Short course of grass allergen peptides immunotherapy over 3 weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without asthma: A randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND: Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 µg LPP administered subcutaneously over 3 weeks. METHODS: In a randomized, double-blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 µg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) was assessed as secondary endpoints. RESULTS: The mean reduction in CSMS in the LPP vs placebo group was -15.5% (P = .041) during the peak period and -17.9% (P = .029) over the entire pollen season. LPP-treated group had a reduced reactivity to CPT (P < .001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤30 minutes in 10.5% of LPP-treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication. CONCLUSION: Lolium perenne pollen peptides administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms and was generally safe and well-tolerated.

EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

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.

A randomized, double-blind, placebo-controlled, dose-finding trial with Lolium perenne peptide immunotherapy.

BACKGROUND: A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety. METHODS: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170 or 370 µg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment. RESULTS: Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 µg; P = .023), 46.3% (370 µg), and 38.6% (70 µg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-µg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 µg: 17.1%; 170 µg: 18.8%; 370 µg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 µg), 3.1-fold (170 µg) and 3.9-fold (370 µg) (mPP). CONCLUSION: Three-week immunotherapy with 170 µg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

Multi-morbidities of allergic rhinitis in adults: European Academy of Allergy and Clinical Immunology Task Force Report.

This report has been prepared by the European Academy of Allergy and Clinical Immunology Task Force on Allergic Rhinitis (AR) comorbidities. The aim of this multidisciplinary European consensus document is to highlight the role of multimorbidities in the definition, classification, mechanisms, recommendations for diagnosis and treatment of AR, and to define the needs in this neglected area by a literature review. AR is a systemic allergic disease and is generally associated with numerous multi-morbid disorders, including asthma, eczema, food allergies, eosinophilic oesophagitis (EoE), conjunctivitis, chronic middle ear effusions, rhinosinusitis, adenoid hypertrophy, olfaction disorders, obstructive sleep apnea, disordered sleep and consequent behavioural and educational effects. This report provides up-to-date usable information to: (1) improve the knowledge and skills of allergists, so as to ultimately improve the overall quality of patient care; (2) to increase interest in this area; and (3) to present a unique contribution to the field of upper inflammatory disease.

[Georg Schlöndorff-the father of computer-assisted surgery]. / Georg Schlöndorff - Vater der "computerassistierten Chirurgie".

Georg Schlöndorff (1931-2011) developed the idea of computer-assisted surgery (CAS) during his time as professor and chairman of the Department of Otorhinolaryngology at the Medical Faculty of the University of Aachen, Germany. In close cooperation with engineers and physicists, he succeeded in translating this concept into a functional prototype that was applied in live surgery in the operating theatre. The first intervention performed with this image-guided navigation system was a skull base surgical procedure 1987. During the following years, this concept was extended to orbital surgery, neurosurgery, mid-facial traumatology, and brachytherapy of solid tumors in the head and neck region. Further technical developments of this first prototype included touchless optical positioning and the computer vision concept with three orthogonal images, which is still common in contemporary navigation systems. During his time as emeritus professor from 1996, Georg Schlöndorff further pursued his concept of CAS by developing technical innovations such as computational fluid dynamics (CFD).

Efficacy and tolerability of bromelain in patients with chronic rhinosinusitis--a pilot study.

OBJECTIVES: To evaluate the efficacy, tolerability, and impact on quality of life (QoL) of bromelain tablets (500 FIP) in patients with chronic rhinosinusitis (CRS). METHODS: In this prospective, open-label observational pilot study, 12 patients suffering from CRS with (CRS+NP) or without (CRS-NP) nasal polyps who had undergone prior sinus surgery were treated with bromelain tablets (500 FIP) for three months. Efficacy was evaluated using symptom scores (Total Symptom Scores: TSS); a Total Rhinoscopy Score (TRS) was also determined. QoL was assessed by using the German, adapted version of the Sinonasal Outcome Test 20 (SNOT-20 GAV). RESULTS: Treatment with bromelain tablets (500 FIP) improved TSS, TRS and SNOT-20 GAV on average. This treatment was found to be more effective, however, for CRS-NP than for CRS+NP. The average intake was six tablets, equivalent to a daily dosage of 3000 FIP. No adverse events were observed. CONCLUSION: Preliminary results indicate good tolerability, symptom control, and improvement in QoL for the treatment of CRS using bromelain tablets (500 FIP).

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.

Local and systemic safety of intranasal corticosteroids.

