Pulmonary Function Tests May Underdiagnose Interstitial Lung Disease in Juvenile Systemic Sclerosis

Interstitial pulmonary fibrosis (IPF). Computed tomography (CT) scan of lungs affected by IPF. The two dark structures are the lungs. The white space in the upper center is the heart. The left lung is the most severely affected, with diseased tissue appearing white. IPF is characterized by progressive thickening and stiffening of the lining of the air sacs in the lungs, causing breathlessness and pain. The cause is often unknown but in some cases the disease is thought to result from an autoimmune disorder. Without treatment IPF can lead to heart failure or bronchopneumonia. Treatment depends on the suspected underlying cause.
Study authors determined the performance of pulmonary screening vs HRCT in detecting interstitial lung disease in juvenile SSc.

Pulmonary function tests (PFTs) may be insufficient in detecting interstitial lung disease (ILD) in patients with juvenile systemic sclerosis (jSSc), according to study results published in Arthritis Care & Research. Study authors noted that PFT parameters had limited detection performance compared to high-resolution computed tomography (HRCT).

Study authors extracted data from the international inception cohort for jSSc, a multicenter, prospective, observational study enrolling pediatric patients from 42 academic institutions around the world. Clinical characteristics, laboratory values, and jSSc treatment were reported to the cohort every 6 months by the treating rheumatologist. Lung-specific data collection included the PFT parameters, forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). Results of FVC and DLCO less than 80% of the reference value were considered indicative of ILD. Abnormal HRCT findings were also reported to the cohort, including ground glass opacities, reticulations, and honeycombing.

The current analysis included patients enrolled in the cohort between 2008 and 2020 who had recorded PFT parameters and HRCT results. Sensitivity, specificity, and area under the receiver operating characteristics curve (AUC) were calculated for FVC and DLCO, using HRCT findings as the comparator. Logistic regression was used to identify correlates of positive findings on HRCT.

The analytic cohort included data from 86 patients with jSSc (mean disease duration, 3.1±3.0 years; mean age at onset of Raynaud phenomenon, 10.1±3.9 years), among whom 80% were girls and 77% had diffuse jSSc subtype. The majority of patients (92%) were aged 8 years or older at the time of PFT and HRCT assessment. Prevalence of ILD as determined by HRCT was 44%. In regression models, gastrointestinal involvement was significantly more common in patients with ILD on HRCT compared with patients with no evidence of ILD on imaging (P =.046).

Using FVC less than 80% as a cutoff value, the AUC was 0.58 (95% CI, 0.48-0.68), suggesting poor to moderate discrimination between ILD and no ILD. The sensitivity of this method was 40%, suggesting that 60% of patients with ILD would have received a false negative result with FVC. The specificity of FVC was higher, at 77%. Among the 71 patients with recorded DLCO readings, prevalence of ILD was 43%. The AUC of DLCO was 0.73 (95% CI, 0.61-0.85). Sensitivity and specificity were 76% and 70%, respectively. Among patients who had both FVC and DLCO below 80%, 75% had abnormal HRCT findings. The discriminative capacity of combined FVC and DLCO was 0.76 (95% CI, 0.61-0.91), with combined sensitivity and specificity of 64% and 88%, respectively.

Results from the analysis indicated that PFT alone may be insufficient in detecting all cases of ILD in jSSc. A combination of PFT with HRCT may be necessary for appropriate lung screening in patients with jSSc.

Study limitations were the small patient cohort and the observational design because of which PFT and HRCT were collected clinically and not as a requirement for all patients.

“Further study in our cohort once a higher number of [participants] are enrolled and screened for ILD could include the analysis of the discriminatory properties of these parameters if the FVC and DLCO thresholds were modified from the 80% cutoffs, and the utility of the addition of other clinical characteristics that might predict ILD,” the study authors wrote.


Foeldvari I, Klotsche J, Hinrichs B, et al. Under detection of interstitial lung disease in juvenile systemic sclerosis (jSSc). Arthritis Care Res (Hoboken). Published online November 3, 2020. doi:10.1002/acr.24499