Abstracts from the North American Rhinology & Allergy Conference, February 3, 2011, Puerto Rico.

INTRODUCTION: To establish the efficacy of bepotastine besilate ophthalmic solution (bepotastine) 1.5%, a dual acting histamine H1 receptor antagonist approved for treatment of ocular itching associated with allergic conjunctivitis, compared to placebo in relieving ocular itching and redness for subjects with active allergic rhinoconjunctivitis. METHODS: A randomized, double-masked, placebo-controlled, confirmatory natural exposure study of bepotastine 1.5% and placebo was conducted during allergy season at 12 clinical sites throughout the U.S. Following a 7-day screening period, eligible subjects ≥12 years old were assigned in a 1:1 ratio to dosing OU b.i.d. either bepotastine 1.5% (n = 123) or placebo (n = 122). Subjects recorded instantaneous grades for their ocular symptoms prior to their next dose for 14 consecutive days. Clinically significant reduction in ocular sign or symptom grades between treatment groups required p ≤ 0.05 as determined by ANCOVA analysis. RESULTS: Significant clinical effectiveness with bepotastine 1.5% was demonstrated over the 2-week treatment period in comparison to placebo in the intent-to-treat population for reducing mean instantaneous grades for both ocular itching (p = 0.007) and redness (p = 0.001). Investigator rating of efficacy over the 2-week treatment period across response categories was also superior for bepotastine 1.5% compared to placebo (p = 0.024). Only one subject discontinued participation in the study due to an adverse event. CONCLUSIONS: These data support bepotastine 1.5% as an effective treatment for allergen-induced signs and symptoms in a clinical study designed to closely resemble the conditions under which patients with allergic rhinoconjunctivitis would require treatment.

Efficacy and safety of formoterol for the treatment of chronic obstructive pulmonary disease.

Formoterol is a selective long-acting beta2-adrenergic receptor agonist (LABA) that provides significant and sustained bronchodilatory effect for up to 12h following a single dose. The onset of effect is significantly faster with formoterol compared with an alternative LABA, salmeterol, although both have a similar duration of action. The overall efficacy of formoterol in improving lung function and controlling symptoms of chronic obstructive pulmonary disease (COPD) is comparable to that of salmeterol and potentially superior to that of ipratropium or theophylline. Formoterol provides additional benefit when administered in combination with other bronchodilators or inhaled corticosteroids. In clinical studies, formoterol was well tolerated and had an adverse-event profile similar to that of other beta2-adrenergic receptor agonists. Formoterol is a rapidly acting, well-tolerated, effective beta2-adrenergic receptor agonist that can be regularly used as a long-acting bronchodilator for patients with moderate to severe COPD, as per recommendations of the current treatment guidelines.

Treatment update: allergic rhinitis.

In addition to the introduction of several new pharmacologic agents, two of the most significant recent developments in the management of allergic rhinitis have been the renewed emphasis on preventive measures, such as allergen avoidance and immunotherapy, and the importance of performing an accurate differential diagnosis of the disease. Recently, these evolving management trends were delineated in an algorithm proposed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, which suggests that an initial evaluation be performed by a primary care physician. Based on findings at the initial evaluation, the patient should be treated either empirically in the primary care setting or referred to an allergist-immunologist for consultation. The allergist uses an evidence-based therapeutic approach based on a differential diagnosis of the type of rhinitis, which uses information derived from a detailed medical history, physical examination of the airway, and ancillary tests, particularly skin tests. Rhinitis management by an allergist emphasizes a three-pronged approach that incorporates avoidance, immunotherapy, and pharmacologic therapy. However, because both avoidance and immunotherapy have their limitations, pharmacologic therapy remains the mainstay of rhinitis management, and allergists usually recommend that optimal first-line therapy be broad based and capable of safely alleviating the symptoms of both allergic and nonallergic disease. First generation oral antihistamines, topical corticosteroids and the topical antihistamine azelastine are the most broad-based treatments available. Second-generation oral antihistamines and leukotriene antagonists also are useful in treating allergic rhinitis.

Allergic rhinitis in children.

Epidemiologic and pathophysiologic evidence indicates that allergic rhinitis, whether seasonal or perennial, is one piece of a larger atopic clinical picture that often occurs concomitantly with asthma. Allergic rhinitis usually develops during childhood and has a prevalence of up to 40% in the pediatric population. Careful attention to food allergies and the presence of household allergens during infancy and early childhood may limit potential sensitizations. Many antihistamines and topical corticosteroids now are available for the treatment of allergic rhinitis in children, which is all the more important because optimal management may improve quality of life and curtail the development of serious sequelae.

