[show abstract][hide abstract] ABSTRACT: 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.
Allergy Asthma and Clinical Immunology 06/2012; 8(1):7.
[show abstract][hide abstract] ABSTRACT: Uncomplicated acute rhinosinusitis (ARS) is usually a self-limiting inflammatory condition often treated with antibiotics.
To assess the safety and efficacy of fluticasone furoate nasal spray (FFNS) compared with placebo for symptomatic relief of uncomplicated ARS.
A randomised, double-blind, placebo-controlled, parallel-group, multicentre, 2-week treatment study of FFNS 110μg once and twice daily was undertaken in adults/adolescents.
A statistically significant reduction was seen in the daily major symptoms score, a composite score of three individual symptoms (nasal congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and postnasal drip on a 0-3 scale) by both FFNS doses compared with placebo (least square mean differences vs. placebo of -0.386 (p=0.008) and -0.357 (p=0.014) for once daily and twice daily FFNS, respectively). The differences in median times to symptom improvement were not statistically significant between each dose of FFNS (7 days) and placebo (8 days). There were no treatment differences in antibiotic use for possible fulminant bacterial rhinosinusitis (3% in each group). The safety profile of FFNS was similar to placebo.
FFNS reduces symptoms of uncomplicated ARS compared with placebo and is well tolerated, providing support for withholding antibiotics in selected patients.
Primary care respiratory journal: journal of the General Practice Airways Group 05/2012; 21(3):267-75.
[show abstract][hide abstract] ABSTRACT: This document provides health care 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 the development of guidelines and do not address the particulars of the Canadian health care 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 the strength of the evidence base and the degree of endorsement by the multidisciplinary expert group preparing the document.These guidelines have been copublished in both Allergy, Asthma, and Clinical Immunology and the Journal of Otolaryngology-Head and Neck Surgery.
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale 05/2011; 40 Suppl 2:S99-193. · 0.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Nasal allergen challenge (NAC) is useful to study the pathophysiology of rhinitis, and multiple challenges may more adequately approximate natural exposure.
To determine the effect of 4 consecutive daily NAC, on clinical and inflammatory parameters in rhinitics with or without asthma.
Rhinitic subjects were recruited: 19 with mild asthma and 13 without asthma. Subjects underwent a control challenge (normal saline) followed by 4 consecutive daily NAC. Allergen challenge consisted of spraying the chosen allergen extract into each nostril until a positive nasal response occurred. Symptoms were recorded on a Likert scale, and oral peak expiratory and nasal peak inspiratory flows allowed assessment of a nasal blockage index (NBI), for a period of 7 hours. Induced sputum and nasal lavage were performed on control day and after 1 and 4 days of NAC.
Compared with the control day, there was a significant increase in symptom scores and NBI 10 minutes after each last daily NAC in both groups (p < 0.05). Symptom scores and NBI were similar for the 2 groups, except for nasal obstruction and rhinorrhea, which were more marked in subjects with asthma and rhinitis, respectively. Nasal lavage eosinophils were increased after 4 days of challenges in both groups, but there was no change in sputum eosinophils. No cumulative effect or any late response were observed in any of the groups over the challenge period.
Multiple NAC may be a useful tool to study the pathophysiology of allergic rhinitis or its relationships with asthma.
Allergy Asthma and Clinical Immunology 01/2011; 7(1):8.
[show abstract][hide abstract] ABSTRACT: Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.
In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.
A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.
In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
New England Journal of Medicine 08/2010; 363(6):532-41. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema.
To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010).
The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review.
This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference.
Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.
Allergy Asthma and Clinical Immunology 01/2010; 6(1):24.
[show abstract][hide abstract] ABSTRACT: Nasal and ocular symptoms of allergic rhinitis (AR) are reported by >70% of patients and have a profound impact on quality of life while also incurring substantial healthcare costs. It has been suggested that intranasal corticosteroids (INS), in addition to effectively treating the nasal components of AR, are effective in treating the ocular symptoms.
This review provides a comprehensive, updated assessment of available data in the public domain to determine the consistency of INS efficacy in treating ocular AR symptoms.
MEDLINE and EMBASE searches, and research of governmental and regulatory institution sources identified 35 randomised, placebo-controlled trials of INS and seasonal AR (SAR) published between 1990 and May 2009 that specifically contained ocular efficacy as part of the study analyses.
Examination of these studies reveals substantial inconsistency of effect of some INS across, and even within, trials, casting doubt on the suggestion that ocular efficacy is a class effect of INS. Conflicting, inconsistent or even negative effects were observed for most INS examined including mometasone furoate and fluticasone propionate. Only fluticasone furoate nasal spray, in addition to established efficacy in treating nasal symptoms, demonstrated a consistent positive effect on ocular symptoms of SAR compared with placebo in a large number of patients across all of its prospective studies. Moreover, these results were consistent across different allergy seasons, including grass, ragweed, and mountain cedar seasons, and different geographical locations throughout Europe and the USA.
While additional prospective head-to-head clinical trials comparing the efficacy of INS in treating ocular symptoms of AR are needed to fully elucidate the benefits of one INS compared with another, data available to date suggest that not all INS are equally consistent in managing ocular symptoms of SAR. Fluticasone furoate is currently the most consistent.
Current Medical Research and Opinion 08/2009; 25(8):2021-41. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Asthma, allergic rhinitis, nasal polyposis, chronic rhinosinusitis, and related forms of upper and lower airway diseases are often characterized by eosinophilic and basophilic inflammation, involving systemic processes. Eosinophil/basophil (Eo/B) lineage-committed progenitor cells in cord blood, peripheral blood, bone marrow, lung tissue, and sputum are up-regulated in the above conditions, and respond to allergen and other stimuli with increased differentiative and migratory capacity. A considerable body of evidence now exists showing that activation of such Eo/B-selective hemopoietic processes is not only associated with the onset and maintenance of allergic inflammation in atopic adults, but also with the development of the allergic diathesis. Moreover, eosinophilopoietic processes within hemopoietic compartments and, importantly, at mucosal tissue sites during an allergic inflammatory response provide novel targets for the treatment of allergy as a systemic process and disease.
[show abstract][hide abstract] ABSTRACT: Allergic rhinitis (AR) is a highly prevalent disorder, which often manifests as both nasal (congestion, sneezing, itching and rhinorrhoea) and ocular (redness, watery eyes, itching and burning) symptoms. Until recently, efficacy against the ocular symptoms of AR has been inconsistent for any single intranasal corticosteroid (INS). Fluticasone furoate is an enhanced-affinity glucocorticoid with potent anti-inflammatory activity.
To assess better the efficacy of an INS in the treatment of both the nasal and ocular symptoms of seasonal AR (SAR).
Data from all four trials of fluticasone furoate nasal spray (FFNS) in the treatment of SAR are reviewed and critically considered.
FFNS consistently and significantly improved the nasal and ocular symptoms of SAR in patients sensitised to several different seasonal allergens (grass, ragweed and mountain cedar pollen) in all trials. An integrated analysis of the results also confirmed improvements in both nasal and ocular symptom scores in previously under-represented adolescent patients treated with FFNS.
FFNS is the first INS to show consistent nasal and ocular efficacy across all SAR trials.
Expert Opinion on Pharmacotherapy 11/2008; 9(15):2707-15. · 2.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004.
To ensure that this consensus remains current.
In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted.
This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings.
There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2008; 100(1 Suppl 2):S30-40. · 3.45 Impact Factor