Abstract

Background Despite negative association between 25-hydroxy vitamin D and incidence of many chronic respiratory diseases, this feature was not well studied in sarcoidosis. Current study investigated the association between 25-hydroxy vitamin D deficiency with sarcoidosis chronicity, disease activity, extra-pulmonary skin manifestations, urine calcium level and pulmonary function status in Iranian sarcoidosis patients. Results of this study along with future studies, will supply more effective programs for sarcoidosis treatment. Methods Eighty sarcoidosis patients in two groups of insufficient serum level and sufficient serum level of 25-hydroxy vitamin D were studied. Course of sarcoidosis was defined as acute and chronic sarcoidosis. Pulmonary function test (PFT) was assessed by spirometry. Skin involvements were defined as biopsy proven skin sarcoidosis. 24-hour urine calcium level was used to specify the disease activity. Stages of lung involvements were obtained by CT-scan and chest X-ray. The statistical analyses were evaluated using Statistical Package for the Social Sciences. Results A significant negative correlation was obtained between vitamin D deficiency in sarcoidosis patients and disease chronic course and stages two to four of lung involvements. Considering other parameters of the disease and vitamin D deficiency, no significant correlation was detected. Conclusions In conclusion, results of the current study implies in the role of vitamin 25(OH)D deficiencies in predicting the course of chronic sarcoidosis. Furthermore, it was concluded that vitamin 25(OH)D deficiency can direct pulmonary sarcoidosis toward stage 2–4 of lung involvements.
J Med Biochem 2018; 37 (2) DOI: 10.1515/jomb-2017-0041
UDK 577.1 : 61 ISSN 1452-8258
J Med Biochem 37: 103 –109, 2018 Original paper
Originalni nau~ni rad
ASSOCIATION BETWEEN VITAMIN D DEFICIENCIES IN SARCOIDOSIS
WITH DISEASE ACTIVITY, COURSE OF DISEASE AND STAGES
OF LUNG INVOLVEMENTS
POVEZANOST DEFICIJENCIJE VITAMINA D U SARKOIDOZI SA TE@INOM
I TOKOM OBOLJENJA, KAO I O[TE]ENJEM PLU]A
Arda Kiani1, Atefeh Abedini2, Ian M. Adcock3,4, Maryam Sadat Mirenayat2,
Kimia Taghavi2, Esmaeil Mortaz5, Mehdi Kazempour-Dizaji6
1Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD),
Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis
and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute,
Imperial College London, Dove house Street, London, UK.10
4Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle,
Newcastle, New South Wales, Australia
5Department of Immunology, Faculty of Medicine, Clinical Tuberculosis and Epidemiology Research Center,
National Research Institute of Tuberculosis and Lung Diseases (NRITLD),
Shahid Beheshti University of Medical Sciences, Tehran, Iran
6Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD),
Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Address for correspondence:
Atefeh Abedini
Address: Chronic Respiratory Disease Research Center,
Massih Daneshvari Hospital, Shaheed Bahonar Ave,
Tehran 1956944413, Iran
Tel: +9821-27122031, fax: +982126109590
e-mail: dr.abedini110ªgmail.com
Summary
Background:
Despite negative association between 25-
hydroxy vitamin D and incidence of many chronic respiratory
diseases, this feature was not well studied in sarcoidosis.
Current study investigated the association between 25-
hydroxy vitamin D deficiency with sarcoidosis chronicity, dis-
ease activity, extra-pulmonary skin manifestations, urine cal-
cium level and pulmonary function status in Iranian
sarcoidosis patients. Results of this study along with future
studies, will supply more effective programs for sarcoidosis
treatment.
Methods:
Eighty sarcoidosis patients in two groups of insuf-
ficient serum level and sufficient serum level of 25-hydroxy
vitamin D were studied. Course of sarcoidosis was defined as
Kratak sadr`aj
Uvod:
Uprkos negativnoj povezanosti izme|u 25-hidroksi vi -
tamina D i u~estalosti brojnih hroni~nih respiratornih obo -
ljenja, ovaj uticaj jo{ uvek nije ispitivan u sarkoidozi. Ova
istra`ivanja izu~avaju vezu izme|u deficijencije 25-hidroksi
vitamina D sa stepenom hroni~nosti kod sarkoidoze,
aktivnosti oboljenja, ekstra pulmonalnih ko`nih manifestaci-
ja, nivoa kalcijuma u urinu i statusa pulmonalne funkcije kod
Iranskih pacijenata sa sarkoidozom. Rezultati ovih izu~avanja
sa budu}im istra`ivanjima mogu ukazati na mnogo bolji
uspeh u tretmanu sarkoidoze.
Metode:
Prou~avano je osamdeset pacijenata sa sarkoido-
zom podeljenih u dve grupe u odnosu na insuficijentni i
zadovoljavaju}i nivo 25-hidroksi vitamina D. Stepen sarko i -
104 Kiani et al.: Vitamin D associates with sarcoidosis features
Introduction
Sarcoidosis is a multi-organization disease char-
acterized by granuloma formation and enhanced
immune operation activities (1, 2). Several studies
have advocated that the innate immune failure in
responding to persistent antigens causes Granuloma
formation of sarcoidosis (1–3). Sarcoidosis disease
occurs in winter and in regions with increased latitude
in which lack of sun-exposure leads to vitamin D defi-
ciency (4, 5). Vitamin D pro hormone plays many
potential roles in immune regulatory structure (5, 3).