Clinical trials results of a unique monoclonal antibody in asthma.

IgE binds to high affinity receptors (Fc epsilon RI) on mast cells, basophils, alveolar macrophages, and antigen-presenting cells. This results in the degranulation of effector cells and the release of mediators, such as histamine, leukotrienes, cytokines, that are causally linked to the pathophysiology of allergic asthma. It made for an attractive target for the development of a unique humanized monoclonal antibody, rhuMAb-E25 (E25). E25 offers a novel strategic approach to allergy treatment, it is expected that using E25 to significantly decrease IgE levels will result in improved control of allergic asthma.

Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.

OBJECTIVES: To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL). DESIGN: Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids. INTERVENTIONS: FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid. MEASUREMENTS AND RESULTS: Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid. CONCLUSION: In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.

Double-blind trials of azelastine nasal spray monotherapy versus combination therapy with loratadine tablets and beclomethasone nasal spray in patients with seasonal allergic rhinitis. Rhinitis Study Groups.

BACKGROUND: Azelastine hydrochloride is an H1-receptor antagonist with antiinflammatory properties that is available in the US as Astelin Nasal Spray for the treatment of seasonal allergic rhinitis. The symptoms of seasonal allergic rhinitis can initially be treated with monotherapy using either an antihistamine or an intranasal corticosteroid. Patients whose symptoms do not respond adequately are often prescribed a combination of both an antihistamine and an intranasal corticosteroid. OBJECTIVE: Three multicenter, randomized, double-blind studies were conducted to determine whether patients with moderate-to-severe symptoms of seasonal allergic rhinitis who had responded inadequately to monotherapy with either an oral antihistamine or an intranasal corticosteroid, and who were candidates for combination therapy with both an oral antihistamine and an intranasal corticosteroid, could be effectively treated with azelastine nasal spray monotherapy. METHODS: Following a 1- to 2-week washout period, patients were randomized to 7 days of double-blind treatment with either azelastine nasal spray (2 sprays per nostril bid, 1.1 mg/day) monotherapy or combination therapy with oral loratadine (Claritin, one 10-mg tablet/day) plus intranasal beclomethasone dipropionate monohydrate (Beconase AQ, 2 sprays per nostril bid, 336 microg/day). Efficacy was determined at the end of the study by both a physician assessment of the need for additional anti-rhinitis medication and a patient global evaluation of therapeutic effectiveness. The three studies were conducted at 71 investigational sites during the 1998 spring allergy season. Three separate studies were conducted to verify the reproducibility of the new study design. RESULTS: In all three studies a total of 1,070 patients were randomized to double-blind treatment. There were no statistically significant differences in the percentage of patients treated with azelastine nasal spray versus patients treated with a combination of loratadine tablets and beclomethasone nasal spray who did not require additional anti-rhinitis medication (32% to 45% and 39% to 46%, respectively). The patient global evaluation indicated that 77% to 84% of the patients treated with azelastine nasal spray had symptomatic improvement and 85% to 90% of the patients treated with loratadine tablets and beclomethasone nasal spray had symptomatic improvement. The most commonly reported adverse experience with azelastine nasal spray was a transient aftertaste (8%), while the most commonly reported adverse experience with loratadine tablets and beclomethasone nasal spray in combination was headache (6%). CONCLUSIONS: Based on the percentage of patients not requiring additional antirhinitis medication and the patient assessment of efficacy, azelastine nasal spray monotherapy was as effective as the combination of oral loratadine plus intranasal beclomethasone in treating moderate-to-severe symptoms of seasonal allergic rhinitis.

A dose-ranging study of mometasone furoate aqueous nasal spray in children with seasonal allergic rhinitis.

BACKGROUND: The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 microg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized. OBJECTIVE: This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population. METHODS: This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 microgram once daily, MFNS 100 microgram once daily, MFNS 200 microgram once daily, beclomethasone dipropionate 84 microgram twice daily (168 microgram/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29. RESULTS: The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group (P

Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.

BACKGROUND: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use. OBJECTIVE: This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma. METHODS: Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria. RESULTS: Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P

Algorithm for the diagnosis and management of asthma: a practice parameter update: Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology.

This algorithm on the diagnosis and treatment of asthma is intended to complement and update the previously published Practice Parameters for the Diagnosis and Treatment of Asthma. Both documents were developed by the Joint Task Force on Practice Parameters, representing the AAAAI, ACAAI, and the JCAAI. The authors of this asthma algorithm have attempted to include all the elements essential for the diagnosis and care of patients with asthma. Every effort was made to keep the algorithm clear and concise, yet thorough and complete (Fig 1). Each component of the algorithm is elaborated further in a brief annotation. For further discussion, the reader is referred to the more extensive Practice Parameters for the Diagnosis and Treatment of Asthma.

Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma.

BACKGROUND: Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children. However, data regarding therapy with this class of compounds, especially in children under age 6 years, is limited. Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index. Few large prospective clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children. OBJECTIVE: We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma. METHODS: Fluticasone propionate powder (50 microg or 100 microg twice daily) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children (4 to 11 years old) with persistent asthma for 12 weeks in a randomized, double-blind, parallel-group, multi-center trial. Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone. RESULTS: Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 (mean increase from baseline of 0.22 to 0.24 L; p < or = 0.023), clinic morning peak expiratory flow (mean increase from baseline of 48 to 55 L/min; p < or = 0.006), patient-measured morning (p < or = 0.001) and evening (p < or = 0.003) peak expiratory flow, and asthma symptom scores (in all but the 50 microg Diskus group; p < or = 0.036), as well as reduced albuterol use (p < or = 0.002) and nighttime awakenings (p < or = 0.019) at endpoint. Efficacy parameters were not significantly different between the two doses with either device. More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group (p < 0.001). Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion. Adverse events were primarily pharmacologic effects of inhaled corticosteroids, and those related to the study drug occurred with low frequency. Patient satisfaction with both the Diskus and Diskhaler devices was high, with a majority of patients (> 80%) rating them favorably. CONCLUSION: This study demonstrated that fluticasone propionate powder, at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler, was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone.

Fluticasone propionate powder administered through Diskhaler versus triamcinolone acetonide aerosol administered through metered-dose inhaler in patients with persistent asthma.

BACKGROUND: Attempts to delineate efficacy and safety differences among inhaled corticosteroids have been difficult because of the lack of well-controlled, comparative studies reported in the medical literature. METHODS: A randomized, double-blind, double-dummy study was conducted in 24 outpatient centers. A total of 291 male and female patients at least 12 years of age with asthma (FEV1 between 50% and 80% of predicted value), who had previously received maintenance therapy with beclomethasone dipropionate or triamcinolone acetonide, were switched to treatment with fluticasone propionate powder (250 microg twice daily), triamcinolone acetonide aerosol (200 microg four times daily), or placebo for 24 weeks. RESULTS: Mean increase in FEV1 from baseline to end point was significantly (p = 0.009) greater in patients switched to treatment with fluticasone compared with patients switched to treatment with triamcinolone (0.27 L and 0.07 L, respectively). At end point, mean increase in morning peak expiratory flow from baseline was 21 L/min with fluticasone compared with mean decreases of 6 L/min and 28 L/min with triamcinolone and placebo, respectively (p < 0.001 vs triamcinolone and placebo). Supplemental rescue albuterol use decreased by 30% from baseline with fluticasone (p < 0.05 vs triamcinolone and placebo) compared with triamcinolone (6%) or placebo (increased by 50%). The percentage of patients withdrawn from the study because they met predefined lack-of-efficacy criteria was higher with placebo (60%) and triamcinolone (27%) than with fluticasone (17%). Incidence of adverse events and low morning plasma cortisol concentrations were similar across treatment groups except for oral candidiasis (p = 0.035, fluticasone vs placebo). CONCLUSION: Fluticasone propionate powder twice daily (500 microg/day) was superior in efficacy to triamcinolone acetonide aerosol four times daily (800 microg/day) in patients with persistent asthma.

A case-management system for coronary risk factor modification after acute myocardial infarction.

OBJECTIVE: To evaluate the efficacy of a physician-directed, nurse-managed, home-based case-management system for coronary risk factor modification. DESIGN: Randomized clinical trial in which patients received a special intervention (n = 293) or usual medical care (n = 292) during the first year after acute myocardial infarction. SETTING: 5 Kaiser Permanente Medical Centers in the San Francisco Bay area. PATIENTS: 585 men and women aged 70 years or younger who were hospitalized for acute myocardial infarction. INTERVENTION: In the hospital, specially trained nurses initiated interventions for smoking cessation, exercise training, and diet-drug therapy for hyperlipidemia. Intervention after discharge was implemented primarily by telephone and mail contact with patients in their homes. All medically eligible patients received exercise training; all smokers received the smoking cessation intervention; and all patients received dietary counseling and, if needed, lipid-lowering drug therapy. OUTCOME: Smoking prevalence and plasma low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months after infarction, and functional capacity was measured 6 months after infarction. RESULTS: In the special intervention and usual care groups, the cotinine-confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL cholesterol levels were 2.77 +/- 0.69 mmol/L and 3.41 +/- 0.90 mmol/L (107 +/- 30 mg/dL and 132 +/- 30 mg/dL) (P = 0.001), and functional capacities were 9.3 +/- 2.4 METS and 8.4 +/- 2.5 METS (P = 0.001), respectively. CONCLUSION: In a large health maintenance organization, a case-management system was considerably more effective than usual medical care for modification of coronary risk factors after myocardial infarction.

