Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells.

BACKGROUND: A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. METHODS: Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). RESULTS: Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207+ Langerhans cells (LCs) and CD11c+ myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68+ macrophages, CD117+ mast cells, and CD4+ /CD8+ T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207+ LCs found in oral tissues from patients with OAS, when compared to OAS- patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE+ cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68+ macrophages located in the LP, and to a lesser extent CD207+ LCs in the epithelium. CONCLUSION: Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207+ LCs possibly involved in the physiopathology of OAS and (ii) CD68+ macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT.

Implementation of pre-seasonal sublingual immunotherapy with a five-grass pollen tablet during optimal dosage assessment.

BACKGROUND: The optimal dose (300IR) of a five-grass pollen sublingual immunotherapy tablet in terms of efficacy was previously demonstrated from the first pollen season. OBJECTIVE: Here, we aim to confirm whether this dose remained optimal during the peak of the pollen season by assessing the efficacy and quality of life data. METHODS: A total of 628 subjects with grass pollen rhinoconjunctivitis were randomized in a double-blind, placebo-controlled, multi-centre, pan-European trial. Subjects received once-daily tablets (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before and throughout the 2005 grass pollen season. The pollen season was defined as the first day of 3 consecutive days with a grass pollen count above 30 grains/m(3) of air, recorded using Hirst-type volumetric pollen traps, to the last day before 3 consecutive days with a pollen count below 30 grains/m(3). RESULTS: The grass pollen season lasted an average of 30 days, with a peak of 12 days. The mean treatment duration before the grass pollen season was similar in the four treatment groups (121.4+/-31.1 to 128.6+/-15.4 days in the safety population). Both the 300IR and 500IR groups had highly significant improvements in Rhinoconjunctivitis Total Symptom Score (RTSS) vs. placebo at the peak pollen season (P=0.0005 and 0.0014, respectively), which agreed with improvements in RTSS in the primary evaluations. The average RTSS scores were slightly elevated during the peak pollen season in all treatment groups. The overall Rhinoconjunctivitis Quality of Life Questionnaire score confirmed the optimal dosage 300IR at peak (P<0.0001) and at the end (P< or =0.0031) of the pollen season. All doses were well tolerated. CONCLUSION: At the peak pollen season, the efficacy and quality of life data for both 300IR and 500IR groups was significantly improved vs. the placebo group. These results confirm the conclusions of the primary evaluations and validate the use of 300IR tablets for clinical practice.

Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis.

BACKGROUND: The optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double-blind, placebo-controlled study in 628 adults. Patients were randomized to receive once-daily 5-grass pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season. OBJECTIVE: The aim of this complementary analysis was to determine whether 300 IR 5-grass pollen SLIT-tablets is effective in different subtypes of patients who are allergic to grass pollen. METHODS: Different subgroups could be identified regarding comorbidities (with or without asthma during the grass-pollen season), sensitization (mono/polysensitization) and symptom severity. An additional exploratory analysis was performed within four subgroups based on pre-treatment assessment: Group 1=high specific IgE; Group 2=high symptom scores; Group 3=high skin sensitivity; Group 4=any of Group 1, 2 or 3. RESULTS: Asthma and sensitization status were not significant covariates as the average Rhinoconjunctivitis Total Symptom Score (RTSS) was identical for patients with and without grass-pollen asthma, as well as for mono- and polysensitized patients. Across the four subgroups, average RTSSs (+/- SD) for the optimal dosage (300 IR) were 3.91 +/- 3.16, 3.83 +/- 3.14, 2.55 +/- 2.13 and 3.61 +/- 2.97, for subgroups 1, 2, 3 and 4, respectively. ANCOVA showed that in Group 1 average RTSS did not differ significantly with different doses of SLIT. In Groups 2, 3 and 4, doses of 300 IR and 500 IR were significantly more effective than 100 IR and placebo (P< or =0.035). All doses of SLIT administered in this study can be considered safe in the patients investigated. CONCLUSIONS: The risk-benefit ratio validates the use of 300 IR tablets in clinical practice in all of these patient subgroups, regardless of severity profile, sensitization status and presence of asthma.

Agreement of efficacy assessments for five-grass pollen sublingual tablet immunotherapy.

