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 [Cl] 0.64 to 1.28), with a number needed to treat (NNT) to benefit of 176 (95% CI NNT to benefit 39 to infinity to NNT to harm 65). The adjusted OR in the anaphylaxis subgroup was 1.12 (95% Cl 0.41 to 3.27). In the allergic reaction group, the adjusted OR was 0.91 (95% Cl 0.63 to 1.31), with an NNT to benefit of 173 (95% Cl NNT to benefit 38 to infinity 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. Copyright (C) 2015 by the American College of Emergency Physicians.

Background Immunoglobulin replacement therapy is standard of care for patients with primary humoral immunodeficiency [1]. Compared with intravenous immunoglobulin (IVIG), subcutaneous immunoglobulin (SCIG) offers comparable efficacy, lower costs and reduced systemic reactions [2,3]. However, little is known about effects on quality of life when patients transition from IVIG to SCIG. It was our objective to assess changes in quality of life, mood, sleepiness and fatigue in patients transitioning from IVIG to SCIG.

CONTEXTE : Un nouveau traitement anti-immunoglobuline E (anti-IgE) contre l’asthme, l’omalizumab, a été approuvé au Canada.

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 fourweek 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 omalizumabtreated 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.

The article by Wu and colleagues in this issue describes an interesting case of asthma secondary to exposure to bloodworms in a laboratory setting. The use of bloodworms as a fish food has led to a number of differing manifestations dependent on the route of exposure. These include anaphylaxis, asthma, and urticaria/angioedema secondary to contact. A person who worked in an office setting in our hospital was referred to me after three admissions to our emergency department for marked angioedema and inflammation of the right side of the face, chemosis of the right eye, and blurred vision with onset in the morning at work. She had no atopic history and had eaten no food on the day of one of the reactions. Only after persistent questioning regarding what she may have transferred from her hand to her face (she was right-handed) did she divulge that she fed the fish in her aquarium in the office. She did not know the source of the fish food, and I requested that she place a tiny amount on her forearm the following day. This produced a swelling of the entire forearm. The fish food was freeze-dried bloodworms. Interestingly, at the annual meeting of the Canadian Society of Allergy and Clinical Immunology (CSACI) that same week, Dr. J. Roberts presented the case of a girl who had developed anaphylaxis after accidental ingestion of residual fish food that was on her hands when she was eating dinner. This individual had a striking reaction to a dilute preparation of the bloodworm fish food on skin testing and did not react to other fish food preparations. Subsequent to these cases, a colleague mentioned additional cases of asthma symptoms in employees at the Vancouver Aquarium, where bloodworms are raised and processed as a food source. The well-defined case presented in this issue and the others mentioned suggest that bloodworm may be a more common cause of allergic reactions than generally recognized and warrants consideration when the patient's history is reviewed. R. Robert Schellenberg, MD, FRCP

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.

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.

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.

To the Editor: Recent studies1–3 have suggested that cyclooxygenase-2 (COX-2) inhibitors can be safely used in patients with asthma who have documented intolerance to COX-1 inhibitors such as aspir...

Studies of human basophils have been limited by the low number present in peripheral blood and the difficulties of purification to homogeneity with reasonable yield and functional status. Reproducible purification of human basophils to 96.5±0.5% with a yield of 40.8±5.3% was obtained by negative selection using immunomagnetic beads following initial separation by density gradient centrifugation. Isolated cells demonstrated complete viability by vital dye exclusion and spontaneous histamine release following incubation of <5%. Stimulation with anti-IgE or calcium ionophore A23187 caused histamine release and leukotriene C4 production. Basophils demonstrated dose-dependent chemotaxis to monocyte chemotactic protein-3. This simplified methodology results in fully functional basophils in very high purity and good yield.