Asthma outcomes workshop: overview.

BACKGROUND: Asthma clinical research will highly benefit from standardization of major outcomes in terms of definition and assessment methodology. This will permit useful comparisons across interventional or observational studies and will allow more effective data sharing. OBJECTIVE: National Institutes of Health (NIH) institutes and the Agency for Healthcare Research and Quality convened a workshop involving 7 expert subcommittees to propose which asthma outcomes should be assessed with standardized methodology in future asthma clinical research studies. METHODS: Each subcommittee utilized comprehensive literature reviews and expert opinion to compile a list of asthma outcomes and classified them as either core (required in future studies), supplemental (to be used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011. RESULTS: Outcomes for study participant characterization, as well as for prospective clinical trial intervention and observational studies, were proposed for adults and children, and methodologies for outcome collection and reporting were determined. Furthermore, the workshop identified areas in which new outcomes or instruments for their measurement need to be developed and validated. CONCLUSIONS: Standardized outcomes for clinical research in asthma have been proposed. Participating NIH institutes and other federal agencies will consider these recommendations in future clinical research initiatives in asthma.

Mediators of asthma outcomes.

BACKGROUND: Patient adherence, the level of asthma self-management skills, exposure to stress, and depression can have considerable influence on a wide range of asthma outcomes and thus are considered asthma outcome mediators. OBJECTIVE: National Institutes of Health institutes and other federal agencies convened an expert group to recommend standardized measures for 7 domains of asthma clinical research outcomes measures. Although the review of mediators of these outcomes was not within the scope of any specific outcome topic, a brief summary is presented so that researchers might consider potential mediators. METHODS: We prepared a summary of key mediators of asthma outcomes based on expertise and knowledge of the literature. RESULTS: The rationale for including measures of adherence, self-management skills, and exposures to stress in asthma clinical research is presented, along with a brief review of instruments for collecting this information from clinical research participants. CONCLUSIONS: Appropriate measurement of adherence, self-management skills, and exposures to stress will enhance characterization of study participants and provide information about the potential impact these factors can have on mediating the effects of treatment interventions.

Asthma outcomes: quality of life.

BACKGROUND: "Asthma-related quality of life" (QOL) refers to the perceived impact that asthma has on the patient's QOL. OBJECTIVE: National Institutes of Health institutes and other federal agencies convened an expert group to recommend standardized measures of the impact of asthma on QOL for use in future asthma clinical research. METHODS: We reviewed published documentation regarding the development and psychometric evaluation; clinical research use since 2000; and extent to which the content of each existing QOL instrument provides a unique, reliable, and valid assessment of the intended construct. We classified instruments as core (required in future studies), supplemental (used according to the study's aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an National Institutes of Health-organized workshop convened in March 2010 and finalized in September 2011. RESULTS: Eleven instruments for adults and 6 for children were identified for review. None qualified as core instruments because they predominantly measured indicators of asthma control (symptoms and/or functional status); failed to provide a distinct, reliable score measuring all key dimensions of the intended construct; and/or lacked adequate psychometric data. CONCLUSIONS: In the absence of existing instruments that meet the stated criteria, currently available instruments are classified as either supplemental or emerging. Research is strongly recommended to develop and evaluate instruments that provide a distinct, reliable measure of the patient's perception of the impact of asthma on all of the key dimensions of QOL, an important outcome that is not captured in other outcome measures.

Comparative effectiveness research in lung diseases and sleep disorders: recommendations from the National Heart, Lung, and Blood Institute workshop.

The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed.

Ensuring a scientific basis for community interventions for asthma.

Community based interventions are an important part of public health management of many diseases, including asthma. However, there are few scientifically proven and readily available community interventions for asthma. In an effort to increase the number of available interventions, we have identified ongoing asthma intervention research, identified potentially effective asthma interventions based on completed research, and prepared several of the effective interventions for widespread implementation through a process called "translation." We provide an example of one of these effective interventions now available for widespread implementation, "Creating a medical home for asthma." This intervention grew out of need for an intervention in New York City Department of Health (NYCDOH) clinics. The intervention includes training all clinic staff in a comprehensive, preventive approach to asthma care. All of the materials needed to implement the intervention are available to all through the NYCDOH web site (www.nyc.gov/ html/doh/html/cmha/index.html). This example points to the importance of making the tools needed to implement effective interventions available across the country and the role of public/private partnerships to assure the availability of science-based interventions for asthma control.

