Association Between Age and the 28-Day All-Cause Mortality in Tuberculosis Complicated by Sepsis in ICU Patients: A Retrospective Cohort Study

Figures & data

Figure 1 Flow chart of participants included in this analysis.

Table 1 Baseline Characteristics of the Study Participants by Age Quartiles

	Overall	Age(Years)				P-value	Statistic
		Q1 (18–48)	Q2 (49–63)	Q3 (64–72)	Q4 (73–80)
No.	520	129	128	130	133
Age	64.0 (49.0, 73.0)	37.0 (27.0, 44.0)	56.0 (53.0, 60.0)	68.0 (66.0, 70.0)	77.0 (75.0, 80.0)	< 0.001	486.952
Gender (Female)	120 (23.1)	52 (40.3)	19 (14.8)	24 (18.5)	25 (18.8)	< 0.001	29.402
Race						< 0.001	39.738
Han Chinese	419 (80.6)	80 (62)	106 (82.8)	114 (87.7)	119 (89.5)
Other^a	101 (19.4)	49 (38)	22 (17.2)	16 (12.3)	14 (10.5)
Smoking	291 (56.0)	48 (37.2)	87 (68)	83 (63.8)	73 (54.9)	< 0.001	29.236
Alcohol use	195 (37.5)	28 (21.7)	63 (49.2)	60 (46.2)	44 (33.1)	< 0.001	26.492
Immunosuppressive therapy^b	34 (6.5)	6 (4.7)	11 (8.6)	8 (6.2)	9 (6.8)	0.641	1.68
BMI	19.0 (18.3, 21.3)	19.3 (18.5, 23.0)	19.1 (18.3, 21.3)	19.0 (18.3, 20.1)	19.0 (18.2, 21.0)	0.222	4.391
Drug resistant tuberculosis	86 (16.5)	39 (30.2)	21 (16.4)	18 (13.8)	8 (6)	< 0.001	28.88
Severity of illness
APACHE II score	17.0 (13.0, 21.0)	15.0 (13.0, 20.0)	17.0 (12.0, 21.0)	17.0 (15.0, 21.0)	18.0 (16.0, 23.0)	< 0.001	23.18
SOFA score	4.0 (3.0, 6.0)	4.0 (3.0, 5.0)	4.0 (3.0, 6.0)	4.0 (3.0, 6.0)	4.0 (3.0, 6.0)	0.203	4.603
Main site of infection
Intra-abdominal infection	28 (5.4)	6 (4.7)	6 (4.7)	7 (5.4)	9 (6.8)	0.86	0.757
Urinary tract infection	2 (0.4)	0 (0)	1 (0.8)	0 (0)	1 (0.8)	0.745^d	Fisher
Main site of tuberculosis infection
Pulmonary tuberculosis	480 (92.3)	121 (93.8)	118 (92.2)	119 (91.5)	122 (91.7)	0.902	0.577
TBM	46 (8.8)	15 (11.6)	9 (7)	10 (7.7)	12 (9)	0.576	1.981
Intra-abdominal tuberculosis	59 (11.3)	15 (11.6)	16 (12.5)	15 (11.5)	13 (9.8)	0.916	0.511
Urinary system tuberculosis	11 (2.1)	4 (3.1)	4 (3.1)	1 (0.8)	2 (1.5)	0.46^d	Fisher
Tuberculosis in other parts of the body^c	28 (5.4)	8 (6.2)	9 (7)	6 (4.6)	5 (3.8)	0.639	1.691
Comorbidities
Hypertension	113 (21.7)	2 (1.6)	22 (17.2)	30 (23.1)	59 (44.4)	< 0.001	72.625
