Document Type : Original Article
Authors
1 Chest department Faculty of Medicine, Al-Azhar university, cairo,Egypt.
2 Rheumatology and Rehabilitation Department, faculty of Medicine, AL-Azhar university, Cairo, Egypt
3 Chest department Faculty of Medicine, Al-Azhar University, cairo,Egypt.
Abstract
Keywords
INTRODUCTION
Rheumatoid arthritis (RA) is a systemic inflammatory disease that most typically affects the joints, producing progressive, symmetric, erosive destruction of cartilage and bone, and is often accompanied with autoantibody production. Extraarticular symptoms, such as pulmonary signs, are also linked to an increased risk of morbidity and mortality. They may even occur before articular symptoms. 1
In rheumatoid arthritis, respiratory symptoms can be caused by a variety of conditions affecting the parenchyma, pleura, airways, or vasculature. Complications can occur as a result of rheumatoid arthritis or as a side effect of immune-suppressing medications used to treat rheumatoid arthritis. Within the first five years of disease, the bulk of respiratory signs arise. 2
Vitamin D may have a significant impact on both the innate and adaptive immune systems. The presence
of its receptors on several types of cells supports this, and its insufficiency is linked to the progression and result of RA. 3
According to a 2012 Greek study published in Therapeutic Advances in Endocrinology and Metabolism, vitamin D insufficiency is closely linked to disabling symptoms in people with rheumatoid arthritis. This could be because RA can impair the body's ability to absorb vitamin D from the foods we eat, and low vitamin D levels can exacerbate RA symptoms and pain. 4
Vitamin D reduces autoimmunity by modulating antigen-presenting cells' synthesis of pro-inflammatory and anti-inflammatory cytokines. A decrease in 25(OH) D3 is caused by polymorphisms in the vitamin D receptor and 1-hydroxylase genes, which may increase the risk of inflammation.5
The aim of the study to detect the prevalence of vitamin D deficiency and its relationship to pulmonary affection in RA patients and correlate it with disease Activity.
PATIENTS AND METHODS
The study was a cross sectional one, carried out on 50 patients diagnosed with RA recruited from the Chest and Rheumatology Outpatient Clinics of Al Hussein University Hospital in period between August 2021 and May 2022.
Ethical Considerations: The selection of subjects done after prior explanation of the aim of the study, and a free-will written approval consent is taken, and the whole work done according to the ethical committee, Faculty of medicine, Al-Azhar University
Inclusion criteria include: All patients diagnosed with RA who fulfilled the American Colleague of Rheumatology/European League against Rheumatism 2010 classification criteria.
Exclusion criteria include: No specific contraindications.
All studied patients are subjected to: Detailed history taking. Physical examinations, Laboratory investigations were performed including complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein titer, liver enzymes, and renal function tests. Rheumatoid factor (RF) titer was determined using the latex agglutination test kit and anti-CCP antibody titer using the ELISA technique, serum 25-hydroxy vitamin D [25(OH) D] levels was performed using ELISA, Chest x-ray, High Resolution Computed Tomography( HRCT) Chest, and Spirometry Statistical analysis:The Statistical Program for Social Science (SPSS) version 24 was used to examine the data. The mean and standard deviation were used to express quantitative data. Frequency and percentage were used to express qualitative data. The central value of a discrete set of numbers, namely the sum of values divided by the number of values, is called the mean (average). The standard deviation (SD) is a measure of a set of values' dispersion. A low SD implies that the values are spread out over a wider range, whereas a high SD shows that the values are close to the set's mean. When comparing non-parametric data, the Chi-square test was utilized. To compare quantitative data on vitamin D levels, the Kruskal Willis test was utilized. For data correlation, the Pearson correlation coefficient was applied. P-values less than 0.05 were considered significant, P-values less than 0.001 were regarded very significant, and P-values more than 0.05 were considered inconsequential.
