Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma.

BACKGROUND: Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children. METHODS: We randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis. RESULTS: Among the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone-salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone-salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone-salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01). CONCLUSIONS: In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344 .).

A comparison of fluticasone propionate nasal spray and cetirizine in ragweed fall seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are generally considered the most effective medication class for controlling allergic rhinitis. Previous comparative studies with oral antihistamines have been only partially informative due to a variety of variables encountered during their execution. OBJECTIVE: To compare fluticasone propionate nasal spray (FPNS) with the second-generation antihistamine cetirizine (oral tablet) and with placebo in a head-to-head study in a 2-week treatment study during fall ragweed season. METHODS: A total of 978 subjects were screened for this study. Six hundred and eighty-two subjects were randomized into the study (170 subjects, FPNS 200 mcg once daily; 170, cetirizine 10 mg once daily; 171, FPNS placebo; 171, cetirizine placebo) and comprised the intent-to-treat population. A 1-week placebo run-in was followed by a 2-week active treatment period during which time a total nasal symptom score (TNSS), total ocular symptom score, and the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire were collected. RESULTS: The primary efficacy end point was the mean change from baseline over the entire treatment period in A.M. reflective TNSS. The TNSS was the sum of the four individual nasal congestion, nasal itching, rhinorrhea, and sneezing scores, in which each symptom was scored on a scale of 0 to 3. Both FPNS and cetirizine improved the primary end point when compared with placebo during the active treatment period. Although there was a trend that favored FPNS with regard to the primary and secondary end points, there was not a statistical difference between the two treatments. CONCLUSION: FPNS and cetirizine were equally effective in treating fall seasonal allergic rhinitis during a 2-week head-to-head treatment investigation. Clinical trial NCT01916226, www.clinicaltrials.gov.

Adding montelukast to fluticasone propionate/salmeterol for control of asthma and seasonal allergic rhinitis.

Limited information exists comparing fluticasone propionate/salmeterol combination (FSC) versus montelukast (MON) in patients with coexistent asthma and allergic rhinitis. The purpose of this study was to compare the addition of MON to patients receiving FSC on asthma control while experiencing asthma and allergy symptoms. Additionally, the effect of fluticasone propionate aqueous nasal spray (FPANS) and MON were assessed in allergic rhinitis control. Symptomatic patients (n = 1385) with asthma and seasonal allergic rhinitis were randomized to receive FSC, 100/50 micrograms twice daily; FSC twice daily + FPANS, 200 micrograms once daily; FSC twice daily + MON, 10 mg once daily; or MON once daily for 4 weeks during the allergy pollen season. Patients recorded peak expiratory flow, rescue albuterol use, and asthma and rhinitis symptoms. No additional improvements in overall asthma control were seen when MON was added to FSC. Treatment with FSC produced significant (p < 0.001) improvements in all clinical and patient-reported measures versus MON. FSC + FPANS was superior to FSC + MON (p < or = 0.001) in improving daytime and nighttime total nasal symptom scores. Adverse events were similar. In patients with asthma and allergic rhinitis, adding MON to FSC provided no additional benefit in asthma control. FSC resulted in superior improvement in asthma control compared with MON. FPANS also provided superior nasal symptom control versus MON in allergic patients treated with FSC for asthma. Optimal disease control in patients with asthma and allergic rhinitis should be achieved by the most effective therapy directed toward each disease component.

Undiagnosed OSA May Significantly Affect Outcomes in Adults Admitted for COPD in an Inner-City Hospital.