Future research directions in asthma: an NHLBI Working Group report.

Over the last 20 years, the prevalence of asthma has nearly doubled and now affects 8-10% of the population in the United States. Asthma also remains a major illness in terms of morbidity and suffering, and is the leading cause of hospitalizations in children under 15 years of age. Because asthma poses a lifelong burden to patients and society, efforts to increase the understanding of its pathogenesis are a key factor leading to its control and cure. Consequently, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of extramural experts, entitled "Future Research Directions in Asthma," on April 9-10, 2003, to identify research areas of greatest promise and opportunity in the field of asthma. The priority areas identified for research in asthma include: (1) innate immunity, adaptive immunity, and tolerance; (2) mechanisms and consequences of persistent asthma and asthma exacerbations; (3) airway remodeling: clinical consequences and reversibility (clinical relevance and resolution); (4) genetics/gene-environment interactions, pharmacogenetics; (5) intervention/prevention/therapeutics; and (6) vascular basis of asthma.

Population-based screening or case detection for asthma: are we ready?

Asthma is a prevalent health problem for which there are effective treatments. By identifying people with asthma and treating them effectively, the burden of asthma in the United States should be reduced. Detecting people with asthma through screening programs seems a logical approach to the problem. This article assesses our readiness for population-based screening and case detection programs for asthma and examines these activities in relation to World Health Organization criteria for determining the appropriateness of screening programs. Given that, at this time, a number of the criteria have not been met, we conclude that population-based approaches to screening and case detection of asthma are of unproven benefit and need further research. A more appropriate focus may be to ensure that all people who are diagnosed with asthma receive appropriate medical care.

Reducing disparities in asthma care: priorities for research--National Heart, Lung, and Blood Institute workshop report.

Minority groups with diverse racial and ethnic heritages and persons living in poverty are much more likely to die of asthma and to require emergency care for exacerbations of asthma than white persons not living in poverty. The National Heart, Lung, and Blood Institute convened a multidisciplinary group of expert scientists and clinicians to review current research aimed at understanding risk factors for these disparities in asthma health outcomes, to describe key barriers to improving asthma outcomes, and to establish priorities for future research. Education programs for asthma and other chronic diseases were reviewed. Successful elements of clinic and community-based programs were identified. Factors potentially involved in producing disparities include gene-environment interaction, psychologic and social factors, and socioeconomic status. Stress potentially contributes to asthma morbidity at both the individual and community level. Recommendations are made to stimulate research to understand risk factors for disparities and their mechanisms (e.g., gene-by-environment interactions and the role of stress), to define appropriate research designs and methods for evaluating behavioral and community interventions, and to examine how differential access to care contributes to morbidity. Research is encouraged to identify strategies that improve cultural adaptation and adoption of proven programs in a variety of populations.

Long-term effects of budesonide or nedocromil in children with asthma.

BACKGROUND: Antiinflammatory therapies, such as inhaled corticosteroids or nedocromil, are recommended for children with asthma, although there is limited information on their long-term use. METHODS: We randomly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide (311 children), 8 mg of nedocromil (312 children), or placebo (418 children) twice daily. We treated the participants for four to six years. All children used albuterol for asthma symptoms. RESULTS: There was no significant difference between either treatment and placebo in the primary outcome, the degree of change in the forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. As compared with the children assigned to placebo, the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity (FVC, expressed as a percentage) before the administration of a bronchodilator (decline in FEV1:FVC, 0.2 percent vs. 1.8 percent). The children given budesonide also had lower airway responsiveness to methacholine, fewer hospitalizations (2.5 vs. 4.4 per 100 person-years), fewer urgent visits to a caregiver (12 vs. 22 per 100 person-years), greater reduction in the need for albuterol for symptoms, fewer courses of prednisone, and a smaller percentage of days on which additional asthma medications were needed. As compared with placebo, nedocromil significantly reduced urgent care visits (16 vs. 22 per 100 person-years) and courses of prednisone. The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group (22.7 vs. 23.8 cm, P=0.005); this difference was evident mostly within the first year. The height increase was similar in the nedocromil and placebo groups. CONCLUSIONS: In children with mild-to-moderate asthma, neither budesonide nor nedocromil is better than placebo in terms of lung function, but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil. The side effects of budesonide are limited to a small, transient reduction in growth velocity.