The safety and efficacy of intranasal corticosteroids (INCs) are well established for the management of allergic rhinitis, rhinosinusitis, and nasal polyps. As seen in numerous studies, INCs demonstrate markedly reduced systemic bioavailability compared with oral and even inhaled corticosteroids and have shown an excellent safety profile over 3 decades of use. Nonetheless, concerns remain among some prescribers and patients that these agents may reach the systemic circulation in sufficient concentration to produce adverse effects (AEs). Available evidence does not support these concerns. A review of the published literature indicates that the side effect profiles of INCs consist primarily of a low incidence of mostly mild and often transient local AEs, such as nasal irritation and epistaxis.The second-generation INC agents currently in use (mometasone furoate nasal spray, fluticasone propionate, ciclesonide, and fluticasone furoate) have favorable pharmacokinetic characteristics that further minimize systemic bioavailability (< 1%) compared with older INCs and compared with oral agents, thereby limiting the risk for systemic adverse events.

Liposomes: a new non-pharmacological therapy concept for seasonal-allergic-rhinoconjunctivitis.

Mucosal barrier disorders play an important role in the pathomechanism of the allergic disease. A new approach for their treatment uses liposomes, which consist of phospholipids that make up 75% of the protective nasal surfactant layer. Our aim was to investigate the efficacy of liposomal-based therapy, as a comprehensive treatment alternative to guideline cromoglycate-based therapy, in the treatment of seasonal allergic rhinoconjunctivitis (SAR). We compared nasal and conjunctival symptom reduction with LipoNasal n nasal spray used as monotherapy (LNM), or LipoNasal n nasal spray and Tears Again eye spray combination therapy (LTC), against standard cromoglycate combination therapy (CGC). This prospective, controlled, open observational study was conducted monocentrically. According to their symptoms and preferences 72 patients with SAR were distributed in three equal groups. The study comprised two visits at an interval of 7 days. The efficacy was examined by daily documenting nasal and conjunctival symptom scores. The Nasal-Spray-Sensory-Scale and the Eye-Drops/Spray-Sensory-Scale were used to investigate the tolerability. Quality of life (QoL) was evaluated, using the RHINASTHMA QoL German adapted version. LNM achieved significant improvement in nasal (p < 0.001) and conjunctival symptoms (p = 0.050). The symptom reduction using CGC was equally significant. LTC led to significant nasal symptom relief (p = 0.045). QoL did not improve significantly in all groups (p > 0.05). The tolerability of all treatments was good and no adverse reactions were observed. In all treatment groups the improvement of the nasal and conjunctival symptom scores exceeds the minimal clinically important difference (MCID). The results demonstrate good tolerability and efficacy of non-pharmaceutical liposomal-based treatment (LipoNasal n and Tears Again), given as monotherapy or combination therapy, for nasal and conjunctival symptoms caused by SAR. This study indicates that liposomal-based treatment for SAR may be a comparable alternative to cromoglycate therapy. Further studies are needed to verify these findings.

[What is the evidence for non-antibiotic drug therapy of Rhinosinusitis?]. / Wie ist die Evidenzlage bei der nicht-antibiotischen medikamentösen Therapie der Rhinosinusitis?

The German AWMF-guideline for rhinosinusitis and nasal polyps is to be reassessed. By searching the literature for the reevaluation we investigate in this systematic review to what extent existing recommendations can be affirmed, have to be changed or if there are new recommendations to give.We searched PUBMED, MEDLINE and other databases via MEDPILOT, and the Cochrane Central Register of Controlled Trials without limiting the publication date range. Relevant clinical trials identified by 2 reviewers out of the search results were assessed for their methodical quality using an extended Jadad scale. Datas were extracted and study design, therapy/application, control group and results were analysed. Furthermore, levels of evidence for the different therapeutics have been determined.Out of 1 346 search results 227 potentially eligible trials were identified; for this review we considered only the 47 trials published since 01/2006. Former recommendations are mainly supported by the identified relevant publications and several Cochrane reviews published in the last years.Levels of evidence are Ia for topical and systemic corticosteroid therapy for acute and chronic rhinosinusitis. Additionally, there is evidence that the application of saline solutions is useful not only for chronic but also for acute rhinosinusitis. New therapy options are under examination, but there is not enough evidence for adding them to actual recommendations.

[Nasal douching in acute rhinosinusitis]. / Nasenspülungen bei akuter Rhinosinusitis.

