Hereditary angioedema has been attributed to an inherited deficiency of C1 esterase inhibitor that increases vascular permeability. The role of C1 esterase inhibitor in burn patients has not been described previously. In this study, we attempted to identify the relationship between serial changes of C1 esterase inhibitor activity and the clinical course in major burn patients. This study was a single-center, prospective, observational study. C1 esterase inhibitor activity values were serially examined in major burn patients admitted into the burn center from April 2014 to December 2016. Inclusion criteria were age ≥16 years old and %TBSA burned ≥20%. This study included 38 patients with major burn. C1 esterase inhibitor activity after burn dropped acutely on days 1 and 2 but increased immediately until days 3 to 5, after which it continued to gradually increase to above the reference value. C1 esterase inhibitor activity on admission showed significant inverse correlation with the volume of infusion per body weight required in the first 24 hours after injury and %TBSA burned (r = -0.405, P = 0.01; r = -0.375, P = 0.02, respectively). C1 esterase inhibitor activity on admission was significantly lower in the nonsurvivors than in the survivors during the 28-day evaluation period (59% vs 90%, P = 0.01). These findings suggest that C1 esterase inhibitor may play a critical role in regulating vascular permeability in the acute phase following the burn injury.
These findings suggest that C1 esterase inhibitor may play a critical role in regulating vascular permeability in the acute phase following the burn injury.
vascular permeability was not directly measured in this observational cohort
C1 esterase inhibitor activity after burn dropped acutely on days 1 and 2 but increased immediately until days 3 to 5.
serial measurements directly show the reported early decline and recovery
C1 esterase inhibitor activity on admission showed significant inverse correlation with the volume of infusion per body weight required in the first 24 hours after injury and %TBSA burned.
unadjusted correlations support direction but cannot separate burn severity from related clinical factors
C1 esterase inhibitor activity on admission was significantly lower in the non-survivors than in the survivors during the 28-day evaluation period.
severe prognostic confounding and a potentially inappropriate group test undermine the significance claim
Derived from the full evaluation — not a separate score.
Strengths
Serial measurements show reduced C1 esterase inhibitor activity on days 1 and 2, recovery by days 3–5, and elevation after one week. This adds a detailed temporal profile to the limited prior burn literature.
↳ Results, p. 12; Figure 2
The cohort was enrolled prospectively, treated under a unified resuscitation protocol, and sampled at prespecified intervals using named commercial assays.
↳ Methods, pp. 7–10
The discussion connects the clinical observations to prior burn studies, sepsis research, hereditary angioedema biology, and animal thermal-injury experiments.
↳ Introduction, pp. 5–6; Discussion, pp. 15–20
Limitations
The Methods and Figure 4 legend report a Wilcoxon signed-rank test for survivors versus non-survivors. Because these are independent groups, the reported significance of this central comparison may be invalid.
↳ Methods, Statistical analysis, p. 11; Figure 4 legend, p. 32
Non-survivors were substantially older and had higher APACHE II and SOFA scores and more full-thickness burn area. No adjusted analysis separates C1 inhibitor activity from these prognostic differences.
↳ Table 2, p. 30; Results, p. 14
The study did not directly measure vascular permeability or test C1 inhibitor replacement, yet the abstract and conclusion assign the inhibitor an important regulatory role. The therapeutic proposal therefore remains hypothesis-generating.
↳ Abstract, pp. 3–4; Discussion, pp. 18–20; Conclusions, p. 20
The prospective serial measurements support the reported early fall and later recovery of C1 esterase inhibitor activity. Confidence in the survival comparison is substantially lower because Table 2 shows large age and severity imbalances, while the Methods and Figure 4 legend specify a paired test for independent groups. The correlations with burn size and fluid volume are informative descriptively but remain unadjusted. The discussion provides a coherent biological and translational rationale, although direct claims about permeability regulation and replacement therapy extend beyond what was measured.
Nabu’s assessment, alongside the field’s view.
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Limited2.8
Confidence mediumThe study adds prospective serial data on C1 esterase inhibitor activity after major burns and relates admission activity to burn size, resuscitation volume, and survival. The advance is genuine but incremental because it comes from 38 patients at one centre.
“There are a few studies of C1 esterase inhibitors in major burns”
Prospective sampling, a unified resuscitation protocol, and commercial assays support the descriptive analysis. The mortality comparison is unadjusted for large age and severity differences, and the reported signed-rank test may be inappropriate for independent groups.
“The Wilcoxon signed-rank test was used to assess differences”
The manuscript has a traceable structure connecting the protocol, serial results, and interpretation. Its headline permeability interpretation is stronger than warranted by unadjusted associations without direct measurement of vascular permeability.
“may play a critical role in regulating vascular permeability”
The discussion connects the results to burn physiology, hereditary angioedema, sepsis studies, and animal thermal-injury models. Its limitations section omits the age-and-severity confounding visible in the survivor comparison.
“This study has some limitations.”
Concerns4 of 4 checks
The statistical test reported for the independent survivor and non-survivor groups is a paired-sample test, so the central mortality-group P value may be invalid. A minor abstract-to-table P-value discrepancy does not alter the direction or nominal significance of the result.
Institutional approvals and written informed consent are declared, and the funding source is disclosed. No text-grounded research-conduct concern was identified.
Flags: 2 declared / 5 total
40 of 40 checkable references verified
41 references in manuscript 1 have no canonical index record — counted, but not index-checkable 1 reference confirmed by manual review
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No retraction or expression of concern found in Crossref (includes Retraction Watch).
Sources: Crossref (incl. Retraction Watch) ✓
Where this paper’s evidence sits on the path from initial observation to real-world use.
The study characterises a biomarker trajectory in patients but tests neither C1 inhibitor treatment nor a prognostic decision rule. Readiness therefore remains at an early observational stage.
“intravenous infusion of C1 esterase inhibitor could have benefit”
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