Clinical Rheumatology

https://doi.org/10.1007/s10067-019-04846-1

ORIGINAL ARTICLE

A retrospective study on the predictive implications of clinical

characteristics and therapeutic management in patients
with rheumatoid arthritis-associated interstitial lung disease
Luling Li 1 & Ran Liu 1 & Yongfeng Zhang 1 & Junfei Zhou 1 & Yifan Li 1 & Yuetong Xu 1 & Shuai Gao 2 & Yi Zheng 1

Received: 15 June 2019 / Revised: 8 October 2019 / Accepted: 4 November 2019

# International League of Associations for Rheumatology (ILAR) 2019

Abstract
Background Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is associated with significant morbidity and is a
critical cause of mortality in patients with RA.
Objective Our aim was to evaluate predictive and prognostic factors for RA-ILD and to describe the therapeutic management of
the condition from a large China cohort.
Methods This was a retrospective cohort study. We collected data of 1121 RA patients who underwent chest HRCT from 2008 to
2017. Patients without ILD at RA diagnosis were included in the analysis. The development and evolution of ILD in RA patients
were followed up. Determinants of ILD development and progression were identified through multivariable logistic analysis.
Cox hazards analysis was used to determine significant variables associated with survival.
Results A total of 923 patients without ILD at RA diagnosis were identified and enrolled. Among them, 278 cases (30.12%) were
diagnosed as ILD during follow-up. Logistic regression analysis showed that advanced age (> 60 years old) at RA onset (OR:
1.485), male (OR: 1.882), short duration of RA (0~5 years) (OR: 2.099), RF positive (OR: 1.728), elevated lactate dehydrogenase
(LDH) (OR: 3.032), and no medication (OR: 1.833) were closely correlated to the development of RA-ILD. No correlation was
found between ILD development and traditional DMARDs such as methotrexate and leflunomide. According to the follow-up
data, 83 RA-ILD patients were identified as interstitial lung disease (ILD) progression, and 102 participants were stable. Logistic
regression modeling demonstrated that DLCO% < 45% (OR: 3.025) and UIP possible pattern on HRCT (OR: 3.476) were
independent risk factors for the ILD progression. No correlation was found between ILD progression and traditional DMARDs
such as methotrexate and leflunomide. A total of 53 RA-ILD deaths occurred during follow-up. Cox hazards analysis revealed
that advanced age (> 60 years old) at RA-ILD diagnosis (HR: 3.181) and extensive lung involvement on HRCT (HR: 2.401) were
associated with worse survival. Treatment with cyclophosphamide (HR: 0.210) was associated with better survival.
Conclusions Advanced age, male, short duration of RA, RF positive, elevated LDH, and no medication are closely correlated
with RA-ILD. No correlation was found between traditional DMARDs and ILD development. DLCO% < 45% and UIP possible
pattern are predictive factors for ILD progression. No correlation was found between traditional DMARDs and ILD progression.
Advanced age and extensive lung involvement on HRCT independently predict mortality; cyclophosphamide treatment helps to
improve the prognosis of RA-ILD.
Key points 1. We designed this study to investigate the predictive and prognostic factors for RA-ILD and to explore the potential
role of DMARDs in the evolution of RA-ILD from the development to progression and death.2. Patients without ILD at RA
diagnosis were enrolled and followed up retrospectively. 3. Our results showed that no correlation was found between traditional
DMARDs and the development and progression of ILD, and regular treatment may improve the development of RA-ILD. 4. Our
results revealed that clinical variables appeared predictive implications for the diagnosis of ILD and physiological and radiolog-
ical variables appeared predictive implications for the prognosis of ILD, which can provide reference to rheumatologists and help
to improve poor prognosis of RA-ILD.

* Yi Zheng
scicyfs@sina.com

1
Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
2
Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