RESULTS
|
Studied patients (N = 50) |
||
Age (years) |
M±SD |
46.7 ± 6.6 |
|
Min – Max |
38 – 61 |
||
Duration of RA disease (years) |
M ±SD |
13.9 ± 5.6 |
|
Min – Max |
1 – 23 |
||
Sex |
Male |
10 |
20% |
Female |
40 |
80% |
|
Smoking |
Non-smoker |
45 |
90% |
Smoker |
5 |
10% |
Table 1: Description of demographic data in all studied patients
The result of our study showed that the description of demographic data in all RA patients with pulmonary affection shown that the mean age of all studied patients was 46.7 ± 6.6 years with minimum age of 38 years and maximum age of 61 years. As regard duration, the mean duration of all studied patients was 13.9 ± 5.6 years with minimum duration of 1 year and maximum duration of 23 years. As regard sex, there were 10 males (20%) and 40 females (80%) in the studied patients. As regard smoking, there were 5 smokers (10%) and 45 non-smokers (90%) in the studied patients. Table (1)
Vitamin D level |
Studied patients (N = 50) |
|
Deficient ( |
22 |
44% |
Insufficient (20 – 30 ng/ml) |
22 |
44% |
Sufficient (>30 ng/ml) |
6 |
12% |
Table 2:Vitamin D serum level in all studied patients.
In our study, the description of vitamin D status in all studied patients were 22 deficient patients (44%), 22 insufficient patients (44%) and 6 sufficient patients. Table (2)
|
Studied patients (N = 50) |
||
CT findings |
Normal CT |
0 |
0% |
Bronchiectasis |
30 |
60% |
|
Honey combing |
13 |
26% |
|
Emphysema |
20 |
40% |
|
Reticulations |
32 |
64% |
|
Pleural effusion |
5 |
10% |
|
pleural thickening |
15 |
30% |
|
Nodule |
5 |
10% |
|
GGO |
27 |
54% |
|
Sub-pleural cysts |
2 |
4% |
|
CT pattern of ILD |
NSIP |
24 |
48% |
UIP |
17 |
34% |
|
RB-ILD |
9 |
18% |
Table 3: Description of CT chest findings in all studied patients
As regard CT pattern of interstitial lung affection, the most common pattern was NSIP in 24 patients (48%), UIP in 17 patients (34%) and RB-ILD in 9 patients (18%). Table (3)
|
Vitamin D status |
Stat. test |
P-value |
|||
Deficient (n = 22) |
Insufficient (n = 22) |
Sufficient (n = 6) |
||||
DAS-28 score |
Mean |
5.4 |
4.9 |
4.1 |
KW = 12.7 |
0.002 S |
±SD |
0.8 |
0.4 |
0.8 |
Table 4:The correlation between vitamin D level and DAS- 28 score
DAS-28 (disease activity score) and 28 mention to the count of peripheral joints examined for tenderness in rheumatoid arthritis patient
In all patients, A relationship is present between vitamin D level and DAS-28 in Vit-d deficient patients, study found a significant (p-value = 0.002) rise in DAS-28 score.(5.4 ± 0.8) when compared with insufficient patients (4.9 ± 0.4) and sufficient patients (4.1 ± 0.8). Table (4)
|
Vitamin D status |
X2 |
P-value |
||||||
Deficient (n = 22) |
Insufficient (n = 22) |
Sufficient (n = 6) |
|||||||
Exertional Dyspnea |
No |
14 |
63.6% |
14 |
63.6% |
6 |
100% |
3.2 |
0.201 NS |
Yes |
8 |
36.4% |
8 |
36.4% |
0 |
0% |
|||
Dry Cough |
No |
14 |
63.6% |
14 |
63.6% |
5 |
83.3% |
0.9 |
0.634 NS |
Yes |
8 |
36.4% |
8 |
36.4% |
1 |
16.7% |
|||
Chest Pain |
No |
20 |
90.9% |
20 |
90.9% |
4 |
66.7% |
2.9 |
0.230 NS |
Yes |
2 |
9.1% |
2 |
9.1% |
2 |
33.3% |
|||
Wheezing |
No |
18 |
81.8% |
21 |
95.5% |
5 |
83.3% |
2.1 |
0.354 NS |
Yes |
4 |
18.2% |
1 |
4.5% |
1 |
16.7% |
|||
Leathery Crepitation |
No |
17 |
77.3% |
17 |
77.3% |
6 |
100% |
1.7 |
0.426 NS |
Yes |
5 |
22.7% |
5 |
22.7% |
0 |
0% |
Table 5: Relation between vitamin D status and clinical manifestations in all studied patients
In our study there no statistically significant relation (p-value < 0.05) between vitamin D status and clinical manifestations (Exertional Dyspnea, Dry Cough, Chest Pain, Wheezing and Leathery Crepitation). Table (5)
|
Vitamin D status |
KW |
P-value |
|||
Deficient (n = 22) |
Insufficient (n = 22) |
Sufficient (n = 6) |
||||
FVC |
Mean |
89.3 |
113.4 |
114.8 |
16.6 |
< 0.001 HS |
±SD |
20.1 |
7.1 |
3.4 |
|||
FEV1 |
Mean |
80.1 |
84.8 |
86.0 |
4.36 |
0.113 NS |
±SD |
8.4 |
4.7 |
5.0 |
|||
FEV1/FVC |
Mean |
89.9 |
74.7 |
74.5 |
3.8 |
0.144 NS |
±SD |
22.0 |
4.2 |
3.3 |
Table 6: Relation between vitamin D status and Spirometric indices in all studied patients
There is significant decrease in FVC (p-value < 0.001) in Vit-D deficient patients (89.3 ± 20.1) when compared with insufficient patients (113.4 ± 7.1) and sufficient patients (114.8 ± 3.4). No significant difference (p-value > 0.05) in vitamin D status and FEV1 & FEV1/FVC. Table (6)
|
Vitamin D status |
X2 |
P-value |
||||||
Deficient (n = 22) |
Insufficient (n = 22) |
Sufficient (n = 6) |
|||||||
PFTs pattern |
Small airway disease |
1 |
4.5% |
7 |
31.8% |
3 |
50% |
29.8 |
0.001 S |
Mild restrictive |
7 |
31.8% |
0 |
0% |
3 |
50% |
|||
Moderate restrictive |
6 |
27.3% |
5 |
22.7% |
0 |
0% |
|||
severe restrictive |
5 |
22.7% |
0 |
0% |
0 |
0% |
|||
Mild obstructive |
0 |
0% |
3 |
13.6% |
0 |
0% |
|||
Mixed |
3 |
13.6% |
7 |
31.8% |
0 |
0% |
Table 7: Relation between vitamin D status and PFTs pattern in all studied patients
The study shows that there was statistically significant difference between vitamin D deficient patients, insufficient patients, and sufficient patients as regard PFTs pattern. Table (7)
|
Vitamin D status |
X2 |
P-value |
||||||
Deficient (n = 22) |
Insufficient (n = 22) |
Sufficient (n = 6) |
|||||||
Bronchiectasis |
No |
0 |
0% |
14 |
63.6% |
6 |
100% |
28.8 |
< 0.001 HS |
Yes |
22 |
100% |
8 |
36.4% |
0 |
0% |
|||
Honey combing |
No |
10 |
45.5% |
21 |
95.5% |
6 |
100% |
16.7 |
< 0.001 HS |
Yes |
12 |
54.5% |
1 |
4.5% |
0 |
0% |
|||
Emphysema |
No |
2 |
9.1% |
22 |
100% |
6 |
100% |
42.4 |
< 0.001 HS |
Yes |
20 |
90.9% |
0 |
0% |
0 |
0% |
|||
Reticulations |
No |
10 |
45.5% |
6 |
27.3% |
2 |
33.3% |
1.59 |
0.449 NS |
Yes |
12 |
54.5% |
16 |
72.7% |
4 |
66.7% |
|||
Pleural Effusion |
No |
19 |
86.4% |
20 |
90.9% |
6 |
100% |
1.01 |
0.603 NS |
Yes |
3 |
13.6% |
2 |
9.1% |
0 |
0% |
|||
pleural thickening |
No |
16 |
72.7% |
16 |
72.7% |
3 |
50% |
1.29 |
0.522 NS |
Yes |
6 |
27.3% |
6 |
27.3% |
3 |
50% |
|||
Sub-pleural cysts |
No |
18 |
81.8% |
21 |
95.5% |
6 |
100% |
3.03 |
0.220 NS |
Yes |
4 |
18.2% |
1 |
4.5% |
0 |
0% |
|||
Nodule |
No |
10 |
45.5% |
7 |
31.8% |
6 |
100% |
8.8 |
0.012 S |
Yes |
12 |
54.5% |
15 |
68.2% |
0 |
0% |
|||
GGO |
No |
22 |
100% |
20 |
90.9% |
6 |
100% |
2.6 |
0.266 NS |
Yes |
0 |
0% |
2 |
9.1% |
0 |
0% |
Table 8: Relation between vitamin D status and CT findings in all studied patients
In our study there was no significant difference between vitamin D status and the following CT findings (reticulations, pleural effusion, pleural thickening, sub-pleural cysts and GGO). Statistically significant (p-value = 0.012) increased percentage of nodule in deficient patients (12 patients, 54.5%) and insufficient patients (15 patients, 68.2%) when compared with sufficient patients (0 patients, 0%). Highly statistical significant (p-value < 0.001) increased percentage of emphysema in deficient patients (12 patients, 54.5%) when compared with insufficient patients (0 patients, 0%) and sufficient patients (0 patients, 0%). Highly statistical significant (p-value < 0.001) increased percentage of honey combing in deficient patients (12 patients, 54.5%) when compared with insufficient patients (1 patient, 4.5%) and sufficient patients (0 patients, 0%). Highly statistical significant (p-value < 0.001) increased percentage of Bronchiectasis in deficient patients (22 patients, 100%) when compared with insufficient patients (8 patients, 36.4%) and sufficient patients (0 patients, 0%). Table (8)
DISCUSSION
The association between RA and serum levels of vit D and 1,25(O.H)2D has been controversial in previous studies.6
A large meta-analysis study carried out by Lin et al. 4 that included 3489 patients showed that RA patients had lower vitamin D levels than the healthy controls.
