Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease

Figures & data

Table 1. Demographics and clinical characteristics of all patients with ulcerative colitis and Crohn’s disease, stratified by relapse during the study period.

Ulcerative colitis	All	Relapse	Remission
n	55	21	34
Age (years; median (min–max))	59 (19-83)	57 (42–65)	59 (51–65)
Males/Females	26/29	8/13	18/16
Disease duration (years; median ( P25–P75))	16 (7–27)	12 (5.8–16)	21 (11–30)
Baseline ECP (µg/g; median (P25–P75))	2.5 (0.9–8.8)	2.1 (1.0–9.3)	2.6 (0.9–8.7)
Baseline EDN (µg/g; median (P25–P75))	1.2 (0.6–4.5)	2.4 (1.0–5.6)	1.0 (0.3–3.2)
Extent
E1 (Proctitis)	6 (11%)	2 (10%)	4 (12%)
E2 (Left-sided)	25 (45%)	9 (43%)	16 (47%)
E3 (Extensive)	24 (44%)	10 (48%)	14 (41%)
Treatments at inclusion
None	6 (11%)	1 (5%)	5 (15%)
Topical corticosteroids and/or 5-ASA	4 (7%)	2 (10%)	2 (6%)
Oral 5-ASA or sulfasalazine	32 (58%)	8 (38%)	22(65%)
Oral corticosteroids	7 (13%)	5 (24%)	2 (6%)
Immunomodulators	19 (35%)	7 (33%)	12 (35%)
Anti-TNF therapy	2 (4%)	0	2 (6%)
Crohn's disease
n	49	16	33
Age (years; median (min-max))	57 (21–79)	51 (44–62)	58 (42–65)
Sex (males/females)	24/25	7/9	17/16
Disease Duration (years; median ( P25–P75))	21 (13–30)	19 (11–23)	25 (14–38)
Previous resection	29 (59%)	7 (44%)	22 (67%)
Baseline ECP (µg/g; median ( P25–P75))	3.4 (1.5– 8.2)	5.7 (1.9–11.5)	2.9 (1.4–7.7)
Baseline EDN (µg/g; median ( P25–P75))	3.4 (0.7–5.8)	2.9 (0.6–5.1)	3.6 (0.9–5.8)
Location
L1 (Ileal)	13 (27%)	4 (25%)	9 (27%)
L2 (Colonic)	15 (31%)	7 (44%)	8 (24%)
L3 (Ileocolonic)	21 (43%)	5 (31%)	16 (48%)
Behaviour
B1 (Non-stricturing/non-penetrating)	18 (37%)	8 (50%)	10 (30%)
B2 (Stricturing)	18 (37%)	4 (25%)	14 (42%)
B3 (Penetrating)	13 (27%)	4 (25%)	9 (27%)
P (Perianal Disease)	8 (16%)	1 (6%)	7 (21%)
Treatments at inclusion
None	14 (29%)	3 (19%)	11 (33%)
Topical corticosteroids and/or 5-ASA	2 (4%)	0	2 (6%)
Oral 5-ASA or sulfasalazine	15 (31%)	5 (31%)	10 (30%)
Oral corticosteroids	7 (14%)	4 (25%)	3 (9%)
Immunomodulators	24 (49%)	8 (50%)	16 (48%)
Anti-TNF therapy	2 (4%)	1 (6%)	1 (3%)

Figure 1. Serial faecal EDN- and ECP measurements (µg/g) in patients with ulcerative colitis: time 0 refers to the time of relapse or end of study period. Data is shown as bars corresponding to interquartile range (IQR), separate for patients who experienced a relapse (black) and patients who remained in sustained remission (grey). Median values are marked with a black horizontal line. *p < .05 for comparison.

Table 2. Median (IQR) concentrations for ulcerative colitis patients in relapse vs. remission. Results are presented for time 0 (relapse/end of study) and -3 (three months prior). The difference between concentrations in relapse vs. remission groups was only significant for EDN.