Keywords Clinical characteristics . Interstitial lung disease . Rheumatoid arthritis . Therapeutic management
Introduction
Rheumatoid arthritis (RA) is a chronic, systemic, inflammato-
ry disease, and pulmonary involvement is common [1].
Interstitial lung disease (ILD) is the primary pulmonary man-
ifestation of RA [2, 3]. The most common symptoms associ-
ated with RA-ILD are dry cough and dyspnea on exertion, and
a physical examination may reveal inspiratory crackles. ILD is
the commonest pulmonary cause of death in RA and a signif-
icant contributor to morbidity [4, 5]. As much RA-ILD is
subclinical and progression varied, the significance of abnor-
malities is not clear, and in the absence of validated prognostic
indicators, it presents a challenge to clinicians [6]. Moreover,
the use of disease-modifying antirheumatic drugs (DMARDs)
in RA-ILD is controversial, because of reports of drug-related
lung toxicity and possible exacerbation of underlying ILD [7,
8].
In view of high morbidity, mortality, and drug-related
reactions in RA-ILD, we designed this study which
aimed to screen out predictive indicators and focused
on the potential impact of DMARDs on ILD. In our
cohort, we included patients without ILD at RA diagno-
sis and followed up clinically. We observed the evolu-
tion of ILD in these patients from development to dis-
ease progression and death, with the investigation of
symptoms and structural and functional abnormalities
in terms of both presence, severity, and change over
time. Our results will help to better recognize RA-
ILD, as well as provide important information on ther-
apeutic strategies.
Materials and methods
Patients
We performed a retrospective cohort study involving pa-
tients who received medical care at Beijing Chaoyang
Hospital, Capital Medical University. The patients were
enrolled in our study consecutively from May 2008 to
October 2017. The inclusion criterion for RA in this study
was the fulfillment of 1987 ACR or 2010 ACR/EULAR
classification criteria for RA [9, 10]. Exclusion criteria
were other autoimmune or infectious diseases, neoplasm,
lung surgery, and other respiratory diseases. Taking lung
high-resolution CT (HRCT) results into consideration, a
work group which included experienced rheumatologists
and radiologists comprehensively assessed the absence/
presence of RA-ILD. Of 1121 consecutive RA patients
Clin Rheumatol
who completed chest HRCT, 101 patients with ILD before
or meantime to RA onset were excluded; 97 patients
could not be contacted. Finally, 923 patients without
ILD at RA diagnosis were included (Fig. 1). Follow-up
of those 923 patients was finished, but not all test or
examination results were available. The research received
ethical approval from Ethics Committee in Beijing
Chaoyang Hospital, Capital Medical University, and the
principles of the Declaration of Helsinki were followed
throughout the study.
The medical records of the cases were obtained from
the medical record database. Demographic characteris-
tics, clinical features, inspection, test data, and the ther-
apeutic management were extracted from the database.
RF and anti-CCP antibody high titer positive were de-
fined as a threefold increase in titer greater than normal
[11].Anti-CCP was quantified by ELISA using commer-
cial kits (Euro Diagnostica, Sweden). No medication
was defined as neither glucocorticoid nor DMARDs (in-
cluding methotrexate, leflunomide, tripterygium,
hydroxychloroquine, salazosulfapyridine, TNF inhibitors,
and so on) which were taken before the endpoint of the
study. Irregular medication was defined as glucocorti-
coid and/or DMARDs taken under doctors’ advice for
less than 3 months. Drugs only regularly taken under
doctors’ advice for more than 3 months were incorpo-
rated into the analysis of treatment. In the tables of this
manuscript, csDMARDs refer to conventional synthetic
DMARDs except for methotrexate and leflunomide.
The predefined endpoints of the present study were
RA-ILD development, progression, and mortality. RA-
ILD development referred to the occurrence of ILD in
RA patients. In this first section, RA duration (measured
in month) was calculated from the date of the first onset
of RA to either the date of ILD development (RA-ILD
patients) or the date of the latest follow-up (RA-N-ILD
patients).
ILD progression was defined as meeting any of the
following: a decrease of forced vital capacity (FVC) >
10% or diffusion capacity of the lung for carbon mon-
oxide (DLCO) > 15% predicted and worsening of ILD
score or death from respiratory failure due to ILD and/
or pneumonia; lung stable was defined as not meeting
the above conditions [12, 13]. Pulmonary function test
and HRCT data were collected at the time of baseline
and at the latest follow-up.
Survival time (measured in month) was calculated
from the date of the first diagnosis of RA-ILD to either
the date of death or the date of the latest updated date
Clin Rheumatol
Fig. 1 Study flow diagram
(October 2018). In the sections of RA-ILD progression
and mortality, RA duration was calculated from the date
of the first onset of RA to the date of the latest follow-
up.
Pulmonary function tests and HRCT
Pulmonary function tests were performed according to
American Thoracic Society standards/European Respiratory
Society guidelines [14], using MasterScreen PFT System
(JAEGER, Germany). We collected the data on baseline
FVC and DLCO, which were both expressed as a percentage
of predicted values. In the univariate analysis, the cutoff
values of FVC and DLCO were defined as 70% and 45%
[15, 16].
All patients had completed HRCT imaging scan of the
chest, using 1~2 mm thickness cuts. The HRCT scans were
performed during end inspiration in the supine positions, and
those images were evaluated in a blinded manner by two ex-
perienced radiologists. Disagreements regarding HRCT inter-
pretation were resolved by a consensus between both
radiologists.
HRCT results were analyzed for both ILD subtypes and
extent of lung involvement [17]. According to the new guide-
lines of American Thoracic Society, HRCT patterns were clas-
sified into usual interstitial pneumonia (UIP) pattern, nonspe-
cific interstitial pneumonia (NSIP) pattern, organized pneu-
monia (OP) pattern, and lymphocytic interstitial pneumonia
(LIP) pattern. UIP pattern of CT-based certainty was further
classified into definite UIP, possible UIP [18]. Cellular NSIP
(c-NSIP) and fibrotic NSIP (f-NSIP) were evaluated as de-
scribed by Travis [19]. Definite UIP pattern: subpleural and
basal predominance, reticular opacities, and honeycombing
with or without traction bronchiectasis; possible UIP pattern:
based on the same criteria, but with honeycombing being ab-
sent; cellular NSIP pattern: on the basis of NSIP characteris-
tics, a fine reticular pattern was presented, but the dominant
finding was ground-glass opacity; fibrotic NSIP pattern:
superimposed ground-glass opacity within the reticular pat-
tern, and characteristic features of UIP (e.g., honeycombing)
were absent. We defined disease extent based on the percent-
age of lung involved as assessed by HRCT (< 10% = limited,
10~30% = moderate, > 30% = extensive) [15].
The ILD score of HRCT, including alveolitis score and
fibrosis score, was used to evaluate the severity and extent
of ground-glass opacity, reticular pattern, and honeycombing
in the six lung zones, with a maximum possible total score of
24 [20, 21]. ①Extent evaluation, a full chest was
nonanatomically divided into six zones (upper, middle, and
lower lung zones) by the levels of trachea carina and inferior
pulmonary vein. The extent of lung abnormalities was evalu-
ated visually for each lung zone, and the final percentage of
involvement was obtained by averaging the six zones and
scored by using a scale from 0 to 5, as follows: 0, absent; 1,
l to 10%; 2, 11 to 25%; 3, 26 to 50%; 4, 51 to 75%; and 5, 76
to 100%. ②Severity evaluation, the lung abnormalities con-
sidered in the score were rated from 1 to 5 according to sever-
ity: 1, ground-glass opacity; 3, reticular pattern; and 5,
honeycombing. The scores on the initial CT and follow-up
CT were both calculated and made comparison. Worsening

