This study was done on the PSS patients receiving medical care in the rheumatology clinic of Kashan Shahid-Beheshti hospital over 2015-16 and it was aimed to study the relationship between the serum level of IL-6 and the involvement of lung as ILD in PSS patients. The patients were studied in two groups of PSS with ILD as cases (N = 30) and those without ILD as controls (N = 30). All the patients of case group had diffuse PSS, while 85% of the patients of control group had the diffuse type. In the case group, there were 22 females (73.4%) and 8 males (26.6%), while in the control group there were 18 females (60.0%) and 12 males (40.0%) (Table-1). The average age was 52.5 ± 9.3 years in the case group, and 43.9 ± 9.7 in the control group, the difference of which was significant (p = 0.001) (Table-1). The disease duration was 11.6 ± 6.4 years in the case group, and 7.4 ± 4.2 in the control group, which showed significant difference (p = 0.002) (Table-1).
Table-1. The demographic data of the patients in both groups of the study
|
Variable
|
Case group (N = 30)
|
Control group (N = 30)
|
p-value
|
Age (years)
|
52.5 ± 9.3
|
43.9 ± 9.7
|
0.001*
|
Sex
|
|
|
0.237**
|
male
|
8 (26.6%)
|
12 (40.0%)
|
|
female
|
22 (73.4%)
|
18 (60.0%)
|
|
Disease duration (years)
|
11.6 ± 6.4
|
7.4 ± 4.2
|
0.002*
|
* Mann-Whitney test ** Chi-square test
|
As it is shown in Table-2, the frequency of scleroderma activity based on EUSTAR score was significantly different between the two groups (p < 0.001).
Table-2. The frequency of scleroderma activity based on EUSTAR score in both groups of the study
|
Variable
|
Case group
|
Control group
|
p-value*
|
Scleroderma activity (EUSTAR score)
|
|
|
< 0.001
|
Active
|
21 (70%)
|
6 (20%)
|
|
Inactive
|
9 (30%)
|
24 (80%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
* Chi-square test
|
The mean serum levels of IL-6 and hemoglobin of the two groups are shown in Table-3. The serum levels of IL-6 were 73.1 ± 95.4 and 46.6 ± 83.6 pg/mL in case and control groups, respectively, the difference of which was not significant (p = 0.267).
Table-3. The mean serum levels of IL-6 and hemoglobin in both groups of the study
|
variable
|
Case group (N = 30)
|
Control group (N = 30)
|
p-value*
|
Serum level of IL-6 (pg/mL)
|
73.1 ± 95.4
|
46.7 ± 83.6
|
0.267
|
Hemoglobin (g/dL)
|
12.5 ± 1.4
|
13.0 ± 1.7
|
0.257
|
* Mann-Whitney test (The data are in form of mean ± standard deviation.)
|
As seen in Table-4, the mean serum level of IL-6 in males was 141.7 ± 103.2 and 14.3 ± 19.3 pg/mL in the case and control groups, respectively, the difference of which was significant (p = 0.007). However, it was 48.1 ± 81.2 and 68.2 ± 102.2 pg/mL in females of the case and control groups, respectively, which showed no significant difference (p = 0.693).
Table-4. The mean serum level of IL-6 (pg/mL) in terms of sex in both groups of the study
|
Sex
|
Group
|
Frequency
|
Mean ± standard deviation
|
p-value*
|
Male
|
case
|
8
|
141.7 .7 ± 103.2
|
0.007
|
control
|
12
|
14.3 ± 19.3
|
Female
|
case
|
22
|
48.1 ± 81.2
|
0.693
|
control
|
18
|
68.2 ± 102.2
|
* Mann-Whitney test
|
As evident in Table-5, the mean serum level of IL-6 in those with active disease was 79.9 ± 94.3 and 51.1 ± 88.1 pg/mL in the case and control groups, respectively, the difference of which was not significant (p = 0.414). Moreover, in those with inactive disease, it was 57.1 ± 101.8 and 45.6 ± 84.4 pg/mL in the case and control groups, respectively, which showed no significant difference as well (p = 0.793).
