contributed to the efficacy of MF/F.

Rhinitis: a complication to asthma.

BACKGROUND: Asthma and rhinitis often co-occur, and this potentially increases the disease severity and impacts negatively on the quality of life. We studied disease severity, airway responsiveness, atopy, quality of life and treatment in subjects with both asthma and rhinitis compared to patients with asthma or rhinitis alone. METHODS: We examined 878 patients: 182 with asthma, 362 with rhinitis and 334 with both asthma and rhinitis. All had a clinical interview concerning severity of symptoms, treatment, and quality of life, a skin prick test, a lung function test and a bronchial provocation with methacholine. RESULTS: Patients with both asthma and rhinitis had less severe asthma based on the frequency of respiratory symptoms compared to patients with asthma alone (55%vs 66%P = 0.01). On the contrary, they were more airway responsive (P < 0.05) and had more perennial allergy (P < 0.001). Asthmatics had poor perception of the general health, independent of rhinitis (P < 0.001). No differences were found in asthma-specific quality of life, whereas rhinitis-specific quality of life was worse in those with both asthma and rhinitis compared to those with rhinitis alone (P < 0.01). Subjects with both diseases were undertreated in 85% of the cases. CONCLUSION: We encourage that these observations be used in the evaluation and treatment of patients with asthma and rhinitis and that they contribute to the understanding of asthma and rhinitis as a uniform airways disease.

Unawareness and undertreatment of asthma: follow-up in a different geographic area in Denmark.

BACKGROUND: Early detection and treatment of asthma is important to minimize morbidity and healthcare costs. The objective of this study was to investigate asthma awareness and management in a western society. METHODS: In a random sample of 10 400 subjects aged 14-44 years, 686 (6.6%) reported symptoms of asthma in a standardized screening questionnaire. All 686 were evaluated by respiratory specialists and diagnosed by history, symptoms, lung function tests, bronchial challenges and allergy testing. Of these 686 participants, 69 (10%) had asthma alone, 205 (30%) had rhinitis alone and 217 (32%) had both asthma and rhinitis; 195 (28%) had nonasthmatic respiratory reports. RESULTS: Awareness of asthma was found among 163 (57%) of the 286 asthmatics, and 204 (95%) had doctor-diagnosed rhinitis as well. In a multivariate regression analysis, comorbidity with rhinitis (beta = 0.489, P < 0.001), smoking (beta = -0.116, P < 0.01), doctor-diagnosed bronchitis (beta = 0.086, P < 0.05), and earlier emergency visits at hospital (beta = 0.147, P < 0.001) was significantly associated with awareness. A difference in awareness was found between those who had asthma and rhinitis (62.2%) and those who had asthma alone (40.6%) (P < 0.01). Inhaled corticosteroids (ICS) were used by 27% of those with asthma, including 12% who used both ICS and long-acting beta-agonist. CONCLUSIONS: More than half of the persons with asthma were aware of their disorder; and the awareness was more likely in those with comorbidity of rhinitis. In general, asthma management was inadequate.

Differences between allergic and nonallergic rhinitis in a large sample of adolescents and adults.

BACKGROUND: The aim of this study was to describe differences between allergic rhinitis (AR) and nonallergic rhinitis (NAR) in a large community-based sample of Danish adolescents and adults. METHODS: A total of 1,186 subjects, 14-44 years of age, who in a screening questionnaire had reported a history of airway symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms and furthermore skin test reactivity, lung function and airway responsiveness were measured using standard techniques. RESULTS: A total of 77% of the subjects with rhinitis had AR, whereas 23% had NAR. Subjects with NAR were more likely to be females, OR = 2.05 (1.31-3.20), P = 0.002, to have persistent symptoms within the last 4 weeks, OR = 1.88 (1.23-2.89), P = 0.003, and to have recurring headaches, OR = 1.94, (1.12-3.37), P = 0.019. On the other hand, subjects with NAR were less likely to have airway hyperresponsiveness, OR = 0.40, (0.24-0.66), P < 0.001, food allergy, OR = 0.40, (0.19-0.36), P = 0.009 and to have been treated with antihistamines in the last 4 weeks, OR = 0.22, (0.13-0.38), P < 0.001 compared with subjects with AR. Subjects with AR were symptomatically worse within their season in terms of sneezing (P < 0.001) and itchy eyes (P < 0.001), compared to subjects with NAR, whereas nasal congestion and rhinorrhea were equally frequent in the two groups (P = 0.901 and P = 0.278, respectively). CONCLUSIONS: The proportion of subjects with NAR in an adolescent and adult population with rhinitis is around one-fourth. Women have NAR twice as often as men. In general, subjects with NAR have more persistent but equally severe symptoms compared to subjects with AR. However, subjects with AR have more sneezing and itchy eyes within their particular season of allergy compared to subjects with NAR.

A 3-year longitudinal study of asthma quality of life in undiagnosed and diagnosed asthma patients.

SETTING: Juniper's Asthma Quality of Life Questionnaire with standardised activities (AQLQ(S)) is commonly used to evaluate the effect of interventions in pharmaceutical trials, but rarely, if ever, used clinically in long-term follow-up of undiagnosed or diagnosed asthma patients. DESIGN: The AQLQ(S) was administered to 493 asthma patients who were randomised to treatment in primary or specialist care over a 3-year period. RESULTS: Of the 493 patients, 249 had not been diagnosed before screening and 244 had a doctor's diagnosis of asthma. At entry, known patients had a lower total AQLQ(S) score (median 6.03, 95%CI 3.9-7.0) than undiagnosed patients (median 6.54, 95%CI 4.8-7.0, P < 0.001). Treatment with inhaled corticosteroids induced lower scores (median 5.7, 95%CI 3.5-7.0) than no treatment (median 6.5, 95%CI 4.8-7.0, P < 0.01). Half of the patients (n = 260) were randomly invited to participate in a follow-up survey in a specialist setting. In the first 3 months of follow-up, a decrease in AQLQ(S) score among the undiagnosed patients (median -0.24, 95%CI -1.6-0.9, P = 0.02) was observed. After 3 years, the score improved significantly (by >0.5 points) in 45% of the undiagnosed patients (n = 107) compared to 26% of the known patients (n = 116, P < 0.05). CONCLUSION: The initial total AQLQ(S) score was higher in undiagnosed asthma patients. After diagnosis the AQLQ(S) initially decreased but then increased, followed by an overall improvement that exceeded that of the known asthma patients.

Side-effects of allergen-specific immunotherapy: a prospective multi-centre study.

BACKGROUND AND OBJECTIVE: The safety of allergen-specific immunotherapy (SIT) is a parameter of great interest in the overall assessment of the treatment. A clinical database was developed in order to obtain early warnings of changes in the frequency and severity of side-effects and sufficient data for the evaluation of possible risk factors. METHODS: During a 3-year period, four allergy centres in Copenhagen, Denmark, included data from all patients initiating SIT to a common database. Information on initial allergic symptoms, allergens used for treatment, treatment regimens and systemic side-effects (SSEs) during the build-up phase was collected. RESULTS: A total of 1,038 patients received treatment with 1,709 allergens (timothy, birch, mugwort, house dust mite (HDM), cat, and wasp and bee venom), 23,047 injections in total. Most SIT patients completed the updosing phase without side-effects, but there was a significant difference between allergens: wasp (89%), birch (82%), HDM (81%), cat (74%) and grass (70%) (P=0.004). A total of 582 SSEs were registered in 341 patients. Most side-effects were mild grade 2 reactions (78%). A difference in severity between allergens was observed (P=0.02), with grass giving most problems. The type of allergen but not patient- or centre-related parameters seemed predictive of side-effects. CONCLUSIONS: Allergen extracts differ in their tendency to produce side-effects. Multi-centre studies like the present one allow more patients to be evaluated, and thereby provide a more efficient surveillance of side-effects. Online Internet-based registration to a central national database of every allergen injection would be an even more powerful tool for evaluation of risk factors and surveillance of side-effects.

Prevalence of skin test reactions to natural rubber latex in hospital personnel in Russia and eastern Europe.

