Surfactant phosphatidylcholine metabolism and surfactant function in preterm, ventilated lambs

Preterm lambs were delivered at 138 days gestational age and ventilated for periods up to 24 h in order to study surfactant metabolism and surfactant function. The surfactant-saturated phosphatidylcholine pool in the alveolar wash was 13 +/- 4 mumol/kg and did not change from 10 min to 24 h after birth. Trace amounts of labeled natural sheep surfactant were mixed with fetal lung fluid at birth. By 24 h, 80% of the label had become lung-tissue-associated, yet there was no loss of label from phosphatidylcholine in the lungs when calculated as the sum of the lung tissue plus alveolar wash. De novo synthesized phosphatidylcholine was labeled with choline given by intravascular injection at 1 h of age. Labeled phosphatidylcholine accumulated in the lung tissue linearly to 24 h, and the labeled phosphatidylcholine moved through lamellar body to alveolar pools. The turnover time for alveolar phosphatidylcholine was estimated to be about 13 h, indicating an active metabolic pool. A less surface-active surfactant fraction recovered as a supernatant after centrifugation of the alveolar washes at 40,000 x g increased from birth to 10 min of ventilation, but no subsequent changes in the distribution of surfactant phosphatidylcholine in surfactant fractions occurred. The results were consistent with recycling pathway(s) that maintained surface-active surfactant pools in preterm ventilated lambs.     

Surfactant protein-A inhibits lavage-induced surfactant secretion in newborn rabbits.

In vitro experiments with granular pneumocytes suggest that surfactant protein-A (SP-A) inhibits secretion of pulmonary surfactant. We examined whether SP-A inhibits surfactant secretion induced by lung distention during lung lavage. Human SP-A was obtained by lung lavage in a patient with pulmonary alveolar proteinosis. After centrifugation of the lavagate, the pellet was repeatedly washed with saline and then extracted with chloroform:methanol. The methanol:saline phase was separated and lyophilized to yield the SP-A product. SDS-PAGE and immunoblot analysis indicated that our preparation of SP-A had only minor contamination with human plasma proteins. To examine secretion, we used freshly killed newborn rabbit pups of 29.5 days gestation and lavaged the lungs by 10 sequential, fresh saline washes. Littermate neighbor pairs were lavaged with SP-A or human plasma protein at concentrations of 1, 6, 10, and 50 micrograms/ml, and disaturated phosphatidylcholine (DSPC) was analyzed as a marker for surfactant. The inhibition of surfactant secretion was maximal at a concentration of 10 micrograms/ml; the average yield by the last two pairs of washes, an index of surfactant secretion, was 286 +/- 41 micrograms/g dry lung weight for SP-A, compared to 405 +/- 37 micrograms/g dry lung weight for controls, an inhibition of 30% (p < 0.005). There were no changes in the volumes of returned lavage or in the concentrations of lactate dehydrogenase or DNA. To test whether SP-A increased cellular uptake of DSPC in the lungs, we prepared radioactive exogenous surfactant, lavaged it into the lungs, and monitored recovery of radioactivity by continued lavage. Recovery was the same in treated and control lungs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of maternal treatment with corticosteroids, T3, TRH, and their combinations on lung function of ventilated preterm rabbits with and without surfactant treatments

Pregnant does were treated with betamethasone, T3, TRH, or combinations of betamethasone plus T3 or TRH using doses of each agent known to effect lung maturation. Preterm rabbits were then delivered at 27 days gestational age, half of each group was treated with Surfactant TA, and the rabbits were ventilated in a ventilator-plethysmograph system such that tidal volumes were regulated to mean values of 12 to 13 ml/kg. At 30 min of age when mean PCO2 values for the study groups were between 33 and 42 mm Hg, lung function of each rabbit was evaluated by the peak inspiratory pressure needed to achieve the desired tidal volume, by compliance, and by the ventilation efficiency index. These measures of lung function showed no benefit of corticosteroids or T3 in the absence of surfactant, whereas TRH significantly improved lung function. Although surfactant treatment improved lung function in all groups, the best effect after a single hormone treatment was with corticosteroids. The combined use of corticosteroids and TRH in surfactant-treated animals resulted in the best overall responses. The leak of protein into and out of the lungs was measured with radiolabeled albumins. The leak decreased as peak ventilatory pressures decreased in all groups and decreased with surfactant treatments of all groups. Corticosteroids decreased the protein leak into the airways more than could be accounted for by the effects of corticosteroids on ventilatory pressures alone (p less than 0.01). None of the hormone treatments significantly increased the saturated phosphatidylcholine pool sizes from the low values noted in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of exogenous surfactant in ventilated immature newborn rabbits