BACKGROUND: The optimal dose of five-grass pollen sublingual tablet immunotherapy (SLIT) was established recently by the primary criteria Rhinoconjunctivitis Total Symptom Score (RTSS) from the first treatment season. Secondary and exploratory criteria, such as RTSS at peak pollen season, exploratory combined symptom and rescue medication use score, quality of life and immunological markers are calculated and described in this analysis. METHODS: Six hundred and twenty-eight patients with grass pollen rhinoconjunctivitis (> or =2 years duration) were randomized in a double-blind, placebo-controlled trial conducted in Europe. Patients received once-daily SLIT (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before grass pollen season and throughout the 2005 season. Patients were instructed to take rescue medication only if symptoms were severe and record symptom severity on using the RTSS. RESULTS: Both 300IR and 500IR doses significantly reduced mean RTSS at pollen peak (P = 0.0005 and P = 0.0014, respectively) and the exploratory combined score (P = 0.0001 and P = 0.0026, respectively) compared with placebo. Compared with patients in the placebo group, those who were taking the 300IR and 500IR doses reported significantly improved quality of life using the mean Rhinoconjunctivitis Quality of Life Questionnaire scores during the peak of the pollen season (P < 0.0001) and at the end of the pollen season (P = 0.0031 and P < or = 0.0001, respectively). Specific immunoglobulin G4 increased significantly depending on the SLIT dose (P < 0.0001). CONCLUSIONS: All secondary efficacy criteria, including efficacy at pollen peak, combined score, quality of life and immunological changes, indicate that 300IR tablets represent the optimal dose and suggest it is appropriate for use in clinical practice.

Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study.

BACKGROUND: A single-centre, randomized, double-blind, placebo-controlled study. AIMS: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis. METHODS: Thirty subjects sensitized to grass pollen were enrolled and allocated to four groups. Sublingual immunotherapy was administered in tablets daily for 10 days. Groups 1 and 2 received incremental sublingual doses of 100, 200, 300, 400 and 500 IR, Group 1 daily and Group 2 increments every second day. Repeated constant dose regimens of 300 IR and 500 IR were administered in Groups 3 and 4 respectively. Safety assessments included adverse events (AE), vital signs, electrocardiogram (ECG) and clinical laboratory tests. RESULTS: Sublingual immunotherapy 300 IR (Group 3) administered in a constant dose and incremental doses up to 500 IR (Groups 1 and 2) were generally well tolerated. The majority of AEs were mild to moderate, the most common being oral pruritus, throat irritation and swollen tongue. Severe local AEs (swelling of throat) were observed only for Group 4. No serious systemic AEs were reported. There were no relevant changes in clinical laboratory, vital signs and ECG data. CONCLUSION: Adverse events were mostly local (sublingual), were not severe and resolved rapidly. Using a 5-day induction regimen high-dose treatment up to 500 IR could be administered without important side-effects, in contrast to initiating with a constant dose of 500 IR. The data indicate that a short dose increase phase may reduce the incidence of AEs when high-dose SLIT is administered.

[Confusion syndromes in hospitalized aged patients: polymorphism of symptoms and course. Prospective study of 183 patients]. / Les syndromes confusionnels du sujet âgé hospitalisé: polymorphisme sémiologique et évolutif. Etude prospective de 183 patients.

Using explicit criteria contained in the DSM III R, we collected in a prospective cohort study clinical features, outcome and risk factors from two cohorts of delirium in hospitalized elderly patients: 138 hospitalized in geriatric department and 45 patients admitted to an acute and comprehensive care hospital. The clinical features were assessed using a quantitative scale (developed by Derouesné). Delirium was unrecognized or misdiagnosed by physicians in 34% of the cases. The onset was known only two thirds of cases. The incidence of hyperactive type, prolonged hospital stay, poor outcomes (persistent delirium leading up to dementia) were highest in subjects admitted in comprehensive hospital. The etiology of delirium is complex and multifactorial. An underlying cause was identified in 80% of patients. The length or the worsening of delirium was significantly higher in patients with psychiatric or dementia comorbidity (OR: 0.2; IC 95%: 0.1-0.5). The prognosis was better in patients without psychoactive medications (OR: 0.2; IC 95%: 0.1-0.4) or with metabolic abnormalities or acute diseases and disorders (OR: 3.3; IC 95%: 1.5-7.6). The predisposing factors to the development of dementia were prior use of psychoactive medications and signs of prior cognitive impairment. This article suggests delirium in elderly patients is associated with several outcomes. The prognosis should be improved at admission by specific scale and an evaluation of predisposing and precipitating factors.