High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD

Figures & data

Table 1 Baseline Characteristics of Patients Acutely Hospitalized with Prevalent COPD

	N (%) or Median (IQR)
Total N	4022
Men	1803 (44.8%)
Women	2219 (55.2%)
Age (years)	73.1 (63.7–81.1)
Comorbidities:
Hypertension^a	1009 (25.1%)
Cardiovascular disease	1010 (25.1%)
Myocardial infarction	165 (4.1%)
Stroke	224 (5.6%)
Dementia	162 (4.0%)
Peptic ulcer disease	101 (2.5%)
Liver disease (mild and moderate/severe)	113 (2.8%)
Diabetes (with and without complications)	538 (13.4%)
Type 2 diabetes	520 (12.9%)
Renal disease	148 (3.7%)
Cancer	448 (11.1%)
Lung cancer	149 (3.7%)
Other comorbidities^b	97 (2.4%)
Charlson score	1 (1–2)
History of acute exacerbations in past 2 years	785 (19.5%)
Length of hospital stay (days)	2.1 (0.6–6.7)
C-reactive protein (mg/L), n=3848	16.0 (4.0–65.0)
Blood eosinophil count (cells/μL), n=3849	100 (20–220)
suPAR (ng/mL)	3.9 (2.9–5.6)

Notes: ^aThe category “Hypertension” was defined as ICD-10 diagnoses I10-I15 and was not part of the Charlson score. ^bThe category “Other comorbidities” includes the Charlson groups connective tissue disease – rheumatic isease (n=72), hemiplegia and paraplegia (n=17), and AIDS/HIV (n=9).

Abbreviations: COPD, chronic obstructive pulmonary disease; IQR, interquartile range; suPAR, soluble urokinase plasminogen activator receptor.

Table 2 Causes of Index Admission and 365-Day Readmission in 4022 Patients with Prevalent COPD

	Index Admissions N (%)	First Readmission N (%)	Total Respiratory Readmissions N (%)
Total events	4022 (100)	2326	1268
Certain infections and parasitic diseases	191 (4.7)	132 (5.7)
Endocrine, nutritional and metabolic diseases	139 (3.5)	110 (4.7)
Circulatory diseases	441 (11.0)	252 (10.8)
Respiratory diseases	1982 (49.3)	938 (40.3)
Acute upper respiratory infections	17 (0.9)^a	2 (0.2)^a	5 (0.4)
Influenza or pneumonia	501 (25.3)^a	252 (26.9)^a	370 (29.2)
Other acute lower respiratory infections	21 (1.1)^a	4 (0.4)^a	7 (0.6)
Chronic lower respiratory diseases	941 (47.5)^a	432 (46.1)^a	554 (43.7)
Acute respiratory distress syndrome or pulmonary edema	6 (0.3)^a	4 (0.4)^a	4 (0.3)
Other interstitial pulmonary diseases	4 (0.2)^a	3 (0.3)^a	5 (0.4)
Pleural effusion	17 (0.9)^a	7 (0.7)^a	11 (0.9)
Pneumothorax	16 (0.8)^a	9 (1.0)^a	10 (0.8)
Respiratory failure	542 (27.3)^a	300 (32.0)^a	406 (32.0)
Diseases of the digestive system	108 (2.7)	121 (5.2)
Musculoskeletal and connective tissue disease	104 (2.6)	56 (2.4)
Diseases of the genitourinary system	119 (3.0)	94 (4.0)
Symptoms, signs, and abnormal findings	372 (9.2)	283 (12.2)
Factors influencing health status and contact with health services	416 (10.3)	208 (8.9)
Other causes of admission^b	338 (8.4)	316 (13.6)

Notes: ^aPercent of Respiratory disease (re)admissions. ^bCauses of admission are based on ICD-10 chapters. The category “Other causes of admission” includes the ICD-10 chapters: II “Neoplasms” and III “Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism” (n=89 for index admissions; n=79 for readmissions); V “Mental and behavioral disorders” (n=90 for index admissions; n=54 for readmissions); VI “Diseases of the nervous system” (n=35 for index admissions; n=37 for readmissions); VII “Diseases of the eye and adnexa” and VIII “Diseases of the ear and mastoid process” (n=8 for index admissions; n=3 for readmissions); XII “Diseases of the skin and subcutaneous tissue” (n=20 for index admissions; n=19 for readmissions); XV “Pregnancy, childbirth and the puerperium” (n=1 for index admissions; n=3 for readmissions); and XIX “Injury, poisoning and certain other consequences of external causes” (n=98 for index admissions; n=127 for readmissions). It should be noted that a patient can have more than one cause of admission/readmission, e.g., if a patient was transferred between wards during the admission.

Abbreviation: COPD – Chronic obstructive pulmonary disease.

Table 3 Rates of Readmission and Mortality Within 365 Days in 4022 Patients with COPD Following Hospitalization Stratified by suPAR Quartiles or Blood Eosinophil Counts

	No Event	Respiratory Readmission	All-Cause Readmission	All-Cause Mortality
	1275 (31.7%)	1268 (31.5%)	2326 (57.8%)	1051 (26.1%)
suPAR (ng/mL)	3.3 (2.6–4.4)	4.0 (2.9–5.5)*	4.1 (3.0–5.7)*	5.3 (3.8–7.1)*
First quartile (<2.9), n=980	437 (44.5%)	309 (31.5%)	511 (52.1%)	109 (11.1%)
Second quartile (2.9–3.8), n=1003	388 (38.7%)	286 (28.5%)	551 (54.9%)	175 (17.4%)
Third quartile (3.9–5.5), n=1014	268 (26.4%)	365 (36.0%)	643 (63.4%)	287 (28.3%)
Fourth quartile (≥5.6), n=1025	182 (17.8%)	308 (30.0%)*	621 (60.6%)*	480 (46.8%)*
Eosinophils (cells/μL)	120 (30–250)	100 (20–240)*	100 (30–230)*	50 (10–150)*
Low (<150), n=2366	678 (28.7%)	735 (31.1%)	1367 (57.8%)	746 (31.5%)
Intermediate (150–300), n=886	312 (35.2%)	266 (30.0%)	520 (58.7%)	169 (19.1%)
High (>300), n=597	222 (37.2%)	218 (36.5%)*	354 (59.3%)*	86 (14.4%)*

