Latent Class Analysis-Derived Hypoinflammatory and Hyperinflammatory Phenotypes Are Generalisable to Sepsis Patients Requiring Intensive Care

Sinha, Parul; He, Junnan; Delucchi, K.; Zhuo, H.; Abbott, J.; Jones, C.; Wickersham, Nancy; Neyton, L.; McNeil, Barbara J.; Desco, A.L.; Alejandra, J.; Gómez, Antonio; Hendrickson, Carolyn M.; Kangelaris, K.N.; Sarma, Aartik; Leligdowicz, A.; Matthay, M.A.; Liu, K.; Ware, L.B.; Calfee, C.S.

doi:10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3431

Cited by 2 publications

(4 citation statements)

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“…This study has several strengths. First unlike some prior studies [11], phenotypes were assigned by LCA, a robust method [16] with consistent and well-replicated findings [2,5,[25][26][27]. Moreover, sensitivity analysis provided similar results, even when using another approach (propensity scoring) to estimate attributable mortality.…”

Section: Discussionmentioning

confidence: 72%

“…With recent data suggesting that hypoinflammatory and hyperinflammatory phenotypes are generalizable to sepsis [5,6], we chose to study the AF ARDS and PAF ARDS within each sepsis phenotype. This approach considers ARDS as a complication of each phenotype of sepsis, rather than considering each phenotype of ARDS as a complication of overall sepsis or more broadly of critical illness.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the hypoinflammatory phenotype, representing approximately two-thirds of ARDS cases, is associated with lower levels of inflammatory biomarkers and reduced mortality rates [2][3][4]. These phenotypes have also been identified in sepsis, with similar characteristics, prognosis and differential response to activated protein C, suggesting this schema captures phenotypes of critical illness overall and not only ARDS [5,6].…”

Section: Introductionmentioning

confidence: 98%

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Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis

Evrard,

Sinha,

Delucchi

et al. 2024

Crit Care

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Background Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype. Methods We studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. Results The PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004). Conclusions The PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis

Evrard,

Sinha,

Delucchi

et al. 2024

Crit Care

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“…Identification of endotypes has implications for personalized treatment, risk stratification, and our understanding of pathophysiology. This approach has been used by our group to identify two ARDS and sepsis phenotypes using clinical and biological data (3, 4).…”

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confidence: 99%

Advancing Sepsis Endotyping Globally: Lessons From a Prospective Study in Uganda*

Neyton,

Spottiswoode

2024

Critical Care Medicine

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Latent Class Analysis-Derived Hypoinflammatory and Hyperinflammatory Phenotypes Are Generalisable to Sepsis Patients Requiring Intensive Care

Cited by 2 publications

References 0 publications

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis

Advancing Sepsis Endotyping Globally: Lessons From a Prospective Study in Uganda*

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