The objective of IFALT Project is to identify new diagnostic approaches that could avert fatal outcomes among bilateral and single orthotopic lung transplant recipients presenting with respiratory failure. Respiratory failure is the most common postoperative complications in lung transplant recipients and it is associated with high morbidity and mortality (one-year mortality 24%). According to the registry of the International Society for Heart and Lung Transplantation, allograft rejections and lung infections account for a significant percentage of cases of respiratory failure in this population. However, discriminating graft rejections from other causes of respiratory failure and identifying the causative pathogen of lung infections remain still problematic. Developing new approaches for identifying the etiology of respiratory failure is essential to improve survival among lung transplant patients. As a consequence, the specific aims of the IFALT project are to: i) develop new diagnostic approaches for discriminating allograft rejection from other causes of respiratory failure among lung transplant recipients based on host gene expression strategies (Aim 1); ii) develop new diagnostic approaches for the identification of the infective causal agents of lung infections among lung transplant recipients based on host gene expression strategies (Aim 2); iii) develop new diagnostic approaches for discriminating allograft rejection from infectious causes of respiratory failure among lung transplant recipients based on microbiome profiling (Aim 3). Project aims will be achieved by the IFALT partners, which include private and public institutions located in southern Italy and northern Italy. IFALT partners in northern Italy will be responsible for the identification of disease classifiers (IFALT Project Phase 1). Based on the disease classifiers identified by IFALT partners in northern Italy, IFALT partners in southern Italy will be in charge of migrating the disease classifiers into widely applicable point-of-care tests for diagnosing graft rejections and lung infections among lung transplant recipients presenting with respiratory failure (IFALT Project Phase 2). Doing so is consistent with the Ministero dell’Istruzione e della Ricerca’s mission to develop new diagnostic approaches for severe illness and to promote the technical and economic growth of southern Italy through a bidirectional exchange of scientific and management expertise.