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

Loratadine provides early symptom control in seasonal allergic rhinitis.

Allergic rhinitis (AR) affects approximately 500 million people worldwide, and prevalence is increasing. Second-generation nonsedating antihistamines are first-line treatments for seasonal AR (SAR). This study was performed to evaluate early SAR symptom relief with second-generation antihistamines through a retrospective analysis of previously published data. In this study, 835 subjects aged 12-60 years with a > or = 2-year history of SAR were randomized to receive loratadine, 10 mg, once daily; fexofenadine, 60 mg, twice daily; or placebo for 7 days. Each subject recorded the severity of five symptoms of SAR on a scale of 0-3. This primary post hoc efficacy analysis was the mean change from baseline in daily average A.M./P.M. reflective and instantaneous total symptom score (TSS) on days 2 and 3. Significantly greater mean reductions from baseline were shown with loratadine compared with fexofenadine in average A.M./P.M. reflective TSS on days 2 (-3.51 versus -2.84, respectively; p < 0.002) and 3 (-3.80 versus -3.19, respectively; p = 0.007) and in average A.M./P.M. instantaneous TSS on day 3 (-3.68 versus -3.15, respectively; p = 0.022). Similar results were noted in average A.M./P.M. reflective and instantaneous total nasal symptom scores and for 10 of 20 individual symptom time points (p < 0.05). Loratadine was significantly more effective than placebo for all time points (p < 0.001). Early, sustained symptom relief was seen with loratadine, suggesting that it may be more effective for treating SAR symptoms.

Compliance and noncompliance in asthma.

Compliance and noncompliance are big issues in asthma management. It has been well established that compliant patients experience less exacerbations than less compliant patients and that compliance rates often are <50%. The reasons for noncompliance are multiple and complex and not always clearly understood. Methods proposed to improve compliance include patient education, more partnership care, less frequent dosing, simple schedules, diaries, etc. Less dosing and simple schedules are most effective. It is difficult to improve compliance overall and despite extensive research and efforts, rates of compliance remain low. Noncompliance in asthma management is a fact of life and no single compliance-improving strategy probably will be as effective as a good physician-patient relationship.

Fluticasone furoate nasal spray: a single treatment option for the symptoms of seasonal allergic rhinitis.

BACKGROUND: Fluticasone furoate (USAN-approved name) is a novel, enhanced-affinity glucocorticoid administered in a unique side-actuated device for the management of seasonal allergic rhinitis (SAR). OBJECTIVE: We sought to evaluate the efficacy and safety of once-daily fluticasone furoate nasal spray, 110 microg, in patients aged 12 years or older with fall SAR. METHODS: Patients (n = 299) received fluticasone furoate or placebo for 2 weeks in this double-blind, parallel-group randomized study. Patients evaluated nasal and ocular symptoms using a 4-point categoric scale. Efficacy was assessed on the basis of the mean change from baseline in reflective and instantaneous total nasal symptom scores and reflective total ocular symptom scores. RESULTS: Fluticasone furoate produced significantly greater improvements than placebo in daily reflective total nasal symptom score (-1.473, P < .001; primary end point), morning predose instantaneous total nasal symptom score (-1.375, P < .001), daily reflective total ocular symptom score (-0.600, P = .004), and patient-rated overall response to therapy (P < .001). The onset of therapeutic effect occurred at 8 hours after initial administration. Fluticasone furoate was well tolerated. CONCLUSION: Fluticasone furoate, 110 microg once daily, was effective and well tolerated for the treatment of nasal symptoms of SAR in patients aged 12 years and older. Treatment also produced significant improvements in ocular symptoms. Fluticasone furoate was fast acting, as indicated by an 8-hour onset of action, and provided 24-hour symptom control. CLINICAL IMPLICATIONS: New treatments for the bothersome symptoms of SAR are needed. One such treatment, fluticasone furoate nasal spray, provides effective relief of the symptom profile of SAR.

Relationship of complete respiratory dysfunction: one linked airway. A selective clinical discussion.

