Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18–19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma.
Future Research Directions in Asthma
September 18 and 19, 2014
Asthma Origins and Primary Prevention
- Develop methods to assess the developing human infant immune system and lung.
- Define the critical windows in human development when environmental exposures are most likely to increase the risk of asthma or its onset, specifying the relevance of interactions between specific risk factors and the timing (critical window) of the exposure.
- Elucidate the critical windows in human development when non-environmental risk factors cause or influence the onset of asthma, specifying the relevance of interactions between specific risk factors and the timing (critical window) of the exposure.
- Test in utero or early-life strategies targeted to mitigate potential determinants of asthma onset (primary prevention).
- Generate and evaluate methods to measure and analyze the asthmarelevant “exposome” at different stages of human development (e.g., determine how peripubertal changes in the exposome differ by sex and the associated differences in immune response, lung development, and the onset of asthma).
Asthma Heterogeneity: Phenotypes and Endotypes
- Sustain basic and translational research into the mechanisms underlying endotypes and phenotypes of asthma, including, but not limited to, the molecular phenotypes that underlie type 2–low asthma.
- Develop new models for molecular phenotyping, including organotypic cultures of cells from patients.
- Foster public–private scientific collaborations between academia and industry to uncover endotypes in human asthma as revealed by the increasing use of newly developed type 2–specific antagonists.
- Promote investigation of asthma by multidisciplinary groups of scientists and clinicians with diverse expertise, and the ability to use new tools and animal models to explore the heterogeneity of disease mechanisms identify the critical pathobiological mechanisms of disease, and understand the dynamic interactions between such processes.
- Evaluate the relationship between pathobiological pathways and clinical manifestations of disease to enable the identification of appropriate targets for DMATs.
- Assess critical windows for disease modification and clarify when endeffector mechanisms (e.g., smooth muscle structure or function, mucous production, or airway fibrosis) are reversible or modifiable.
Personalized Asthma Control Strategies and Management
- Design nontraditional clinical trials to identify the causes of disease heterogeneity and to facilitate the discovery of diagnostic and prognostic biomarkers.
- Evaluate alternative methods to assess risk factors, mechanisms, and predictors of heterogeneity in the response to treatment, including medication-related adverse effects and morbidity.
- Identify effective longitudinal asthma management models that integrate essential components of care (e.g., diagnosis, monitoring, education, exposures, medications, adherence) to prevent asthma, improve asthma control, or mitigate disease progression while improving efficiency and adaptation over time.
- Asthma control strategies and management models should address the needs and behaviors of patients of all ages (soliciting patient feedback to do so), with different social, economic, and cultural backgrounds in a variety of healthcare settings.
- Create a continuous learning/training collaborative of implementation researchers with the following goals:
- Develop new study designs and methodologies that enable the integration of evidence into clinical practice efficiently while assessing implementation outcomes to meet the dynamic needs of patients with asthma. This will require patient engagement in the research process.
- Investigate best practices for the dissemination of scientific discoveries and evidence-based practices in a variety of clinical care settings.
- Study how novel models of health care and its delivery promote implementation and dissemination in vulnerable and underserved populations that have a disproportionate burden of asthma, as well as in novel contexts, including nonmedical facilities (e.g., school, community center) and alternative healthcare providers (e.g., patient navigator, community health worker).
- Develop a standard training curriculum within the implementation research collaborative for junior investigators to learn how to overcome challenges and attain success in implementation research.
- Establish a comparative costeffectiveness core center within the collaborative that uses a systematic approach to compare various interventions for asthma.
- Serpil C. Erzurum, M.D. Cleveland Clinic Lerner College of Medicine
- Bruce D. Levy, M.D., Brigham and Women’s Hospital
- Kathleen C. Barnes, PhD, Johns Hopkins University
- Bruce G. Bender, PhD, National Jewish Health
- Carlos A. Camargo Jr, MD, Dr.PH, Massachusetts General Hospital
- Geoff L. Chupp, MD, Yale University School of Medicine
- Michelle M. Cloutier, MD, University of Connecticut Health Center
- Loren C. Denlinger, MD PhD, University of Wisconsin
- John V. Fahy, MD, University of California at San Francisco
- Anne M. Fitzpatrick, PhD, RN, Emory University School of Medicine
- Anne Fuhlbrigge, MD, Brigham and Women’s Hospital
- Ben M. Gaston, MD, Case Western Reserve University
- Steve N. Georas, MD, University of Rochester
- Tina V. Hartert, MD, Vanderbilt University School of Medicine
- Nizar N. Jarjour, MD, University of Wisconsin
- Jay K. Kolls, MD, University of Pittsburgh School of Medicine
- Susan V. Lynch, PhD, University of California at San Francisco
- Wendy C. Moore, MD, Wake Forest School of Medicine
- Wayne J. Morgan, MD, University of Arizona
- Kari C. Nadeau, MD, PhD, Stanford School of Medicine
- Carole Ober, PhD, The University of Chicago
- Dennis R. Ownby, MD, Georgia Regents University
- Julian Solway, MD, The University of Chicago
- Stanley J. Szefler, MD, Children’s Hospital Colorado and the University of Colorado School of Medicine
- Sally E. Wenzel, MD, University of Pittsburgh School of Medicine
- Prescott G.Woodruff, MD, University of California at San Francisco
- Rosalind J. Wright, MD, Icahn School of Medicine at Mount Sinai
- Michelle M. Freemer, MD, DLD
- Patricia J. Noel, PhD, DLD
- Robert A. Smith, PhD, DLD