Immature newborn rabbits were treated at birth by tracheal instillation of porcine surfactant (100 microliters, phospholipid concentration 80 mg.ml-1), to which [14C]dipalmitoylphosphatidylcholine had been added as a marker. They were kept in a body plethysmograph/pneumotachygraph system at 37 degrees C. During a 120 min period of artificial ventilation with a peak insufflation pressure of 20 cm H2O, there was a gradual decrease in tidal volumes (36%.h-1). This decrease was correlated to an elevation of minimum surface tension (r = 0.81; P less than 0.01) and to a prolongation of the adsorption rate (r = 0.80; P less than 0.01) of surfactant recovered by lung lavage from the same animals. There was also correlations between duration of ventilation and minimum surface tension (r = 0.56; P less than 0.01), and between duration of ventilation and adsorption rate (r = 0.73; P less than 0.01). The surface properties of phospholipids extracted from the lavage fluid were similar to those of the original surfactant preparation. Our data suggest that, in immature newborn rabbits subjected to artificial ventilation, exogenous surfactant may become inactivated, probably due to protein leakage into the airspaces.     

血清肺表面活性蛋白A、D在间质性肺疾病中的价值

开胸肺活检取得病理诊断是对间质性肺疾病(interstitial lung disease,ILD)的诊断起决定作用的.然而,需要一种非侵入性的血清标志物来区别ILD,尤其是对于最常见、预后最差的寻常型间质性肺炎.肺表面活性蛋白A、D在ILD鉴别诊断及评定疾病活动性上有提示意义.近年来这类蛋白的研究进展显著,现对ILD的价值作一综述.     

Intrasubject variability of repeated pulmonary function measurements in preterm ventilated infants

This study set out to describe the variability and assess the reproducibility of repeated pulmonary function measurements in ventilated preterm infants. We measured tidal volume (V_T), lung compliance (C_L), and resistance (R_L) in 16 infants (mean ± SD: birthweight 1222 ± 343 g) during spontaneous breathing and during mechanical ventilation, suppressing breathing efforts by mild hyperventilation. C_L and R_L were calculated from the equation of motion using linear regression analysis (LR), and by the Mead and Wittenberger method (MW). Flow and transpulmonary pressure were recorded for at least two consecutive periods, after which the esophageal tube was removed and replaced 1 hour later for a second set of recordings. The mean percent change (% Δ) between the initial and the repeated measurements with their respective 95% confidence intervals were calculated. Reproducibility was assessed by the intraclass correlation coefficient (ICC) (total agreement = 1, good reproducibility ≥0.75). The mean % Δ between initial and repeat measurements during spontaneous breathing ranged from 11% to 14% for C_L and V_T, and from 22% to 32% for R_L. The variation for R_L was even higher when the analysis was done separately for the inspiratory and expiratory phase. C_L and V_T had good reproducibility (ICC >0.9), while R_L was significantly less reproducible (ICC <0.75). Measurements obtained from mechanical breaths had less variability than from spontaneous breaths, ranging from 8% to 15% for C_L and V_T, and from 13% to 21% for R_L. Reproducibility assessed by the ICC was good for most measurements during mechanical breaths. The variability and reproducibility of measurements were similar for both methods of analysis during mechanical ventilation, but during spontaneous breathing showed larger variability with the MW method than with LR analysis. We concluded that V_T and C_L were reproducible during spontaneous and mechanical breathing. However, R_L measurements were reproducible only during mechanical ventilation. The high variability of R_L in spontaneously breathing preterm infants may reduce the clinical usefulness of this measurement for individual patients. Pediatr Pulmonol. 1996; 21:35–41. © 1996 Wiley-Liss, Inc.     

