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Ragweed Allergy Immunotherapy Tablet Reduces Nasal and Ocular Symptoms of Allergic Rhinoconjunctivitis Over the Peak Ragweed Pollen Season in North America
Abstracts AB249
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
eosinophil numbers were increased in aged, but decreased in young mice sensitized during acute-infection, and decreased in both ages when sensitized after infection was resolved. CONCLUSION: There are several age-related differences including AHR, airway inflammation, and IgE production in the response to antigen sensitization and timing of viral infections.
Ragweed Allergy Immunotherapy Tablet Reduces Nasal and Ocular Symptoms of Allergic Rhinoconjunctivitis Over the Peak Ragweed Pollen Season in North America G. Berman1, H. Nolte2, J. Maloney2, P. Creticos3, A. Cheema4, A. Kaur2, J. Hebert5; 1Minneapolis Allergy & Asthma Specialists, Minneapolis, MN, 2Merck Research Laboratories, Kenilworth, NJ, 3Johns Hopkins University School of Medicine, Baltimore, MD, 4Alpha Medical Research, Mississauga, ON, CANADA, 5Centre de Recherche Appliquee en Allergie de Quebec, Quebec, QC, CANADA. RATIONALE: Peak season nasal and ocular symptoms of allergic rhinoconjunctivitis (ARC) are bothersome and can profoundly impact quality of life. The effects of sublingual ragweed allergy immunotherapy tablet (AIT) on nasal and ocular symptoms were investigated in North American ragweed allergic adults with or without asthma. METHODS: 565 adults were randomized to daily ragweed AIT 6 or 12 Amb a 1-U (Amb) or placebo. Treatment was initiated approximately 4 months before and continued throughout ragweed season (RS). Daily four nasal and two ocular symptoms were assessed on a scale from 0 (no symptoms) to 3 (severe). The peak RS was defined as the 15 consecutive days with the highest 15-day moving average pollen count. RESULTS: The ragweed AIT 12 Amb a 1-U and 6 Amb a 1-U groups showed mean improvement in total nasal scores compared to placebo of 14.8% (diff 5 -0.58 points; p50.03) and 11.7% (diff 5 -0.46 points; p50.09), respectively during peak RS. Total ocular scores revealed improvements of 21.8% (diff5-0.37 points; p50.01) and 18.9% (diff50.32 points; p50.03) for the 12 Amb a 1-U and 6 Amb a 1-U doses. Furthermore, a significant effect (p<0.05) on individual symptoms was noted for 12 Amb a 1-U dose on watery and itchy eyes, runny nose and sneezing. Treatment with ragweed AIT was well tolerated with no observed difference between 6 and 12 Amb. There were no reports of systemic allergic reactions. CONCLUSIONS: These results demonstrate that once-daily administration of ragweed AIT effectively treats the nasal and ocular symptoms of ragweed-induced ARC.
Diesel Exhaust Particles Induce Cysteine Oxidation and S-Glutathionylation in House Dust Mite Induced Murine Asthma G. B. Lee1, E. B. Brandt2, A. M. Gibson2, T. D. Le Cras2, L. S. Brown3, A. M. Fitzpatrick3, G. K. Khurana Hershey2; 1University of Louisville School of Medicine, Louisville, KY, 2Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 3Emory University School of Medicine, Atlanta, GA. RATIONALE: Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. We hypothesized that DEP exposure would alter the Cys or GSH oxidation-reduction state in the asthmatic airway. METHODS: Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM) induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography. RESULTS: Compared with HDM exposure alone, DEP co-administered with HDM decreased total Cys (0.058 mM vs. 0.024 mM, p < 0.001), increased CySS (0.0043 mM vs. 0.025 mM, p < 0.0001), and increased CySSG (0.11 mM vs. 0.21 mM, p < 0.05) without significantly altering GSH or GSSG. CONCLUSIONS: DEP exposure promotes oxidation and s-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses.
