Abstract

BackgroundThe exact risk assessment is crucial for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. In the present study, we develop a nomogram to predict 3‑ and 5-year mortality by using machine learning approach and test the ILD-GAP model in Chinese CTD-ILD patients.MethodsCTD-ILD patients who were diagnosed and treated at the First Affiliated Hospital of Zhengzhou University were enrolled based on a prior well-designed criterion between February 2011 and July 2018. Cox regression with the least absolute shrinkage and selection operator (LASSO) was used to screen out the predictors and generate a nomogram. Internal validation was performed using bootstrap resampling. Then, the nomogram and ILD-GAP model were assessed via likelihood ratio testing, Harrell’s C index, integrated discrimination improvement (IDI), the net reclassification improvement (NRI) and decision curve analysis.ResultsA total of 675 consecutive CTD-ILD patients were enrolled in this study, during the median follow-up period of 50 (interquartile range, 38–65) months, 158 patients died (mortality rate 23.4%). After feature selection, 9 variables were identified: age, rheumatoid arthritis, lung diffusing capacity for carbon monoxide, right ventricular diameter, right atrial area, honeycombing, immunosuppressive agents, aspartate transaminase and albumin. A predictive nomogram was generated by integrating these variables, which provided better mortality estimates than ILD-GAP model based on the likelihood ratio testing, Harrell’s C index (0.767 and 0.652 respectively) and calibration plots. Application of the nomogram resulted in an improved IDI (3- and 5-year, 0.137 and 0.136 respectively) and NRI (3- and 5-year, 0.294 and 0.325 respectively) compared with ILD-GAP model. In addition, the nomogram was more clinically useful revealed by decision curve analysis.ConclusionsThe results from our study prove that the ILD-GAP model may exhibit an inapplicable role in predicting mortality risk in Chinese CTD-ILD patients. The nomogram we developed performed well in predicting 3‑ and 5-year mortality risk of Chinese CTD-ILD patients, but further studies and external validation will be required to determine the clinical usefulness of the nomogram.

Highlights

  • The exact risk assessment is crucial for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD) patients

  • The patients would be included if they met four of the following inclusion criteria: (1) Patients were diagnosed Connective tissue disease (CTD)-ILD recommendated by the American Rheumatism Association and the American College of Rheumatology [6,7,8,9,10,11,12], including polymyositis/dermatomyositis (PM/DM), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), sjogren syndrome (SS), mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), undifferentiated connective tissue disease (UCTD) and overlap syndromes (OCTD)

  • UCTD patients should followed the diagnostic criteria for UCTD-ILD established by the previous research [13]; (2) having clinical symptoms; (3) having signs suggestive of ILD; (4) having radiographic signs of ILD confirmed by high-resolution computed tomography (HRCT)

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Summary

Introduction

The exact risk assessment is crucial for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. We develop a nomogram to predict 3‐ and 5-year mortality by using machine learning approach and test the ILD-GAP model in Chinese CTD-ILD patients. CTD could involve multiple organs and systems, among which interstitial lung disease (ILD) remains a main cause of morbidity and mortality [2]. The exact risk assessment is crucial for the management of CTD-ILD patients. The risk prediction of CTD-ILD remains challenging, due to the heterogeneity in patient-specific and disease-specific variables. The ILD-GAP model has not been validated in Chinese CTD-ILD patients. More inclusive studies are needed to validate and improve the prediction accuracy of the existing assessment model

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