Economic burden of impairment in children with severe or difficult-to-treat asthma Stanley J. Szefler, MD*; Robert S. Zeiger, MD, PhD†; Tmirah Haselkorn, PhD‡*; David R. Mink, MS§; Tripthi V. Kamath, PhD‡; James E. Fish, MD‡¶; and Bradley E. Chipps, MD Background: The cost associated with asthma impairment in children with severe asthma has not been determined. Objective: To assess the asthma cost burden in children with severe or difficult-to-treat asthma based on asthma impairment. Methods: Children aged 6 to 12 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with available data at baseline (n = 628), month 12 (n = 385), and month 24 (n = 280) corresponding to the National Heart, Lung, and Blood Institute asthma guidelines’ impairment domain were included. Children were categorized as either very poorly controlled (VPC), not well controlled (NWC), or well controlled (WC) and assessed cross-sectionally and longitudinally. Mean total asthma costs based on direct (medication usage, unscheduled office visits, emergency department visits, hospitalizations) and indirect (school/work days lost) asthma costs were assessed. Results: Mean annual total asthma costs were more than twice as high in the VPC group compared with NWC and WC groups (baseline: $7,846, $3,526, $3,766.44, respectively; month 12: $7,326, $2,959, $2,043, respectively; month 24: $8,879, $3,308, $1,861, respectively (all P  .001). Indirect costs accounted for approximately half the total asthma costs for VPC asthma patients at each time point. Significantly lower costs were observed for patients whose impairment status improved or temporarily improved from VPC after baseline. Conclusion: The economic burden of severe or difficult-to-treat asthma in children is associated with VPC asthma and improvement in asthma control and is associated with reducing cost. Further attention to patients with poorly controlled asthma, through better management strategies or more effective medications, may significantly reduce this burden of illness. Ann Allergy Asthma Immunol. 2011;107:110 –119. INTRODUCTION Asthma, one of the most common chronic diseases, affects 20% of children worldwide. 1,2 Among children younger than 18 years of age in the United States, 13.0% have been diagnosed with asthma, and 8.9% (6.5 million) currently have asthma. 3 Recent analysis of data from the 2003/2004 National Survey of Children’s Health demonstrated a significant rela- tionship between severe asthma and lower health-related quality of life (P = .005). 4 In 2007, the total incremental cost of asthma to society was $56 billion, with direct costs accounting for $50.1 billion, pro- ductivity losses attributable to morbidity accounting for $3.8 billion, and productivity losses attributable to mortality account- ing for $2.1 billion. 5 More than 80% of healthcare resources are used by 20% of asthma patients, 6 likely reflecting a patient subgroup with severe or uncontrolled disease, because overall costs are related to severity 7 and uncontrolled disease. 8 Studies of children with asthma indicate that high rates of medication use and healthcare utilization (HCU) are related to uncontrolled disease 9 and increased cost burden. 9-12 Al- though studies have assessed the costs associated with pedi- atric asthma as a whole, 13-15 none has focused on the costs of uncontrolled asthma or whether changes in control affect costs. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) observational study assessed a large cohort of patients with severe or difficult-to-treat asthma and provided relevant data regarding this understudied population. 9,16,17 The current analysis as- sessed the burden in children aged 6 to 12 years in relation to Affiliations: * National Jewish Health, Denver, Colorado; † Kaiser-Perma- nente Medical Center, San Diego, California; ‡ Genentech, Inc., South San Francisco, California; § ICON Clinical Research, San Francisco, California;  Capital Allergy & Respiratory Disease Center, Sacramento, California ¶ Cur- rent affiliation: Merck Research Laboratories, North Wales, Pennsylvania Funding Sources: Genentech, Inc., South San Francisco, CA, and No- vartis Pharmaceuticals, East Hanover, NJ, provided support for the prepara- tion of this manuscript. Disclosures: Dr. Szefler has consultant arrangements with Abbott, Boehringer- Ingelheim, Genentech, GlaxoSmithKline, Merck, and Novartis, received grant/re- search support from GlaxoSmithKline, and currently receives grant support from the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Environmental Health Sci- ences/Environmental Protection Agency, the Colorado Cancer, Cardiovascular, and Pulmonary Disease Program, and the Caring for Colorado Foundation. Dr. Zeiger has consultant arrangements with AstraZeneca, Aerocrine, Genentech, GlaxoSmith- Kline, MedImmune, Merck, and Schering-Plough and receives grant/research sup- port from AstraZeneca, Aerocrine, Genentech, GlaxoSmithKline, and Merck. Dr. Haselkorn is a paid consultant to Genentech. Mr. Mink is employed by ICON Clinical Research. Dr. Kamath is an employee of Genentech. Dr. Fish was an employee of Genentech at the time the study was conducted and is currently an employee of Merck. Dr. Chipps has consultant arrangements with Alcon, Aventis, Genentech, AstraZeneca, GlaxoSmithKline, Medpoint, Novartis, Schering, Sepra- cor, and Merck, has received grant/research support from Alcon, Aventis, Genen- tech, AstraZeneca, GlaxoSmithKline, Novartis, Schering, Sepracor, and Merck, and has participated on speaker bureaus for Alcon, Aventis, Genentech, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Medpoint, Novartis, Pfizer, Schering- Plough, Sepracor, and Merck. Received for publication November 15, 2010; Received in revised form April 13, 2011. © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.anai.2011.04.008 110 ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY