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1.
Chest ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38768777

RESUMO

BACKGROUND: ARDS is a heterogeneous condition with two subphenotypes identified by different methodologies. Our group similarly identified two ARDS subphenotypes using nine routinely available clinical variables. However, whether these are associated with differential response to treatment has yet to be explored. RESEARCH QUESTION: Are there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS? STUDY DESIGN AND METHODS: We evaluated data from two prior ARDS trials (Higher vs Lower Positive End-Expiratory Pressures in Patients With the ARDS [ALVEOLI] and the Alveolar Recruitment in ARDS Trial [ART]) that compared different PEEP strategies. We classified patients into one of two subphenotypes as described previously. We assessed the differential effect of PEEP with a Bayesian hierarchical logistic model for the primary outcome of 28-day mortality. RESULTS: We analyzed data from 1,559 patients with ARDS. Compared with lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in patients with subphenotype A disease in the ALVEOLI study (OR, 1.61; 95% credible interval [CrI], 0.90-2.94) and ART (OR, 1.73; 95% CrI, 1.01-2.98), with a probability of harm resulting from higher PEEP in this subphenotype of 94.3% and 97.7% in the ALVEOLI and ART studies, respectively. Higher PEEP was not associated with mortality in patients with subphenotype B disease in each trial (OR, 0.95 [95% CrI, 0.51-1.73] and 1.00 [95% CrI, 0.63-1.55], respectively), with probability of benefit of 56.4% and 50.7% in the ALVEOLI and ART studies, respectively. These effects were not modified by Pao2 to Fio2 ratio, driving pressure, or the severity of illness for the cohorts. INTERPRETATION: We found evidence of differential response to PEEP strategies across two ARDS subphenotypes, suggesting possible harm with a higher PEEP strategy in one subphenotype. These observations may assist with predictive enrichment in future clinical trials.

2.
BMJ Open ; 12(1): e053297, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34992112

RESUMO

OBJECTIVES: The acute respiratory distress syndrome (ARDS) is a heterogeneous condition, and identification of subphenotypes may help in better risk stratification. Our study objective is to identify ARDS subphenotypes using new simpler methodology and readily available clinical variables. SETTING: This is a retrospective Cohort Study of ARDS trials. Data from the US ARDSNet trials and from the international ART trial. PARTICIPANTS: 3763 patients from ARDSNet data sets and 1010 patients from the ART data set. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was 60-day or 28-day mortality, depending on what was reported in the original trial. K-means cluster analysis was performed to identify subgroups. Sets of candidate variables were tested to assess their ability to produce different probabilities for mortality in each cluster. Clusters were compared with biomarker data, allowing identification of subphenotypes. RESULTS: Data from 4773 patients were analysed. Two subphenotypes (A and B) resulted in optimal separation in the final model, which included nine routinely collected clinical variables, namely heart rate, mean arterial pressure, respiratory rate, bilirubin, bicarbonate, creatinine, PaO2, arterial pH and FiO2. Participants in subphenotype B showed increased levels of proinflammatory markers, had consistently higher mortality, lower number of ventilator-free days at day 28 and longer duration of ventilation compared with patients in the subphenotype A. CONCLUSIONS: Routinely available clinical data can successfully identify two distinct subphenotypes in adult ARDS patients. This work may facilitate implementation of precision therapy in ARDS clinical trials.


Assuntos
Síndrome do Desconforto Respiratório , Adulto , Biomarcadores , Testes de Coagulação Sanguínea , Humanos , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Fatores de Tempo
3.
Shock ; 57(3): 384-391, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35081076

RESUMO

PURPOSE: Among patients with vasodilatory shock, gene expression scores may identify different immune states. We aimed to test whether such scores are robust in identifying patients' immune state and predicting response to hydrocortisone treatment in vasodilatory shock. MATERIALS AND METHODS: We selected genes to generate continuous scores to define previously established subclasses of sepsis. We used these scores to identify a patient's immune state. We evaluated the potential for these states to assess the differential effect of hydrocortisone in two randomized clinical trials of hydrocortisone versus placebo in vasodilatory shock. RESULTS: We initially identified genes associated with immune-adaptive, immune-innate, immune-coagulant functions. From these genes, 15 were most relevant to generate expression scores related to each of the functions. These scores were used to identify patients as immune-adaptive prevalent (IA-P) and immune-innate prevalent (IN-P). In IA-P patients, hydrocortisone therapy increased 28-day mortality in both trials (43.3% vs 14.7%, P = 0.028) and (57.1% vs 0.0%, P = 0.99). In IN-P patients, this effect was numerically reversed. CONCLUSIONS: Gene expression scores identified the immune state of vasodilatory shock patients, one of which (IA-P) identified those who may be harmed by hydrocortisone. Gene expression scores may help advance the field of personalized medicine.


Assuntos
Anti-Inflamatórios/uso terapêutico , Expressão Gênica/fisiologia , Hidrocortisona/uso terapêutico , Imunidade/genética , Choque/tratamento farmacológico , Choque/imunologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Estudos Retrospectivos , Choque/genética
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