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Videophone Technology, a Novel Measure of True Treatment Compliance in a 6-week Pediatric Safety Study of Fluticasone Furoate∗ Nasal Spray ∗USAN approved name
S306 Abstracts
1194
Lack of Correlation Between Physical Exam(PE), Mini RQLQ (MRQLQ), and Nasal Peak Inspiratory Flow (nPIF) as Measures of Nasal Congestion in Obstructive Sleep Apnea (OSA) Patients With Rhinitis M. R. Rupp, Jr.1 A. S. Baran2, G. D. Marshall, Jr.2; 1Allergy and Asthma Clinic of Southern New Mexico Las Cruces, NM, 2University of Mississippi Medical Center, Jackson, MS. RATIONALE: OSA is an increasingly common problem which often requires treatment with nasal CPAP therapy. Nasal congestion alters the effectiveness of CPAP therapy. We sought to evaluate the effectiveness of various measures of nasal congestion that might assist physicians in diagnosing and treating this problem. METHODS: 42 patients age 18-65 with OSA and rhinitis participated. Those with lower respiratory disease or previous surgical modification of the nose or upper airway were excluded. Patients were asked to complete a nPIF measurement (best of three), a questionnaire including the MRQLQ, and a physical exam. Results were analyzed using InStat to look for statistical correlation between the different measures of rhinitis. RESULTS: No correlation was found between any of the congestion measures. There was no correlation between the congestion domain of the MRQLQ and nPIF (r 5 0.1685 95% CI -0.4528 to 0.1468 P 5 0.29), the congestion domain of MRQLQ and PE (r 5 0.01660 95% CI -0.3092 to 0.3389 P 5 0.9223), and nPIF and PE (r 5 0.02745 95% CI -0.2993 to 0.3484 P 5 0.8719). When patients were divided into allergic and non-allergic groups and the same measures tested for correlation, no correlation was found between any of the measures. CONCLUSION: Nasal congestion as part of a rhinitis syndrome can adversely effect OSA treatment with CPAP. However, our results show that no one measure of congestion can be trusted for diagnosis. We recommend that physicians employ several measures to ensure proper diagnosis and treatment, especially for patients with OSA. Research with more objective congestion measures like acoustic rhinometry is needed. Funding: Division of Clinical Immunology and Allergy
1195
TUESDAY
Videophone Technology, a Novel Measure of True Treatment Compliance in a 6-week Pediatric Safety Study of Fluticasone Furoate* Nasal Spray *USAN approved name D. Clements, W. Wu, E. Philpot; GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: Reliance on treatment compliance is quite important in validating safety data for pediatric clinical trials especially when traditional compliance measures may not be considered sufficient. The use of videophone technology as an innovative compliance measure was piloted in a 6-week pediatric fluticasone furoate nasal spray safety study. METHODS: Real-time observance of daily dosing of fluticasone furoate nasal spray via videophone along with conventional compliance assessments that included diary card recordings, efficacy assessments and changes in bottle weights was used in this pediatric study. Upon IRB approval and parental consent, a Vialta Beamer FXä videophone with home phone (analog) line set-up instructions was dispensed to each subject’s parent/guardian (P/G). A central research organization (CRO) contacted the P/G each morning by appointment to conduct the observational session. Daily observational information was data-based by the CRO and provided to the investigative site and study sponsor at the completion of the study. RESULTS: Mean and median numbers of doses actually observed via videophone for active and placebo treatment groups ranged from 85.2% to 90.7%. This compliance data was consistent with data from the other three conventional methods utilized in this study. CONCLUSIONS: Daily treatment compliance data from this videophone observational methodology was high (85%) for the 6-week pediatric fluticasone furoate nasal spray study. As a novel measure, videophone technology provides a reliable assessment of true treatment compliance. Funding: GlaxoSmithKline
J ALLERGY CLIN IMMUNOL JANUARY 2007
1196
Positron Emission Tomography of the Airway Distribution of Intranasal Challenge Solutions L. Conejero1, M. L. Soto1, J. J. Vaquero1, M. L. Baeza1, E. Lage1, I. Varela-Nieto2, M. Desco1, J. M. Zubeldia1; 1Hospital Gregorio Maranon, Madrid, SPAIN, 2Instituto Investigaciones Biomedicas Alberto Sols. CSIC-UAM, Madrid, SPAIN. RATIONALE: Intranasal administration is one of the main routes of allergen challenge in mouse models of airway disease. Although it is widely used, it is not well established the amount of allergen that reaches the lung or is lost to the gastrointestinal tract. The local distribution of the challenge solution within the airways is also unknown. The aim of this study was to assess the distribution immediately after intranasal delivery using a Positron Emission Tomography scanner (PET). METHODS: Fifteen BALB/c mice, 15-20 weeks-old, were studied. Thirty microliters containing 300 mCi of 2-deoxy-2-[18F] fluoro-D-glucose (FDG) were administered intranasally. Mice were anesthetized and imaged during 30 min in a dedicated small-animal