Advances in research on the risk factors and pathogenesis of connective tissue disease-associated interstitial lung disease

Abstract

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a group of lung diseases caused by connective tissue diseases, with an incidence ranging from 10% to 50% and a mortality rate as high as 20%. The clinical manifestations and imaging features are heterogeneous. However, its pathogenesis is not fully understood. Exploring the risk factors and pathogenesis is crucial for the diagnosis, treatment and prognosis management of CTD-ILD. The risk factors for CTD-ILD are diverse. Firstly,genetic factors play an important role in pathogenesis. Mutation rate of telomere-related genes (including TERT, RTEL1, PARN, and SFTPC) in CTD-ILD patients is three times as high as that of general population. The risk of developing CTD-ILD in patients with the mutation in MUC5B promoter is more than twice that of normal people. The mutations in the TOLLIP and HLA-DRB1 are also associated with increased disease susceptibility. In addition, medications used to treat CTD may also increase the risk of developing ILD. Approximately one-third of CTD-ILD patients also suffer from gastroesophageal reflux disease. Chronic smoking and exposure to air pollution may also increase the incidence of CTD-ILD. CTD-ILD patients with infections have a higher risk of severe outcomes (OR 1.34-2.73) and increased mortality risk (OR 1.2-4.3). The pathogenesis of CTD-ILD involves the abnormality of the immune system, which is mainly manifested in the production of autoantibodies (such as systemic sclerosis-related antibodies and myositis-specific antibodies), the dysfunction of immune cells (such as neutrophils, natural killer cells, Th2 and Th17) and the extensive release of cytokines (such as TNF-α, TGF-β, IL-6 and IL-8), which exist in more than 50% of CTD-ILD patients. The risk factors and pathogenesis of CTD-ILD are complex. Risk prediction model based on these factors may help identify high-risk individuals accurately, which can provide new strategies for the prevention and treatment of the disease, improve the long-term prognosis of patients.

Keywords

• |connective tissue disease|interstitial lung disease|risk factors|pathogenesis