Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes.
Sally E WentzelPublished in: American journal of respiratory and critical care medicine (2021)
Evaluation and effective management of asthma, and in particular severe asthma, remains at the core of pulmonary practice. Over the last 20-30 years, there has been increasing appreciation that "severe asthma" encompasses multiple different subgroups or phenotypes, each with differing presentations. Using clinical phenotyping, in combination with rapidly advancing molecular tools and targeted monoclonal antibodies (human knockouts), the understanding of these phenotypes, and our ability to treat them, have greatly advanced. Type-2 (T2)-high and -low severe asthmas are now easily identified. Fractional 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. Despite these advances, little guidance is available to determine which class of biologic is appropriate for a given patient, and current "breakthrough" therapies remain expensive and even inaccessible to many patients. Many of the most severe asthmas, with and without T2-biomarker elevations, remain poorly understood and treated. Nevertheless, conceptual understanding of "the severe asthmas" has evolved dramatically in a mere 25 years, leading to dramatic improvements in the lives of many.
Keyphrases
- nitric oxide
- early onset
- rheumatoid arthritis
- primary care
- endothelial cells
- ejection fraction
- newly diagnosed
- chronic obstructive pulmonary disease
- type diabetes
- public health
- high throughput
- lung function
- metabolic syndrome
- drug induced
- insulin resistance
- young adults
- chronic kidney disease
- air pollution
- patient reported outcomes
- peripheral blood
- weight loss