Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Jun 27:15:3709-3718.
doi: 10.2147/JIR.S369703. eCollection 2022.

Anti-Inflammatory Effect of Ulinastatin on the Association Between Inflammatory Phenotypes in Acute Type A Aortic Dissection

Hong Liu #  1 , Si-Chong Qian #  2 , Yong-Feng Shao  1 , Hai-Yang Li  2 ; Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) Investigators Group
Affiliations
Clinical Trial

Anti-Inflammatory Effect of Ulinastatin on the Association Between Inflammatory Phenotypes in Acute Type A Aortic Dissection

Hong Liu et al. J Inflamm Res. .

Abstract

Background: Acute type A aortic dissection (ATAAD) is a heterogeneous systemic inflammatory response syndrome. Identification of distinct inflammatory phenotypes may allow more precise therapy and improved care. We aim to investigate whether distinct inflammatory subphenotypes exist in ATAAD patients and respond differently to pharmacotherapies.

Methods: Retrospective analysis of data sets was conducted from the Additive Anti-inflammatory Actions for Aortopathy & Arteriopathy (5A) III study. Inflammatory subphenotypes were derived among 2008 ATAAD patients who received surgical repair at 11 Chinese hospitals (2016-2020) using latent class analysis applied to 14 laboratory signatures within 6 hours of hospital admission. Outcomes included operative mortality (Society of Thoracic Surgeons definition), derived subphenotype frequency, and the potential consequences of phenotype frequency distributions on the treatment effects.

Results: The median (interquartile range) age of patients was 54 (45-62) years, and 1423 (70.9%) were male. A two-class (two subphenotype) model was an improvement over a one-class model (P<·001), with 1451 (72.3%) patients in the hypoinflammatory subphenotype group and 557 (27.7%) in the hyperinflammatory subphenotype group. Patients with the hyperinflammatory subphenotype had higher operative mortality (71 [12.7%] vs 127 [8.8%]; P=0·007) than did those with the hypoinflammatory subphenotype. Furthermore, the interaction between ulinastatin treatment and subphenotype is not significant for operative mortality (P=0.15) but for ventilator time (P=0·04).

Conclusion: Two subphenotypes of ATAAD were identified in the 5A cohort that correlated with clinical outcomes, with significant interaction effect between anti-inflammatory treatment and subphenotypes for ventilator time, suggesting these phenotypes may help in understanding heterogeneity of treatment effects.

Trial registration: Clinical Trials. Gov: number NCT04918108.

Keywords: aortic dissection; inflammatory response; latent class analysis.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in relation to this work.

Figures

Figure 1
Figure 1
Patient selection flow chart.
Figure 2
Figure 2
Differences in standardised values of each continuous variable by subphenotype. Variables are sorted on the basis of the degree of separation between the subphenotypes, from maximum positive separation on the left (ie, hyperinflammatory subphenotype higher than hypoinflammatory subphenotype) to maximum negative separation on the right (ie, hyperinflammatory subphenotype lower than hypoinflammatory subphenotype). The y-axis represents standardised variable values, in which all means are scaled to 0 and SDs to 1. A value of +1 for the standardised variable signifies that the mean value for a given subphenotype was 1 SD higher than the mean value in the cohort as a whole. Mean values are joined by lines to facilitate display of subphenotype profiles.
Figure 3
Figure 3
Kaplan-Meier survival curves. 90-day patient survival in stratified by acute type A aortic dissection inflammatory subphenotype.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Allaire E, Schneider F, Saucy F, et al. New insight in aetiopathogenesis of aortic diseases. Eur J Vasc Endovasc Surg. 2009;37(5):531–537. doi:10.1016/j.ejvs.2009.02.002 - DOI - PubMed
    1. Depner M, Fuchs O, Genuneit J, et al.; PASTURE Study Group. Clinical and epidemiologic phenotypes of childhood asthma. Am J Respir Crit Care Med. 2014;189(2):129–138. doi:10.1164/rccm.201307-1198OC - DOI - PubMed
    1. Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2(8):611–620. doi:10.1016/S2213-2600(14)70097-9 - DOI - PMC - PubMed
    1. Seymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321(20):2003–2017. doi:10.1001/jama.2019.5791 - DOI - PMC - PubMed
    1. Takano H, Inoue K, Shimada A, Sato H, Yanagisawa R, Yoshikawa T. Urinary trypsin inhibitor protects against liver injury and coagulation pathway dysregulation induced by lipopolysaccharide/D-galactosamine in mice. Lab Invest. 2009;89(7):833–839. doi:10.1038/labinvest.2009.35 - DOI - PubMed

Associated data