of ILD score was defined as the increase of the score on
follow-up CT.
Statistical analysis
Statistical analysis was performed using the SPSS 19.0. The
normal distribution data was expressed as the mean ± standard
deviation, and the non-normal distribution data was expressed
as the median (M) and the interquartile range (P25, P75).
Measurement data were analyzed by Student’s t test or
Wilcoxon signed-rank test. Categorical data were analyzed
by chi-square test or Fisher’s exact test. To identify indepen-
dent risk factors for ILD development and progression, mul-
tivariate logistic regression analyses were used. Survival was
evaluated using the Kaplan-Meier method and the log-rank
test according to the observation period. Cox hazards analysis
was used to determine significant variables associated with
survival. Any variables with a P value of < 0.2 on univariate
or bivariate analysis were included in multivariate analysis.
All P values < 0.05 were considered statistically significant.
Results
Patient characteristics
Totally, 923 RA patients without ILD at baseline were includ-
ed in this study cohort. Two hundred fifty-three patients
(27.41%) were males; 240 patients (26.00%) had a history
of smoking. The mean age of RA onset was 52.62 ± 14.95
years, ranging from 17 to 89 years.
The median disease duration of 923 RA patients was 72
months (range 1~ 600 months). During the follow-up period,
278 cases (30.12%) had developed ILD and 645 cases
(69.88%) had no ILD. The median ILD duration was 36
months (range 1~ 480 months). One hundred sixty-five cases
(59.35%) had ILD within 5 years of RA onset, and 209 cases
(75.18%) had ILD within 10 years of RA onset.
One RA patient had been diagnosed as drug-induced ILD.
She was a 56-year-old female patient, complained of progres-
sive shortness of breath during DMARDs medication. HRCT
revealed diffuse patchy opacity after treatment with LEF for 3
months in August 2013 and multiple ground-glass opacity
after treatment with MTX for 3 months in November 2014.
And the clinical and radiological conditions were strongly
improved after cessation of MTX/LEF and treatment with
glucocorticoid (1 mg/kg/d oral administration). This case of
drug-induced lung injury, as part of RA-ILD, was included
into the overall RA-ILD group.
One hundred nine RA-ILD patients (39.21%) showed re-
spiratory symptoms, of which shortness of breath was most
frequent (87/109, 79.82%). Usual interstitial pneumonia (UIP)
and nonspecific interstitial pneumonia (NSIP) patterns were
Clin Rheumatol
the common patterns of RA-ILD, accounting for 33.09% and
28.06%, respectively. Extent of lung involvement analysis
showed that limited was predominant (147/278, 52.88%),
with smaller numbers of moderate (70/278, 25.18%) and ex-
tensive (61/278, 21.94%) lung involvement. Only 143 pa-
tients had baseline pulmonary function test results, and 9 pa-
tients were unable to perform spirometry. The average FVC%
was 85.69 ± 22.77%, and DLCO% was 56.24 ± 21.13%.
The median observation period of 278 RA-ILD patients
was 51 months (range 1~ 480 months). The 3-year survival
rate was 89.21%, and the 5-year survival rate was 83.45%.
During the follow-up period, 53 patients died, 7 (13.21%) died
within 1 year after diagnosis, and 30 (56.60%) died within 3
years after diagnosis. Among the 53 deaths, 41 cases died in
the ILD progressive group, 7 cases died in the stable lung
group, and 5 cases could not be grouped. The reason these 5
patients that were not grouped was that there was no full
follow-up data in our center except the death information
through the telephone follow-up, so the pulmonary condition
could not be evaluated. Causes of death for the progressive
group were respiratory failure due to ILD and/or pneumonia.
And causes of death for the other 12 patients (stable lung
patients and non-grouped patients) included malignancies (2
cases with lung cancer and 3 cases with extrapulmonary can-
cer), cerebrovascular events (3 cases), cardiovascular events
(2 cases), gastrointestinal bleeding (1 case), and aortic dissec-
tion rupture (1 case).
Risk factors for the development of RA-ILD
Compared with the RA without ILD development (RA-N-
ILD) group, the mean ages of RA onset, the rate of advanced
age (> 60 years old), males, and smoking were higher, while
the RA duration was shorter in the RA with ILD development
(RA-ILD) group (P < 0.01). The absolute value of ESR, C-
reactive protein, and serum lactate dehydrogenase (LDH), and
the rate of LDH positive and RF positive was higher in the
RA-ILD group (P < 0.05 ) (Table 1).
The medication status and DMARDs/GC prescription pat-
terns of 923 RA patients were shown in Table 2. The rate of no
medication was higher, and the rate of irregular medication
was lower in RA-ILD group (P < 0.05). No significant differ-
ence was found for the usage of GC and DMARDs including
methotrexate (MTX), leflunomide (LEF), tripterygium,
hydroxychloroquine (HCQ), salazosulfapyridine (SASP),
and tumor necrosis factor inhibitor (TNFi) (P > 0.05). MTX
was administered orally in all RA patients, and MTX duration
was shorter in RA-ILD patients (P < 0.05) (Table 2).
With regard to the prescription patterns, most RA patients
(> 90%) had received combination therapy. Only 3.14% of
patients received MTX monotherapy, and 3.03% of patients
received LEF monotherapy. There was no significant differ-
ence in MTX monotherapy, LEF monotherapy, MTX
Clin Rheumatol

Table 1 Clinical manifestations and laboratory test results in patients of RA-ILD and RA-N-ILD

RA-ILD(n = 278) RA-N-ILD(n = 645) P value

Clinical manifestations
Age at RA onset (years) 57.41 ± 13.84 50.55 ± 14.95 0.000
Advanced age (> 60 years old) 115 (41.37%) 174 (26.98%) 0.000
Male patients 108 (38.85%) 145 (22.48%) 0.000
Ever smoker 106 (38.13%) 134 (20.78%) 0.000
RA duration (months) 36 (10, 118) 86 (36, 184) 0.000
DAS28 5.10 (3.45, 6.52) 4.79 (3.29, 6.08) 0.066
Laboratory test
ESR (mm/h) 43 (26, 61) 38 (23, 60) 0.022
CRP (mg/dl) 2.36 (0.81, 6.79) 1.85 (0.72, 5.28) 0.031
RF titer (IU/ml) 119.5 (20, 449.5) 89.7 (18.3, 324) 0.082
RF positive 230/270 (85.19%) 440/566 (77.74%) 0.012
RF high titer positive 197/270 (72.96%) 376/566 (66.43%) 0.057
Anti-CCP antibody titer (IU/ml) 526 (107.34, 1143) 484.73 (54.28, 1129.29) 0.261
Anti-CCP antibody positive 221/270 (81.85%) 427/543 (78.64%) 0.243
Anti-CCP antibody high titer positive 210/270 (77.78 %) 392/543 (72.19%) 0.093
ANA positive 134/261 (51.34%) 261/552 (47.28%) 0.370
Globulin (g/L) 35 (30.55, 40.45) 34.6 (29.8, 39.5) 0.286
LDH (U/L) 183 (115, 217) 168 (145, 198) 0.000
Elevated LDH 49/267 (18.35%) 52/593 (8.77%) 0.000

