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. 2023 Mar 17;14:1100461. doi: 10.3389/fimmu.2023.1100461

Table 6.

Overview of observational clinical studies evaluating complement role in ARDS/ALI.

Patients Participants Role of complement/References
ARDS 124 BALF levels of sCR1 were significantly increased in ARDS patients (281)
ARDS 36 BALF levels of C proteins were differentially expressed between survivors and non-survivors (282)
ARDS 26 Blood C activation was associated with ARDS pathological mechanism (283)
ARDS 15 Plasma C3a and C4a were helpful in predicting ADRS 16hrs post-injury (4)
ARDS 8 Elevated plasma C3a had better predictive value than WBC counts for ARDS during the first 24hrs (284)
ARDS 10 Plasma and BALF C3 and PFB activation and C5a were increased in ARDS patients (47)
RDS 53 Poor responders to surfactant had lower plasma C4 and C3c at admission and 24hrs after birth (285)
RDS 48 Poor responders to surfactant showed lower plasma C1q and C4 and higher plasma C3a and C5a 24hrs after birth (71)
RDS 35 There was no evidence of significant C activation in RDS (286)
ALI (allograft) 32/8 Pulmonary subendothelial C4d deposition was associated with HLA-Ab-induced ALI; elevated the plasma levels of C4d, Bb, iC3b, and C5b-9 after OKT3 administration in kidney and lung transplant recipients (287, 288)
Trauma-induced ARDS 208 Increased plasma C5b-9 was associated with ARDS development (94)
Trauma-induced ARDS 108 C activation was associated with ARDS development (5)
Trauma-induced ARDS 38 Increased plasma C3a was associated with ARDS development; C3a/C3 ratio discriminated ARDS and non-ARDS (53)
Trauma-induced ALI 54 Complement activation after traumatic injury, and complement activation is correlated with clinical outcomes in trauma patients (256)
Trauma/sepsis-induced ARDS 48 Plasma C3a was associated with ARDS development (289)
Trauma/sepsis-induced ARDS 26 Plasma C3a correlated with alveolar-capillary permeability (113)
Trauma/sepsis-induced ARDS N/A Plasma C1 inhibitor activity was significantly reduced in ARDS patients (290)
Sepsis-induced ARDS 87 Increased plasma C5b-9, C1rC1s-C1 inhibitor and C3bbP preceded ARDS development and resolution; plasma C5b-9 was more sensitive than C3a, C4a, C5a and CH50 (241, 291)
Sepsis-induced ARDS 48 Increased plasma C3a was useful for prognosis and diagnosis of sepsis and septic shock but not for ARDS (292)
Sepsis-induced ALI 40 Plasma C3a and C5a were increased in patients but did not predict the development of ALI (293)
H1N1-induced ARDS (H1N1) 97 Elevated baseline blood levels of MBL were associated with high mortality (NCT03641690)
COVID-19-induced ARDS 276 Complement consumption was associated with the severity of COVID-19 patients (165)
COVID-19-induced ARDS 100 Show an overexpression of C5a receptor in patients with ARDS secondary to COVID-19 compared to control patients (NCT04369820)
COVID-19-induced ARDS Increased plasma levels of C3a, C3c and C5b-9 were related to disease severity in COVID-19 patients (48)
COVID-19-induced ALI 19 Elevated plasma levels of C3a, C3d/g, C4d, and C5b-9 were associated lung damage in COVID-19 patients (190)
COVID-19-induced ARDS/ALI High expression levels of C3a, C3bc, C4bc, C5a and factor P were positively correlated with IL-8, CCL5, and the fatality rate in COVID-19 patients (294, 295)
COVID-19-induced ALI/ARDS Significant deposits of C4d, C5b-9 and MASP-2, and colocalization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa microvasculature in COVID-19 patients (57)
ECMO 2 Rapid activation of the complement alternative pathway by ECMO (296)

Ab, antibody; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; BALF, bronchoalveolar lavage fluid; CCL5, C-C motif chemokine ligand 5; ECMO, extracorporeal membrane oxygenation; HLA, human leukocyte antigen; MASP-2, mannan-biding lectin serine protease 2; PFB, properdin factor B; RDS, respiratory distress syndrome; sCR1, soluble complement receptor 1; WBC, white blood cell; N/A, not available.