RationaleAttempt to demonstrate nasal fluticasone propionate 200 μg daily (FP200QD) for 14 days is superior to placebo in relieving ocular symptoms.MethodsThis was a randomized, double-blind, parallel group, multicenter study comparing FP200QD with placebo in patients (n = 626, age 12 to 79 years) with seasonal allergic rhinitis. The primary endpoint was change from baseline in patient-rated reflective Total Ocular Symptoms Score (rTOSS). Secondary endpoints included change from baseline in the am and pm rTOSS, end-of-treatment assessment of response, and daily activities impact. Primary analysis was analysis of covariance (linear fixed-effects mode).ResultsFP200QD was more efficacious in ocular symptoms relief than placebo utilizing primary endpoint (difference = -0.36, p = 0.0024). It improved am and pm rTOSS vs placebo (AM: difference = -0.33, p = 0.0057; PM: difference = -0.41, p = 0.0009). More patients on FP200QD reported overall improvement at end of treatment (177 vs 146 in placebo, p = 0.0118). FP200QD significantly improved daily activities as measured by MiniRQLQ (p<0.0001) and was well tolerated.ConclusionsThe study results support that FP200QD relieves ocular symptoms in AR. RationaleAttempt to demonstrate nasal fluticasone propionate 200 μg daily (FP200QD) for 14 days is superior to placebo in relieving ocular symptoms. Attempt to demonstrate nasal fluticasone propionate 200 μg daily (FP200QD) for 14 days is superior to placebo in relieving ocular symptoms. MethodsThis was a randomized, double-blind, parallel group, multicenter study comparing FP200QD with placebo in patients (n = 626, age 12 to 79 years) with seasonal allergic rhinitis. The primary endpoint was change from baseline in patient-rated reflective Total Ocular Symptoms Score (rTOSS). Secondary endpoints included change from baseline in the am and pm rTOSS, end-of-treatment assessment of response, and daily activities impact. Primary analysis was analysis of covariance (linear fixed-effects mode). This was a randomized, double-blind, parallel group, multicenter study comparing FP200QD with placebo in patients (n = 626, age 12 to 79 years) with seasonal allergic rhinitis. The primary endpoint was change from baseline in patient-rated reflective Total Ocular Symptoms Score (rTOSS). Secondary endpoints included change from baseline in the am and pm rTOSS, end-of-treatment assessment of response, and daily activities impact. Primary analysis was analysis of covariance (linear fixed-effects mode). ResultsFP200QD was more efficacious in ocular symptoms relief than placebo utilizing primary endpoint (difference = -0.36, p = 0.0024). It improved am and pm rTOSS vs placebo (AM: difference = -0.33, p = 0.0057; PM: difference = -0.41, p = 0.0009). More patients on FP200QD reported overall improvement at end of treatment (177 vs 146 in placebo, p = 0.0118). FP200QD significantly improved daily activities as measured by MiniRQLQ (p<0.0001) and was well tolerated. FP200QD was more efficacious in ocular symptoms relief than placebo utilizing primary endpoint (difference = -0.36, p = 0.0024). It improved am and pm rTOSS vs placebo (AM: difference = -0.33, p = 0.0057; PM: difference = -0.41, p = 0.0009). More patients on FP200QD reported overall improvement at end of treatment (177 vs 146 in placebo, p = 0.0118). FP200QD significantly improved daily activities as measured by MiniRQLQ (p<0.0001) and was well tolerated. ConclusionsThe study results support that FP200QD relieves ocular symptoms in AR. The study results support that FP200QD relieves ocular symptoms in AR.

