Effect of air pollutants on the pulmonary surfactant system

Air pollutants have been recognized to influence the structure and function of the surfactant system. Agents that have received the most attention include ozone, nitrogen dioxide, hyperoxia, diesel exhaust, tobacco smoke, silica and fibrous materials such as asbestos. The deleterious effects of air pollutants on the surfactant system depend on the size of the agent, on its solubility in aqueous solutions and chemical reactivity and on its concentration and the duration of exposure. Hereby the following general rules apply: the smaller the agent's size and the less water soluble the pollutant is, the greater the tendency to reach the alveoli during breathing. In addition, the reactivity also determines the depth of penetration into alveoli. Compounds with high reactivity such as O₃, which also fulfil the earlier rules, will react with the upper respiratory tract compared with compounds with slightly reduced reactivity, such as NO₂, which will penetrate the alveoli. The common consequence of exposure to air pollutants is an accumulation of surfactant phospholipids and surfactant-specific proteins in the bronchoalveolar lavage fluid. These components also are structurally altered, mainly by oxidant gases, resulting in impairment of their biological activity. Thus, for surfactant phospholipids, there is impaired adsorption to the air–liquid interface due to oxidation of their fatty acids. Also, surfactant protein A, regarded as a modulator of the surfactant system, shows impaired functions after exposure to oxidants. It is likely that in addition to the effects described in this review not all effects are known because the molecular effects of several key components (e.g SP-B and C) have not been well studied.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

目的 探讨不同剂量肺表面活性物质(PS)替代治疗早产儿肺透明膜病(HMD)与发生支气管肺发育不良(BPD)的关系.方法 将2005年1月至2007年12月入住本院新生儿科并出现生后进行性呼吸困难且胸片提示考虑诊断为HMD的403例早产儿,依据家属经济条件使用旨剂PS情况分三组进行前瞻性的临床对照研究:低剂量PS组(L-PS组,剂量≤100 mg/kg,n=188)、高剂量PS组(H-PS组,剂量>100mg/kg,n=94)和未使用PS组(N-PS组, n=121);采用自身对照和组间比较观察PS治疗6 h后患儿吸氧浓度(FiO2)、肺部氧合功能,以及三组问观察总氧疗时间、机械通气时间、再次插管机械通气率、住院时间和BPD发生情况.结果 与N-PS组患儿比较,在给予Ps治疗6 h后,L-PS组和H-PS组两组患儿的FiO2,OI明显降低,PO2和a/A PO2比值均明显升高(P<0.05);氧疗时间和机械通气时间均明显缩短,较少发生再次插管机械通气(P<0.05);且以H-PS组患儿改变显著,差异均具有统计学意义(P<0.05).H-PS组患儿BPD发生(11例,11.7%)明显低于N-PS组(29例,24.0%),差异具有统计学意义(F1-3=4.267,P=0.006);L-PS组BPD发牛(34例,18.1%)虽然低于N-PS组,但差异无统计学意义(F1-2=1.354,P=0.062).结论 PS替代治疗能有效地改善肺部氧合功能,减少机械通气时间和再次插管机械通气发生率,且以大剂量(>100mg/kg)的效果更明显,并能有效地预防BPD的发生.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺表面活性物质替代治疗与支气管肺发育不良的关系

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.     

肺泡表面活性物质在急性呼吸窘迫综合征治疗中的应用

目的 观察肺泡表面活性物质对急性呼吸窘迫综合征（ARDS）患者通气、氧合功能的影响。方法 选择我院ICU2002-01-2005-01由各种病因导致的ARDS患者15例。均在人工呼吸机支持下，选用固尔苏（Curosurf）按100mg／kg剂量经纤维支气管镜行肺泡灌洗补充外源性肺泡表面活性物质，并于灌洗前及以后24h内连续观察患者心率、血压、经皮血氧饱和度（TcSaO2），每6h采动脉血进行血气分析调整并记录呼吸机相关参数。结果 肺泡灌洗补充肺泡表面活性物质后6h内PaO2／FiO2明显改善（P〈0．05），12h迭高峰（P〈0.01），以后逐渐下降。结论 肺泡灌洗补充肺泡表面活性物质能够明显缓解临床症状。改善氧合功能，但持续时间相时较短。     

