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1.
Crit Care ; 25(1): 404, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1745432

ABSTRACT

Identifying new effective treatments for the acute respiratory distress syndrome (ARDS), including COVID-19 ARDS, remains a challenge. The field of ARDS investigation is moving increasingly toward innovative approaches such as the personalization of therapy to biological and clinical sub-phenotypes. Additionally, there is growing recognition of the importance of the global context to identify effective ARDS treatments. This review highlights emerging opportunities and continued challenges for personalizing therapy for ARDS, from identifying treatable traits to innovative clinical trial design and recognition of patient-level factors as the field of critical care investigation moves forward into the twenty-first century.


Subject(s)
Precision Medicine , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials as Topic , Humans , Respiratory Distress Syndrome/virology
2.
Crit Care ; 25(1): 404, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1533274

ABSTRACT

Identifying new effective treatments for the acute respiratory distress syndrome (ARDS), including COVID-19 ARDS, remains a challenge. The field of ARDS investigation is moving increasingly toward innovative approaches such as the personalization of therapy to biological and clinical sub-phenotypes. Additionally, there is growing recognition of the importance of the global context to identify effective ARDS treatments. This review highlights emerging opportunities and continued challenges for personalizing therapy for ARDS, from identifying treatable traits to innovative clinical trial design and recognition of patient-level factors as the field of critical care investigation moves forward into the twenty-first century.


Subject(s)
Precision Medicine , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials as Topic , Humans , Respiratory Distress Syndrome/virology
3.
Ann Am Thorac Soc ; 18(4): 698-708, 2021 04.
Article in English | MEDLINE | ID: covidwho-1186616

ABSTRACT

Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a ß-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute.Clinical trial registered with www.clinicaltrials.gov (NCT04193878).


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Adult , Humans , Respiration, Artificial , Respiratory Insufficiency/therapy , SARS-CoV-2
4.
Intensive Care Med ; 46(12): 2136-2152, 2020 12.
Article in English | MEDLINE | ID: covidwho-932503

ABSTRACT

Although the acute respiratory distress syndrome (ARDS) is well defined by the development of acute hypoxemia, bilateral infiltrates and non-cardiogenic pulmonary edema, ARDS is heterogeneous in terms of clinical risk factors, physiology of lung injury, microbiology, and biology, potentially explaining why pharmacologic therapies have been mostly unsuccessful in treating ARDS. Identifying phenotypes of ARDS and integrating this information into patient selection for clinical trials may increase the chance for efficacy with new treatments. In this review, we focus on classifying ARDS by the associated clinical disorders, physiological data, and radiographic imaging. We consider biologic phenotypes, including plasma protein biomarkers, gene expression, and common causative microbiologic pathogens. We will also discuss the issue of focusing clinical trials on the patient's phase of lung injury, including prevention, administration of therapy during early acute lung injury, and treatment of established ARDS. A more in depth understanding of the interplay of these variables in ARDS should provide more success in designing and conducting clinical trials and achieving the goal of personalized medicine.


Subject(s)
Phenotype , Respiratory Distress Syndrome/genetics , Biomarkers , Humans , Precision Medicine/trends , Radiography/methods , Radiography/trends , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/physiopathology
5.
JCI Insight ; 5(17)2020 09 03.
Article in English | MEDLINE | ID: covidwho-676865

ABSTRACT

BACKGROUNDElevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes.METHODSWe used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1ß, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTSFifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1ß, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONLevels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDINGFunding was received from NHLBI K23 HL125663 (AJR); The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16; Stanford Maternal Child Health Research Institute; and Chan Zuckerberg Biohub (CAB).


Subject(s)
Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Cytokines/immunology , Pneumonia, Viral/immunology , Respiratory Distress Syndrome/immunology , Sepsis/immunology , Adult , Aged , COVID-19 , Case-Control Studies , Coronavirus Infections/blood , Cytokine Release Syndrome/blood , Cytokines/blood , Female , Humans , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin 1 Receptor Antagonist Protein/immunology , Interleukin-18/blood , Interleukin-18/immunology , Interleukin-1beta/blood , Interleukin-1beta/immunology , Interleukin-6/blood , Interleukin-6/immunology , Interleukin-8/blood , Interleukin-8/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Respiratory Distress Syndrome/blood , Sepsis/blood , Severity of Illness Index , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunology
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