Anne K. Ellis

Anaphylaxis--a practice parameter update 2015.

Phillip Lieberman, MD; Richard A. Nicklas, MD; Christopher Randolph, MD; John Oppenheimer, MD; David Bernstein, MD; Jonathan Bernstein, MD; Anne Ellis, MD; David B.K. Golden, MD; Paul Greenberger, MD; Steven Kemp, MD; David Khan, MD; Dennis Ledford, MD; Jay Lieberman, MD; Dean Metcalfe, MD; Anna Nowak-Wegrzyn, MD; Scott Sicherer, MD; Dana Wallace, MD; Joann Blessing-Moore, MD; David Lang, MD; Jay M. Portnoy, MD; Diane Schuller, MD; Sheldon Spector, MD; and Stephen A. Tilles, MD Chief Editors: Phillip Lieberman, MD; Richard A. Nicklas, MD; John Oppenheimer, MD; Christopher Randolph, MD Members of the Joint Task Force: David Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard Nicklas, MD; John Oppenheimer, MD; Jay M. Portnoy, MD; Christopher Randolph, MD; Diane Schuller, MD; Sheldon Spector, MD; Stephen A. Tilles, MD; Dana Wallace, MD Practice ParameterWorkgroup: David Bernstein, MD; Jonathan Bernstein, MD; Anne Ellis, MD; David B.K. Golden, MD; David Khan, MD; Dennis Ledford, MD; Jay Lieberman, MD; Dean Metcalfe, MD; Dana Wallace, MD

Onset of Action, Efficacy, and Safety of a Single Dose of Fexofenadine Hydrochloride for Ragweed Allergy Using an Environmental Exposure Unit

BACKGROUND Fexofenadine hydrochloride is the active acid metabolite of terfenadine. Fexofenadines anti-allergic properties require confirmation in a clinical setting. OBJECTIVE The purpose of this study was to characterize the time to onset of clinically important relief of symptoms of allergic rhinitis in subjects taking single doses of either 60 mg or 120 mg fexofenadine HCl, or placebo, after exposure to ragweed pollen in a controlled environment. Other objectives were to assess the efficacy and safety of single doses of fexofenadine HCl. METHODS One hundred forty-six ragweed-sensitive subjects were primed in the off-season with ragweed pollen in the environmental exposure unit. One hundred thirty-six subjects who adequately responded to priming entered a single-dose placebo phase. Placebo-responders were disqualified from the study, leaving 99 subjects with adequate symptoms to be randomized and given a single dose of either fexofenadine HCl 120 mg (33), 60 mg (33) or placebo (33), after 60 minutes of allergen exposure. Exposure continued over five hours and subjects recorded symptoms every 20 minutes. This study was of a randomized, placebo-controlled, double-blind, parallel design. RESULTS Median time to onset for relaxed criteria clinically important relief was 60 minutes for both fexofenadine treatment groups, and 100 minutes for placebo (P = .018). The proportion with relief was 82% at 60 mg, 85% at 120 mg, and 64% for placebo. Treated groups had reductions in symptom scores double that of placebo. CONCLUSIONS Fexofenadine is safe and efficacious at single doses of 60 mg and 120 mg. Average time to onset was 60 minutes using controlled pollen exposure in an environmental exposure unit.

Quality of Life in Women With Urinary Tract Infections: Is Benign Disease a Misnomer?

Background: The objective of this study was to undertake an exploratory evaluation of quality-of-life indicators for women suffering from urinary tract infections. Methods: The RAND 36-Item Health Survey 1.0 (SF-36) was administered to 47 women with a diagnosed urinary tract infection who were being cared for in the Family Medicine Center, Student Health Services, or Urology Outpatient Clinic. A control population of 71 women was obtained from the female members of an undergraduate geography class, a community basketball league, and a local womens choir. Results: All subsections of the SF-36 quality-of-life indices were significantly decreased in the subject population compared with the control population (lower score indicates lower quality of life): patient general health perception (63.3 vs 78.9, P < .001) physical functioning (76.6 vs 87.6, P = .012), role limitation owing to physical health (53.8 vs 93.0, P < .001) and emotional health (67.4 vs 88.3, P < .001), vitality (43.0 vs 64.9, P < .001), emotional well-being (64.4 vs 80.2, P < .001), pain (58.7 vs 91.5, P < .001), and social functioning (60.4 vs 90.4. P < .001). Conclusion: Suffering from an urinary tract infection has a detrimental influence on patient quality of life. The effect of urinary tract infections on women and their perception of quality of life have not been hitherto reported in the medical literature. The Significant findings in this study call into question whether acute, non-life-threatening illness should be regarded as benign.

