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\begin{document}

\title{THE EVALUATION OF LUNG INVOLVEMENT AND FUNCTIONAL CAPACITIES IN PAT\selectlanguage{polish}İ\selectlanguage{english}ENTS
D\selectlanguage{polish}İ\selectlanguage{english}AGNOSED WITH PRIMARY SJOGREN'S SYNDROME\selectlanguage{english}}



\author[1]{Tugce Sahin Ozdemirel}%
\author[2]{Ali Erhan Ozdemirel}%
\author[3]{Berna Akinci Ozyurek}%
\author[4]{Derya Yenibertiz}%
\author[5]{Yurdanur Erdogan}%
\affil[1]{Department of Chest Disease, University of Health Sciences Ankara Atatürk Chest Diseases and Chest Surgery Training and Research Hospital, Ankara-Turkey.}%
\affil[2]{Department of Rheumatology, University of Health Sciences, Gaziler Physical Therapy And Rehabilitation Training And Research Hospital, Ankara, Turkey}%
\affil[3]{Affiliation not available}%
\affil[4]{University of Health Sciences Keçiören Training and Research Hospital, Ankara-Turkey.}%
\affil[5]{Department of Chest Disease, University of Health Sciences, Atatürk Chest Diseases and Chest Surgery Training and Research Hospital, Ankara, Turkey}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
ABSTRACT Introduction: Sj\selectlanguage{ngerman}ögren syndrome is a chronic, systemic,
inflammatory disease characterized with lymphocytic infiltration of the
exocrine glands, frequently manifested by dryness in the region
affected. Although the most common extraglandular involvement in SS is
pulmonary involvement. Early diagnosis and treatment is considered to be
important. It was aimed to evaluate the frequency of early lung
involvement, high resolution computed tomography (HRCT) findings and
data of pulmonary function test (PFT) in SS in this study.
Material-Method: Thirty five patients diagnosed with SS and referred by
the Department of Rheumatology to determine potential lung involvement
to the 8th chest diseases outpatient clinic of our hospital between
September 2015 and December 2018 were included in this study.
Respiratory signs, demographic features, length of disease and treatment
regimens, PFT, data of 6-minute walk test (MWT) and findings of HRCT of
the patients were retrospectively obtained from hospital information
system and patient files. Results: The mean age of the patients was 54.4
± 9.2. The majority of the patients were women (94.3\%). When the HRCT
findings were evaluated, 28 (80\%) patients had CT findings, while 7
(20\%) patients had no CT findings. The most common HRCT findings found
in patients were peribronchial thickening (48.6 \%), ground glass
appearance (28.6\%) and prominence in interstitial scars. Conclusion: We
think that the evaluation of HRCT and PFTs in patients diagnosed with SS
for assessing early pulmonary involvement will be guiding in terms of
follow-up and treatment.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{INTRODUCTION}

Sjogren's syndrome (SS) is a chronic, systemic, inflammatory disease
characterized with lymphocytic infiltration of the exocrine glands,
frequently manifested by dryness in the region affected. Women are
mostly affected by it and it is seen between the ages of 40-50 (1,2).
Local involvement may be seen in salivary and lacrimal glands but it may
also cause systemic, extraglandular involvement (3).

Although the most common extraglandular involvement in SS is pulmonary
involvement; it is an under-researched disorder with important clinical
consequences. The prevalence of pulmonary involvement in SS patients has
been reported to be about 20\% (4). Pulmonary involvement in SS is in
the form of interstitial lung disease (ILD) and airway disease. While
patients are generally asymptomatic, the most common symptoms described
are dyspnea on exertion and cough. Dry cough is more common due to
decreased secretions in the airways. Due to drying of the secretions and
impaired clearance; bronchiectasis, bronchiolitis, pneumonia and small
airway obstruction can be observed. The disease is more mortal with
reduced quality of life in interstitial involvement and is one of the
independent risk factors for poor prognosis. Therefore, early diagnosis
and treatment is considered to be important (1).

Lung involvement is the main cause of mortality in patients with
systemic sclerosis and the development of interstitial lung involvement
in the first 3 years, i.e in the early period, is one of the poor
prognostic factors (5).

