Robert A. Nathan

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.

Growth in asthmatic children treated with fluticasone propionate

OBJECTIVE To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma. STUDY DESIGN In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year. Growth was evaluated monthly, whereas other safety variables and pulmonary function were evaluated periodically. RESULTS The prepubescent patients showed no statistically significant differences in mean height, mean growth velocity, or mean skeletal age between any of the treatment groups at any time. Over a period of 1 year, mean height (+/- SE) increased 6.15 +/- 0.17 cm in the placebo group, 5.94 +/- 0.16 cm in the fluticasone propionate 50 microg group, and 5.73 +/- 0.13 cm in the fluticasone propionate 100 microg group (p = 0.308, overall). CONCLUSIONS Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age.

Objective monitoring of nasal patency and nasal physiology in rhinitis

Nasal obstruction can be monitored objectively by measurement of nasal airflow, as evaluated by nasal peak flow, or as airways resistance/conductance as evaluated by rhinomanometry. Peak flow can be measured during inspiration or expiration. Of these measurements, nasal inspiratory peak flow is the best validated technique for home monitoring in clinical trials. The equipment is portable, relatively inexpensive, and simple to use. One disadvantage, however, is that nasal inspiratory peak flow is influenced by lower airway as well as upper airway function. Rhinomanometry is a more sensitive technique that is specific for nasal measurements. The equipment, however, requires an operator, is more expensive, and is not portable. Thus, it is applicable only for clinic visit measures in clinical trials. Measurements require patient cooperation and coordination, and not all can achieve repeatable results. Thus, this objective measure is best suited to laboratory challenge studies involving smaller numbers of selected volunteers. A nonphysiological measure of nasal patency is acoustic rhinometry. This sonic echo technique measures internal nasal luminal volume and the minimum cross-sectional area. The derivation of these measures from the reflected sound waves requires complex mathematical transformation and makes several theoretical assumptions. Despite this, however, such measures correlate well with the nasal physiological measures, and the nasal volume measures have been shown to relate well to results obtained by imaging techniques such as computed tomography scanning or magnetic resonance imaging. Like rhinomanometry, acoustic rhinometry is not suitable for home monitoring and can be applied only to clinic visit measures or for laboratory nasal challenge monitoring. It has advantages in being easy to use, in requiring little patient cooperation, and in providing repeatable results. In addition to nasal obstruction, allergic rhinitis is recognized to be associated with impaired mucociliary clearance and altered nasal responsiveness. Measures exist for the monitoring of these aspects of nasal dysfunction. Although measures of mucociliary clearance are simple to perform, they have a poor record of reproducibility. Their incorporation into clinical trials is thus questionable, although positive outcomes from therapeutic intervention have been reported. Measures of nasal responsiveness are at present largely confined to research studies investigating disease mechanisms in allergic and nonallergic rhinitis. The techniques are insufficiently standardized to be applied to multicenter clinical trials but could be used in limited-center studies to gain insight into the regulatory effects of different therapeutic modalities.

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.

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

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.

Efficacy and Safety of Fexofenadine Hydrochloride for Treatment of Seasonal Allergic Rhinitis

BACKGROUND H1-receptor antagonists are effective for the treatment of seasonal allergic rhinitis. In rare circumstances, some second-generation H1-receptor antagonists have been associated with prolongation of the corrected QT interval (QTc), thus increasing the risk of ventricular arrhythmias. Fexofendine HCl, the carboxylic acid metabolite of terfenadine, is a new second-generation antihistamine that is nonsedating and does not cause electrocardiographic effects. OBJECTIVE To investigate the clinical efficacy and safety of fexofenadine HCl in the treatment of ragweed seasonal allergic rhinitis and to characterize the dose-response relationship of fexofenadine HCl at dosages of 60, 120, and 240 mg bid. METHODS A multicenter, 14-day, placebo-controlled, double-blind trial was conducted with patients suffering from moderate to severe ragweed seasonal allergic rhinitis who met symptom severity criteria after a 3-day placebo baseline period. Patients with minimal or very severe symptoms during the baseline period were excluded. Patients were randomized to receive fexofenadine HCl (60, 120, or 240 mg bid) or placebo at 12-hour dosing intervals (7:00 AM and 7:00 PM). The primary efficacy measure was patient-assessed 12-hour reflective total symptom score before the evening dose (trough). RESULTS Five hundred seventy patients completed the trial. Fexofenadine HCl at each dosage provided significant improvement in total symptom score (P < or = .003) and in all individual nasal symptoms compared with placebo. The frequency of adverse events was similar among fexofenadine HCl and placebo groups, with no dose-related trends. No sedative effects or electrocardiographic abnormalities, including prolongations in QTc were detected. CONCLUSIONS Fexofenadine HCl is both effective and safe for the treatment of ragweed seasonal allergic rhinitis. Because there was no additional efficacy at higher dosages, 60 mg bid appears to be the optimal therapeutic dosage for these patients.