There is increasing clinical, immunologic, and pathophysiological consensus that allergic rhinitis (AR) and asthma are different manifestations of a single condition: inflammation of the upper and lower airways characterized by nasal and bronchial hyperresponsiveness. Most patients with asthma have AR and asthma is present in a large percentage of patients with AR. Rhinitis is a major riskfactor for asthma. Treating rhinitis in patients with AR and asthma improves not only the rhinitis but also the asthma. It is becoming clinically evident and studies have confirmed that improving the upper airway also helps the lower airway. There appears to be a connection between upper and lower airway dysfunction, suggesting one linked airway. There also seems to be a relationship between AR and asthma, suggesting that the two conditions are manifestations of one syndrome of complete respiratory dysfunction. The evidence is compelling but it is not completely established.

Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma.

BACKGROUND: Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events. OBJECTIVE: To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma. METHODS: This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator. RESULTS: For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate. CONCLUSIONS: These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.

Risk factors in allergy/asthma.

The incidence of allergic rhinitis and asthma is increasing. Nobody knows why with certainty, but there are many theories including better diagnosis, urban living, higher exposure to dust mites, atmospheric pollution, nutrition, lifestyle changes, maternal smoking, diesel fumes, geography, the "hygiene hypothesis," and several others. It has been known that atopic disease runs in families and a family history is the strongest risk factor for the development of allergies/asthma. Molecular studies also have identified some specific atopic entities that are determined genetically (eosinophils, interleukin-5, etc.). Environmental issues and lifestyle changes are becoming increasingly more important as significant risk factors but the evidence can be confusing, controversial, and even contradictory. There is overwhelming evidence that sensitization to indoor allergens is a major risk factor for the development of clinical atopic disease in genetically susceptible individuals. Not everyone agrees and there are newer data to suggest that early exposure to endotoxin and/or living on a farm and even early exposure to cats and dogs protects against sensitization by driving the immune system to a TH1 lymphocyte response. To this point, the new data are impressive if not compelling. The "hygiene hypothesis" suggests that lack of exposure to a childhood infection, endotoxin, and bacterial products is an important determinant regarding development of atopic disease. It is clear that a family history (genetics) is the strongest risk factor for the development of clinic atopic disease but it is also clear that environmental issues play a significant role and that there is a lot we still do not know.

Triamcinolone acetonide and fluticasone propionate nasal sprays provide comparable relief of seasonal allergic rhinitis symptoms regardless of disease severity.

The aim of this study was to examine the effects of aqueous triamcinolone acetonide (TAA AQ) and fluticasone propionate (FP) nasal sprays on seasonal allergic rhinitis (SAR) symptoms and health-related quality of life (HRQL) in patients stratified into cohorts based on symptom severity. In a multicenter, investigator-blinded, parallel-group study, 295 patients with a > or =2-year history of SAR received once-daily TAA AQ, 220 microg, or FP, 200 microg, for 3 weeks. Median baseline total nasal symptom score (TNSS; sum of nasal congestion, rhinorrhea, sneezing, and nasal itching scores) for all patients was 8.14 (range, 0-12). Patients were stratified by baseline TNSS into a moderate (<814) or severe (> or =8.14) cohort. Changes from baseline TNSS, individual symptom scores, and HRQL were assessed. Sixty-nine TAA AQ and 76 FP patients were included in the moderate stratum (baseline mean TNSS = 6.14 and 6.22, respectively), and 79 (TAA AQ) and 71 (FP) patients were included in the severe stratum (TNSS = 10.03 and 9.47, respectively). At the study end, patients showed significant (p < 0.0001 all comparisons) and comparable improvements in TNSS in both the moderate (TAA AQ, -2.40 [95% confidence interval [CI, -2.92, -1.87], 39% improvement; FP, -2.22 [95% CI, -2.72, -1.73], 36% improvement) and the severe (TAA AQ, -3.85 [95% CI, -4.36, -3.33], 38% improvement; FP, -3.84 [95% CI, -4.43, -3.24], 41% improvement) strata. TAA AQ and FP significantly and comparably improved HRQL in both strata versus baseline. Once-daily TAA AQ and FP nasal sprays in patients with moderate or severe SAR provided significant and comparable symptom relief and improvements in HRQL.