Other research, on the other hand, found no such link. Differences in prior studies' results could be due to a variety of factors, including the population investigated, sample size, study design, analytical procedures utilized, and testing tools. 6 to 1
Abourazzak et al.7 discovered vitamin D deficiency in 64.4 (0.9 percent) and insufficiency in 35.5 and 99.1 percent of their RA patients, respectively.
Vitamin D and IPF have a statistically significant inverse relationship, according to Allam et al. (r=0.234, P=0.017). 3
In a previous study of 67 patients with ILD secondary to connective tissue disease including RA and 51 patients with other causes of ILD, significant vitamin D deficiency (52 vs. 20%,P<0.0001) and insufficiency (79 vs. 31%, P<0.0001) were found among those with connective tissue disease-ILD than those with other forms of ILD.2
Our study agrees with that done by Sherin et al.8 which showed an association between pulmonary affection in RA patients and hypovitaminosis D as in RA patients with pulmonary affection 45% of patients have vitamin D deficit and 45% had vitamin D insufficiency versus 16.7 and 63.3% in RA patients without pulmonary affection.
The description of CT results in all studied patients. As regard CT findings, there was bronchiectasis in 30 patients (60%), honey combing in 13 patients (26%), emphysema in 20 patients (40%), reticulations in 32 patients (64%), pleural effusion in 5 patients (10%), pleural thickening in 15 patients (30%), nodule in 5 patients (10%), GGO in 27 patients (54%) and sub-pleural cyst in 2 patients (4%).
Our study agrees with that done by Haque U et al.9, Sherin et al.8 andTurhanoflu AD et al.10which showed that there were inverse associations between vitamin D level with RA disease activity (DAS-28 score).
A meta-analysis by Lin et al.,4reported the same association and reported a relatively stronger negative correlation between 25(OH)D and DAS-28 in low latitude areas and in developing countries than in developed countries.
This result agrees with that done by Sherin et al.8abnormal spirometric parameters were more among the deficient and insufficient groups than the sufficient group, P=0.01, and the most common pattern among the vitamin D deficiency and insufficient groups was the restrictive pattern in 21.4% in both groups. Significant decrease in DLCO level in deficient group more than insufficient and sufficient groups (P=0.03).
In contrary with the study done by Sherin et al.8the 40 RA patients with pulmonary affection as diagnosed by HRCT chest, a ground glass appearance was found in 22 (55%) RA patients, pleural thickening in 12 (30%) patients reticulation in 26 (65%) patients, honey combing in 10 (25%) patients, nodules in four (10%) patients, emphysema in 16 (40%) patients,bronchiectasis in 24 (60%) patients, and pleural effusion in four (10%) patients
CONCLUSION
Vitamin D insufficiency appears to be very common among RA patients., This study suggests that pulmonary manifestations in RA patients more prevalent with vitamin D deficiency, This study suggests that vitamin D is associated with RA disease activity, and may have a role in functional disability in RA patients.
REFERENCES
Turhanoflu AD, Guler H, Yonden Z, Aslan F, Mansuroglu A, Ozer C. The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis. Rheumatol Int. 2011; 31:911–91