Asthma therapeutics: Past, present, and future.

Abstract

Asthma is a disease of airway inflammation and bronchial hyperresponsiveness affecting over 300 million individuals worldwide. Although described as early as 460 BC, the recognition of asthma as a disease, and the development and implementation of therapies to control it, emerged in the early 1900s. The subsequent century introduced the utilization of immunotherapy, inhaled medications, and anti-inflammatory corticosteroids for disease control. Since the beginning of the 21st century, however, the emergence of novel asthma pharmacotherapies has accelerated greatly. Our understanding of various asthma phenotypes and their underlying mechanisms (endotypes) has crystallized, leading to an era of precision medicine. Management strategies increasingly use targeted biologic medications aimed at interrupting key components of the inflammatory cascade. Monoclonal antibodies targeting the IgE, thymic stromal lymphopoietin, or interleukin-4, -5, and -13 pathways have revolutionized the care we provide our patients, resulting in a reduction in exacerbations and oral corticosteroid (OCS) dose, while improving lung function and asthma-related quality of life. Although they are able to provide relief for many sufferers of severe disease, and even remission in some, these biologic therapies are still in their infancy. Because their roles become further established, new therapeutic targets and modalities offer significant promise of an even greater personalized medicine approach. This review addresses historical standard-of-care strategies for asthma treatment, current recommendations, and a glimpse into future novel therapies that are likely to help millions worldwide. SIGNIFICANCE STATEMENT: Asthma affects hundreds of millions of individuals worldwide. In the last few decades, asthma treatment paradigms have transformed from recommendations to use anti-inflammatory and bronchodilatory inhalation-based therapies including corticosteroids and beta-agonists, to more precisely targeted add-on biologic therapies that employ monoclonal antibodies addressing specific mechanistic pathways associated with specific patient characteristics. Future therapies promise utilization of personalized medicine to a greater extent with novel therapeutic approaches to help improve the health and quality of life of those suffering from asthma.