Emergency Department Corticosteroid Use for Allergy or Anaphylaxis Is Not Associated With Decreased Relapses.

STUDY OBJECTIVE: Corticosteroids (steroids) are often used to mitigate symptoms and prevent subsequent reactions in emergency department (ED) patients with allergic reactions, despite a lack of evidence to support their use. We sought to determine the association of steroid administration with improved clinical outcomes. METHODS: Adult allergy-related encounters to 2 urban EDs during a 5-year period were identified and classified as "anaphylaxis" or "allergic reaction." Regional and provincial databases identified subsequent ED visits or deaths within a 7-day period. The primary outcome was allergy-related ED revisits in the steroid- and nonsteroid-exposed groups, adjusting for potential confounders with a propensity score analysis; secondary outcomes included the number of clinically important biphasic reactions and deaths. RESULTS: Two thousand seven hundred one encounters (473 anaphylactic) were included; 48% were treated with steroids. Allergy-related ED revisits occurred in 5.8% and 6.7% of patients treated with and without steroids, respectively (adjusted odds ratio [OR] 0.91; 95% confidence interval [CI] 0.64 to 1.28), with a number needed to treat (NNT) to benefit of 176 (95% CI NNT to benefit 39 to ∞ to NNT to harm 65). The adjusted OR in the anaphylaxis subgroup was 1.12 (95% CI 0.41 to 3.27). In the allergic reaction group, the adjusted OR was 0.91 (95% CI 0.63 to 1.31), with an NNT to benefit of 173 (95% CI NNT to benefit 38 to ∞ to NNT to harm 58). In the steroid and nonsteroid groups, there were 4 and 1 clinically important biphasic reactions, respectively. There were no deaths. CONCLUSION: Among ED patients with allergic reactions or anaphylaxis, corticosteroid use was not associated with decreased relapses to additional care within 7 days.

Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis.

STUDY OBJECTIVE: Allergic reactions are common presentations to the emergency department (ED). An unknown proportion of patients will develop biphasic reactions, and patients are often monitored for prolonged periods to manage potential reactions. We seek to determine the incidence of clinically important biphasic reactions. METHODS: Consecutive adult patients presenting to 2 urban EDs with allergic reactions during a 5-year period were identified. Encounters were dichotomized as "anaphylaxis" or "allergic reaction" with an explicit algorithm. A comprehensive chart review was conducted on each index and all subsequent visits to detail patient presentations, comorbidities, ED management, and predefined clinically important biphasic reactions. Regional and provincial databases were linked to identify subsequent ED visits and deaths within a 7-day period. The primary outcome was the proportion of patients with a clinically important biphasic reaction, and the secondary outcome was mortality. RESULTS: Of 428,634 ED visits, 2,819 (0.66%) encounters were reviewed (496 anaphylactic and 2,323 allergic reactions). Overall, 185 patients had at least 1 subsequent visit for allergic symptoms. Five clinically important biphasic reactions were identified (0.18%; 95% confidence interval [CI] 0.07% to 0.44%), with 2 occurring during the ED visit and 3 postdischarge. There were no fatalities (95% CI 0% to 0.17%). In the anaphylaxis and allergic reaction groups, clinically important biphasic reactions occurred in 2 patients (0.40%; 95% CI 0.07% to 1.6%) and 3 patients (0.13%; 95% CI 0.03% to 0.41%), respectively. CONCLUSION: Among ED patients with allergic reactions or anaphylaxis, clinically important biphasic reactions and fatalities are rare. Our data suggest that prolonged routine monitoring of patients whose symptoms have resolved is likely unnecessary for patient safety.

The burden of allergic rhinitis (AR) in Canada: perspectives of physicians and patients.

BACKGROUND: Allergic rhinitis (AR) is a common problem and we sought to examine the burden of disease and its management in Canada from the perspectives of patients and physicians. METHODS: Two parallel, Canadawide structured telephone interviews surveyed 1,001 AR patients and 160 physicians in July 2006. RESULTS: 44% of patients had experienced nasal symptoms unrelated to a cold and 20% had a physician diagnosis of AR. At screening 27% reported asthma, 15% chronic or recurrent sinusitis and 5% nasal polyps. With attacks nasal congestion and runny nose were the most bothersome symptoms. Other problems experienced were fatigue (46%), poor concentration (32%), and reduced productivity (23%). Most (77%) had not seen a physician in the past year. Physicians estimated they prescribed intranasal cortico steroids (INCS) to most AR patients (77%) consistent with guidelines but only 19% of patients had used one in the last month. Only 48% of patients were very satisfied with their current INCS. 41% of AR patients reported discontinuing their INCS with the most common reason being a perceived lack of long-lasting symptom relief (44%). 52% of patients felt that their current INCS lost effectiveness over 24 h. The most common INCS side effects included dripping down the throat, bad taste, and dryness. Most AR patients reported lifestyle limitations despite treatment (66%). 61% of patients felt that their symptoms were only somewhat controlled or poorly/not controlled during their worst month in the past year. CONCLUSIONS: AR symptoms are common and many patients experience inadequate control. Physicians report they commonly prescribe intranasal corticosteroids, but patient's perceived loss of efficacy and side effects lead to their discontinuation. Persistent relief of allergic rhinitis symptoms remains a major unmet need. Better treatments and education are required.

Canadian clinical practice guidelines for acute and chronic rhinosinusitis.

This document provides healthcare practitioners with information regarding the management of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) to enable them to better meet the needs of this patient population. These guidelines describe controversies in the management of acute bacterial rhinosinusitis (ABRS) and include recommendations that take into account changes in the bacteriologic landscape. Recent guidelines in ABRS have been released by American and European groups as recently as 2007, but these are either limited in their coverage of the subject of CRS, do not follow an evidence-based strategy, or omit relevant stakeholders in guidelines development, and do not address the particulars of the Canadian healthcare environment.Advances in understanding the pathophysiology of CRS, along with the development of appropriate therapeutic strategies, have improved outcomes for patients with CRS. CRS now affects large numbers of patients globally and primary care practitioners are confronted by this disease on a daily basis. Although initially considered a chronic bacterial infection, CRS is now recognized as having multiple distinct components (eg, infection, inflammation), which have led to changes in therapeutic approaches (eg, increased use of corticosteroids). The role of bacteria in the persistence of chronic infections, and the roles of surgical and medical management are evolving. Although evidence is limited, guidance for managing patients with CRS would help practitioners less experienced in this area offer rational care. It is no longer reasonable to manage CRS as a prolonged version of ARS, but rather, specific therapeutic strategies adapted to pathogenesis must be developed and diffused.Guidelines must take into account all available evidence and incorporate these in an unbiased fashion into management recommendations based on the quality of evidence, therapeutic benefit, and risks incurred. This document is focused on readability rather than completeness, yet covers relevant information, offers summaries of areas where considerable evidence exists, and provides recommendations with an assessment of strength of the evidence base and degree of endorsement by the multidisciplinary expert group preparing the document.These guidelines have been copublished in both Allergy, Asthma & Clinical Immunology and the Journal of Otolaryngology-Head and Neck Surgery.

On the terminology for describing the length-force relationship and its changes in airway smooth muscle.

The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of length-force relationship, many of our concepts regarding smooth muscle mechanical properties, including the notion that the muscle possesses a unique optimal length that correlates to maximal force generation, are likely to be incorrect. To facilitate accurate and efficient communication among scientists interested in the function of airway smooth muscle, a revised and collectively accepted nomenclature describing the adaptive and dynamic nature of the length-force relationship will be invaluable. Setting aside the issue of underlying mechanism, the purpose of this article is to define terminology that will aid investigators in describing observed phenomena. In particular, we recommend that the term "optimal length" (or any other term implying a unique length that correlates with maximal force generation) for airway smooth muscle be avoided. Instead, the in situ length or an arbitrary but clearly defined reference length should be used. We propose the usage of "length adaptation" to describe the phenomenon whereby the length-force curve of a muscle shifts along the length axis due to accommodation of the muscle at different lengths. We also discuss frequently used terms that do not have commonly accepted definitions that should be used cautiously.

Montelukast as add-on therapy with inhaled corticosteroids alone or inhaled corticosteroids and long-acting beta-2-agonists in the management of patients diagnosed with asthma and concurrent allergic rhinitis (the RADAR trial).

OBJECTIVE: To evaluate the effectiveness of montelukast as add-on therapy for patients diagnosed with asthma and concurrent allergic rhinitis who remain uncontrolled while receiving inhaled corticosteroid (ICS) monotherapy or ICS/long-acting beta-2-agonist (LABA) therapy in a community practice setting. DESIGN: An eight-week, multicentre, open-label, observational study. Patients were 15 years of age or older and, while treated with an ICS or ICS/LABA, had allergic rhinitis and uncontrolled asthma symptoms by at least two criteria as per the Canadian Asthma Consensus Guidelines. The primary outcome measure was the percentage of patients with controlled asthma symptoms after eight weeks of treatment with montelukast 10 mg once daily added to ICS or ICS/LABA therapy. RESULTS: In total, 1004 patients participated in the survey phase of the study. Of these patients, 319 continued in the treatment phase and 301 (94.4%) completed the eight-week assessment. At baseline, all patients had uncontrolled asthma symptoms based on the Canadian Asthma Consensus Guidelines; at the eight-week assessment, 229 patients (76.1%) achieved asthma control. According to the Asthma Control Questionnaire (as determined by scores of 0.75 or less), 164 patients (54.7%) achieved well-controlled asthma at week 8. The mean (+/- SD) Asthma Control Questionnaire score decreased from 2.03+/-0.80 to 0.92+/-0.80 (P<0.001) for all patients, representing a clinically significant improvement. A statistically and clinically significant reduction in the overall Mini Rhinitis Quality of Life Questionnaire score was achieved with a decrease from 2.57+/-1.20 to 1.12+/-1.00 (-1.45+/-1.35; P<0.001). Patient and physician satisfaction rates with montelukast add-on therapy were also significantly increased when compared with baseline treatment. CONCLUSION: Montelukast add-on therapy is effective for managing asthma and allergic rhinitis symptoms in patients who were previously uncontrolled with ICS or ICS/LABA treatment.

The role of omalizumab in the treatment of severe allergic asthma.

BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada. OBJECTIVE: To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada. METHODS: A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use. RESULTS: Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or four-week intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment. RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

Interleukin-3, but not granulocyte-macrophage colony-stimulating factor and interleukin-5, inhibits apoptosis of human basophils through phosphatidylinositol 3-kinase: requirement of NF-kappaB-dependent and -independent pathways.

Basophils are key effector cells of allergic reactions. Although proinflammatory cytokines, such as interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5, inhibit eosinophil apoptosis in vitro, little is known about basophil apoptosis, and the signalling mechanisms required for basophil survival remain undefined. To address this issue, we used a novel negative-selection system to isolate human basophils to a purity of > 95%, and evaluated apoptosis by morphology using light and transmission electron microscopy, and by annexin-V binding and propidium iodide incorporation using flow cytometry. In this study, we demonstrated that the spontaneous rate of apoptotic basophils was higher than that of eosinophils as, at 24 hr, 57.6 +/- 4.7% of basophils underwent apoptosis compared with 39.5 +/- 3.8% of eosinophils. In addition, basophil cell death was significantly inhibited when cultured with IL-3 for 48 hr (84.6 +/- 4.9% vehicle-treated cells versus 40.9 +/- 3.9% IL-3-treated cells). IL-3 also up-regulated basophil CD69 surface expression. The effects of IL-3 on apoptosis and CD69 surface expression of human basophils were completely blocked by LY294002 (LY), a potent inhibitor of phosphatidylinositol 3-kinase (PI3-K), but only partially inhibited by lactacystin, a proteasome inhibitor that prevents degradation of IkappaB and NF-kappaB translocation. These observations reveal the novel finding that IL-3 prevents basophil apoptosis through the activation of PI3-K, which is only partially NF-kappaB dependent. As basophils are active participants in allergic reactions and IL-3 is one of the abundant proinflammatory cytokines in secretions from allergic tissue, we suggest that IL-3-mediated inhibition of basophil apoptosis may exacerbate the inflammation associated with allergic disorders.

Tissue elastance influences airway smooth muscle shortening: comparison of mechanical properties among different species.

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus approximately 60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only approximately 12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (approximately 22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to approximately 9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.