Diabetes	102 (19.6)	12 (9.3)	30 (23.4)	31 (23.8)	29 (21.8)	0.008	11.767
COPD	109 (21.0)	4 (3.1)	11 (8.6)	44 (33.8)	50 (37.6)	< 0.001	71.89
CKD	33 (6.3)	3 (2.3)	8 (6.2)	9 (6.9)	13 (9.8)	0.102	6.213
Chronic liver disease	29 (5.6)	5 (3.9)	15 (11.7)	7 (5.4)	2 (1.5)	0.003	14.077
SLE	7 (1.3)	3 (2.3)	1 (0.8)	0 (0)	3 (2.3)	0.297^d	Fisher
RA	12 (2.3)	0 (0)	3 (2.3)	5 (3.8)	4 (3)	0.154^d	Fisher
Pneumothorax	31 (6.0)	13 (10.1)	7 (5.5)	4 (3.1)	7 (5.3)	0.112	5.999
Vital signs
Temperature	36.8 (36.5, 37.5)	36.9 (36.6, 38.0)	36.7 (36.5, 37.6)	37.0 (36.6, 37.7)	36.8 (36.5, 37.1)	0.013	10.751
Heart rate	115.0 (100.0, 130.0)	126.0 (113.0, 140.0)	117.0 (97.8, 131.2)	112.5 (99.0, 125.8)	109.0 (98.0, 122.0)	< 0.001	41.877
Respiratory rate	32.0 (30.0, 35.0)	35.0 (31.0, 40.0)	32.0 (30.0, 35.0)	32.0 (30.0, 33.8)	32.0 (30.0, 34.0)	< 0.001	27.099
MAP	91.5 (78.0, 102.0)	88.0 (77.0, 101.0)	92.5 (78.8, 104.2)	95.0 (79.2, 104.0)	92.0 (77.0, 101.0)	0.250	4.11
Laboratory test indicators
WBC	8.4 (6.0, 11.7)	9.3 (6.7, 13.3)	7.9 (5.5, 11.7)	8.1 (6.2, 10.8)	8.0 (5.9, 11.4)	0.083	6.688
RBC	3.9 (3.3, 4.5)	4.0 (3.6, 4.7)	3.9 (3.2, 4.6)	3.8 (3.3, 4.4)	3.7 (3.1, 4.2)	0.003	14.095
HGB	108.0 (91.0, 125.0)	110.0 (92.0, 126.0)	109.0 (91.0, 131.0)	109.0 (92.0, 123.0)	101.0 (86.0, 123.0)	0.130	5.654
PLT	201.0 (124.5, 281.0)	235.0 (146.0, 314.0)	185.0 (105.0, 274.8)	193.5 (111.0, 271.5)	197.0 (126.0, 265.0)	0.025	9.308
PCT	0.5 (0.2, 1.5)	0.6 (0.2, 2.4)	0.5 (0.1, 1.4)	0.4 (0.1, 1.2)	0.4 (0.1, 1.3)	0.484	2.451
CRP	89.4 (51.0, 137.0)	83.7 (43.0, 124.9)	85.9 (51.0, 137.0)	96.1 (52.2, 144.2)	89.7 (53.9, 144.0)	0.425	2.79
Lactate	2.0 (1.5, 2.8)	2.1 (1.5, 2.9)	2.3 (1.5, 3.3)	1.9 (1.4, 2.6)	2.0 (1.6, 2.5)	0.121	5.812
Interventions
Invasive mechanical ventilation use	107 (20.6)	35 (27.1)	24 (18.8)	22 (16.9)	26 (19.5)	0.187	4.801
Vasopressor use	132 (25.4)	38 (29.5)	32 (25)	24 (18.5)	38 (28.6)	0.162	5.142
Outcome
28day los (Days)	19.5 (7.0, 28.0)	28.0 (9.0, 28.0)	22.0 (7.0, 28.0)	24.0 (8.0, 28.0)	12.0 (4.0, 28.0)	< 0.001	17.552
28-day mortality (Death)	241 (46.3)	52 (40.3)	53 (41.4)	51 (39.2)	85 (63.9)	< 0.001	22.292