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Age-related Differences in Antigen Sensitization and the Allergic Airway Responses in Acute and Resolved Viral Respiratory Infection J. Birmingham, K. Srivastava, X. Li, P. Busse; Mount Sinai School of Medicine, New York, NY. RATIONALE: Clinical data suggests that viral respiratory infections in younger patients may promote allergen sensitization. This project investigated age-related effects of acute and resolved viral respiratory infection on antigen sensitization and allergic airway response in mice. METHODS: Six-week and 18-month BALB/c mice (5-10/group) were infected with non-lethal dose of influenza virus A (H/HKx31). Young and aged mice were ovalbumin (OVA) sensitized during acute-infection (3days post inoculation) or during resolved-infection (30-days post inoculation), and OVA-challenged 3 times intratracheally at weekly intervals. Aged-matched, non-infected OVA-sensitized/challenged, infected-alone and na€ıve mice were controls. Forty-eight hours after final OVA-challenge, airway hyperreactivity (AHR) to acetylcholine provocation was determined by airway-pressure time-index (APTI); bronchioalveolar fluids (BALF), sera, and lung tissues were collected. RESULTS: APTI-values significantly increased in both young (p<0.001) and aged (p<0.05) mice sensitized during acute-infection compared to non-infected, antigen-sensitized/challenged mice. However, APTI values were significantly elevated in young, but not aged mice sensitized after resolved-infection. Serum OVA-specific IgE was significantly increased in young mice sensitized during acute-infection (105.665.1ng/ml) compared with young non-infected/OVA-sensitized (74.661.3ng/ml, p50.0001). OVA-specific IgE was not significantly different between aged mice sensitized during acute-infection (177.5623.27ng/ml) or non-infected/ OVA-sensitized (207.2622.58ng/ml, p50.38) mice. OVA-specific IgE was significantly decreased in young (36.365.8ng/ml) and aged mice (16.8664.2ng/ml) when sensitized after resolved infection. BALF
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The Gut Mucosa Microenvironment Affects Allergic Sensitization vs tolerance to Food proteins K. Adel-Patient, H. Bernard, S. Wavrin, S. Ah-Leung, J. Wal; INRA, Gifsur-Yvette, FRANCE. RATIONALE: Oral administrations of food proteins may influence further oral tolerance or sensitization by changing the gut mucosa microenvironment. METHODS: In a first experiment, BALB/cJ mice were sensitized by gavage with the purified cow’s milk (CM) allergen bovine b-lactoglobulin (BLG) mixed with Cholera toxin (CT). Mice were then gavaged with CM, without adjuvant. In a second experiment, mice were first tolerized to BLG by gavage1 and then sensitized to CM by gavage with CT. In both experiments, the specific antibodies to the different CM proteins (CMPs) were determined in sera collected from individual mice. RESULTS: No specific antibodies to any CMPs were evidenced in control mice gavaged with CM without adjuvant. Conversely, mice previously sensitized to BLG produced specific IgG1 antibodies against caseins, alactalbumin and lactoferrin. Mice tolerized with BLG did not produce antiBLG IgE or IgG1 antibodies after sensitization with CM+CT. Interestingly, the concentrations of antibodies against all the other CMPs were also significantly reduced in this group. CONCLUSIONS: BLG present in CM likely elicits a specific local allergic reaction in mice previously sensitized with BLG which may then favour a Th2-type response to other bystander proteins. On the other side, the Treg cells induced after gavage with BLG alone1 would result in a proregulatory microenvironment and induction of a tolerogenic response to other CMPs. These results demonstrate the crucial role of the gut mucosa microenvironment in the nature of the immune response to a food protein. 1 Adel-Patient et al., Allergy. 2011, 66(10):1312-21
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J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
eosinophil numbers were increased in aged, but decreased in young mice sensitized during acute-infection, and decreased in both ages when sensitized after infection was resolved. CONCLUSION: There are several age-related differences including AHR, airway inflammation, and IgE production in the response to antigen sensitization and timing of viral infections.
Ragweed Allergy Immunotherapy Tablet Reduces Nasal and Ocular Symptoms of Allergic Rhinoconjunctivitis Over the Peak Ragweed Pollen Season in North America G. Berman1, H. Nolte2, J. Maloney2, P. Creticos3, A. Cheema4, A. Kaur2, J. Hebert5; 1Minneapolis Allergy & Asthma Specialists, Minneapolis, MN, 2Merck Research Laboratories, Kenilworth, NJ, 3Johns Hopkins University School of Medicine, Baltimore, MD, 4Alpha Medical Research, Mississauga, ON, CANADA, 5Centre de Recherche Appliquee en Allergie de Quebec, Quebec, QC, CANADA. RATIONALE: Peak season nasal and ocular symptoms of allergic rhinoconjunctivitis (ARC) are bothersome and can profoundly impact quality of life. The effects of sublingual ragweed allergy immunotherapy tablet (AIT) on nasal and ocular symptoms were investigated in North American ragweed allergic adults with or without asthma. METHODS: 565 adults were randomized to daily ragweed AIT 6 or 12 Amb a 1-U (Amb) or placebo. Treatment was initiated approximately 4 months before and continued throughout ragweed season (RS). Daily four nasal and two ocular symptoms were assessed on a scale from 0 (no symptoms) to 3 (severe). The peak RS was defined as the 15 consecutive days with the highest 15-day moving average pollen count. RESULTS: The ragweed AIT 12 Amb a 1-U and 6 Amb a 1-U groups showed mean improvement in total nasal scores compared to placebo of 14.8% (diff 5 -0.58 points; p50.03) and 11.7% (diff 5 -0.46 points; p50.09), respectively during peak RS. Total ocular scores revealed improvements of 21.8% (diff5-0.37 points; p50.01) and 18.9% (diff50.32 points; p50.03) for the 12 Amb a 1-U and 6 Amb a 1-U doses. Furthermore, a significant effect (p<0.05) on individual symptoms was noted for 12 Amb a 1-U dose on watery and itchy eyes, runny nose and sneezing. Treatment with ragweed AIT was well tolerated with no observed difference between 6 and 12 Amb. There were no reports of systemic allergic reactions. CONCLUSIONS: These results demonstrate that once-daily administration of ragweed AIT effectively treats the nasal and ocular symptoms of ragweed-induced ARC.
