The effects of intranasal triamcinolone acetonide and intranasal fluticasone propionate on short-term bone growth and HPA axis in children with allergic rhinitis.

OBJECTIVE: The purpose of this study was to evaluate the effects of triamcinolone acetonide (TAA) and fluticasone propionate (FP) aqueous nasal sprays on short-term lower-leg growth velocity and hypothalamic-pituitary-adrenal (HPA-axis function in pediatric subjects. METHODS: In this controlled, double-blinded (TAA) or single-blinded (FP), four-way crossover trial, 59 subjects (mean age: 7.2 years) were randomized to receive each of four 2-week treatments in random order: TAA nasal spray 110 microg, TAA nasal spray 220 microg, FP nasal spray 200 microg, and placebo, administered by a third party once daily with a 2-week washout period between treatments. Lower-leg growth velocity was measured by knemometry, and HPA-axis function was measured using 12-hour overnight urinary cortisol levels. RESULTS: Forty-nine subjects completed all four treatments and were included in the analyses. Mean growth velocity (+/- standard error) was 0.46 (+/- 0.06) mm/week for placebo, 0.37 (+/- 0.06) and 0.31 (+/- 0.06) mm/week for TAA nasal spray 110 and 220 microg, respectively, and 0.37 (+/- 0.06) mm/week for FP nasal spray. The treatment effect on mean growth velocity compared with placebo was -19.6% with TAA 110 microg, -32.6% with TAA 220 microg, and -21.7% with FP; none of these effects was considered statistically or clinically significant according to predefined criteria. No significant differences in changes in urine cortisol/creatinine ratios were observed between TAA 110 microg or 220 microg and placebo (4.38, 3.60, and -0.67, respectively, P > or = 0.157). In contrast, the change in mean urine cortisol/creatinine ratio values for FP (-3.59) were significantly lower compared with TAA 220 microg (P = 0.033) and placebo (P = 0.003). Knemometry exhibited less time-dependent variability than overnight urinary cortisol measurements. CONCLUSIONS: Neither TAA nor FP had a clinically significant effect on lower-leg growth velocity. In contrast to FP, TAA nasal spray did not significantly affect HPA-axis function when used over a 2-week interval.     

Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray

BACKGROUND: Intranasal corticosteroids are recommended as first-line therapy for allergic rhinitis (AR), and because of their pharmacologic class, hypothalamic-pituitary-adrenal (HPA) axis function is evaluated. OBJECTIVE: To evaluate whether cortisol production was suppressed (as a measure of HPA axis function) by 6 weeks of treatment with fluticasone furoate nasal spray, 110 microg once daily, in patients with perennial AR. METHODS: A double-blind, randomized, placebo- and active-controlled (prednisone), parallel-group study. Outpatients aged 12 to 65 years with perennial AR for 2 years or more were from 1 center in the United States and 1 center in Canada. Pharmacodynamic and pharmacokinetic samples were collected during 24-hour domiciled visits (overnight in clinic). Measurements included change from baseline in 24-hour serum cortisol weighted mean and 24-hour urinary free cortisol excretion, total 24-hour urinary free cortisol excretion and 6-beta hydroxycortisol excretion, and plasma concentration of fluticasone furoate. RESULTS: A total of 112 of 183 patients were randomized. Fluticasone furoate was noninferior to placebo with respect to the ratio from baseline in serum cortisol weighted mean (treatment ratio, 0.98; 95% confidence interval, 0.89 to 1.07). In contrast, use of prednisone, 10 mg once daily, significantly reduced the ratio from baseline compared with placebo. Change from baseline in 24-hour urinary cortisol excretion was similar in the fluticasone furoate and placebo groups. Plasma levels of fluticasone furoate were undetectable after 6 weeks of treatment. CONCLUSION: Fluticasone furoate nasal spray, 110 microg once daily, was not associated with HPA axis suppression in patients 12 years and older with perennial AR.     

Effect of budesonide aqueous nasal spray on hypothalamic-pituitary-adrenal axis function in children with allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are safe and effective for treating allergic rhinitis in adults. Since children may receive more systemic corticosteroid on a dose-per-weight basis than adults, the safety of corticosteroid therapy in pediatric patients is an important issue. OBJECTIVE: To determine the effects of treatment with budesonide aqueous nasal spray using the recommended once-daily dose for adults and children 6 years and older on hypothalamic-pituitary-adrenal (HPA) axis function in pediatric patients with allergic rhinitis. METHODS: In a 6-week, multicenter, double-blind, placebo-controlled study, 78 patients aged 2 to 5 years with allergic rhinitis were treated with budesonide aqueous nasal spray (64 microg/d) or placebo. Mean change in morning plasma cortisol levels from baseline to study end 0, 30, and 60 minutes after low-dose (10-microg) cosyntropin stimulation and mean change in the difference from 0 to 30 minutes and from 0 to 60 minutes after cosyntropin stimulation were used to evaluate HPA axis function. RESULTS: Mean change from baseline to study end in plasma cortisol levels 0, 30, and 60 minutes after cosyntropin stimulation and the difference from 0 to 30 minutes and from 0 to 60 minutes were not significantly different between the treatment and placebo groups (P > .05 for all). At the end of the study, 3 budesonide aqueous nasal spray and 6 placebo patients were classified as having subnormal HPA axis function. The safety and tolerability profile of budesonide aqueous nasal spray was comparable to that of placebo. CONCLUSIONS: Administration of budesonide aqueous nasal spray for 6 weeks was well tolerated and safe and had no measurable suppressive effects on HPA axis function in patients aged 2 to 5 years with allergic rhinitis.     

Long-term safety of fluticasone furoate nasal spray in adults and adolescents with perennial allergic rhinitis

BACKGROUND: Fluticasone furoate is a novel-enhanced affinity glucocorticoid and its long-term safety must be assessed. This study was designed to assess the safety and tolerability of 12-month intranasal administration of fluticasone furoate in adult and adolescent patients with perennial allergic rhinitis (PAR). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 806 patients with PAR were randomized to once daily (od) fluticasone furoate nasal spray 110 microg (n = 605) or vehicle placebo nasal spray (n = 201) for 12 months, following a 7- to 14-day screening period. Safety was assessed by monitoring adverse events (AEs), 24-h urinary cortisol excretion, nasal and ophthalmic examinations, electrocardiograms and clinical laboratory tests. Plasma concentrations of fluticasone furoate were determined from blood samples. RESULTS: Fluticasone furoate was well tolerated. The incidence of most AEs was similar to that observed with placebo, with the exception of epistaxis, which was more frequently reported on active treatment. There were no clinically meaningful differences between fluticasone furoate and placebo in terms of safety assessments, including mean changes in ophthalmic parameters and 24-h urine cortisol excretion. Plasma concentrations of fluticasone furoate were not quantifiable in the majority of patients following intranasal administration. CONCLUSIONS: Long-term (12-month) administration of fluticasone furoate 110 microg od revealed an AE profile typical of the intranasal corticosteroid class in both adult and adolescent patients with PAR, with no evidence of clinically relevant systemic corticosteroid exposure.     

Fluticasone propionate aqueous nasal spray does not influence the recurrence rate of chronic rhinosinusitis and nasal polyps 1 year after functional endoscopic sinus surgery