Ulcerative colitis
Group	Time	Median (IQR) µg/g	p-value
EDN
Relapse	0	3.37 (1.04–8.41)	<.001
Remission	0	0.83 (0.26–1.91)
Relapse	−3	2.47 (1.7–7.11)	.005
Remission	−3	0.62 (0.33–2.67)
ECP
Relapse	0	4.53 (1.30–11.43)	.11
Remission	0	2.60 (1.02–5.16)
Relapse	−3	5.34 (1.3–12.61)	.34
Remission	−3	2.74 (0.89–5.84)

EDN: eosinophil-derived neurotoxin; ECP: eosinophil cationic protein.

Table 3. Information from extended Cox regression on predictors of clinical relapse in patients with ulcerative colitis analysed by Model A, including time-variant faecal EDN, age, and sex; and Model B, including time-variant faecal EDN, age, sex, and treatment factors as a sensitivity analysis.

Ulcerative colitis
Predictors	HR	95% CI	p-value
Model A
EDN (log2)	1.31	1.09–1.58	.004
Age	0.99	0.96–1.02	.604
Sex	0.48	0.19–1.25	.133
Model B
EDN (log2)	1.32	1.10–1.59	.003
Age	1.00	0.96–1.03	.850
Sex	0.59	0.22–1.56	.284
Oral 5ASA	0.77	0.26–2.22	.623
Oral sulfasalazine	0.38	0.08–1.90	.240
Topical 5ASA	1.42	0.18–11.43	.743
Immunomodulator	0.74	0.24–2.32	.605

EDN: eosinophil-derived neurotoxin; ECP: eosinophil cationic protein; 5ASA: 5-aminosalicylate.

Figure 2. Serial faecal EDN-measurements and ECP-measurements (µg/g) in patients with Crohn’s disease: time 0 refers to the time of relapse or end of study period. Data is shown as bars corresponding to interquartile range (IQR), separate for patients who experienced a relapse (black) and patients who remained in sustained remission (grey). Median values are marked with a black horizontal line.

Table 4. Median (IQR) concentrations of EDN and ECP in Crohn's disease: relapse versus remission. Results are presented at time 0 (relapse/end of study) and -3 (three months prior).

Crohn's disease
Group	Time	Median (IQR) µg/g	p-value
EDN
Relapse	0	2.26 (0.73–4.58)	.31
Remission	0	4.40 (1.49–6.82)
Relapse	−3	1.35 (0.45–3.73)	.08
Remission	−3	4.56 (1.49–7.66)
ECP
Relapse	0	4.18 (2.23–10.5)	.27
Remission	0	2.56 (1.26–7.72)
Relapse	−3	7.10 (1.38–13.7)	.15
Remission	−3	2.57 (1.26–6.12)

EDN: eosinophil-derived neurotoxin; ECP: eosinophil cationic protein.

Table 5. Spearman’s rank correlation coefficients (r_s) for ECP, EDN and faecal calprotectin (FC). Results for all patients in the disease groups, and stratified by relapse during the study period. All results were significant (p < .001) except those marked with ‘†’.

	rs: All	rs: Relapse	rs: Remission
Ulcerative colitis
FC vs. ECP	0.71	0.72	0.71
FC vs. EDN	0.57	0.65	0.50
ECP vs. EDN	0.58	0.68	0.57
Crohn's disease
FC vs. ECP	0.74	0.79	0.73
FC vs. EDN	0.47	0.06†	0.72
ECP vs. EDN	0.64	0.13†	0.85

^† not significant, p > .05.

r_s Spearman’s rank correlation coefficient.

FC: faecal calprotectin; ECP: eosinophil cationic protein; EDN: eosinophil-derived neurotoxin.

Figure 3. Correlation between faecal calprotectin and ECP/EDN in patents with ulcerative colitis (top) and Crohn's disease (bottom). p < .05 for all rs (Spearman’s rank correlation coefficient). Note, broken axis in graphs.