血管内皮生长因子对肺表面活性物质合成的影响

目的研究血管内皮生长因子（vascular endothelial growth factor VEGF）对肺表面活性物质合成、分泌的影响,探讨防治早产儿呼吸窘迫综合征（ARDS）的新途径。方法孕19d Wistar大鼠剖腹取胎鼠,原代培养肺泡Ⅱ型细胞,试验分组：VEGF组、地塞米松组、VEGF加地塞米松组和对照组;薄层层析法测定肺表面活性物质总磷脂、磷脂酰胆碱（PC）、磷脂酰甘油（PG）、鞘磷脂（SM）含量;统计学方法：数据以均数±标准差（-↑x±s）表示,多组间差异比较采用双侧t检验和方差分析。结果VEGF组、地塞米松组与VEGF加地塞米松组总磷脂及各成分含量增加,VEGF组和地塞米松组PC、SM、PG含量有显著性差异。结论VEGF能促进肺表面活性物质的合成和分泌,VEGF、地塞米松对肺泡磷脂各成分的影响各不相同,两者可能通过不同的机制,增加了肺泡表面活性物质的合成和分泌,改善了肺泡上皮细胞的功能。     

Effect of body position on pulmonary function

Pulmonary physical therapy has focused largely on improving ventilation. Bronchial drainage techniques have incorporated body positioning to effect gravity-assisted mucous clearance and to enhance air entry. Body position directly affects ventilation and perfusion matching and arterial oxygen levels. This article briefly describes the role of body positioning on lung function and the clinical implications of this as a treatment priority. The effect of body position on arterial oxygen levels and lung function is discussed for the following positions: erect, lean forward, supine, lateral, prone, head-down tilt, hands and knees, and upside down. The implications of these positions are discussed for both the patient who has lung dysfunction and for the individual who may be at risk for developing pulmonary complications. Research is needed to investigate the principles of therapeutic positioning for optimal gas exchange and lung function. Such work may help to refine pulmonary physical therapy procedures and to identify the role of judicious positioning in a therapeutic exercise regimen.     

NG-硝基-L-精氨酸对脂多糖诱导大鼠肺损伤时肺表面活性物质和细胞凋亡的影响

目的 探讨NG-硝基-L-精氨酸(L-NA)对内毒素性肺损伤大鼠肺表面活性物质(PS)和细胞凋亡的影响.方法 雄性SD大鼠24只,按随机数字表法均分为对照组、模型组、L-NA治疗组.模型组、L-NA治疗组舌下静脉注射脂多糖(LPS)复制内毒素性肺损伤模型;对照组给予等量生理盐水.L-NA治疗组于注射LPS 3 h后给予L-NA 20 mg/kg;对照组和模型组给予等量生理盐水.6 h后处死动物,取肺组织,用原位杂交法测定肺组织表面活性物质相关蛋白A(SP-A)mRNA表达;用流式细胞术检测肺组织细胞凋亡率;用蛋白质免疫印迹法(Western blotting)检测天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)蛋白表达;用免疫组化法测定Bcl-2和Bax蛋白表达.结果 与对照组比较,模型组SP-A mRNA表达[吸光度(A)值]明显下降(0.071±0.017比0.113±0.021),细胞凋亡率[(25.04±4.57)%比(11.37±3.08)%]、caspase-3蛋白表达(A值:298.64±37.11比110.24±14.35)、Bax蛋白表达(A值:0.145±0.011比0.076±0.010)明显升高,Bcl-2蛋白表达(A值:0.064±0.011比0.073±0.009)和Bcl-2/Bax比值(0.447±0.086比0.976±0.157)明显下降(均P<0.01).与模型组比较,L-NA治疗组SP-A mRNA表达(A值:0.085±0.015)和Bcl-2蛋白表达(A值:0.070±0.087)明显增强(P<0.01和P<0.05),但细胞凋亡率[(20.67±1.35)%]、caspase-3蛋白表达(A值:268.75±42.56)、Bax蛋白表达(A值:0.142±0.012)和Bcl-2/Bax比值(0.498±0.069)均无明显变化(均P>0.05).结论 L-NA不通过抑制肺细胞凋亡来减轻内毒素性肺损伤的程度,对调节凋亡相关基因caspase-3和Bax也无明显影响;而是可通过增强PS表达减轻内毒素性肺损伤.     

