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Rhinorrhea Not Responding to Nasal Corticosteroids
S232 Abstracts
909
Lack of Effect on Hypothalamic-Pituitary-Adrenal (HPA) Axis Function by Once-daily Fluticasone Furoate* Nasal Spray (FFNS) 110 mcg in Children with Perennial Allergic Rhinitis (PAR) *USAN approved name I. Tripathy1, R. Sterling2, D. Clements3, W. Wu3, M. Faris3, E. Philpot3; 1 Clinical Research of the Ozarks, Rolla, MO, 2Carolina Research, Orangeburg, SC, 3GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: Despite the effectiveness of intranasal corticosteroids in managing rhinitis, physicians may be reluctant to prescribe them as long-term treatment to children due to concerns of potential systemic effects. The objective of this study was to determine if there is a reduction in 24-hour serum or urine cortisol, indicative of HPA axis suppression, in children treated with FF, a novel, enhanced-affinity corticosteroid. Bioavailability was determined via serial pharmacokinetic sampling. METHODS: Randomized, double-blind, parallel-group, placebo-controlled, 6-week trial assessing the effects of once-daily FFNS 110mcg on 24-hour serum and urine cortisol in PAR subjects 2 to <12 years of age in a controlled, domiciled environment. Endpoints included change from baseline (expressed as a ratio) in serum cortisol (primary) and urinary free cortisol excretion and serial plasma concentrations of FF. Safety was assessed by adverse events, ECGs, and laboratory tests. Treatment compliance was assessed via several means. RESULTS: Geometric mean serum cortisol ratios from baseline at Week 6 were similar for FFNS (0.94) and placebo (0.98). Adjusting for baseline weighted mean and center, FFNS was non-inferior to placebo (treatment ratio 0.97, 95% CI [0.88, 1.07]). No subjects had urinary free cortisol excretion levels below normal range at Week 6. FF levels were generally not quantifiable after 6 weeks dosing. No safety issues were identified. Conventional and novel compliance assessments provided validation of the safety data. CONCLUSIONS: Once-daily FFNS 110mcg was well-tolerated and not associated with HPA axis suppression following 6 weeks of treatment in children aged 2 to <12 years with PAR. Funding: GlaxoSmithKline
MONDAY
910
Once-daily Fluticasone Furoate* Nasal Spray (FFNS) is Effective for the Treatment of Seasonal Allergic Rhinitis (SAR) Caused by Ragweed *USAN-approved name H. B. Kaiser1, R. Naclerio2, J. Given3, E. Philpot4, T. Toler4, A. Ellsworth4; 1Asthma and Allergy Specialists, Minneapolis, MN, 2University of Chicago Hospitals, Chicago, IL, 3Allergy and Respiratory Center, Canton, OH, 4GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: To investigate the efficacy and safety of a novel, enhancedaffinity corticosteroid, FFNS, in treating SAR from ragweed. METHODS: Two hundred ninety-nine subjects (12 years) were randomized to double-blind treatment for two weeks with FFNS 110mcg or vehicle placebo administered using a unique, side-actuated device. Primary endpoint was the mean change from baseline (MCFB) over the two-week treatment period in daily reflective total nasal symptom scores (rTNSS). (Daily rTNSS 5 average of the morning [AM] and evening score totals for nasal congestion, nasal itching, rhinorrhea, and sneezing, each rated on a 0-3 scale [none to severe]). Key secondary endpoints included MCFB in AM pre-dose, instantaneous (i)TNSS and subject-rated response to therapy (RT). Time of onset of effect was evaluated by MCFB in iTNSS at 4, 6, 8, 10, and 12 hours post-first dose. Safety assessments included adverse events (AEs) and laboratory tests. RESULTS: Baseline scores were similar. Least squared (LS) MCFB for daily rTNSS was -2.07 (placebo) and -3.55 (FFNS) (p<0.001) demonstrating significantly greater improvement with FFNS. FFNS also showed sustained efficacy over 24-hours based on the LS MCFB for AM pre-dose iTNSS (-1.53, placebo; -2.90, FFNS; p<0.001). Onset of effect was observed at 8 hours (p50.028). RT ratings for moderate/significant improvement were 21% (placebo) and 42% (FFNS) (p<0.001). FFNS was well tolerated with a drug-related AE incidence of 1% (placebo) and 4% (FFNS).
J ALLERGY CLIN IMMUNOL JANUARY 2007
CONCLUSIONS: FFNS 110mcg demonstrated clinically significant, sustained 24-hour efficacy against the common nasal symptoms of ragweed SAR beginning at 8 hours after the first dose. Funding: GlaxoSmithKline
911
Rhinorrhea Not Responding to Nasal Corticosteroids P. N. Patel1, B. Oyefara1, R. Aarstad2, S. L. Bahna1; 1Allergy/ Immunology Section, Louisiana State University Health Sciences Center, Shreveport, LA, 2Otolaryngology Department, Louisiana State University Health Sciences Center, Shreveport, LA. RATIONALE: Rhinorrhea in asthma patients is commonly due to allergic rhinitis but can be secondary to more dangerous causes. METHODS: Case report. RESULTS: A woman with multiple illnesses including allergic rhinitis, asthma, and atopic dermatitis presented for follow-up in our Allergy/ Immunology clinic with constant runny nose for two weeks despite regular use of nasal steroids. Two weeks earlier, after heavy drinking and doubling her medications for missed doses, including anti-hypertensives, she felt dizzy and fell on her face. In the ER, the records documented headache, bradycardia, hypotension, dehydration, and right infraorbital swelling (without notation on nasal findings). She was admitted for hydration and observation, and was discharged after two days without radiologic evaluation of the head. Our examination showed clear watery discharge from the right nostril and pale turbinates bilaterally. CSF rhinorrhea was suspected but glucose testing was not available. Neurosurgery was contacted and the patient was admitted. A Beta-2transferrin test confirmed CSF from the right nostril. Head CT showed a left maxillary sinus cyst but no reported fractures. Repeat CT additionally revealed fluid in the right sphenoid sinus. A lumbar drain was placed to release the pressure and antibiotic prophylaxis was started. Nasal endoscopy revealed CSF leak from the cribriform plate with 2 3 0.6 cm bone dehiscence and 3 mm dural tear. A graft from nasal septal cartilage and temporalis fascia was applied using TissealÓ fibrin glue. CONCLUSION: This case demonstrates the importance of considering CSF rhinorrhea, particularly when it is unilateral, even in patients known to have allergic rhinitis.
912
Viremia is Associated with Sleep Disturbances, Neurocognitive Disorders and Cytokine Dysregulation in Pediatric HIV Infection S. B. Foster1, M. E. Paul1, D. G. Glaze1, J. M. Reuben2, L. L. Harris1, E. N. Cohen2, B. Lee2, C. A. Kozinetz1, H. L. Schwarzwald1, M. W. Kline1, C. D. Jackson1, A. J. Loeb1, P. E. Frerking1, J. E. Fehlis1, P. Y. Brouwers1, W. T. Shearer1; 1Baylor College of Medicine, Houston, TX, 2 University of Texas, MD Anderson Cancer Center, Houston, TX. RATIONALE: The cytokine dysregulation experienced by HIV-infected children favors overall clinical worsening, including the development of sleep disturbances and neurocognitive disorders. METHODS: Validated questionnaires, actigraphy, and neurocognitive tests assessed the sleep habits and neuropsychological performance of 15 HIV-infected children and 15 controls (8-17 years). Plasma levels of proand anti-sleep cytokines were measured every 2 to 4 hours. Inducible secretion of cytokines by activated lymphocytes was also measured by flow cytometry on samples collected at 4 am and 4 pm. Statistical methods: Spearman correlations; Wilcoxon, Kruskal-Wallis, Mann-Whitney, and T-tests. RESULTS: HIV-infected children slept more overall and slept longer at night than controls (p<0.05). Increased sleep during the day was associated with decreased performance on 3 tests of attention in the HIV-infected subjects (n513, p<0.05). Plasma IL-12 (pro-sleep) and IL-10 (anti-sleep) levels were higher in HIV-infected subjects with higher viral loads (>400 copies/ml, n58) at 4 and 8 am or at 8 am alone, respectively, when compared with HIV-infected subjects with lower viral loads (<400 copies/ ml, n57) or controls (n514, p<0.05). A significantly higher percentage of SEB-activated CD81 T-cells of HIV-infected patients with higher viral loads (n58) secreted IFN-gamma than those of controls (n515, p<0.05).
