Rapid increases in epinephrine concentration following presumed intra-blood vessel administration via epinephrine autoinjector.

While epinephrine autoinjectors have been the standard of care for the out-of-hospital treatment of anaphylaxis, their use has been associated with potential cardiovascular risks including intravascular injection, resulting in rapid increases in blood pressure and pulse rate. ARS Pharmaceuticals, Inc conducted a clinical trial designed to assess the pharmacokinetics and pharmacodynamics of ARS-1, an intranasal epinephrine spray in development, compared to EpiPen in subjects with a documented history of seasonal allergies. During the conduct of this study, a presumed intrablood vessel injection following EpiPen administration by a medical professional was observed in a female subject. The subject reported palpitations within 1 minute of receiving EpiPen injection; at 4 minutes postinjection, blood pressure was 221/128 mmHg (baseline 118/79), and pulse rate was 71 (baseline 56). In contrast, across all subjects (N = 36) the mean maximum increases in systolic blood pressure, diastolic blood pressure, and pulse rate were 12.0 mmHg, 2.8 mmHg, and 16.3 bpm, respectively. When this subject was removed from the pharmacokinetic analysis, the mean epinephrine Cmax of the remaining subjects was 801.1 pg/mL after administration of EpiPen; however, at 4 minutes postinjection this subject had a plasma epinephrine level of 4390 pg/mL, a >6.3-fold increase, illustrating the risks that may be associated with out-of-hospital epinephrine injections that are included as warnings in the product labeling. Despite the potential risks associated with accidental intravessel injection, it is important to note that intramuscular administration of epinephrine is currently the best currently available out-of-hospital treatment for severe allergic reactions and anaphylaxis.

Chapter 14: Nonallergic rhinitis.

Rhinitis is characterized by one or more of the following nasal symptoms: congestion, rhinorrhea (anterior and posterior), sneezing, and itching. It is classified as allergic or nonallergic, the latter being a diverse syndrome that is characterized by symptoms of rhinitis that are not the result of IgE-mediated events. Excluding infectious rhinitis and underlying systemic diseases, clinical entities that can be classified among the disorders that make up the nonallergic rhinitis syndromes include gustatory rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES), atrophic, drug-induced (rhinitis medicamentosa), hormone induced, senile rhinitis (of the elderly), rhinitis associated with chronic rhinosinusitis with or without nasal polyps, and the idiopathic variant formerly known as vasomotor rhinitis but more accurately denoted as nonallergic rhinopathy (NAR). The prevalence of nonallergic rhinitis has been observed to be one-third that of allergic rhinitis, affecting ~7% of the U.S. population or ~22 million people. NAR is the most common of the nonallergic rhinitis subtypes, comprising at least two-thirds of all nonallergic rhinitis sufferers. Although certain precipitants such as perfume, strong odors, changes in temperature or humidity, and exposure to tobacco smoke are frequently identified as symptom triggers, NAR may occur in the absence of defined triggers. The diagnosis of nonallergic rhinitis is purely clinical and relies on a detailed history and physical exam. Skin testing or in vitro testing to seasonal and perennial aeroallergens is required to make the diagnosis of nonallergic rhinitis. Because of the heterogeneous nature of this group of disorders, treatment should be individualized to the patient's underlying pathophysiology and/or symptoms and is often empiric.

Chapter 14: Nonallergic rhinitis.

Rhinitis is characterized by one or more of the following nasal symptoms: congestion, rhinorrhea (anterior and posterior), sneezing, and itching. It is classified as allergic or nonallergic, the latter being a diverse syndrome that is characterized by symptoms of rhinitis that are not the result of IgE-mediated events. Excluding infectious rhinitis and underlying systemic diseases, clinical entities that can be classified among the disorders that make up the nonallergic rhinitis syndromes include gustatory rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES), atrophic, drug-induced (rhinitis medicamentosa), hormone induced, senile rhinitis (of the elderly), rhinitis associated with chronic rhinosinusitis with or without nasal polyps, and the idiopathic variant formerly known as vasomotor rhinitis but more accurately denoted as nonallergic rhinopathy (NAR). The prevalence of nonallergic rhinitis has been observed to be one-third that of allergic rhinitis, affecting ∼7% of the U.S. population or ∼22 million people. NAR is the most common of the nonallergic rhinitis subtypes, comprising at least two-thirds of all nonallergic rhinitis sufferers. Although certain precipitants such as perfume, strong odors, changes in temperature or humidity, and exposure to tobacco smoke are frequently identified as symptom triggers, NAR may occur in the absence of defined triggers. The diagnosis of nonallergic rhinitis is purely clinical and relies on a detailed history and physical exam. Skin testing or in vitro testing to seasonal and perennial aeroallergens is required to make the diagnosis of nonallergic rhinitis. Because of the heterogeneous nature of this group of disorders, treatment should be individualized to the patient's underlying pathophysiology and/or symptoms and is often empiric.