Background: Allergic rhinitis (AR) is an inflammatory condition of the nasal mucosa characterized by symptoms of nasal discharge, itching, sneezing, and congestion. Ocular symptoms are commonly associated with AR and include itching or burning, tearing or watering, and redness. Intranasal corticosteroids are a mainstay of treatment, and their effect on nasal symptoms is well described.Objective: To demonstrate that a 14-day course of 200 mg/d of nasal fluticasone propionate is superior to placebo in relieving ocular symptoms associated with AR.Methods: This was a randomized, double-blind, parallel group, multicenter study comparing 200 mg/d of fluticasone propionate with placebo in patients with seasonal allergic rhinitis. The primary end point was mean change from baseline in patient-rated reflective total ocular symptom score (rTOSS). Key secondary end points included mean change from baseline in the morning and evening rTOSS, end-of-treatment assessment of response, and effect on activities of daily living. The primary analysis was performed using analysis of covariance with a linear fixed-effects model.Results: Fluticasone was statistically significantly more efficacious in reducing the ocular symptoms of AR than placebo. The least squares mean difference in the change from baseline of rTOSS was -0.36 (P=.002). A statistically significant difference in mean change from baseline was observed in favor of fluticasone for morning and evening rTOSS. Significantly more patients taking fluticasone achieved an overall response compared with placebo. Fluticasone had a significantly greater effect on daily living activities and was well tolerated.Conclusion: This study supports the efficacy of fluticasone in treating ocular symptoms associated with AR. Trial Registration: clinicaltrials.govIdentifier: NCT01817790. (C) 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A nasal aerosol formulation of ciclesonide with a hydrofluoroalkane propellant (CIC-HFA) is currently in development for treatment of allergic rhinitis (AR). This study evaluated the efficacy and safety of once-daily administration of CIC-HFA 74 or 148 micrograms compared with placebo in patients with seasonal AR (SAR) from mountain cedar pollen. Patients ≥12 years of age with a ≥2-year history of SAR from mountain cedar pollen were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 micrograms, CIC-HFA 148 micrograms, or placebo once daily in the morning for 2 weeks. Change from baseline in reflective total nasal symptom score (rTNSS), instantaneous TNSS (iTNSS), and reflective total ocular symptom score (rTOSS) in patients with baseline rTOSS ≥5.00 were evaluated. Adverse events (AEs) were monitored throughout the study. A statistically significant improvement in rTNSS (least squares [LS] mean change from baseline 1.04 and 1.02 respectively; p < 0.0001 versus placebo for both) and iTNSS (LS mean change from baseline 0.90 and 0.83 respectively; p < 0.001 vs placebo for both) was observed after treatment with CIC-HFA 74- or 148-microgram doses. Only the CIC-HFA 74-micrograms treatment group showed a statistically significant improvement in rTOSS (LS mean change from baseline 0.52; p = 0.0124) compared with placebo. The overall incidence of AEs was low and comparable between the treatment groups. In this study, statistically significant improvements in nasal symptoms of SAR were observed after treatment with CIC-HFA 74-microgram or CIC-HFA 148-microgram doses. Both active treatments were well tolerated. Clinical trial registry URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01010971.

A previous study with azelastine nasal spray in patients with seasonal allergic rhinitis (SAR) demonstrated that increasing the azelastine concentration from 0.1% to 0.15% allowed for once‐daily dosing without increasing the incidence of adverse effects. This study evaluated the efficacy of azelastine 0.15% nasal spray administered once daily for treating symptoms of SAR.

Azelastine nasal spray is commercially available as a 0.1% w/v solution and is recommended for twice-daily dosing. Increasing the azelastine concentration to 0.15% may be effective with once-daily dosing without increasing the incidence of adverse events. This study evaluated the efficacy and safety of azelastine 0.15% nasal spray at a dosage of 2 sprays/nostril once daily. This randomized, double-blind, placebo-controlled study was conducted in subjects with moderate-to-severe seasonal allergic rhinitis (SAR) during the 2007/2008 Texas Mountain Cedar season. In total, 536 subjects were randomized to 2 sprays/nostril once daily (A.M.) of azelastine 0.15% or placebo. The primary efficacy variable was change from baseline in a 12-hour reflective Total Nasal Symptom Score (TNSS), consisting of nasal congestion, runny nose, itchy nose, and sneezing. The key secondary variable was change from baseline in 24-hour instantaneous TNSS, which determines the duration of action and effective dosing interval. After 2 weeks, the mean improvement in 12-hour reflective TNSS and percentage improvement in 12-hour reflective TNSS were significant (p < 0.001) with azelastine 0.15% (19%) compared with placebo (10%). The improvement in 24-hour instantaneous TNSS also was significant (p < 0.001) for azelastine 0.15% compared with placebo, supporting efficacy with once-daily dosing. All individual TNSS symptoms were significantly (p < 0.01) improved with azelastine 0.15% compared with placebo. With the exception of bitter taste (4.5%) and nasal discomfort (4.5%), adverse events with azelastine 0.15% were reported with an incidence similar to placebo. Azelastine 0.15% nasal spray was effective and well tolerated in subjects with SAR with once-daily dosing.