BACKGROUND: Nasal douching is recommended for the treatment of a variety of diseases of the nose and paranasal sinuses. Nasal douching with saline solution has proven to be effective in chronic rhinosinusitis and after sinus surgery and is recommended by different otolaryngologic societies. MATERIAL AND METHODS: A systematic review of the literature was performed to determine whether nasal douching is effective in the treatment of acute rhinosinusitis and in preventing recurrent upper respiratory tract infections. We also reviewed whether nasal douching has adverse eff ects and can lead to recurrent upper respiratory tract infections if performed regularly over a longer period of time. RESULTS: Nasal douching with saline solution has a limited effect in adults with acute rhinosinusitis (level of evidence Ia). It is effective in children with acute rhinosinusitis in addition to the standard medication (level of evidence Ib) and can prevent recurrent infections (level of evidence IIb). It is assumed that nasal douching improves the function of the mucous membranes. There is currently no evidence that daily nasal douching with isotonic saline solution over a longer period of time has an adverse effect on the individual health or leads to a higher rate of infections. CONCLUSION: Nasal douching with saline solutions can be recommended for adults with acute rhinosinusitis (grade of recommendation A), in addition to the standard medication in children with acute rhinosinusitis (grade of recommendation A) and to prevent recurrent infections (grade of recommendation B).

Treatment of hypertrophic palatine tonsils using bipolar radiofrequency-induced thermotherapy (RFITT.).

CONCLUSION: Radiofrequency volume reduction of palatine tonsils is a gentle and safe treatment method in selected patients, which should carefully be considered as an alternative to tonsillectomy or tonsillotomy. OBJECTIVES: The aim of this study was the evaluation of bipolar radiofrequency-induced thermotherapy (RFITT) compared to standard blunt dissection tonsillectomy (TE) for the volume reduction of palatine tonsils in chronic tonsillar hypertrophy. PATIENTS AND METHODS: A total of 137 patients (98 children) were treated in two groups in a prospective controlled, randomized clinical trial. The TE group underwent standard tonsillectomy using blunt dissection. The RFITT group underwent interstitial RF ablation. Perioperative blood loss and duration of surgery were monitored. Tonsil volume reduction in the RFITT group was measured by sonography. Postoperative pain, as well as difficulty in swallowing and speaking, were evaluated using visual analog scales. RESULTS: In the RFITT group, we found an average tonsil volume reduction of 40%, at about 3 weeks after treatment. Postoperative pain, swallowing and speaking difficulties, and perioperative blood loss were significantly lower, and the duration of surgery was significantly shorter (all p<0.05) in the RFITT group. Preservation of the treatment results was monitored until 6 months after treatment, with no after effects during this time period.

[The Cologne internet-manual of pain therapy--33 months online, experiences and evaluation]. / Das Kölner Internet-Schmerzmanual. 33 Monate online--Erfahrungen und Evaluation.

OBJECTIVE: The improvement of ambulant treatment for patients with chronic headache or cancer pain. METHODS: Distribution of accepted guidelines and standards by means of the internet in order to make this knowledge known among general practitioners and to give patients better access to this information. RESULTS: We have built an internet manual about the treatment of chronic headache and cancer pain. About 9100 readers accessed the manual during a period of 33 months. The manual has been completely downloaded 279 times. Physicians and patients very often used search engines to access the manual in their search for information about headache. The terms "migraine" and "tension type headache" were looked up the most. CONCLUSIONS: It is worthwhile editing medical information for use on the internet and thus making it available to the public.

Effect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients.

OBJECTIVE: Test of dose-response relationship for Ginkgo biloba extract EGb 761 (oral) in outpatients with acute idiopathic sudden sensorineural hearing loss (ISSHL) of at least 15 dB at one frequency within the speech range occurring less than 10 days before study inclusion. DESIGN: Multicentre, randomized, double-blind phase III study comparing dosages of 120 mg twice daily and 12 mg twice daily over 8 weeks. MAIN ENDPOINT: Recovery (in dB) of the auditory threshold from the initial measurement to the value on the last day of treatment, averaged over those frequencies from 0.25, 0.5, 1, 2, and 3 kHz for which the initial hearing loss amounted to 15 dB or more compared to the level on the opposite side. PATIENTS: 106 patients with an average age of 44+/-16 years and with hearing loss at affected frequencies 26 dB +/- 9 dB included between December 1995 and July 1997. RESULTS: Large majorities of both treatment groups recovered completely. In exploratory analyses of the 96 patients included according to the protocol, patients given the higher dose had less risk of not recovering well (< or =10 dB residual hearing loss) (one-sided Fisher test: P = 0.0061), especially if they had no tinnitus (n = 44, P = 0.00702). CONCLUSION: A higher dosage of EGb 761 (oral) appears to speed up and secure the recovery of ISSHL patients, with a good chance that they will recover completely, even with little treatment. This was already observed after one week of treatment. We find it justified to treat patients who have unilateral ISSHL of less than 75 dB and neither tinnitus nor vertigo with 120 mg oral EGb 761 twice daily.