Nonallergic rhinopathy (formerly known as vasomotor rhinitis).

This review focuses on the poorly understood condition of nonallergic rhinopathy (NAR) at a clinical level, with an eye on current optimal treatment. NAR is the new designation for the conditions formerly referred to as vasomotor rhinitis or nonallergic idiopathic rhinitis. The clinical characteristics and differential diagnosis are provided in detail in this review, and the disease should now be characterized sufficiently for clinical studies.

The efficacy of intranasal antihistamines in the treatment of allergic rhinitis.

OBJECTIVES: To discuss the new use of intranasal antihistamines as first-line therapies, compare and contrast this class of medication with the traditionally available medications, and discuss the potential for intranasal antihistamines to provide relief superior to second-generation oral antihistamines. DATA SOURCES: Review articles and original research articles were retrieved from MEDLINE, OVID, PubMed (1950 to November 2009), personal files of articles, and bibliographies of located articles that addressed the topic of interest. STUDY SELECTION: Articles were selected for their relevance to intranasal antihistamines and their role in allergic rhinitis. Publications included reviews, treatment guidelines, and clinical studies (primarily randomized controlled trials) of both children and adults. RESULTS: This panel was charged with reviewing the place of intranasal antihistamines in the spectrum of treatment for allergic rhinitis. Intranasal antihistamines have been shown in numerous randomized, placebo-controlled trials to be more efficacious than the oral antihistamines. Although intranasal corticosteroids are considered by some to be superior to intranasal antihistamines, multiple studies have shown an equal effect of the 2 classes of medication. Both intranasal corticosteroids and intranasal antihistamines have been shown to reduce all symptoms of allergic rhinitis. In addition, some intranasal antihistamines have a more rapid onset of action than intranasal corticosteroids. CONCLUSIONS: The future of allergy treatment will likely involve a combination of both intranasal corticosteroids and intranasal antihistamines because of the benefits of local administration and their additive effect on efficacy.

Comprehensive review of olopatadine: the molecule and its clinical entities.

Olopatadine is a tricyclic compound with antihistaminic, mast cell-stabilizing, and anti-inflammatory properties. In the United States olopatadine is approved as a b.i.d. ophthalmic solution, Patanol (Alcon Laboratories, Inc., Fort Worth, TX) to treat all signs and symptoms of allergic conjunctivitis and as a q.d. formulation, Pataday (Alcon Laboratories, Inc.), to treat itching associated with allergic conjunctivitis. A nasal spray, Patanase (Alcon Laboratories, Inc.), was approved in 2008 for treatment of the symptoms of seasonal allergic rhinitis. The available data on olopatadine was assessed with regard to future uses through a comprehensive literature review and a Roundtable Discussion held at the 2009 meeting of the American Academy of Allergy Asthma and Immunology. The unique mechanisms of action of olopatadine still under study include mast cell stabilization, potent H(1)-anthistaminic activity, and anti-inflammatory effects. Data support consideration of nasal olopatadine for as-needed use for episodic symptoms of allergic rhinitis, for treatment of nonallergic rhinitis, and for use in combination with topical steroids for patients with moderate-to-severe allergy symptoms.

Section 4. What the guidelines have missed: a general discussion of the faculty: highlights of the asthma summit 2009: beyond the guidelines.

The sessions during the 2 days of the Asthma Summit focused largely on some specific aspects of the current European and U.S. guidelines for managing asthma. By way of summary, the faculty addressed the question of what they thought the guidelines missed, starting with consideration of those aspects of their own practice management that they believed are not clearly discussed in current guidelines.

Azelastine and olopatadine in the treatment of allergic rhinitis.