Fluticasone propionate aqueous nasal spray improves nasal symptoms of seasonal allergic rhinitis when used as needed (prn).

BACKGROUND: Few published clinical trials document the efficacy of intranasal corticosteroids used as needed for treatment of seasonal allergic rhinitis. OBJECTIVE: To evaluate the efficacy and safety of 4 weeks' treatment with fluticasone propionate aqueous nasal spray 200 microg used as needed (FP200PRN) in patients with seasonal allergic rhinitis. METHODS: A randomized, double-blind, placebo-controlled study in 241 patients (> or = 12 years of age) with a positive skin test result to a relevant fall allergen and who were symptomatic at randomization. The primary endpoint was the mean change from baseline in total nasal symptom score (TNSS; the sum of nasal congestion, rhinorrhea, sneezing, and nasal itching, each rated on a 4-point scale from 0 = none to 3 = severe). RESULTS: The mean percentage of days that patients used the study medications in the FP200PRN and placebo groups was 61.8% (SD = 30.4%) and 70.1% (SD = 28.3%), respectively. Patients treated with FP200PRN had a significantly greater reduction from baseline in TNSS compared with those treated with vehicle placebo (mean +/- SE = -2.02 +/- 0.18 vs -1.06 +/- 0.22, P < 0.001), representing a 91% greater improvement with FP200PRN than vehicle placebo. The FP200PRN group also had a significantly greater (P < 0.001) mean reduction in individual nasal symptoms of rhinorrhea, sneezing, nasal itching, and nasal congestion compared with placebo. FP200PRN was well tolerated, with an incidence of adverse events comparable to vehicle placebo. CONCLUSIONS: FP200PRN in patients 12 years and older is effective for treatment of nasal symptoms associated with seasonal allergic rhinitis. It has a lower incidence of adverse events than typically associated with regular once-daily use.

Pharmacokinetics of beclomethasone 17-monopropionate from a beclomethasone dipropionate extrafine aerosol in adults with asthma.

OBJECTIVE: The objectives of this study were to test the dose and strength proportionalities of beclomethasone dipropionate (BDP) delivered from two strengths of a pressurized extrafine solution formulation. METHODS: Thirty adults with mild, stable asthma, aged between 18 years and 70 years, completed the study; written informed consent was obtained from all patients. Each patient received, according to a randomized four-period crossover design, 100 microg BDP as two inhalations from 50-microg/actuation strength, 100 microg BDP as one inhalation from 100-microg/actuation strength, 400 microg BDP as eight inhalations from the 50-microg/actuation strength, and 400 microg BDP as four inhalations from the 100-microg/actuation strength. Patients self-administered all inhalations at the same time of day during the study. Blood samples were collected for 12 h during each period to assay for the presence of BDP and metabolites. The log-transformed pharmacokinetic data were compared for proportionality equivalence using a confidence-interval approach. RESULTS: Almost all the BDP-derived material in the plasma was the active metabolite beclomethasone 17-monopropionate (17-BMP). Due to low levels, neither elimination half-life ( t(1/2)) nor the area under the plasma concentration-time curve (AUC) for 17-BMP could be calculated for the 100-microg BDP doses. Dose proportionality of the 100-microg and 400-microg BDP doses, using 17-BMP maximum plasma concentration (C(max)) was demonstrated for each strength. Strength proportionality of the 50-microg and 100-microg/actuation strengths was observed for C(max) at both dose levels and for AUC at the higher dose level. The t(1/2) of 17-BMP was found to be approximately 2.8 h. CONCLUSION: This study demonstrated both the strength and dose proportionalities of the BDP extrafine aerosol. This important information will allow physicians maximum flexibility in prescribing this aerosol product.