Pathways through which asthma risk factors contribute to asthma severity in inner-city children - 06/10/16
, Denise C. Babineau, PhD c, Rebecca Z. Krouse, MS c, Edward M. Zoratti, MD d, Jacqueline A. Pongracic, MD e, George T. O'Connor, MD, MS f, Robert A. Wood, MD g, Gurjit K. Khurana Hershey, MD, PhD h, Carolyn M. Kercsmar, MD h, Rebecca S. Gruchalla, MD, PhD i, Meyer Kattan, MD j, Stephen J. Teach, MD, MPH k, Melanie Makhija, MD e, Dinesh Pillai, MD k, Carin I. Lamm, MD j, James E. Gern, MD l, Steven M. Sigelman, RN, MHA m, Peter J. Gergen, MD, MPH m, Alkis Togias, MD m, Cynthia M. Visness, PhD c, William W. Busse, MD lAbstract |
Background |
Pathway analyses can be used to determine how host and environmental factors contribute to asthma severity.
Objective |
To investigate pathways explaining asthma severity in inner-city children.
Methods |
On the basis of medical evidence in the published literature, we developed a conceptual model to describe how 8 risk-factor domains (allergen sensitization, allergic inflammation, pulmonary physiology, stress, obesity, vitamin D, environmental tobacco smoke [ETS] exposure, and rhinitis severity) are linked to asthma severity. To estimate the relative magnitude and significance of hypothesized relationships among these domains and asthma severity, we applied a causal network analysis to test our model in an Inner-City Asthma Consortium study. Participants comprised 6- to 17-year-old children (n = 561) with asthma and rhinitis from 9 US inner cities who were evaluated every 2 months for 1 year. Asthma severity was measured by a longitudinal composite assessment of day and night symptoms, exacerbations, and controller usage.
Results |
Our conceptual model explained 53.4% of the variance in asthma severity. An allergy pathway (linking allergen sensitization, allergic inflammation, pulmonary physiology, and rhinitis severity domains to asthma severity) and the ETS exposure pathway (linking ETS exposure and pulmonary physiology domains to asthma severity) exerted significant effects on asthma severity. Among the domains, pulmonary physiology and rhinitis severity had the largest significant standardized total effects on asthma severity (−0.51 and 0.48, respectively), followed by ETS exposure (0.30) and allergic inflammation (0.22). Although vitamin D had modest but significant indirect effects on asthma severity, its total effect was insignificant (0.01).
Conclusions |
The standardized effect sizes generated by a causal network analysis quantify the relative contributions of different domains and can be used to prioritize interventions to address asthma severity.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Asthma, children, inner-city, allergy, sensitization, inflammation, lung function, pulmonary physiology, rhinitis, environmental tobacco smoke exposure
Abbreviations used : APIC, BMI, ETS
Plan
| This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (under contract nos. HHSN272200900052C and HHSN272201000052I, and 1UM1AI114271-01). Additional support was provided by the National Center for Research Resources (NCRR), and the National Center for Advancing Translational Sciences (NCATS), NIH (under grant nos. NCRR/NIH UL1TR000451, UL1RR025780, UL1TR000075 and NCATS/NIH UL1TR000154, UL1TR001082, UL1TR000077-04, UL1TR000040, UL1TR000150, and UL1TR001105). GlaxoSmithKline (GSK) provided Ventolin, Flovent, Advair, and Flonase under a clinical trial agreement with NIH NIAID; GSK did not have a role in the development or approval of the protocol, conduct of the trial, data analysis, manuscript preparation, or the decision to submit the manuscript for publication. |
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| Disclosure of potential conflict of interest: A. H. Liu has received a grant from the National Institutes of Health, is a member of the Data Monitoring Committee for an asthma study for GlaxoSmithKline (GSK), and has received payment for lectures from Merck. D. C. Babineau, R. Z. Krouse, and C. M. Visness have received grants from the National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases (NIAID). E. M. Zoratti, G. K. K. Hershey, M. Makhija, D. Pillai, C. I. Lamm, and S. M. Sigelman have received grants from the NIH. J. A. Pongracic has received travel support and a subcontract from the University of Wisconsin; has received writing assistance, medicines, equipment, or administrative support from GSK; and has received study drugs for other studies from GSK, Teva, Merck, Boehringer-Ingelheim, and Genentech/Novartis. G. T. O'Connor has received grants from the NIH and has consultant arrangements with AstraZeneca. R. A. Wood has received grants from the NIH, DBV, and Aimmune; has consultant arrangements with Sanofi and Stallergenes; is employed by Johns Hopkins University; and has received royalties from Up To Date. C. M. Kercsmar has received a grant from the NIH and was the chair of the Data Safety Monitoring Board on GSK-funded, Food and Drug Administration–mandated trial evaluating the safety of inhaled corticosteroid + long-acting beta-agonist versus inhaled corticosteroid alone in children (ClinicalTrials.gov Identifier: NCT01462344). R. S. Gruchalla is employed by the Center for Biologics Evaluation and Research and has consultant arrangements with the Massachusetts Medical Society. M. Kattan has received a grant from the NIH-NIAID and is on the advisory board for Novartis Pharma. S. J. Teach has received grants from the NIH-NIAID, Novartis, Patient-Centered Outcomes Research Institute, Fight for Children Foundation, EJF Philanthropies, and the NIH-National Heart, Lung, and Blood Institute; has consultant arrangements with Novartis; and has received royalties from Up To Date. J. E. Gern has received grants from the NIH and GSK; has consultant arrangements with GSK, Genentech, Amgen, Novartis, Janssen, and Regeneron; has received payment for the development of educational presentations from Boehringer-Ingelheim; and has stock/stock options in 3V BioSciences. W. W. Busse has received a grant from the NIH-NIAID; has received partial study funding and provision of study drug and placebo from Novartis; is a member of the Data Safety Monitoring Boards for Boston Scientific and Circassia; is a member of the Study Oversight Committee for ICON; and has consultant arrangements with Novartis, GSK, Genentech, Roche, Pfizer, Merck, Boehringer-Ingelheim, Sanofi, AstraZeneca, Teva, Tekeda, Aerocrine, and 3M. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 138 - N° 4
P. 1042-1050 - octobre 2016 Retour au numéro
Article précédent
- Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents
- Jacqueline A. Pongracic, Rebecca Z. Krouse, Denise C. Babineau, Edward M. Zoratti, Robyn T. Cohen, Robert A. Wood, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Rebecca S. Gruchalla, Meyer Kattan, Stephen J. Teach, Christine C. Johnson, Leonard B. Bacharier, James E. Gern, Steven M. Sigelman, Peter J. Gergen, Alkis Togias, Cynthia M. Visness, William W. Busse, Andrew H. Liu
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