OBJECTIVE: To review the literature supporting current recommendations for nasal antihistamines as first-line therapy for allergic rhinitis. DATA SOURCES: Published articles in the peer-reviewed medical literature. STUDY SELECTION: Clinical trials focusing on the efficacy, safety, and recommended uses of the currently approved nasal antihistamines in the United States: azelastine nasal spray, 0.1%, and olopatadine nasal spray, 0.6%. RESULTS: Azelastine nasal spray, 0.1%, and olopatadine nasal spray, 0.6%, have rapid onsets of action, are well tolerated, and have clinical efficacy for treating allergic rhinitis that is equal or superior to oral second-generation antihistamines. Both also have a clinically significant effect on nasal congestion. Azelastine is also approved for nonallergic rhinitis. Although older data suggest that intranasal steroids have greater clinical efficacy than nasal antihistamines, more recent comparisons in patients with mild to moderate disease have shown equal or noninferior efficacy. In addition, in contrast to oral antihistamines or leukotriene antagonists, the combination of a nasal antihistamine and intranasal steroid may provide additive benefits for treating patients with more severe disease. CONCLUSION: The data support current recommendations for nasal antihistamines as first-line therapy for allergic rhinitis. Future studies should address possible as needed use, the use of premixed antihistamine-steroid combinations, and the treatment of mixed rhinitis.

Comparison of olopatadine 0.6% nasal spray versus fluticasone propionate 50 microg in the treatment of seasonal allergic rhinitis.

The efficacy of nasal antihistamines (NAHs) for allergic rhinitis (AR) is comparable with or better than second-generation oral antihistamines, with faster onset of action and greater effect on congestion. Limited data suggest that NAHs may be equivalent to intranasal corticosteroids at reducing the full range of nasal seasonal AR (SAR) symptoms, including congestion. The efficacy of olopatadine 0.6% nasal spray (2 sprays/nostril b.i.d.) for symptoms of SAR was compared with fluticasone 50 microg nasal spray (2 sprays/nostril q.d.) in a double-blind, randomized, parallel-group, 2-week noninferiority trial. A total of 130 symptomatic patients were randomized to treatment and they recorded nasal and ocular allergy symptom scores b.i.d. (morning and evening) in a diary. Both treatments reduced reflective and instantaneous assessments of nasal and ocular symptoms from baseline throughout the 2-week study period (p < 0.05). The reflective total nasal symptom score (the primary efficacy variable) decreased by an average of -45.4% for patients treated with olopatadine 0.6% and by -47.4% for those treated with fluticasone; statistical significance favoring olopatadine was demonstrated at day 1. No significant between-treatment differences were determined for the average 2-week percent changes from baseline for congestion, runny nose, sneezing, itchy nose, and ocular symptoms, although olopatadine had a faster onset of action for reducing all symptoms. Both treatments were safe and well tolerated. Olopatadine and fluticasone nasal sprays both reduced nasal and ocular SAR symptoms with no significant between-treatment differences except for a faster and greater onset of action with olopatadine.

Costs of second-generation antihistamines in the treatment of allergic rhinitis: US perspective.

OBJECTIVE: To review the pharmacoeconomic literature evaluating use of antihistamines in treating allergic rhinitis (AR) in the US. METHODS: Three independent reviewers conducted a comprehensive search of the current literature with PubMed. They identified articles describing original research comprising US cost analyses or pharmacoeconomic evaluations that reported both costs and consequences of using second-generation anthistamines (SGAs), first-generation antihistamines (FGAs), or both for the treatment of patients with AR. The search was limited to studies performed in humans and published in English between 1998 and 2008. RESULTS: Five of 200 articles met the inclusion criteria and examined costs associated primarily with chlorpheniramine, diphenhydramine, cetirizine, and fexofenadine. The first two studies retrospectively analyzed a claims database and concluded that fexofenadine was associated with slightly lower overall costs than loratadine and cetirizine. A third study compared total healthcare costs associated with FGAs and SGAs, concluding that despite their higher prescription cost, SGAs result in lower medical resource use and lower cost for treatment of AR versus FGAs, although no individual SGA could be distinguished as providing substantial healthcare cost savings or increased cost-effectiveness over the other SGAs. Two studies investigated the impact of transitioning a prescription SGA to over-the-counter status and concluded that such a transition would provide cost savings to healthcare plans, but did not address the cost or health effect of such a switch on specific populations whose plans might no longer cover prescription SGAs. CONCLUSIONS: Preliminary evidence suggests that newer SGAs offer clinical, pharmacodynamic, and pharmacokinetic advantages that may translate into superior cost-effectiveness in the treatment of AR. Further study is warranted to clarify the pharmacoeconomic impact of the newer SGAs and to establish their relative cost-effectiveness.

Barriers to asthma treatment in the United States: results from the global asthma physician and patient survey.