The prevalence of nasal symptoms attributed to allergies in the United States: findings from the burden of rhinitis in an America survey.

Although the annual prevalence of physician-diagnosed hay fever has been previously reported, the prevalence of allergic rhinitis symptoms in the United States is uncertain. The purpose of this study was to estimate the prevalence of allergic rhinitis symptoms in the United States. A self-administered 10-item screening questionnaire regarding nasal symptoms was sent to representative households in the United States in January 2004. A total of 8,708 members (44.3%) reported nasal symptoms on > or =7 days in the past 12 months. The majority of these responders described their symptoms as seasonal or perennial allergies (n = 5,944) compared with cold or flu only (n = 1,841), cold or flu and vasomotor rhinitis (n = 175), or vasomotor rhinitis only (n = 748). The prevalence of self-reported seasonal and perennial allergic rhinitis symptoms on > or =7 days in the past 12 months was 30.2%, which corresponds to 89.6 million persons in the United States. The prevalence of self-reported physician-diagnosed seasonal or perennial allergic rhinitis with symptoms on > or =7 days was 22%, or approximately 65 million persons nationwide. Among responders with a higher burden of nasal symptoms (> or =30 days), the prevalence of physician-diagnosed hay fever, allergic rhinitis, or nasal allergies was 11.9% of the total population. The prevalence of nasal symptoms attributed to rhinitis related to seasonal and perennial allergies in the United States ranged between 11.9 and 30.2% depending on duration of symptoms and physician diagnosis. Almost one-half of Americans experience troublesome nasal symptoms on at least 7 days throughout the year, with most attributing their symptoms to allergies.

Quality of life and rhinitic symptoms: Results of a nationwide survey with the SF-36 and RQLQ questionnaires

Health care delivery is increasingly driven by results of outcomes studies. The best single instrument or combination of instruments for measurement of outcome in patients with symptoms of rhinitis has not been determined. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), a generic instrument, and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), a disease-specific instrument, have both been used. We carried out a population-based study in 312 subjects with nasal/ocular symptoms who filled out both questionnaires. We then compared their responses with those of healthy controls. Statistically significant differences between patients and controls were observed in seven of nine dimensions in the SF-36 questionnaire and in all of the seven dimensions and the aggregate score of the RQLQ. In all cases, the direction of the changes in health status indicated impairment of quality of life, particularly in ability to perform normal physical roles. Patients were troubled by repeated nose blowing, had a disrupted sleep pattern, were fatigued, and had a reduced ability to concentrate. We conclude that these outcomes should be incorporated into clinical trials, effectiveness research, and therapeutic strategies.

The economic impact of allergic rhinitis

Allergic rhinitis is the most common chronic allergic disease. Symptoms include continuous or periodic nasal congestion, rhinorrhea, sneezing, itching of the nose and eyes, generalized malaise, irritability, and fatigue. We conducted an evaluation of the costs related to management of allergic rhinitis in a U.S. population. Data are based on self-reported trends in medication and health care services usage from a nationwide population sample selected from a base of 15,000 households. The average per-patient expenditure for prescription medications was

Fluticasone Propionate Nasal Spray Is Superior to Montelukast for Allergic Rhinitis While Neither Affects Overall Asthma Control

56 yearly. The mean per-patient expenditure for nonprescription medications was