Birch profilin 121 Bronchial hyperreactivity, allergic rhinitis 14

Budesonide inhalation powder via the dry-powder multidose inhaler Turbuhaler (budesonide Turbuhaler) has been shown to improve lung function and symptoms in adults with asthma. In this double-blind, placebo-controlled, multicenter trial, we evaluated the effects of once-daily budesonide Turbuhaler on health-related quality of life (HRQL) in 177 adults (aged 18-70 years) with non-steroid-dependent asthma. Patients were randomized to receive budesonide Turbuhaler (400 micrograms) once daily or placebo for 12 weeks. HRQL was assessed at baseline and weeks 4 and 12 using the Asthma Quality of Life Questionnaire (AQLQ). In addition to assessment based on the four AQLQ domains (activity limitations, asthma symptoms, emotional function, and response to exposure to environmental stimuli), AQLQ overall scores were analyzed for both treatment groups. Compared with placebo, patients using budesonide Turbuhaler once daily had statistically significant (p < 0.001) improvements from baseline to weeks 4 and 12 in AQLQ overall scores. Statistically significant improvements from baseline to weeks 4 and 12 in all four individual domains also were observed in the budesonide Turbuhaler group compared with placebo. Differences between the two treatment groups in mean changes from baseline in AQLQ overall, asthma symptoms, and emotional function reached the level required for patients to achieve a minimal important difference of change (> or = 0.5 U) at week 12. A retrospective analysis of the data showed that approximately 70% of patients treated with budesonide Turbuhaler experienced a minimal important difference of change in AQLQ overall scores. Overall, improvements in AQLQ correlated significantly (p < or = 0.04) with improvements in forced expiratory volume in 1 second, morning peak expiratory flow measurements, asthma symptoms, and breakthrough bronchodilator use at the study end. Thus, patients with corticosteroid-naïve asthma can experience improved HRQL when using budesonide Turbuhaler.

BACKGROUND:The safety and efficacy of intranasal corticosteroids for the treatment of allergic rhinitis is well documented in the literature. Additionally, an expert panel has concluded that intranasal corticosteroids are the first line of therapy when obstruction is a major component of rhinitis. Montelukast is a leukotriene receptor antagonist recently approved for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE:This randomized, double-blind, double-dummy, parallel-group study was conducted to compare the effectiveness of a 15-day course of intranasal fluticasone propionate 200 microg, once daily (FP200QD), to oral montelukast 10 mg, once daily (MON10QD), in relieving daytime and nighttime nasal symptoms associated with SAR. METHODS:The intent-to-treat (ITT) analysis population consisted of 705 eligible males and females (> or = 15 years) with SAR randomized to either FP200QD (N = 353) or MON10QD (N = 352). The primary efficacy endpoint was the mean change from baseline in subject-rated daytime total nasal symptom scores (the sum of four individual scores: nasal congestion, itching, rhinorrhea, and sneezing), evaluated via visual analog scales, and averaged over weeks 1 to 2. Secondary endpoints included the four daytime individual nasal symptom scores, the nighttime total, and individual nasal symptom scores (each evaluated on a four-point scale from 0 to 3). RESULTS:Statistically significant differences favoring FP200QD over MON10QD were observed for the mean change from baseline in daytime total nasal symptom scores (P < 0.001), daytime individual nasal symptom scores (P < 0.001), nighttime total (P < 0.001), and all individual nasal symptom scores (P < or = 0.002) over the 15-day treatment period. FP200QD and MON10QD were both well tolerated. CONCLUSIONS:The results of this well controlled study demonstrated that FP200QD was consistently superior to MON10QD with regard to every efficacy endpoint evaluated, including daytime and nighttime nasal congestion, in subjects with SAR.

