Geospatial and temporal trends of interstitial lung disease subtypes and KL-6 biomarker in China: a nationwide study (2016–2024)

The burden of interstitial lung diseases (ILDs) in China is rising, yet large-scale, subtype-specific epidemiological data remain limited. We retrospectively analyzed 7,195 hospitalized patients at the First Affiliated Hospital of Guangzhou Medical University (January 2016—June 2024), including 6,824 ILD cases and 371 pneumonia controls. Clinical data included demographics, smoking, BMI, geographic region, and serum KL-6 levels. Among the 6,824 ILD patients, autoimmune-related ILD was the most prevalent subtype (34.33%), followed by idiopathic ILD (22.70%). Regionally analysis revealed significant variations: idiopathic ILD accounted for 52.14% of ILDs in Northeast China, while autoimmune-related ILD comprised 50.64% in South China, proportions significantly higher than in other regions. Serum KL-6 levels were highest in autoimmune-related ILD (1,140 U/mL), followed by idiopathic ILD (1,023 U/mL), both were significantly elevated compared to other subtypes. Notably, pulmonary alveolar proteinosis (PAP) exhibited the highest KL-6 levels among all subgroups (median: 2,503 U/mL). Logistic regression (vs. PN) identified smoking as an independent risk factor for idiopathic ILD (OR = 2.087, p < 0.001). Furthermore, KL-6 positivity (≥ 500 U/mL) was strongly associated with both idiopathic ILD (OR = 13.521, p < 0.001) and autoimmune-related ILD (OR = 16.682, p < 0.001). This study reveals a distinct “Northeast–Idiopathic and South–Autoimmune” distribution of ILD subtypes in China and highlights KL-6 variations among phenotypes. Extreme KL-6 elevation in pulmonary alveolar proteinosis suggests a biomarker for disease severity. These findings suggest that KL-6 can serve as an adjunctive aid in the differential diagnosis of certain ILD subtypes and provide a basis for precision medicine in ILD management.