Functional, tomographic and exercise evaluation of patients with bronchiolitis obliterans after bilateral lung transplantation and after allogeneic hematopoietic cell transplantation

• Grant number: 24/01600-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: André Nathan Costa
• Grantee: André Nathan Costa
• 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
• Associated researchers: Bruno Guedes Baldi ; Gabriella França Pogorzelski

Abstract

Lung transplantation (LTx) and allogeneic hematopoietic stem cell transplantation (HSCT) are therapeutic options for advanced lung diseases and hematological disorders, respectively. Although they are effective procedures, they are associated with complications, which can limit long-term survival. In this context, chronic graft dysfunction (CGD) is a common cause of reduced survival in TxP and graft-versus-host disease (GVHD) is a frequent complication in allogeneic HSCT.Bronchiolitis obliterans syndrome (BOS) is the main complication in both TxP and allogeneic HSCT, which leads to respiratory dysfunction. It can be triggered by factors such as previous lung changes, type of conditioning regimen, seropositivity for cytomegalovirus, among others. The pathophysiological mechanisms of BOS and pulmonary GVHD are not yet fully understood, but they involve activation of the immune system and airway remodeling.To diagnose BOS, spirometric criteria for airflow obstruction are used, in addition to excluding other causes. Currently, other diagnostic methods are being studied to detect changes in the small airways, including plethysmography, impulse oscillometry, and multiple-breath nitrogen washout. The cardiopulmonary exercise test (CPET) is used to evaluate exercise limitation and the mechanisms involved and there is little data on this type of analysis in the context of SBO and, in particular, in the detection of dynamic hyperinflation.High-resolution computed tomography (HRCT) is a useful tool for the differential diagnosis of respiratory conditions in these patient profiles. In BOS, the most common radiological findings of airway changes are centrilobular micronodules and mosaic attenuation. More recently, densitovolumetric analysis using chest CT has been used, which allows the evaluation and quantification of this type of involvement, especially through the quantification of air trapping.The use of serum biomarkers appears to be promising for the early detection of bronchiolar changes and as prognostic markers for individuals with diagnosed BOS. The most studied in the context of BOS are KL-6, TGF beta, metalloproteinases and TNF alpha.This cross-sectional and physiological study seeks to analyze the functional, tomographic and exercise limitation characteristics in patients with BOS post-bilateral TxP and pulmonary GVHD post-allogeneic HSCT. It also aims to compare the accuracy of different diagnostic methods and identify useful biomarkers. The objective is to improve the understanding and early diagnosis of these complications, contributing to the approach and definition of patient prognosis. (AU)