Effects of inhaled formoterol compared with salbutamol in ventilated preterm infants

BACKGROUND: Short-acting beta(2)-agonists have shown beneficial effects in preterm infants, but data on long acting beta(2)-agonists are still lacking. OBJECTIVES: To compare the effects of inhaled formoterol with salbutamol in preterm infants. METHODS: Randomized, double-blind, crossover design of salbutamol (100 microg every 6 h) or formoterol (12 microg every 12 h) delivered by metered dose inhaler on two consecutive days to very low birth weight infants on assisted mechanical ventilation (n=12; gestational age 25.7+/-2 weeks; birth weight 720+/-254 g; postnatal age 25+/-9 days; mean+/-SD). Treatment with the second drug was administered until day 7 in eight infants. Outcome variables were minute volume MV, respiratory mechanics, heart rate HR, blood pressure, serum potassium and blood glucose levels. RESULTS: Mean MV increased by maximal 26% (salbutamol) and by 22% (formoterol) differing from baseline values until 6 and 8 h through increased mean tidal volume (Vt) in both groups (max. 14%). Mean static compliance (Crs) increased by 26% (salbutamol) and by 32% (formoterol) until 60 min post-administration. There was no tachyphylaxis. CONCLUSION: Inhaled salbutamol and formoterol equally increase MV, Vt, Crs and HR in mechanically ventilated infants with a longer lasting systemic effect of formoterol.     

Positive end-expiratory pressure preserves surfactant function in preterm lambs.

Ventilation style influences lung injury and the amount of large-aggregate biophysically active surfactant in adult lungs. We asked how positive end-expiratory pressures (PEEP) would influence clinical responses and surfactant pools in surfactant-treated preterm lambs ventilated for 7 h with tidal volumes (VT) of 10 ml/kg. The 126-d gestation preterms were delivered and treated with 100 mg/kg recombinant human surfactant protein C (rSP-C) containing surfactant and ventilated with zero, 4, or 7 cm H(2)O of PEEP. A comparison group was treated with natural sheep surfactant and ventilated with zero PEEP. Physiologic measurements were similar for lambs treated with rSP-C surfactant and natural surfactant. PEEP 4 and 7 improved oxygenation and compliance relative to either group of lambs ventilated with PEEP zero. The maximal lung volumes measured at 40 cm H(2)O pressure after 7 h ventilation for the PEEP 4 and 7 groups were more than double those measured for either PEEP zero group. Alveolar surfactant pools were larger for the PEEP 7 group, and the large-aggregate fraction was increased for the PEEP 4 and 7 groups, resulting in large-aggregate pool sizes that were 3-fold higher for the PEEP 4 and 4-fold higher for the PEEP 7 groups relative to the PEEP zero group treated with rSP-C surfactant. All large-aggregate surfactants lowered minimal surface tensions of a captive bubble to less than 5 mN/m. In preterm surfactant-treated lambs PEEP improved lung function and maintained more of an rSP-C surfactant in the biophysically active form.     

Inhaled nitric oxide effects on lung structure and function in chronically ventilated preterm lambs

RATIONALE: Inhaled nitric oxide (iNO) can reverse neonatal pulmonary hypertension and bronchoconstriction and reduce proliferation of cultured arterial and airway smooth muscle cells. OBJECTIVES: To see if continuous iNO from birth might reduce pulmonary vascular and respiratory tract resistance (PVR, RE) and attenuate growth of arterial and airway smooth muscle in preterm lambs with chronic lung disease. METHODS: Eight premature lambs received mechanical ventilation for 3 weeks, four with and four without iNO (5-15 ppm). Four term lambs, mechanically ventilated without iNO for 3 weeks, served as additional control animals. MEASUREMENTS: PVR and RE were measured weekly. After 3 weeks, lung tissue was processed for quantitative image analysis of smooth muscle abundance around small arteries (SMart) and terminal bronchioles (SMtb). Radial alveolar counts were done to assess alveolar number. Endothelial NO synthase (eNOS) protein in arteries and airways was measured by immunoblot analysis. MAIN RESULTS: At study's end, PVR was similar in iNO-treated and untreated preterm lambs; PVR was less in iNO-treated preterm lambs compared with term control animals. RE in iNO-treated lambs was less than 40% of RE measured in preterm control animals. SMart was similar in iNO-treated and both groups of control lambs; SMtb in lambs given iNO was significantly less (approximately 50%) than in preterm control animals. Radial alveolar counts of iNO-treated lambs were more than twice that of preterm control animals. eNOS was similar in arteries and airways of iNO-treated preterm lambs compared with control term lambs. CONCLUSIONS: iNO preserves structure and function of airway smooth muscle and enhances alveolar development in preterm lambs with chronic lung disease.     

Pulmonary mechanics in ventilated preterm infants with respiratory distress syndrome after exogenous surfactant administration: A comparison between two surfactant preparations

The effects of two surfactant preparations on lung mechanics have been studied on 24 ventilated premature infants with respiratory distress syndrome (RDS): 13 were given artificial surfactant (Exosurf Neonatal, Burroughs–Wellcome) and 11 natural porcine surfactant (Curosurf, Laboratoire Serono France). Measurements of respiratory system compliance (C_dyn C_rs) and resistance (R_rs) were performed immediately before surfactant administration and repeated 6, 18, 24, 48, and 72 hours later. With Exosurf treatment, 6 hours after surfactant administration inhaled O₂ concentration (F_IO₂) could be lowered from (0.72 ± 0.20, to 0.62 ± 0.33; P < 0.05), whereas (C_rs)did not change (0.37 mL/cmH₂O/kg, ± 0.14 vs. 0.39 ± 0.12, NS). After 24 hours and during the following days a significant increase in (C_rs) occurred (24 hours post-Exosurf: 0.51 ± 0.18, P < 0.05). With Curosurf treatment, the improvement in oxygenation was greater and F_IO₂ could be lowered much more after 6 hours (from (F_IO₂), 0.78 2 ± 0.23 to 0.34 ± 0.11, P < 0.01). This was associated with an increase in (C_rs) (from 0.39 ± 0.09 to 0.59 ± 0.17, P < 0.05). During the following days, (C_rs) was significantly higher in the group treated with Curosurf. Resistance was not altered by the type of surfactant preparation used except after 72 hours, when R_rs increased in the group treated with Exosurf. In conclusion, Curosurf appears to be more effective than Exosurf with regard to immediate pulmonary changes in ventilator treated premature infants with RDS. A rapid increase in (C_rs) after Curosurf treatment indicates that recruitment of new functional areas of the lung is likely to be associated with a stabilization of small airways and alveolar units. Pediatr Pulmonol. 1994;18:273–278 © Wiley-Liss, Inc. © Wiley-Liss, Inc.     

Exogenous surfactant restores lung function but not peripheral immunosuppression in ventilated surfactant-deficient rats

The authors have previously shown that mechanical ventilation can result in increased pulmonary inflammation and suppressed peripheral leukocyte function. In the present study the effect of surfactant therapy on pulmonary inflammation and peripheral immune function in ventilated surfactant-deficient rats was assessed. Surfactant deficiency was induced by repeated lung lavage, treated rats with surfactant or left them untreated, and ventilated the rats during 2 hours. Nonventilated rats served as healthy control group. Expression of macrophage inflammatory protein (MIP)-2 was measured in bronchoalveolar lavage (BAL), interleukin (IL)-1beta, and heat shock protein 70 (HSP70) were measured in total lung homogenates. Outside the lung phytohemagglutinin (PHA)-induced lymphocyte proliferation, interferon (IFN)-gamma and IL-10 production, and natural killer activity were measured in splenocytes. After 2 hours of mechanical ventilation, expression of MIP-2, IL-1beta, and HSP70 increased significantly in the lungs of surfactant-deficient rats. Outside the lung, mitogen-induced proliferation and production of IFN-gamma and IL-10 reduced significantly. Only natural killer cell activity remained unaffected. Surfactant treatment significantly improved lung function, but could not prevent increased pulmonary expression of MIP-2, IL-1beta, and HSP70 and decreased peripheral mitogen-induced lymphocyte proliferation and IFN-gamma and IL-10 production in vitro. In conclusion, 2 hours of mechanical ventilation resulted in increased lung inflammation and partial peripheral leukocyte suppression in surfactant-deficient rats. Surfactant therapy ameliorated lung function but could not prevent or restore peripheral immunosuppression. The authors postulate that peripheral immunosuppression may occur in ventilated surfactant deficient patients, which may enhance susceptibility for infections.     

Lung function in prematurely delivered rabbits treated with a synthetic surfactant

We treated prematurely delivered rabbit pups with the synthetic surfactant that has been named Exosurf. By weight, Exosurf is 61.8% dipalmitoylphosphatidylcholine, 6.8% hexadecanol, 4.6% tyloxapol, and 26.7% NaCl. This simple mixture, suspended at 15 mg lipid X ml-1 water, has appropriate in vitro characteristics for a lung surfactant substitute. As determined by static pressure volume relationships performed after 30 min ventilation, lungs treated with Exosurf accepted significantly more gas at maximal inflation (36 versus 15 ml X kg-1 body weight) and had significantly greater volumes during deflation that did saline-treated control lungs; lungs treated with natural rabbit surfactant (SAM) had significantly larger volumes at maximal inflation (65 versus 35 ml X kg-1) and during deflation than did the Exosurf-treated lungs. After 30 min of ventilation with oxygen and fixation at 10 cm H2O pressure, the ratio of air space to tissue space was determined by a point-counting technique, and mean linear intercepts were measured for air spaces. Exosurf-treated lungs were intermediate between SAM and saline-treated lungs in both measurements. With positive pressure ventilation to maintain a tidal volume of 6.5 to 7.5 ml X kg-1, total compliance was significantly greater and inspiratory pressure significantly lower in both SAM- and Exosurf-treated animals than in saline-treated control animals, although the lungs of the SAM-treated animals were more compliant than the lungs of animals treated with Exosurf. During the first minute of positive pressure ventilation, lungs treated with SAM or Exosurf expanded equally rapidly, both expanding more rapidly than the saline-treated lungs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hyperoxia and beta-adrenergic stimulation on pulmonary surfactant in neonatal rabbits.