RA-ILD RA with ILD development, RA-N-ILD RA without ILD development, DAS disease activity score, RF rheumatoid factor, Anti-CCP antibody
anti-cyclic citrullinated peptide antibody, ANA antinuclear antibody, LDH lactate dehydrogenase

combined with LEF, and MTX and/or LEF combined with
csDMARDs or TNFi between the two groups (Table 2).
Variables with a P value of < 0.2 in univariate analysis were
included in logistic regression model. Considering that treat-
ment with LEF may be related to the development of ILD, so
this factor was also included in the model. Logistic regression
analysis showed that advanced age (OR: 1.485), male (OR:
1.882), short duration of RA (0~5 years) (OR: 2.099), RF
positive (OR: 1.728), elevated LDH (OR: 3.032), and no med-
ication (OR: 1.833) were closely correlated to RA-ILD devel-
opment. No correlation was found between treatments with
MTX, LEF, TNFi, csDMARDs, and ILD development
(Table 3).
Risk factors for the progression of RA-ILD
Due to the lack of data on lung HRCT and pulmonary function
test during the follow-up period, some patients could not be
evaluated. Finally, a total of 83 RA-ILD patients were identi-
fied as ILD progression, and 102 cases were stable. On uni-
variate analysis, advanced age (> 60 years old) at RA-ILD
diagnosis, anti-CCP antibody high titer positive, DLCO % <
45%, possible UIP pattern, c-NSIP pattern, and high fibrosis
score on HRCT were associated with ILD progression in RA-
ILD patients (P < 0.05, Table 4).
The medication status and DMARDs/GC prescription
patterns of 185 RA-ILD patients were shown in
Table 5. The rates of no medication and irregular med-
ication were similar between the two groups with or
without ILD progression (P > 0.05). There was no sig-
nificant difference in the usage of GC and DMARDs
including MTX, LEF, tripterygium, HCQ, SASP, and
TNFi between the two groups (P > 0.05) and no sig-
nificant difference in the dosage and duration of MTX
between the two groups (P > 0.05).
With regard to the prescription patterns, most RA pa-
tients (> 90%) had received combination therapy. None
of the RA patients received MTX or cyclophosphamide
(CYC) monotherapy, only 2.7% of patients received LEF
monotherapy, and 3.78% of patients received GC mono-
therapy. There was no significant difference in drug
monotherapy and combination therapy (e.g., MTX and/
or LEF combined with CYC, csDMARDs, or TNFi) be-
tween the two groups (P > 0.05).
Variables with a P value of < 0.2 in univariate analysis were
included into logistic regression model. Logistic regression
analysis showed that DLCO% < 45% (OR: 3.025) and UIP
possible pattern on HRCT (OR: 3.476) were independent risk
factors for the ILD progression. No correlation was found
between MTX, LEF, csDMARDs, and ILD progression
(Table 6).
 Clin Rheumatol

Table 2 Treatment in patients of RA-ILD and RA-N-ILD

Treatment RA-ILD (n = 278) RA-N-ILD (n = 645) P value

No medication 98 (35.25%) 94 (14.57%) 0.000

Irregular medication 48 (17.27%) 161 (24.96%) 0.010
Drugs for RAa
GC 48 (17.27%) 140 (21.71%) 0.124
MTX 83 (29.86%) 233 (36.12%) 0.066
Dosage (mg/w) 10 (10, 10) 10 (10, 10) 0.190
Duration (months) 16 (9, 34) 36 (19, 66) 0.000
LEF 76 (27.34%) 200 (31.01%) 0.264
Tripterygium b 67 (24.10%) 162 (25.12%) 0.743
HCQ 56 (20.14%) 152 (25.57%) 0.254
SASP 13 (4.68%) 35 (5.43%) 0.638
TNFi 9 (3.24%) 41 (6.36%) 0.055
Prescription patterns
GC with no DMARDs 2 (0.72%) 16 (2.48%) 0.076
MTX 55 (19.78%) 143 (22.17%) 0.418
MTX monotherapy 5 (1.80%) 24 (3.72%) 0.125
MTX + GC 3 (1.08%) 11 (1.71%) 0.475
MTX + csDMARDs 33 (11.87%) 74 (11.47%) 0.863
MTX + csDMARDs + GC 13 (4.68%) 21 (3.26%) 0.426
MTX + TNFi 1 (0.36%) 4 (0.62%) 0.621
MTX + csDMARDs + TNFi 2 (0.72%) 9 (1.40%) 0.385
LEF 43 (15.47%) 110 (17.05%) 0.552
LEF monotherapy 5 (1.80%) 23 (3.57%) 0.151
LEF + GC 4 (1.44%) 11 (1.71%) 0.769
LEF + csDMARDs 23 (8.27%) 50 (7.75%) 0.725
LEF + csDMARDs + GC 10 (3.60%) 20 (3.10%) 0.696
LEF+ TNFi 0 (0%) 2 (0.31%) 0.353
LEF + csDMARDs + TNFi 1 (0.36%) 4 (0.62%) 0.621
MTX + LEF 22 (7.91%) 69 (10.70%) 0.193
MTX + LEF 3 (1.08%) 18 (2.79%) 0.110
MTX + LEF + GC 3 (1.08%) 5 (0.78%) 0.648
MTX + LEF + csDMARDs 9 (3.24%) 28 (4.34%) 0.433
MTX + LEF + csDMARDs + GC 4 (1.44%) 15 (2.33%) 0.384
MTX + LEF+ TNFi 3 (1.08%) 3 (0.47%) 0.287
MTX + LEF + csDMARDs + TNFi 0 (0%) 3 (0.47%) 0.255
Alternate use of MTX and LEF 4 (1.44%) 21 (3.26%) 0.119
MTX/LEF 0 (0%) 3 (0.47%) 0.255
MTX/LEF + GC 0 (0%) 3 (0.47%) 0.255
MTX/LEF + csDMARDs 4 (1.44%) 8 (1.24%) 0.807
MTX/LEF + csDMARDs + GC 0 (0%) 5 (0.78%) 0.141
MTX/LEF + TNFi 0 (0%) 1 (0.16%) 0.511
MTX/LEF + csDMARDs + TNFi 0 (0%) 1 (0.16%) 0.511
Others 6 (2.16%) 31 (4.81%) 0.060

aDrugs for RA refer to drugs regularly taken under doctors’ advice for more than 3 months
bTripterygium is an extract of Tripterygium wilfordii, a traditional Chinese medicine, which has immunosuppression effects
RA-ILD RA with ILD development, RA-N-ILD RA without ILD development, MTX methotrexate, LEF leflunomide, HCQ hydroxychloroquine, SASP
salazosulfapyridine, TNFi tumor necrosis factor inhibitor, GC glucocorticoid, csDMARDs conventional synthetic DMARDs except for methotrexate and
leflunomide
Clin Rheumatol