BACKGROUND: COPD is the second most common cause of hospital admission in the United States. OSA is a highly prevalent and underdiagnosed condition that may affect the outcome of COPD. RESEARCH QUESTION: We hypothesized that presence of unrecognized and untreated OSA will increase hospital readmissions in patients admitted for COPD exacerbation. STUDY DESIGN AND METHODS: We reviewed patients admitted for COPD exacerbation from May 2017 through July 2018 who were also screened for previously unrecognized and untreated OSA with a sleep questionnaire, and who subsequently underwent a high-resolution pulse oximetry or portable sleep monitoring study. We compared the rates of 30-, 90-, and 180-day readmission or death across OSA categories and compared overall survival in patients with and without OSA. RESULTS: Of 380 patients admitted for COPD exacerbation, 256 were screened for OSA with a sleep questionnaire (snoring, tiredness during daytime, observed apnea, high BP). Of these, 238 underwent an overnight high-resolution pulse oximetry/portable sleep monitoring. Of the 238 total patients, 111 (46.6%) were found to have OSA; 28.6% had mild, 9.7% moderate, and 8.4% severe OSA. Baseline characteristics and demographics were compared between the cohorts of participants with OSA and without OSA and were similar except that patients with OSA had a higher mean BMI (33.9 vs 30.3 kg/m2) and an increased prevalence of heart failure (19.8% vs 7.1%). For patients with COPD and mild OSA, odds of 30-day readmission were 2.05 times higher than for patients without OSA (32.4% vs 18.9%). Additionally, odds of 30-day readmission were 6.68 times higher for patients with moderate OSA vs patients without OSA (60.9% vs 18.9%) and 10.01 times high for patients with severe OSA vs patients without OSA (70% vs 18.9%). Readmission rates were also greater at 90 and 180 days. All-cause mortality was lower for patients without OSA than for patients with OSA (P < .01). The time to hospital readmission or death was shorter with greater OSA severity (P < .01). INTERPRETATION: Patients hospitalized for COPD exacerbation and who have unrecognized OSA; 30-, 90-, and 180-day readmission rates; and 6-month mortality rates are higher than in those without OSA.

Sleep Disordered Breathing in Hospitalized African-Americans.

RATIONALE: Sleep-disordered breathing (SDB) is a common disorder in general population, with higher prevalence in population with comorbid cardiovascular disease, and yet it remains frequently undiagnosed. Prior published data show that hospitalized obese patients have a high incidence of unrecognized SDB. However, limited data exists on the incidence, prevalence, and impact of SDB in hospitalized obese African-American (AA) patients. This study was performed to better understand the burden of undiagnosed SDB in hospitalized AA patients and its implications on readmission. METHODS: A total of 1243 consecutive obese AA patients admitted to medical or telemetry service were screened utilizing a screening questionnaire (STOP/STOPBANG) from October 2016 to October 2017. If the results of the screening questionnaire were positive, the patients were offered inpatient testing with either High Resolution Pulse Oximetry (HRPO), or a type 3 portable monitor (PM). SDB was suspected if the Oxygen Desaturation Index (ODI) or Apnea Hypopnea Index (AHI) ≥ 5. We collected 30-day readmission and emergency department (ED) visit data on all patients and requested a formal outpatient sleep study for patients identified as SDB positive. RESULTS: Of the 1243 AA patients screened, 852 (68.5%) patients screened positive for SDB. Of these high-risk screens, 538 (63.1%) patients underwent inpatient testing with either High Resolution Pulse Oximetry (HRPO) or PM. Of these 538 patients, 319 (59.3%) were found to have suspected obstructive sleep apnea (OSA) based on ODI/AHI >5. Mild SDB (AHI 5-14) was present in 149 (46.7%) patients; moderate (AHI 15-29) in 74 (23.2%) patients; and severe (AHI >30) in 96 (30.1%) patients. The patients with suspected SDB were educated and encouraged to get an out-patient polysomnogram (PSG) but only 32 (10.0%) returned to undergo a formal PSG. The 30-day readmission rate/ED visits for patient with SDB was 13.5% compared to 13.7% of patients without SDB. CONCLUSION: This is the largest SDB registry that included obese hospitalized AA patients in a tertiary care academic center and reveals a high prevalence of undiagnosed SDB in this cohort. Despite proactive screening and patient education only 3.8% (32/852) of patients returned post-discharge for formal polysomnography. The presence of SDB did not impact the 30-day readmission rate/ED visit rate in this cohort.

Does measuring BHR add to guideline derived clinical measures in determining treatment for patients with persistent asthma?

RATIONALE: Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR. METHODS: After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR. RESULTS: The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037). CONCLUSION: This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.

Deterioration in asthma control when subjects receiving fluticasone propionate/salmeterol 100/50 mcg Diskus are "stepped-down".

In this study, 647 subjects stable on fluticasone propionate/salmeterol Diskus 100/50 mcg BID (FSC) were randomized to continue FSC 100/50 mcg BID or "step down" to either fluticasone propionate (FP) 100 mcg BID, salmeterol (SAL) 50 mcg BID, or montelukast (MON) 10 mg once daily for 16 weeks. Overall asthma control significantly improved in the FSC group; whereas, "stepping down" to FP, SAL, or MON resulted in deterioration in asthma control, as determined by decreased measures of lung function and clinical features. This study provides support that treatment of both inflammation and smooth muscle dysfunction may be necessary to achieve and maintain asthma control in patients uncontrolled on ICS.

