- Email: [email protected]
Current views on Self-injectable Epinephrine Prescriptions for Immunotherapy Patients
Abstracts AB237
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2
Current views on Self-injectable Epinephrine Prescriptions for Immunotherapy Patients P. Gupta, P. Kapur, J. Stern, B. Silverman, A. Schneider; Long Island College Hospital, New York, NY. RATIONALE: Prescribing self-injectable epinephrine (SIE) is appropriate for patients with an increased risk of anaphylaxis, but there is no current consensus regarding the use of SIE prescriptions for patients on immunotherapy (IT). This study investigates current practices among allergists and those in-training on writing SIE prescriptions for IT patients. METHODS: A survey was sent to allergist-immunologists by email. Demographic information was obtained as well as information on their experience with IT and the role of SIE prescriptions for IT patients. Approval was obtained from the Long Island College Hospital IRB. RESULTS: 248 surveys were returned and 5 were excluded because they were incomplete. The majority of respondents were out of training (90%). Only 34.9% prescribe SIE to all of their patients on IT. 14.4% do not prescribe SIE for any of their IT patients. Of the remaining 50.6% of respondents, the three largest categories of patients prescribed SIE include: those with a history of previous systemic reaction, those on Omalizumab or those on Omalizumab and venom IT. Respondents who prescribe SIE for all of their patients have fewer years in practice (avg 14.5 years, range 0-44 years) compared to those who do not prescribe (avg 22 years, range 1-40 years) SIE. Interestingly, of those who prescribe SIE to all their IT patients, 61% give IT even if the patient fails to bring their SIE to their appointment. CONCLUSIONS: Among this sample of allergists there was a wide range of practices. Specific SIE prescribing recommendations for patients on IT may be helpful to practicing allergists.
927
Measurement Of Allergen-specific Igg4 By Cap System In Respiratory Allergic Patients During House Dust Mite Immunotherapy Y. W. Lee1, J. Y. Kim2, J. H. Sohn2, S. R. Agrawal2, J. H. Lee1, J. W. Park1, C. S. Hong1; 1Div. of Allergy and Immunology, Institute of Allergy, Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA, 2Institute of Allergy, Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA. RATIONALE: Allergen-specific IgG4 (-IgG4) tends to increase after immunotherapy (SIT). Recently, CAP-IgG4 was introduced, but has not yet been validated. We evaluated CAP-IgG4 in respiratory allergic patients on house dust mite (HDM)-SIT. METHODS: D. farinae (Df)-IgG4 was measured by ImmunoCAP system with 60 sera which were periodically (15 before SIT, 20 at 1 year, 16 at 2 years, and 9 at more than 3 years) drawn from 27 respiratory allergic patients (M/F57/20, 35.8611.6 years) during HDM-SIT. Two different vaccines ‘‘H’’ and ‘‘A’’ were mainly used (n514, and 11, respectively). Maintenance dose of ‘‘H’’ was 6516376 AU, but dosage data of ‘‘A’’ was not released by the manufacturer. ELISA of Df-IgG4 was also done for validating CAP-Df-IgG4 with some sera (n517). RESULTS: CAP-Df-IgG4 increased significantly according to SIT duration (p50.002). Such increment was prominent at 1, 2, and more than 3 years after SIT than before (2.2263.63, 2.3562.60, and 1.3060.69 vs. 0.5360.73 mgA/L, p<0.01, respectively). There was strong correlation between CAP- and ELISA-Df-IgG4 (rs50.89, p<0.0001). Before SIT, CAPDf-IgG4 levels were not different between the two vaccine groups (‘‘H’’: 0.4460.65, and ‘‘A’’: 0.8161.05 mgA/L, p50.374). On ‘‘H’’ vaccine group, CAP-Df-IgG4 levels were higher at 1 year (3.0864.69 mgA/L, p<0.01), and 2 years (3.2563.14, p50.028) after SIT than before. However, such increment of Df-IgG4 was not prominent in ‘‘A’’ vaccine group. CONCLUSIONS: CAP-Df-IgG4 increased after HDM-SIT, and showed good correlation with ELISA results. Such increment patterns were different between vaccine manufacturers. Further investigations for validation and clinical application of CAP-IgG4 are needed.