Table 3 Logistic regression analysis of characteristics associated with Discussion

the development of RA-ILD

Characteristics OR 95% CI P value Interstitial lung disease (ILD) is a frequent extra-articular

manifestation of rheumatoid arthritis (RA). RA-ILD signifi-
Advanced age 1.485 1.011–2.181 0.044 cantly impacts prognosis and is associated with increased
Male patients 1.882 1.177–3.009 0.008 morbidity and mortality [2]. In a clinical setting, routine
Ever smoker 1.070 0.663–1.726 0.783 screening for ILD is recommended for all RA patients, and
RA duration positive intervention is required for RA-ILD patients. But a
Duration 1 (0~5 years vs. > 10 years) 2.099 1.369–3.217 0.001 consensus treatment for RA-ILD has not yet been established,
Duration 2 (5~10 years vs. > 10 years) 0.922 0.559–1.522 0.751 and the evidence for therapy and its potential adverse effects
DAS28 0.958 0.867–1.058 0.396 were absent. Therefore, we designed this long-term retrospec-
ESR 1.006 0.999–1.014 0.074 tive cohort study to screen out risk factors for ILD develop-
CRP 1.002 0.995–1.010 0.495 ment, progression, and death and to explore the potential role
RF positive 1.728 1.042–2.867 0.034 of antirheumatic drugs in the evolution of RA-ILD.
Anti-CCP antibody high titer positive 1.359 0.870–2.122 0.178 Furthermore, the participants enrolled in the cohort were pa-
Elevated LDH 3.032 1.814–5.068 0.000 tients without ILD at the time of RA diagnosis, which is dif-
Treatment ferent from most previous studies and of great reference value
No medication 1.833 1.022–3.290 0.042 for clinical practice.
Irregular medication 1.477 0.774–2.820 0.237 In this study, the prevalence of ILD in RA patients entirely
GC 0.740 0.457–1.198 0.221 undergoing HRCT examination is 30.12%, of whom 39.12%
MTX 1.229 0.766–1.973 0.393 were presenting with respiratory symptoms. HRCT is
LEF 1.476 0.928–2.348 0.100 regarded to be a practical method of excellent sensibility for
TNFi 0.677 0.280–1.638 0.387 detecting lung abnormalities and is capable of detecting the
early stages of ILD in patients without respiratory symptoms
DAS disease activity score, RF rheumatoid factor, LDH lactate dehydro- [22]. The currently reported prevalence of RA-ILD varied
genase, GC glucocorticoid, MTX methotrexate, LEF leflunomide, TNFi
tumor necrosis factor inhibitor
widely, mainly depending on the methods of detection and
patient selection [2, 23, 24].
Our results revealed that advanced age, male, short dura-
Prognostic factors for survival in RA-ILD patients tion of RA, RF positive, elevated LDH, and no medication
were risk factors for the development of ILD. The predictive
Considering the number of missing values, pulmonary implications of advanced age, male, and RF positive are con-
function test results were not included within the sur- sistent with most previous studies [2, 3, 25]. Moreover, we
vival analysis. On bivariate analysis in RA-ILD patients, found that 75.18% ILD occurred within 10 years of RA onset,
advanced age (> 60 years old) at RA-ILD diagnosis, and most of them occurred within 5 years of RA onset.
definite UIP pattern on HRCT, extensive lung involve- Logistic regression analysis indicates that the incidence of
ment, high fibrosis score, and treatment with CYC were ILD is approximately two times higher in RA patients with
associated with survival (P < 0.05, Table 7). Cox haz- less than 5 years of disease duration than patients with over 10
ards modeling revealed that advanced age (HR: 3.181) years of disease duration. A variety of activated immune cells,
and extensive lung involvement on HRCT (HR: 2.401) antibodies, and inflammatory cytokines are involved in the
were associated with worse survival. Treatment with cy- early and active stages of RA pathogenesis and associated
clophosphamide (HR: 0.210) was associated with better with the development of ILD [26]. In the early stage of RA,
survival (Table 7). especially before treatment with antirheumatic drugs, inflam-
As CYC treatment was clearly associated to survival, a mation and dysimmunity have not been effectively sup-
comparison between CYC-treated patients and CYC not pressed, so patients may be more susceptible to ILD.
treated patients was done (see Table 8). CYC was admin- Meanwhile, in this study, elevated LDH is closely related to
istered orally in 24 RA-ILD patients with a majority dos- RA-ILD. The significance of LDH in IPF was first reported by
age of 50 mg/day, intravenously pulsed in 15 patients Japanese scholar Kusume K [27], and its synthesis increased
with an equivalent dosage of 0.8 g/month, and prescribed in alveolar type II epithelial cells, endothelial cells, and neu-
with sequential therapy in 4 patients with intravenous trophils during lung injury. The release of LDH into the blood-
pulses first and oral medicine later. No significant differ- stream caused increased serum LDH levels. The diagnostic
ence was found for HRCT patterns, extent of lung in- value of LDH has also been confirmed in our previous studies
volvement, ILD score, and parameters of pulmonary func- of ILD in RA and pSS [25, 28], suggesting the elevated LDH
tion test between the two groups. in patients with RA should alert the presence of ILD.
 Clin Rheumatol

Table 4 Baseline clinical characteristics in RA-ILD patients with and without disease progression

RA-ILD patients who had lung progression RA-ILD patients with stable lung P value
(n = 83) (n = 102)