A patient preference study that evaluated fluticasone furoate and mometasone furoate nasal sprays for allergic rhinitis.

BACKGROUND: Corticosteroid nasal sprays are the mainstay of treatment for allergic rhinitis. These sprays have sensory attributes such as scent and/or odor, taste and aftertaste, and run down the throat and/or the nose, which, when unpleasant, can affect patient preference for, and compliance with, treatment. OBJECTIVE: This study examined patient preference for fluticasone furoate nasal spray (FFNS) or mometasone furoate nasal spray (MFNS) based on their sensory attributes after administration in patients with allergic rhinitis. METHODS: This was a multicenter, randomized, double-blind, cross-over study. Patient preferences were determined by using three questionnaires (Overall Preference, Immediate Attributes, and Delayed Attributes). RESULTS: Overall, 56% of patients stated a preference for FFNS versus 32% for MFNS (p < 0.001); the remaining 12% stated no preference. More patients stated a preference for FFNS versus MFNS for the attributes of "less drip down the throat" (p < 0.001), "less run out of the nose" (p < 0.05), "more soothing" (p < 0.05), and "less irritating" (p < 0.001). More patients responded in favor of FFNS versus MFNS for the immediate attributes, "run down the throat" (p < 0.001), and "run out of the nose" (p < 0.001), and, in the delayed attributes, "run down the throat" (p < 0.001), "run out of the nose" (p < 0.01), "presence of aftertaste" (p < 0.01), and "no nasal irritation" (p < 0.001). CONCLUSION: Patients with allergic rhinitis preferred FFNS versus MFNS overall and based on a number of individual attributes, including "less drip down the throat," "less run out of the nose," and "less irritating." Greater preference may improve patient adherence and thereby improve symptom management of the patient's allergic rhinitis.

Fluticasone propionate nasal spray is superior to montelukast for allergic rhinitis while neither affects overall asthma control.

BACKGROUND: Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients. OBJECTIVE: To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis (SAR) and persistent asthma. METHODS: A total of 863 patients (mean baseline FEV1 81% predicted) were randomized to receive open-label fluticasone propionate/salmeterol (FSC), 100/50 microg bid for 4 weeks, plus either blinded fluticasone propionate aqueous nasal spray (FPANS) 200 microg/d, montelukast 10 mg/d, or placebo. Patients kept daily records of peak expiratory flow (PEF), asthma, and rhinitis symptoms and rescue albuterol use. RESULTS: FPANS added to FSC resulted in superior outcomes for daytime total nasal symptom scores (D-TNSS) and individual daytime nasal specific symptoms (congestion, rhinorrhea, sneezing, and itching) compared with montelukast plus FSC and placebo plus FSC (p < or = 0.001). Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing. Morning PEF, asthma symptoms, and rescue albuterol use improved significantly (p < or = 0.001) in all treatment groups, but improvements were comparable across the treatment groups. CONCLUSION: In patients with persistent asthma treated with FSC, the addition of montelukast or FPANS for the treatment of SAR resulted in no additional improvements in overall asthma control compared with FSC alone. However, FPANS provided superior rhinitis control compared with montelukast. These data suggest that asthma and rhinitis should each be optimally treated.

The association between seasonal asthma exacerbations and viral respiratory infections in a pediatric population receiving inhaled corticosteroid therapy with or without long-acting beta-adrenoceptor agonist: a randomized study.

BACKGROUND: A seasonal peak in asthma exacerbations in the fall has previously been reported. The association between fall exacerbations and viral respiratory tract infections (RTI) remains uncertain. OBJECTIVE: To investigate the number of fall exacerbations and the incidence of RTIs in a pediatric asthmatic population using an at-home mucus collection methodology. METHODS: This was a 16-week, multicenter, randomized, double-blind, parallel-group exploratory study. Children, 4-11 years of age with a clinical diagnosis of asthma requiring use of an inhaled corticosteroid, a morning peak expiratory flow ≥70% predicted and a history of ≥1 asthma exacerbation during the previous respiratory viral season were eligible for enrollment. Subjects were randomized (1:1) to receive fluticasone propionate/salmeterol (FP/SAL) 100/50 mcg or FP 100 mcg prior to starting school. Subjects collected mucus samples using an at-home kit when they experienced respiratory symptoms. Mucus samples obtained during symptomatic periods were analyzed for common respiratory viruses by multiplex polymerase chain reaction. The number of exacerbations requiring systemic corticosteroids was recorded. RESULTS: In total, 339 (FP/SAL, n = 171; FP, n = 168) subjects were randomized and included in the intent-to-treat population; 292 (86%) completed the study. Of the 537 mucus samples collected, 64% tested positive for viruses, but only 6% of positive samples were associated with an asthma exacerbation. Exacerbations were infrequent, with only 41 subjects reporting 49 exacerbations in total. Adverse events were reported in 66% of subjects. CONCLUSIONS: In a susceptible population, the fall asthma exacerbation rates in children were low despite frequent detection of viral RTIs. NCT01192178; GSK ID: ADA113872.