As explained in third national health and nutrition sur-
vey, vitamin D deficiency is associated with sarcoidosis
prevalence (6). Indeed, sarcoidosis treatment with
corticosteroids leads to osteoporosis, which so physi-
cians include calcium and vitamin D (CAD) supple-
ments in line with routine treatment. But, some con-
cerning issues about sarcoidosis insist. In this light,
hypercalcemia is a known feature of sarcoidosis in 5
to 11% of cases (7, 8). Activated macrophages in the
sarcoidosis granuloma are responsible for overpro-
duction of vitamin D3 active form.
Overproduction of active form of vitamin D3
(calcitriol or 1,25-dihydroxy vitamin D (1,25(OH)2D)),
provides hypercalcemia, hypercalciuria and osteoar-
ticular manifestations (9–12). In addition, hyper-
parathyroidism can cause hypercalcemia (1). In such
cases although vitamin D serum level deficiency
insists, but 1,25(OH)2D normal serum level remains
a prime obstacle in efficiency of 1,25(OH)2D evalua-
tion (10, 13, 14). Most sarcoidosis patients exhibit
normal levels of 1,25(OH)2D. But, these patients
represent low levels of 25-(OH)D (15, 16). As a
result, measuring Vitamin D-25 as the major circulat-
ing form of vitamin D is the most efficient administra-
tor to test the adequacy of vitamin D level (1, 17).
Objectives
Negative association was reported between 25-
hydroxy vitamin D, active sarcoidosis, sarcoidosis chro -
nicity and pulmonary function status in sarcoidosis
patients, in recent studies (1, 4, 5, 18). But, correlation
of 25-(OH)D status with sarcoidosis factors has not
been yet studied in Iranian sarcoidosis population. The
purpose of this non-experimental de signed survey was
to investigate association of 25-hydroxy vitamin D defi-
ciency with sarcoidosis chronicity, active form of dis-
ease, skin extra-pulmonary manifestations, urine calci-
um and pulmonary function status in a group of Iranian
sarcoidosis patients at referral respiratory hospital of
Iran. Since this study is the first study of its kind, the
results will be more effective treatment of Iranian
patients by considering the level of 25(OH)D.
Material and Methods
Study Design
This correlational descriptive study was conduct-
ed at the sarcoidosis clinic of Masih Daneshvari
Hospital, Tehran. To figure the possible correlations
between vitamin D status and other limits in sarcoidosis
patients, this study was conducted between November
2013 and November 2016. Thereby, the study was
approved by the Ethics Committee of Shahid Beheshti
medical sciences university (SBMU 1.REC.1393.71).
An expert methodologist estimated the study popula-
tion size due to statistics guidelines (19, 20).
Inclusion and exclusion criteria
Inclusion criteria: Greater than 18 years old sar-
coidosis patients with biopsy-proven disease and no
co existing chronic respiratory disease.
acute and chronic sarcoidosis. Pulmonary function test (PFT)
was assessed by spirometry. Skin involvements were defined
as biopsy proven skin sarcoidosis. 24-hour urine calcium
level was used to specify the disease activity. Stages of lung
involvements were obtained by CT-scan and chest X-ray. The
statistical analyses were evaluated using Statistical Package
for the Social Sciences.
Results:
A significant negative correlation was obtained
between vitamin D deficiency in sarcoidosis patients and dis-
ease chronic course and stages two to four of lung involve-
ments. Considering other parameters of the disease and vita-
min D deficiency, no significant correlation was detected.
Conclusions:
In conclusion, results of the current study
implies in the role of vitamin 25(OH)D deficiencies in pre-
dicting the course of chronic sarcoidosis. Furthermore, it was
concluded that vitamin 25(OH)D deficiency can direct pul-
monary sarcoidosis toward stage 2–4 of lung involvements.
Keywords: vitamin D (D014807), hypercalciuria
(D053565), sarcoidosis (D012507)
doze je definisan kao akutna i hroni~na sarkoidoza. Pulmo -
nalni fnkcionalni test (PFT) je izveden spirometrijom.
Uklju~enost ko`e je definisana biopsijom. Nivo kalcijuma u
24-urinu je kori{}en za dokazivanje stepena aktivnosti obo -
ljenja. Stepen uklju~enosti promena na plu}ima je dobijen
primenom CT-skenera i snimanjem plu}a rendgenski. Za
statisti~ku procenu rezultata kori{}en je statisti~ki program
Social Sciences (SPSS).
Rezultati:
Dobijena je zna~ajno negativna korelacija izme|u
deficijencije vitamina D kod pacijenata sa sarkoidozom i
hroni~nog toka bolesti i stupnjeva u dva do ~etiri plu}na ste-
pena. Nije na|ena zna~ajna korelacija izme|u drugih para-
metara oboljenja i deficijencije vitamina D.
Zaklju~ak:
Mo`e se zaklju~iti da dobijeni rezultati ukazuju na
ulogu deficijencije vitamina 25(OH)D u predvi|anju toka
hroni~ne sarkoidoze. Tako|e, mo`e se zaklju~iti da deficijen-
cija vitamina 25(OH)D mo`e ukazati na pulmonalnu sarkoi -
dozu sa uklju~enjem plu}a stepena 2–4.