BACKGROUND: : The Global Asthma Physician and Patient (GAPP) survey evaluated the perceptions of both physicians and patients on the management of asthma. Here we present the results from the United States (US) subpopulation of the GAPP survey. METHODS: : The GAPP Survey was a large, global study (physicians, n = 1733; patients, n = 1726; interviews, n = 3459). In the US, 208 adults (aged ≥18 years) with asthma and 224 physicians were recruited. Respondents were questioned using self-administered online interviews with close-ended questionnaires. RESULTS: : Physician and patient responses were found to differ in regard to perception of time spent on asthma education, awareness of disease symptoms and their severity, asthma medication side effects, and adherence to treatment and the consequence of nonadherence. Comparison of the US findings with the global GAPP survey results suggest the US physician-patient partnership compared reasonably well with the other countries in the survey. Both patients and physicians cited a need for new asthma medication. CONCLUSIONS: : Similar to the global GAPP survey, the US-specific findings indicate that in general there is a lack of asthma control, poor adherence to therapy, and room for improvement in patient-physician communication and partnership in treating asthma.

Nonallergic rhinitis, with a focus on vasomotor rhinitis: clinical importance, differential diagnosis, and effective treatment recommendations.

The term "rhinitis" denotes nasal inflammation causing a combination of rhinorrhea, sneezing, congestion, nasal itch, and/or postnasal drainage. Allergic rhinitis is the most prevalent and most frequently recognized form of rhinitis. However, nonallergic rhinitis (NAR) is also very common, affecting millions of people. By contrast, NAR is less well understood and less often diagnosed. Nonallergic rhinitis includes a heterogeneous group of conditions, involving various triggers and distinct pathophysiologies. Nonallergic vasomotor rhinitis is the most common form of NAR and will be the primary focus of this review. Understanding and recognizing the presence of NAR in a patient is essential for the correct selection of medications and for successful treatment outcomes.

Recommendations for competency in allergy training for undergraduates qualifying as medical practitioners: a position paper of the world allergy organization.

The Council acknowledges specific comments from: The American Academy of Allergy, Asthma and Immunology (AAAAI) (Amal H Assa'ad); The American College of Allergy, Asthma and Immunology (ACAAI) (Mark Dykewicz, D. Betty Lew, Bryan L. Martin); The Argentine Association of Allergy and Immunology (Ledit RF Ardusso); The Argentine Society of Allergy and Immunopathology (Estrella Asayag); The Australasian Society of Clinical Immunology and Allergy (ASCIA) (Jill Smith); The British Society for Allergy and Clinical Immunology (Stephen Durham); The Brazilian Society of Allergy and Immunopathology (Nelson Rosario); The Bulgarian Society of Allergology (Vasil Dimitrov); The Canadian Society of Allergy and Clinical Immunology (CSACI) (Richard Warrington); The Chilean Society of Allergy and Immunology (Jessica Salinas); The Chinese Society of Allergology (Zhang Hongyu, Yin Jia); The Czech Society of Allergology and Clinical Immunology (Jiri Litzman); The Danish Society of Allergology (Lone Winther, Peter Plaschke); The Egyptian Society of Allergy and Clinical Immunology (Kamal Maurice Hanna); The Egyptian Society of Pediatric Allergy and Immunology (Yehia El-Gamal); The German Society for Allergy and Clinical Immunology (Thilo Jakob, Claus Bachert, Bernhard Przybilla); The Hungarian Society of Allergology and Clinical Immunology (Kristof Nekam); The Icelandic Society of Allergy and Clinical Immunology (Björn R. Lúdvíksson); The Italian Association of Territorial and Hospital Allergists (Riccardo Asero); The Italian Society of Allergy and Clinical Immunology (Luigi Fontana); The Japanese Society of Allergology (Sankei Nishima); The Korean Academy of Asthma Allergy and Clinical Immunology (Joon Sung Lee, Hae-Sim Park); The Latvian Association of Allergists (Ieva Cirule); The Lebanese Society of Allergy & Immunology (Fares Zaitoun); The Mongolian Society of Allergology (S. Munkhbayarlakh); The Allergy and Clinical Immunology Society (Singapore) (Chng Hiok Hee); The Allergy Society of South Africa (Sharon Kling); The Spanish Society of Allergy and Clinical Immunology (Tomás Chivato); The Swiss Society for Allergology and Immunology (SSAI-SGAI) (Beat A. Imhof, Andreas Bircher); The Allergy and Immunology Society of Thailand (Pakit Vichyanond); The Turkish National Society of Allergy and Clinical Immunology (Omer Kalayci); and The Venezuelan Society of Allergy, Asthma and Immunology (Luis F Sarmiento).