The role of epigenetics in the developmental origins of allergic disease.

OBJECTIVE To review current research findings in the field of epigenetics pertaining to the developmental origins of allergic disease. DATA SOURCES We examined original research and review articles identified from MEDLINE, OVID, and PubMed that addressed the topic of interest, using the search terms atopy, allergy, asthma, development, IgE, origins, and cord blood paired with epigenetic(s). Relevant references from each article were also procured for review. STUDY SELECTION Articles were selected based on their relevance to the contributory role of epigenetic modifications in asthma and other atopic diseases. RESULTS There is increasing evidence pointing to the influence of prenatal and early life exposures on the development of allergic disease. A growing body of literature supports the theory that transient environmental pressures can have permanent effects on gene regulation and expression through epigenetic mechanisms. Histone modifications have been associated with degree of bronchial hyperresponsiveness and corticosteroid resistance in asthma. Epigenetic mechanisms can operate independently in various cell types; recent studies have suggested a role in the differentiation of human T cells. Murine studies have revealed that a maternal diet rich in methyl donors can enhance susceptibility to allergic inflammation in the offspring, mediated through increased DNA methylation. Murine studies have also implicated epigenetically modified dendritic cells in the transmission of allergic risk from mothers to offspring. CONCLUSION The current literature offers exciting data to support a role for epigenetics in the development and persistence of asthma and allergic rhinitis. However, further human studies are necessary to explore these mechanisms and assess future clinical applicability.

Haemopoietic processes in allergic disease: eosinophil/basophil development

Haemopoietic myeloid progenitors contribute to the ongoing recruitment of pro‐inflammatory cells, such as eosinophils and basophils (Eo/B), to target tissue sites in allergic diseases. It is apparent that the development of allergic inflammation is critically dependent on the ability of the bone marrow to support the proliferation, differentiation and mobilization of haemopoietic progenitors. The haemopoietic inductive microenvironment in the bone marrow is crucial for providing signals necessary for maintenance of progenitor populations at varying stages of lineage commitment and permitting these cells to circulate in the bloodstream. Progenitors demonstrate responsiveness to specific cytokines, which varies with stage of differentiation. Pro‐inflammatory signals, Th2 cytokines in particular, generated following allergen challenge, can impact on haemopoietic progenitor differentiation and mobilization, leading to accelerated Eo/B production. Allergen inhalation by allergic asthmatics induces a time‐dependent change in cytokine levels within the bone marrow compartment, influencing differentiation of Eo/B progenitors, as evidenced by the relationship between increased bone marrow IL‐5 levels and Eo/B production. It is proposed that inhaled allergen induces trafficking of IL‐5‐producing T lymphocytes to the bone marrow, further promoting eosinophilopoiesis through IL‐5R signalling. In this manner, Th2 lymphocyte trafficking from the airway may regulate events occurring in the bone marrow. Negative regulators of Eo/B differentiation, including Th1 cytokines, may prove to be important for restoring homeostasis. Eo/B progenitors are also altered in cord blood of infants at risk of atopy and asthma, offering a potential biomarker for, and raising the possibility that Eo/B progenitors are directly involved in the development of allergic disease. For example, changes in the expression of haemopoietic cytokine receptors on cord blood progenitor cells are associated with maternal allergic sensitization, atopic risk and its development, suggesting that haemopoietic processes underlying the allergic phenotype may begin to evolve in the perinatal period.

Factors associated with initiation and completion of the quadrivalent human papillomavirus vaccine series in an ontario cohort of grade 8 girls

BackgroundAlthough over a hundred million dollars have been invested in offering free quadrivalent human papillomavirus (HPV) vaccination to young girls in Ontario, there continues to be very little information about its usage. In order to successfully guide future HPV vaccine programming, it is important to monitor HPV vaccine use and determine factors associated with use in this population.MethodsLinking administrative health and immunization databases, we conducted a population-based, retrospective cohort study of girls eligible for Ontarios Grade 8 HPV vaccination program in Kingston, Frontenac, Lennox, and Addington. We determined the proportion of girls who initiated (at least one dose) and completed (all three doses) the vaccination series overall and according to socio-demographics, vaccination history, health services utilization, medical history, and program year. Multivariable logistic regression was used to estimate the strength of association between individual factors and initiation and completion, adjusted for all other factors.ResultsWe identified a cohort of 2519 girls, 56.6% of whom received at least one dose of the HPV vaccine. Among vaccinated girls, 85.3% received all three doses. Vaccination history was the strongest predictor of initiation in that girls who received the measles-mumps-rubella, meningococcal C, and hepatitis B vaccines were considerably more likely to also receive the HPV vaccine (odds ratio 4.89; 95% confidence interval 4.04-5.92). Nevertheless, HPV vaccine uptake was more than 20% lower than that of these other vaccines. In addition, while series initiation was not influenced by income, series completion was. In particular, girls of low income were the least likely to receive all three indicated doses of the HPV vaccine (odds ratio 0.45; 95% confidence interval 0.28-0.72).ConclusionsThe current low level of HPV vaccine acceptance in Kingston, Frontenac, Lennox, and Addington will likely have important implications in terms of the health benefits and cost-effectiveness of its publicly funded program. We identified important factors associated with series initiation and completion that should be considered in efforts to improve HPV vaccine use in this population.