Klju~ne re~i: vitamin D (D014807), hiperkalciurija
(D053565), sarkoidoza (D012507)
J Med Biochem 2018; 37 (2) 105
Exclusion criteria: The smoker or tuberculosis
patient. Disease with vitamin D levels changing prop-
erties.
Study subjects
Forty sarcoidosis patients with 25(OH)D 50
nmol/L or less were selected as experimental group
which was comprised of two subgroups: deficient
group with 25(OH)D 25 nmol/L and insufficient
group with 27.5 25(OH)D 0 nmol/L (6). To cut diffi-
culties of two unequal groups’ analyses, 40 unknown
sarcoidosis patients with 25(OH)D > 50 nmol/L
defined as enough vitamin D were included in the
control group. Groups were selected without consid-
ering the exact result of vitamin D level or other
required clinical and para clinical parameters data
such as the amount of CD4/CD8 T cell ratio, Angio -
tensin-converting enzyme blood levels and the radio-
logical stage of the disease. All patients signed the
written consent forms in regard of human rights and
patient's privacy. On the same day of disease diagno-
sis, the blood samples, 24-hour urine, CT-scan and
chest X-ray (CXR) were got. The patients without
parenchymal lesions were defined as stage 0–1 of the
lung disease and the patients with parenchymal lesions
were classified in stage 2–4 of the lung disease.
Patients underwent primary tests such as parathyroid
test. Pulmonary function test (PFT) was performed by
spirometer (Spiro lab II, Italy) on the basis of the
European Respiratory Society criteria (18). Forced
expiratory volume in the 1st second (FEV1); forced
vital capacity (FVC) and the FEV1/FVC were expres -
sed as a percentage of the reference values and mil-
liliters (mm) (21). The primary demographic data,
such as age, gender, smoking status, course of dis-
ease and the time of diagnosis were also recorded in
the sarcoidosis clinic forms. Extra-pulmonary skin
involvements were characterized by dermatologist.
Sarcoidosis patients were registered in the national
sarcoidosis patient’s registry scheme (http://nritld-
rer.ir/#/Sarcoidosis/). Finally, patients received rele-
vant to the involved organ and disease severity steroid
treatment or oral non-steroidal anti-inflammatory
drugs. Vitamin D supplementations were prescribed
with vitamin D deficiency.
Vitamin D-25(OH) serum level
Vitamin D-25(OH) serum level was assessed
using the Elecsys® Vitamin D test by electro-chemo-
luminescence method (ECLIA). In this regard, Roche
reagents (Roche Diagnostics GmH, Mannheim,
Germany) were utilized. Following values was used to
define different 25-OH-vitD serum levels:
A) Deficiency: 25(OH)D 25 nmol/L serum
level.
B) Insufficiency: a serum level of 27.5 nmol/L –
50 nmol/L 25(OH)D.
C) Sufficient: a serum level of >52.5 nmol/L
25(OH)D.
Course of sarcoidosis
Lofgren syndrome as the acute form of sar-
coidosis was defined as treatable disease in less than
2 years. Chronic sarcoidosis was defined as the form
of the disease in which both symptoms and signs of
disease remained stable and active for over two years
despite the therapy. Patients were followed up for
three years to pursue the disease symptom improve-
ment and managing everyday tasks without com-
plaints of disease.
Disease activity
24-hour urine calcium level was used to specify
the active form of disease. The normal range of 24-
hour urine calcium level was considered 100 to 300
mg/24h. The amounts above the greatest level were
defined as hypercalciuria.
Statistical analysis
The statistical analyses were evaluated using
Statistical Package for the Social Sciences (SPSS) (ver.
22.0; SPSS Inc. Chicago, IL, USA) software.
Statistical analyses were conducted under internation-
al statistical reporting standards (22). So, descriptive
variables like 25-OH-vitD serum level were expressed
as mean (±standard deviation) or median (mini-
mum–maximum). Categorical shifts were expressed
as frequencies and percentages. Shapiro-Wilk
Normality test for normality of distribution showed
that 25-OH-vitD distribution was not normal. P value
of < 0.05 was significant. After classifying patients
into two groups due to vitamin D, correlation between
vitamin D deficiencies with qualitative variables were
tested using Pearson Chi-Square test and correlation
between vitamin D deficiencies with quantitative vari-
ables were tested using two independent sample
Mann-Whitney test.
Results
Normal distribution was only got in FEV1% vari-
able by Shapiro-Wilk normality test. 80 biopsy proven
sarcoidosis patients were studied during one year.
Age and sex central Indices were approximately same
in both groups. The mean age was 46.3 ± 8.1 with
the range of 19–78 yrs. Most of patients were in the
40–50-year old age group. Regarding the sex item,
female patients were predominant (n=48, 60%)
(Table I). Suggesting vitamin D level; 53% of men and
48% of women patients had vitamin 25(OH)D defi-
ciencies. Considering the sex of patients, no statistical
significance correlation was found between the vita-
min 25(OH)D serum levels of male and female
patients in Chi-Square test (p=0.812). So, no statisti-
cal significance correlation was found between the
age of patients and vitamin 25(OH)D serum levels
(p=0.328).
On the basis of seasonal distribution, spring was
the most referred season with the frequency of
26.25%. The mean of disease treatment duration in
the patients was 1.31±1.01 years, ranging from two
months (in one patient) to two years (in 21 patients).
May was the most common month for establishing
the disease in our clinic. None of the patients showed
primary hyperparathyroidism. 37 (46.2%) patients
were overweight according to the Body Mass Index
(BMI > 25). Most of the patients showed high levels
of ACE (63.7±45). Overall, the most commonly
involved organ was the respiratory tract (51 cases;
63.75%) with wheezing and crackle as the common
pulmonary abnormalities. The prevalence of joint
manifestations in patients was 41.7% and Joint man-
ifestation was a dominant feature of the patients with
a diagnosis of Lofgren syndrome (87.2%).
Vitamin D serum level and clinical information
The value of serum level 25(OH)D in our study
was measured at the moment of referring to the clin-
ic, thus mostly in the mid-spring. The mean value was
54.32 nmol/L, the percentiles ranging from 5 nmol/L
to 145 nmol/L. No statistical significant correlation
was detected considering the vitamin D levels and
duration of sarcoidosis treatment (p=0.061).
Skin manifestations of disease were reported in
30 (37.5%) patients. Arthritis, arthralgia and joint
swelling were seen in 16 cases (20%). No statistical
significant correlation was obtained between vitamin
D levels and categorical variable skin manifestations
of disease (independent sample Mann-Whitney test)
(p=0.706).
With respect to CT-scan chest X-ray (CXR)
results, patients were classified into a group with
lymph node involvement, (stage 0–1 of the lung dis-
ease) (38.7%) and a group with parenchymal lesions,
(stage 2– 4 of the lung disease) (61.3%). When ana-
lyzing the lung involvements of sarcoidosis (parenchy-
mal vs. non-parenchymal) in the light of vitamin
25(OH)D deficiency, a statistically significant negative
correlation was found in patients with parenchymal
lung involvements of sarcoidosis and low levels of
serum vitamin 25(OH)D (Pearson Chi-Square=
4.266; df=1; p=0.039). 72% of sarcoidosis patients
with vitamin D deficiency showed parenchymal
involvement. This proportion was 50% in sarcoidosis
patients with enough vitamin D serum level. In con-
trast, no statistically significant correlation was
obtained between the patients’ lymph node involve-
ment and the levels of vitamin 25(OH)D (Mann-
Whitney test; p=0.243).
Studied sarcoidosis patients were contained of
47 (58.8%) acute sarcoidosis patients and 33
(41.3%) chronic sarcoidosis patients. About, 55% of
sarcoidosis patients with vitamin D deficiency showed
chronic disease. Only 28% of sarcoidosis patients with
sufficient vitamin D serum level showed chronic dis-
ease. Considering the course of sarcoidosis (acute vs.
chronic), a significant positive correlation was found
in patients with chronic disease, in the light of vitamin
25(OH)D deficiency (Pearson Chi-Square=4.142;
DF=1; p=0.012) (Table I).
The mean urinary calcium level was 189.7 ±
111.9 mg/24hr with the range of 19–789 mg/24hr.
18.9% of patients showed hypercalciuria. Absolute
vitamin 25(OH)D deficiencies were identified in
patients with high levels of calcium in the 24 hr urine
sample. No significant correlation was obtained
between the continuous variable urinary calcium level
(24 hour urine) and serum levels of vitamin D in
current study (Spearman correlation test) (p=0.053)
(Figure I).
Considering the correlation between vitamin D
serum levels and the continuous variable pulmonary
106 Kiani et al.: Vitamin D associates with sarcoidosis features
Table I Vitamin 25(OH)D level (nmol/L) and course of sar-
coidosis.
25(OH)D
To t a l
Course of
sarcoidosis 25(OH)D>50 25(OH)D>50
47 29 (72.5%) 18 (45.0%) Acute
33 11 (27.5%) 22 (55.0%) Chronic
80 40 40 To t a l
1000.00 57
26
*
800.00
600.00
400.00
VCa24Hr
Vitamin D – Sufficient Vitamin D – Deficient
vitd_cat
.00
200.00
Figure 1 24 hr. urine calcium level (mg/24hrs) box plot
based on level of vitamin D.
J Med Biochem 2018; 37 (2) 107
function FEV1 and FVC, no statistically significant
correlation was obtained in current study (Spearman
correlation test) (p=0.289, p=0.084). However, FVC
in patients with vitamin D levels above 50 nmol/L
included a mean of 340 mL higher than patients with
50 nmol/L serum vitamin 25(OH)D. In this case
FEV1was 220 mL higher. Nevertheless, no statistically
significant differences was obtained between the vol-
umes of FEV1 and FVC in patients with vitamin D lev-
els above 50 nmol/L and the patients with serum vita-
min 25(OH)D 50 nmol/L.
Discussion
Ever since the first study was tested on the rela-
tionship between chronic respiratory diseases and
vitamin D as a regulatory factor, many studies were
conducted worldwide on this issue (23). But, the
association of vitamin D deficiency with different fea-
tures of sarcoidosis is not still well-studied (1). The
purpose of this study was to investigate the relation
between vitamin 25(OH)D serum level with Course of
sarcoidosis, Status of Pulmonary function, Skin extra-
pulmonary involvement, Lung involvement stage and
Disease activity among sarcoidosis cases of Iran.
