Respiratory distress syndrome, surfactant

There are also several examples of natural surfactants and foams in the human body. The understanding of the pulmonary surfactant system, although discovered in 1929, has only been applied clinically since about 1990 for the treatment of respiratory distress syndrome. Surfactant replacement therapy may also be used in treating other forms of lung disease, such as meconium aspiration syndrome, neonatal pneumonia and congenital diaphragmatic hernia [881]. Lung surfactant, composed of phospholipids and proteins [882,883], is necessary to maintain a low surface tension at the alveolar air-liquid interface. When there is a deficiency of surfac-... 

There is a clinical need for non-natural, functional mimics of the lung surfactant (LS) proteins B and C (SP-B and SP-C), which could be used in a biomimetic LS replacement to treat respiratory distress syndrome (RDS) in premature infants [56]. An effective surfactant replacement must meet the following performance requirements (i) rapid adsorption to the air-liquid interface, (ii) re-spreadabihty... 

For the treatment of lung surfactant deficiency in premature human infants suffering from respiratory distress syndrome, limited clinical trials were performed showing that liposomes in the lung-instilled intratracheally either as an aerosolized mist (Ivey et al., 1977) or as a suspension via an endotracheal tube (Fujiwara et al., 1980)—rapidly improved lung function. No adverse effects were observed as a result of the supplementation with surfactant-like material. It appears, therefore, that liposomes are a suitable system for the delivery of major phospholipid components of endogenous lung surfactant. 

Deficiency of Lung Surfactant Causes Respiratory Distress Syndrome... 

Lung surfactant is composed mainly of lipid with some proteins and carbohydrate and prevents the alveoli from collapsing. Surfactant activity is largely attributed to dipalmitoylphosphatidylcholine, which is synthesized shortly before parturition in full-term infants. Deficiency of lung surfactant in the lungs of many preterm newborns gives rise to respiratory distress syndrome. Administration of either natural or artificial surfactant has been of therapeutic benefit. 

Phospholipids and sphingolipids are involved in several disease processes, including respiratory distress syndrome (lack of lung surfactant), multiple sclerosis... 

Infant respiratory distress syndrome (IRDS), also known as hyaline membrane disease, is one of the most common causes of respiratory disease in premature infants. In fact, it occurs in 30,000 to 50,000 newborns per year in the U.S. — most commonly in neonates bom before week 25 of gestation. IRDS is characterized by areas of atelectasis, hemorrhagic edema, and the formation of hyaline membranes within the alveoli. IRDS is caused by a deficiency of pulmonary surfactant. Alveolar type II cells, which produce surfactant, do not begin to mature until weeks 25 to 28 of... 

A liposomal formulation containing a surfactant, which usually coats the mucosa of the bronehi and prevents a collapse of the alveolar vesieles of the lung, has been developed for patients who suffer from infant respiratory distress syndrome (IRDS) or adult-aequired respiratory distress syndrome (ARDS). Premature babies often suffer IRDS before the development of a funetional lung surfaetant and pulmonary gas exehange. ARDS is also a life-threatening failure and loss of the lung function and is usually acquired by illness or accident. Clinieal trials with liposomal surfactant have proved to be effective in prophylaetie treatment of IRDS and ARDS. 

Failure to synthesise sufficient surfactant or the synthesis of abnormal surfactant, so that surface tension cannot be lowered, may play a role in several conditions respiratory distress syndrome of the newborn sudden infant death ( cot death ) and adult respiratory distress syndrome. The enzymes involved in the synthesis of surfactant only appear during the third trimester of pregnancy, so that surfactant is not produced in premature babies and they have difficulty breathing. 

T Kobayashi, K Tashiro, X Cui, T Konzaki, Y Xu, C Kabata, K Yamamoto. Experimental models of acute respiratory distress syndrome clinical relevance and response to surfactant therapy. Biology Neonate 80 Suppl 1 26—28, 2001. 

Up to 15% of premature infants and even some babies delivered by cesarean section have inadequate levels of surfactant, producing respiratory distress syndrome, which is characterized by cyanosis and symptoms of labored breathing. 

Infants born prematurely are at risk for respiratory distress syndrome. In such cases, it is common to administer surfactant, the purpose of which is to alter which of the following properties of water at the alveolar interface with air ... 

Conversely, the role of perfluorocarbons for oxygen transport and in vivo delivery is investigated. In addition to possible use as temporary blood substitute, these fluorocarbon molecules can be applied as respiratory gas carriers, for instance as lung surfactant replacement compositions for neonates and possibly for the treatment of acute respiratory distress syndrome for adults. Another... 

Tyloxapol Surfactant Mucolytic, respiratory distress syndrome... 

Phospholipid that is the major component of Tung surfactant, and the syndrome caused by its deficiency Dipalmitoylphosphatidylcholine (DPPC, also called dipalmitoyllecithin, DPPL) is the major lipid component of lung surfactant. It is made and secreted by type II granular pneu-mocytes. Insufficient surfactant production causes respiratory distress syndrome, which can occur in preterm infants or adults whose surfactant-producing pneumocytes have been damaged or destroyed. 

When air is exhaled the small alveoli of the lungs could collapse if it were not for the surface active material (surfactant) present in the fluid that coats the lungs. e In fact, the lack of adequate surfactant is the cause of respiratory distress syndrome, a major cause of death among premature infants and a disease that may develop in acute form in adults. The surfactant material forms a thin film of high fluidity at the air-liquid interface and lowers the surface tension from the 72 mN/m of pure water to <10 mN/mfs (Pay attention to the definition of surface tension.11)... 

