PULMONARY FUNCTION TRAJECTORY IN A PROSPECTIVE COHORT OF GRANULOMATOUS LYMPHOCITIC INTERSTITIAL LUNG DISEASE (GLILD) PATIENTS

• Grant number: 25/10413-8
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2026
• End date: May 31, 2029
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Bruno Guedes Baldi
• Grantee: Bruno Guedes Baldi
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Cristina Maria Kokron ; Ronaldo Adib Kairalla

Abstract

Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) is a severe and underrecognized complication affecting approximately 10-20% of individuals with Common Variable Immunodeficiency (CVID) and other primary antibody deficiencies. This condition is characterized by lymphocytic and/or granulomatous infiltration of the lung interstitium, leading to progressive pulmonary dysfunction, increased morbidity, and reduced survival. Notably, GLILD often affects relatively young patients-frequently in the third to fifth decades of life-with otherwise preserved life expectancy based on their primary disease. However, the presence of interstitial lung involvement has been consistently associated with significant functional decline and higher mortality.Despite its clinical relevance, the natural history of GLILD remains poorly understood. Current evidence is limited to small, retrospective cohorts from high-income countries, with no prospective data available in Latin America. This knowledge gap critically hampers clinical decision-making, including the timing of therapeutic interventions in a population that may remain asymptomatic for extended periods before developing irreversible lung damage.This study aims to prospectively characterize the trajectory of pulmonary function in patients with GLILD over a one-year period. The primary outcome is the absolute change in forced vital capacity (FVC), complemented by secondary assessments of gas exchange (DLCO), radiological progression via quantitative computed tomography, functional capacity through the six-minute walk test, symptom burden, quality of life, and circulating biomarkers.A prospective observational design will be employed, enrolling patients with GLILD under follow-up at a national reference center for interstitial lung diseases and primary immunodeficiencies. Participants will undergo comprehensive evaluations at baseline and after 12 months, incorporating pulmonary function testing, high-resolution computed tomography with quantitative analysis, functional exercise testing, validated quality-of-life instruments, and detailed immunological and biochemical biomarker profiling.The project is scheduled for immediate initiation following ethics approval. Patient recruitment will occur over the first year, with follow-up completed in the second year. Data analysis, interpretation, and dissemination of results-including publication in peer-reviewed journals-are planned for the final semester. This initiative represents the first prospective study on GLILD in Latin America and is expected to generate critical knowledge to improve clinical management, inform early intervention strategies, and contribute to the global understanding of this rare but life-limiting disease. (AU)