ABSTRACT
The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement therapies (SRT). It took some time to close the gap between the identification of the biophysical and molecular causes of the high mortality associated with respiratory distress syndrome in very premature babies and the development of a proper therapy. Closing the gap required the elucidation of some key questions defining the structure-function relationships in surfactant as well as the particular role of the different molecular components assembled into the surfactant system. On the other hand, the application of SRT as part of treatments targeting other devastating respiratory pathologies, in babies and adults, is depending on further extensive research still required before enough amounts of good humanized clinical surfactants will be available. This review summarizes our current concepts on the compositional and structural determinants defining pulmonary surfactant activity, the principles behind the development of efficient natural animal-derived or recombinant or synthetic therapeutic surfactants, as well as a the most promising lines of research that are already opening new perspectives in the application of tailored surfactant therapies to treat important yet unresolved respiratory pathologies.
Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Respiratory Distress Syndrome , Animals , Humans , Infant, Newborn , Pulmonary Surfactants/chemistry , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/drug therapy , Surface-Active Agents/pharmacology , Surface-Active Agents/therapeutic useSubject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumocystis carinii/immunology , Pneumonia, Pneumocystis/immunology , Pneumonia, Viral/immunology , Pulmonary Surfactant-Associated Proteins/chemistry , Pulmonary Surfactants/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Amino Acid Sequence , Antibodies, Viral/chemistry , Antibodies, Viral/genetics , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus 229E, Human/immunology , Coronavirus Infections/genetics , Coronavirus Infections/pathology , Coronavirus Infections/virology , Coronavirus OC43, Human/immunology , Cross Reactions , Epitopes/chemistry , Epitopes/genetics , Epitopes/immunology , Gene Expression , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Oligopeptides/chemistry , Oligopeptides/genetics , Oligopeptides/immunology , Pandemics , Pneumocystis carinii/pathogenicity , Pneumonia, Pneumocystis/genetics , Pneumonia, Pneumocystis/pathology , Pneumonia, Pneumocystis/virology , Pneumonia, Viral/genetics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Binding , Pulmonary Surfactant-Associated Proteins/genetics , Pulmonary Surfactant-Associated Proteins/immunology , Pulmonary Surfactants/immunology , Pulmonary Surfactants/metabolism , SARS-CoV-2 , Sequence Homology, Amino Acid , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
Coronavirus disease 2019 (COVID-19) is an RNA virus-based disease that can be deadly. For critically ill patients, mechanical ventilation is an important life-saving treatment. However, mechanical ventilation shows a trade-off between supporting respiratory function and ventilator-induced lung injury (VILI). Surfactant therapy is a medical administration of exogenous surfactant to supplement or replace deficient or dysfunctional endogenous surfactant. Surfactant therapy can be used to postpone or shorten the use of mechanical ventilation to minimize or avoid VILI, because surfactants can reduce surface tension, improve lung compliance, and enhance oxygenation. In addition, nanotechnology can be applied to improve the therapeutic effect and reduce the adverse effects of surfactants. In this perspective, we discussed how nanoparticles deliver surfactants through intravenous injection and inhalation to the expected lung disease regions where surfactants are mostly needed, and discussed the prospects of nanoparticle-mediated surfactant therapy in the treatment of patients with severe COVID-19.