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. 2022 Sep;14(9):3552-3564.
doi: 10.21037/jtd-22-1122.

Intestinal barrier dysfunction is involved in the development of systemic inflammatory responses and lung injury in type A aortic dissection: a case-control study

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Intestinal barrier dysfunction is involved in the development of systemic inflammatory responses and lung injury in type A aortic dissection: a case-control study

Jianrong Li et al. J Thorac Dis. 2022 Sep.

Abstract

Background: The definite pathogenesis of lung injury complicated by type A aortic dissection (TAAD) remains unclear. In this paper, we investigated the relationship between intestinal injury, lung injury, and systemic inflammatory responses, with the aim of exploring the mechanism underlying intestinal injury and its impact on systemic inflammatory responses and lung injury in patients with TAAD.

Methods: Patients with TAAD (n=36) and those with aortic root aneurysm (ARA) (n=30) were compared. TAAD patients were younger and had higher creatinine (Cr) than ARA patients. White blood cell (WBC) count, neutrophil count, neutrophil percentage, interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), C-reactive protein (CRP), histamine (HIS) levels, PaO2-FiO2 ratio, diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), and peptidoglycan (PGN) were measured using the same laboratory methods between the two groups.

Results: Increased WBC [(9.70±4.05)×109/L vs. (5.88±1.2)×109/L, P<0.001], neutrophil [(7.65±4.27)×109/L vs. (3.40±0.97)×109/L, P<0.001], neutrophil percentage [(74.73±13.42)% vs. (57.67±9.45)%, P<0.001], IL-6 (37.48±4.87 vs. 20.90±0.92 pg/mL, P<0.001), IL-8 (97.15±9.11 vs. 69.46±3.17 pg/mL, P<0.001), TNF-α (71.32±10.35 vs. 33.90±2.27 pg/mL, P<0.001), CRP (10.67±1.62 vs. 4.43±0.26 µg/mL, P<0.001), HIS (13.29±1.88 vs. 7.63±0.58 ng/mL, P<0.001), DAO (24.94±4.72 vs. 10.92±2.44 U/L, P<0.001), iFABP (879.01±190.12 vs. 206.35±42.20 pg/mL, P<0.001), and PGN (31.10±5.51 vs. 12.52±2.20 ng/mL, P<0.001) and decreased PaO2-FiO2 ratio (365.35±146.47 vs. 447.86±70.80 mmHg, P=0.01) were detected in TAAD group relative to ARA group. In TAAD group, positive correlations were detected between DAO and inflammatory cytokines [IL-6 (r=0.56, P<0.001), IL-8 (r=0.61, P<0.001), TNF-α (r=0.71, P<0.001), and CRP (r=0.68, P<0.001)], between iFABP and inflammatory cytokines [IL-6 (r=0.72, P<0.001), IL-8 (r=0.71, P<0.001), TNF-α (r=0.90, P<0.001), and CRP (r=0.89, P<0.001)], between DAO and PGN (r=0.52, P<0.001), between iFABP and PGN (r=0.74, P<0.001), between PGN and inflammatory cytokines [IL-6 (r=0.85, P<0.001), IL-8 (r=0.44, P<0.001), TNF-α (r=0.61, P<0.001), and CRP (r=0.73, P<0.001)]. In acute TAAD subgroup, PGN and PaO2-FiO2 ratio were negatively correlated (r=-0.50, P=0.036).

Conclusions: Systemic inflammatory responses in TAAD patients may lead to lung and intestine injury, and the latter may be involved in the development of systemic inflammatory responses and lung injury in these patients.

