Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome.

Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of approximately 5 ml/kg after 30 min of ventilation. However, treatment with phospholipids containing both SP-B and SP-C/SP-C33 approximately doubled lung gas volumes. Doubling the SP-C33 content did not affect lung gas volumes. The tidal volumes were similar in all groups receiving surfactant. This shows that SP-B and SP-C exert different physiological effects, since both proteins are needed to establish alveolar stability at end expiration in this animal model of respiratory distress syndrome, and that an optimal synthetic surfactant probably requires the presence of mimics of both SP-B and SP-C.     

Lung volumes and alveolar expansion pattern in immature rabbits treated with serum-diluted surfactant.

In acute respiratory distress syndrome, mechanical ventilation often induces alveolar overdistension aggravating the primary insult. To examine the mechanism of overdistension, surfactant-deficient immature rabbits were anesthetized with pentobarbital sodium, and their lungs were treated with serum-diluted modified natural surfactant (porcine lung extract; 2 mg/ml, 10 ml/kg). By mechanical ventilation with a peak inspiration pressure of 22.5 cm H2O, the animals had a tidal volume of 14.7 ml/kg (mean), when 2.5 cm H2O positive end-expiratory pressure was added. This volume was similar to that in animals treated with nondiluted modified natural surfactant (24 mg/ml in Ringer solution, 10 ml/kg). However, the lungs fixed at 10 cm H2O on the deflation limbs of the pressure-volume curve had the largest alveolar/alveolar duct profiles (> or =48,000 microm2), accounting for 38% of the terminal air spaces, and the smallest (<6,000 microm2), accounting for 31%. These values were higher than those in animals treated with nondiluted modified natural surfactant (P <0.05). We conclude that administration of serum-diluted surfactant to immature neonatal lungs leads to patchy overdistension of terminal air spaces, similar to the expansion pattern that may be seen after dilution of endogenous surfactant with proteinaceous edema fluid in acute respiratory distress syndrome.     

A natural surfactant from pig lungs

An exogenous natural lung surfactant obtained from minced pig lungs can be produced by a technology using a low cost, DEAE-cellulose adsorbent. This surfactant is composed mainly with phospholipids and the two hydrophobic polypeptides, SP-B and SP-C, both of which are necessary for optimal function of surfactants used for treatment of respiratory distress syndrome.     

Pulmonary surfactant therapy.

Surfactant replacement therapy is now an integral part of the care of neonates since several clinical trials of natural surfactant extracts and synthetic preparations have shown efficacy in the treatment of infants with hyaline membrane disease. In these studies, early treatment with exogenous surfactant substantially reduced mortality and the incidence of air leak, although it did not appear to reduce the incidence of other complications, in particular bronchopulmonary dysplasia. Early reports of exogenous surfactant therapy in patients with the adult respiratory distress syndrome, although promising, remain limited in number. More research is needed to improve on current modes of therapy and to investigate the possible role of surfactant in other lung diseases of both newborns and adults.     

Strategies for reducing coronary risk factors in primary care: which is most cost effective?

OBJECTIVE--To examine the relative cost effectiveness of a range of screening and intervention strategies for preventing coronary heart disease in primary care. SUBJECTS--7840 patients aged 35-64 years who were participants in a trial of modifying coronary heart disease risk factors in primary care. DESIGN--Effectiveness of interventions assumed and the potential years of life gained estimated from a risk equation calculated from Framingham study data. MAIN OUTCOME MEASURE--The cost per year of life gained. RESULTS--The most cost effective strategy was minimal screening of blood pressure and personal history of vascular disease, which cost 310 pounds-930 pounds per year of life gained for men and 1100 pounds-3460 pounds for women excluding treatment of raised blood pressure. The extra cost per life year gained by adding smoking history to the screening was 400 pounds-6300 pounds in men. All strategies were more cost effective in men than in women and more cost effective in older age groups. Lipid lowering drugs accounted for at least 70% of the estimated costs of all strategies. Cost effectiveness was greatest when drug treatment was limited to those with cholesterol concentrations above 9.5 mmol/l. CONCLUSIONS--Universal screening and intervention strategies are an inefficient approach to reducing the coronary heart disease burden. A basic strategy for screening and intervention, targeted at older men with raised blood pressure and limiting the use of cholesterol lowering drugs to those with very high cholesterol concentrations would be most cost effective.     

A High-Value,Low-Cost Bubble Continuous Positive Airway Pressure System for Low-Resource Settings: Technical Assessment and Initial Case Reports

Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately $350. Moreover, because of its simple design—consumer-grade pumps, medical tubing, and regulators—it requires only the simple replacement of a <$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device.     

CPAP联合肺表面活性物治疗新生儿呼吸窘迫综合征的临床疗效及对患者血气指标的影响

目的:探讨CPAP(Continuous Positive Airway Pressure)联合肺表面活性物质治疗新生儿呼吸窘迫综合征(NRDS)临床疗效及对血气指标的影响。方法:选择2014年8月至2018年8月本院收治的新生儿呼吸窘迫综合征患者200例,将其随机分为2组,每组100例。A组给予CPAP(持续正压通气)联合肺表面活性物质治疗,B组给予CPAP(持续正压通气)治疗,分析和比较两组的临床疗效及治疗前后血气指标的变化。结果:治疗后,两组新生儿患者PaO_2均较治疗前均显著升高,PaCO_2较治疗前明显降低,且A组PaO_2显著高于B组(P0.05),PaCO_2显著低于B组(P0.05);A组住院时间显著短于B组(P0.05),临床总有效率显著高于B组(P0.05);两组新生儿患者的胸部X线评分均较治疗前显著降低(P0.05),A组12 h和24 h胸部X线评分均显著性低于B组(P0.05);A组PEEP/cmH_2O水平显著低于B组(P0.05),Fi O_2水平显著高于B组(P0.05);两组生儿患者的的OI指数均较治疗前显著升高,且A组明显高于B组(P0.05)。结论:CPAP联合肺表面活性物质治疗NRDS的临床效果显著优于单用CPAP(持续正压通气)治疗,且且可显著改善患儿血气指标。     

What can be concluded from the Oxcheck and British family heart studies: commentary on cost effectiveness analyses.

OBJECTIVES--To provide a commentary on the economic evaluations of the Oxcheck and British family heart studies: direct comparison of their relative effectiveness and cost effectiveness; comparisons with other interventions; and consideration of problems encountered. DESIGN--Modelling from cost and effectiveness data to estimate of cost per life year gained. SUBJECTS--Middle aged men and women. INTERVENTIONS--Screening for cardiovascular risk factors followed by appropriate lifestyle advice and drug intervention in general practice, and other primary coronary risk management strategies. MAIN OUTCOME MEASURES--Life years gained; cost per life year gained. RESULTS--Depending on the assumed duration of risk reduction, the programme cost per discounted life year gained ranged from 34,800 pounds for a 1 year duration to 1500 pounds for 20 years for the British family heart study and from 29,300 pounds to 900 pounds for Oxcheck. These figures exclude broader net clinical and cost effects and longer term clinical and cost effects other than coronary mortality. CONCLUSIONS--Despite differences in underlying methods, the estimates in the two economic analyses of the studies can be directly compared. Neither study was large enough to provide precise estimates of the overall net cost. Modelling to cost per life year gained provides more readily interpretable measures. These estimates emphasise the importance of the relatively weak evidence on duration effect. Only if the effect lasts at least five years is the Oxcheck programme likely to be cost effective. The effect must last for about 10 years to justify the extra cost associated with the British family heart study.     

A concentration-dependent mechanism by which serum albumin inactivates replacement lung surfactants.

Endogenous lung surfactant, and lung surfactant replacements used to treat respiratory distress syndrome, can be inactivated during lung edema, most likely by serum proteins. Serum albumin shows a concentration-dependent surface pressure that can exceed the respreading pressure of collapsed monolayers in vitro. Under these conditions, the collapsed surfactant monolayer can not respread to cover the interface, leading to higher minimum surface tensions and alterations in isotherms and morphology. This is an unusual example of a blocked phase transition (collapsed to monolayer form) inhibiting bioactivity. The concentration-dependent surface activity of other common surfactant inhibitors including fibrinogen and lysolipids correlates well with their effectiveness as inhibitors. These results show that respreading pressure may be as important as the minimum surface tension in the design of replacement surfactants for respiratory distress syndrome.     