Objective-The AERx insulin Diabetes Management System (AERx iDMS) (Aradigm, Hayward, CA) delivers an aerosol of liquid human insulin to the deep lung for systemic absorption. This study examined the effects on pulmonary function, pharmacokinetics, and pharmacodynamics of inhaled insulin in asthmatic and nonasthmatic subjects without diabetes.Research Design and Methods-A total of 28 healthy and 17 asthmatic (forced expiratory volume during the first second [FEV1] 50-80% of predicted value) subjects were enrolled in a two-part, open-label trial. To assess insulin pharmacokinetics and pharmacodynamics, a single inhalation dose of 1.57 mg (45 IU) was given on each of the 2 dosing days in part 1. A dose of 4.7 mg (135 IU) of insulin was inhaled in part 2 to assess effects on pulmonary function.Results-inhaled insulin showed area under the curve (AUC)((0-360 min)) values that were significantly greater for healthy subjects than for asthmatic subjects (P=0.013), whereas no difference was observed for maximum concentration (C-max) in the two groups. A greater reduction of serum glucose as indicated by area over the curve (AOC)((0-360 min)) was observed in healthy subjects (P=0.007). Asthmatic subjects had greater intrasubject variations in insulin AUC((0-360 min)) and C-max values than healthy subjects, but similar variations in glucose AOC((0-360 min)), No significant changes in FEV1 forced vital capacity (FVC), and FEV1/FVC were observed from pre- to postdose times, and there were no observed safety issues.Conclusions-After inhaling insulin using the AERx iDMS, asthmatic subjects absorbed less insulin than healthy subjects, resulting in less reduction of serum glucose. No effects on airway reactivity were observed. Diabetic patients with asthma may need to inhale more insulin than patients with normal respiratory function in order to achieve similar glycemic control.

Although allergic rhinitis is commonly associated most with symptoms of nasal congestion, rhinorrhea, sneezing, and itching, the symptom of sinus pain and pressure often prompts the patient to seek medical attention. The effect of fluticasone propionate on this symptom has not been studied. The purpose of this study was to compare the efficacy and safety of fluticasone propionate aqueous nasal spray to placebo vehicle in the treatment of patients with sinus pain and pressure arising from allergic rhinitis. A multicenter, double-blind, parallel-group trial was conducted in 206 symptomatic patients > or = 12 years with seasonal or perennial allergic rhinitis. Patients were treated for 14 days with either fluticasone propionate aqueous nasal spray, 200 mcg once daily, or placebo vehicle. Patients attended clinic visits and kept diary cards rating sinus pain and pressure (measured as one symptom) and nasal congestion symptoms during the study. Treatment with fluticasone propionate provided significantly greater relief of symptoms of sinus pain and pressure compared with placebo over the entire 14-day treatment period. Nasal congestion scores also were significantly reduced compared with placebo at each time point. Treatments were well tolerated, and the incidence of adverse events attributable to study treatments was similar between groups. Our data indicate that symptoms of sinus pain and pressure and nasal congestion can be significantly reduced in patients with allergic rhinitis when treated with fluticasone propionate aqueous nasal spray, 200 mcg once daily.

Background: Previous studies have demonstrated the efficacy and safety of twice-daily budesonide Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Wilmington, DE) for the treatment of mild to severe asthma.Objective: To compare the efficacy and safety of budesonide Turbuhaler administered once daily each morning with placebo in inhaled corticosteroid-naive adults with persistent asthma.Methods: In this randomized, double-blind, placebo-controlled, multicenter study, 177 adults (aged 18 to 70 years) received placebo or once-daily budesonide Turbuhaler (400 mug) for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1,) and AM/PM peak expiratory flow rate (PEFR), and nighttime/daytime asthma symptom scores, patient discontinuations, use of breakthrough medication (albuterol), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), and quality of life assessments. Safety was evaluated based on adverse events, physical examinations, vital signs, and laboratory tests.Results: Demographic and baseline characteristics were comparable between study groups. The mean percentages of predicted FEV1 at baseline were 71.9 +/- 9.8 in patients receiving budesonide Turbuhaler and 70.6 +/- 11.0 in patients receiving placebo. Mean changes from baseline over the 12-week treatment period in FEV1 were significantly (P = 0.007) improved in patients receiving once-daily budesonide Turbuhaler compared with placebo (0.31 L and 0.17 L, respectively). Significant (P less than or equal to 0.037) improvements over placebo also were observed in AM PEEP, nighttime/daytime asthma symptoms, and albuterol use with budesonide Turbuhaler treatment. Adverse events were generally mild or moderate in intensity and similar between study groups.Conclusions: Budesonide Turbuhaler 400 mug administered once daily in the AM is efficacious and safe for inhaled corticosteroid-naive asthmatic adults.