The highest annual incidence of sarcoidosis is
found in northern Europe with 5–40 cases per
100,000 people (8, 22). Sarcoidosis incidence in Iran
is not obvious. Based on the registry organization of
Iranian Sarcoidosis patients in Referral Masih danesh-
vari hospital, Tehran, the incidence of sarcoidosis in
Iran is almost 1–2 cases per 100,000 people. Vitamin
D deficiency is considered playing an important role
in sarcoidosis development (23). In people living in
regions with far areas from the Equator, lack of sun-
exposure leads to vitamin D deficiency. Vitamin D
deficiency and chronic course of sarcoidosis occur
with a higher incidence in dark-pigmented individuals
and African-Americans living in the Southern United
States (2, 8). Iran is a country with low latitude (32°
00' N) and white skinned population. This confirms
higher incidence of acute course of sarcoidosis
among the studied patients.
The diagnosis of majority of our sarcoidosis
patients was established in May, however, on average,
patients are involved for over 3 months before diag-
nosis. Due to poverty, many Iranian patients postpone
visiting health care providers. Duration of sarcoidosis
diagnosis is there for extended in Iran. Based on this,
we may conclude that sarcoidosis occurred in our
patients in January to February, when vitamin D
serum levels are insufficient.
Study of vitamin D was tested on 25(OH)D
serum level in our study. Current study design was
based on earlier studies represented that free
25(OH)D showed higher correlation with the actual
vitamin D deficient states than 25(OH)D (23). Similar
to some earlier studies, female patients were predom-
inant sex group and most of patients belonged to the
age group 40–50 (n=48, 60%) (1, 20). Joint mani-
festations proportion were higher than previous
reports (14%–36%) (24). In current study 87.2% of
patients with a diagnosis of Lofgren's syndrome
showed joint manifestations under the study by
Moore (80%) (24).
With correlation between the stage of the lung
disease and parenchymal lung involvement with the
low levels of vitamin 25(OH)D, statistical significant
associations were detected (p=0.039). This is at odd
with a former study which studied 226 sarcoidosis
patients with no correlation found between stage of the
lung disease and vitamin 25(OH)D serum levels (1).
This variation may be due to different studied popula-
tions in two studies. 226 studied patients in mentioned
study were Serbians with a high incidence of chronic
course of sarcoidosis and high prevalence of vitamin D
deficiency on the basis of long latitude of their country.
Current study showed that existence of respira-
tory involvements of stage 0 –1 is not correlated with
vitamin D deficiency in sarcoidosis patients. A signifi-
cant negative correlation was detected between
stages 2–4 of lung involvements in sarcoidosis
patients with 25(OH)D deficiency. This shows that
Vitamin D deficiency has an important immune mod-
ulatory impression on lung impairments in a sar-
coidosis patient.
Current study results showed that sarcoidosis
patients with acute course of disease possessed high-
er level of vitamin D serum level comparing to the sar-
coidosis patients with chronic course of disease. So,
results of the current study implies in the role of vita-
min 25(OH)D deficiencies in leading the course of
sarcoidosis to chronicity. This confirmed an earlier
study on 25(OH)D deficiencies correlation with
course of chronic sarcoidosis and data from 86 sar-
coidosis patients with 29.5% of acute patients with
25(OH)D deficiency and 64.2% of chronic patients
with 25(OH)D deficiencies (5).
Results of current study on pulmonary function-
ing statues were following an earlier study (1, 6). This
implies in that 25(OH)D deficiencies may have rela-
tion with pulmonary function reduction (FVC). Since
this issue was not showed in current study, future
studies on this field are recommended.
As showed earlier, hypercalcemia and hypercal-
ciuria occur in 10% and 30% of the sarcoidosis
patients (13, 14, 25). In current study, Absolute vita-
min 25(OH)D deficiencies were recognized in
patients with hypercalciuria. Hence, we suggest that
active sarcoidosis occurs in patients with deficient
serum level of vitamin 25(OH)D. Our study confirms
an earlier work which showed that 25(OH)D deficien-
cies was a potential risk factor in emerging active type
of sarcoidosis (1). Patients with hypercalciuria are rec-
ommended avoiding the sunlight and consuming
supplementations of vitamin D. We monitor urine cal-
cium level of sarcoidosis patients to prevent renal fail-
ure in the patients.
Current study was tested on a sample size of
patients that can affect the generalization of the
results.
Conclusion
In conclusion, results of the current study
implies in the role of vitamin 25(OH)D deficiencies in
predicting the course of chronic sarcoidosis. Vitamin
25) OH) D deficiency can lead the stage of lung
involvement in pulmonary sarcoidosis toward stage 2-
4. But, since no correlations between vitamin
25(OH)D deficiency and calcium level in urine (dis-
ease activity) or pulmonary function status were
observed, further researches in these fields are rec-
ommended.
Acknowledgment. Authors would like to thank
all the hospital cooperators for their favor in conduct-
ing current study. The authors declare no conflict of
interests.
