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Effects of Repetitive Allergen Challenge on Expression of TGF-β, Activin -A and Its Receptor ALK4 in Nasal Mucosa of Allergic Rhinitis
AB208 Abstracts
781
The First Phase of Instrument Development: The Conventional and Alternative Management (CAM) for Asthma Questionnaire M. George1, C. Rand2, J. A. Shea3; 1University of Pennsylvania School of Nursing, Philadelphia, PA, 2Johns Hopkins University School of Medicine, Baltimore, MD, 3University of Pennsylvania School of Medicine, Philadelphia, PA. RATIONALE: Use of inhaled corticosteroids (ICS) for persistent asthma is especially low among urban low income patients, even when barriers to access are removed. This has been attributed, in part, to negative attitudes and beliefs about ICS and a preference for alternative management. A brief tool with low literacy demands that identifies these attitudes, beliefs and preferences may serve as a communication aid between patients and primary care providers (PCPs). METHODS: A comprehensive literature review identified 115 positive and negative beliefs, attitudes, and preferences regarding conventional and unconventional asthma treatment. From these, 50 candidate items that reflected a broad range of beliefs, attitudes and preferences were selected. 15 content experts (CEs) (2 asthma educators, 8 PCPs, 2 allergists and 3 patients) were asked to identify items with the greatest likelihood of being endorsed by adults with persistent asthma on ICS. RESULTS: The 39-item Conventional and Alternative Management (CAM) for Asthma questionnaire (composed of 35 of the candidate items and 4 items added by the CEs) was piloted in 210 subjects. Psychometrics allowed the CAM to be reduced to 17-items: 9 items reflected positive attributes of using unconventional asthma treatment (e.g., herbs, coffee) and 8 items addressed ICS beliefs (2 positive beliefs (e.g., helps asthma) and 6 negative beliefs (e.g., not needed regularly). Re-piloting is underway. CONCLUSIONS: A brief low literacy tool, like the CAM for Asthma, may be useful in identifying negative ICS beliefs or preferences for unconventional care that may otherwise go undiscovered due to the time constraints inherent in PCP visits.
782
MONDAY
Local Allergic Rhinitis is Highly Prevalent in a Population Attended for the Evaluation of Rhinitis C. Rodon Segovia1, P. Campo Mozo1, L. Galindo Reyes2, G. Campos1, J. L. Rodriguez-Bada2, C. De Leyva1, M. J. Torres Jaen1, M. Blanca Gomez1; 1Allergy Service, Carlos Haya Hospital, Malaga, SPAIN, 2Research Laboratory, Carlos Haya Hospital-Fundacin IMABIS, Malaga, SPAIN. RATIONALE: Evidence demonstrates the existence of local allergic rhinitis (LAR) in an important group of non-atopic patients. In this study we evaluated the prevalence and clinical characteristics of LAR in Malaga, Spain. METHODS: A group of 388 adult rhinitis patients attended in our allergy service last year was randomly selected. Clinical questionnaire, SPT, spirometry, serum total and specific IgE (sIgE) were evaluated. Nasal allergen provocation test with multiple aeroallergens (NAPT-M) including D. pteronyssinus, pollens, and alternaria were performed in patients with negative SPT and serum sIgE. RESULTS: A total of 364 patients were studied, 24 were excluded because of nasal hyperreactivity. The prevalence of LAR was 23%, systemic allergic rhinitis (SAR) 65%, and non-allergic rhinitis (NAR) 12%. LAR and SAR patients had a similar clinical profile: a non-smoker woman with severe-persistent perennial rhinitis with 6 years of evolution, frequently associated to conjunctivitis (68.1% vs 67.6%, p>0.05) and asthma (41.2% vs 44.1%, p>0.05). NAPT-M detected aeroallergens polysensitization in 40.4% of LAR patients. D. pteronyssinus was the main sensitizing aeroallergen in LAR (75.6% vs 55.9%, p50.071), and pollens in SAR (82.4% vs 62.5%, p50.059). NAR diagnosis was achieved in 88 visits by NAPT-M instead of 352 visits that would be required by NAPT with a single aeroallergen. CONCLUSIONS: This study shows a high prevalence of LAR in rhinitis patients, with a clinical history of persistent and severe nasal symptoms frequently associated to conjunctivitis and asthma, and an important proportion of cases with aeroallergens polysensitization. NAPT-M is useful diagnostic test for screening of LAR.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
783
