Asthma and lower airway disease
Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents

https://doi.org/10.1016/j.jaci.2016.06.059Get rights and content

Background

Treatment levels required to control asthma vary greatly across a population with asthma. The factors that contribute to variability in treatment requirements of inner-city children have not been fully elucidated.

Objective

We sought to identify the clinical characteristics that distinguish difficult-to-control asthma from easy-to-control asthma.

Methods

Asthmatic children aged 6 to 17 years underwent baseline assessment and bimonthly guideline-based management visits over 1 year. Difficult-to-control and easy-to-control asthma were defined as daily therapy with 500 μg of fluticasone or greater with or without a long-acting β-agonist versus 100 μg or less assigned on at least 4 visits. Forty-four baseline variables were used to compare the 2 groups by using univariate analyses and to identify the most relevant features of difficult-to-control asthma by using a variable selection algorithm. Nonlinear seasonal variation in longitudinal measures (symptoms, pulmonary physiology, and exacerbations) was examined by using generalized additive mixed-effects models.

Results

Among 619 recruited participants, 40.9% had difficult-to-control asthma, 37.5% had easy-to-control asthma, and 21.6% fell into neither group. At baseline, FEV1 bronchodilator responsiveness was the most important characteristic distinguishing difficult-to-control asthma from easy-to-control asthma. Markers of rhinitis severity and atopy were among the other major discriminating features. Over time, difficult-to-control asthma was characterized by high exacerbation rates, particularly in spring and fall; greater daytime and nighttime symptoms, especially in fall and winter; and compromised pulmonary physiology despite ongoing high-dose controller therapy.

Conclusions

Despite good adherence, difficult-to-control asthma showed little improvement in symptoms, exacerbations, or pulmonary physiology over the year. In addition to pulmonary physiology measures, rhinitis severity and atopy were associated with high-dose asthma controller therapy requirement.

Section snippets

Study design

Asthma Phenotypes in the Inner City (APIC) was a prospective longitudinal study of 6- to 17-year-old children with asthma living in 9 urban areas. Participant selection criteria included residence in an area with greater than 20% of residents below the poverty level, a physician's diagnosis of asthma, at least 2 episodes of short-acting β-agonist administration within the past 12 months (exclusive of use associated with exercise-induced symptoms), and 50% or greater adherence to controller

Results

Between August 2011 and September 2013, 1195 children were recruited, 845 were eligible for screening, and 717 became part of the longitudinal cohort (Fig 2). Of these, 619 (86.3%) completed at least 4 of the 6 bimonthly visits for evaluation and management of asthma and rhinitis and were included in this analysis. Two hundred fifty-three (40.9%) participants met the criteria for difficult-to-control asthma, 232 (37.5%) had easy-to-control asthma, and 134 (21.6%) had indeterminate asthma.

Discussion

This is the first study to date of a large population of children characterized prospectively while receiving guideline-based management for asthma and rhinitis. The unique and novel aspects of the study are its longitudinal assessment of participants to help characterize and establish the stability of the groups over time; inclusion of standardized, guideline-based asthma and rhinitis assessments and computerized management algorithms; and collection of variables in a broad range of domains,

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    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 Q1 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.

    Disclosure of potential conflict of interest: 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 GlaxoSmithKline; and has received study drugs for other studies from GlaxoSmithKline, Teva, Merck, Boehringer Ingelheim, and Genentech/Novartis. R. Z. Krouse, D. C. Babineau, 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. Khurana Hershey, C. C. Johnson, and S. M. Sigelman have received grants from the NIH. 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 UpToDate. C. M. Kercsmar has received a grant from the NIH and was the chair of Data Safety Monitoring Boards on the GlaxoSmithKline funded, US Food and Drug Administration–mandated VESTRI trial evaluating safety of ICS+LABA vs ICS alone in children. 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, PCORI, 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 UpToDate. L. B. Bacharier has consultant arrangements with Aerocrine, GlaxoSmithKline, Genentech/Novartis, Cephalon, Teva, and Boehringer Ingelheim; has received payment for lectures from Aerocrine, GlaxoSmithKline, Genentech/Novartis, Merck, Teva, Boehringer Ingelheim, and AstraZeneca; has served on the Scientific Advisory Board for Merck; has served on the Data Safety Monitoring Board for DBV Technologies; has received honoraria for CME program development from WebMD/Medscape; and has served on Advisory Boards for Sanofi and Vectura. J. E. Gern has received grants from the NIH and GlaxoSmithKline; has consultant arrangements with GlaxoSmithKline, Genentech, Amgen, Novartis, Janssen, and Regeneron; has received payment for 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, GlaxoSmithKline, Genentech, Roche, Pfizer, Merck, Boehringer-Ingelheim, Sanofi, AstraZeneca, Teva, Takeda, Aerocrine, and 3M. A. H. Liu has received a grant from the NIH, is a member of the Data Monitoring Committee for an asthma study for GlaxoSmithKline, and has received payment for lectures from Merck. The rest of the authors declare that they have no relevant conflicts of interest.

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