The course of lung involvement and the factors causing it, are not clear
as in systemic sclerosis. It is stated in the current literature that
although interstitial involvement may be seen as a late manifestation of
SS in SS patients, it may sometimes appear at the onset of the disease.
However, studies investigating early involvement and its effect on the
course are not adequate.

Therefore it was aimed to evaluate the frequency of early lung
involvement, HRCT findings and data of PFT in SS in this study.

\textbf{MATERIALS-METHODS}

Thirty five patients diagnosed with SS and referred by the Department of
Rheumatology to determine potential lung involvement to the 8th chest
diseases outpatient clinic of our hospital between September 2015 and
december 2018 were included in this study. Respiratory signs,
demographic features, length of disease and treatment regimens,
pulmonary function test (PFT), data of 6-minute walk test (MWT) and
findings of high resolution computed tomography (HRCT) of the patients
were retrospectively obtained from hospital information system and
patient files.

The diagnosis of SS was made according to the 2002 international
classification Criteria for SS and / or 2016 ACR / EULAR Classification
criteria when the hospital registration details was examined (6,7).

A clinical spirometer was used to conduct pulmonary function tests
(PFTs) (SensorMedics Vmax spectra 229, Bilthoven, The Netherlands).
Patients performed the maximal expiratory flow maneuver. Forced
expiratory volume at 1 second (FEV1), forced vital capacity (FVC),
maximum expiratory flow at 50\% of vital capacity (FEF25- 75\%) and DLCO
values were obtained and FEV1 / FVC was measured. According to the
previously defined guidelines, standard PFTs like spirometry and lung
volumes were examined (8).

The patients were classified into four groups according to their PFT :
obstructive (FEV1 / FVC \textless{}70\%), restrictive (FEV1 / FVC
\textless{}70\% and FVC \textless{}80\% and DLCO \textless{}80\%) and
small airway obstruction (FEF25-75\% \textless{}65\%) and normal (8).

6MWT is a technique that measures exercise capasity within six minutes
in individuals with chronic lung disease. The distance walked, initial
and final oxygen saturation, the changes in the heart rate and dyspnea
indoors within six minutes at a distance of 30 meters were recorded.

According to the HRCT findings, the patients were classified into two
groups as with or without CT findings, and the ground glass densities in
the lung parenchyma, consolidation, bronchiectasis, interstitial
thickening, peribronchial thickening, reticular appearance, and
honeycomb appearance were identified as positive findings.

\textbf{RESULTS}

The mean age of the patients was 54.4 \selectlanguage{ngerman}± 9.2. The majority of the
patients were women (94.3\%). Dyspnea (28.6 \%), effort dyspnea (22.9
\%) and dry cough (17.1 \%) were the most common clinical complaints of
patients at the time of admission.

Median diagnosis time was 74 months. When the medical treatments of the
patients were examined, Hydroxychloroquine (88.6\%) and Corticosteroid
(68.6\%) were the most common. Most of the patients (79\%) using steroid
were using prednisolone less than 10 mg or its equivalent. When the
comorbid lung diseases were investigated, 5 patients had asthma and 4
patients had chronic obstructive pulmonary disease (COPD) (11.4\%). The
general characteristics of the patients are shown in Table 1.

When the HRCT findings were evaluated, 28 (80\%) patients had CT
findings, while 7 (20\%) patients had no CT findings. Distribution of CT
findings; Peribronchial thickening in 17 (48.6\%) patients, ground glass
in 10 (28.6\%) patients, prominence in interstitial scars in 8 (22.9\%)
patients, bronchiectasis in 7 (20\%) patients, reticular appearance in 6
(17.1\%) patients, 5 (14.3\%) reticulonodular infiltration in the
patient, consolidation in 4 (11.4\%) patients, solitary nodule in 2
(5.7\%), mosaic perfusion in 2 (5.7\%), honeycomb appearance in 2
(5.7\%) patients, parenchymal band appearance in 1 (2.9\%) patient.

No significant difference was found when the data of PFT were evaluated
in patients with and without CT findings. Although DLCO values were not
statistically significant, lower values were found in patients with CT
findings (Table 2).

No statistically significant difference was observed between patients
with and without CT findings when we grouped the PFT data as normal,
obstructive, restrictive and small airway obstruction (p = 0.471, Table
3).