928
Reguation of FceRI Expression During Murine Basophil Maturation: The Interplay Between IgE, Cell Division and FceRI Synthetic Rate A. K. Zaidi, D. W. MacGlashan; Johns Hopkins University, Baltimore, MD. RATIONALE: Previous studies have noted in vivo FceRI receptor expression dynamics on human basophils that are discordant with expectations derived from in vitro studies. The current study tests the hypothesis that rapid changes in receptor expression results from cell turnover rather than re-equilibration of IgE binding to receptor. The assumptions tested were that IgE does not change the rate of basophil egress and can regulate basophil receptor expression in the bone marrow. METHODS: FceRI expression on basophils was estimated by FACS using IgE/anti-IgE-FITC and CD49b-PE antibody. Egress was examined by labeling of marrow and blood basophils at various times after BrdU injection with and without IgE injection. RESULTS: A murine model of receptor expression on basophils recapitulates observations of human basophils. In the proposed model, egress rates from bone marrow were assumed to be unaffected by changes in IgE concentration. We found that IgE did not alter the appearance of BrdU label (egress) in blood basophils. In addition, marrow and blood basophils were responsive to the elevations in IgE, with receptor expression increasing on marrow basophils before blood basophils. It was noted that blood basophils expressed approximately 50% of the receptor density of marrow basophils. There was a 3 fold greater synthetic rate of FceRI on marrow basophils that explained the difference. CONCLUSIONS: These results support 1) the proposed hypothesis of rapid changes in receptor expression being controlled by cell replacement, 2) a model whereby receptor expression is limited by cell division and that basophils, once mature, slow their rate of receptor synthesis.
929
The Nlrp3 Inflammasome Affects Airway Inflammation, IgE/IL13 Production And Mast Cell Function In A Subchronic Model Of Asthma M. Kwan, I. C. Allen, W. J. Brickey, M. Hernandez, D. B. Peden, J. P. Y. Ting; University of North Carolina, Chapel Hill, NC. RATIONALE: The inflammasome is a crucial regulator of innate immunity resulting in the secretion of IL-1b, IL-18, and possibly IL-33. Its role in asthma, however, is not defined. We surveyed asthmatics for IL-1b production and investigated the role of the predominant inflammasome NLR, NLRP3 (cryopyrin/NALP3), in a mouse asthma model. METHODS: Human: Mild allergic asthmatics were challenged with inhaled D Farinae extract. Responders had a 15% decrease in FEV1 from baseline. Sputum was analyzed 24 hours post challenge versus baseline. Mouse: WT and Nlrp3-/- mice were sensitized with OVA without alum intraperitoneally and challenged with OVA intranasally. Mice were harvested for BALF, histological, and serum analysis. Bone marrow mast cells (BMMCs) were isolated and gene expression demonstrated by qPCR. BMMCs were LPS/IL-33 stimulated and supernatants analyzed by ELISA. RESULTS: Asthmatic responders had increased sputum levels of IL1b compared to non-responders. Therefore, Nlrp3-/- mice were studied in a subchronic OVA asthma model without alum. Exclusion of alum was important as its adjuvanticity is Nlrp3 dependent. Nlrp3-/- mice had reduced histopathology with decreased BAL macrophages and peribronchial infiltrates. BAL IL-13 and total serum IgE were also reduced. As BMMCs are important in this model, we examined Nlrp3-/- BMMCs. They show decreased secretion of IL-1b/IL-18 with LPS and decreased IL-13 with LPS and IL-33 treatment. CONCLUSIONS: Asthmatics who responded to challenge had increased sputum IL-1b inferring inflammasome activation. In agreement, Nlrp3-/mice have attenuated airways inflammation. Mast cells are implicated in this model as they have decreased elaboration of IL-13 in response to LPS and IL-33.