Effect of exogenous surfactant on phosphatidylinositol 3-kinase-Akt pathway and peroxisome proliferator activated receptor-γ during endotoxin induced acute respiratory distress syndrome

Lipopolysaccharide induced acute respiratory distress syndrome (ARDS) leads to an unacceptably high mortality. In this regard, the anti-inflammatory properties of surfactant may provide a therapeutic option. Phosphoinositide 3-kinase (PI3-K) and the downstream serine/threonine kinase Akt/protein kinase B have a central role in modulating neutrophil function, including respiratory burst, chemotaxis, and apoptosis. This study explores the mechanisms of surfactant dependent protection by regulating PPAR-γ in a rat model of ARDS. Sprague-Dawley male rats were divided into four groups: buffer controls; rats challenged with LPS (055:B5 E. coli); challenged with LPS and treated with porcine surfactant; and challenged with LPS and treated with synthetic surfactant. Expression of PI3-K, Akt, GSK3-β, and PPAR-γ were studied by western immunoblot, immunofluorescence and by immunohistochemistry. In vivo endotoxin administration to rat resulted in activation of PI3-K and Akt in the lungs. The severity of endotoxemia-induced ALI was significantly diminished in rat with surfactant administration. Similar results were also seen in PPAR-γ expression. These results show that PI3-K occupies a central position in regulating endotoxin-induced ALI involving inflammatory responses. Surfactant treatment conferred protection in rat model dependent on PPAR-γ and inhibition of PI3-K/Akt pathway.     

肺表面活性物质救治近足月儿呼吸窘迫综合征的临床疗效观察

目的:观察肺表面活性物质在近足月儿呼吸窘迫综合征救治中的作用。方法:按照家属自愿的原则将41例确诊为新生儿呼吸窘迫综合征且胎龄介于34周-36周之间的近足月儿分为治疗组及对照组,治疗组23例,对照组18例,比较两组患儿血气分析结果、呼吸机参数、气管插管率、上机时间、存活率及住院时间。结果:治疗组患儿,用药后无论临床表现还是胸片均有不同程度的改善。用药后6小时,治疗组PaO2及PaCO2均优于对照组(P<0.05);比较两组中机械通气患儿呼吸机参数,治疗组明显低于对照组(P<0.05);治疗组气管插管率明显低于对照组,且上机时间(nCPAP、nIPPV、气管插管机械通气)也较对照组明显缩短(P<0.05),但两组患儿存活率及住院时间差异无统计学意义。结论:对于近足月呼吸窘迫综合征患儿,尽早明确诊断并在发病早期给予PS替代治疗,可提高此类患儿的生存率及预后,对降低早产儿病死率有重要意义!     

Expression of SP-C and Ki67 in lungs of preterm infants dying from respiratory distress syndrome

This study aimed at exploring the expression of Surfactant protein-C (SP-C) and Ki67 in autopsy lung tissues of premature infants dying from respiratory distress syndrome (RDS) who were exposed to mechanical ventilation and elevated oxygen concentrations. The possible influence of pulmonary surfactant (PS) on the expression of SP-C and Ki67 was also investigated. Thirty preterm infants were selected who were histologically and clinically diagnosed as RDS. Preterm infants with RDS were divided into 4 groups, according to the time of death: infants ventilated for 1–3 days, 4–8 days, 9–16 days and >6 days. Five premature infants died within 1 day after delivery for non- pulmonary reasons served as controls. The expression of SP-C and Ki67 in lungs was detected by immunohistochemistry. Compared with the control group, the expression of SP-C and Ki67 in RDS infants decreased significantly after 1–3 days of ventilation, but increased after 4 days and reached peak value after 9–16 days. No significant difference in the expression of SP-C and Ki67 was found between infants treated with PS and those without. Thus our results suggest SP-C and Ki67 may have participated in the pulmonary pathological process in ventilated/oxygen treated preterm infants with RDS, and exogenous surfactant had no effect on the expression of SP-C and Ki67 in the lungs of ventilated/oxygen treated preterm infants with RDS.Key words: respiratory distress syndrome, surfactant protein-C, Ki67, preterm.     

肺表面活性物质救治近足月儿呼吸窘迫综合征的临床疗效观察

目的：观察肺表面活性物质在近足月儿呼吸窘迫综合征救治中的作用。方法：按照家属自愿的原则将41例确诊为新生儿呼吸窘迫综合征且胎龄介于34周．36周之间的近足月儿分为治疗组及对照组,治疗组23例,对照组18例,比较两组患儿血气分析结果、呼吸机参数、气管插管率、上机时间、存活率及住院时间。结果：治疗组患儿,用药后无论临床表现还是胸片均有不同程度的改善。用药后6小时,治疗组PaO2及PaCO2均优于对照组（P〈0．05）;比较两组中机械通气患儿呼吸机参数,治疗组明显低于对照组（P〈0．05）：治疗组气管插管率明显低于对照组,且上机时间（nCPAP、nIPPV、气管插管机械通气）也较对照组明显缩短（P〈0．05）．但两组患儿存活率及住院时间差异无统计学意义。结论：对于近足月呼吸窘迫综合征患儿,尽早明确诊断并在发病早期给予PS替代治疗。可提高此类患儿的生存率及预后,对降低早产儿病死率有重要意义!     