The relationship between the patients' age and duration of illness with
PFT parameters is shown in Table 4. According to this no statistically
significant difference was found between the duration of illness and PFT
results. On the other hand, the disparity between age and FEV1 (p
\textless{}0.001), FEV1\% (p = 0.011), FVC (p \textless{}0.001), FEV1 /
FVC (p = 0.005) and FEF25-75 (p = 0.046) was statistically significant.
In elderly patients at 6MWT, the walking distance was statistically
significantly shorter (p = 0.029).

When the CT outcomes were analyzed by dividing the duration of the
disease into the first 3 years and after; no significant difference was
found (Table 5).

\textbf{STATISTICAL ANALYSIS}

The Statistical Package for the Social Sciences (SPSS) version 21.0 was
used for the statistical analyses. The categorical variables are
presented as frequencies and percentages. The continuous variables were
assessed by Kolmogorov-Smirnov test and histograms to find out if their
distributions were normal or not. The normally distributed numerical
parameters were compared by student's t-test in two groups, while those
with non-normal distributions were analyzed by Mann-Whitney U test. The
categorical variables were compared by Chi-squares or Fisher's Exact
tests where appropriate. The strength of the relationship between the
two variables was carried out using Spearman's or Pearson correlation
coefficient. A p-value \textless{} 0.05 was considered as statistically
significant.

\textbf{DISCUSSION}

The most common pathological findings in pulmonary involvement of SS are
ILD and small airway defects. HRCT is the most sensitive diagnostic
method for the detection of noninvasive and early parenchymal injury
(9).

The number of studies evaluating the characteristic results of HRCT in
ILD due to primary SS is quite limited. The most common involvement
patterns among the HRCT findings in SS lung involvement are
peribronchial wall thickening, ground glass appearance, nodules and
bronchiectasis (10,11).

It has been reported in a study conducted by Dong et al.with 527
patients diagnosed with primary SS, that SS-related involvement is found
to be widespread and affects multiple anatomical structures (airways,
alveoli, vascular structures and pleura) and also it has been stated
that different histological patterns may be seen simultaneously such as
nonspecific interstitial pneumonia (NSIP), organized pneumonia (OP) and
the union of NSIP and usual interstitial pneumonia (UIP) (12).

In our study, the most common HRCT findings found in patients were
peribronchial thickening (48.6 \%), ground glass appearance (28.6\%) and
prominence in interstitial scars were, in accordance with the
literature.

We think that the absence of NSIP and OP patterns are due to the fact
that our patients were in the early phase of disease and they had mild
disease findings. Patients with ILD show restrictive functional
dysfunction. PFT data is also a tool used to diagnose this respiratory
disorder ( even in asymptomatic patients) in the early period (13).

Decreased FVC, FEV1 and DLCO in PFT are among the predicted findings.
However, the most important parameter among these is the decreased DLCO
levels that were detected in the early period, and it is associated with
the high mortality rate (13,14).

Although it was not possible to compare PFT results since there was no
control group in our study; there was a significant decrease in FEV1 and
FVC values in older SS patients. However, it was not possible to exclude
possible age-related changes in these patients. In studies carried out,
\selectlanguage{polish}İ\selectlanguage{english}t was detected that decreased DLCO is generally associated with
widespread involvement in HRCT (15).

In our study, while the DLCO value in patients with CT findings was
found to be lower, it was not statistically significant. Again, no
substantial difference was observed in our research when the patients
with and without CT findings were compared according to the PFT results.

The relatively younger age of our patients, shorter illness length and
limited involvement in HRCT findings may explain this circumstance. The
inability of PFT to detect early findings, especially in CT, was shown
to be similar to our outcome In the analysis of Palm et al.

While 85\% of the patients had HRCT findings in this study, only 15\% of
the patients were diagnosed with PFT alone (14).

6MWT is an exercise test used to assess exercise capacity and treatment
response in patients with chronic lung diseases such as chronic
obstructive pulmonary disease (COPD), interstitial fibrosis, pulmonary
arterial hypertension, and it has been used as a prognostic tool in
patients with heart failure and lung disease in recent years (16).

According to the American Thoracic Society guidelines, 6MWT is stated to
be a simple, low-cost, reproducible and easy-to-apply method (17).

Generally, there are studies evaluating pulmonary functional capacity in
conditions such as idiopathic pulmonary fibrosis and chronic obstructive
pulmonary disease (18-20).

However, there are not enough studies on 6MWT data for lung involvement
in SS. In our study, the lack of significant difference between 6MWT and
lung involvement supports the absence of diffuse pulmonary involvement.

The prevalence of pulmonary symptoms in primary SS patients is stated to
be between 9-25\%; in the literature consistent with our research
(12,21).

Dry cough and/or effort dyspnea are the most common among the clinical
findings. In a report, it was reported that symptoms were linked to the
underlying chronic respiratory conditions in 1/3 of the patients who had
clinical symptoms (21).

This rate was approximately \selectlanguage{ngerman}¼ in our study. It has been reported in the
literature that respiratory symptoms are observed in 10\% of patients
within 1 year after diagnosis, reaching 20\% in 5 years (4,12).

In our research, more than half of the patients had CT findings in the
first 3 years. However, its correlation with the clinic could not be
clearly evaluated because of the small number of patients. However,
these results show that, lung involvement in patients typically occurs
in the first years of the illness in line with the literature. In a
study, it was found that 15-20 \% of patients had chronic ILD outcomes
even before an overt connective tissue disease develops (22).

In another cohort study, it was demonstrated that 60\% of patients were
diagnosed with ILD before the diagnosis of SS in 60\% of patients (13).

It was stated in some research, that pulmonary findings did not have a
negative effect on prognosis. In the study of Davidson et al. involving
30 British patients, it was shown that after 10 years of follow-up,
pulmonary functions remained stable in most patients (23).

However, there are several studies contradicting these studies in the
literature. ILD is a poor prognostic factor in SS patients and the
cumulative mortality rate reaches 16\% in 5 years (14, 24,25).

In addition, in a study by Chen et al. high HRCT scores were found to be
an independent risk factor for mortality (9).

It is very important to determine the predictive factors of the disease
in the prevention and early treatment of pulmonary disease. Studies
investigating prognostic variables of lung involvement in SS are not
sufficient and the findings are contradictory. Although some studies
have shown that advanced age and long duration of the disease may be
associated with poor prognosis, publication is also available. There are
also researches that indicate that this relationship is not important
(26).

When the laboratory parameters are examined; Although it has been
reported that hypergammaglobulinemia, lymphopenia, rheumatoid factor
(RF) and anti Ro / La positivity may be predictive factors in lung
involvement, the results of the study are not statistically significant
(15).

In our study, the relationship of these parameters with pulmonary
involvement could not be investigated because the patients' laboratory
parameters were not analyzed in a single center and the findings of
certain patients were not available.

In researches investigating clinical results and lung involvement, it
was observed that the Reynoud syndrome was more prominent in patients
with lung involvement (14,27).

This situation can be interpreted as the development of ischemic process
depends on microangiopathy due to the initiation of ILD development.
Similarly, CT involvement was detected in 6 of 8 patients with the
Reynoud phenomenon in our study.

The treatment of primary SS pulmonary involvement is generally based on
clinical practice and no widely accepted algorithm is currently
available. The use of immunosuppressants such as Cyclophosphamide,
Azathioprine and high-dose steroids and biological agents such as
Rituxumab and Belimumab, along with symptomatic therapy, is used to
manage the treatment of these patients. The most common use in our
patients was hydroxychloroquine and / or low-dose steroid use.

This outcome indicates that there was no widespread intervention and no
associated symptoms in our patients.

Its retrospective nature, the limited number of patients, and the
inability to assess the relationship between autoantibodies and lung
involvement were the limitations of our research.

\textbf{CONCLUSION}

We think that the evaluation of HRCT and pulmonary function tests in
patients diagnosed with SS for assessing early pulmonary involvement
will be guiding in terms of follow-up and treatment.

\textbf{Funding sources} : All support for this study came from
institutional and departmental resources.

\textbf{Conflict of interest} : We declare that there is no conflict of
interest, in particular no financial funding potentially relevant to the
contents of manuscript

\textbf{TABLES}

\textbf{Table 1. Main characteristics of the participants}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Parameters}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Total (n=35)}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Without CT findings (n=7)}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{With CT findings (n=28)}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{p}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
54.4 \selectlanguage{ngerman}± 9.2\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
52.1 \selectlanguage{ngerman}± 8.4\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
55 \selectlanguage{ngerman}± 9.4\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.469\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Gender Female, n (\%) Male, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
33 (94.3) 2 (5.7)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
7 (100) 0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
26 (92.9) 2 (7.1)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.466\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Asthma, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (28.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (10.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.256\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
COPD, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (11.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.562\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
DM, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (8.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (10.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.365\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
HT, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
CRF, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (2.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.612\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
CAD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (2.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.612\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Hypothyroidism, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (5.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (7.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.466\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
RA\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (2.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.612\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Alergic rhinitis,n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (2.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.612\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
ILD, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (2.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.612\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Multiple Sclerosis, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (2.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.200\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Hydroxychloroquine, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
31 (88.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (57.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
27 (96.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.019}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Steroid, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
24 (68.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (71.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
19 (67.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.856\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
MTX, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (5.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (28.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.035}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Azathioprine, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8 (22.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (42.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (17.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.312\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Colchicine, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (5.7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (28.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.035}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Dry cough, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 (17.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (28.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.576\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Effort dyspnea, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8 (22.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (28.6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 (21.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.648\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Raynaud phenomenon, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8 (22,8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (28,5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 (21,4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.644\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Duration of illness, median (min-max)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
74 (1-180)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
80 (2-120)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
32 (1-180)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.214\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

COPD: Chronic obstructive lung disease, CAD: Coronary artery disease,
DM: diabetes mellitus, HT: hipertansion, CRD: Chronic renal disease, RA:
Rheumatoid arthritis, ILD: Interstitial lung disease, CT: computed
tomography

\textbf{Table 2: Comparison of functional parameters of patients with
and without CT findings}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Parameters} & \textbf{Total (n=35)} & \textbf{Without CT
findings (n=7)} & \textbf{With CT findings (n=28)} &
\textbf{p}\tabularnewline
\midrule
\endhead
FVC & 2.45 \selectlanguage{ngerman}± 0.9 & 2.44 \selectlanguage{ngerman}± 0.22 & 2.46 \selectlanguage{ngerman}± 0.59 & 0.945\tabularnewline
FVC \% & 91.87 \selectlanguage{ngerman}± 2.66 & 91.5 \selectlanguage{ngerman}± 7.09 & 91.96 \selectlanguage{ngerman}± 16.72 &
0.916\tabularnewline
FEV1 & 2.22 \selectlanguage{ngerman}± 0.9 & 2.09 \selectlanguage{ngerman}± 0.19 & 2.25 \selectlanguage{ngerman}± 0.54 & 0.255\tabularnewline
FEV1 \% & 90.51 \selectlanguage{ngerman}± 2.94 & 93.66 \selectlanguage{ngerman}± 6.37 & 89.81 \selectlanguage{ngerman}± 18.47 &
0.390\tabularnewline
FEV1/FVC \% & 82.12 \selectlanguage{ngerman}± 1.36 & 84.83 \selectlanguage{ngerman}± 6.04 & 81.51 \selectlanguage{ngerman}± 8.13 &
0.356\tabularnewline
Fef 25-75 \% & 67 (45-111) & 67 (64-84) & 67 (45-111) &
0.887\tabularnewline
DLCO & 94.16 \selectlanguage{ngerman}± 3.58 & 108.6 \selectlanguage{ngerman}± 12.70 & 91.28 \selectlanguage{ngerman}± 19.70 &
0.071\tabularnewline
6MWT, metre & 450 (60-570) & 450 (260-485) & 443 (60-570) &
0.549\tabularnewline
Pre-test Saturation & 97 (92-99) & 96 (93-99) & 97 (92-98) &
0.466\tabularnewline
Post-test Saturation & 96 (74-98) & 95 (89-98) & 97 (74-98) &
0.736\tabularnewline
Test time & 6 (2-6) & 6 (6-6) & 6 (2-6) & 0.372\tabularnewline
\bottomrule
\end{longtable}