Table-5. The mean serum level of IL-6 (pg/mL) in terms of disease activity in both groups of the study
|
Disease activity
|
Group
|
Frequency
|
Mean ± standard deviation
|
p-value*
|
Active
|
case
|
21
|
79.9 ± 94.3
|
0.414
|
control
|
6
|
51.1 ± 88.1
|
Inactive
|
case
|
9
|
57.1 ± 101.8
|
0.793
|
control
|
24
|
45.6 ± 84.4
|
* Mann-Whitney test
|
The mean serum levels of IL-6 in terms of age are shown in Table-6. In patients less than 50 years old, it was 32.7 ± 59.1and 55.5 ± 93.3 pg/mL in the case and control groups, respectively, the difference of which was not significant (p = 0.987). Furthermore, in those aged 50 years or more, it was 103.9 ± 107.5 and 17.6 ± 23.9 pg/mL in the case and control groups, respectively, which showed no significant difference as well (p = 0.057).
Table-6. The mean serum level of IL-6 (pg/mL) in terms of age in both groups of the study
|
Age
|
Group
|
Frequency
|
Mean ± standard deviation
|
p-value*
|
< 50 years
|
case
|
13
|
32.7 ± 59.1
|
0.987
|
control
|
23
|
55.5 ± 93.3
|
≥ 50 years
|
case
|
17
|
103.9 ± 107.5
|
0.057
|
control
|
7
|
17.6 ± 23.9
|
* Mann-Whitney test
|
As seen in Table-7, the mean serum level of IL-6 in those with a disease duration less than 10 years was 103.9 ± 110.0 and 51.4 ± 92.6 pg/mL in the case and control groups, respectively, the difference of which was not significant (p = 0.140). Moreover, in those with a disease duration of 10 years or more, it was 59.8 ± 88.0 and 27.6 ± 22.2 pg/mL in the case and control groups, respectively, which showed no significant difference as well (p = 0.770).
Table-7. The mean serum level of IL-6 (pg/mL) in terms of disease duration in both groups of the study
Disease Duration
|
Group
|
Frequency
|
Mean ± standard deviation
|
p-value*
|
<10 years
|
case
|
9
|
103.9 ± 110.0
|
0.140
|
control
|
24
|
51.4 ± 92.6
|
≥10 years
|
case
|
21
|
59.8 ± 88.0
|
0.770
|
* Mann-Whitney test
In Table-8, the frequencies of the involved organs by PSS and concurrent other rheumatologic diseases are shown for both groups of the study. As it can be seen, eight patients (26.6%) had cardiac involvement in the case group. There were also five patients (16.7%) with concurrent other rheumatologic diseases in the case group.
Table-8. The frequencies of the involved organs by PSS and concurrent other rheumatologic diseases in both groups of the study
|
Variable
|
Case group (N=30)
|
Control group (N=30)
|
p-value
|
Skin involvement
|
30 (100%)
|
30 (100%)
|
1*
|
Cardiac involvement
|
8 (26.6%)
|
0 (0%)
|
0.003*
|
Heart failure
|
1 (12.5%)
|
0 (0%)
|
|
Pericarditis
|
7 (87.5%)
|
0 (0%)
|
|
Other rheumatologic diseases
|
5 (16.7%)
|
6 (20%)
|
0.739*
|
Osteoporosis
|
5 (100%)
|
2 (33.3%)
|
|
Rheumatoid arthritis
|
0 (0%)
|
2 (33.3%)
|
|
Polymyositis
|
0 (0%)
|
1 (16.7%)
|
|
Sjögren disease
|
0 (0%)
|
1 (16.7%)
|
|
* Fisher’s exact test ** Chi-square test
|
As evident in Table-9, 8 (26.7%), 9 (30%), 7 (23.3%), and 6 (20%) patients in the case group, and 17 (56.7%), 5 (16.7%), and 1 (3.3%) patients in the control group had a qualitative CRP of Negative, +1, +2, and +3, respectively. The difference between the two groups was significant (p<0.05).
Table-9. The frequency distribution of qualitative CRP in both groups of the study
|
variable
|
Case group
|
Control group
|
p-value*
|
qualitative CRP
|
|
|
0.010
|
Negative
|
8 (26.7%)
|
17 (56.7%)
|
|
+1
|
9 (30%)
|
7 (23.3%)
|
|
+2
|
7 (23.3%)
|
5 (16.7%)
|
|
+3
|
6 (20%)
|
1 (3.3%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
*Fisher’s exact test
|
The frequency distribution of chest X-ray findings is shown in Table-10. The most common finding was reticulonodular pattern (66.7%) in the case group, and normal pattern (93.3%) in the control group with the difference being significant (p < 0.001).
