TY - JOUR
T1 - Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index
AU - Hoch, Heather E.
AU - Calatroni, Agustin
AU - West, Joseph B.
AU - Liu, Andrew H.
AU - Gergen, Peter J.
AU - Gruchalla, Rebecca S.
AU - Khurana Hershey, Gurjit K.
AU - Kercsmar, Carolyn M.
AU - Kim, Haejin
AU - Lamm, Carin I.
AU - Makhija, Melanie M.
AU - Mitchell, Herman E.
AU - Teach, Stephen J.
AU - Wildfire, Jeremy J.
AU - Busse, William W.
AU - Szefler, Stanley J.
N1 - Funding Information:
Disclosure of potential conflict of interest: H. E. Hoch, A. Calatroni, J. B. West, and J. J. Wildfire have received grants from the National Institutes of Health–National Institute of Allergy and Infectious Diseases. A. H. Liu has received a grant from the National Institutes of Health, has a board membership with GlaxoSmithKline, and has received payment for lectures from Merck. R. S. Gruchalla is employed by the Center for Biologics Evaluation and Research and has provided consultation for the Massachusetts Medical Society. G. K. Khurana Hershey has received a grant from the National Institutes of Health. C. M. Kercsmar has received a grant from the National Institutes of Health and was chair of the Data Safety Materials Board on a GlaxoSmithKline-funded, US Food and Drug Administration–mandated 6-month Safety and Benefit Study of ADVAIR in Children 4-11 Years Old (VESTRI) trial. H. Kim has received a grant and travel support from the National Institutes of Health–National Institute of Allergy and Infectious Diseases. C. I. Lamm and M. M. Makhija have received grants from the National Institutes of Health. H. E. Mitchell has received a grant from the National Institutes of Health–National Institute of Allergy and Infectious Diseases. S. J. Teach has received grants from the National Institutes of Health–National Institute of Allergy and Infectious Diseases, Novartis, PCORI, Fight for Children Foundation, EJF Philanthropies, and the National Institutes of Health–National Heart, Lung, and Blood Institute; has consultant arrangements with Novartis; and has received royalties from UpToDate. W. W. Busse has received a grant from the National Institutes of Health–National Institute of Allergy and Infectious Diseases; has received partial study funding and drug and placebo from Novartis; has board memberships with Boston Scientific, Ciracassia, and ICON; and has consultant arrangements with Novartis, GlaxoSmithKline, Genentech, Roche, Pfizer, Merck, Boehringer-Ingelheim, Sanofi, AstraZeneca, Teva, Tekeda, Aerocrine, and 3M. S. J. Szefler has received grants from the National Institute of Allergy and Infectious Diseases– Inner City Asthma Consortium and GlaxoSmithKline and has consultant arrangements with Merck, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Aerocrine, Novartis, AstraZeneca, Daiichi Sankyo, and Roche. P. J. Gergen declares that he has no relevant conflicts of interest.
Funding Information:
Supported in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract numbers HHSN272200900052C, HHSN272201000052I, 1UM1AI114271-01, and UM2AI117870. Additional support was provided by the National Center for Research Resources, National Center for Advancing Translational Sciences, and National Institutes of Health under grants NCRR/NIH UL1TR000451, 1UL1RR025780, UL1TR000075; NCATS/NIH UL1 TR000154, UL1TR001082, UL1 TR000077-04, NCATS/NIH UL1TR000040, UL1TR000150; UL1TR001105, NIH NIAID 5R01AI098077; and UM1AI109565. The following were donated: omalizumab and matching placebo by Novartis, and fluticasone and matching placebo by Glaxo Smith Kline, under a clinical trial agreement with the University of Wisconsin-Madison; EpiPens by Mylan; and Ayr nasal rinse by B. F. Ascher and Company, Inc. None of these companies had a role in the development or approval of the protocol, conduct of the trial, data analysis, manuscript preparation, or the decision to submit for publication.
Funding Information:
Supported in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract numbers HHSN272200900052C, HHSN272201000052I, 1UM1AI114271-01, and UM2AI117870. Additional support was provided by the National Center for Research Resources , National Center for Advancing Translational Sciences , and National Institutes of Health under grants NCRR/NIH UL1TR000451 , 1UL1RR025780 , UL1TR000075 ; NCATS/NIH UL1 TR000154 , UL1TR001082 , UL1 TR000077-04 , NCATS/NIH UL1TR000040 , UL1TR000150 ; UL1TR001105 , NIH NIAID 5R01AI098077 ; and UM1AI109565 . The following were donated: omalizumab and matching placebo by Novartis, and fluticasone and matching placebo by Glaxo Smith Kline, under a clinical trial agreement with the University of Wisconsin-Madison; EpiPens by Mylan; and Ayr nasal rinse by B. F. Ascher and Company, Inc. None of these companies had a role in the development or approval of the protocol, conduct of the trial, data analysis, manuscript preparation, or the decision to submit for publication.
Publisher Copyright:
© 2017 American Academy of Allergy, Asthma & Immunology
PY - 2017/10
Y1 - 2017/10
N2 - Background: A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials. Objective: This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. Methods: The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab. Results: A higher saEPI was associated with an exacerbation in both the GBT alone (P <.001; area under the curve, 0.76) and the GBT + omalizumab group (P <.01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with those who had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups. Conclusions: An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.
AB - Background: A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials. Objective: This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. Methods: The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab. Results: A higher saEPI was associated with an exacerbation in both the GBT alone (P <.001; area under the curve, 0.76) and the GBT + omalizumab group (P <.01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with those who had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups. Conclusions: An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.
KW - Fall asthma exacerbation
KW - Seasonal Asthma Exacerbation Predictive Index (saEPI)
KW - asthma exacerbation predictors
KW - guidelines-based therapy
KW - omalizumab
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U2 - 10.1016/j.jaci.2017.01.026
DO - 10.1016/j.jaci.2017.01.026
M3 - Article
C2 - 28238748
AN - SCOPUS:85016443921
VL - 140
SP - 1130-1137.e5
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 4
ER -