Clinical manifestation
Age at RA-ILD diagnosis (years) 68.44 ± 10.59 61.94 ± 12.31 0.000
Advanced age (>60 years old) 65 (78.31%) 65 (63.73%) 0.031
Male patients 36 (43.37%) 39 (38.24%) 0.479
Ever smoker 39 (46.99%) 41 (40.20%) 0.354
RA duration 48 (8, 120) 48 (12, 108) 0.901
DAS28 5.04 ± 2.00 4.80 ± 2.03 0.423
Patients with respiratory symptoms 37 (44.58%) 35 (34.31%) 0.154
Laboratory test
RF high titer positive 61 (73.49%) 71 (69.61%) 0.561
Anti-CCP antibody high titer positive 66 (79.52%) 67 (65.69%) 0.037
LDH (U/L) 183 (155, 231) 181 (152, 209) 0.541
Elevated LDH 16 (19.28%) 14 (13.73%) 0.308
Pulmonary function test
FVC (% predicted) 82.95 ± 21.58 87.77 ± 23.62 0.309
FVC%<70% 14/57 (24.56%) 11/64 1(7.19%) 0.317
DLCO (% predicted) 51.21 ± 22.15 60.41 ± 19.51 0.044
DLCO%<45% 26/57 (46.51%) 15/64 (23.43%) 0.010
HRCT
CT interval period 27 (15, 48) 26.5 (13.75, 53.75) 0.710
HRCT pattern
UIP 40 (48.19%) 28 (27.45%) 0.004
Definite UIP 16 (19.28%) 16 (15.69%) 0.521
Possible UIP 24 (28.92%) 12 (11.77%) 0.009
NSIP 17 (20.48%) 30 (29.41%) 0.165
c-NSIP 7 (8.43%) 22 (21.57%) 0.015
f-NSIP 10 (12.05%) 8 (7.84%) 0.337
OP 3 (3.62%) 5 (4.90%) 0.699
LIP 0 (0%) 1 (0.98%) 0.366
Indeterminate 23 (27.71%) 38 (37.26%) 0.170
Extent of lung involvement
Limited (< 10% of lung involvement) 34 (40.96%) 54 (52.84%) 0.105
Moderate (10~30% of lung involvement) 30 (36.15%) 30 (29.41%) 0.331
Extensive (> 30% of lung involvement) 19 (22.89%) 18 (16.67%) 0.375
ILD score
Alveolitis score 2 (2, 2) 2 (2, 3) 0.673
Fibrosis score 4 (4, 10) 4 (2.5, 4) 0.006

RA-ILD RA with ILD, RF rheumatoid factor, Anti-CCP antibody anti-cyclic citrullinated peptide antibody, LDH lactate dehydrogenase, FVC forced vital
capacity, DLCO diffusion capacity of the lung for carbon monoxide, UIP usual interstitial pneumonia, NSIP nonspecific interstitial pneumonia, OP
organized pneumonia, LIP lymphocytic interstitial pneumonia

In addition to the ILD developed during the pathogenesis
of rheumatic diseases, an increasing number of clinical studies
demonstrate both conventional DMARDs, such as MTX, and
biologics correlate with RA-ILD [6, 29]. Thus, in this large
sample’s cohort study, we specifically included drug factors
into the risk assessment of RA-ILD. Univariate analysis
showed that the rate of no medication was higher in RA-ILD
patients (P < 0.01). The usage rates of MTX and TNFi were
relatively low in RA-ILD patients (P values were 0.066 and
0.055, respectively), which might be related to the high pro-
portion of no medication and irregular medication in the
group. Our results also showed that MTX duration was shorter
Clin Rheumatol

Table 5 Treatment in RA-ILD patients with and without disease progression

Treatment RA-ILD patients who had lung progression RA-ILD patients with stable lung P value
(n = 83) (n = 102)

No medication 2 (2.41%) 2 (1.96%) 0.833

Irregular medication 13 (15.66%) 10 (9.80%) 0.230
Drugs for RA-ILD a
GC 39 (46.99%) 53 (51.96%) 0.501
CYC 19 (22.89%) 18 (17.65%) 0.375
MTX 25 (30.12%) 40 (39.22%) 0.197
Dosage (mg/w) 10 (10, 10) 10 (8.75, 10) 0.483
Duration (months) 12.5 (8, 21) 20 (9, 36) 0.290
LEF 31 (37.35%) 35 (34.31%) 0.668
Tripterygium b 39 (46.99%) 45 (44.12%) 0.697
HCQ 31 (37.35%) 43 (42.16%) 0.507
SASP 3 (3.62%) 4 (3.92%) 0.913
TNFi 4 (4.82%) 4 (3.92%) 0.765
Prescription patterns
GC with no DMARDs 4 (4.82%) 3 (2.94%) 0.505
MTX 17 (20.48%) 32 (31.37%) 0.095
MTX monotherapy 0 0
MTX + GC 2 (2.41%) 4 (3.92%) 0.564
MTX + CYC 0 0
MTX + CYC + GC 1 (1.21%) 1 (0.98%) 0.883
MTX + CYC + csDMARDs 2 (2.41%) 0 (0%) 0.113
MTX + CYC + csDMARDs + GC 3 (3.62%) 1 (0.98%) 0.221
MTX + csDMARDs 5 (6.02%) 14 (13.73%) 0.086
MTX + csDMARDs + GC 4 (4.82%) 12 (11.77%) 0.095
LEF 20 (24.10%) 29 (28.43%) 0.506
LEF monotherapy 2 (2.41%) 3 (2.94%) 0.825
LEF + GC 3 (3.62%) 4 (3.92%) 0.913
LEF + CYC 0 (0%) 1 (0.98%) 0.366
LEF + CYC + GC 1 (1.21%) 1 (0.98%) 0.883
LEF + CYC + csDMARDs 1 (1.21%) 2 (1.96%) 0.686
LEF + CYC + csDMARDs + GC 2 (2.41%) 3 (2.94%) 0.825
LEF + csDMARDs 8 (9.64%) 8 (7.84%) 0.666
LEF + csDMARDs + GC 3 (3.62%) 7 (6.86%) 0.331
MTX + LEF 5 (6.02%) 5 (4.90%) 0.737
MTX + LEF 1 (1.21%) 0 (0%) 0.266
MTX + LEF + csDMARDs 0 (0%) 2 (1.96%) 0.200
MTX + LEF + GC 1 (1.21%) 2 (1.96%) 0.686
MTX + LEF + csDMARDs + GC 2 (2.41%) 1 (0.98%) 0.444
MTX + LEF + csDMARDs + GC + CYC 1 (1.21%) 0 (0%) 0.266
Alternate use of MTX and LEF 2 (2.41%) 0 (0%) 0.115
MTX/LEF + GC 1 (1.21%) 0 (0%) 0.266
MTX/LEF + csDMARDs + GC 1 (1.21%) 0 (0%) 0.266
TNFi 4 (4.82%) 4 (3.92%) 0.765
TNFi + MTX + GC 1 (1.21%) 1 (0.98%) 0.883
TNFi + LEF 1 (1.21%) 1 (0.98%) 0.883
TNFi + LEF + csDMARDs 1 (1.21%) 0 (0%) 0.266
TNFi + csDMARDs + GC 1 (1.21%) 2 (1.96%) 0.686
CYC 8 (9.64%) 9 (8.82%) 0.849
CYC monotherapy 0 0
CYC + GC 3 (3.62%) 2 (1.96%) 0.490
CYC + csDMARDs 3 (3.62%) 1 (0.98%) 0.221
CYC + csDMARDs + GC 2 (2.41%) 6 (5.88%) 0.248
GC + csDMARDs 3 (3.62%) 3 (2.94%) 0.797
Others 5 (6.02%) 5 (4.90%) 0.737

aDrugs for RA refer to drugs regularly taken under doctors’ advice for more than 3 months
bTripterygium is an extract of Tripterygium wilfordii, a traditional Chinese medicine, which has immunosuppression effects
RA-ILD RA with ILD, RA-N-ILD RA without ILD, MTX methotrexate, LEF leflunomide, HCQ hydroxychloroquine, SASP salazosulfapyridine, TNFi
tumor necrosis factor inhibitor, GC glucocorticoid, CYC cyclophosphamide, csDMARDs conventional synthetic DMARDs except for methotrexate and
leflunomide
 Clin Rheumatol

Table 6 Logistic regression analysis of characteristics associated with high proportion of no medication. Additionally, disease sever-
the progression of RA-ILD
ity, personal educational levels, economic conditions, and oth-
Characteristics OR 95% CI P value er factors may all contribute to the high proportion. And due to
absence of treatment with GC and DMARDs, the activated
Advanced age (>60 years old) 0.902 0.370–2.400 0.902 immune cells, antibodies, and inflammatory cytokines cannot
Patients with respiratory symptoms 1.118 0.469–2.663 0.801 be effectively inhibited in RA patients, which may contribute
Anti-CCP antibody high titer positive 1.715 0.695–4.232 0.242 to ILD development.
DLCO%<45% 3.025 1.139–8.033 0.026 In this manuscript, we also compared the prescription pat-
HRCT terns of various drugs. The comparisons revealed that no dif-
Possible UIP pattern in HRCT 3.476 1.086–11.131 0.036 ference was present between the two groups in the monother-
c-NSIP pattern in HRCT 0.368 0.093–1.457 0.155 apy (such as MTX, LEF, GC) and combination therapy (such
Limited lung involvement 0.808 0.350–1.862 0.616 as MTX combined with LEF). Logistic regression analysis
Fibrosis score 0.959 0.852–1.080 0.493 showed that no medication (OR: 1.833) was closely correlated
Treatment to the development of RA-ILD, and no correlation was found
MTX 1.112 0.451–2.741 0.817 between the treatment with DMARDs (such as MTX) and the
development of ILD. Therefore, regular therapy under doc-
tors’ advice was recommended to RA patients. Furthermore,
in RA-ILD patients; however, in this study, MTX duration the result that MTX, LEF, and other DMARDs which have
was limited by RA disease duration or follow-up period which potential lung toxicity does not significantly increase the inci-
were relatively shorter in RA-ILD group; thus its reference dence of ILD and can provide a reference for clinical drug
value was limited. As for the high proportion of no medication selection.
in RA-ILD group, it should be noted here that the medications Considering the potential risk of exacerbating underlying
of RA-ILD patients were collected from the date of the first ILD for the biologic and nonbiological DMARDs, we also
onset of RA, but not the date of diagnosis of RA. The defini- included drug factors into the logistic regression model of
tion of starting points in our study may result in the relatively ILD progression. We compared the usage rates and

Table 7 Cox hazard analysis of prognostic factors for death in RA-ILD patients

Bivariate Multivariate

Characteristics χ2 P value HR 95% CI P value

Advanced age (>60 years old) 9.996 0.002 3.181 1.274–7.941 0.013
Male patients 3.475 0.062 1.373 0.713–2.644 0.343
Anti-CCP antibody high titer positive 2.830 0.092 1.803 0.790–4.114 0.162
HRCT
Denifite UIP pattern on HRCT 4.932 0.026 1.615 0.523–4.988 0.405
Extensive lung involvement 4.696 0.030 2.401 1.075–5.362 0.033
Fibrosis score 17.297 0.044 0.978 0.856–1.117 0.739
Drugs for RA-ILD a
GC 2.448 0.118 0.893 0.358–2.223 0.893
CYC 5.875 0.015 0.210 0.049–0.895 0.035
MTX 1.784 0.182 0.722 0.366–1.425 0.348
LEF 0.609 0.435
Tripterygium b 1.405 0.236
HCQ 1.114 0.291
SASP 0.009 0.924
TNFi 1.052 0.305

aDrugs for RA-ILD refer to drugs regularly taken under doctors’ advice for more than 3 months
bTripterygium is an extract of Tripterygium wilfordii, a traditional Chinese medicine, which has immunosuppression effects
RA rheumatoid arthritis, ILD interstitial lung disease, Anti-CCP antibody anti-cyclic citrullinated peptide antibody, UIP usual interstitial pneumonia,
NSIP nonspecific interstitial pneumonia, GC glucocorticoid, CYC cyclophosphamide, MTX methotrexate, LEF leflunomide, HCQ hydroxychloroquine,
SASP salazosulfapyridine, TNFi tumor necrosis factor inhibitor
Clin Rheumatol

Table 8 Comparison of pulmonary function test and HRCT evaluations between CYC-treated patients and CYC not treated patients

CYC-treated patients (n = 43) CYC not treated patients P value

(n = 235)

Pulmonary function test

FVC (% predicted) 80.83 ± 21.21 90.63 ± 26.85 0.107
DLCO (% predicted) 51.10 ± 18.99 58.06 ± 22.86 0.172
HRCT
HRCT pattern
UIP 15 (%) 71 (27.45%) 0.542
Definite UIP 8 (18.61%) 38 (16.17%) 0.693
Possible UIP 7 (16.28%) 33 (14.04%) 0.701
NSIP 11 (20.48%) 53 (29.41%) 0.665
c-NSIP 7 (16.28%) 35 (14.89%) 0.816
f-NSIP 4 (9.30%) 18 (7.66%) 0.714
OP 0 (0%) 12 (5.11%) 0.130
LIP 0 (0%) 2 (0.85%) 0.544
Indeterminate 17 (39.54%)17 97 (41.28%) 0.831
Extent of lung involvement
Limited (< 10% of lung involvement) 24 (55.82%) 109 (46.38%) 0.255
Moderate (10~30% of lung involvement) 12 (27.91%) 74 (31.49%) 0.640
Extensive (> 30% of lung involvement) 7 (16.28%) 52 (22.13%) 0.388
ILD score
Alveolitis score 2 (2, 3) 2 (2, 3) 0.061
Fibrosis score 4 (4, 6) 4 (4, 5) 0.131