Table-10. The frequency distribution of chest X-ray findings in both groups of the study
|
variable
|
Case group
|
Control group
|
p-value*
|
chest X-ray finding
|
|
|
> 0.001
|
Normal
|
1 (3.3%)
|
28 (93.3%)
|
|
Reticulonodular pattern
|
20 (66.7%)
|
2 (6.7%)
|
|
Fibrotic pattern
|
9 (30%)
|
0 (0%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
*Fisher’s exact test
|
The lung HRCT finding of the greatest frequency was honeycombing (76.7%) in the case group, while all the patients of the control group had normal pattern with the difference being significant (Table-11).
Table-11. The frequency distribution of lung HRCT findings in both groups of the study
variable
|
Case group
|
Control group
|
p-value*
|
HRCT finding
|
|
|
>0.001
|
Normal
|
0 (0%)
|
30 (93.3%)
|
|
Honeycombing
|
23 (76.7%)
|
0 (0%)
|
|
Fibrosis
|
5 (16.7%)
|
0 (0%)
|
|
Peribronchial thickening
|
2 (6.7%)
|
0 (0%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
* Fisher’s exact test
As shown in Table-12, 26 patients (86.7%) in the case group and one patient (3.3%) in the control group demonstrated restrictive respiratory pattern, the difference of which was significant (p<0.001). Table-12. The frequency distribution of spirometry patterns in both groups of the study VariableCase group Control groupp-value* spirometry pattern>0.001 Normal4 (13.3%)29 (96.7%) Restrictive26 (86.7%)1 (3.3%) Total30 (100%)30 (100%)
Table-12. The frequency distribution of spirometry patterns in both groups of the study
|
Variable
|
Case group
|
Control group
|
p-value*
|
spirometry pattern
|
|
|
>0.001
|
Normal
|
4 (13.3%)
|
29 (96.7%)
|
|
Restrictive
|
26 (86.7%)
|
1 (3.3%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
*Chi-square test
The heart ejection fraction (EF) of the greatest frequency was 55% (11 patients) in the case group and 60% (17 patients) in the control group, the difference of which was significant (Table-13).
Table-13. The frequency distribution of heart ejection fraction (EF) in both groups of the study
|
Variable
|
Case group
|
Control group
|
p-value*
|
Ejection Fraction (%)
|
|
|
>0.001
|
40
|
1 (3.3%)
|
0 (0%)
|
|
45
|
3 (10%)
|
0 (0%)
|
|
48
|
1 (3.3%)
|
0 (0%)
|
|
50
|
5 (16.7%)
|
0 (0%)
|
|
55
|
11 (36.7%)
|
12 (40%)
|
|
60
|
8 (26.7%)
|
17 (56.7%)
|
|
65
|
0 (0%)
|
1 (3.3%)
|
|
67
|
1 (3.3%)
|
0 (0%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
*Fisher’s exact test
|
As evident in Table-14, there were 10 patients (33.3%) with abnormal echocardiography pattern in the case group, whereas all the patients of the control group had normal echocardiography, the difference of which was significant (p = 0.001).
Table-14. The frequency distribution of echocardiography findings in both groups of the study
|
Variable
|
Case group
|
Control group
|
p-value*
|
echocardiography finding
|
|
|
> 0.001
|
Normal
|
20 (66.7%)
|
30 (100%)
|
|
Abnormal
|
10 (33.3%)
|
0 (0%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
*Chi-square test
|
As shown in Table-15, the most frequent pulmonary artery pressures (PAP) were 45 and 50 mmHg (six and six patients, respectively) in the case group, while it was normal (25 patients) in the control group with the difference being significant (p < 0.001).
Table-15. The frequency distribution of pulmonary artery pressure (PAP) in both groups of the study
|
variable
|
Case group
|
Control group
|
p-value
|
PAP (mmHg)
|
|
|
> 0.001
|
Normal
|
4 (13.3%)
|
25 (83.3%)
|
|
20
|
5 (16.7%)
|
2 (6.7%)
|
|
25
|
2 (6.7%)
|
1 (3.3%)
|
|
40
|
2 (6.7%)
|
2 (6.7%)
|
|
45
|
6 (20%)
|
0 (0%)
|
|
50
|
6 (20%)
|
0 (0%)
|
|
55
|
2 (6.7%)
|
0 (0%)
|
|
60
|
2 (6.7%)
|
0 (0%)
|
|
63
|
1 (3.3%)
|
0 (0%)
|
|
Total
|
30 (100%)
|
30 (100%)
|
|
*Fisher’s exact test
|