Background/Purpose: Interstitial lung disease (ILD) is a leading cause of mortality in systemic sclerosis (SSc) but it is not severe or progressive in all patients. Serial pulmonary function tests (PFTs) can predict outcomes but there are no established data regarding what is a clinically meaningful decline in these variables in SSc-ILD. We sought to quantify change in pulmonary function as a predictor of outcome in SSc-ILD.

Methods: Patients with SSc with ILD defined by high resolution CT lung scan were identified through a nationwide cohort study. All PFTs performed during follow-up, including forced expiratory volume in one second (FEV1) (L), forced vital capacity (FVC) (L), FEV1/FVC ratio (%), diffusing capacity of the lung for carbon monoxide (DLCO) (ml/min/mmHg) and  DLCO by alveolar volume ratio (DLCO/VA) (ml/min/mmHg/L) were retrieved. Demographic and disease-related data were prospectively collected. The rate of change over four years in the absolute value for each variable was calculated for each patient using a regression line of best fit. Percentage change in absolute values over the first year of follow-up from diagnosis of SSc-ILD (±90 days) was determined.  The composite outcome variable was deterioration, defined as need for home oxygen or lung transplantation, or death.  Univariable Cox regression models were used to determine the relationship between each of rate of decline and percentage decline in each PFT variable and outcome.  Receiver operating characteristics (ROC) curves were used to determine the best cut-off points to predict adverse outcomes.

Results: Among 264 patients in whom PFT data were available from time of ILD diagnosis, there were 49 events (38 deaths, 10 prescribed supplemental oxygen, one lung transplant) over a mean (±SD) follow-up of 3.0 (±1.7) years. The rates of decline over time in each of FVC, DLCO & DLCO/VA were significantly predictive of deterioration or death (hazard ratios [HR] of 0.06, 0.637 and 0.06 respectively, p values all <0.0001). Cut-off values of zero (i.e. no overall change in PFTs over four years) gave the optimal sensitivity-specificity trade-off with negative predictive values (NPVs) of 88-96%. The percentage changes in FVC, DLCO and DLCO/VA over one year from diagnosis (±90 days) were significantly associated with outcome (HRs 1.06 [p<0.04], 1.07  [p<0.0001] and 1.05 [p<0.04] respectively). The best trade-off between sensitivity and specificity was a decline in FVC of 10% and in DLCO and DLCO/VA of 15% with NPVs of 92-93%. A decline in DLCO/VA of 15% predicted a poor outcome with a likelihood ratio of 7.62.

Conclusion: The course that SSc-ILD takes is evident within the first 1-4 years following its diagnosis. Patients who have no decline in PFTs over the first 4 years do well. As seen in idiopathic pulmonary fibrosis, a decline within the first year in FVC of 10% or more and DLCO or DLCO/VA of 15% or more bodes badly and identifies patients who should be monitored more closely and considered for therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/quantifying-change-in-pulmonary-function-as-a-prognostic-marker-in-systemic-sclerosis-related-interstitial-lung-disease/