Institute Asthma Research Articles

Management of Preschool Children with Recurrent Wheezing: Lessons from the NHLBI's Asthma Research Networks

Recurrent wheezing in the preschool children is a common clinical problem, often associated with significant morbidity related to acute episodes. The management of these children has been complicated by a paucity of high-quality clinical trials in this age group. To fill this knowledge gap, National Heart, Lung,and Blood Institute's asthma research networks have performed a series of clinical trials in an effort to provide practitioners with guidance on appropriate management strategies. These studies establish daily inhaled corticosteroid (ICS) therapy in toddlers at high risk for subsequent asthma as an effective approach for the prevention of exacerbations and symptom reduction, but without evidence of disease-modifying properties. Additional studies have confirmed substantial heterogeneity in ICS response, in terms of both efficacy and effect on linear growth.Treatment with intermittent high-dose ICS was demonstrated to be an alternative approach to daily low-dose ICS for preventingsevere exacerbations in toddlers with intermittent butsignificant wheeze and a positive modified asthma predictive index. This review details the findings and clinical implications derived fromthese studies, discuss the utility of biomarkers andthe roleof oral corticosteroids during acute exacerbations, and summarizes ongoing clinical trials in this age group.

Implementing asthma guidelines using practice facilitation and local learning collaboratives: a randomized controlled trial.

Guideline implementation in primary care has proven difficult. Although external assistance through performance feedback, academic detailing, practice facilitation (PF), and learning collaboratives seems to help, the best combination of interventions has not been determined. In a cluster randomized trial, we compared the independent and combined effectiveness of PF and local learning collaboratives (LLCs), combined with performance feedback and academic detailing, with performance feedback and academic detailing alone on implementation of the National Heart, Lung and Blood Institute's Asthma Guidelines. The study was conducted in 3 primary care practice-based research networks. Medical records of patients with asthma seen during pre- and postintervention periods were abstracted to determine adherence to 6 guideline recommendations. McNemar's test and multivariate modeling were used to evaluate the impact of the interventions. Across 43 practices, 1,016 patients met inclusion criteria. Overall, adherence to all 6 recommendations increased (P ≤.002). Examination of improvement by study arm in unadjusted analyses showed that practices in the control arm significantly improved adherence to 2 of 6 recommendations, whereas practices in the PF arm improved in 3, practices in the LLCs improved in 4, and practices in the PF + LLC arm improved in 5 of 6 recommendations. In multivariate modeling, PF practices significantly improved assessment of asthma severity (odds ratio [OR] = 2.5, 95% CI, 1.7-3.8) and assessment of asthma level of control (OR = 2.3, 95% CI, 1.5-3.5) compared with control practices. Practices assigned to LLCs did not improve significantly more than control practices for any recommendation. Addition of PF to performance feedback and academic detailing was helpful to practices attempting to improve adherence to asthma guidelines.

Products at Risk

In this issue of the Journal, we publish the results of a clinical trial investigating step-up control in adult patients with asthma whose disease was not well controlled by low-dose inhaled glucocorticoids.1 This study, which compared the utility of treating such patients with inhaled tiotropium bromide, inhaled salmeterol, or higher doses of inhaled glucocorticoids, was conceived and implemented by the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network (ACRN). The study constitutes comparative effectiveness research, in which the products of a number of different companies are compared in a well-defined clinical setting. Simply put, the companies' products are . . .

A matched crossover design for clinical trials

Two design principles are used frequently in clinical trials: 1) A subject is “matched” or “paired” with a similar subject to reduce the chance that other variables obscure the primary comparison of interest. 2) A subject serves as his/her own control by “crossing over” from one treatment to another during the course of an experiment. There are situations in which it may be advantageous to use the two design principles — crossing over and matching — simultaneously. That is, it may be advantageous to conduct a “paired crossover design,” in which each subject, while paired with a similar subject, crosses over and receives each experimental treatment. In this paper, we describe two clinical trials conducted by the National Heart, Lung and Blood Institute's Asthma Clinical Research Network that used a paired 2 × 2 crossover design. The Beta Adrenergic Response by GEnotype (BARGE) Study compared the effects of regular use of inhaled albuterol on mildly asthmatic patients with different genotypes at the 16th position of the beta-agonist receptor gene. The Smoking Modulates Outcomes of Glucocorticoid (SMOG) Therapy in Asthma Study evaluated the hypothesis that smoking reduces the response to inhaled corticosteroids. For such paired crossover designs, the primary parameter of interest is typically the treatment-by-pairing interaction term. In evaluating the relative efficiency of the paired 2 × 2 crossover design to two independent crossover designs with respect to this interaction term, we show that the paired 2 × 2 crossover design is more efficient if the correlations between the paired members on the same treatments are greater than their correlations on different treatments. This condition should hold in most circumstances, and therefore the paired crossover design deserves serious consideration for any clinical trial in which the crossing over and matching of subjects is deemed simultaneously beneficial.

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

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

Preface: Civic Support and Leadership as a Catalyst for Addressing the Problem of Urban Asthma: The Otho S. A. Sprague Memorial Institute's Asthma Initiative

Preface: Civic Support and Leadership as a Catalyst for Addressing the Problem of Urban Asthma: The Otho S. A. Sprague Memorial Institute's Asthma Initiative

Scheduled and as-needed albuterol were equivalent for mild asthma

Source Citation Drazen JM, Israel E, Boushey HA, et al., for the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network. Comparison of regularly scheduled with as-needed use o...