BACKGROUND: Local corticosteroids are widely used in the treatment of nasal polyps and chronic rhinosinusitis both before and after nasal surgery. Their efficacy after functional endoscopic sinus surgery (FESS) has not been fully established by placebo-controlled trials. OBJECTIVE: This double-blind placebo-controlled randomized study was performed in order to investigate whether fluticasone propionate aqueous nasal spray (FPANS) reduces the recurrence rate of nasal polyps and chronic rhinosinusitis during the first year after FESS. PATIENTS AND METHODS: The trial looked at 162 patients aged 18 years and older requiring FESS for chronic rhinosinusitis or nasal polyps. After FESS combined with peri-operative systemic corticosteroids, patients were randomized and given FPANS 400 microg b.i.d., FPANS 800 microg b.i.d. or placebo b.i.d. for the duration of 1 year. Patients were withdrawn from the trial (but still included in the study for statistical purposes) if there were recurrent or persistent diseases, defined as progressive regrowth of nasal polyps, recurrent signs and symptoms of chronic sinusitis combined with abnormalities on computed tomography scan and persistent complaints for at least 2 months after FESS. RESULTS: A significant reduction of symptoms was seen after FESS. After 1 year, 46 patients had been withdrawn from the trial because of recurrent diseases and 32 patients because of persistent symptoms. No differences in the number of patients withdrawn because of recurrent or persistent diseases were found between the patients treated with FPANS and patients treated with placebo. We were also unable to find a positive effect of FPANS compared with placebo in several subgroups such as patients with nasal polyps, high score at FESS or no previous sinus surgery. CONCLUSION: This placebo-controlled study does not show that treatment with FPANS up to 1 year after FESS had a positive effect compared with placebo.     

A placebo-controlled study of fluticasone propionate aqueous nasal spray and beclomethasone dipropionate in perennial rhinitis: efficacy in allergic and non-allergic perennial rhinitis

Background: Fluticasone propionate is a new potent, topically active corticosteroid with ncgligahle oral bioavailability. Data on its comparative efficacy in perennial allergic and non-allergic rhinitis are limited. Objective: To compare the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200μg once or twice daily with beclomethasone dipropionate aqueous nasal spray (BDP) 200μg twice daily and placebo in patients with allergic and nonallergic perennial rhinitis. Methods: The 12-week study had a multicenlre, double-blind, randomized, parallel group design. Efficacy was assessed from symptom scores recorded on daily diary cards. Results: FPANS 200μg once or twice daily was significantly better than placebo but not better than BDP in relieving the nasal symptoms of rhinitis. FPANS at either dose was equally effective in the treatment of allergic and non-allergic perennial rhinitis. There were few adverse events and no treatment-related abnormalities in laboratory measurements in either FPANS-treated group. Comparisons between treatment groups indicated that FPANS was as well tolerated as placebo and BDP at the doses studied. Conclusions: In the majority of patients FPANS 200μg once daily is as effective as BDP 200μg twice daily in the relief of perennial allergic rhinitis.     

Comparison of a nasal glucocorticoid,antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis

BACKGROUND: Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihistamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis. OBJECTIVE: We evaluated how such a combination treatment would affect symptoms and local mucosal eosinophilia in comparison with a nasal glucocorticoid. METHODS: In a double-blind, randomized study 62 patients with grass pollen-induced allergic rhinitis received a nasal glucocorticoid (fluticasone propionate aqueous nasal spray [FPANS], 200 microg/d), an antileukotriene (montelukast, 10 mg/d), a combination of montelukast with an antihistamine (loratadine, 10 mg/d), or placebo throughout the season. Cromoglycate eyedrops and a limited amount of loratadine were allowed as rescue medication for severe symptoms. Patients recorded their symptoms for nasal blockage, itching, rhinorrhea, and sneezing. Before and during the season, nasal biopsy specimens were obtained from patients for evaluation of local eosinophilic inflammation. RESULTS: During the peak season, both FPANS and combined montelukast-loratadine were significantly more effective than placebo and montelukast alone for daytime symptom prevention. For nighttime symptoms, FPANS was significantly more effective compared with all other treatments, whereas combined montelukast-loratadine and montelukast alone did not provide significant symptom prevention compared with placebo. The pollen-induced increase in the numbers of epithelial eosinophils was significantly lower for FPANS-treated patients compared with that seen in all other treatment groups. CONCLUSION: In patients with seasonal allergic rhinitis, intranasal glucocorticoids are more effective than an antileukotriene drug or combined antileukotriene-antihistamine for the reduction of pollen-induced nasal eosinophilic inflammation and for control of nasal symptoms.     