To study the effects of hyperoxia and beta-adrenergic stimulation on pulmonary surfactant in the neonatal lung, we measured disaturated phosphatidylcholine (DSPC) and [14C]choline incorporation into DSPC, obtained from alveolar lavage and lung tissue. We used an isolated salt-perfused rabbit lung preparation from neonatal rabbits exposed to room air or greater than 95% oxygen for 3 days. There were four experimental groups: room air, basal condition; room air, beta-adrenergic stimulation; hyperoxia, basal conditions; and hyperoxia, beta-adrenergic stimulation. Hyperoxia caused a significant decrease in lavage and intracellular [14C]DSPC specific activity, and a decrease in intracellular DSPC suggesting depressed surfactant synthesis. Beta-stimulation in room air caused a decrease in lavage DSPC, an increase in DSPC, and [14C]DSPC fraction released, consistent with increased uptake for reutilization. With hyperoxia and beta-stimulation, there is an increase in total DSPC in the lavage; lavage [14C]DSPC specific activity is similar to that of the basal hyperoxia group (i.e., depressed compared with the room air state); intracellular [14C]DSPC specific activity does not differ from basal, hyperoxia, or beta-stimulated, room air groups, all being depressed compared with basal, room air conditions. Intracellular DSPC in the beta-stimulated group is less affected by hyperoxia than the basal groups. It appears that prolonged exposure to hyperoxia is manifested primarily by a decrease in [14C]DSPC specific activity suggesting alterations in surfactant synthesis, though DSPC in the lavage is not altered. Beta-adrenergic stimulation may enhance release of newly synthesized surfactant into the alveoli, and possibly enhances uptake for reutilization. The enhancement of surfactant release seems to be preserved after prolonged hyperoxia.     

Growth of pulmonary microvasculature in ventilated preterm infants

RATIONALE: Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. OBJECTIVE: To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants. METHODS: Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels. MEASUREMENTS: Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels. MAIN RESULTS: Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern. CONCLUSIONS: The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.     

Effect of neonatal surfactant therapy on lung function at school age in children born very preterm

Our aim was to evaluate long-term effects of exogenous surfactant therapy on pulmonary functional outcome in children born very preterm. We examined 40 children aged 7–12 years who were born before 30 weeks of gestation with an immature surfactant system, and were randomized to one of three treatment groups: human surfactant given at birth (prophylactic), human surfactant given after development of neonatal respiratory distress syndrome (rescue), and placebo (air) treatment. Spirometric parameters of preterm born children were compared with those of 20 children born at term. In addition, spirometric parameters were monitored twice daily for 4 weeks using a home spirometer. All spirometric parameters were significantly lower in the preterm groups than in the controls, except for the forced vital capacity (FVC) in the prophylactically treated group. Bronchial obstruction was found in 53% of the prophylactically treated group, in 36% of the rescue group, in 67% of the placebo group, and in 0% of the control group. Peak expiratory flow (PEF) and FVC values were higher in those children who received surfactant compared with the placebo group (P < 0.05). In 16 children (40%) born preterm, a β₂-agonist induced an increase in PEF ≥15% at least three times during 2 weeks of home monitoring; eight children (20%) had abnormal diurnal PEF variation. Multiple regression analysis indicated that the independent variables associated with favorable outcomes in spirometric parameters were surfactant therapy (P = 0.012–0.045) and short intubation time after birth (P = 0.0009–0.0044). Bronchial obstruction, responsiveness to a β₂-agonist, and high diurnal PEF variation are common in children born before 30 gestational weeks. Surfactant supplementation reducing the need for mechanical ventilation or supplementary oxygen after birth may decrease the severity of immaturity related bronchial obstruction in childhood. Pediatr. Pulmonol. 1998; 25:182–190. © 1998 Wiley-Liss, Inc.     