Prevalence of airway obstruction assessed by lung function questionnaire.

OBJECTIVE: To estimate the prevalence of unidentified chronic obstructive pulmonary disease (COPD) and determine the screening accuracy of the Lung Function Questionnaire (LFQ). PATIENTS AND METHODS: Cigarette smokers who had a smoking history of 10 or more pack-years and were aged 30 years or older were recruited from 36 centers from February 18, 2009, to May 29, 2009. A total of 1575 patients completed a Web-based survey including the 5-item LFQ. Spirometry was performed on patients with an LFQ total score of 18 or less and on a subset scoring more than 18. The primary outcome was the proportion of patients at risk of airflow obstruction as measured by the LFQ (score, ≤ 18) in whom an airflow obstruction was confirmed by spirometry. RESULTS: Of the patients who completed the LFQ, 849 (54%) had standardized spirometry data available. On the basis of LFQ and spirometry results, the estimated prevalence of possible COPD was 17.9% (95% confidence interval, 15.3%-20.6%). At a cut point of 18 or less, sensitivity, specificity, positive predictive value, and negative predictive value of the LFQ were 88%, 25%, 21%, and 90%, respectively. Approximately 1 in 5 patients (21%) aged 30 years or older and 1 in 4 (26%) aged 50 years or older scored 18 or less on the LFQ and had a ratio of forced expiratory volume in the first second of expiration to forced vital capacity less than 0.70. CONCLUSION: On the basis of postbronchodilator spirometry results using weighted estimates, approximately 1 in 5 patients (21%) aged 30 years or older with a smoking history of 10 or more pack-years seen in a primary care setting is likely to have COPD. The LFQ could be a helpful COPD case-finding tool for clinicians to identify patients who need further evaluation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01013948.

Comparison of patient preference for sensory attributes of fluticasone furoate or fluticasone propionate in adults with seasonal allergic rhinitis: a randomized, placebo-controlled, double-blind study.

BACKGROUND: Intranasal corticosteroids are first-line treatment for moderate-to-severe seasonal allergic rhinitis (AR). OBJECTIVES: To compare preferences for fluticasone furoate and fluticasone propionate nasal sprays after 1 week of treatment in patients with symptomatic seasonal AR. METHODS: Patients with seasonal AR were enrolled (n = 360) and randomized 1:1 to active treatment (fluticasone furoate, 110 microg, or fluticasone propionate, 200 microg, followed by crossover treatment for 1 week each) or matched placebo sequence with a 1-week washout before crossover dosing. Fluticasone furoate and fluticasone propionate efficacy was measured by change from baseline during 1 week in daily reflective total nasal symptom score (rTNSS) that assessed severity of rhinorrhea, nasal congestion, nasal itching, and sneezing. Patient preference for fluticasone furoate or fluticasone propionate was assessed at the end of the study by questionnaire. RESULTS: Three hundred sixty patients from 29 clinical sites in the Unites States were randomized and treated between August 1, 2007 and November 30, 2007. Most patients were white (73%) and female (59%), with a mean age of 38.3 years, and had had seasonal AR for at least 10 years (74%). Fluticasone furoate and fluticasone propionate each reduced the daily rTNSS compared with their respective placebos (least squares mean [SD] difference, -0.8 [0.24], P < .001, and -0.6 [0.24], P = .01, respectively). More patients (P < .001) preferred fluticasone furoate to fluticasone propionate based on attributes of scent or odor (58% vs 27%), aftertaste (60% vs 18%), leaking out of the nose and down the throat (59% vs 21%), and mist gentleness (57% vs 26%). No statistically significant differences were seen in preferences regarding ease of use, delivery method, or device comfort. CONCLUSION: Both fluticasone furoate and fluticasone propionate significantly improved symptoms in adult patients with seasonal AR. Most patients preferred the sensory attributes of fluticasone furoate to those of fluticasone propionate after 1 week of treatment.

Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy.

Nasal symptoms of allergic rhinitis are an important cause of sleep disturbance. Reduction of nasal symptoms, particularly nasal obstruction, has been linked to improvements in self-reported sleep quality. The enhanced-affinity intranasal corticosteroid fluticasone furoate and the oral antihistamine fexofenadine were compared with respect to nighttime symptoms of seasonal allergic rhinitis. In two randomized, double-blind, double-dummy, parallel-group studies, patients received fluticasone furoate nasal spray (FFNS),110 microg (study 1, n = 312; study 2, n = 224); fexofenadine, 180 mg (study 1, n = 311; study 2, n = 227); or placebo (study 1, n = 313; study 2, n = 229) once daily for 2 weeks. Fluticasone furoate was more effective (p < 0.001) than fexofenadine and placebo in both studies with respect to the mean changes from baseline over the treatment period in the nighttime symptoms score, nighttime reflective total nasal symptom score, predose instantaneous nasal symptom score, and morning peak nasal inspiratory flow. Fluticasone furoate was more effective than placebo (p

Preferences of adult patients with allergic rhinitis for the sensory attributes of fluticasone furoate versus fluticasone propionate nasal sprays: a randomized, multicenter, double-blind, single-dose, crossover study.

BACKGROUND: Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR). OBJECTIVE: The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR. METHODS: This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked "Based on these attributes, which product did you prefer overall?" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment. RESULTS: Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF. CONCLUSION: In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration.

Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for the treatment of seasonal allergic rhinitis symptoms.

BACKGROUND: Few studies have directly compared the efficacy of intranasal corticosteroids with that of leukotriene receptor antagonists for the treatment of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE: To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with oral montelukast, 10 mg daily, for the relief of SAR symptoms. METHODS: Patients with SAR 15 years or older were randomized to receive either fluticasone propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy, parallel-group study. The primary efficacy measure was the mean change from baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime individual nasal symptom scores [INSSs] assessing nasal congestion, itching, rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2. RESULTS: Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P < .001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed significant differences favoring fluticasone propionate over montelukast across 2 weeks of treatment. CONCLUSION: Compared with montelukast, fluticasone propionate provided significantly greater improvement in daytime and nighttime SAR symptoms.

Improved ability to perform strenuous activities after treatment with fluticasone propionate/salmeterol combination in patients with persistent asthma.

Patients with asthma experience disruptions in usual activities that can impair their quality of life, and in patients whose daily routine involves an active lifestyle, these disruptions can be severe. We assessed the patient-perceived effect of treatment with fluticasone propionate/salmeterol combination (FSC), compared with fluticasone propionate (FP) or salmeterol (SAL) alone, on activity limitations, particularly strenuous physical activities. The Asthma Quality of Life Questionnaire (AQLQ) was administered in two 12-week, randomized, double-blind, placebo-controlled trials comparing FSC 100/50 or 250/50 microg twice daily vs. the individual components alone in 686 adults and adolescents with asthma. In one study, patients were stratified by prior treatment [low to medium doses of inhaled corticosteroids (ICS) or SAL], and in the other study, all patients were previously treated with medium to high doses of ICS. Patients prospectively identified five activities they performed regularly and were asked how these activities were limited by their asthma. The effect of randomized treatment on strenuous activities (e.g., aerobics, cycling, hiking, and basketball) was assessed. In both studies, treatment with FSC resulted in clinically meaningful improvements (i.e., change in AQLQ of > or = 0.5) and was statistically significantly better than SAL in both studies and FP in one study. Treatment of the two main components of asthma--inflammation and bronchoconstriction--with FSC results in clinically meaningful improvements in the ability of patients with persistent asthma to perform not only their usual activities but also strenuous activities.

Concurrent use of intranasal and orally inhaled fluticasone propionate does not affect hypothalamic-pituitary-adrenal-axis function.