Improvement of pulmonary surfactant activity by introducing D-amino acids into highly hydrophobic amphiphilic α-peptide Hel 13-5

The high costs of artificial pulmonary surfactants, ranging in hundreds per kilogram of body weight, used for treating the respiratory distress syndrome (RDS) premature babies have limited their applications. We have extensively studied soy lecithins and higher alcohols as lipid alternatives to expensive phospholipids such as DPPC and PG. As a substitute for the proteins, we have synthesized the peptide Hel 13-5D3 by introducing D-amino acids into a highly lipid-soluble, basic amphiphilic peptide, Hel 13-5, composed of 18 amino acid residues. Analysis of the surfactant activities of lipid-amphiphilic artificial peptide mixtures using lung-irrigated rat models revealed that a mixture (Murosurf SLPD3) of dehydrogenated soy lecithin, fractionated soy lecithin, palmitic acid (PA), and peptide Hel 13-5D3 (40:40:17.5:2.5, by weight) superior pulmonary surfactant activity than a commercially available pulmonary surfactant (beractant, Surfacten®). Experiments using ovalbumin-sensitized model animals revealed that the lipid-amphiphilic artificial peptide mixtures provided significant control over an increase in the pulmonary resistance induced by premature allergy reaction and reduced the number of acidocytes and neutrophils in lung-irrigated solution. The newly developed low-cost pulmonary surfactant system may be used for treatment of a wide variety of respiratory diseases.     

老年急性呼吸窘迫综合征肺内及肺外源性危险因素分析

目的:探讨老年急性呼吸窘迫综合征肺内及肺外源性危险因素。方法:回顾性分析130例老年ARDS患者,对其中的肺内及肺外源性危险因素进行分析。结果:肺内源性ARDS病因以误吸和肺炎为主,而肺外源性ARDS则以脓毒血症、大手术后等为主;在死亡上均与多器官功能障碍综合征、呼吸衰竭为主要因素,且两组死亡率接近。结论:在老年急性呼吸窘迫综合征中,肺外源性在器官功能衰竭和氧合指数上重于肺内源性,但是在其他因素和死亡结局上均无明显差异性。     

Interfacial behavior and structural properties of a clinical lung surfactant from porcine source

Surfacen? is a clinical surfactant preparation of porcine origin, partly depleted of cholesterol, which is widely used in Cuba to treat pre-term babies at risk or already suffering neonatal respiratory distress. In the present study we have characterized the interfacial behavior of Surfacen in several in vitro functional models, including spreading and compression-expansion cycling isotherms in surface balances and in a captive bubble surfactometer, in comparison with the functional properties of whole native surfactant purified from porcine lungs and its reconstituted organic extract, the material from which Surfacen is derived. Surfacen exhibited similar properties to native porcine surfactant or its organic extract to efficiently form stable surface active films at the air-liquid interface, able to consistently reach surface tensions below 5mN/m upon repetitive compression-expansion cycling. Surfacen films, however, showed a substantially larger and stable compression-driven segregation of condensed lipid phases than exhibited by films formed by native surfactant or its organic extract. In spite of structural differences observed at microscopic level, Surfacen membranes showed a similar thermotropic behavior to membranes from native surfactant or its organic extract, characterized by calorimetry or fluorescence spectroscopy of samples doped with the Laurdan probe. On the other hand, analysis by atomic force microscopy of films formed by Surfacen or by the organic extract of native porcine surfactant revealed a similar network of interconnected condensed nanostructures, suggesting that the organization of the films at the submicroscopic level is the essential feature to support the proper stability and mechanical properties permitting the interfacial surfactant films to facilitate the work of breathing.     

Oral versus intravenous antibiotics for community acquired lower respiratory tract infection in a general hospital: open,randomised controlled trial.