TUESDAY
926
J ALLERGY CLIN IMMUNOL VOLUME 125, NUMBER 2
Current views on Self-injectable Epinephrine Prescriptions for Immunotherapy Patients P. Gupta, P. Kapur, J. Stern, B. Silverman, A. Schneider; Long Island College Hospital, New York, NY. RATIONALE: Prescribing self-injectable epinephrine (SIE) is appropriate for patients with an increased risk of anaphylaxis, but there is no current consensus regarding the use of SIE prescriptions for patients on immunotherapy (IT). This study investigates current practices among allergists and those in-training on writing SIE prescriptions for IT patients. METHODS: A survey was sent to allergist-immunologists by email. Demographic information was obtained as well as information on their experience with IT and the role of SIE prescriptions for IT patients. Approval was obtained from the Long Island College Hospital IRB. RESULTS: 248 surveys were returned and 5 were excluded because they were incomplete. The majority of respondents were out of training (90%). Only 34.9% prescribe SIE to all of their patients on IT. 14.4% do not prescribe SIE for any of their IT patients. Of the remaining 50.6% of respondents, the three largest categories of patients prescribed SIE include: those with a history of previous systemic reaction, those on Omalizumab or those on Omalizumab and venom IT. Respondents who prescribe SIE for all of their patients have fewer years in practice (avg 14.5 years, range 0-44 years) compared to those who do not prescribe (avg 22 years, range 1-40 years) SIE. Interestingly, of those who prescribe SIE to all their IT patients, 61% give IT even if the patient fails to bring their SIE to their appointment. CONCLUSIONS: Among this sample of allergists there was a wide range of practices. Specific SIE prescribing recommendations for patients on IT may be helpful to practicing allergists.
927
Measurement Of Allergen-specific Igg4 By Cap System In Respiratory Allergic Patients During House Dust Mite Immunotherapy Y. W. Lee1, J. Y. Kim2, J. H. Sohn2, S. R. Agrawal2, J. H. Lee1, J. W. Park1, C. S. Hong1; 1Div. of Allergy and Immunology, Institute of Allergy, Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA, 2Institute of Allergy, Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA. RATIONALE: Allergen-specific IgG4 (-IgG4) tends to increase after immunotherapy (SIT). Recently, CAP-IgG4 was introduced, but has not yet been validated. We evaluated CAP-IgG4 in respiratory allergic patients on house dust mite (HDM)-SIT. METHODS: D. farinae (Df)-IgG4 was measured by ImmunoCAP system with 60 sera which were periodically (15 before SIT, 20 at 1 year, 16 at 2 years, and 9 at more than 3 years) drawn from 27 respiratory allergic patients (M/F57/20, 35.8611.6 years) during HDM-SIT. Two different vaccines ‘‘H’’ and ‘‘A’’ were mainly used (n514, and 11, respectively). Maintenance dose of ‘‘H’’ was 6516376 AU, but dosage data of ‘‘A’’ was not released by the manufacturer. ELISA of Df-IgG4 was also done for validating CAP-Df-IgG4 with some sera (n517). RESULTS: CAP-Df-IgG4 increased significantly according to SIT duration (p50.002). Such increment was prominent at 1, 2, and more than 3 years after SIT than before (2.2263.63, 2.3562.60, and 1.3060.69 vs. 0.5360.73 mgA/L, p<0.01, respectively). There was strong correlation between CAP- and ELISA-Df-IgG4 (rs50.89, p<0.0001). Before SIT, CAPDf-IgG4 levels were not different between the two vaccine groups (‘‘H’’: 0.4460.65, and ‘‘A’’: 0.8161.05 mgA/L, p50.374). On ‘‘H’’ vaccine group, CAP-Df-IgG4 levels were higher at 1 year (3.0864.69 mgA/L, p<0.01), and 2 years (3.2563.14, p50.028) after SIT than before. However, such increment of Df-IgG4 was not prominent in ‘‘A’’ vaccine group. CONCLUSIONS: CAP-Df-IgG4 increased after HDM-SIT, and showed good correlation with ELISA results. Such increment patterns were different between vaccine manufacturers. Further investigations for validation and clinical application of CAP-IgG4 are needed.
