The PhD research by Yu-Hsiang Chiu (UMC Utrecht) provided provides valuable insights for risk assessment, biomarker identification, and potential treatment strategies for patients with connective tissue disease-associated instertitial lung disease. For example, decreases in disease biomarkers such CXCL11, CTGF and KL-6 were associated with improved pulmonary outcomes.

Connective tissue diseases (CTDs) are a group of systemic autoimmune diseases characterized by inflammation and tissue destruction, of which some develop fibrosis thereafter, including skin, internal organs and joints. CTD can present heterogeneously, but pulmonary involvement, including airway disease and interstitial lung disease (ILD), can occur in all classifiable CTD. The prevalence of ILD is significant in systemic autoimmune diseases such as rheumatoid arthritis (RA), systemic sclerosis (SSc) and primary Sjögren’s syndrome (pSS). CTD-associated ILD (CTD-ILD) is one of the leading causes of morbidity and mortality in CTD patients and impairs quality of life substantially due to shortness of breath, chest pain and coughing. Extrapulmonary manifestations include skin tightness, muscle weakness, enthesitis, arthritis, cardia involvement, pulmonary hypertension and fatigue.

Risk factors and biomarkers

The studies by Chiu and colleagues identified that in CTD-ILD patients older age, smoking, extent of fibrosis, and poor lung function were associated with poor prognosis and increased mortality. The criteria for defining PPF showed similar prognostication, with variable performance between various patient groups. A panel of 38 serum biomarkers was explored and decreases in certain disease biomarkers such as CXCL11, CTGF and KL-6 were associated with improved pulmonary outcomes.

Stem cell transplantation

The thesis also reviewed the potential benefit and risk of hematopoietic stem cell transplantation (HSCT) in rapid progression of SSc-associated ILD. Profibrotic mechanisms in SSc, including cellular senescence and endothelial-to-mesenchymal transition, were evaluated. In patients with SSc-ILD, HSCT resulted in stabilization and modest improvements in lung volume and disease extent, but with fewer effects on diffusion capacity.In addition, HSCT is associated with severe treatment-related complications. HSCT should therefore only be provided by experienced multidisciplinary teams is carefully selected patients.

The PhD thesis by Yu-Hsiang Chiu provides valuable insights for risk assessment, biomarker identification, and potential (personalized) treatment strategies to improve clinical outcomes for CTD-ILD patients.

PhD defense