PET scanner (rPET, SUINSA). Images were reconstructed by the 3D-Filtered Back Projection (3D-FBP) method and Regions of Interest (ROIs) were drawn on coronal and axial sections to obtain quantitative data of lung activity. Dynamic curves were obtained at 40 sec/frame and the value at initial time was extrapolated after exponential fitting. RESULTS: Of the total dose administered, 31.2%68.5% (mean6SD) reached the lower airways. A comparable percentage was delivered to each lung with a 51612% estimate located into the right lung. The tracer distribution was homogeneous within the areas reached, as previously assessed visually. CONCLUSION: PET imaging confirms that intranasal route is a suitable technique for delivering allergenic fluids into the lower airways. However, it should be taken into account that, in average, only one third of the administered dose reaches the anatomical target. Funding: FIS 01/0598 and Foundation SEAIC
1197
VEGF Receptor 2 (KDR) is Up-regulated in the Nasal Mucosa of Seasonal Allergic Rhinitics A. Tarun1, D. Shusterman2; 1Seattle Biomedical Research Institute, Seattle, WA, 2University of Washington, Seattle, WA. RATIONALE: We were interested in exploring the role of vascular endothelial growth factor (VEGF) in augmented nasal reactivity to sensory irritants in allergic rhinitics (AR) vs. nonrhinitic (NR) controls. In this study, we compared the relative quantitative expression of genes coding for VEGF, VEGF receptor-1 (FLT-1) and VEGF receptor-2 (KDR) in superficial nasal scrapings from AR and NR subjects. METHODS: Total RNAwas extracted from nasal scrapings obtained from 16 non-asthmatic subjects, including 8 seasonal AR and 8 NR controls, evenly divided by gender, with ages ranging from 21-63 years. Allergy status was confirmed by concordant history and epicutaneous skin test results, and sampling occurred outside of subjects’ relevant aeroallergen seasons. cDNA was synthesized from total RNA and used as templates for quantitative real-time PCR with TaqMan probes for VEGF, FLT-1, KDR and GAPDH. The relative expression of VEGF and VEGF receptor genes was normalized to the expression of GAPDH and expressed in DCT units. RESULTS: mRNA for VEGF is more abundant than either FLT-1 or KDR in superficial nasal scrapings. mRNAs for VEGF and KDR were detected in all subjects, whereas mRNA for FLT-1 was nondetectable in one AR subject. As a group, AR subjects had 3.8-fold higher mRNA levels for KDR than NR subjects (p < 0.05). CONCLUSIONS: We observed increased transcriptional message for KDR (VEGF receptor 2) in superficial nasal scrapings of AR vs NR subjects. Whether this differential gene expression contributes to ‘‘nasal hyperreactivity’’ to irritants remains to be determined.
1194
Lack of Correlation Between Physical Exam(PE), Mini RQLQ (MRQLQ), and Nasal Peak Inspiratory Flow (nPIF) as Measures of Nasal Congestion in Obstructive Sleep Apnea (OSA) Patients With Rhinitis M. R. Rupp, Jr.1 A. S. Baran2, G. D. Marshall, Jr.2; 1Allergy and Asthma Clinic of Southern New Mexico Las Cruces, NM, 2University of Mississippi Medical Center, Jackson, MS. RATIONALE: OSA is an increasingly common problem which often requires treatment with nasal CPAP therapy. Nasal congestion alters the effectiveness of CPAP therapy. We sought to evaluate the effectiveness of various measures of nasal congestion that might assist physicians in diagnosing and treating this problem. METHODS: 42 patients age 18-65 with OSA and rhinitis participated. Those with lower respiratory disease or previous surgical modification of the nose or upper airway were excluded. Patients were asked to complete a nPIF measurement (best of three), a questionnaire including the MRQLQ, and a physical exam. Results were analyzed using InStat to look for statistical correlation between the different measures of rhinitis. RESULTS: No correlation was found between any of the congestion measures. There was no correlation between the congestion domain of the MRQLQ and nPIF (r 5 0.1685 95% CI -0.4528 to 0.1468 P 5 0.29), the congestion domain of MRQLQ and PE (r 5 0.01660 95% CI -0.3092 to 0.3389 P 5 0.9223), and nPIF and PE (r 5 0.02745 95% CI -0.2993 to 0.3484 P 5 0.8719). When patients were divided into allergic and non-allergic groups and the same measures tested for correlation, no correlation was found between any of the measures. CONCLUSION: Nasal congestion as part of a rhinitis syndrome can adversely effect OSA treatment with CPAP. However, our results show that no one measure of congestion can be trusted for diagnosis. We recommend that physicians employ several measures to ensure proper diagnosis and treatment, especially for patients with OSA. Research with more objective congestion measures like acoustic rhinometry is needed. Funding: Division of Clinical Immunology and Allergy
1195
TUESDAY
