Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes in Severe Adult Asthma

UPMC and the University of Pittsburgh asthma expert Sally Wenzel, MD, published her work on severe adult asthma phenotypes and the need for better treatment guidance in the American Journal of Respiratory and Critical Care Medicine. 

Dr. Wenzel is internationally renowned in the field of severe asthma phenotyping and one of the leaders of conceptualizing asthma as a heterogeneous disease consisting of numerous different phenotypes and influenced by both environmental and genetic factors. 

Identification of Phenotypes

In the last 20–30 years, there has been an increased emphasis on the fact that severe asthma encompasses multiple different phenotypes with differing presentations. Using clinical phenotyping, in combination with rapidly advancing molecular tools and targeted monoclonal antibodies, the understanding of these phenotypes and ability to treat them have greatly advanced.

Type 2 high and low severe asthmas are now easily identified. Fraction exhaled nitric oxide and blood eosinophil counts can be routinely employed in clinical settings to identify these phenotypes and predict responses to specific therapies, meeting the initial goals of precision medicine. Integration of molecular signals, biomarkers, and clinical responses to targeted therapies has enabled identification of critical molecular pathways and in certain phenotypes, advanced them to near endotype status.

Determining Appropriate Treatments

While advances have been made to better identify the endotypes and phenotypes of severe asthma, little guidance is available to determine which treatments are appropriate for a given patient and current breakthrough therapies remain expensive and even inaccessible to many patients.

Many of the most severe asthmas remain poorly understood and treated. Yet, conceptual understanding of these severe asthmas has evolved dramatically, leading to remarkable improvements in the lives of many. 

About Dr. Wenzel

Sally Wenzel, MD, is chair of Environmental and Occupational Health, Rachel Carson chair of Environmental Health, and director of the University of Pittsburgh Asthma and Environmental Lung Health Institute. 

Dr. Wenzel is dedicated to understanding and improving the treatment of asthma, particularly severe asthma. She has worked to promote severe asthma as a disease whose pathogenesis goes beyond issues of non-compliance/adherence. Her studies of asthma phenotypes have led the field in understanding the complexities of asthma and she is internationally recognized for her efforts in this area.

Dr. Wenzel’s lab has focused on understanding both the subtypes of human asthma and the combination of environmental and genetic factors which drive them. Research has been intensive on the role of airway epithelial cells in human disease, given the position of these cells to link the environment with the host. Work encompasses use of large epidemiologic/research databases, including those both local and national, to define patient characteristics and relationships to environmental triggers, but also to include studies of specific human immunology, both in human samples and model systems. Current pathways of interest include those related to environmental and innate lung oxidative stress, as well as their intersections with inflammation, mucins, and cell death pathways.

Dr. Wenzel has been chosen to be the American Thoracic Society (ATS) 2021 Amberson Lecturer at this year’s ATS Conference. The Amberson Lecture recognizes exemplary professionalism, collegiality and citizenship through mentorship and leadership in the ATS community. The Amberson Lecturer is an individual with a career of major lifetime contributions to clinical or basic pulmonary research and/or clinical practice. The Lecture is given in honor of James Burns Amberson, an international authority on chest disease and tuberculosis.