Return to work after uncomplicated myocardial infarction: a trial of practice guidelines in the community.

OBJECTIVE: To evaluate the effectiveness of practice guidelines for return to work after acute myocardial infarction when disseminated from a university-based setting to a practice-based setting. DESIGN: Randomized clinical trial. PATIENTS: A total of 187 patients with uncomplicated acute myocardial infarction. INTERVENTION: Patients were randomly assigned to the intervention (n = 95) or to usual care (n = 92). The intervention consisted of a treadmill test, a counseling session based on the test results, and a consultation letter from a cardiologist to the primary care physician. Individualized recommendations for the timing of return to work, contained in the consultation letter, were based on the patient's risk for recurrent cardiac events. MEASUREMENTS: Questionnaire, chart review, and a phone interview documented the timing of return to work and the rates of cardiac death, coronary angioplasty, coronary artery surgery, and recurrent myocardial infarction. RESULTS: Median intervals between acute myocardial infarction and return to work were similar in both groups (intervention, 54 days; usual care, 67 days; P greater than 0.2). Among patients without myocardial ischemia, however, the interval was shorter in the intervention group than in the usual care group (38 days compared with 65 days, respectively, P = 0.008). Among patients with myocardial ischemia, intervals were similar in both groups (80 days compared with 76 days, respectively, P greater than 0.2). CONCLUSION: Practice guidelines developed in a university-based setting were not as successful in hastening return to work after uncomplicated acute myocardial infarction when tested in a practice-based setting. Physicians' reluctance to follow guidelines for patients with myocardial ischemia reflected their concern with prognosis even though medical outcome was good.

Skin testing compared with in vitro testing for screening allergic patients.

A new FDA-cleared product has been introduced for screening suspected allergic patients using a small blood sample. The QUIDEL Allergen Screens (AS) are simple to use dipstick tests that measure allergen-specific IgE to ten of the most important regional allergens. We compared the results obtained by prick-puncture skin testing (ST) to those obtained with the AS on 103 patients with allergic symptoms. Of the 103 patients studied, there were 67 with positive skin tests, and 57 of those were positive by AS and ten were AS negative. Of the 36 with negative skin tests, 2 were positive by AS and 34 were AS negative. Compared with ST, the AS results gave a sensitivity of 85% and a specificity of 94% for identifying the allergic patient. Of the ten patients positive by ST but negative by AS, five were ST positive at the 1+ level; the other five were repeatedly negative by AS and confirmed negative by RAST. On an allergen basis, the ST and AS methods showed an 85% agreement. A subset of 24 patients from the foregoing group was studied for total IgE and allergen-specific IgE with products from both Pharmacia (P) and QUIDEL (Q). In this group of patients, skin test results gave seven patients negative and 18 patients positive to one or more allergens. While the overall Total IgE results were higher for ST patients, the Total IgE results alone did not effectively discriminate between ST-positive and ST-negative patients. The allergen-specific, however, results by both methods showed excellent agreement with the ST results.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-benefit analysis of early return to work after uncomplicated acute myocardial infarction.

The economic consequences of an Occupational Work Evaluation designed to identify low risk patients recovering from uncomplicated acute myocardial infarction (AMI) and hasten their return to work was evaluated in a randomized trial. Two hundred one employed, clinically low risk men recovering from AMI were randomized to undergo an intervention (intervention group, 99 patients) consisting of an Occupational Work Evaluation or to receive usual care (usual care group, 102 patients). The time to return to work was reduced from 75 days in usual care patients to 51 days in intervention patients (p less than 0.002). Significant differences were found between groups for medical costs and occupational income during follow-up. Total medical costs per patient were lower in the intervention patients than in the usual care patients in the 6 months after AMI ($2,970 vs $3,472). Occupational income per patient was higher in intervention patients than in the usual care group in the 6 months after AMI ($9,655 vs $7,553). The per capita benefit accounting for medical costs and occupational income was $6,685 for intervention patients and $4,081 for usual care patients. Projected to the greater than 300,000 low risk, employed survivors of AMI annually in this country, the savings generated by the Occupational Work Evaluation could yield an annual economic benefit greater than 800 million dollars.