Eli O. Meltzer

Rhinosinusitis: Establishing definitions for clinical research and patient care

Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Methods Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusion The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.

A Randomized, Controlled, Phase 2 Study of AMG 317, an IL-4Rα Antagonist, in Patients with Asthma

RATIONALE IL-4 and IL-13 share many biological functions important in the development of allergic airway inflammation and are implicated in the pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL-4Ralpha that blocks both IL-4 and IL-13 pathways. OBJECTIVES To evaluate efficacy and safety of AMG 317 in patients with moderate to severe asthma. METHODS In this phase 2, randomized, double-blind, placebo-controlled study, patients received weekly subcutaneous injections of placebo or AMG 317 (75-300 mg) for 12 weeks, followed by a 4-week follow-up period. The primary endpoint was change from baseline at Week 12 in Asthma Control Questionnaire (ACQ) symptom score. MEASUREMENTS AND MAIN RESULTS Mean ACQ change (SE) was -0.49 (0.09) in placebo (n = 74), and -0.43 (0.11), -0.58 (0.12), and -0.70 (0.09) in the AMG 317 75 mg (n = 73), 150 mg (n = 73), and 300 mg (n = 74) groups, respectively (treatment effect P = 0.25). No statistically significant differences were observed in the secondary endpoints. Numerical decreases in number of and time to exacerbations were noted in patients receiving AMG 317 150 mg and 300 mg. Preplanned analyses by tertile of baseline ACQ revealed that patients with higher baseline ACQ scores (>or=2.86) were more likely to respond to AMG 317. Serious adverse events were reported in three patients, each noted as not related to study drug. CONCLUSIONS AMG 317 did not demonstrate clinical efficacy across the overall group of patients. Clinically significant improvements were observed in several outcome measures in patients with higher baseline ACQ scores. AMG 317 was safe and well tolerated in this study population. Clinical trial registered with www.clinicaltrials.gov (NCT 00436670).

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008

J. Bousquet, N. Khaltaev, A. A. Cruz, J. Denburg, W. J. Fokkens, A. Togias, T. Zuberbier, C. E. Baena-Cagnani, G. W. Canonica, C. van Weel, I. Agache, N. A t-Khaled, C. Bachert, M. S. Blaiss, S. Bonini, L.-P. Boulet, P.-J. Bousquet, P. Camargos, K.-H. Carlsen, Y. Chen, A. Custovic, R. Dahl, P. Demoly, H. Douagui, S. R. Durham, R. Gerth van Wijk, O. Kalayci, M. A. Kaliner, Y.-Y. Kim, M. L. Kowalski, P. Kuna, L. T. T. Le, C. Lemiere, J. Li, R. F. Lockey, S. Mavale-Manuel , E. O. Meltzer, Y. Mohammad, J. Mullol, R. Naclerio, R. E. O Hehir, K. Ohta, S. Ouedraogo, S. Palkonen, N. Papadopoulos, G. Passalacqua, R. Pawankar, T. A. Popov, K. F. Rabe, J. Rosado-Pinto, G. K. Scadding, F. E. R. Simons, E. Toskala, E. Valovirta, P. van Cauwenberge, D.-Y. Wang, M. Wickman, B. P. Yawn, A. Yorgancioglu, O. M. Yusuf, H. Zar Review Group: I. Annesi-Maesano, E. D. Bateman, A. Ben Kheder, D. A. Boakye, J. Bouchard, P. Burney, W. W. Busse, M. Chan-Yeung, N. H. Chavannes, A. Chuchalin, W. K. Dolen, R. Emuzyte, L. Grouse, M. Humbert, C. Jackson, S. L. Johnston, P. K. Keith, J. P. Kemp, J.-M. Klossek, D. Larenas-Linnemann, B. Lipworth, J.-L. Malo, G. D. Marshall, C. Naspitz, K. Nekam, B. Niggemann, E. Nizankowska-Mogilnicka, Y. Okamoto, M. P. Orru, P. Potter, D. Price, S. W. Stoloff, O. Vandenplas, G. Viegi, D. Williams