CYC cyclophosphamide, FVC forced vital capacity, DLCO diffusion capacity of the lung for carbon monoxide, UIP usual interstitial pneumonia, NSIP
nonspecific interstitial pneumonia, OP organized pneumonia, LIP lymphocytic interstitial pneumonia

prescription patterns of various drugs between the two groups
with or without ILD progression. Univariate and multivariate
analysis both showed no correlation between the drug usage
rates, monotherapy (such as MTX, LEF, CYC), combination
therapy (such as MTX combined with LEF), and the progres-
sion of ILD. Our findings revealed that, although DMARDs
have been reported with lung toxicity, these reactions are rare
and should not preclude the use of DMARDs in the majority
of RA patients.
Impaired DLCO is a common pathophysiological change
in the early stage of ILD. DLCO decline can not only reflect
the severity of lung damage but also is one of the most sensi-
tive indicators. Our result is that, consistent with the previous
research of our team [30], DLCO% < 45% of the predicted
value was an independent risk factor for the ILD progression.
It is currently agreed that DLCO reduction is a useful factor
not only for the development of RA-ILD but also for the poor
prognosis of ILD [16, 31, 32].
HRCT evaluations, in this study, included radiological pat-
terns, extent of lung involvement, and ILD score. The most
prevalent HRCT pattern of RA-ILD was UIP (33.09%),
followed by NSIP (28.06%). In view of definite UIP and pos-
sible UIP patterns, c-NSIP and f-NSIP patterns have their own
specific radiological and histopathological characteristics; we
evaluated each subtype separately. The rate of possible UIP
pattern and the fibrosis score were higher in ILD progression
group, and the rate of c-NSIP pattern was higher in the stable
group (P < 0.05). When the above three variables, together
with limited involvement (P = 0.105), were all included into
the logistic regression model, the result showed that possible
UIP pattern was an independent risk factor for the ILD pro-
gression. Another study of our team on CT signs in patients
with RA-ILD showed that a wide distribution of subpleural
reticular pattern and/or interlobular septal thickening appears
predictive of radiographic progressive fibrosis [33]. These CT
abnormalities accord with the CT features of possible UIP
pattern, suggesting that patients with this pattern should be
monitored closely.
A total of 53 RA-ILD patients died during the follow-up
period. The main cause of death was respiratory failure due to
ILD progression and/or pneumonia. On bivariate analysis,
definite UIP pattern, extensive lung involvement, and high
fibrosis score on HRCT were associated with survival in our
study. Meanwhile, we used multivariable COX regression
model to identify clinical predictors of mortality. It was shown
that, among CT variables, only extensive lung involvement
was independently associated with poor survival after
adjusting for possible confounders. Sathi et al. studied 29

patients with RA-ILD, followed 13 to 15 years, and revealed
that patients with extensive (> 25%) lung involvement had a
poor prognosis [34]. Recently, a large cohort study in UK
showed that UIP pattern and extensive disease were associated
with increased mortality [31]. Although the presence of the
UIP pattern on biopsy or HRCT and extent of fibrosis have
been reported as poor prognostic factors of RA-ILD in previ-
ous studies [31, 35, 36], they have not been confirmed in our
research. In addition, Solomon et al. found that pulmonary
function impairment, rather than the baseline HRCT pattern,
independently predicted mortality [32]. Pulmonary function is
also an important predictor of mortality in patients with RA-
ILD. However, the lack of pulmonary function indicators in
survival analysis in this study may lead to some bias of the
results. Our results need to be further verified. Based on above
data and considering the significant difference of definite UIP
pattern and fibrosis score in bivariate analysis, it still advised
to take both HRCT pattern and extent of lung involvement
into consideration for prognosis.
With regard to treatment of RA-ILD, the evidence is of low
quality or absent. Treatment decisions are often made clinically,
based on exacerbating or mitigating factors such as functional
impairment and comorbidity burden or based on experience
from the IIPs. In our study, after controlling for possible influ-
ences, the multivariable survival analysis found that cyclophos-
phamide helps to improve the prognosis in RA-ILD patients. At
present, the significant beneficial effect of cyclophosphamide
comes from clinical trials of scleroderma lung disease [37]. Our
previous research has ever indicated that cyclophosphamide
therapy improves prognosis of RA-ILD [30]. In this article,
we select different subjects to analyze and draw the same con-
clusion, which may provide more evidence for the application
of cyclophosphamide in real-world RA-ILD treatment. We’ll
further our exploration in appropriate clinical researches.
As for the timing of CYC treatment, in the clinical practice,
it should take into account the activity of RA, the severity of
ILD, and the possibility of ILD progression. As even for the
same patient, the medications for different stages of the dis-
ease will also be different. Our results showed no significant
difference was found for HRCT patterns and extent of lung
involvement between the two groups. The value of FVC%
and DLCO% seemed to be lower, and alveolitis/fibrosis score
seemed to be higher in CYC-treated patients, but the differ-
ence was not statistically significant. However, the data in our
study just presented the examination and medications of RA-
ILD patients at a certain stage, which cannot necessarily re-
flect patients’ whole conditions. Therefore, the present results
need to be further validated, and therapeutic strategies for RA-
ILD deserved more exploration to effectively prevent or even
reverse ILD, thereby maximally preserving lung function.
Our research has some limitations. First, this is a single-
center, retrospective study, with certain selection bias and re-
call bias. Second, due to the lack of adequate pulmonary
Clin Rheumatol
function test results at baseline and follow-up periods, those
data were not included within the survival analysis. However,
this a large sample cohort study that enrolled RA patients
without ILD at baseline, observed the evolution of ILD, and
systemically evaluated the potential role of DMARDs in the
disease process. Our findings offer both an insight into the
predictive and prognostic factors of RA-ILD and some treat-
ment options for clinicians.
Conclusions
In summary, this cohort study revealed that advanced age,
male, short duration of RA, RF positive, elevated LDH, and
no medication are closely correlated with the development of
RA-ILD; no correlation was found between traditional
DMARDs and the development of ILD. DLCO% < 45%
and UIP possible pattern on HRCT are predictive factors for
ILD progression; no correlation was found between traditional
DMARDs and ILD progression. Advanced age and extensive
lung involvement on HRCT independently predict mortality;
cyclophosphamide treatment helps to improve the prognosis
of RA-ILD. We recommend that RA patients should receive
regular treatment to improve the development of the disease,
and clinicians should pay close attention to the pulmonary
function and HRCT findings for patients with ILD.
Compliance with ethical standards
Disclosures None.
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