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      An update on clinical surfactant preparations and respiratory disease Translated title: Una actualización sobre las preparaciones clínicas de surfactantes y enfermedades respiratorias

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          Abstract

          The pulmonary surfactant and respiratory disease are tightly linked. Adequate surfactant activity remains critical for optimal lung function throughout life, and secondary surfactant dysfunction may contribute to the process of many lung diseases, including Acute Respiratory Distress Syndrome, asthma, cystic fibrosis and pneumonia among others. Attempts to treat these lung diseases with exogenous surfactants have been only partially successful. The objective of this article is to carry out an update on clinical surfactant preparations and immunomodulatory properties, as well as all related to clinical trials of clinical surfactant preparations and respiratory diseases in the pharmaceutical market today. The results show the potential to extent the use of the exogenous surfactant preparations to other respiratory disease different than Neonatal Respiratory Disease Syndrome. The importance of immunomodulatory functions of lung surfactant and the aim to evaluate the effectiveness of including different drugs as ingredient of a surfactant preparation represent the research's active field on surfactant topic.

          Translated abstract

          El surfactante pulmonar y las enfermedades respiratorias están estrechamente relacionados. La actividad adecuada del surfactante es esencial para la función óptima del pulmón en los seres humanos. Una disfunción secundaria del surfactante pulmonar puede contribuir al proceso de enfermedades pulmonares como el síndrome de insuficiencia respiratoria aguda, el asma, la fibrosis cística y las neumonías, entre otras. Los intentos de tratar estas enfermedades con surfactantes exógenos han sido parcialmente exitosos. Esta es una actualización referente a las preparaciones clínicas de surfactantes y sus funciones inmunomoduladoras, y lo que acontece en el mercado en relación con los ensayos clínicos que emplean estas preparaciones para mitigar enfermedades pulmonares. Los resultados de un análisis informacional muestran el potencial para extender tales preparaciones en el tratamiento de enfermedades respiratorias diferentes al síndrome de insuficiencia respiratoria aguda del neonato. La relevancia de las funciones inmunomoduladoras del surfactante pulmonar y la evaluación de su potencial formulación de conjunto con otros medicamentos, son un campo de investigación activo.

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          Most cited references60

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          The acute respiratory distress syndrome: pathogenesis and treatment.

          The acute respiratory distress syndrome (ARDS) causes 40% mortality in approximately 200,000 critically ill patients annually in the United States. ARDS is caused by protein-rich pulmonary edema that causes severe hypoxemia and impaired carbon dioxide excretion. The clinical disorders associated with the development of ARDS include sepsis, pneumonia, aspiration of gastric contents, and major trauma. The lung injury is caused primarily by neutrophil-dependent and platelet-dependent damage to the endothelial and epithelial barriers of the lung. Resolution is delayed because of injury to the lung epithelial barrier, which prevents removal of alveolar edema fluid and deprives the lung of adequate quantities of surfactant. Lymphocytes may play a role in resolution of lung injury. Mortality has been markedly reduced with a lung-protective ventilatory strategy. However, there is no effective pharmacologic therapy, although cell-based therapy and other therapies currently being tested in clinical trials may provide novel treatments for ARDS.
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            Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome.

            Preclinical studies suggest that exogenous surfactant may be of value in the treatment of the acute respiratory distress syndrome (ARDS), and two phase 2 clinical trials have shown a trend toward benefit. We conducted two phase 3 studies of a protein-containing surfactant in adults with ARDS. In two multicenter, randomized, double-blind trials involving 448 patients with ARDS from various causes, we compared standard therapy alone with standard therapy plus up to four intratracheal doses of a recombinant surfactant protein C-based surfactant given within a period of 24 hours. The overall survival rate was 66 percent 28 days after treatment, and the median number of ventilator-free days was 0 (68 percent range, 0 to 26); there was no significant difference between the groups in terms of mortality or the need for mechanical ventilation. Patients receiving surfactant had a significantly greater improvement in blood oxygenation during the initial 24 hours of treatment than patients receiving standard therapy, according to both univariate and multivariate analyses. The use of exogenous surfactant in a heterogeneous population of patients with ARDS did not improve survival. Patients who received surfactant had a greater improvement in gas exchange during the 24-hour treatment period than patients who received standard therapy alone, suggesting the potential benefit of a longer treatment course. Copyright 2004 Massachusetts Medical Society
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              Immunomodulatory functions of surfactant.

              J. Wright (1997)
              The possibility that the lipoprotein complex of lung surfactant functions in pulmonary host defense as well as lowering surface tension at the air-liquid interface has been the subject of renewed interest in light of the finding that surfactant proteins A and D (SP-A and SP-D) are members of a family of proteins known as collectins. The collectins, so named because they have in common an NH2-terminal collagen-like domain and a COOH-terminal lectin (carbohydrate binding) domain, are found in both lung and serum and participate in "innate" immunity, acting before induction of an antibody-mediated response. In vitro, many of the collectins stimulate phagocytosis, chemotaxis, and production of reactive oxygen and regulate cytokine release by immune cells. It has been known for several years that surfactant lipids suppress a variety of immune cell functions, most notably lymphocyte proliferation, which, conversely, is augmented by SP-A. Thus surfactant lipids and proteins may be counterregulatory, and changes in lipid-to-protein ratios may be important in regulating the immune status of the lung. That these ratios change in disease states is clear, but it is not known whether the alterations are a cause or an effect. Important future studies with mice in which the SP-A and SP-D genes have been ablated will help clarify the role of surfactant in immune function.
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                Author and article information

                Journal
                bta
                Biotecnología Aplicada
                Biotecnol Apl
                Editorial Elfos Scientiae (La Habana, , Cuba )
                1027-2852
                June 2012
                : 29
                : 2
                : 53-59
                Affiliations
                [01] San José de Las Lajas orgnameCentro Nacional de Sanidad Agropecuaria, Censa orgdiv1Grupo de Química-Farmacología-Toxicología Cuba oblancocensa.edu.cu, odalysbh@ 123456infomed.sld.cu
                Article
                S1027-28522012000200001 S1027-2852(12)02900201
                900fa986-1172-417d-b0d0-b0ce9e081b75

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : September 2011
                : March 2012
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 60, Pages: 7
                Product

                SciELO Cuba

                Self URI: Full text available only in PDF format (EN)
                Categories
                REVIEW

                surfactante pulmonar exógeno,inflamación,enfermedades respiratorias,surfactante pulmonar clínico,Surfactante pulmonar,inflammation,respiratory disease,clinical pulmonary surfactant,exogenous pulmonary surfactant,Pulmonary surfactant

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