Reviews and feature articlesGuideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network
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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Perspectives in beta 2-agonist therapy: vox clamantis in deserto vel lux in tenebris?
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Characterization of within-subject responses to fluticasone and montelukast in childhood asthma
J Allergy Clin Immunol
Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma
J Allergy Clin Immunol
The clinical trials in the initial five-year award period of the Asthma Clinical Research Network
Control Clin Trials
The use of beta-agonists and the risk of death and near death from asthma
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Comparison of regularly scheduled with as-needed use of albuterol in mild asthma
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A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma
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Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma
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Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial
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Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids
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Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma
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Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial
JAMA
Cited by (43)
Insights into glucocorticoid responses derived from omics studies
2021, Pharmacology and TherapeuticsCitation Excerpt :For example, glucocorticoid pharmacogenomics studies in asthma have been based on cohorts of patients taking inhaled corticosteroids (ICS) over variable time courses while using the number of asthma exacerbations and/or improved lung function over a time period as outcomes. Some of these cohorts consist of subjects in clinical trials that had wash-out periods and monitored drug use carefully (Denlinger, Sorkness, Chinchilli, & Lemanske Jr., 2007; Mosteller et al., 2017; Strunk and Childhood Asthma Management Program Research, 2007), while other studies included subjects with varying levels of disease severity and no medication adherence data (Dahlin et al., 2015; Hernandez-Pacheco et al., 2019). Early genetics studies of glucocorticoid responses focused on single nucleotide polymorphisms (SNPs) of the NR3C1 gene due to its direct role in glucocorticoid action.
Designing clinical trials to address the needs of childhood and adult asthma: The National Heart, Lung, and Blood Institute's AsthmaNet
2014, Journal of Allergy and Clinical ImmunologyCitation Excerpt :A significant component of the AsthmaNet scientific agenda grew out of observations made by NHLBI-supported research networks, in particular the Asthma Clinical Research Network (adult asthma studies) and the Childhood Asthma Research and Education Network (CARE). As reviewed elsewhere,5,6 trials conducted over the lifespans of these networks resulted in seminal advances in asthma care. In the field of adult asthma, Asthma Clinical Research Network studies (1) evaluated and identified predictors of inhaled corticosteroid (ICS) dose response with regard to lung function and airway hyperresponsiveness7-9; (2) further defined the role of β-adrenergic agonists in the treatment of asthma with particular regard to efficacy, safety, and pharmacogenetics10-15; (3) determined approaches by which therapeutic escalation (step-up) should occur12,13,16; (4) tested intermittent and biomarker-based ICS treatment strategies17,18; and (5) assessed novel immunomodulatory and bronchodilator therapeutic approaches,19-21 as well as treatment approaches in specific patient subsets.22
Advancing asthma care: The glass is only half full!
2011, Journal of Allergy and Clinical ImmunologyCitation Excerpt :During the 1990s, there was a move toward evidence-based medicine and the introduction of National Institutes of Health asthma networks to address gaps in asthma management, including inner-city asthma.21-28 With the emergence of key asthma network studies, it was possible to identify comparative efficacy of medications, explore variability in treatment response, and obtain information on areas of need, including inner-city asthma, severe asthma, and early development of asthma.21-29 Also, studies were reported that demonstrated the role of intermittent ICSs in place of continuous daily dosing of these medications to minimize the risk of adverse effects.30-32
Achieving and maintaining asthma control in inner-city children
2011, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Several randomized controlled trials targeting inner-city minority children with asthma have had limited effects, demonstrating difficulties in achieving improvement in this population despite intensive interventions.28-31 It is unclear why African American patients tend to have more difficult to control asthma, as observed in our study and by other investigators.8,31 Further investigation is required to identify specifically which factors including environmental, socioeconomic, psychosocial, behavioral, or genetic explain this phenomenon.
Key observations from the NHLBI Asthma Clinical Research Network
2012, ThoraxCitation Excerpt :The clinical questions we explored in relation to β agonists answered the initial questions posed and led us to investigate areas regarding personalisation of asthma treatment and pharmacogenomics. The BAGS (β-Agonists)1 and BARGE (β-Agonist Response by Genotype)7 trials, conducted in adults, have been previously reviewed,15 and showed that as-needed albuterol was just as good as scheduled albuterol, but that participants with the Arg/Arg genotype affecting the 16th amino acid of the ß2 adrenergic receptor experienced a deterioration in peak flow, FEV1, symptoms, and increased need for rescue inhaler when using albuterol regularly whereas the participants with the Gly/Gly genotype experienced an improvement in all these indices when using albuterol regularly. These data suggested that bronchodilator treatments avoiding albuterol may be appropriate for patients bearing the Arg/Arg genotype who are not using ICS.
The Saudi initiative for asthma – 2024 update: Guidelines for the diagnosis and management of asthma in adults and children
2024, Annals of Thoracic Medicine
(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.