Zentrum fur Rhinologie und Allergologie

Wiesbaden, Germany

Zentrum fur Rhinologie und Allergologie

Wiesbaden, Germany
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Klimek L.,Zentrum fur Rhinologie und Allergologie | Bousquet J.,Montpellier University | Price D.,University of Aberdeen
Expert Opinion on Drug Safety | Year: 2016

Introduction: As a chronic disease, allergic rhinitis (AR) requires regular use of allergy medications for the effective management of symptoms. It is therefore imperative that AR treatments not only provide adequate symptom control but are also well tolerated.Areas covered: MP29-02 (Dymista, Meda, Solna, Sweden) is the first new class of AR medication (WHO ATC R01AD58) since the introduction of intranasal corticosteroids (INS) almost 50 years ago. It is a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate delivered in a single spray. Here we review all the safety information relevant to MP29-02, from the initial phase I bioavailability and disposition data, to the phase III 14-day and 52-week data and finally to phase IV safety data collected during MP29-02 use in routine clinical practice.Expert opinion: MP29-02 is the first real therapeutic advance in AR since the introduction of INS and has the potential to change the way this disease is managed, simplifying AR treatment regimens to a single puff in each nostril twice a day. Patients will benefit from superior symptom relief MP29-02 compared to INS with the added assurance that the safety of MP29-02 has been confirmed in the short term and long term as well as in real life. © 2015 Taylor & Francis.


Kirsche H.,Universitatsklinikum Munster | Klimek L.,Zentrum fur Rhinologie und Allergologie | Klimek L.,University of Heidelberg
HNO | Year: 2015

Background: A differential diagnosis of persistent chronic rhinosinusitis is ASA-intolerance syndrome (AIS), also known as Aspirin®‑exacerbated respiratory disease (AERD), Samter-Trias (Samter’s disease, Morbus Widal). Particularly in cases of frequent recurrency of nasal polyps in combination with bronchial asthma and hypersensitivity reactions to acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAR) can often be referred to an underlying AIS. The pathogenesis of this syndrome is attributed to a misallocation of the arachidonic acid metabolism, resulting in an increased leukotriene production. Methods: The diagnosis may be difficult in the early stages of the disease with incomplete triad of symptoms. Results: Therapy may consist of paranasal sinuses surgery, drug therapy and adaptive deactivation as the only causal treatment option for patients with AIS. Conclusion: For adaptive desactivation, positive effects were actually shown even in patients with long-term recurrent or persistent complaints of chronic rhinosinusitis. © 2015, Springer-Verlag Berlin Heidelberg.


Klimek L.,Zentrum fur Rhinologie und Allergologie | Sperl A.,Zentrum fur Rhinologie und Allergologie | Raulf M.,Ruhr University Bochum
Allergologie | Year: 2015

Allergic rhinitis (AR) affects ca. 20% of the population. Approximately 1/3 of patients affected by AR are suffering from perennial rhinitis due to mite allergy. Perennial rhinitis is the form of the disease that is most frequently associated with other allergy-related comorbidities such as asthma and atopic dermatitis, sleep disorders, chronic sinusitis, eustachian tube dysfunction and others. The often non-specific symptoms and the insidious course may lead to misinterpretations in diagnosing the disease. Therapeutic options include allergen avoidance with regard to environmental measures, encasings and personal actions. Drug therapy in mite-AR consists mainly in the administration of mast cell stabilizers, H1-antihistamines, glucocorticosteroids (GCS), leukotriene receptor antagonists and decongestants. It is particularly important to ensure a good antiinflammatory activity. Thus, a combination of H1-antihistamine and topical nasal GCS seems to be a rational approach. The only causal treatment form besides allergen avoidance is allergen-specific immunotherapy (AIT). In addition to established subcutaneously administered AIT forms, recent studies have demonstrated effective, safe, simple and patientfriendly AIT using a sublingual preparation of a mite tablet. © 2015 Dustri-Verlag Dr. Karl Feistle.


Currently, preparations containing native allergens or allergoids are used predominantly in allergen-specific immunotherapy (SIT) of inhaled allergies. The safety and efficacy of these preparations has been demonstrated. However, their reproducible production and standardisation requires substantial effort. Besides this, improved efficacy is often associated with higher doses and an increase in adverse events. The production of recombinant allergens could make SIT preparations more precisely definable, purer, more reproducible, safer and more efficacious. Furthermore, a more specific and individually tailored therapy would be conceivable. These effects could be further amplified by modification to hypoallergenic variants and peptides, or by the addition of adjuvants. Results of clinical trials with recombinant grass, birch and ragweed pollen, as well as with cat hair allergens have already been published. Particularly broad clinical experience exists for recombinant birch and grass pollen preparations, and results are promising for commercial application. Taken as a whole, this new technology can both improve the therapy of allergic diseases and deepen the understanding of the molecular mechanisms of SIT. © 2013 Springer-Verlag Berlin Heidelberg.


Allergic rhinitis (AR) is a common airway disease characterized by mucosal swelling leadingto congestion, mucosal hyperreactivityand increased secretions. Inflammatory processes in the mucosa are responsible for most symptoms and are characterized by mucosal remodeling after longer time periods. The early phase response, which is characterized by sneezing, rhinorrhea and nasal congestion, is the response of the sensory nerve terminals and blood vessels in the nasal mucosa to chemical mediators such as histamine, prostaglandins and leukotrienes. Nasal exposure to allergens leads to infiltration of inflammatory cells, such as activated eosinophils and T helper type 2 (TH2) cells, into the nasal mucosa by chemoattractant factors such as cytokines including interleukin 5 (IL- 5), chemical mediators including cysLTs and chemokines including eotaxin. Edema of the nasal mucosa develops as a secondary reaction with inflammatory cells. This inflammation, referred to as the late-phase response, develops 6-10 h after allergen challenge andcauses prolonged nasal congestion. In addition, a neurogenic mechanism is activated after liberation of substance P and others. Therefore, allergic rhinitis is a complex immunogenic disease that also activates mechanisms of the immune system in general. Antiallergic and antiinflammatory medications such as nasal glucocorticosteroids (nGCS) arethought to be the most effective treatment for controlling the symptoms and inflammatory mechanisms of AR. The antiinflammatory action of nGCS depends on at least two different mechanisms: transactivation and transrepression. Moreover, they regulate immune functions by inducing regulatory cytokines and forkhead box P3 (Foxp3). Foxp3 is of upmost importance as a transcription factor of regulatory tcells, allowing the inhibition of effector function and proliferation of other CD4+ cells. © Springer-Verlag 2012.


Klimek L.,Zentrum fur Rhinologie und Allergologie | Sperl A.,Zentrum fur Rhinologie und Allergologie
HNO | Year: 2013

Allergic diseases in the area of otolaryngology (ENT) are common, increasing and associated with a number of comorbid disorders, such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causative treatment option. Options for pharmacotherapy are mast cell stabilizers, antihistamines, glucocorticoids, leukotriene receptor antagonists and nasal decongestants. In type 1 allergic reactions, topical glucocorticoids are currently the most effective treatment and are considered to be the first-line therapy together with nonsedating antihistamines. A novel formulation (MP29-02) combining a nasal glucocorticoid and antihistamine in one single preparation has demonstrated an improvement of the effective total nasal symptom score by 39 % in comparison to monotherapy with fluticasone propionate. In type IV allergies, such as eczema treatment with topical glucocorticoids or calcineurin inhibitors is standard. © 2013 Springer-Verlag Berlin Heidelberg.


Allergic rhinitis is a common immune-mediated disease that affects a large part of the global population. Its symptoms may not be life-threatening but nonetheless have a strong impact on quality of life and productivity. Current therapeutic options are manifold and include intranasal glucocorticoids, antihistamines and leukotriene receptor antagonists. The current guidelines recommend intranasal glucocorticoids and antihistamines as effective and safe first-line therapies. However, some patients remain uncontrolled with the current treatment options. Therefore, it is necessary to develop new treatment strategies and/or improve current therapy options. Over the last years a few new agents have been developed which may have an impact on the way allergic rhinitis is treated in the nearest future. These include new compounds such as SYK-inhibitors, which inhibit the signalling pathway of the allergic reaction, new antihistamines targeting not only the H,-receptor but also the H3-receptor, new improved glucocorticoids in the form of prodrugs as well as a novel formulation (MP29-02) combining the administration of a nasal antihistamine and glucocorticoid. In allergen-specific immunotherapy, new promising approaches such as intralympha- Tic and epicutaneous immunotherapy are currently being investigated.


Klimek L.,Zentrum fur Rhinologie und Allergologie
Haut | Year: 2012

Food allergies are immunological reactions. In adults, fruits, vegetables and nuts are among the most common triggers. Symptoms may be caused by minimal to moderate amounts of the respective food. Complete elimination of the respective allergens from nutrition results in a complete remission of the symptoms. The spectrum of symptoms comprises both relatively harmless oral allergy syndrom as well as life-threatening anaphylaxis.


Klimek L.,Zentrum fur Rhinologie und Allergologie | Pfaar O.,Zentrum fur Rhinologie und Allergologie
HNO | Year: 2011

Allergic rhinitis is one of the most common diseases to affect humans. It is important to note that it is an immunological disease which is associated with significant changes in the mucous membrane of the respiratory tract. Clinical symptoms of allergic rhinitis include sneezing, rhinorrhea, nasal itching, and nasal congestion. The mechanism underlying the development of symptoms associated with allergic rhinitis are complex, including activation and infiltration of inflammatory cells, edema, increased and altered gland activity, nerve terminal activation, triggering of neurogenic inflammation and morphologically detectable remodelling processes in the mucous membrane. Finally, a systematic activation of immune processes also takes place. Thus, allergic rhinitis is clearly a serious disease requiring prompt and effective treatment; moreover, it has been unjustly trivialized to date, not least because of its high incidence. © 2011 Springer-Verlag.


In a subgroup of patients with symptoms of allergic rhinitis (AR), no systemic sensitization can be detected in skin tests or serum. These patients are considered to be afflicted with so-called “local allergic rhinitis” (LAR) with IgE-production exclusively at the site of the nasal mucosa. Patients without any positive allergy test results but seasonal (intermittent) or perennial (persistent) allergic symptoms were often misdiagnosed as having “non-allergic rhinitis” (NAR) in the past. However, there is evidence for a specific IgE-production in the nasal mucosa in these patients without systemic sensitization. The diagnosis of LAR is confirmed by clinical symptoms, the detection of specific IgE production in the nasal mucosa and/or nasal provocation tests. We report on two cases of LAR to Alternaria alternata with symptoms of persistent allergic rhinitis that have been diagnosed by positive allergenspecific nasal challenge tests and specific IgE determinations in nasal secretions. According to an actual literature research, this is the second report published on LAR caused by Alternaria alternata. © 2015, Springer-Verlag Berlin Heidelberg.

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