Risk Factors for Pulmonary Involvement in Patients with ANCA-associated Vasculitis: A Systematic Review and...

Pulmonary involvement (PI) in ANCA-associated vasculitis (AAV), especially interstitial lung disease (ILD) and diffuse alveolar hemorrhage (DAH), predicts poor outcomes, but a synthesis distinguishing these phenotypes is lacking. We searched seven databases up to April 1, 2026, and included observational studies. Using univariate and multivariate meta-analyses, we calculated pooled odds ratios (OR) or mean differences (MD). Nineteen studies (2,944 patients) were included. For ILD, robust independent risk factors were age > 65 years (OR = 3.60) and male gender (OR = 2.57). MPO-ANCA positivity was more frequent in the ILD group (OR = 2.29). Potential associated factors included smoking, D-dimer, ANA, low C4, and CA199. MPA subtype, cough, and dyspnea were more frequent in the ILD group. Factors associated with lower ILD frequency included GPA subtype, PR3-ANCA positivity, c-ANCA positivity, ENT involvement, gastrointestinal involvement, and a higher BVAS score. For DAH, potential associated factors included proteinuria, high BVAS score, Cr, BUN, PCT, decreased Hb, and low C3. PR3-ANCA positivity and hemoptysis were more frequent in the DAH group. For overall PI, independent risk factors were age (continuous OR = 1.04, > 65 years OR = 4.20), male gender (OR = 3.08), and high BVAS (OR = 3.03). MPO-ANCA positivity (OR = 2.55) was more frequent in the overall PI group, which largely overlapped with those for ILD, suggesting that ILD is the main driver of overall PI. This first meta-analysis combining univariate and multivariate approaches with an evidence-grading framework for ILD demonstrates distinct clinical patterns for ILD versus DAH, offering a clinically actionable tool for risk stratification and personalized management of PI in AAV.