Systemic Sclerosis Patients Show Lung Function Decline Before Meeting Classification Criteria

A substantial minority of patients diagnosed with very early systemic sclerosis experience measurable pulmonary function decline before fulfilling formal systemic sclerosis classification criteria, according to a retrospective longitudinal analysis published in Arthritis Research & Therapy. Drawing data from two independent cohorts within the STRIKE and EUSTAR databases, the multi-center study evaluated respiratory trajectories in individuals with very early diagnosis of systemic sclerosis, known as VEDOSS. The findings indicate that significant functional deterioration in the lungs can unfold prior to the clinical milestone at which standard classification criteria for systemic sclerosis are formally met.

The investigation was prompted by prior observations within the EUSTAR registry indicating that the mean forced vital capacity at the time interstitial lung disease is diagnosed stands at approximately 87 percent. This clinical baseline value suggested that a measurable period of pulmonary function deterioration occurs well before interstitial lung disease is formally detected during routine care. To examine whether lung function loss is already active at this initial phase, the investigators systematically tracked longitudinal pulmonary function testing trajectories in patients who presented with very early systemic sclerosis features.

To evaluate these trajectories, the research team conducted a retrospective analysis that brought together two independent cohorts comprising a total of 455 patients across the STRIKE and EUSTAR databases. Specifically, 77 patients were analyzed from the STRIKE cohort, while 378 patients were drawn from the EUSTAR registry. Patients were eligible for inclusion at baseline if they fulfilled the established VEDOSS criteria but did not meet the 2013 ACR/EULAR systemic sclerosis classification criteria, and had completed at least one follow-up pulmonary function test.

Within the analytical protocol, very early pulmonary function decline was defined using specific objective thresholds during follow-up testing. The primary threshold required an absolute decline of at least 10 percent in forced vital capacity, abbreviated as FVC. Alternatively, pulmonary function decline was documented if patients demonstrated a 5 to 9 percent decline in forced vital capacity that was accompanied by an absolute decline of at least 15 percent in diffusing capacity of the lung for carbon monoxide, abbreviated as DLCO, recorded at any time during patient follow-up.

Across the two independent groups, pulmonary function tests revealed measurable decline in notable proportions of participants. Respiratory function decline defined by these pulmonary function thresholds occurred in 22.1 percent of patients in the STRIKE cohort and in 17.2 percent of patients in the EUSTAR cohort. A time-to-event statistical analysis of the combined study population demonstrated an estimated cumulative incidence of very early pulmonary function decline of 20.4 percent, with a 95 percent confidence interval spanning from 15.0 to 25.4 percent, at five years of follow-up.

Baseline assessments revealed that diffusing capacity of the lung for carbon monoxide was already reduced in both cohorts despite normal forced vital capacity measurements. In the STRIKE cohort, mean baseline DLCO was 90 percent plus or minus 18, while mean forced vital capacity remained preserved at 102 percent plus or minus 15. Similarly, in the EUSTAR cohort, baseline DLCO averaged 85 percent plus or minus 16, whereas mean forced vital capacity was 106 percent plus or minus 16. Among the subset of patients who experienced confirmed pulmonary function decline, 46.3 percent went on to fulfill the 2013 ACR/EULAR systemic sclerosis classification criteria over the course of subsequent clinical follow-up.

The study also examined biological indicators by comparing clinical features and available circulating markers between patients categorized as progressors and non-progressors. In the STRIKE cohort, circulating serum markers of extracellular matrix turnover, which together comprise the Enhanced Liver Fibrosis score, were observed to be higher in progressors at baseline and during follow-up compared with non-progressors. These elevated extracellular matrix markers provide molecular evidence supporting the active presence of early fibrotic remodeling within this progressing patient subgroup.

Reflecting on these longitudinal findings, the researchers concluded that measurable loss of pulmonary capacity emerges in a substantial minority of patients with very early systemic sclerosis well before conventional classification criteria are satisfied. The authors noted that the observed functional deterioration and concurrent extracellular matrix turnover warrant the implementation of early interstitial lung disease detection strategies in individuals diagnosed with very early systemic sclerosis, even when they do not fulfill established classification criteria for the systemic disease.

Subject of Research: Longitudinal pulmonary function decline in very early systemic sclerosis

Article Title: Very early pulmonary function decline in systemic sclerosis: longitudinal evidence from the STRIKE and EUSTAR VEDOSS cohorts

Article References: Kakkar, V., Di Donato, S., Ortalli, N., Iannone, F., Kumánovics, G., Bečvář, R., Smith, V., Balanescu, A., Mueller-Ladner, U., Foti, R., Chatelus, E., Colic, J., De Santis, M., Blaise, S., Pirkmajer, K. P., Thornton, L., Batani, V., Bissell, L.-A., Bellando-Randone, S., … Del Galdo, F. (2026). Very early pulmonary function decline in systemic sclerosis: longitudinal evidence from the STRIKE and EUSTAR VEDOSS cohorts. Arthritis Research & Therapy. https://doi.org/10.1186/s13075-026-03945-0

Image Credits: AI Generated

DOI: 10.1186/s13075-026-03945-0

Keywords: Systemic Sclerosis, VEDOSS, Pulmonary Function Test, Forced Vital Capacity, Diffusing Capacity, DLCO, Interstitial Lung Disease, STRIKE Cohort, EUSTAR Database, Enhanced Liver Fibrosis Score, Extracellular Matrix Turnover, Fibrosis, ACR EULAR Criteria, Pulmonary Function Decline, Longitudinal Cohort Study, Rheumatology, Early Diagnosis, Time to Event Analysis