Interleukin-35 Suppresses Allergen-specific Th2 Response in Patients with Grass pollen induced Seasonal Allergic Rhinitis D. Achkova, F. W. Chung, J. A. Leyhadi, G. W. Scadding, J. Charlesworth, D. Phippard, S. Durham, M. H. Shamji; Imperial College London, South Kensington, UNITED KINGDOM. RATIONAL: Regulatory T cells maintain peripheral tolerance to allergens in non-atopic individuals. IL-35 is a novel cytokine consisting of EBI3 and p35 subunit of IL-12. Recent studies have revealed IL-35 in regulating immunologic responses through induction of inducible IL-35producing Treg cells. We hypothesized that IL-35 suppresses T effector (Teff) functions. We further hypothesized that IL-35 suppresses grass pollen-specific Th2 responses following in-vitro stimulation. METHOD: CD4+CD25- T effector cells were purified from PBMCs (8 non-atopic and 7 grass pollen allergics) by magnetic separation. Teff cells were stimulated with anti-CD3/CD28 +/- rhIL-35:Fc for 6 days. The effect of rhIL-35:fc on grass pollen-specific Teff cell proliferative responses (n56) was assessed. Gene expression was assessed by RT-PCR. RESULTS: A dose-dependent suppression of anti-CD3/CD28-stimulated CD4+CD25- Teff cell proliferation was demonstrated. This suppression was optimal at 10ng/mL of rhIL-35:Fc (n515; p<0.005) and was associated with increases in relative gene expression of EBI3 (p50.03), IL-12p35 (p50.02), IL-12p28 (p50.02), IFN-g (p50.02), FoxP3 (p50.03) but not IL-10. A downward trend in IL-4 mRNA was demonstrated (p50.06). An increase in CD4+CD25hiFoxp3+ (p50.04) and CD4+CD25+TGF-b+ (p50.009) T cells was demonstrated in the presence of IL-35; however, PBMC proliferative responses were not affected. Timothy grass pollen-driven CD4+CD25- Teff cell proliferative responses (n56; p50.03) and Th2 cytokine production (IL-4, p50.03; IL-9, p50.03 and IL-13, p50.02) were suppressed by rhIL-35. CONCLUSIONS: IL-35 supresses antigen-specific T cell responses and is associated with the induction of CD4+CD25hiFoxp35+ and inducible IL-35+CD4+CD25+ (EBI3+IL-12p35+) Tregs. The mechanisms by which iIL35 Treg cells immunomodulate Th2 responses remains to be fully determined.
784
Effects of Repetitive Allergen Challenge on Expression of TGF-b, Activin -A and Its Receptor ALK4 in Nasal Mucosa of Allergic Rhinitis H. Wu, N. Orban, M. Jacobson, D. Lee, S. R. Durham; Imperial College London. NHLI, London, UNITED KINGDOM. RATIONALE: Transforming growth factor (TGF)-b and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-b, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge. METHODS: 12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-b in the biopsies was assessed by immunohistochemistry and image analysis. RESULTS: There were significant higher in the numbers of Activin-A and TGF- b immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.937.5); p50.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p50.04 for TGF-b respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p50.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls. CONCLUSIONS: Our data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-b in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis.
781
The First Phase of Instrument Development: The Conventional and Alternative Management (CAM) for Asthma Questionnaire M. George1, C. Rand2, J. A. Shea3; 1University of Pennsylvania School of Nursing, Philadelphia, PA, 2Johns Hopkins University School of Medicine, Baltimore, MD, 3University of Pennsylvania School of Medicine, Philadelphia, PA. RATIONALE: Use of inhaled corticosteroids (ICS) for persistent asthma is especially low among urban low income patients, even when barriers to access are removed. This has been attributed, in part, to negative attitudes and beliefs about ICS and a preference for alternative management. A brief tool with low literacy demands that identifies these attitudes, beliefs and preferences may serve as a communication aid between patients and primary care providers (PCPs). METHODS: A comprehensive literature review identified 115 positive and negative beliefs, attitudes, and preferences regarding conventional and unconventional asthma treatment. From these, 50 candidate items that reflected a broad range of beliefs, attitudes and preferences were selected. 15 content experts (CEs) (2 asthma educators, 8 PCPs, 2 allergists and 3 patients) were asked to identify items with the greatest likelihood of being endorsed by adults with persistent asthma on ICS. RESULTS: The 39-item Conventional and Alternative Management (CAM) for Asthma questionnaire (composed of 35 of the candidate items and 4 items added by the CEs) was piloted in 210 subjects. Psychometrics allowed the CAM to be reduced to 17-items: 9 items reflected positive attributes of using unconventional asthma treatment (e.g., herbs, coffee) and 8 items addressed ICS beliefs (2 positive beliefs (e.g., helps asthma) and 6 negative beliefs (e.g., not needed regularly). Re-piloting is underway. CONCLUSIONS: A brief low literacy tool, like the CAM for Asthma, may be useful in identifying negative ICS beliefs or preferences for unconventional care that may otherwise go undiscovered due to the time constraints inherent in PCP visits.