909
Lack of Effect on Hypothalamic-Pituitary-Adrenal (HPA) Axis Function by Once-daily Fluticasone Furoate* Nasal Spray (FFNS) 110 mcg in Children with Perennial Allergic Rhinitis (PAR) *USAN approved name I. Tripathy1, R. Sterling2, D. Clements3, W. Wu3, M. Faris3, E. Philpot3; 1 Clinical Research of the Ozarks, Rolla, MO, 2Carolina Research, Orangeburg, SC, 3GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: Despite the effectiveness of intranasal corticosteroids in managing rhinitis, physicians may be reluctant to prescribe them as long-term treatment to children due to concerns of potential systemic effects. The objective of this study was to determine if there is a reduction in 24-hour serum or urine cortisol, indicative of HPA axis suppression, in children treated with FF, a novel, enhanced-affinity corticosteroid. Bioavailability was determined via serial pharmacokinetic sampling. METHODS: Randomized, double-blind, parallel-group, placebo-controlled, 6-week trial assessing the effects of once-daily FFNS 110mcg on 24-hour serum and urine cortisol in PAR subjects 2 to <12 years of age in a controlled, domiciled environment. Endpoints included change from baseline (expressed as a ratio) in serum cortisol (primary) and urinary free cortisol excretion and serial plasma concentrations of FF. Safety was assessed by adverse events, ECGs, and laboratory tests. Treatment compliance was assessed via several means. RESULTS: Geometric mean serum cortisol ratios from baseline at Week 6 were similar for FFNS (0.94) and placebo (0.98). Adjusting for baseline weighted mean and center, FFNS was non-inferior to placebo (treatment ratio 0.97, 95% CI [0.88, 1.07]). No subjects had urinary free cortisol excretion levels below normal range at Week 6. FF levels were generally not quantifiable after 6 weeks dosing. No safety issues were identified. Conventional and novel compliance assessments provided validation of the safety data. CONCLUSIONS: Once-daily FFNS 110mcg was well-tolerated and not associated with HPA axis suppression following 6 weeks of treatment in children aged 2 to <12 years with PAR. Funding: GlaxoSmithKline
MONDAY
910
Once-daily Fluticasone Furoate* Nasal Spray (FFNS) is Effective for the Treatment of Seasonal Allergic Rhinitis (SAR) Caused by Ragweed *USAN-approved name H. B. Kaiser1, R. Naclerio2, J. Given3, E. Philpot4, T. Toler4, A. Ellsworth4; 1Asthma and Allergy Specialists, Minneapolis, MN, 2University of Chicago Hospitals, Chicago, IL, 3Allergy and Respiratory Center, Canton, OH, 4GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: To investigate the efficacy and safety of a novel, enhancedaffinity corticosteroid, FFNS, in treating SAR from ragweed. METHODS: Two hundred ninety-nine subjects (12 years) were randomized to double-blind treatment for two weeks with FFNS 110mcg or vehicle placebo administered using a unique, side-actuated device. Primary endpoint was the mean change from baseline (MCFB) over the two-week treatment period in daily reflective total nasal symptom scores (rTNSS). (Daily rTNSS 5 average of the morning [AM] and evening score totals for nasal congestion, nasal itching, rhinorrhea, and sneezing, each rated on a 0-3 scale [none to severe]). Key secondary endpoints included MCFB in AM pre-dose, instantaneous (i)TNSS and subject-rated response to therapy (RT). Time of onset of effect was evaluated by MCFB in iTNSS at 4, 6, 8, 10, and 12 hours post-first dose. Safety assessments included adverse events (AEs) and laboratory tests. RESULTS: Baseline scores were similar. Least squared (LS) MCFB for daily rTNSS was -2.07 (placebo) and -3.55 (FFNS) (p<0.001) demonstrating significantly greater improvement with FFNS. FFNS also showed sustained efficacy over 24-hours based on the LS MCFB for AM pre-dose iTNSS (-1.53, placebo; -2.90, FFNS; p<0.001). Onset of effect was observed at 8 hours (p50.028). RT ratings for moderate/significant improvement were 21% (placebo) and 42% (FFNS) (p<0.001). FFNS was well tolerated with a drug-related AE incidence of 1% (placebo) and 4% (FFNS).