Notes: Values presented as percentages or median (IQR). Chi²-tests by increasing suPAR quartiles or blood eosinophil count groups, compared to patients without an event during the follow-up period. *p<0.05 in comparison to “No event”

Abbreviations: COPD, chronic obstructive pulmonary disease; IQR, interquartile range; suPAR, soluble urokinase plasminogen activator receptor.

Figure 1 Cumulative incidence plot of mortality (top) and readmission (bottom) within 365 days, stratified by quartiles of suPAR, for 4022 patients acutely admitted with chronic obstructive pulmonary disease.

Table 4 HRs for Readmission and Mortality Within 365 Days Following Hospitalization in Patients with COPD (n=4022), for Continuous suPAR (Log2-Transformed) or Stratified by suPAR Quartiles

	Respiratory Readmission		All-Cause Readmission		All-Cause Mortality
	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Unadjusted
Continuous suPAR	1.18 (1.10–1.28)	<0.0001	1.36 (1.29–1.44)	<0.0001	2.20 (2.04–2.37)	<0.0001
First suPAR quartile^b	1		1		1
Second suPAR quartile	0.93 (0.80–1.10)	0.41	1.13 (1.00–1.27)	0.054	1.64 (1.29–2.08)	<0.0001
Third suPAR quartile	1.30 (1.11–1.51)	0.0008	1.52 (1.35–1.71)	<0.0001	2.83 (2.27–3.52)	<0.0001
Fourth suPAR quartile	1.28 (1.10–1.50)	0.0019	1.74 (1.55–1.96)	<0.0001	5.49 (4.46–6.76)	<0.0001
Multivariable^a
Continuous suPAR	1.04 (0.95–1.14)	0.42	1.31 (1.22–1.39)	<0.0001	1.76 (1.62–1.92)	<0.0001
First suPAR quartile^b	1		1		1
Second suPAR quartile	0.86 (0.72–1.02)	0.09	1.10 (0.96–1.25)	0.17	1.49 (1.13–1.97)	0.0050
Third suPAR quartile	1.11 (0.93–1.32)	0.24	1.44 (1.27–1.64)	<0.0001	2.12 (1.63–2.75)	<0.0001
Fourth suPAR quartile	1.00 (0.83–1.20)	0.97	1.61 (1.40–1.85)	<0.0001	3.40 (2.64–4.39)	<0.0001

Notes: ^aAdjusted for age, sex, Charlson score, blood eosinophil count, and C-reactive protein. ^bCut-offs for the suPAR quartiles: Q1: <2.9 ng/mL (n=980, 24.4%), Q2: 2.9–3.8 ng/mL (n=1003, 24.9%), Q3: 3.9–5.5 ng/mL (n=1014, 25.2%), Q4: ≥5.6 ng/mL (n=1025, 25.5%).

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; suPAR, soluble urokinase plasminogen activator receptor.

Table 5 HRs for Readmission and Mortality Within 365 Days Following Hospitalization in Patients with COPD (n=3849), for Continuous Blood Eosinophil Count (Log2-Transformed) or Stratified by Low, Intermediate, and High Blood Eosinophil Count

	Respiratory Readmission		All-Cause Readmission		All-Cause Mortality
	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Unadjusted
Continuous	0.99 (0.96–1.03)	0.62	0.97 (0.94–0.99)	0.0071	0.83 (0.79–0.86)	<0.0001
Low^b	1		1		1
Intermediate	0.85 (0.74–0.98)	0.026	0.92 (0.83–1.02)	0.12	0.55 (0.46–0.65)	<0.0001
High	1.04 (0.89–1.21)	0.64	0.89 (0.79–1.00)	0.044	0.40 (0.32–0.50)	<0.0001
Multivariable^a
Continuous	1.01 (0.97–1.05)	0.56	0.97 (0.95–1.00)	0.051	0.85 (0.82–0.89)	<0.0001
Low^b	1		1		1
Intermediate	0.88 (0.76–1.02)	0.10	0.92 (0.83–1.02)	0.12	0.60 (0.50–0.71)	<0.0001
High	1.09 (0.93–1.27)	0.28	0.90 (0.80–1.02)	0.09	0.49 (0.39–0.62)	<0.0001

Notes: ^aAdjusted for age, sex, Charlson score, suPAR, and C-reactive protein. ^bCut-offs defined as Low (<150 cells/μL, n=2366), Intermediate (150–300 cells/μL, n=886), and High (>300 cells/μL, n=597).

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; suPAR, soluble urokinase plasminogen activator receptor.

Figure 2 Heatmap of 365-days all-cause readmission (A) and mortality (B) events in 3849 patients with chronic obstructive pulmonary disease acutely admitted to a hospital, stratified by suPAR and blood eosinophil count on admission. Colors in the figure represent the percentage of patients with an event and the numbers represent the total number of patients in strata. P-values represent Chi²-tests by suPAR quartile after stratification for blood eosinophil count, versus event-free patients.

Abbreviation: suPAR, soluble urokinase plasminogen activator receptor.