Footnotes
Author contributions
Literature search: Arda Kiani, Atefeh Abedini,
Kimia Taghavi, Maryam mienayat, Mehdi Kazem -
pour-Dizaji, Ian M. Adcock, Esmaeil Mortaz
Data collection: Arda Kiani, Atefeh Abedini,
Maryam mienayat
Study design: Arda Kiani, Atefeh Abedini, Kimia
Taghavi, Maryam mienayat, Mehdi Kazempour-Dizaji,
Ian M. Adcock, Esmaeil Mortaz
Data analysis: Kimia Taghavi, Mehdi Kazem -
pour-Dizaji
Manuscript preparation: Atefeh Abedini, Kimia
Taghavi, Ian M. Adcock
Manuscript review: Arda Kiani, Atefeh Abedini,
Kimia Taghavi, Maryam mienayat, Mehdi Kazem -
pour-Dizaji, Ian M. Adcock, Esmaeil Mortaz
Author declaration
Authors certify that the manuscript represents a
valid work and neither this manuscript nor one with
substantially similar content under named authorship
has been published or is being considered for publi-
cation elsewhere. The study was performed at the
Masih Daneshvari referral respiratory hospital of Teh -
ran, Iran. Authors have participated in the research
and the shaping of the manuscript.
Conflict of interests
Authors have no conflicts of interest to declare.
Authors give consent to submission and publication
of the work. Authors disclose no relationship to any
organization or industrial manufacture in any material
of discussed.
108 Kiani et al.: Vitamin D associates with sarcoidosis features
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Received: May 29, 2017
Accepted: July 28, 2017
... Саркоидоз. Обследование 80 больных, страдающих острым и хроническим саркоидозом с дефицитом ВD, показало, что он может быть предиктором течения хронических форм, но не острого саркоидоза, а также ухудшения поражения легких до 2-4 стадий [55]. У пациентов с саркоидозом происходит неконтролируемая конверсия кальцидиола в кальцитриол активированными макрофагами (эпителиоидными клетками) в гранулемах [5]. ...
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... The FAS questionnaire is a one-dimensional scale for fatigue testing and consists of 10 statements, of which five examine physical fatigue and the other five examine mental health. The intensity of fatigue, presented by the total score, is between 10 and 50 (20,21). The FAS includes 10 statements with 5 options, ranging between "1 = never" and "5 = always." ...
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... In a descriptive study by Kiani et al., who reported on 81 sarcoidosis patients with deficient and insufficient vitamin D serum values reported a significant negative correlation (r = 4.22, P = 0.039) between vitamin D deficiency and chronic disease progression. 67 In a small study conducted by the current authors we report on 36 patients with ILD/IPF of which 34% had insufficient or deficit 25(OH)D levels using the Endocrine Society Clinical Practice Guidelines 68 and 90% were not meeting their Dietary Recommended Intakes for vitamin D (unpublished data). We were unable to report any significant association between vitamin D intake and serum levels likely due to the low sample size. ...
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... Vitamin D is a secosteroid hormone (1) with the essential role of maintaining Ca and phosphorus homoeostasis to support bone metabolism (2) . Furthermore, vitamin D also has important functions in the intestine (3) , kidney (4) , brain (5) , lung (6) and immune system (7) , due to the widespread distribution of the vitamin D receptor (8) . ...
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Sarcoidosis is a systemic inflammatory disease of unknown etiology. The pathogenesis rests on an aberrant T cell response to unidentified antigens in individuals predisposed by genetic and environmental factors. Increased expression of polarized macrophages and disequilibrium between effector and regulator T cells contribute to the formation of noncaseating granulomas, that are frequently found in affected organs. The main kidney abnormalities in sarcoidosis are granulomatous interstitial nephritis (GIN) and hypercalcemia-related disorders. The clinical diagnosis is difficult. The outcome is variable, ranging from spontaneous remission to end-stage kidney disease (ESKD). Early diagnosis and prompt treatment with corticosteroids can improve the prognosis. Hypercalcemia may be responsible for acute kidney injury (AKI) caused by vasoconstriction of afferent arterioles. Complications of persistent hypercalcemia include nephrocalcinosis and renal stones. In patients with ESKD, dialysis and transplantation can offer results comparable to those observed in patients with other causes of kidney failure. Based on a review of the literature, we present an overview of the etiopathogenesis, the renal manifestations of sarcoidosis and their complications, management and prognosis.
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Background: Accelerated aging and telomere shortening have been studied in many chronic diseases such as interstitial pulmonary fibrosis and chronic obstructive pulmonary disease. Different studies have shown that patients with these diseases have shorter telomere lengths than controls; this can be a marker of the progression and outcome of the disease. So far, a few studies have been evaluated the telomere length in sarcoidosis. In this study we determine the telomere length in patients with sarcoidosis and compare it with control subjects. Objective: Our aim is to compare telomere length in patients with sarcoidosis and normal population. Methods: We select 58 patients with sarcoidosis who were visited in the sarcoidosis clinic of Masih Daneshvari Hospital. 58 sex and age-matched (with±2 years) healthy control subjects were selected. Telomere length was measured by quantitative real time PCR as described by Cawthon on peripheral blood sample. The telomere repeat copy number (T) to single-gene copy number(S) ratio was calculated using the comparative Ct method. Results: The mean and standard deviation of telomere length in the patient and control group was 0.65 ± 0.05 and 0.72 ± 0.07 respectively. There was a statistically significant difference between the two groups. (P = 0.031). Conclusion: Sarcoidosis is an inflammatory disease that can involve many organs. Like other chronic diseases, aging phenomenon occurs in that; which led to decrease cellular and tissue telomere length. This article demonstrates shorter telomere length in Iranian sarcoidosis patients compared to normal population.
