The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of Network organization, procedures, and interventions

Abstract

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.

The Role of Nutrition in Mitigating the Effects of COVID-19 from Infection through PASC

“…Recently asthma, which is a pulmonary disease that has many symptoms in common with COVID-19 and is also a comorbid condition related to elevated risk of COVID-19 and PASC severity, has been shown to have a metabolic underpinning [ 77 ]. The unique metabolic underpinning in asthma has yet to be fully elucidated but may involve a shift in fuel preference (i.e., nutrient utilization), away from carbohydrates towards lipids or ketones [ 78 , 79 ]. In agreement with the shift away from carbohydrate metabolism, ketosis shows a therapeutic benefit in murine asthma models by reducing bronchoconstriction in the airway smooth muscle; bronchoconstriction being the primary airway symptoms leading to wheezing and difficulty breathing [ 80 ].…”

Individualized interventions and precision health: Lessons learned from a systematic review and implications for analytics‐driven geriatric research

“…A review of http://clinicaltrials.gov shows a series of other SMARTs underway, including those focused on psychiatric diseases (NCT01588457), back pain (NCT05396014), and cancer pain (NCT02791646). Precision health‐based platforms have also been developed to characterize subtypes of asthma and their responses to various interventions 40,41 . Particularly relevant to older adult patients, individualized treatment rules have been applied to determine optimal exercise therapies 42 and multicomponent treatment regimes for patients with osteoarthritis 43,44 .…”

“…Precision health-based platforms have also been developed to characterize subtypes of asthma and their responses to various interventions. 40,41 Particularly relevant to older adult patients, individualized treatment rules have been applied to determine optimal exercise therapies 42 and multicomponent treatment regimes for patients with osteoarthritis. 43,44 At this time, our team is also actively developing new studies, which will leverage SMART designs and precision health analytics to individualize and optimize health promotion among older adults; the goal of these studies is to generate data-driven, robust algorithms that can help providers to empirical approaches to tailor obesity and diabetes management within geriatric populations for their best possible clinical and patient-oriented outcomes, using information from similar patients and their responses to different interventions.…”

Upper airway disease diagnosis as a predictive biomarker of therapeutic response to biologics in severe asthma

“…The biomarkers that are currently validated in asthma relate to type 2 (T2) immunity, namely blood (or sputum) eosinophils and exhaled nitric oxide (FeNO), which are elevated in more than half of patients with severe asthma ( 7 – 9 ). In addition, those T2 biomarkers may overlap with allergy/atopic sensitization, which is also present in approximately half of the patients with SA, resulting in a large overlap between allergic and non-allergic patients with T2/eosinophilic asthma.…”