Bronchoalveolar lavage fluid surfactant protein-A and surfactant protein-D are inversely related to inflammation in early cystic fibrosis

The pulmonary collectins surfactant protein (SP)-A and SP-D play important roles in innate lung defense, enhancing opsonization of microbes and limiting lung inflammatory responses. To quantify relationships among collectins, bacteria, and inflammation in early cystic fibrosis (CF) airway secretions, bronchoalveolar lavage fluids (BALFs) were collected from children undergoing clinically indicated bronchoscopy. Quantitative bacteriology, differential cell counts, and ELISA for SP-A and SP-D were assessed. Significantly increased numbers of neutrophils relative to bacteria were noted in BALF from CF compared with non-CF subjects. Although SP-A levels tended to be lower in CF compared with non-CF, this was only significant in the presence of bacterial infection. Among CF patients, SP-A concentrations in BALF were inversely related to inflammation, bacterial colony-forming units per milliliter, and age. SP-D levels were significantly decreased in CF patients, and SP-D was rarely detectable in the presence of infection. Among CF patients, SP-D correlated inversely with inflammation and bacterial colony-forming units per milliliter, and there was decreased immunostaining of BALF cells for SP-D in CF. Immunohistochemistry of CF autopsy lung sections for SP-A and SP-D confirmed their paucity at sites of infection and inflammation. We conclude that relative collectin deficiency occurs early in CF airways and is inversely related to inflammation in CF airways.     

Serum surfactant protein-A levels in chronic bronchitis and its relation to smoking

BACKGROUND: Surfactant protein-A (SP-A), which is an important constituent of natural surfactant, occurs physiologically in small amounts in blood. Tobacco smoke induces increased alveolo-capillary leakage of surfactant proteins into blood and its level in blood may help in the assessment of lung injury caused by smoke. Little is known on the SP-A levels in patients with chronic obstructive pulmonary disease (COPD). METHODS: Prospective analytical study of 30 patients with clinical diagnosis of chronic bronchitis, which was made on the basis of symptoms, signs and chest radiographic findings. Serum SP-A and serum cotinine levels were measured. RESULTS: Out of 30 patients, 21 were smokers and nine were non-smokers. The serum SP-A level in smokers with chronic bronchitis is significantly higher than the non-smokers. The plasma cotinine levels are also high in smokers. However, there was no correlation between the serum SP-A level and plasma cotinine level (r=0.044). Serum SP-A levels were related to age in smokers (r=0.566, p<0.01) but not in non-smokers with chronic bronchitis (r=0.017, p>0.05). CONCLUSION: The increase in SP-A level in smokers with chronic bronchitis suggests that tobacco smoking causes a chronic increase in permeability of the lung parenchyma. The SP-A, a lung-specific secretory protein, is a potential marker for non-invasive assessment of the integrity of the lung epithelium. Further studies are required to find out whether SP-A can be used as a marker for early identification of smokers who are at risk of COPD.     

Increased surfactant protein-A levels in patients with newly diagnosed idiopathic pulmonary fibrosis

STUDY OBJECTIVES: To measure surfactant protein-A (SP-A) in the BAL of patients with idiopathic pulmonary fibrosis (IPF). DESIGN: We examined SP-A in BAL and lung tissue of patients with IPF who met the stricter recommended criteria for IPF at the time of diagnosis and prior to the beginning of treatment. PATIENTS: Twenty-six patients with IPF confirmed at biopsy and 22 patients with hypersensitivity pneumonitis (HP) were compared with 9 normal volunteers. INTERVENTIONS: All patients were subjected to pulmonary function testing, BAL, and lung biopsy prior to the beginning of treatment. Measurements and results: We measured SP-A in BAL fluids and performed SP-A immunohistochemistry on lung specimens. Lung tissues of patients with IPF showed extensive type II cell hyperplasia, usually containing greatly increased levels of immunoreactive SP-A. By enzyme-linked immunosorbent assay, we found a twofold increase over normal values in BAL SP-A without changes in total phospholipids. These data were in agreement with semiquantitative assessments of SP-A by protein immunoblotting and by Western blotting of sodium dodecyl sulfate gels. Patients with HP exhibited a threefold increase of BAL SP-A. CONCLUSIONS: The reasons for the difference between our results and previously published reports describing decreased SP-A levels in IPF is not clear. It may relate to the stricter criteria for diagnosis, the absence of treatment prior to BAL, differences in the patient population, or to other methodologic differences.