An apparent association between severe retinopathy of prematurity and dexamethasone therapy has been shown in a retrospective study (SEDA-20, 372 76). Infants treated with dexamethasone required longer periods of mechanical ventilation (44 versus 26 days), had a longer duration of supplemental oxygen (57 versus 29 days), had a higher incidence of patent ductus arteriosus (28/38 versus 18/52), and required surfactant therapy more often for respiratory distress syndrome (17/38 versus 11/52). Prospective, randomized, controlled studies are needed to correct for differences in severity of cardiorespiratory disease. Until such studies are available, careful consideration must be given to indications, dosage, time of initiation, and duration of treatment with dexamethasone in infants of extremely low birthweight. 

Alveoli represent the primary site for gas exchange within the lung, and thus their health is vital for survival. Alveolar conditions with a primary genetic cause, such as surfactant protein-B (SP-B) deficiency and SP-C deficiency, are prime candidates for a rAAV-gene therapy approach. Diseases in which alveoli are damaged secondary to other defects might also be treated with gene transfer. Such conditions include environmental toxin exposure, infectious diseases, and adult respiratory distress syndrome (ARDS) (Table 4.1) (Rolls et al., 1997, 1998, 2001 Cheers et al 1999 Ruan et al., 2002). 

Lung surfactant decreases the surface tension and thereby maintains the morphology and function critical for respiration. Deficiency of surfactant in the newborn infant is a condition known as respiratory distress syndrome (RDS) and in adults as adult respiratory distress syndrome (ARDS). A number of commercial artificial surfactants, e.g. Exosurf and ALEC, together with natural surfactant preparations, e g. Surventa and Curosurf, are currently available to treat these conditions. 

Dipalmitoyl phosphatidyl choline is one component of human lung surfactant, which coats the inner surfaces of the lung membranes and prevents them from clinging together and collapsing. Premature infants often produce little or no lung surfactant, which can lead to collapsed alveoli and other symptoms of infant respiratory distress syndrome (IRDS). 

In 1959, surfactant deficiency was identified as the major pathogenic factor in respiratory distress syndrome in infants. Pulmonary surfactant is a complex mixture of phospholipids, neutral lipids, and specific proteins which spread as a monolayer at the air-liquid... 

One of the medical problems already raised in sec. I.l, is that premature babies may not have produced enough of the surfactant mixtures, leading to so-called respiratory distress syndrome (RDS), This disease is nowadays readily overcome by letting the baby inhale a spray containing the mixture. The remedy is facilitated by the non-specificity of the mixture the composition is not as critical as it would have been in say, implants. 

Therapeutically, lecithin and derivatives have been used as a pulmonary surfactant in the treatment of neonatal respiratory distress syndrome. 

Dipalmitoylphosphatidylcholine serves as the lung surfactant in adults, allowing the lungs to function normally. This phospholipid develops in the fetus after week 30 of gestation. Premature infants do not have an adequate amount of this phospholipid. As a result, acute respiratory distress syndrome is a leading cause of morbidity and death in premature infants. 

D. Respiratory distress syndrome is caused by a deficiency of lung surfactant, which is composed mainly of dipalmitoylphosphatidylcholine. 

Once one knows the problem and has devised a solution, then the real job begins. National Center for Health Statistics data show a decline in total US infant mortality from 1982 to 1992, but marked geographic and racial differences remain. The 1992 overall US rate of infant death was 8.5 per 1000 live births (California, 6.9 Texas, 7.7 New York, 8.5 New Jersey, 8.5 Pennsylvania, 8.6 Ohio, 8.7 Florida, 9.1 Illinois, 10.0 Georgia, 10.4 Michigan, 10.5) - a decline attributed not to reductions in the numbers of birth defects or premature births but to improved neonatal intensive care units and the introduction of synthetic pulmonary surfactants and consequent reductions in death from acute neonatal respiratory distress syndrome. Still, the years of potential life lost due to birth defects ranks fifth, just behind that of homicide and suicide (1, unintentional injury 2, cancer 3, cardiovascular disease) prematurity/low birth weight ranks sixth and sudden infant death syndrome seventh. Ethnic discrepancy remains pronounced rates of White (5.8 per 1000 live births) and Cuban Hispanic (3.7 per 1000 live births) infant death are similar, but the 2002 rate for Blacks (13.9 per 1000 live births) increased compared to the previous year. 

Indications Prevention of respiratory distress syndrome Category Pulmonary surfactant Half-life N/A... 

Clements JA, Piatzker ACG, Tierney DF, Hobel CJ, Creasy RK, MargoHs AJ, et al. Assessment of the risk of the respiratory-distress syndrome by a rapid test for surfactant in amniotic fluid. N Engl J Med 1972 286 1077-81. 

Hallman M, Merritt TA, Jarvenpaa AL, Boynton B, Mannino F, Gluck L, et al. Exogenous human surfactant for treatment of severe respiratory distress syndrome a randomized prospective clinical trial. J Pediatr 1985 106 963-9. 

A large package of data, and two well-con-trolled pivotal studies of safety and efficacy are rarely required, with the exception of diseases specific to childhood, such as surfactant studies in respiratory distress syndrome. This is especially the case if the drug has similar effects in both adult and pediatric populations, for example antihistamines. 

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