A comparison of the effect of diphenhydramine and desloratadine on vigilance and cognitive function during treatment of ragweed-induced allergic rhinitis

BACKGROUND Decrements in cognitive performance are associated with the use of sedating antihistamines. Most, but not all, second-generation antihistamines have been found to be nonsedating. OBJECTIVE To examine the central nervous system (CNS) profile of a new second-generation antihistamine, desloratadine. METHODS Subjects with ragweed-induced allergic rhinitis (aged 18-60 years) who demonstrated a predetermined severity of symptoms after priming with ragweed pollen in the Environmental Exposure Unit were randomized to receive a single dose of desloratadine, 5 mg; diphenhydramine, 50 mg; or placebo. A comprehensive battery of repeatable, automated neuropsychological tests was administered to subjects before treatment (symptomatic baseline) and 90 minutes after taking study medication. RESULTS Both desloratadine (P = .04) and diphenhydramine (P < .01) alleviated the symptoms of allergic rhinitis compared with placebo, but treatment with diphenhydramine was associated with clinically meaningful decrements on all vigilance parameters (P < .05 for desloratadine-diphenhydramine contrasts). Also, subjects treated with diphenhydramine performed significantly worse than subjects given desloratadine or placebo across all cognitive domains evaluated. Most effect sizes for the mean desloratadine and diphenhydramine differences were between 0.4 and 0.8 (moderate to high). Stanford Sleepiness Scale scores also indicated significantly more somnolence with diphenhydramine vs desloratadine or placebo (P < .001). There were no significant differences on any of the cognitive parameters between subjects treated with desloratadine and those given placebo. CONCLUSIONS Desloratadine improved ragweed-induced allergic rhinitis symptoms without adversely affecting performance. Diphenhydramine improved allergic rhinitis symptoms but caused significant decrements in vigilance and cognitive functioning. Thus, efficacy of antihistamine treatment must be balanced against the associated effects on CNS functioning.

Sublingual or subcutaneous immunotherapy for seasonal allergic rhinitis: an indirect analysis of efficacy, safety and cost

RATIONALE, AIMS AND OBJECTIVES The standard of preventive care for poorly controlled seasonal allergic rhinitis (AR) is subcutaneous immunotherapy (SCIT) with allergen extracts, administered in a physicians office. As an alternative to SCIT, sublingual immunotherapy (SLIT) is now an option for patients with seasonal AR. Oralair, a SLIT tablet containing freeze-dried allergen extracts of five grasses [cocksfoot (Dactylis glomerata), meadow grass (Poa pratensis), rye grass (Lolium perenne), sweet vernal grass (Anthoxanthum odoratum) and timothy grass (Phleum pratense)], and Grazax, a SLIT tablet containing a standardized extract of grass pollen allergen from timothy grass (P pratenase), are two such agents currently available in many countries. However, head-to-head comparative data are not available. In this study, an indirect comparison on efficacy, safety and cost was undertaken between Oralair, Grazax and SCIT. METHODS A systematic review was conducted for double-blind placebo-controlled randomized trials evaluating Oralair, Grazax or SCIT in patients with grass-induced seasonal AR. Using placebo as the common control, an indirect statistical comparison between treatments was performed using meta regression analysis with active drug as the primary independent variable. An economic analysis, which included both direct and indirect costs for the Canadian setting, was also undertaken. RESULTS Overall, 20 placebo-controlled trials met the study inclusion criteria. The indirect analysis suggested improved efficacy with Oralair over SCIT [standardized mean difference (SMD) in AR symptom control = -0.21; P = 0.007] and Grazax (SMD = -0.18; P = 0.018). In addition, there were no significant differences in the risk of discontinuation due to adverse events between therapies. Oralair was associated with cost savings against year-round SCIT (

Effects of phthalates on the development and expression of allergic disease and asthma

2471), seasonal SCIT (

Environmental exposure unit: a sensitive, specific, and reproducible methodology for allergen challenge

948) and Grazax (