In this study, data was collected from 79 patients with sepsis, as shown in Table 1, featuring the following characteristics: the patients' average age was 68.0 ± 14.2 years, with a male proportion of 69.6%. The BMI of all participants was 23.3 ± 4.4 kg/m². Among these patients, 51.9% had hypertension, 36.7% had diabetes mellitus, 15.2% had coronary heart disease, and 36.7% had chronic kidney disease. Platelet count was 192.5 ± 129.2*10^9/L, and White blood cell count was 14.5 ± 8.4 * 10^9/L. Albumin level was 30.3(28.2–34.5) g/L, bilirubin level was 10.9(6.6–18.5) umol/L, and creatinine level was 119.0(61.5-189.5) umol/L. The cytokine levels were as follows: IL-2 was 1.4(1.0-2.5) pg/ml, IL-4 was 1.6(0.8–2.7) pg/ml, IL-5 was 0.8(0.4–1.9) pg/ml, IL-6 was 116.1(27.6-387.1) pg/ml, IL-8 was 172.3(73.0-365.3)pg/ml, IL-1β was 2.0(1.3–3.2) pg/ml, IL-17A was 16.0(6.0-27.4) pg/ml, IL-10 was 13.1(6.7–36.9) pg/ml, IFN-γ was 1.8 (1.1–3.1)pg/ml, TNF-α was 2.8(1.9–5.1) pg/ml, IL-12p70 was 2.4 (1.4–3.3)pg/ml, and IFN-α was 3.0 (2.2–4.6)pg/ml.
Table 1
Demographic characteristics and biochemical values of the subjects.
Variables | All |
Number | 79 |
Age(years), Mean ± SD | 68.0 ± 14.2 |
Sex(male), n (%) | 55 (69.6) |
BMI(Kg/m2), Mean ± SD | 23.3 ± 4.4 |
Hypertension, n (%) | 41 (51.9) |
Diabetes mellitus, n (%) | 29 (36.7) |
Coronary heart disease, n (%) | 12 (15.2) |
Chronic kidney disease, n (%) | 29 (36.7) |
Platelet(10^9/L), Mean ± SD | 192.5 ± 129.2 |
White blood cell(10^9/L), Mean ± SD | 14.5 ± 8.4 |
Albumin(g/L), Median (IQR) | 30.3 (28.2, 34.5) |
Bilirubin(umol/L), Median (IQR) | 10.9 (6.6, 18.5) |
Creatinine(umol/L), Median (IQR) | 119.0 (61.5, 189.5) |
IL-2(pg/ml), Median (IQR) | 1.4 (1.0, 2.5) |
IL-4(pg/ml), Median (IQR) | 1.6 (0.8, 2.7) |
IL-5(pg/ml), Median (IQR) | 0.8 (0.4, 1.9) |
IL-6(pg/ml), Median (IQR) | 116.1 (27.6, 387.1) |
IL-8(pg/ml), Median (IQR) | 172.3 (73.0, 365.3) |
IL-1β(pg/ml), Median (IQR) | 2.0 (1.3, 3.2) |
IL-17A(pg/ml), Median (IQR) | 16.0 (6.0, 27.4) |
IL-10(pg/ml), Median (IQR) | 13.1 (6.7, 36.9) |
IFN-γ(pg/ml), Median (IQR) | 1.8 (1.1, 3.1) |
TNF-α(pg/ml), Median (IQR) | 2.8 (1.9, 5.1) |
IL-12p70 (pg/ml), Median (IQR) | 2.4 (1.4, 3.3) |
IFN-α(pg/ml), Median (IQR) | 3.0 (2.2, 4.6) |
We examined the relationship between each index in Table 1 and the number of pathogenic microorganisms measured by mNGS in bronchoalveolar lavage fluid using univariate analysis. Among them, the platelet count was negatively correlated with the number of pathogenic microorganisms (β: -0.002,95%CI: -0.004~-0.001,P = 0.003), meaning that as the platelet count increased, the number of pathogenic microorganisms decreased. The cytokine IL-6 was significantly positively correlated with the number of pathogenic microorganisms (β:0.001,95%CI:0 ~ 0.001,P<0.001), indicating that as the level of IL-6 increased, the number of pathogenic microorganisms also increased. The cytokine IL-10 was also significantly positively correlated with the number of pathogenic microorganisms (β:0.018,95%CI:0.014 ~ 0.021,P = 0.018), meaning that as the level of IL-10 increased, the number of pathogenic microorganisms also increased. These results suggest that in sepsis, an increase in levels of IL-6 and IL-10 may be associated with an increased burden of pulmonary pathogenic microorganisms.
For other variables such as gender, age, BMI, hypertension, diabetes, coronary heart disease, chronic kidney disease, white blood cell count, serum albumin, total bilirubin, serum creatinine, and other cytokines (IL-2, IL-4, IL-5, IL-8, IL-1β, IL-17A, IFN-γ, TNF-α, IL-12p70, IFN-α), the relationship with the number of pathogenic microorganisms did not reach statistical significance. Detailed results are shown in Table 2.
