A Research Agenda for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome: An Official American Thoracic Society Research Statement

Abstract

Background: Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. The recent success of precision medicine in non–critical care settings has resulted from the confluence of large clinical and biospecimen repositories, innovative bioinformatics, and novel trial designs. Similar advances for precision medicine in sepsis and in the acute respiratory distress syndrome (ARDS) are possible but will require further investigation and significant investment in infrastructure. Methods: This project was funded by the American Thoracic Society Board of Directors. A multidisciplinary and diverse working group reviewed the available literature, established a conceptual framework, and iteratively developed recommendations for the Precision Medicine Research Agenda for Sepsis and ARDS. Results: The following six priority recommendations were developed by the working group: 1 ) the creation of large richly phenotyped and harmonized knowledge networks of clinical, imaging, and multianalyte molecular data for sepsis and ARDS; 2 ) the implementation of novel trial designs, including adaptive designs, and embedding trial procedures in the electronic health record; 3 ) continued innovation in the data science and engineering methods required to identify heterogeneity of treatment effect; 4 ) further development of the tools necessary for the real-time application of precision medicine approaches; 5 ) work to ensure that precision medicine strategies are applicable and available to a broad range of patients varying across differing racial, ethnic, socioeconomic, and demographic groups; and 6 ) the securement and maintenance of adequate and sustainable funding for precision medicine efforts. Conclusions: Precision medicine approaches that incorporate variability in genomic, biologic, and environmental factors may provide a path forward for better individualizing the delivery of therapies and improving care for patients with sepsis and ARDS.

Monitoring Lung Injury Severity and Ventilation Intensity during Mechanical Ventilation

“…250 This of course may impact on the estimation of the lung injury severity and on the heterogeneity of treatment effects. This might open new scenarios in the field of lung injury monitoring and ventilation intensity reappraised by ARDS phenotypes 11 and might help enhance enrichment strategies for ARDS trial designs. 12…”

“…8 9 The lack of specific established treatments for ARDS is worrisome 10 and this explains why this condition still requires major efforts in terms of clinical management, ICU resources, and research and development. 11 12 13 The hallmark of the ARDS is the presence of the diffuse alveolar damage (DAD). 14 15 16 Although the clinical criteria of ARDS often do not match the presence of DAD at lung autopsy, 17 18 19 20 the presence of DAD is associated with a higher mortality rate.…”

Acute respiratory distress syndrome among patients with severe COVID-19 admitted to treatment center of Wollega University Referral Hospital, Western Ethiopia

“…ARDS was diagnosed clinically and radiologic investigation by the Physician from the patient on admission. Clinically, ARDS was diagnosed when the patient reports two or more clinical manifestations such as cough, fever, sore throat, and shortness of breath [ 22 ], whereas, Radiologic definition of ARDS was defined according to Kigali modification which is the presence of bilateral opacities at chest radiograph or lung ultrasound and hypoxia with a cutoff of SpO2/FIO2 less than or equal to 315 [ 1 ].…”

Inhaled nitric oxide: role in the pathophysiology of cardio-cerebrovascular and respiratory diseases

“…This makes the clinical evidence available not conclusive so far. Hopefully, the current insights of the ARDS stratification into phenotypes—that are biologically and clinically different features within the same definition of ARDS [ 219 , 220 ]—may help the understanding of the effects of numerous pharmacological treatments in ARDS including iNO [ 221 ].…”