The efficacy and tolerability of fluticasone propionate aqueous nasal spray in children with seasonal allergic rhinitis

Fluticasone propionate aqueous nasal spray (FPANS) contains fluticasone propionate, which is a new topically active glucocorticoid with approximately twice the potency of beclomethasone dipropionate. In this European multicentre study, 143 children with seasonal allergic rhinitis were recruited: 47 received FPANS 100 jag once a day (od), 46 received FPANS 200 μg od, and 50 patients received placebo od, for 4 weeks. Treatment efficacy was assessed using diary card nasal symptom scores for sneezing, rhinorrhoea, blockage and itching, and eye watering/irritation. Patients receiving FPANS 100 μg or FPANS 200 μg demonstrated statistically significant improvements in median nasal symptom scores in all the symptoms recorded, when compared with placebo. There were no statistically significant differences between the FPANS 100 μg and FPANS 200 μg groups in improvement in nasal symptom scores. There was no effect on eye watering/irritation symptoms which could be attributed to either FPANS 100 μg or FPANS 200 μg when compared with placebo. Use of rescue antihistamine medication was significantly reduced in the FPANS 100 μg group when compared with placebo. The adverse events profile was similar in all three treatment groups, and the events reported were generally mild and related to the patients' rhinitis.     

A double-blind, placebo-controlled comparison of treatment with fluticasone propionate and levocabastine in patients with seasonal allergic rhinitis. FLNCO2 Italian Study Group

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P<0.02 and P<0.01) and rhinorrhea (P<0.01) than levocabas tine. In addition, fewer patients treated with FPANS used rescue medication (P<0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 microg, once daily, provides a better clinical effect than levocabastine 200 microg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.     

Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.

BACKGROUND: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels. OBJECTIVES: 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression. METHODS: Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level. RESULTS: One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results. CONCLUSIONS: Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.     

Long-term effects of corticosteroid nasal spray on nasal inflammatory cells in patients with perennial allergic rhinitis

BACKGROUND: The effect of long-term topical nasal corticosteroid therapy on nasal inflammatory cells is unclear. OBJECTIVES: To investigate the long-term effect of fluticasone propionate aqueous nasal spray (FPANS) on nasal mucosal inflammatory cells and efficacy in a 1-year study in patients with perennial allergic rhinitis. METHODS: In a 1-year, double-blind, placebo-controlled study of duration we investigated the influence of a topical corticosteroid (FPANS), on Langerhans' cells (CD1a+ cells), T cells, mast cells, eosinophils and macrophages in nasal mucosa in 42 patients with perennial allergic rhinitis. Efficacy was evaluated by nasal symptom score. RESULTS: The FPANS group experienced significantly less sneezing and nasal itching compared with the placebo group. The total symptom score in the FPANS group declined significantly in comparison with baseline (P = 0.007) and placebo group (P = 0.009). After 1 year of active treatment, a significant decrease was seen in the epithelium in numbers of Langerhans' cells, CD3+, CD4+, CD8+ cells, mast cells and eosinophils. In the lamina propria, there was a significant decrease in eosinophils. CONCLUSION: These findings show that FPANS treatment results in a decrease of nasal inflammatory cells. Furthermore, the efficacy of FPANS improves after prolonged treatment.     

Comparison of once daily fluticasone propionate aqueous nasal spray with once daily budesonide reservoir powder device in patients with perennial rhinitis