Background: The proportion of older adults in the US population will increase dramatically in the near future, yet the frequency and nature of care furnished to older adults by Allergy/Immunology practitioners has not been described.Objective: To determine the extent and nature of care being provided to adults and older adults by Allergy/Immunology practitioners.Methods: ACAAI members and fellows were surveyed to obtain information regarding certification and training as well as their practice patterns.Results: The distribution of diagnoses among patients aged 40 to 54 years were very similar to distributions found among adults age 55 to 69 years and greater than or equal to 70 years of age. Virtually all respondents indicated they provide inhalant allergen immunotherapy for patients age 40 to 54 years with asthma and/or allergic rhinitis; administration of inhalant allergen immunotherapy for asthma and allergic rhinitis was also frequently reported for adults greater than or equal to 55 years. The proportions of respondents providing venom immunotherapy for adults aged 40 to 54, 55 to 69, and greater than or equal to 70 years were 82%, 70%, and 39%, respectively.Conclusion: ACAAI members and fellows commonly provide care to older adults. Our survey findings highlight the need to develop strategies for successful management of Allergy/Immunology conditions specifically pertaining to older adults, including studies to determine the therapeutic utility of inhalant allergen and venom immunotherapy in this age group.

Background: Consensus asthma guidelines recommend antileukotriene agents as alternative therapy to existing anti-inflammatory medications; however the full therapeutic potential of these medications has not yet been determined.Objective: The purpose of this study was to assess the efficacy and safety of the oral leukotriene receptor antagonist zafirlukast (20 mg twice daily) in subgroups of patients who have asthma with the use of integrated data from four 13-week trials.Methods: The trials had comparable designs, entry criteria, and clinical assessments. Patient subgroups were characterized by demographic and baseline asthma characteristics. Analysis of covariance models were tested for overall treatment effect and for interactions between treatment and subgroup characteristics.Results: Patients with mild-to-moderate asthma (12 to 76 years old) who were treated with albuterol alone mere randomized (n(Z) = 879; n(P) = 605) and included in subset analyses. Significant overall treatment effects, favoring zafirlukast, were noted for measures of daytime and nighttime symptoms, beta(2)-agonist use, and pulmonary function (P < .05). A significant, quantitative, treatment-by-age interaction was noted for beta(2)-agonist use (P < .03), suggesting greater reductions in rescue medication use with increasing patient age. Compared with placebo, similar size and/or direction of response was noted with zafirlukast in the various subgroups, indicating a benefit with zafirlukast regardless of subgroup. Significant treatment-by-strata interactions (P < .05), favoring zafirlukast, were noted for various outcome measures in subgroups with the greatest amount of baseline beta(2)-agonist use (>8 puffs/day) and with greater baseline peak flow variability (greater than or equal to 20%) and baseline airflow obstruction (FEV1/forced vital capacity ratio, <0.70). The overall treatment failure rate was significantly lower in the zafirlukast group compared with the placebo group (P < .003). No associations were observed between any adverse events and subgroups defined by demographic characteristics.Conclusions: Exploratory subset analyses showed that zafirlukast is similarly efficacious in patients with asthma who have differing demographic characteristics and degrees of subjective symptoms. Additionally, zafirlukast appears to be incrementally beneficial in patients with more moderate disease, defined by a greater requirement for as-needed rescue medication and more abnormal pulmonary function at baseline. Over 13 weeks, zafirlukast was well tolerated and demonstrated a safety profile clinically indistinguishable from placebo.

BACKGROUND:Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas.METHODS:Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study.RESULTS:Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 micrograms and 42 micrograms administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral beta-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vital signs, electrocardiogram (ECG), and 24-hr ECG (Holter) monitoring. Both the 21-micrograms and 42-micrograms doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV1) (p < or = 0.02) and PEFR (p < or = 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-micrograms dosage producing consistently higher serial FEV1 and PEFR than did the 21-micrograms dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p < or = 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECGs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 micrograms or 42 micrograms twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 micrograms twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 micrograms.