The effect of the inhalation of a single atrovent dose on pulmonary ventilation function and respiratory mechanics in patients with chronic obstructive bronchitis

A study was made of the action of inhalation of a single atrovent dose in 20 patients with chronic obstructive bronchitis. All the patients demonstrated a considerable abatement or disappearance of dyspnea, and a reduction of the number of dry rales. The vital capacity of the lungs, the volume of forced expiration, maximal pulmonary ventilation, MOCmax, MOC50, and MOC75 substantially increased. The respiratory work diminished on the average by 32.3% primarily due to the lessening of non-elastic lung resistance. The rise of pulmonary static extensibility and reduction of pulmonary elastic propulsion were recorded. In patients with and without clinical signs of bronchospasm, the action of atrovent was identical.     

Influence of renal function on the pharmacokinetics of diacerein after a single oral dose

Summary— The pharmacokinetics of diacerein (a new anti-inflammatory analgesic antipyretic drug) following a single oral dose of 50 mg was studied in 12 healthy volunteers and two groups of eight patients with mild or severe renal insufficiency. Statistical analysis using a Kruskal-Wallis rank sum test showed a significant difference between the three groups for the following parameters. In severely uraemic patients, median AUC_0-∞ was multiplied by a factor of ca 2: 40.5 mg h/l versus 21.3 in healthy subjects, P = 0.04; and t_1/2 was prolonged by the same factor: 9.6 h versus 4.3 in the control group, P = 0.003. Apparent drug availability and renal clearance assessed through urinary data decreased with renal failure, respectively: 14.5% and 0.045 l/h versus 35.4% ( P = 0.01) and 0.13 l/h ( P = 0.008) in healthy subjects. Amounts of glucuro and sulfo conjugates in urine were lower in severely uraemic patients. Intermediate values were observed for mildly uraemic patients. Other parameters: lag-time, C_max, t_max, V_ss/F, urinary glucuro- to sulphoconjugate ratios did not change significantly. Apparent total clearance of rhein was poorly correlated with creatinine clearance and this was related to a decrease of non-renal clearance of rhein in renal insufficiency. It was concluded that, from a pharmacokinetic point of view, a reduction (50%) in the maintenance dosage of diacerein should be considered in severe renal failure.     

Immunomodulation by pulmonary surfactant

Canine pulmonary surfactant is recognized to modulate both T and B cell response in vitro. Because both responses involve cell proliferation, it has been suggested that surfactant interferes with the proliferation of lymphocytes. We herein report studies using human surfactant collected from amniotic fluid (HAFS). HAFS inhibited the proliferative response of human lymphocytes to antigen (PPD) and to allogeneic lymphocytes. Inhibition was linear within the dose range examined. Inhibition of the response to phytohemagglutinin was only evident when suboptimal doses of phytohemagglutinin were used. The effect of HAFS on the lysis of K562 human myeloid target cells by natural killer (NK) cells was also studied. Lysis in this system does not require proliferation. HAFS inhibited NK cell-induced lysis by 70% (250 micrograms HAFS per milliliter) to 95% (500 micrograms HAFS per milliliter). Inhibition was evident whether the cells were incubated with HAFS for 4 hours or for 18 hours. The NK suppressor activity was contained in the lipid fraction of HAFS, whereas the protein fraction revealed little activity. The washout experiments demonstrated that the action of HAFS was on NK cells and not on target cells. The immunomodulatory properties of surfactant affect NK cell activity and the proliferative response. Surfactant may protect the lungs from inappropriate immune reactions. Abnormalities of the lipid fraction of surfactant should be considered in studies of the mechanism of pulmonary diseases characterized by local pulmonary immune responses.