Diesel Exhaust Particles Induce Cysteine Oxidation and S-Glutathionylation in House Dust Mite Induced Murine Asthma G. B. Lee1, E. B. Brandt2, A. M. Gibson2, T. D. Le Cras2, L. S. Brown3, A. M. Fitzpatrick3, G. K. Khurana Hershey2; 1University of Louisville School of Medicine, Louisville, KY, 2Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 3Emory University School of Medicine, Atlanta, GA. RATIONALE: Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. We hypothesized that DEP exposure would alter the Cys or GSH oxidation-reduction state in the asthmatic airway. METHODS: Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM) induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography. RESULTS: Compared with HDM exposure alone, DEP co-administered with HDM decreased total Cys (0.058 mM vs. 0.024 mM, p < 0.001), increased CySS (0.0043 mM vs. 0.025 mM, p < 0.0001), and increased CySSG (0.11 mM vs. 0.21 mM, p < 0.05) without significantly altering GSH or GSSG. CONCLUSIONS: DEP exposure promotes oxidation and s-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses.
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Age-related Differences in Antigen Sensitization and the Allergic Airway Responses in Acute and Resolved Viral Respiratory Infection J. Birmingham, K. Srivastava, X. Li, P. Busse; Mount Sinai School of Medicine, New York, NY. RATIONALE: Clinical data suggests that viral respiratory infections in younger patients may promote allergen sensitization. This project investigated age-related effects of acute and resolved viral respiratory infection on antigen sensitization and allergic airway response in mice. METHODS: Six-week and 18-month BALB/c mice (5-10/group) were infected with non-lethal dose of influenza virus A (H/HKx31). Young and aged mice were ovalbumin (OVA) sensitized during acute-infection (3days post inoculation) or during resolved-infection (30-days post inoculation), and OVA-challenged 3 times intratracheally at weekly intervals. Aged-matched, non-infected OVA-sensitized/challenged, infected-alone and na€ıve mice were controls. Forty-eight hours after final OVA-challenge, airway hyperreactivity (AHR) to acetylcholine provocation was determined by airway-pressure time-index (APTI); bronchioalveolar fluids (BALF), sera, and lung tissues were collected. RESULTS: APTI-values significantly increased in both young (p<0.001) and aged (p<0.05) mice sensitized during acute-infection compared to non-infected, antigen-sensitized/challenged mice. However, APTI values were significantly elevated in young, but not aged mice sensitized after resolved-infection. Serum OVA-specific IgE was significantly increased in young mice sensitized during acute-infection (105.665.1ng/ml) compared with young non-infected/OVA-sensitized (74.661.3ng/ml, p50.0001). OVA-specific IgE was not significantly different between aged mice sensitized during acute-infection (177.5623.27ng/ml) or non-infected/ OVA-sensitized (207.2622.58ng/ml, p50.38) mice. OVA-specific IgE was significantly decreased in young (36.365.8ng/ml) and aged mice (16.8664.2ng/ml) when sensitized after resolved infection. BALF
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The Gut Mucosa Microenvironment Affects Allergic Sensitization vs tolerance to Food proteins K. Adel-Patient, H. Bernard, S. Wavrin, S. Ah-Leung, J. Wal; INRA, Gifsur-Yvette, FRANCE. RATIONALE: Oral administrations of food proteins may influence further oral tolerance or sensitization by changing the gut mucosa microenvironment. METHODS: In a first experiment, BALB/cJ mice were sensitized by gavage with the purified cow’s milk (CM) allergen bovine b-lactoglobulin (BLG) mixed with Cholera toxin (CT). Mice were then gavaged with CM, without adjuvant. In a second experiment, mice were first tolerized to BLG by gavage1 and then sensitized to CM by gavage with CT. In both experiments, the specific antibodies to the different CM proteins (CMPs) were determined in sera collected from individual mice. RESULTS: No specific antibodies to any CMPs were evidenced in control mice gavaged with CM without adjuvant. Conversely, mice previously sensitized to BLG produced specific IgG1 antibodies against caseins, alactalbumin and lactoferrin. Mice tolerized with BLG did not produce antiBLG IgE or IgG1 antibodies after sensitization with CM+CT. Interestingly, the concentrations of antibodies against all the other CMPs were also significantly reduced in this group. CONCLUSIONS: BLG present in CM likely elicits a specific local allergic reaction in mice previously sensitized with BLG which may then favour a Th2-type response to other bystander proteins. On the other side, the Treg cells induced after gavage with BLG alone1 would result in a proregulatory microenvironment and induction of a tolerogenic response to other CMPs. These results demonstrate the crucial role of the gut mucosa microenvironment in the nature of the immune response to a food protein. 1 Adel-Patient et al., Allergy. 2011, 66(10):1312-21
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