Prevalence of allergic rhinitis in the United States

The study objective was to examine the current national prevalence of allergic rhinitis by gender, age, geographic region, population density (urban/rural), and household income. A self-administered questionnaire was sent to 15,000 households representative of the U.S. population in respect to these factors. The household member who knew the most about the familys health status and health history in the previous 12 months was asked to estimate the number of days during which household members had experienced sneezing, runny nose, stuffy nose or head, itchy eyes, or watery eyes. They were also asked about physician diagnosis of hay fever, rhinitis, persistent stuffy nose or head, or allergies involving the eyes, nose, or throat. The 9946 households responding (66.3%) represented 22,285 persons, 8394 of whom had experienced the symptoms described. In a follow-up questionnaire sent to a balanced sample of 1450 responders (>90% white, slightly more females than males), subjects were asked to indicate which of the following best described their symptoms: a common cold; a seasonal allergy (i.e., hay fever); an allergy I have all the time; an allergy only when exposed to triggers (i.e., dust, pollution); or sinus problems. Of the 1065 subjects (73.4%) responding, 31.5% reported ≥7 days of nasal/ocular symptoms, and 17.7% reported ≥31 days of symptoms. Physician-diagnosed hay fever was reported by 8.2% and allergic rhinitis (seasonal plus perennial) by 14.2%. Prevalence was highest among those age 18 to 34 years and 35 to 49 years, decreasing after age 50 years. No major trends were evident with regard to other variables studied. Extrapolation based on 1993 census data suggests that at least 35.9 million persons have symptoms associated with allergic rhinitis and up to 79.5 million persons experience ≥7 days of nasal/ocular symptoms yearly.

Cetirizine in patients with seasonal rhinitis and concomitant asthma: prospective, randomized, placebo-controlled trial☆☆☆★★★

OBJECTIVE This study explored the safety and efficacy of cetirizine for treatment of allergic rhinitis and asthma. METHODS Daily treatment for 6 weeks with cetirizine 10 mg (93 patients) was compared with placebo treatment (93 patients) in a randomized, double-blind parallel study of patients with allergic rhinitis and asthma. This multicenter study was started just before onset of the fall pollen season. Rhinitis and asthma symptoms were assessed twice daily; spirometry was performed weekly. RESULTS Placebo-treated patients experienced a worsening of rhinitis symptoms from baseline throughout the study, whereas cetirizine-treated patients had a significant improvement in rhinitis symptoms at week 1, which was maintained after onset of the pollen season. Asthma symptoms in the cetirizine group improved from baseline at week 1; symptoms were significantly better than in the placebo group for 5 of 6 weeks of the study. Pulmonary function did not worsen in patients taking cetirizine or placebo; there were no differences between treatments as determined by spirometry. Albuterol use was less frequent in the cetirizine-treated patients for every week of the study, but differences did not reach significance. Pseudoephedrine use was similar in both groups. More cetirizine-treated patients (90%) completed the trial than did placebo-treated patients (74%). Both treatments were well tolerated. CONCLUSION Cetirizine 10 mg daily is safe and effective in relieving both upper and lower respiratory tract symptoms in patients with seasonal allergic rhinitis and concomitant asthma.

Rhinosinusitis Diagnosis and Management for the Clinician: A Synopsis of Recent Consensus Guidelines

Rhinosinusitis (RS) affects approximately 1 in 7 adults in the United States, and its effect on quality of life, productivity, and finances is substantial. During the past 10 years, several expert panels from authoritative bodies have published evidence-based guidelines for the diagnosis and management of RS and its subtypes, including acute viral RS, acute bacterial RS, chronic RS (CRS) without nasal polyposis, CRS with nasal polyposis, and allergic fungal RS. This review examines and compares the recommendations of the Rhinosinusitis Initiative, the Joint Task Force on Practice Parameters, the Clinical Practice Guideline: Adult Sinusitis, the European Position Paper on Rhinosinusitis and Nasal Polyps 2007, and the British Society for Allergy and Clinical Immunology. Points of consensus and divergent opinions expressed in these guidelines regarding classification, diagnosis, and management of adults with acute RS (ARS) and CRS and their various subtypes are highlighted for the practicing clinician. Key points of agreement regarding therapy in the guidelines for ARS include the efficacy of symptomatic treatment, such as intranasal corticosteroids, and the importance of reducing the unnecessary use of antibiotics in ARS; however, guidelines do not agree precisely regarding when antibiotics should be considered as a reasonable treatment strategy. Although the guidelines diverge markedly on the management of CRS, the diagnostic utility of nasal airway examination is acknowledged by all. Important and relevant data from MEDLINE-indexed articles published since the most recent guidelines were issued are also considered, and needs for future research are discussed.

Sleep, quality of life, and productivity impact of nasal symptoms in the United States: findings from the Burden of Rhinitis in America survey.

Rhinitis is a common chronic condition that has been shown in observational and interventional studies to have a substantial impact on the sufferer. This study was performed to describe the impact of symptoms of allergic rhinitis (AR) on sleep, quality of life, and productivity in a U.S. population. A cohort of AR sufferers and non-AR sufferers was assembled by screening a representative sample of 15,000 households with a self-administered questionnaire in January 2004. A subsample of respondents received a detailed follow-up questionnaire in the May/June pollen season. Of the 7024 individuals with complete data, 3831 met the case definition of AR sufferer; 3193 were non-AR sufferers. Overall, AR sufferers had consistently poorer average scores on the sleep, quality of life, cognition, and productivity scales compared with non-AR sufferers. Subjects with AR symptoms had more sleep impairment (51.2) compared with subjects with non-AR symptoms and those with no symptoms (59.8 and 63.3, respectively). Only 3.6% of subjects with AR symptoms experienced 100% sleep adequacy compared with 11.7% of subjects with non-AR symptoms and 19.2% of subjects with no symptoms. Quality of life and cognition scores were worse in subjects with AR symptoms compared with subjects with non-AR or no symptoms. Work and school productivity was significantly reduced in subjects with AR symptoms in the past 4 weeks compared with subjects with no symptoms (p < 0.05). Individuals who suffer from AR symptoms experience a substantial burden on their ability to sleep, quality of life, cognitive function, and school/workplace productivity.

The economic impact of allergic rhinitis and current guidelines for treatment

OBJECTIVE To describe the economic burden of allergic rhinitis treatment and current guidelines for treatment. DATA SOURCES Review articles and original research were retrieved from MEDLINE, OVID, PubMed (1950-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 the burden of allergic rhinitis and current guidelines for treatment. Publications included reviews, treatment guidelines, and clinical studies. RESULTS Despite the common symptoms of allergic rhinitis, its impact on patient quality of life, and the huge cost to society and individuals of treatment, including pharmacotherapy, many patients do not adhere to their medication regimens because the medications do not adequately address their symptoms or are otherwise problematic for them to use. CONCLUSIONS The economic impact of allergic rhinitis is substantial; the total direct medical cost of allergic rhinitis is approximately

Once-daily fexofenadine HCl improves quality of life and reduces work and activity impairment in patients with seasonal allergic rhinitis

3.4 billion, with almost half of this cost attributable to prescription medications. Multiple treatment options are available, and these were reviewed to provide an update on effectiveness and adverse effects that may affect patient adherence.

A dose-ranging study of fluticasone propionate aqueous nasal spray for seasonal allergic rhinitis assessed by symptoms, rhinomanometry, and nasal cytology

BACKGROUND Fexofenadine HCl (Allegra, Telfast) is approved in the US for twice-daily dosing for treatment of seasonal allergic rhinitis. OBJECTIVE To determine the effect of once-daily fexofenadine HCl on patient-reported quality of life and impairment at work, in the classroom, and in daily activities due to seasonal allergic rhinitis symptoms. METHODS This placebo-controlled, double-blind, randomized study included patients aged 12 to 65 years with moderate-to-severe seasonal allergic rhinitis symptoms. Outcomes were assessed using self-administered questionnaires at baseline, week 1, and week 2. Outcome measures included change from baseline in: overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score; individual RQLQ domain scores; work, classroom, and daily activity impairment measured using the Work Productivity and Activity Impairment (WPAI) instrument; and ratings in 3 generic health domains from the SF-36 Health Survey. RESULTS Intent to treat efficacy analyses included 845 patients from 40 sites. Patients receiving either 120 or 180 mg QD fexofenadine HCl reported significantly greater improvement (P < or = .006) in overall RQLQ score than patients receiving placebo. Similarly, both fexofenadine treatment groups reported significantly greater reductions in overall work impairment and daily activity impairment compared with the placebo group (P < or = .004). There was a trend for improvement in classroom impairment with fexofenadine treatment, although differences from placebo were not statistically significant. Generic health measures demonstrated fexofenadine HCl treatment had a positive effect on general health. CONCLUSION Once-daily fexofenadine HCl, 120 or 180 mg, significantly improved patient-reported quality of life and reduced performance impairment in work and daily activities due to seasonal allergic rhinitis symptoms compared with placebo.