Notes: Values are presented as median (interquartile range, IQR) for continuous variables of non-normal distribution and number (percentage) for categorical variables. ^aIncluding 98 Tibetans and 3 Yi ethnics; ^bTake immunosuppressants for more than 2 weeks before staying in ICU. ^CThere were 17 cases of bone tuberculosis, 6 cases of laryngeal tuberculosis, 3 cases of skin tuberculosis (1 case with bone tuberculosis) and 3 cases of genital tuberculosis; ^dFisher’s exact test.

Abbreviations: BMI, body mass index; APACHE, acute physiology and chronic health evaluation; SOFA, sequential organ failure assessment; TBM, tuberculous meningitis; COPD, obstructive pulmonary disease; CKD, chronic kidney disease; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; MAP, mean arterial pressure; WBC, white blood cell; RBC, red blood cell; HGB, hemoglobin; PLT, platelet; PCT, procalcitonin; CRP, C-reactive protein.

Figure 2 Kaplan-Meier survival curve for 28-day mortality of tuberculosis complicated by sepsis in different age groups.

Notes: Log rank X² = 26.43, df = 3, P < 0.001.

Table 2 Association Between Age and the 28-Day All-Cause Mortality in Tuberculosis Complicated by Sepsis ICU Patients

Exposure	Model I		Model II		Model III		Model IV		Model V
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Age(years)	1.016 (1.007~1.024)	<0.001	1.013 (1.003~1.023)	0.0093	1.012 (1.002~1.022)	0.0162	1.018 (1.008~1.028)	0.001	1.013 (1.003~1.023)	0.008
Age tertiles (years)
Q1 (18–48)	1(Ref)		1(Ref)		1(Ref)		1(Ref)		1(Ref)
Q2(49–63)	1.09 (0.74~1.6)	0.665	1.01 (0.67~1.5)	0.975	0.99 (0.66~1.48)	0.958	1.11 (0.74~1.67)	0.599	0.97 (0.64~1.46)	0.882
Q3 (64–72)	0.99 (0.67~1.46)	0.956	0.88 (0.58~1.34)	0.565	0.87 (0.57~1.33)	0.516	1.16 (0.75~1.8)	0.506	0.99 (0.64~1.55)	0.978
Q4(73–80)	2.02 (1.43~2.86)	<0.001	1.75 (1.18~2.6)	0.006	1.72 (1.15~2.59)	0.009	2.15 (1.43~3.24)	<0.001	1.83 (1.21~2.77)	0.004
P for trend	1.25 (1.11~1.41)	<0.001	1.2 (1.05~1.37)	0.006	1.2 (1.04~1.37)	0.011	1.31 (1.14~1.5)	<0.001	1.25 (1.09~1.43)	0.001

Notes: Model I = not adjusted for covariables; Model II = adjusted for gender + comorbidities (hypertension, diabetes, COPD, CKD, chronic liver disease, SLE, RA, and pneumothorax); Model III = adjusted for model II +drug resistant tuberculosis+Main site of infection(intral-abdominal infection, urinary tract infection) +main site of tuberculosis infection(Pulmonary tuberculosis, TBM, intra-abdominal tuberculosis, urinary system tuberculosis, and tuberculosis in other parts of the body); Model IV =adjusted for gender, BMI, hypertension, COPD, Heart rate, invasive mechanical ventilation use, and vasopressor use; Model V = adjusted for gender, immunosuppressive therapy, BMI, intra-abdominal infection, urinary tract infection, hypertension, diabetes, CKD, temperature, heart rate, MAP, HGB, PLT, lactate, invasive mechanical ventilation use, and vasopressor use.

Abbreviations: HR, hazard ratio; CI, confidence interval; HR, hazard ratio, Ref, reference.

Table 3 Threshold Effect Analysis of the Association of Age and the 28-Day All-Cause Mortality in Tuberculosis with Sepsis ICU Patients

Age (year)	No.	Adjusted Model
		HR(95% CI)	P-value
<66.2	307	0.996 (0.980, 1.012)	0.586
≥66.2	213	1.104 (1.05, 1.16)	< 0.001
Likelihood Ratio test			< 0.001

Notes: Adjusted for gender, immunosuppressive therapy, BMI, intra-abdominal infection, urinary tract infection, hypertension, diabetes, CKD, temperature, heart rate, MAP, HGB, PLT, lactate, invasive mechanical ventilation use, and vasopressor use. All the data are displayed.

Abbreviations: HR, hazard ratio, CI, confidence interval.

Figure 3 The nonlinear relationship of age and the risk of 28-day mortality fit by Cox proportional hazards regression models with multivariate-adjusted RCS analyses.

Notes: Solid and dashed lines represent the predicted value and 95% confidence intervals. It was adjusted for gender, immunosuppressive therapy, BMI, intra-abdominal infection, urinary tract infection, hypertension, diabetes, CKD, temperature, heart rate, MAP, HGB, PLT, lactate, invasive mechanical ventilation use, and vasopressor use. All of the data was displayed.

Figure 4 The relationship between age and the 28-day all-cause mortality in the subgroup analysis based on the tuberculosis complicated by sepsis ICU patients.

Notes: Each stratification was adjusted for gender, immunosuppressive therapy, BMI, intra-abdominal infection, urinary tract infection, hypertension, diabetes, CKD, temperature, heart rate, MAP, HGB, PLT, lactate, invasive mechanical ventilation use, and vasopressor use; Diamonds indicate odds ratios (ORs), with horizontal lines indicating 95%.

Abbreviations: HR, hazard ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease.

Figure 5 The nonlinear relationship of age and the risk of 28-day mortality fit by Cox proportional hazards regression models with unadjusted RCS analyses.

Notes: Solid and dashed lines represent the predicted value and 95% confidence intervals. It was adjusted for model I. All of the data was displayed.