Concise Report

Lupus
2023, Vol. 32(5) 688–693
A 5–year follow-up of pulmonary function © The Author(s) 2023
Article reuse guidelines:
tests in childhood-onset systemic lupus sagepub.com/journals-permissions
DOI: 10.1177/09612033231163831
journals.sagepub.com/home/lup
erythematosus: a single-center
retrospective study

AJ Altchek , LN Moorthy , M Ramagopal, C Salvant and LP Uppaluri

Abstract
Significance: Pulmonary involvement in childhood-onset systemic lupus erythematosus (cSLE), contributes to significant
morbidity and mortality. Manifestations include chronic interstitial pneumonitis, pneumonia, pleuritis, alveolar hemorrhage,
and shrinking lung syndrome. However, many patients can be asymptomatic from a respiratory standpoint and still have
pulmonary function test (PFT) abnormalities. Our aim is to describe PFT abnormalities in patients with cSLE.
Methods: We completed a retrospective review of 42 patients with cSLE followed at our center. These patients were at
least 6 years old (so they could complete PFTs). We collected data from July 2015 to July 2020.
Results: Out of the 42 patients, 10 (23.8%) had abnormal PFTs. These 10 patients had a mean age at diagnosis of 13 ± 2.9
years. Nine were female. One-fifth (20%) self-identified as Hispanic, 20% as Asian, 10% as Black or African American, and
the remaining 50% as “Other.” Of the 10, 3 had restrictive disease only, 3 with diffusion impairment only, and 4 with both
restrictive lung disease and diffusion impairment. Patients with restrictive patterns had a mean total lung capacity (TLC) of
72.5 ± 5.8 throughout the study period. The average diffusing capacity for carbon monoxide corrected for hemoglobin
(DsbHb) among patients with diffusion limitation during the study period was 64.8 ± 8.3.
Conclusions: The most common PFT abnormalities seen in patients with cSLE are alterations in diffusing capacity as well
as restrictive lung disease.

Keywords
Pulmonary function testing, systemic lupus erythematosus, pulmonary, lung function, pediatric

Date received: 22 September 2022; accepted: 27 February 2023

Introduction pulmonary function testing (PFTs). A retrospective analysis

Lung involvement in rheumatologic disorders, specifically
systemic lupus erythematosus (SLE), contributes to a sig-
nificant amount of morbidity and mortality. Around 10%–
20% patients with SLE are diagnosed before the age of 18.1
A range of pulmonary complications have been identified in
children with SLE, including but not limited to chronic
interstitial pneumonitis, pneumonia, alveolar hemorrhage,
and shrinking lung syndrome.2–4 There are few reports that
describe the impact on lung function and pulmonary in-
volvement in patients with childhood-onset SLE (cSLE).
Lilleby et al.4 examined a cohort of sixty patients with
childhood-onset systemic lupus erythematosus (cSLE) in
Norway, finding that over one-third of them had impair-
ments of pulmonary function as seen by alterations in
of 42 patients with cSLE published in Lupus by Veiga et al.5
in 1981 also showed abnormal PFTs in more than one-half
of patients tested. These patients demonstrated restrictive
defects and low diffusion capacity on PFT analysis. Ad-
ditionally, these abnormalities in PFT analysis can often be
subclinical in the pediatric population, making it difficult to
determine which patients, and how many, will develop
clinically relevant impairments.6 An evaluation of 15
Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Corresponding author:
AJ Altchek, Rutgers Robert Wood Johnson Medical School, 1 Robert
Wood Johnson Place, New Brunswick, NJ 08901, USA.
Email: alexa.altchek@rutgers.edu
Altchek et al.
patients with cSLE by Trapani et al.7 demonstrated sig-
nificant lung impairment in 40% of patients, all of whom
were asymptomatic from a pulmonary standpoint. Our aim
is to build on these previous findings to further categorize
the types of pulmonary involvement and abnormalities in
PFTs seen in patients with cSLE at our center.
Methods/study design
We completed a retrospective chart review of 42 patients
over the age of 6 years and diagnosed with cSLE at our
center. This chart review was approved by the Rutgers
Biomedical and Health Sciences Institutional Review Board
with study ID Pro2020002378. The study did not involve
informed consent as it was a retrospective chart review in
which all patient data was deidentified. We collected data on
these patients from July 2015 to July 2020. Patients’
medical charts were reviewed for demographic, clinical, and
laboratory data. The European Respiratory Society (ERS)
and American Thoracic Society (ATS) guidelines were used
when interpreting PFTs results.8 An obstructive ventilatory
impairment was defined by FEV1/FVC below the lower
limit of normal (LLN), which is defined as the 5th percentile
of a normal population. Further, restrictive ventilatory
impairment is characterized by a reduction in total lung
capacity (TLC) below the LLN (5th percentile). The dif-
fusing capacity for carbon monoxide when corrected for
hemoglobin (DsbHb) demonstrates a limitation when it is
below the 5th percentile as well.8,9 The reference source
from which the LLN and percent predicted value are derived
is the Global Lung Function Initiative (GLI).10
Results
Demographics
Out of the 42 patients with cSLE at our center, ten patients
(23.8%) demonstrated abnormalities in PFTs during the
study period and were included in our analysis. Clinical and
PFT data is shown in Table 1. These 10 patients with cSLE
and PFT abnormalities had a mean age at diagnosis of 13 ±
2.9 years. Nine of the 10 patients were female. One-fifth
(20%) self-identified as Hispanic, 20% as Asian, 10% as
Black or African American, and the remaining 50% as other.
Comorbid conditions and medications
We also collected data on other SLE-associated organ in-
volvement seen in these patients. Five of the ten patients, or
50%, were found to have lupus nephritis. Their chronic
kidney disease classification ranged anywhere from stage I
to stage V with end-stage renal disease present in one of the
689
patients. Three (30%) had hypertension noted to be one of
the complications of their disease. Pulmonary involvement
aside from abnormalities in PFTs was seen in two of the 10
patients (20%), with both patients diagnosed with asthma
and one of the two also exhibiting pneumonitis. Eighty
percent (80%) of patients were taking hydroxychloroquine
sulfate as part of their SLE treatment regimen at the time of
the PFTs. Fifty percent (50%), or five of the 10 patients,
were prescribed mycophenolate at this time as well. Seven
(70%) had steroids as a part of their regimen, with five
taking prednisone and the other two patients taking
methylprednisolone for the treatment of their SLE.
PFT abnormalities
We analyzed the pulmonary function tests of these patients
and characterized the abnormalities that were seen. These
characterizations can be seen in Figure 1. Overall, of the ten
patients with PFT abnormalities, 7/10 (70%) of patients had
a decreased TLC below the 5th percentile (LLN), with a
mean TLC of 72.5 ± 5.8. Seven out of ten (70%) patients
had a reduced diffusing capacity for carbon monoxide when
corrected for hemoglobin (DsbHb) below the LLN. These
patients had a mean DsbHb of 64.8 ± 8.3. Four of the 10
patients (40%) within the study group had concomitant
restrictive lung disease and diffusion impairment. None of
the 10 patients exhibited obstructive lung disease. Despite
two patients having asthma, none of the patients within the
study group demonstrated obstructive lung disease on
spirometry during the study period, as characterized by an
FEV1/FVC ratio below the LLN, indicating that their
asthma was well-controlled at this time.
Often, PFTs are performed to assess for organ in-
volvement in cSLE patients around the time of diagnosis or
during the disease course irrespective of pulmonary
symptoms. PFTs are also performed during periods of SLE
flare if there are cardiopulmonary symptoms and when the
patient is able to perform the testing. In this study, the
patients underwent PFTs either at diagnosis to characterize
organ involvement, to further evaluate pulmonary symp-
toms, during a disease flare, or to follow-up on prior ab-
normal PFTs.
The extent of patients’ disease activity at the time of
pulmonary function was quantified using the SLE Disease
Activity Index 2000 (SLEDAI-2K) which was performed
with reviewing the records from within 3 months before or
after PFTs.11 The SLEDAI-2K as well as the pulmonary
symptoms of each patient at the time of PFT analysis has
been included in Table 1. Only five of the 10 patients (50%)
endorsed pulmonary symptoms within 3 months before or
after their initial PFT analysis during the study period, and
 690
Table 1. Clinical features and Pulmonary function testing during study period.

Disease
activity at
Time Disease Time follow- Pulmonary
(yr) activity (yr) to up symptoms PFT
Patient SLE organ since (SLEDAI- Pulmonary PFT follow- (SLEDAI- at follow- abnormality at TLC at DsbHb at
# involvement diagnosis 2k) symptoms abnormality TLC DsbHb up 2k) up follow-up follow-up follow-up Medications

1 Class IV 0 10 Cough Restrictive 74 96 0.5 11 None Data Data Data Hydroxychloroquine

lupus not not not sulfate
nephritis available available available Mycophenolate
mofetil
Methylprednisolone
3 Class I 0 7 Cough, Restrictive 77 98 N/A N/A N/A No No No Hydroxychloroquine
lupus wheezing, follow-up follow- follow- sulfate
nephritis dyspnea up up Prednisolone
Hypertension
(HTN)
9 Cauda equina 0.5 21 Dyspnea Restrictive 77 86 0.5 2 None Data Data Data Mycophenolate
syndrome not not not mofetil
available available available Prednisone
2 Class V 9 10 Cough, Diffusion 89 71 1.5 14 None Diffusion 68 66 Hydroxychloroquine
lupus dyspnea limitation limitation sulfate
nephritis Restrictive Mycophenolate
HTN sodium
Asthma
End-stage
renal
disease
(ESRD)
5 Retinal 5 10 None Diffusion 75 65 2.5 2 None Restrictive 76 84 Mycophenolate
vasculitis limitation, mofetil
Avascular restrictive Prednisone
necrosis of
femoral
heads
8 Pneumonitis 0.5 2 None Diffusion 80 68 3 0 None Diffusion 60 60 Hydroxychloroquine
Asthma limitation limitation sulfate
restrictive Prednisone
10 Class V 0 23 None Diffusion 73 67 0.5 4 None Data Data Data Hydroxychloroquine
lupus limitation, not not not sulfate
nephritis restrictive available available available Methylprednisolone

(continued)
Lupus 32(5)
Table 1. (continued)

Disease
activity at
Time Disease Time follow- Pulmonary
Altchek et al.

(yr) activity (yr) to up symptoms PFT

Patient SLE organ since (SLEDAI- Pulmonary PFT follow- (SLEDAI- at follow- abnormality at TLC at DsbHb at
# involvement diagnosis 2k) symptoms abnormality TLC DsbHb up 2k) up follow-up follow-up follow-up Medications

