Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis.

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.

Proposal for International Standardization of the Use of Lung Ultrasound for Patients With COVID-19: A Simple, Quantitative, Reproducible Method.

Growing evidence is showing the usefulness of lung ultrasound in patients with the 2019 new coronavirus disease (COVID-19). Severe acute respiratory syndrome coronavirus 2 has now spread in almost every country in the world. In this study, we share our experience and propose a standardized approach to optimize the use of lung ultrasound in patients with COVID-19. We focus on equipment, procedure, classification, and data sharing.

Long-term management of patients with end-stage lung diseases.

Long-term management of end-stage lung disease differs from interstitial lung disease to chronic obstructive pulmonary disease to cystic fibrosis to pulmonary vascular disease. The management includes pharmacological therapy that is disease specific such as antibiotic therapy for cystic fibrosis, antifibrotic drugs in idiopathic pulmonary fibrosis; long-acting beta-agonists, long-acting muscarinic antagonist, and inhaled corticosteroids in chronic obstructive pulmonary disease; and vasodilators in pulmonary arterial hypertension. Moreover, non-pharmacological therapy is essential in the treatment of these diseases, in particular, rehabilitation and supportive therapy, which are necessary in all end-stage lung diseases and specific intervention such as non-invasive ventilation in chronic obstructive pulmonary disease and cystic fibrosis, surgical therapy in chronic obstructive pulmonary disease, and airway clearance in cystic fibrosis. The goal is not only to prolong survival, but it is fundamental to keep patients in good general conditions for transplantation. Transplantation, indeed, remains the only therapeutic option that could prolong survival in patients with terminal lung disease when medical or surgical therapies are not available or not effective anymore.