BACKGROUND: Previous studies comparing the corticosteroids fluticasone propionate (FP) and budesonide (BUD) in both perennial and seasonal rhinitis have shown no consistent difference between treatments. However, the therapeutic outcomes may have been influenced by study design. OBJECTIVE: To compare the effect of FP aqueous nasal spray (ANS; 200 microg/day) with BUD reservoir powder device (RPD; 200 microg/day) on rhinitis symptoms, productivity loss and device preference in patients with perennial rhinitis. METHODS: After a 2-week run-in period, 440 patients were randomized to receive either FPANS, BUD RPD or matched placebo (ANS or RPD) for 8 weeks, followed by an open-label 4-week follow-up treatment with FPANS. Patients completed diary card visual analogue scores for nasal symptoms, and questionnaires on satisfaction with the treatment and preferred choice of device. RESULTS: During weeks 1-4, the visual analogue total nasal symptom scores (VATNS) in the FPANS group were significantly lower than scores in the BUD RPD group (mean difference = -17.8; 95% CI = -34.4, -1.3; P = 0.036). FPANS also significantly reduced the VATNS compared with the ANS placebo at all time-points assessed (P < or = 0.005). BUD RPD did not significantly differ from the RPD placebo at weeks 5-8 (P = 0.167), or the ANS placebo at any time-point (P < or = 0.151). Over the 8-week treatment period FPANS was significantly more effective than BUD RPD at reducing sneezing (mean difference = -4.4; 95% CI = -8.6, -0.3; P = 0.036) and nasal itching (mean difference = -5.3; 95% CI = -9.9, -0.8; P = 0.022), and was significantly superior to the ANS placebo for all symptoms assessed at weeks 1-4 and 1-8 (P < 0.016). At the same time-points BUD RPD was no better at alleviating nasal itching than the RPD placebo (P < or = 0.306), and compared with the ANS placebo, significantly reduced only one symptom; nasal blockage (P < or = 0.016). After 8 weeks of treatment, patients preferred the ANS device to the RPD (P < 0.001), and at 12 weeks a significantly greater number of patients were satisfied with FPANS treatment compared with BUD RPD (P = 0.0019) or the respective placebos (P = 0.0001). CONCLUSION: FPANS and BUD RPD are effective therapies with a good safety profile for the treatment of perennial rhinitis but, in this direct placebo-controlled comparison, FPANS was more efficacious than BUD RPD, and the patients preferred the ANS device to the RPD.     

Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis

Background: Topical steroids are first‐line medication to control nasal polyposis (NP), a disease with long‐term clinical course. Objective: The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 μg twice a day (bd) after 1 month of treatment, and to compare FPANS 200 μg bd and FPANS 200 μg once a day (od) in maintenance and long‐term treatment. Methods: Double‐blind, placebo‐controlled, 8‐month study with three treatment periods (1‐month acute period followed with 1‐month maintenance period and 6‐month follow‐up period) was carried out. Group 1 received FPANS 200 μg bd, during acute, maintenance and follow‐up periods, Group 2 received FPANS 200 μg bd during acute period and FPANS 200 μg od during maintenance and follow‐up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 μg bd during follow‐up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade. Results: After acute period and maintenance periods, FPANS 200 μg bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 μg od after 1‐month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6‐month follow‐up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events. Conclusion: The study demonstrated the efficacy of FPANS 200 μg bd in acute treatment and FPANS 200 μg od as a sufficient dose to maintain a long‐term efficacy in the treatment for NP.     

The effect of nasal steroid aqueous spray on nasal complaint scores and cellular infiltrates in the nasal mucosa of patients with nonallergic, noninfectious perennial rhinitis

Topical corticosteroids are the therapy of choice for nonallergic, noninfectious perennial rhinitis (NANIPER). However, the efficacy of steroid therapy in NANIPER is controversial, as is its mode of action. To our surprise, of 300 patients initially diagnosed as having NANIPER, only 65 reached threshold nasal symptom scores. Patients were randomized into four different treatment regimens: placebo administered twice daily (BD) for 8 weeks, fluticasone propionate aqueous nasal spray (FPANS) (200 μg) once daily (OD) and placebo OD for 8 weeks, FPANS (200 μg) OD and placebo OD for 4 weeks followed by FPANS (200 μg) BD for 4 weeks, and FPANS (200 μg) BD for 8 weeks. A small decrease in nasal symptoms was found, which only reached significance for sneezing in the FPANS 200 μg BD group. A significant dose-dependent decrease in immunocompetent cells was found in nasal biopsy specimens obtained before, after 4 weeks, and after 8 weeks of treatment. We conclude that FPANS did not significantly reduce nasal symptoms in this group of selected NANIPER patients, even though a significant effect on cells in the nasal mucosa was seen. (J Allergy Clin Immunol 1997;100:739-47.)     

Once daily fluticasone propionate aqueous nasal spray is an effective treatment for seasonal allergic rhinitis

A multicenter double-blind, randomized, parallel group study was conducted to evaluate the once daily administration of fluticasone propionate, a potent, new corticosteroid preparation, for the treatment of seasonal allergic rhinitis. Adult patients (n = 227) were treated for 2 weeks with fluticasone propionate aqueous nasal spray 200 micrograms QD or 100 micrograms BID or matching placebo during the autumn pollen season. Overall, the administration of fluticasone propionate once daily in the morning was as effective as the twice daily dosage regimen, and either regimen was more effective than placebo. Improvement in clinician-rated and patient-rated nasal symptom scores, including morning nasal obstruction, was evident within three days of fluticasone propionate therapy and continued throughout the treatment period. Fewer patients receiving fluticasone propionate used rescue medication and had nasal eosinophilia compared with patients receiving placebo. Adverse events were similar in frequency and nature in all three treatment groups. Morning plasma cortisol concentrations and response to cosyntropin stimulation were similar across groups and offered no evidence of HPA axis suppression. We conclude that fluticasone propionate aqueous nasal spray administered once daily is a safe and effective treatment for seasonal allergic rhinitis. The convenience of a once daily regimen may encourage better compliance.     

Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis

BACKGROUND: Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms. OBJECTIVE: We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 microg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season. METHODS: One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 microg once daily (n=20) or with FPANS 200 microg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 microg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage. RESULTS: All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK. CONCLUSION: The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.     

Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis.

BACKGROUND: Mometasone furoate nasal spray (MFNS) 400 microg, twice daily, as adjunctive treatment with oral antibiotic significantly improved symptoms of recurrent rhinosinusitis. OBJECTIVE: To evaluate the effectiveness and safety of MFNS 200 microg, twice daily, and 400 microg, twice daily, compared with placebo as adjunctive treatment with oral antibiotic for acute rhinosinusitis. METHODS: In this multicenter, double-blind, placebo-controlled study, 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin/clavulanate potassium (Augmentin, GlaxoSmithKline, Research Triangle Park, NC) 875 mg, twice daily, for 21 days with adjunctive twice daily MFNS 200 microg, MFNS 400 microg, or placebo nasal spray. Patients recorded scores of six rhinosinusitis symptoms and any adverse events twice daily. Pre- and postcosyntropin-stimulation plasma cortisol levels were measured in a subset of patients at selected study sites. RESULTS: Treatment with MFNS 200 microg or 400 microg, twice daily, produced significantly greater improvements in total symptoms score (primary efficacy variable) day 1 to day 15 average (50% and 51%, respectively) than placebo (44%, P < or = 0.017). Both doses of MFNS produced significant total symptoms score improvement over placebo by day 4, and maintained efficacy over the entire 21-day study. Relief of individual symptoms showed a similar pattern. Both doses of MFNS were well tolerated, and adverse events were similar to that of placebo. Cosyntropin stimulation showed no evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 microg or 400 microg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone.     

Long-term safety of budesonide nasal aerosol: a 5.5-year follow-up study

The effects of prolonged treatment with intranasally applied budesonide was studied in twenty-four patients with perennial allergic or non-allergic rhinitis. Patients on continuous treatment were followed up for 5.5 years. At entry and follow-up visits, rhinoscopic findings, nasal symptom scores, blood chemistry, haematology, urine analysis and determination of plasma cortisol levels, before and after stimulation with ACTH (Synacthen®, Ciba-Geigy AG, Basel, Switzerland), were registered. Biopsies of the nasal mucosa were taken before entry into the study, after 1 year of treatment, and after varying time intervals ranging from 2.5 to 5.5 years during the treatment. The biopsy specimens were examined blindly by an independent pathologist. The analyses revealed no histopathological changes in the nasal mucosa. All nasal symptom parameters assessed by the patients were significantly reduced from the baseline during the entire follow-up period. No clinically significant changes in the haematological and blood chemistry parameters were observed. Plasma cortisol analyses before and after challenge with ACTH revealed no influence on the hypothalamic pituitary adrenal (HPA) axis. The present study suggests that intranasal budesonide in the dose of 200–400 μg/day is also a safe treatment for prolonged treatment of perennial rhinitis.     

Chronic subcutaneous leptin infusion diminishes the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in female rhesus monkeys

The fat derived protein leptin has its anorexic action through a number of neuropeptides including an upregulation of corticotropin releasing hormone (CRH) expression in the hypothalamus. However, the influence of leptin on these neuropeptides may be different during stress. The present study used ovariectomized female rhesus monkeys (n=8) to further define the effect of leptin on HPA responsivity. To accomplish this, we assessed the effects of constant leptin infusion on cortisol and ACTH secretion in both a predictable and unpredictable situation as well as in response to dexamethasone suppression-CRH stimulation test. We hypothesized that leptin would attenuate the increase in cortisol and ACTH to a novel, unpredictable situation and would enhance glucocorticoid negative feedback and diminish the response to CRH. Animals were assessed under control placebo conditions and during a 28 day infusion with recombinant human leptin (6 microg/kg/day, SC). Within each treatment condition, HPA responsivity was assessed during no estradiol replacement and acute estradiol replacement that produced serum concentrations of approximately 40 pg/ml. However, the results indicated that neither estradiol alone or in combination with leptin had any consistent effect on the outcome measures. Compared to the control condition, leptin had no effect on the cortisol diurnal rhythm; however, evening but not morning plasma ACTH concentrations were significantly lower during leptin infusion. In contrast, the response in plasma cortisol and ACTH to an unpredictable situation was significantly attenuated by chronic leptin infusion. Furthermore, leptin enhanced glucocorticoid negative feedback and blunted CRH-induced increase in both cortisol and ACTH. Taken together, these data suggest that in the female monkey, leptin has little effect on basal cortisol. However, when the HPA axis is activated, leptin attenuates the neuroendocrine response by enhancing glucocorticoid negative feedback. These data underscore the potential importance of leptin in maintaining homeostasis through its diverse interaction with the HPA axis.     

Efficacy and safety of concurrent use of intranasal flunisolide and oral beclomethasone aerosols in treatment of asthmatics with rhinitis

Steroid-dependent, chronic asthmatic patients with severe rhinitis or nasal polyps are often candidates for treatment with intranasal topical corticosteroids, such as flunisolide. The possibility of additive adrenal suppression, when flunisolide, beclomethasone and prednisone are given together, has not previously been studied. The need to assess this risk is suggested by reports of additive adrenal suppression when aerosol and oral steroids are used together to treat asthma, and by the demonstrably higher systemic availability of aerosol steroid given intranasally rather than via the lung. We performed a double-blind, placebo-controlled crossover assessment of the efficacy and safety of 3 weeks of intranasal flunisolide spray treatment (300 γg/day) in nineteen steroid-dependent chronic asthmatic subjects, who also had nasal polyps or severe rhinitis. During the study, their doses of prednisone and beclomethasone, used for asthma, were held stable. Morning serum cortisol levels and 24-hr urinary-free cortisol excretion were essentially the same after the placebo, and the flunisolide treatments. The intranasal flunisolide improved their nasal symptoms significantly (P < 0.05). Local complications were negligible. Given conventional steroid doses like those used in this study, there appears to be no important risk to endogenous adrenal function from combining the use of intranasal, flunisolide spray with administration of other steroids by other routes, when this is deemed clinically necessary. If higher doses are used, the possibility of some additive adrenal suppressive effect cannot be excluded.