4 None 0 11 None Diffusion Data 68 0.5 2 None No 120 112 Hydroxychloroquine

limitation not abnormality sulfate
available Prednisone
6 Sjogren’s 4 2 Nocturnal Diffusion 99 73 0.5 2 None No 101 88 Hydroxychloroquine
Syndrome cough limitation abnormality sulfate
Mycophenolate
mofetil
Methylprednisolone
7 Antiphospholipid 1 10 None Diffusion 87 45 2 4 Dyspnea Data not Data not Data not Hydroxychloroquine
syndrome limitation available available available sulfate
Class IV lupus Mycophenolate
nephritis mofetil
Vasculitis Prednisone
Libman-Sacks
Endocarditis
HTN
SLEs: systemic lupus erythematosus; SLEDAI-2k: Systemic Lupus Erythematosus Disease Activity Index 2000; TLC: total lung capacity; DsbHb: diffusing capacity for carbon monoxide when corrected for hemoglobin; N/A: not
applicable.
691
692
Figure 1. The characterization of pulmonary function testing abnormalities seen amongst the 10 patients. TLC: total lung capacity; LLN:
lower limit of normal; DsbHb: diffusing capacity for carbon monoxide when corrected for hemoglobin.
only one of the ten patients (10%) had pulmonary symptoms
at the time of their follow-up PFTs.
Imaging
Multiple patients also had radiological studies completed
during the 5-year study period. However, only three of the
patients, patients 4, 8, and 10, (30%) had imaging that was
completed due to their abnormal PFTs. These patients had
imaging in the form of a high-resolution CT (HRCT) to look
for interstitial lung disease (ILD). Patients 1–3, 5, 6–7, and 9
did not have imaging due to PFT results.
Patient 4 was found to have diffusion limitation on
PFTs and thus completed an HRCT without contrast. The
HRCT showed scattered small nodules ranging from
2.4 mm to 5.7 mm, likely benign, with no interstitial
thickening or air trapping. Patient 8 had a diffusion ab-
normality seen on PFTs that was followed with an HRCT
to evaluate for ILD. This HRCT showed normal lungs
with no evidence of ILD along with axillary and superior
mediastinal lymphadenopathy. On follow-up PFTs, Pa-
tient 8 demonstrated continued diffusion impairment with
restrictive lung disease (shown in Table 1), prompting an
additional HRCT. This HRCT showed no evidence of ILD
and resolution of a right-sided pleural effusion that was
seen on unrelated interval imaging. Lastly, Patient 10
demonstrated both restrictive lung disease and diffusion
limitation on PFTs. This patient’s HRCT showed no
evidence of ILD and axillary lymphadenopathy. There-
fore, in our study none of the patients with PFT abnor-
malities had evidence of ILD on radiological imaging.
Six of the ten patients, including Patient 8, had chest
imaging performed during the study period in the form of
chest X-rays, CT angiograms, ventilation-perfusion (V/Q)
Lupus 32(5)
scans, or ultrasounds. However, these were completed in-
dependently of their PFT results and due to interval disease
or symptoms.
Change over time
We followed these patients and analyzed their PFT data
throughout the 5-year study period (Table 1). Fifty per-
cent (50%) or five of the ten patients had spirometry, lung
volume, and diffusion capacity data at follow-up, al-
lowing us to characterize their pulmonary function ab-
normalities over time. Three of the seven (42.9%)
patients who demonstrated diffusion abnormalities dur-
ing baseline measurements demonstrated resolution of
this abnormality at initial follow-up. However, an addi-
tional two of the seven patients with earlier diffusion
abnormalities (28.6%) went on to develop an additional
restrictive defect. Only one patient of the five (20%) with
an initial restrictive impairment had follow-up lung
volume data within the study period. This still demon-
strated this restrictive abnormality 2.5 years after initial
testing.
Discussion
In this review, we present a retrospective review of 10
patients at our center with cSLE and PFTs abnormalities to
characterize the most common findings in patients with
cSLE. In our study population, the most common pulmo-
nary function abnormality was an alteration in diffusing
capacity. Lung volume analysis also showed restrictive lung
disease as a common manifestation. No patients exhibited
obstructive disease. Decreased diffusion capacity is a PFT
finding that is commonly seen in autoimmune diseases
Altchek et al.
including SLE. This is a common pattern seen in our pa-
tients with cSLE as shown in this review. Importantly, this
review recognized that almost a quarter of all patients di-
agnosed with cSLE at our center had abnormalities in PFTs,
regardless of their symptom status. Only 50% of patients
with abnormal PFTs during initial testing endorsed pul-
