Reviews and feature articles
Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network

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Because of an increasing prevalence, morbidity, and mortality associated with asthma, the National Heart, Lung, and Blood Institute created the Asthma Clinical Research Network and the Childhood Asthma Research and Education Network to improve public health. The objectives of these clinical research networks are to conduct multiple, well-designed clinical trials for rapid evaluation of new and existing therapeutic approaches to asthma and to disseminate laboratory and clinical findings to the health care community. These trials comprise a large proportion of the data driving the treatment guidelines established and reviewed by the National Asthma Education and Prevention Program. This article will review the basic design and major findings of selected Asthma Clinical Research Network and Childhood Asthma Research and Education Network trials involving both adults and children with asthma. Collectively, these studies have helped refine the therapeutic role of existing controller medications, establish standard models for side-effect evaluation and risk-benefit models, validate symptom-based assessments for asthma control, and identify baseline characteristics that might predict individual patient responses. Remaining challenges include shaping the role of novel therapeutics in future guidelines, incorporating pharmacogenomic data in treatment decisions, and establishing better implementation strategies for translation to community settings, all with the goal of reducing the asthma burden on society.

Section snippets

The Beta Agonist Study

In the early 1990s, because of observations made primarily with the use of fenoterol, considerable controversy existed regarding the safety of regular β2-agonist use in asthma. Some investigators reported that the regular use of this class of compounds had the potential of increasing both morbidity and mortality from asthma,2 whereas others were not convinced that such angst was warranted.3 To directly address this controversy, the first protocol developed by the ACRN was the Beta Agonist Study

The Prevention of Early Asthma in Kids trial

Based on data generated in both pediatric28 and adult26, 34 patients with asthma, current asthma guidelines recommend that daily controller therapy should be initiated in individuals whose symptoms place them in the mild persistent asthma category. However, in preschool-aged children wheezing is a common manifestation of viral respiratory tract infections,35 and properly diagnosing asthma in this age group so that appropriate treatment can be initiated has posed a challenge for many clinicians.

Summary

This review has highlighted the major contributions of the ACRN and CARE Network trials to the current NAEPP asthma treatment guidelines, as depicted in Fig 1. First, the stepwise positioning (level of severity between intermittent and persistent) of as-needed short-acting β2-agonists was established (BAGS), and later, whether a subgroup of patients might be at risk if these agents were used on a regular basis (the BARGE trial) was established. Second, the use of the long-acting β-agonist

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    (Supported by an unrestricted educational grant from Genentech, Inc. and Novartis Pharmaceuticals Corporation)

    Series editor: Harold S. Nelson, MD

    The Asthma Clinical Research Network (I) is supported by National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) grants 5U10HL051845, 5U10HL051831, 5U10HL051834, 5U10HL051843, 5U10HL056443, 5U10HL051810, and 5U10HL051823. The Childhood Asthma Research and Education Network is also funded by NIH/NHLBI through grants 5U10HL064313, 5U10HL064288, 5U10HL064305, 5U10HL064295, 5U10HL064287, and 5U10HL064307.

    Disclosure of potential conflict of interest: R. F. Lemanske, Jr, has consultant arrangements with Aventis, GlaxoSmithKline, Merck, and AstraZeneca; has received grant support from the National Heart, Lung, and Blood Institute (NHLBI); and is on the speakers' bureau for Novartis, Merck, GlaxoSmithKline, and AstraZeneca. C. A. Sorkness has consultant arrangements with AstraZeneca and GlaxoSmithKline; has received grant support from GlaxoSmithKline; and is on the speakers' bureau for GlaxoSmithKline. V. M. Chinchilli has consultant arrangements with BristolMeyers Squibb and Eli Lilly and has received grant support from the NHLBI. L. C. Denlinger has declared that he has no conflict of interest.

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