Lung surfactant deficiency

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. 

The linear dependence between the threshold dilution and the initial total phospholipid concentration (respectively, DPPC) found allows to determine the threshold dilution for a 100% probability for formation of NBF instead of Ct. Fig. 11.5 shows that if a sample dilution of 3.1 times is applied, then it is possible to detect almost all cases with a developed RDS. Therefore, the threshold dilution of 3.1 times allows to distinguish the mature from immature AF samples which gives a good reason to employ it in diagnosing of RDS, and respectively, to estimate the lung surfactant deficiency. Hence, the formation of black foam films from AF samples taken at different gestation weeks and diluted 3.1 times, indicates that there is no risk of RDS, while film rupture predicts an eventual RDS development. 

Calfactant is a lung surfactant. It is an extract of natural surfactant from calf lungs that restores lung surfactant in premature infants with lung surfactant deficiency causing respiratory distress syndrome (RDS). Calfactant is indicated in RDS in premature infants under 29 weeks of gestational age at high risk for RDS and for the treatment rescue of premature infants under 72 hours of age who develop RDS and require endotracheal inmbation. 

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. 

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. 

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-... 

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. 

Pulmonary gene therapy is attractive for the treatmment of chronic bronchitis, cystic fibrosis, a-1 antitrypsin deficiency, familial emphysema, asthma, pulmonary infections, surfactant deficiency, pulmonary hypertension, lung cancer, and malignant mesothelioma. The pulmonary endothelium may act as a bioreactor for the production and secretion of therapeutic proteins, such as clotting factors and erythropoietin into the blood circulation. There is a potential benefit for acquired lung diseases, as well as cancers, to be controlled and possibly treated by expression of cytokines, surfactant, antioxidant enzymes, or mucoproteins within lung cells. 

In addition to being an important component of cell membranes and the blood lipoproteins, phosphatidylcholine provides the fatty add for the synthesis of cholesterol esters in HDL by the LCAT reaction and, as the dipalmitoyl derivative, serves as lung surfactant. If choline is deficient in the diet, phosphatidylcholine can be synthesized de novo hum glucose (see Figure 6-14). 

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

The respiratory distress syndrome (RDS) of a premature infant such as Colleen Lakker is, in part, related to a deficiency in the synthesis of a substance known as lung surfactant. The major constituents of surfactant are dipalmitoylphosphatidyl-choline, phosphatidylglycerol, apoproteins (surfactant proteins Sp-A,B,C), and cholesterol. 

Jain, A., Martensson, J., Mehta, T., Krauss, A. N., Auld, P. A. M., and Meister, A., 1992, Ascorbic acid prevents oxidative stress in glutathione-deficient mice—effects on lung type 2 cell lamellar bodies, lung surfactant, and skeletal muscle, Proc. Natl. Acad. Sci. USA 89 5093-5097. 

Phospholipids play an important role in lung functions. The surface active material to be found in the alveolar lining of the lung is a mixture of phospholipids, neutral lipids and proteins. Lowering of surface tension by the lung surfactant system and the surface elasticity of the surface layers assists alveolar expansion and contraction. Deficiency of lung surfactants in newborns leads to a respiratory distress syndrome and this led to the suggestion that instillation of phospholipid surfactants could cure the problem. 

LeVine, A.M., et al., Surfactant protein-A binds group B streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice, Am. J. Respir. Cell Mol. Biol. 20, 2, 279, 1999. 

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). 

The answer is a. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159—175. Wilson, pp 287-317.) Acetyl CoA carboxylase deficiency drastically alters the ability of the patient to synthesize fatty acids. The fact that the infant was born at all is due to the body s ability to utilize fatty acids provided to it. However, all processes dependent upon de novo fatty acid biosynthesis are affected. The lungs, in particular, require surfactant, a lipoprotein substance secreted by alveolar type 11 cells, to function prop-... 

Abnormal nutrient delivery may also have an effect on lung growth and development. Subtle deficiencies of vitamin A can affect airway branching and lung epithelial cell differentiation [46]. There are additional effects of vitamin A depletion on surfactant protein production which in turn could affect airway host defence [47]. Collectively, these phenomena are viewed as key abnormalities in asthma. There is, therefore, a potential for aberrant nutrient delivery to have an impact not only on IgE sensitisation to allergen but also on airway development. Clearly further research is required in this area. 

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