J ALLERGY CLIN IMMUNOL JANUARY 2007
CONCLUSIONS: FFNS 110mcg demonstrated clinically significant, sustained 24-hour efficacy against the common nasal symptoms of ragweed SAR beginning at 8 hours after the first dose. Funding: GlaxoSmithKline
911
Rhinorrhea Not Responding to Nasal Corticosteroids P. N. Patel1, B. Oyefara1, R. Aarstad2, S. L. Bahna1; 1Allergy/ Immunology Section, Louisiana State University Health Sciences Center, Shreveport, LA, 2Otolaryngology Department, Louisiana State University Health Sciences Center, Shreveport, LA. RATIONALE: Rhinorrhea in asthma patients is commonly due to allergic rhinitis but can be secondary to more dangerous causes. METHODS: Case report. RESULTS: A woman with multiple illnesses including allergic rhinitis, asthma, and atopic dermatitis presented for follow-up in our Allergy/ Immunology clinic with constant runny nose for two weeks despite regular use of nasal steroids. Two weeks earlier, after heavy drinking and doubling her medications for missed doses, including anti-hypertensives, she felt dizzy and fell on her face. In the ER, the records documented headache, bradycardia, hypotension, dehydration, and right infraorbital swelling (without notation on nasal findings). She was admitted for hydration and observation, and was discharged after two days without radiologic evaluation of the head. Our examination showed clear watery discharge from the right nostril and pale turbinates bilaterally. CSF rhinorrhea was suspected but glucose testing was not available. Neurosurgery was contacted and the patient was admitted. A Beta-2transferrin test confirmed CSF from the right nostril. Head CT showed a left maxillary sinus cyst but no reported fractures. Repeat CT additionally revealed fluid in the right sphenoid sinus. A lumbar drain was placed to release the pressure and antibiotic prophylaxis was started. Nasal endoscopy revealed CSF leak from the cribriform plate with 2 3 0.6 cm bone dehiscence and 3 mm dural tear. A graft from nasal septal cartilage and temporalis fascia was applied using TissealÓ fibrin glue. CONCLUSION: This case demonstrates the importance of considering CSF rhinorrhea, particularly when it is unilateral, even in patients known to have allergic rhinitis.
912
Viremia is Associated with Sleep Disturbances, Neurocognitive Disorders and Cytokine Dysregulation in Pediatric HIV Infection S. B. Foster1, M. E. Paul1, D. G. Glaze1, J. M. Reuben2, L. L. Harris1, E. N. Cohen2, B. Lee2, C. A. Kozinetz1, H. L. Schwarzwald1, M. W. Kline1, C. D. Jackson1, A. J. Loeb1, P. E. Frerking1, J. E. Fehlis1, P. Y. Brouwers1, W. T. Shearer1; 1Baylor College of Medicine, Houston, TX, 2 University of Texas, MD Anderson Cancer Center, Houston, TX. RATIONALE: The cytokine dysregulation experienced by HIV-infected children favors overall clinical worsening, including the development of sleep disturbances and neurocognitive disorders. METHODS: Validated questionnaires, actigraphy, and neurocognitive tests assessed the sleep habits and neuropsychological performance of 15 HIV-infected children and 15 controls (8-17 years). Plasma levels of proand anti-sleep cytokines were measured every 2 to 4 hours. Inducible secretion of cytokines by activated lymphocytes was also measured by flow cytometry on samples collected at 4 am and 4 pm. Statistical methods: Spearman correlations; Wilcoxon, Kruskal-Wallis, Mann-Whitney, and T-tests. RESULTS: HIV-infected children slept more overall and slept longer at night than controls (p<0.05). Increased sleep during the day was associated with decreased performance on 3 tests of attention in the HIV-infected subjects (n513, p<0.05). Plasma IL-12 (pro-sleep) and IL-10 (anti-sleep) levels were higher in HIV-infected subjects with higher viral loads (>400 copies/ml, n58) at 4 and 8 am or at 8 am alone, respectively, when compared with HIV-infected subjects with lower viral loads (<400 copies/ ml, n57) or controls (n514, p<0.05). A significantly higher percentage of SEB-activated CD81 T-cells of HIV-infected patients with higher viral loads (n58) secreted IFN-gamma than those of controls (n515, p<0.05).