Keywords: Type A aortic dissection (TAAD); bacteremia; intestinal injury; lung injury; systemic inflammatory response.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1122/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Comparison of systemic inflammatory response levels between TAAD and ARA. (A) WBC count; (B) Neutrophil count; (C) Neutrophil percentage; (D) IL-6; (E) IL-8; (F) TNF-α; (G) CRP, (H) HIS. (A-H) Two-tailed analysis of covariance, ***, P<0.001. TAAD, n=36; ARA, n=30. Star (★) indicates extremes, which are values more than 3 interquartile ranges from the end of a box. Circle (○) indicates outliers, which are values between 1.5 interquartile ranges and 3 interquartile ranges from the end of a box. WBC, white blood cell; TAAD, type A aortic dissection; ARA, aortic root aneurysm; IL, interleukin; TNF-α, tumor necrosis factor α; CRP, C-reactive protein; HIS, histamine.
Figure 2
Figure 2
Comparison of systemic inflammatory response levels between acute and non-acute TAAD. (A) WBC count; (B) neutrophil count; (C) neutrophil percentage. (A-C) Two-tailed analysis of covariance, ***, P<0.001. Acute TAAD, n=18; non-acute TAAD, n=18. Circle (○) indicates outliers, which are values between 1.5 interquartile ranges and 3 interquartile ranges from the end of a box. WBC, white blood cell; TAAD, type A aortic dissection.
Figure 3
Figure 3
Levels of lung injury, intestinal injury, and bacteremia. (A) Comparison of PaO2-FiO2 ratio between TAAD and ARA, two-tailed analysis of covariance, **, P=0.01. (B) Comparison of PaO2-FiO2 ratio between acute and non-acute TAAD; (C) comparison of DAO activity between TAAD and ARA; (D) comparison of iFABP between TAAD and ARA; (E) comparison of PGN between TAAD and ARA. (B-E) Two-tailed analysis of covariance, ***, P<0.001. TAAD, n=36; ARA, n=30. Acute TAAD, n=18; non-acute TAAD, n=18. Star (★) indicates extremes, which are values more than 3 interquartile ranges from the end of a box. Circle (○) indicates outliers, which are values between 1.5 interquartile ranges and 3 interquartile ranges from the end of a box. TAAD, type A aortic dissection; ARA, aortic root aneurysm; DAO, diamine oxidase; iFABP, intestinal fatty acid binding protein; PGN, peptidoglycan.
Figure 4
Figure 4
Correlations between systemic inflammatory responses and intestinal injury indicators in TAAD. (A) Relationship between IL-6 and DAO; (B) relationship between IL-8 and DAO; (C) relationship between TNF-α and DAO; (D) relationship between CRP and DAO; (E) relationship between IL-6 and iFABP; (F) relationship between IL-8 and iFABP; (G) relationship between TNF-α and iFABP; (H) relationship between CRP and iFABP. Pearson correlation. TAAD, n=36. IL, interleukin; TNF-α, tumor necrosis factor α; CRP, C-reactive protein; HIS, histamine; DAO, diamine oxidase; iFABP, intestinal fatty acid binding protein; TAAD, type A aortic dissection.
Figure 5
Figure 5
Correlation between intestinal injury and bacteremia in TAAD. (A) Relationship between PGN and DAO; (B) relationship between PGN and iFABP. Pearson correlation. TAAD, n=36. PGN, peptidoglycan; DAO, diamine oxidase; iFABP, intestinal fatty acid binding protein; TAAD, type A aortic dissection.
Figure 6
Figure 6
Correlation between bacteremia and systemic inflammatory responses in TAAD. (A) Relationship between IL-6 and PGN; (B) relationship between IL-8 and PGN; (C) relationship between TNF-α and PGN; (D) relationship between CRP and PGN. Pearson correlation. TAAD, n=36. IL, interleukin; TNF-α, tumor necrosis factor α; CRP, C-reactive protein; PGN, peptidoglycan; TAAD, type A aortic dissection.
Figure 7
Figure 7
Correlation between bacteremia and lung injury in acute TAAD. Relationship between PaO2-FiO2 ratio and PGN. Pearson correlation. Acute TAAD, n=18. PGN, peptidoglycan; TAAD, type A aortic dissection.

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