Two double-blind, randomized, placebo-controlled, parallel group safety and efficacy studies included evaluation of the hypothalamic-pituitary-adrenal (HPA)-axis effects of concurrent treatment with intranasal and orally inhaled fluticasone propionate (FP). In the first study, patients with asthma who were > or =12 years of age were assigned randomly to receive twice-daily doses (either 88 or 220 microg) of orally inhaled FP delivered from a metered-dose inhaler (MDI). In the second study, patients were assigned randomly to receive either orally inhaled FP 250 microg or orally inhaled FP 250 microg/salmeterol 50 microg delivered via the Diskus device. In both studies, patients with rhinitis were allowed to continue the use of intranasal FP at their usual dosing. Treatment periods were 26 weeks and 12 weeks for the MDI and Diskus studies, respectively. HPA-axis effects were assessed using response to short cosyntropin stimulation testing. The number and percentage of patients with an abnormal cortisol response, defined as a morning plasma cortisol of <5 microg/dL, a poststimulation peak of <18 microg/dL, or a poststimulation rise of <7 microg/dL, were summarized in two subgroups: patients who used intranasal FP and those who did not. The concurrent administration of intranasal FP and orally inhaled FP via an MDI or Diskus or via Diskus with salmeterol was not associated with HPA-axis effects compared with orally inhaled FP alone. The results of these two studies suggest that concurrent use of intranasal FP with orally inhaled FP administered via MDI or Diskus for treatment of comorbid rhinitis and asthma does not increase the risk of HPA-axis abnormalities.

Relief of sinus pain and pressure with fluticasone propionate aqueous nasal spray: a placebo-controlled trial in patients with allergic rhinitis.

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.

No growth suppression in children treated with the maximum recommended dose of fluticasone propionate aqueous nasal spray for one year.

This randomized, double-blind, placebo-controlled study of fluticasone propionate aqueous nasal spray (at a maximum recommended dose of 200 micrograms each day) administered daily for one year was conducted to evaluate its potential effects on growth, measured by stadiometry, in prepubescent children with perennial allergic rhinitis (n = 150; age 3.5 to 9.0 years). The results demonstrate equivalent growth velocity over a one-year treatment period between children receiving fluticasone propionate aqueous nasal spray and children receiving vehicle placebo. In addition, children in both treatment groups had similar increases in height over the same period. Baseline height was 119.1 cm (SE = 0.72) in the fluticasone propionate group (n = 56) and 119.0 cm (SE = 0.71) in the vehicle placebo group (n = 52). Mean height at the end of one year of treatment was 125.5 cm (SE = 0.18) in the fluticasone propionate group (n = 44) and 125.4 cm (SE = 0.19) in the vehicle placebo group (n = 39) (least-squares mean difference -0.12; 95% confidence interval [-0.600, 0.352]). The effects of fluticasone propionate on one-year growth velocity were also comparable to those of vehicle placebo. The confidence interval for the treatment difference lay within the prospectively defined equivalence bounds (of -0.8, +0.8 cm/year) and contained zero. The incidence of adverse events considered to be at least possibly drug-related did not differ between the fluticasone propionate group and the vehicle placebo group. The results of this one-year, double-blind study demonstrate that fluticasone propionate aqueous nasal spray at the maximum recommended dose of two sprays per nostril (200 micrograms) once daily was equivalent to vehicle placebo with no effects on growth rate in prepubescent children.

Lack of effect of fluticasone propionate aqueous nasal spray on the hypothalamic-pituitary-adrenal axis in 2- and 3-year-old patients.

OBJECTIVE: Fluticasone propionate aqueous nasal spray (FP) at the highest recommended doses does not affect hypothalamic-pituitary-adrenal (HPA) axis function in adults or older children, but its potential effects in children younger than 4 years have not been previously studied. This randomized, double-blind, placebo-controlled study evaluated the effects of FP on HPA axis function measured by 12-hour urinary-free cortisol levels in children 2 to 3 years of age. METHODS: Patients ages 2 to 3 years with symptoms of allergic rhinitis were administered FP 200 microg/day (FP200 QD) or vehicle placebo for 6 weeks. RESULTS: The FP200 QD group (n = 33) was equivalent to the placebo group (n = 32) in mean change from baseline in the primary safety measure of 12-hour creatinine-corrected urinary-free cortisol concentration (geometric mean difference [standard error; SE] for placebo-FP200 QD = 0.96 [1.20]; 95% confidence interval 0.66, 1.39) at the end of the treatment period. The adjusted geometric mean change from baseline value was 0.98 for FP200 QD (SE = 1.14) and 0.94 for placebo (SE = 1.15); a value of 1.0 reflects no change from baseline. Cough and fever were the most common adverse events reported in either group. CONCLUSIONS: FP200 QD was equivalent to placebo with respect to effects on HPA axis function measured by 12-hour urinary-free cortisol in 2- and 3-year-old patients. FP200 QD was well-tolerated in these very young children with allergic rhinitis.