BACKGROUND: Allergic reactions to natural rubber latex have increased during the past 10 years, especially in many health care workers (HCWs) who have high exposure to latex allergens. The prevalence of skin test reactions to natural rubber latex in Russia, the Commonwealth of Independent States (CIS), and eastern Europe is unknown. OBJECTIVE: The purpose of this study was to determine the prevalence of skin test reactivity to natural rubber latex in a population of HCWs exposed to latex. METHODS: Nine hundred one HCWs regularly exposed to latex were evaluated using an allergy history questionnaire. Subjects were tested for latex allergy by titrated skin prick test with a biologically standardized latex extract. The diagnosis of latex allergy was defined by the presence of clinical symptoms when exposed to latex along with a positive skin prick test to latex. RESULTS: Forty-nine (5.4%) HCWs were skin test-positive to latex. Seventeen (1.9%) HCWs were classified as latex-allergic based upon positive skin tests to latex associated with allergy symptoms with exposure. Seven of 901 HCWs had experienced anaphylactic reactions to latex. The most frequently reported symptom related to latex exposure was contact urticaria. CONCLUSIONS: The prevalence of latex allergy among HCWs in Russia, the CIS, and adjacent eastern European countries is considerably less than reported in HCWs exposed to latex in western Europe and the United States. The low prevalence of latex allergy in Russia and the CIS suggests that lessened exposure to natural latex powdered gloves may diminish the prevalence of latex sensitization in HCWs in Russia and the CIS.

Allergen sensitization and allergen exposure in Greenlander Inuit residing in Denmark and Greenland.

The aim of this study was to estimate the prevalence of allergic sensitization and possible risk factors in a genetically homogenous Inuit population living under widely differing climatic and cultural conditions. A written questionnaire and skin prick test for 10 aeroallergens were obtained from 1119 adult Greenlanders residing in Denmark, Nuuk (main city in Southern Greenland) and Uummannaq (rural settlement in Northern Greenland). Allergen exposure was assessed by pollen counts, questions on pet keeping and counts of house dust mites in dust samples. The overall prevalence of at least one positive skin prick test was 22.8% in Denmark, 10.6% in Nuuk, and 6.4% in Uummannaq. In Denmark, the total birch pollen counts were 40-1000 times higher compared to Nuuk, whereas the grass pollen count was 13-30 times higher in Denmark compared to Nuuk. Dogs were held indoor with a similar frequency in Denmark and Nuuk, but much less frequently in Uummannaq. In Denmark, house dust mites were found in 72% of house holds (>10/0.1 g dust). Less than 15% of households in Greenland had measurable levels of house dust mites. The prevalence of sensitization to aeroallergens in Inuit Greenlanders differed significantly between Denmark, Nuuk and Uummannaq. These findings correlated with the observed differences in population allergen exposure in the three regions. Furthermore, differences in lifestyle factors such as educational level, stress and ethnic self-identification seemed to be associated with the risk of allergic sensitization in Greenland.

Rituximab in vivo purging is safe and effective in combination with CD34-positive selected autologous stem cell transplantation for salvage therapy in B-NHL.

The purpose of this study was to evaluate feasibility and efficacy of Rituximab included into a sequential salvage protocol for CD20(+) B-NHL in relapse or induction failure. Twenty-seven patients with CD20(+) B-NHL in relapse or induction failure received Rituximab combined with DexaBEAM (R-DexaBEAM) for stem cell mobilization. Additional ex vivo selection of CD34-positive cells was performed using the CliniMacs device. Two doses of Rituximab were included in the high-dose therapy regimen (HDT). R-DexaBEAM was well tolerated and 26 of 27 patients mobilized sufficient numbers of CD34(+) blood stem cells. Application of R-DexaBEAM resulted in significant depletion of peripheral B cells. No treatment-related deaths occurred after HDT and all patients showed stable engraftment of hematopoesis. Combined immunodeficiency was observed post HDT and eight patients developed CMV antigenemia. Remission rate post HDT was 96% (CR, 24/26; PR, 1/26). Overall and progression-free survival (PFS) at 16 months post HDT (range 6-27) is 95% and 77%, respectively. With regard to histology, PFS was 71% in aggressive lymphoma (n = 11), 74% in indolent FCL (n = 10) and 100% in MCL (n = 5). The treatment protocol has proven feasible, with high purging efficiency and encouraging remission rates.