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Background: The aim was to evaluate the association of plasma 25-hydroxyvitamin D (25-OHD) and vitamin D binding protein (VDBP or Gc-globin) gene polymorphism with oxidant-antioxidant profiles in patients with chronic obstructive pulmonary disease (COPD), and their role as biomarker risk factors in susceptibility and severity of COPD. Methods: Eighty patients diagnosed with COPD (mild, moderate and severe according to lung function tests; FEV 1%) and 80 healthy controls were included in the study. Serum nitric oxide (NO) and lipid peroxide (LP), plasma reduced glutathione (RGSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity, 25-OHD and VDBP polymorphism were analyzed in all subjects. Results: COPD patients had significantly decreased serum NO, plasma SOD, RGSH, GSH-Px, CAT and 25-OHD versus controls, but had significantly increased serum LP. In COPD patients, 25-OHD levels were significantly lower (41.49± 13.65 ng/mL) versus controls, but more lower in severe COPD patients (30.54±9.09 ng/mL; sensitivity 79.2%; spe - cificity 73.2%, p<0.001) versus mild and moderate COPD. VDBP genotypes frequencies were Gc1S-1S=23.8%, Gc1F1S=28.8%, Gc1F-1F=15%, Gc1S-2=20%, Gc1F-2=11.3% and Gc2-2=1.3%. Also, VDBP variants frequencies were Gc1S=48.1%, Gc1F=35% and Gc2=16.6%. How ever, Gc1F-1S genotypes and Gc1F variants were significantly higher than in controls (10%, 12.5%; p=0.009, p=0.001, respectively). Moreover, in severe COPD patients, Gc1F-1S genotype was significantly higher than in mild COPD (41.7% vs 31.3%, p=0.04). Conclusions: COPD patients had significantly lower plasma 25-OHD and were associated with significantly higher VDBP Gc1F-1S genotypes and Gc1F variants frequencies than controls. Low vitamin D levels and VDBP polymorphism may be important as diagnostic risk factors in the susceptibility to and severity of COPD.
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Background: Patients in countries endemic for chronic viral hepatitis are more vulnerable to antituberculosis therapy-induced liver disorders (ATT-LDs). The aim of this study was to explore the role of cholecalciferol in prophylaxis against ATT-LD among patients with pulmonary tuberculosis (TB) receiving ATT. Material and methods: We conducted a hospital-based, prospective, randomized, comparative study which included 300 consecutive, naïve patients with pulmonary TB eligible for ATT. The patients were randomly allocated to Group A (150 patients who received ATT) and Group B (150 patients who received ATT with cholecalciferol) who had clinical evaluation, laboratory investigations, and imaging studies. Statistical analysis used student's t-test and Chi-square test were used as appropriate to compare the variables between the study groups. Results: The study population mean age was 35.6 ± 15.3 years. The overall incidence rate of ATT-LD among the study population was 9.3%; the incidence rate was significantly higher among Group A patients compared to those of Group B (13.3 vs. 5.3%;P = 0.001). The onset of ATT-LD was significantly earlier among patients of Group A compared to those of Group B (31.4 vs. 58.7 days,P = 0.027), while the duration of ATT-LD was significantly longer among patients of Group A compared to those of Group B (34.8 vs. 16.9 days,P = 0.009). No adverse effects related to cholecalciferol use were observed. Conclusions: Adjuvant cholecalciferol supplementation may be protective against ATT-LD without extra adverse effects. Before recommending the routine use of cholecalciferol supplementation for prevention of ATT-LD, larger scale studies are recommended.