OBJECTIVE--To see whether there is a difference in outcome between patients treated with oral and intravenous antibiotics for lower respiratory tract infection. DESIGN--Open controlled trial in patients admitted consecutively and randomised to treatment with either oral co-amoxiclav, intravenous followed by oral co-amoxiclav, or intravenous followed by oral cephalosporins. SETTING--Large general hospital in Dublin. PATIENTS--541 patients admitted for lower respiratory tract infection during one year. Patients represented 87% of admissions with the diagnosis and excluded those who were immunocompromised and patients with severe life threatening infection. MAIN OUTCOME MEASURES--Cure, partial cure, extended antibiotic treatment, change of antibiotic, death, and cost and duration of hospital stay. RESULTS--There were no significant differences between the groups in clinical outcome or mortality (6%). However, patients randomised to oral co-amoxiclav had a significantly shorter hospital stay than the two groups given intravenous antibiotic (median 6 v 7 and 9 days respectively). In addition, oral antibiotics were cheaper, easier to administer, and if used routinely in the 800 or so patients admitted annually would lead to savings of around 176,000 pounds a year. CONCLUSIONS--Oral antibiotics in community acquired lower respiratory tract infection are at least as efficacious as intraveous therapy. Their use reduces labour and equipment costs and may lead to earlier discharge from hospital.     

枸橼酸咖啡因联合肺泡表面活性物质治疗新生儿呼吸窘迫综合征的疗效及对血清BMP-7、CC16、SF水平的影响

目的:探讨枸橼酸咖啡因联合肺泡表面活性物质治疗新生儿呼吸窘迫综合征患儿的疗效及对血清骨形态发生蛋白-7(BMP-7)、Clara细胞分泌蛋白(CC16)、铁蛋白(SF)水平的影响。方法:选择2016年3月到2018年3月我院接诊的新生儿呼吸窘迫综合征患儿90例作为研究对象,以随机数表法分为观察组(n=48)和对照组(n=42)。对照组使用肺泡表面活性物质进行治疗,观察组在对照组的基础上加用枸橼酸咖啡因进行治疗。比较两组治疗后的疗效,治疗前后血清BMP-7、CC16、SF水平、血气指标[氢离子浓度指数(p H)、二氧化碳分压(PCO_2)、氧合指数(PaO_2/Fi O_2)]的变化,通气时间及支气管肺发育不良(BPD)的发生率。结果:治疗后,观察组总有效率为95.83%,明显高于对照组(71.43%,P0.05);两组患儿血清BMP-7、CC16、SF水平较治疗前均显著降低(P0.05),且观察组以上指标均明显低于对照组(P0.05);两组患儿pH、PaO_2/Fi O_2均较治疗前明显升高,而PCO_2较治疗前显著降低(P0.05),且观察组患儿p H、PaO_2/Fi O_2显著高于对照组,而PCO_2明显低于对照组(P0.05)。观察组患儿通气时间明显短于对照组,BPD发生率显著低于对照组(P0.05)。结论:枸橼酸咖啡因联合肺泡表面活性物质治疗新生儿呼吸窘迫综合征的临床效果显著优于单用肺泡表面活性物质治疗,其可有效改善患儿血清BMP-7、CC16、SF水平、缩短机械通气时间,降低支气管肺发育不良发生率。     

Economics of coronary artery bypass grafting.

To decide whether the number of operations for coronary artery bypass grafting should be increased, maintained at the present levels, or decreased we need to know how cost effective they are relative to other claimants on the resources of the National Health Service. For this purpose effectiveness is taken to be the effect on life expectancy adjusted for the quality of life. In an assessment of the cost per quality adjusted life year gained coronary artery bypass grafting rates well for cases of severe angina and extensive coronary artery disease. The cost, however, rises sharply for less severe cases. Bypass grafting seems to compare favourably with valve replacement for aortic stenosis and implantation of pacemakers for heart block; it is distinctly better than heart transplantation and the treatment of end stage renal failure but is probably less cost effective than hip replacement. If the number of operations for coronary artery bypass grafting were to increase it would be a fairly strong claimant only if restricted to the most severe cases. The data on which these judgments are based are crude and in need of refinement. The methodology is powerful, far reaching, and open to comment.     

Morbidity and survival in neonates ventilated for the respiratory distress syndrome.

In a retrospective analysis the records of all (210) infants ventilated to treat the respiratory distress syndrome over three years were reviewed. A mortality of 19% was found. Intraventricular haemorrhage was associated than a significant increase in mortality in infants of less with 30 weeks'' gestation (p less than 0.001) and was the commonest cause of death. Pneumothoraces developed in one third of babies regardless of gestational age but were significantly associated with an increase in mortality only in infants of 27-29 weeks'' gestation. Patent ductus arteriosus was present in 31 infants and was commoner in babies of very low birth weight. The presence of a patent ductus arteriosus was not associated with decreased survival but was significantly related to an increased need for prolonged respiratory support (p less than 0.001). Thirty six infants developed chronic lung disease, three of whom died. Comparison with data from earlier studies indicated a steady improvement over the past decade in outcome for infants ventilated for the respiratory distress syndrome.