monary symptoms at that time. Additionally, only three of
the ten patients (30%) had imaging completed due to their
abnormal PFTs, and none of these HRCT images demon-
strated evidence of ILD.
These alterations in PFTs seen at our center reinforce
the findings seen in the analyses completed in the 1990s,
where primarily restrictive and diffusion pulmonary
abnormalities were characterized amongst this patient
population.4,5 However, our study only demonstrated
PFT abnormalities in 23.8% of patients with cSLE at our
center (10 out of 42 total patients with cSLE), whereas the
studies previously performed looking at PFT alterations
in this population saw abnormalities in anywhere from
one-third to over half of their patients with cSLE. 4,5,7
These studies had a similar sample size to our review,
except Trapani et al.7, which had a patient population of
15, where they found 40% demonstrated PFT
abnormalities.7
These results should be interpreted in the context of this
study’s potential limitations. The sample size of 10 patients
out of 42 cSLE patients overall, was small and located at a
single center, which may decrease the generalizability of
these results. Further, data collection and analysis only took
place over a 5-year period, limiting characterization of
follow-up data. Also, there was insufficient follow-up data
within the study period for some of these patients, partic-
ularly those with restrictive lung disease, due to lack of lung
volume data included in their PFTs at follow-up. This
limited our ability to characterize the progression of their
disease. This study was a retrospective review of patient
charts, leading to potential missing data or charting in-
consistencies. Outcomes may also have been confounded
by uncollected data.
In conclusion, PFTs abnormalities are very common in
patients with cSLE even in the absence of symptoms. These
results reinforce the importance of screening all cSLE pa-
tients with PFTs early in their disease course, regardless of
clinical symptoms, to discover pulmonary abnormalities.
Larger studies with comprehensive follow-up of spirometry,
lung volumes, and diffusion capacity measurements are
warranted to support these findings and provide more in-
sight on implications for prognosis, as well as appropriate
treatment modalities for these patients. Longer-term follow-
up and stronger evidence is needed to fully interpret the
implications of our results for prognosis and disease pro-
gression in cSLE patients.
693
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with re-
spect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, au-
thorship, and/or publication of this article.
ORCID iDs
AJ Altchek  https://orcid.org/0000-0003-4628-1111
LN Moorthy  https://orcid.org/0000-0001-9410-2099
References
1. Harry O, Yasin S and Brunner H. Childhood-onset systemic
lupus erythematosus: a review and update. J Pediatr 2018;
196: 22–30.
2. Delgado EA, Malleson PN, Pirie GE, et al. The pulmonary
manifestations of childhood onset systemic lupus eryth-
ematosus. Semin Arthritis Rheum 1990; 19: 285–293.
3. Nadorra RL and Landing BH. Pulmonary lesions in child-
hood onset systemic lupus erythematosus: analysis of 26
cases, and summary of literature. Pediatr Pathol 1987; 7:
1–18.
4. Lilleby V, Aaløkken TM, Johansen B, et al. Pulmonary in-
volvement in patients with childhood-onset systemic lupus
erythematosus. Clin Exp Rheumatol 2006; 24: 203–208.
5. Caeiro F, Michielson FM, Bernstein R, et al. Systemic lupus
erythematosus in childhood. Ann Rheum Dis 1981; 40:
325–331.
6. Veiga CS, Coutinho DS, Nakaie CMA, et al. Subclinical
pulmonary abnormalities in childhood-onset systemic lupus
erythematosus patients. Lupus 2016; 25: 645–651.
7. Trapani S, Camiciottoli G, Ermini M, et al. Pulmonary in-
volvement in juvenile systemic lupus erythematosus: a study
on lung function in patients asymptomatic for respiratory
disease. Lupus 1998; 7: 545–550.
8. Stanojevic S, Kaminsky DA, Miller MR, et al. ERS/ATS
technical standard on interpretive strategies for routine lung
function tests. Eur Respir J 2022; 60: 2101499.
9. Culver BH, Graham BL, Coates AL, et al. Recommendations
for a standardized pulmonary function report: an official
American Thoracic Society Technical Statement, Am J Respir
Crit Care Med 2017; 196: 1463-1472.
10. Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic ref-
erence values for spirometry for the 3–95-yr age range: the
global lung function 2012 equations. Eur Respir J 2012; 40:
1324–1343.
11. Gladman DD, Ibañez D and Urowitz MB. Systemic lupus
erythematosus disease activity index 2000. J Rheumatol
2002; 29: 288–291.