Table 2
Correlations between Pathogenic Microbial Load and variables.
Variables | β | 95%CI | P value |
Male,n (%) | -0.400 | (-0.839,0.039) | 0.0736 |
Age, years | 0.007 | (-0.008,0.022) | 0.3494 |
BMI, Kg/m2 | -0.021 | (-0.068,0.026) | 0.3838 |
Hypertension,n (%) | -0.123 | (-0.538,0.292) | 0.5576 |
Diabetes mellitus,n (%) | 0.280 | (-0.144,0.704) | 0.1929 |
Coronary heart disease,n (%) | 0.053 | (-0.51,0.616) | 0.8523 |
Chronic kidney disease,n (%) | 0.161 | (-0.27,0.592) | 0.4592 |
White blood cell | 0.013 | (-0.011,0.038) | 0.2859 |
Platelet,10^9/L | -0.002 | (-0.004,-0.001) | 0.003 |
Albumin,g/L | -0.012 | (-0.056,0.032) | 0.5989 |
Bilirubin,umol/L | 0 | (-0.005,0.004) | 0.8414 |
Creatinine,umol/L | 0.002 | (0,0.003) | 0.0535 |
IL-2,pg/ml | 0.009 | (-0.032,0.049) | 0.6781 |
IL-4 ,pg/ml | -0.007 | (-0.063,0.048) | 0.79 |
IL-5 ,pg/ml | 0.002 | (-0.027,0.031) | 0.8934 |
IL-6 ,pg/ml | 0.001 | (0,0.001) | < 0.001 |
IL-8 ,pg/ml | 0 | (0,0) | 0.871 |
IL-1β,pg/ml | -0.004 | (-0.031,0.023) | 0.7614 |
IL-17A ,pg/ml | 0.008 | (-0.002,0.018) | 0.1107 |
IL-10 ,pg/ml | 0.018 | (0.014,0.021) | < 0.001 |
IFN-γ,pg/ml | -0.005 | (-0.023,0.014) | 0.6151 |
TNF-α,pg/ml | -0.007 | (-0.024,0.011) | 0.431 |
IL-12p70 ,pg/ml | 0.031 | (-0.016,0.078) | 0.1908 |
IFN-α,pg/ml | 0.004 | (-0.005,0.013) | 0.404 |
We used polynomial regression to analyze the relationship between IL-10 and the number of pathogenic microorganisms measured by mNGS in bronchoalveolar lavage fluid.The analysis showed a significant positive correlation between IL-10 and the number of pathogenic microorganisms in bronchoalveolar lavage fluid, as visually demonstrated in the curve fitting chart ,as shown in Fig. 1. To further explore this relationship, we conducted a multivariate linear regression analysis, as shown in Table 3. In Model 1, without adjusting for any variables, the value for IL-10 was (β:0.02,95%CI:0.01 ~ 0.02,P<0.001). In Model 2, we adjusted for age, gender, and BMI, and the value for IL-10 was (β:0.02,95%CI:0.01 ~ 0.02,P<0.001). In Model 3, we adjusted for age, gender, BMI, comorbidities, white blood cells, platelets, albumin, bilirubin, creatinine,IL-6, and the value for IL-10 was (β:0.01,95%CI:0.01 ~ 0.02,P<0.001). After conducting a multivariate linear regression analysis for the significant univariate factors, platelets and IL-6, the P value was no longer significant. These results indicate that, after adjusting for patient age, gender, BMI, and all other potential confounding factors, there is still a significant positive correlation between IL-10 and the number of pathogenic microorganisms in bronchoalveolar lavage fluid. This further supports our hypothesis that in patients with sepsis, an increase in IL-10 levels may be associated with an increase in the burden of pulmonary pathogenic microorganisms.
Table 3
The independent correlation between IL-10 and Pathogenic Microbial Load by multivariate linear regression.
Variables | Model 1 | Model 2 | Model 3 |
| β(95%CI) | P value | β(95%CI) | P value | β(95%CI) | P value |
IL-10 | 0.02 (0.01 ~ 0.02) | < 0.001 | 0.02 (0.01 ~ 0.02) | < 0.001 | 0.01 (0.01 ~ 0.02) | < 0.001 |
Model 1: Unadjusted.
Model 2: Adjusted for age, gender, and BMI.
Model 3: Adjusted for age, gender, BMI, comorbidities, white blood cells, platelets, albumin, bilirubin, creatinine, and IL-6.
To further understand the relationship between the number of pathogenic microbial load in bronchoalveolar lavage fluid and the survival status of patients with sepsis, we grouped the patients according to the level of pathogenic microbial load and conducted a Kaplan-Meier survival curve analysis, as shown in Fig. 2. The results revealed that when the pathogenic microbial load reached or exceeded three, the 28-day mortality rate of the patients significantly increased, indicating that the level of pathogenic microbial load might be related to the short-term survival status of patients with sepsis. This finding suggests that for those patients with sepsis who have higher levels of IL-10 and a larger burden of pathogenic microorganisms, greater emphasis needs to be placed on clinical management, with interventions made as early as possible to reduce the risk of death.