FEV1: 1. Forced expiratory volume in 1 second, FVC: Forced vital
capasity, FEF: Forced expiratory flow rate, 6DYT: 6 minute walk test,
DLCO: diffusing capacity of the lungs for carbon monoxide, CT: computed
tomography

\textbf{Table 3: Evaluation of lung involvement in CT according to PFT
findings}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& Pulmonary function test & Pulmonary function test & Pulmonary function
test & Pulmonary function test &\tabularnewline
\midrule
\endhead
& Normal & SAO & Obstructive & Restrictive & p\tabularnewline
With CT findings, n (\%) & 16 (80) & 4 (66.7) & 3 (100) & 4 (100) &
0.471\tabularnewline
Without CT findings, n (\%) & 4 (20) & 2 33.3) & 0 (0) & 0 (0)
&\tabularnewline
\bottomrule
\end{longtable}

SAO: Small airway obstruction, CT: computed tomography, PFT: pulmonary
function test

\textbf{Tablo 4: Relationship between age, duration of disease and other
parameters}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& & \textbf{Age} & \textbf{Duration of illness} & \textbf{Duration of
illness} &\tabularnewline
\midrule
\endhead
Age & & & 0.156 & r & r\tabularnewline
& & & 0.372 & p-value & p-value\tabularnewline
Duration of illness & 0.156 & 0.156 & & r & r\tabularnewline
& 0.372 & 0.372 & & p-value & p-value\tabularnewline
FEV1 & \textbf{-0.609} & \textbf{-0.609} & -0.159 & r & r\tabularnewline
& \textbf{\textless{} 0.001} & \textbf{\textless{} 0.001} & 0.400 &
p-value & p-value\tabularnewline
FEV1 \% & \textbf{-0.438} & \textbf{-0.438} & -0.034 & -0.034 &
r\tabularnewline
& \textbf{0.011} & \textbf{0.011} & 0.851 & 0.851 &
p-value\tabularnewline
FVC & \textbf{-0.612} & \textbf{-0.612} & -0.230 & -0.230 &
r\tabularnewline
& \textbf{\textless{} 0.001} & \textbf{\textless{} 0.001} & 0.220 &
0.220 & p-value\tabularnewline
FVC \% & -0.297 & -0.297 & -0.113 & -0.113 & r\tabularnewline
& 0.094 & 0.094 & 0.532 & 0.532 & p-value\tabularnewline
DLCO & -0.347 & -0.347 & 0.028 & 0.028 & r\tabularnewline
& 0.060 & 0.060 & 0.883 & 0.883 & p-value\tabularnewline
Rate & \textbf{-0.474} & \textbf{-0.474} & -0.087 & -0.087 &
r\tabularnewline
& \textbf{0.005} & \textbf{0.005} & 0.631 & 0.631 &
p-value\tabularnewline
6MWT Distance & \textbf{-0.368} & \textbf{-0.368} & -0.076 & -0.076 &
r\tabularnewline
& \textbf{0.029} & \textbf{0.029} & 0.664 & 0.664 &
p-value\tabularnewline
Fef 25/75 & \textbf{-0.350} & \textbf{-0.350} & \textbf{-0.349} &
\textbf{-0.349} & r\tabularnewline
& \textbf{0.046} & \textbf{0.046} & \textbf{0.046} & \textbf{0.046} &
p-value\tabularnewline
6MWT Time & -0.185 & -0.185 & 0.007 & 0.007 & r\tabularnewline
& 0.288 & 0.288 & 0.970 & 0.970 & p-value\tabularnewline
\bottomrule
\end{longtable}

FEV1: 1. Forced expiratory volume in 1 second, FVC: Forced vital
capasity, FEF: Forced exspiratory flow rate, 6MWT: 6 minute walk test,
DLCO: diffusing capacity of the lungs for carbon monoxide

\textbf{Table 5: The relationship between duration of disease and HRCT
Findings,}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
With CT finding (n=28)\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
Without CT finding (n=7)\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
p\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
3 years and above n (\%) 3 years and below, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
12 (42.9) 16 (57.1)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
6 (85.7) 1 (14.3)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.088\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

CT: computed tomography

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\selectlanguage{english}
\FloatBarrier
\end{document}