928
Reguation of FceRI Expression During Murine Basophil Maturation: The Interplay Between IgE, Cell Division and FceRI Synthetic Rate A. K. Zaidi, D. W. MacGlashan; Johns Hopkins University, Baltimore, MD. RATIONALE: Previous studies have noted in vivo FceRI receptor expression dynamics on human basophils that are discordant with expectations derived from in vitro studies. The current study tests the hypothesis that rapid changes in receptor expression results from cell turnover rather than re-equilibration of IgE binding to receptor. The assumptions tested were that IgE does not change the rate of basophil egress and can regulate basophil receptor expression in the bone marrow. METHODS: FceRI expression on basophils was estimated by FACS using IgE/anti-IgE-FITC and CD49b-PE antibody. Egress was examined by labeling of marrow and blood basophils at various times after BrdU injection with and without IgE injection. RESULTS: A murine model of receptor expression on basophils recapitulates observations of human basophils. In the proposed model, egress rates from bone marrow were assumed to be unaffected by changes in IgE concentration. We found that IgE did not alter the appearance of BrdU label (egress) in blood basophils. In addition, marrow and blood basophils were responsive to the elevations in IgE, with receptor expression increasing on marrow basophils before blood basophils. It was noted that blood basophils expressed approximately 50% of the receptor density of marrow basophils. There was a 3 fold greater synthetic rate of FceRI on marrow basophils that explained the difference. CONCLUSIONS: These results support 1) the proposed hypothesis of rapid changes in receptor expression being controlled by cell replacement, 2) a model whereby receptor expression is limited by cell division and that basophils, once mature, slow their rate of receptor synthesis.
929
The Nlrp3 Inflammasome Affects Airway Inflammation, IgE/IL13 Production And Mast Cell Function In A Subchronic Model Of Asthma M. Kwan, I. C. Allen, W. J. Brickey, M. Hernandez, D. B. Peden, J. P. Y. Ting; University of North Carolina, Chapel Hill, NC. RATIONALE: The inflammasome is a crucial regulator of innate immunity resulting in the secretion of IL-1b, IL-18, and possibly IL-33. Its role in asthma, however, is not defined. We surveyed asthmatics for IL-1b production and investigated the role of the predominant inflammasome NLR, NLRP3 (cryopyrin/NALP3), in a mouse asthma model. METHODS: Human: Mild allergic asthmatics were challenged with inhaled D Farinae extract. Responders had a 15% decrease in FEV1 from baseline. Sputum was analyzed 24 hours post challenge versus baseline. Mouse: WT and Nlrp3-/- mice were sensitized with OVA without alum intraperitoneally and challenged with OVA intranasally. Mice were harvested for BALF, histological, and serum analysis. Bone marrow mast cells (BMMCs) were isolated and gene expression demonstrated by qPCR. BMMCs were LPS/IL-33 stimulated and supernatants analyzed by ELISA. RESULTS: Asthmatic responders had increased sputum levels of IL1b compared to non-responders. Therefore, Nlrp3-/- mice were studied in a subchronic OVA asthma model without alum. Exclusion of alum was important as its adjuvanticity is Nlrp3 dependent. Nlrp3-/- mice had reduced histopathology with decreased BAL macrophages and peribronchial infiltrates. BAL IL-13 and total serum IgE were also reduced. As BMMCs are important in this model, we examined Nlrp3-/- BMMCs. They show decreased secretion of IL-1b/IL-18 with LPS and decreased IL-13 with LPS and IL-33 treatment. CONCLUSIONS: Asthmatics who responded to challenge had increased sputum IL-1b inferring inflammasome activation. In agreement, Nlrp3-/mice have attenuated airways inflammation. Mast cells are implicated in this model as they have decreased elaboration of IL-13 in response to LPS and IL-33.
TUESDAY
926