Videophone Technology, a Novel Measure of True Treatment Compliance in a 6-week Pediatric Safety Study of Fluticasone Furoate* Nasal Spray *USAN approved name D. Clements, W. Wu, E. Philpot; GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: Reliance on treatment compliance is quite important in validating safety data for pediatric clinical trials especially when traditional compliance measures may not be considered sufficient. The use of videophone technology as an innovative compliance measure was piloted in a 6-week pediatric fluticasone furoate nasal spray safety study. METHODS: Real-time observance of daily dosing of fluticasone furoate nasal spray via videophone along with conventional compliance assessments that included diary card recordings, efficacy assessments and changes in bottle weights was used in this pediatric study. Upon IRB approval and parental consent, a Vialta Beamer FXä videophone with home phone (analog) line set-up instructions was dispensed to each subject’s parent/guardian (P/G). A central research organization (CRO) contacted the P/G each morning by appointment to conduct the observational session. Daily observational information was data-based by the CRO and provided to the investigative site and study sponsor at the completion of the study. RESULTS: Mean and median numbers of doses actually observed via videophone for active and placebo treatment groups ranged from 85.2% to 90.7%. This compliance data was consistent with data from the other three conventional methods utilized in this study. CONCLUSIONS: Daily treatment compliance data from this videophone observational methodology was high (85%) for the 6-week pediatric fluticasone furoate nasal spray study. As a novel measure, videophone technology provides a reliable assessment of true treatment compliance. Funding: GlaxoSmithKline
J ALLERGY CLIN IMMUNOL JANUARY 2007
1196
Positron Emission Tomography of the Airway Distribution of Intranasal Challenge Solutions L. Conejero1, M. L. Soto1, J. J. Vaquero1, M. L. Baeza1, E. Lage1, I. Varela-Nieto2, M. Desco1, J. M. Zubeldia1; 1Hospital Gregorio Maranon, Madrid, SPAIN, 2Instituto Investigaciones Biomedicas Alberto Sols. CSIC-UAM, Madrid, SPAIN. RATIONALE: Intranasal administration is one of the main routes of allergen challenge in mouse models of airway disease. Although it is widely used, it is not well established the amount of allergen that reaches the lung or is lost to the gastrointestinal tract. The local distribution of the challenge solution within the airways is also unknown. The aim of this study was to assess the distribution immediately after intranasal delivery using a Positron Emission Tomography scanner (PET). METHODS: Fifteen BALB/c mice, 15-20 weeks-old, were studied. Thirty microliters containing 300 mCi of 2-deoxy-2-[18F] fluoro-D-glucose (FDG) were administered intranasally. Mice were anesthetized and imaged during 30 min in a dedicated small-animal PET scanner (rPET, SUINSA). Images were reconstructed by the 3D-Filtered Back Projection (3D-FBP) method and Regions of Interest (ROIs) were drawn on coronal and axial sections to obtain quantitative data of lung activity. Dynamic curves were obtained at 40 sec/frame and the value at initial time was extrapolated after exponential fitting. RESULTS: Of the total dose administered, 31.2%68.5% (mean6SD) reached the lower airways. A comparable percentage was delivered to each lung with a 51612% estimate located into the right lung. The tracer distribution was homogeneous within the areas reached, as previously assessed visually. CONCLUSION: PET imaging confirms that intranasal route is a suitable technique for delivering allergenic fluids into the lower airways. However, it should be taken into account that, in average, only one third of the administered dose reaches the anatomical target. Funding: FIS 01/0598 and Foundation SEAIC
1197
VEGF Receptor 2 (KDR) is Up-regulated in the Nasal Mucosa of Seasonal Allergic Rhinitics A. Tarun1, D. Shusterman2; 1Seattle Biomedical Research Institute, Seattle, WA, 2University of Washington, Seattle, WA. RATIONALE: We were interested in exploring the role of vascular endothelial growth factor (VEGF) in augmented nasal reactivity to sensory irritants in allergic rhinitics (AR) vs. nonrhinitic (NR) controls. In this study, we compared the relative quantitative expression of genes coding for VEGF, VEGF receptor-1 (FLT-1) and VEGF receptor-2 (KDR) in superficial nasal scrapings from AR and NR subjects. METHODS: Total RNAwas extracted from nasal scrapings obtained from 16 non-asthmatic subjects, including 8 seasonal AR and 8 NR controls, evenly divided by gender, with ages ranging from 21-63 years. Allergy status was confirmed by concordant history and epicutaneous skin test results, and sampling occurred outside of subjects’ relevant aeroallergen seasons. cDNA was synthesized from total RNA and used as templates for quantitative real-time PCR with TaqMan probes for VEGF, FLT-1, KDR and GAPDH. The relative expression of VEGF and VEGF receptor genes was normalized to the expression of GAPDH and expressed in DCT units. RESULTS: mRNA for VEGF is more abundant than either FLT-1 or KDR in superficial nasal scrapings. mRNAs for VEGF and KDR were detected in all subjects, whereas mRNA for FLT-1 was nondetectable in one AR subject. As a group, AR subjects had 3.8-fold higher mRNA levels for KDR than NR subjects (p < 0.05). CONCLUSIONS: We observed increased transcriptional message for KDR (VEGF receptor 2) in superficial nasal scrapings of AR vs NR subjects. Whether this differential gene expression contributes to ‘‘nasal hyperreactivity’’ to irritants remains to be determined.