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Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Despite the availability of novel therapeutic approaches, TB is considered as one of the leading causes of death due to infectious diseases worldwide. Alveolar macrophages are the first line of defense against M. tuberculosis; they ingest and sequester the bacilli within granulomatous structures. Control and resolution of the infection requires activated T lymphocytes as well as Th1 cytokines. There are two forms of TB: active TB and latent TB. Latent TB is a state in which M. tuberculosis survives in the body without causing overt signs and symptoms. People with latent TB are noncontagious. However, M. tuberculosis can become active in the body, multiply, and cause overt TB. Sarcoidosis, on the other hand, is an autoimmune disease of unknown etiology which can affect multiple systems of the body. Nonspecific constitutional symptoms, such as fever, fatigue, malaise, and weight loss, are present in approximately one-third of patients. Chest X-ray usually shows hilar and mediastinal lymphadenopathy. Although the lungs are the most common sites of inflammation, sarcoidosis can also involve other organs, such as the eyes (intraocular and adnexal), skin, lymph nodes, salivary glands, heart, spleen, liver, and the nervous system. Recent investigations have provided further insights into the genetic basis of sarcoidosis and the way genotype determines the clinical presentation and phenotype of patients. Histopathologic features are usually insufficient for diagnosis of sarcoidosis. Diagnosis of sarcoidosis in endemic areas for TB can become a great challenge. Both TB and sarcoidosis are granulomatous diseases; TB is characterized by caseating granulomas, whereas sarcoidosis is characterized by noncaseating granulomas. New cases of sarcoidosis are increasingly being diagnosed in areas endemic for TB due to increased orientation of physicians and availability of diagnostic modalities. However, it is often difficult to differentiate sarcoidosis from TB, especially when caseous necrosis is not seen and acid-fast staining is negative in the biopsy specimen of patient with TB. Granulomatous inflammation in sarcoidosis is believed to be caused by the presence of a persistent poorly degradable unknown antigen in combination with a nonresolving host response. M. tuberculosis has been extensively studied as a possible cause of sarcoidosis. Results suggest that granulomas form in the lungs as a result of the immune response to inhaled M. tuberculosis and serve as the central site of host–pathogen interaction during M. tuberculosis infection. M. tuberculosis DNA detection in sarcoidosis samples by traditional polymerase chain reaction (PCR) has been used for the pathological study of sarcoidosis; however, it is likely that real time quantitative PCR analysis of specific mRNAs and microRNAs will be necessary as a sensitive, precise, and rapid diagnostic test for detecting trace of TB in Sarcoidosis. In conclusion, diagnosis of sarcoidosis in areas with a high burden of TB poses a significant challenge. Improved diagnostic tests including genetic tests can improve our knowledge and help in distinguishing these two diseases.
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Background and objectives: Sarcoidosis is an inflammatory disease that affects multiple organs including the muscles which may lead to physical intolerance. The 6 minute walking test (6MWT) is a method that is frequently used to assess physical capacity in these patients. The aim of this study is to investigate 6MWT results in sarcoidosis patients with different radiographic stages, medication therapy, and spirometric parameters. Materials and methods: We assessed 6MWD and oxygen desaturation as outcome measure of 6MWT in 71 sarcoidosis patients categorized into four groups according to Scadding criteria .we also compared 6MWD among 30 patients based on the medication therapy in three groups 1) prednisolone2) prednisolone plus methotrexate 3) hydroxychloroquine plus prednisolone). Also, correlation between 6MWD and spirometric parameters results including FEV1, FEV1/FVC were investigated in 24 patients. Results: There was statically significant correlation between oxygen desaturation and sarcoidosis severity; but, in spite of finding a tendency in more severe sarcoidosis stages to walk shorter distance the correlation between 6MWD and sarcoidosis severity was not significant. In exploring 6MWD among different medication groups it turned out that patients who were taking methotrexate and prednisolone tended to walk shorter distance in comparison to patients were taking prednisolone alone. Conclusion: Oxygen desaturation during 6MWT is another measure outcome of this test which would be recommended to be considered in assessing sarcoidosis severity. 6MWT can be considered not only to help assess sarcoidosis expansion in body but also help in better medication choose in these patients.
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Background Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme – ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls. Methods Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis. Results Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of .5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on ¹⁸F-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P < 0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (ρ =0.272, P =0.001). Conclusions Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.
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Cite this Article; Nasiri MJ, Varahram M, Shams M, Taghavi K, Farnia P, Velayati AA. Osteoarticular Tuberculosis in Iran, 2002 to 2011. Advances in Research. 2014; 2(9): 509-504. OR; Nasiri MJ, Varahram M, Shams M, Taghavi K, Farnia P, Velayati AA. Osteoarticular Tuberculosis in Iran, 2002 to 2011. https://www.semanticscholar.org/paper/Osteoarticular-Tuberculosis-in-Iran-%2C-2002-to-2011-Nasiri-Varahram/9449c28b5dfc15511fb579a75d87e595a837d092 Keywords : Tuberculosis; osteoarticular; Iran.
Article
Background: Patients in countries endemic for chronic viral hepatitis are more vulnerable to antituberculosis therapy-induced liver disorders (ATT-LDs). The aim of this study was to explore the role of cholecalciferol in prophylaxis against ATT-LD among patients with pulmonary tuberculosis (TB) receiving ATT. Material and Methods: We conducted a hospital-based, prospective, randomized, comparative study which included 300 consecutive, naïve patients with pulmonary TB eligible for ATT. The patients were randomly allocated to Group A (150 patients who received ATT) and Group B (150 patients who received ATT with cholecalciferol) who had clinical evaluation, laboratory investigations, and imaging studies. Statistical analysis used student's t-Test and Chi-square test were used as appropriate to compare the variables between the study groups. Results: The study population mean age was 35.6 ± 15.3 years. The overall incidence rate of ATT-LD among the study population was 9.3%; the incidence rate was significantly higher among Group A patients compared to those of Group B (13.3 vs. 5.3%;P = 0.001). The onset of ATT-LD was significantly earlier among patients of Group A compared to those of Group B (31.4 vs. 58.7 days,P = 0.027), while the duration of ATT-LD was significantly longer among patients of Group A compared to those of Group B (34.8 vs. 16.9 days,P = 0.009). No adverse effects related to cholecalciferol use were observed. Conclusions: Adjuvant cholecalciferol supplementation may be protective against ATT-LD without extra adverse effects. Before recommending the routine use of cholecalciferol supplementation for prevention of ATT-LD, larger scale studies are recommended.