Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients.

BACKGROUND: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol. METHODS: In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8). RESULTS: No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1-fold, P < .001) and V8 (12.2-fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (-54.6%, P < .001) and V8 (-71.6%, P < .001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8. CONCLUSION: Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.

RCAT reflects symptom control and quality of life in allergic rhinoconjunctivitis patients.

BACKGROUND: The Global Allergy and Asthma European Network (GA2 LEN) Taskforce has requested more data on correlations between various patient-reported outcomes (PROs) in clinical trials on allergy. We compared three tools-the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Rhinitis Total Symptom Score (RTSS)-to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis. METHODS: In two double-blind, placebo-controlled immunotherapy studies, 33 patients allergic to grass pollen and 94 to birch pollen completed two questionnaires (RCAT and RQLQ) and kept their own symptom diary from which the RTSS was calculated. RESULTS: Upon comparing RCAT and RQLQ results, we found strong correlations of r = -0.871 for grass pollen-allergic patients and r = -0.795 for birch pollen-allergic patients. The comparison between RCAT and RTSS results showed a strong correlation of r = -0.811 (grass pollen-allergic patients) and a moderate correlation of r = -0.539 (birch pollen-allergic patients). In the RCAT, 69.7% of grass pollen-allergic patients and 45.7% of birch pollen-allergic patients receiving guideline-concordant therapy were regarded as having insufficiently controlled symptoms. CONCLUSION: The strong correlations suggest that the RCAT alone is equivalent to the RQLQ with respect to patients' symptom control and quality of life. Patients with uncontrolled symptoms can be identified using the RCAT. Hence, the physician can decide whether symptomatic therapy can be intensified or allergy immunotherapy should be administered.

A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients.

BACKGROUND: In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite allergoids was to determine the most effective and safe dose. METHODS: In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. RESULTS: The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P < 0.1). The percentage of patients with an improved CPT threshold was higher in the active treatment groups (300 UA/day: 73.9%; 1000 UA/day: 76.0%; 2000 UA/day: 88.5%; 3000 UA/day: 76.0%) than in the placebo group (64.3%). The difference between placebo and 2000 UA/day was statistically significant (P = 0.04). In 13 (10%) exposed patients, a total of 20 treatment-related adverse events of mild severity were observed. CONCLUSIONS: The 12-week daily treatment using 2000 UA/day monomeric allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients.

Tolerability and effects on quality of life of liposomal nasal spray treatment compared to nasal ointment containing dexpanthenol or isotonic NaCl spray in patients with rhinitis sicca.

This study aimed to investigate symptom reduction via the liposomal nasal spray LipoNasal (LN) in patients with rhinitis sicca. Tolerability and the impact on quality of life were also examined. The same parameters were established in parallel for treatment approaches with Bepanthen (BP) nasal ointment containing dexpanthenol and the Rhinomer (RH) nasal spray containing NaCl. This prospective, controlled, open-label observation study was a multicenter trial. 92 patients with rhinitis sicca were allocated to three arms according to their symptoms: LN: n = 33; BP: n = 32 and RH: n = 27. The study comprised three visits at an interval of 14 days. Efficacy was examined by the Rhinitis Sicca Symptom Score (RSSS) documented daily and at the visits based on an endoscopic evaluation. The nasal spray sensory scale was used to investigate the tolerability. Quality of life (QoL) was measured by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the "Short Form 12" of the "Impact on Health-Related Quality of Life (HRQL)" questionnaire on general quality of life. Nasal symptoms improved significantly (p = 0.001) under all three treatment approaches, reflected by the reduction in the RSSS and the Endoscopy Sum Score. A comparison of the three groups showed that no therapy was significantly superior to any of the others (p = 0.410). The tolerability of all treatments was good. Concerning the nasal moisturization, LipoNasal was evaluated better than Bepanthen and Rhinomer. Quality of life improved in all groups, but not significantly. The results show good efficacy and tolerability of the liposomal nasal spray compared to generally recognized treatments of rhinitis sicca with dexpanthenol nasal ointment and NaCl nasal spray. LipoNasal therefore constitutes a good treatment for patients suffering from dry nose.

Carbamylated monomeric allergoids as a therapeutic option for sublingual immunotherapy of dust mite- and grass pollen-induced allergic rhinoconjunctivitis: a systematic review of published trials with a meta-analysis of treatment using Lais® tablets.

Lais® allergoid tablets contain allergens that are modified by carbamylation. Due to their modified chemical structure, they are suitable for sublingual immunotherapy (SLIT) (13, 16, 17, 24). Based on their small molecule size of 12 to 40 kDa, they can be easily absorbed via the oral mucosa (1). In this review, we studied the efficacy of SLIT with carbamylated monomeric allergoid tablets in the treatment of grass pollen- and dust mite-induced allergic rhinoconjunctivitis on the basis of symptom and medication score improvements. Following a selective internet and databank search, six trials-some placebo-controlled-regarding the treatment of grass pollen- (n = 266) and dust mite-induced (n = 241) allergic rhinoconjunctivitis were used to draw conclusions regarding the clinical efficacy of allergoid tablets. The primary endpoints in these trials were decreases in the need for allergy medications and/or reductions in the occurrence of rhinoconjunctivitis symptoms. Data was recorded from patient diaries regarding their symptoms and medications used and conclusions were then drawn about the effectiveness and tolerabieity of Lais® tablets. The average improvement in symptom score in three trials of grass pollen allergy treatment was 34% in comparison to the placebo group. The treatment of dust mite-induced rhinoconjunctivitis produced an average symptom score improvement of 22% compared to the placebo or control groups. The intake of symptomatic rescue medication during allergoid tablet therapy declined. Treatment of grass pollen allergies and dust mite-induced rhinoconjunctivitis showed an average medication score improvement of 49% and 24%, respectively. Few side effects were documented in the trials and predominantly local effects were observed. Severe systemic side effects did not occur. On the basis of the trial results summarized in this review, we suggest that SLIT using Lais® sublingual tablets is an effective and well-tolerated form of treatment.

[Hemorrhage rates following coblation tonsillectomy. A meta-analysis of published trials]. / Nachblutungsrate nach Coblation-Tonsillektomie. Eine Metaanalyse publizierter Studien.

BACKGROUND: With over 100,000 cases annually, tonsillectomy is one of the most frequently performed ENT surgical procedures in Germany. Hemorrhage ranks among its serious postoperative complications. In this systematic review, we analyze hemorrhage following tonsillectomies performed using coblation technique. METHODS: Of the 135 studies identified, 38 could be included in the analysis, most being prospective randomized controlled studies. Data from 6290 patients were gathered. RESULTS: Of all tonsillectomies performed, hemorrhages occurred in 355 patients. Of these, 256 cases could be classified as 41 primary and 215 secondary hemorrhages. Overall, the total hemorrhage rate for the coblation procedure was 4.9% (95%-CI: 0.044-0.054) for the fixed effects model. CONCLUSION: Significantly higher rates of postoperative hemorrhage were found in a few studies, yet they were well above the 95% confidence interval of 4.4-5.4% of the literature. These studies could possibly be interpreted in terms of an autodidactic learning process. As with any surgical technique, proper training is essential.