782
MONDAY
Local Allergic Rhinitis is Highly Prevalent in a Population Attended for the Evaluation of Rhinitis C. Rodon Segovia1, P. Campo Mozo1, L. Galindo Reyes2, G. Campos1, J. L. Rodriguez-Bada2, C. De Leyva1, M. J. Torres Jaen1, M. Blanca Gomez1; 1Allergy Service, Carlos Haya Hospital, Malaga, SPAIN, 2Research Laboratory, Carlos Haya Hospital-Fundacin IMABIS, Malaga, SPAIN. RATIONALE: Evidence demonstrates the existence of local allergic rhinitis (LAR) in an important group of non-atopic patients. In this study we evaluated the prevalence and clinical characteristics of LAR in Malaga, Spain. METHODS: A group of 388 adult rhinitis patients attended in our allergy service last year was randomly selected. Clinical questionnaire, SPT, spirometry, serum total and specific IgE (sIgE) were evaluated. Nasal allergen provocation test with multiple aeroallergens (NAPT-M) including D. pteronyssinus, pollens, and alternaria were performed in patients with negative SPT and serum sIgE. RESULTS: A total of 364 patients were studied, 24 were excluded because of nasal hyperreactivity. The prevalence of LAR was 23%, systemic allergic rhinitis (SAR) 65%, and non-allergic rhinitis (NAR) 12%. LAR and SAR patients had a similar clinical profile: a non-smoker woman with severe-persistent perennial rhinitis with 6 years of evolution, frequently associated to conjunctivitis (68.1% vs 67.6%, p>0.05) and asthma (41.2% vs 44.1%, p>0.05). NAPT-M detected aeroallergens polysensitization in 40.4% of LAR patients. D. pteronyssinus was the main sensitizing aeroallergen in LAR (75.6% vs 55.9%, p50.071), and pollens in SAR (82.4% vs 62.5%, p50.059). NAR diagnosis was achieved in 88 visits by NAPT-M instead of 352 visits that would be required by NAPT with a single aeroallergen. CONCLUSIONS: This study shows a high prevalence of LAR in rhinitis patients, with a clinical history of persistent and severe nasal symptoms frequently associated to conjunctivitis and asthma, and an important proportion of cases with aeroallergens polysensitization. NAPT-M is useful diagnostic test for screening of LAR.
J ALLERGY CLIN IMMUNOL FEBRUARY 2012
783
Interleukin-35 Suppresses Allergen-specific Th2 Response in Patients with Grass pollen induced Seasonal Allergic Rhinitis D. Achkova, F. W. Chung, J. A. Leyhadi, G. W. Scadding, J. Charlesworth, D. Phippard, S. Durham, M. H. Shamji; Imperial College London, South Kensington, UNITED KINGDOM. RATIONAL: Regulatory T cells maintain peripheral tolerance to allergens in non-atopic individuals. IL-35 is a novel cytokine consisting of EBI3 and p35 subunit of IL-12. Recent studies have revealed IL-35 in regulating immunologic responses through induction of inducible IL-35producing Treg cells. We hypothesized that IL-35 suppresses T effector (Teff) functions. We further hypothesized that IL-35 suppresses grass pollen-specific Th2 responses following in-vitro stimulation. METHOD: CD4+CD25- T effector cells were purified from PBMCs (8 non-atopic and 7 grass pollen allergics) by magnetic separation. Teff cells were stimulated with anti-CD3/CD28 +/- rhIL-35:Fc for 6 days. The effect of rhIL-35:fc on grass pollen-specific Teff cell proliferative responses (n56) was assessed. Gene expression was assessed by RT-PCR. RESULTS: A dose-dependent suppression of anti-CD3/CD28-stimulated CD4+CD25- Teff cell proliferation was demonstrated. This suppression was optimal at 10ng/mL of rhIL-35:Fc (n515; p<0.005) and was associated with increases in relative gene expression of EBI3 (p50.03), IL-12p35 (p50.02), IL-12p28 (p50.02), IFN-g (p50.02), FoxP3 (p50.03) but not IL-10. A downward trend in IL-4 mRNA was demonstrated (p50.06). An increase in CD4+CD25hiFoxp3+ (p50.04) and CD4+CD25+TGF-b+ (p50.009) T cells was demonstrated in the presence of IL-35; however, PBMC proliferative responses were not affected. Timothy grass pollen-driven CD4+CD25- Teff cell proliferative responses (n56; p50.03) and Th2 cytokine production (IL-4, p50.03; IL-9, p50.03 and IL-13, p50.02) were suppressed by rhIL-35. CONCLUSIONS: IL-35 supresses antigen-specific T cell responses and is associated with the induction of CD4+CD25hiFoxp35+ and inducible IL-35+CD4+CD25+ (EBI3+IL-12p35+) Tregs. The mechanisms by which iIL35 Treg cells immunomodulate Th2 responses remains to be fully determined.
784
Effects of Repetitive Allergen Challenge on Expression of TGF-b, Activin -A and Its Receptor ALK4 in Nasal Mucosa of Allergic Rhinitis H. Wu, N. Orban, M. Jacobson, D. Lee, S. R. Durham; Imperial College London. NHLI, London, UNITED KINGDOM. RATIONALE: Transforming growth factor (TGF)-b and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-b, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge. METHODS: 12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-b in the biopsies was assessed by immunohistochemistry and image analysis. RESULTS: There were significant higher in the numbers of Activin-A and TGF- b immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.937.5); p50.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p50.04 for TGF-b respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p50.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls. CONCLUSIONS: Our data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-b in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis.