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Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung.

1. During fetal life the lung develops as a liquid-filled organ. This liquid is produced by the fetal lung and leaves via the trachea from where it is either swallowed or enters the amniotic sac. Fetal lung liquid plays a crucial role in the growth and development of the lungs by maintaining them in a distended state. It is now recognized that the retention of liquid within the future airways is required to maintain the lungs at an appropriate level of expansion in order to stimulate their growth. Indeed, it is likely that most, if not all, of the conditions and malformations that lead to inadequate growth of the fetal lung do so by reducing the volume of lung liquid and hence the degree of lung expansion. 2. The volume of fetal lung liquid is principally regulated by the resistance to lung liquid efflux through the fetal upper airway and by the presence of diaphragmatic activity associated with fetal breathing movements (FBM). During non-breathing periods, the relatively high resistance offered by the upper airway to the efflux of lung liquid opposes the loss of liquid from the lung, thereby maintaining fetal lung expansion. During episodes of FBM, when the larynx is actively dilated and the resistance to lung liquid efflux is reduced, lung liquid leaves the lungs at an increased rate. However, selective inhibition of diaphragmatic muscle activity in the foetus leads to a reduction in lung liquid volume, rather than an increase. This finding indicates that during periods of FBM, rhythmical contractions of the diaphragm retard the loss of lung liquid and help to maintain lung expansion when the upper airway resistance is reduced. It is now apparent that the maintenance of lung expansion by FBM is the basis for their role in promoting fetal lung growth. 3. Successful transition from intra-uterine to extra-uterine life is dependent upon the clearance of liquid from the fetal lungs at the time of birth so that the lungs may effectively function as an organ of gas exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparative outcome of heart-lung and lung transplantation for pulmonary hypertension.

Despite the development of several lung transplantation procedures, the most advantageous for pulmonary hypertension remains controversial. Between 1986 and February 1992, 30 patients with end-stage primary pulmonary hypertension (n = 24), chronic pulmonary embolism (n = 4), and hystiocytosis X (n = 2) underwent heart-lung (n = 21), double lung (n = 8), or single lung (n = 1) transplantation. Indications for double lung transplantation were similar to those for heart-lung transplantation, and the preoperative clinical and hemodynamic parameters were not significantly different between the two groups. There were no intraoperative deaths, but two reoperations were needed for pleural hematoma. Five early deaths were related to graft failure (two heart-lung transplantations), mediastinitis (one heart-lung transplantation), multiorgan failure (one double lung transplantation), and aspergillosis (one double lung transplantation). There was a similar improvement in early (days 0 and 2) and late (6 months postoperatively) right-sided hemodynamic function in patients undergoing heart-lung and double lung transplantation. Three double lung transplant recipients had early and reversible left ventricular-failure. The early postoperative course of the one patient who had single lung transplantation was characterized by severe pulmonary edema, left ventricular failure, and persistent desaturation and later on by moderate pulmonary hypertension and an important ventilation/perfusion mismatch. The pulmonary function results were also similar in the heart-lung and double lung transplantation groups. The overall projected 2- and 4-year survivals were 49% and 41%, respectively, and were not significantly different between the heart-lung and double lung recipients. Results demonstrate that heart-lung and double lung transplantation are equally effective in obtaining early and durable right-sided hemodynamic and respiratory improvement and similar respiratory function. In patients with pulmonary hypertension, double lung transplantation should be preferred to single lung transplantation because of the critical postoperative course and the uncertain long-term results of single lung transplantation.

Adolescent↗

A scanographic assessment of pulmonary morphology in acute lung injury. Significance of the lower inflection point detected on the lung pressure-volume curve.

The goal of this study was to assess lung morphology in patients with acute lung injury according to the presence or the absence of a lower inflection point (LIP) on the lung pressure-volume (P-V) curve and to compare the effects of positive end-expiratory pressure (PEEP). Eight patients with and six without an LIP underwent a spiral thoracic CT scan performed at zero end-expiratory pressure (ZEEP) and at two levels of PEEP: PEEP1 = LIP + 2 cm H2O and PEEP2 = LIP + 7 cm H2O, or PEEP1 = 10 cm H2O and PEEP2 = 15 cm H2O in the absence of an LIP. The volumes of air and tissue within the lungs were measured from the gas-tissue ratio and the volumes of overdistended and normally, poorly, and nonaerated lung areas were determined by the analysis of the frequency histogram distribution. In the ZEEP condition, although total lung volume, volume of gas, and volume of tissue were similar in both groups, the percentage of normally aerated lung was lower (24 +/- 22% versus 55 +/- 12%, p < 0.05) and the percentage of poorly aerated lung was greater (40 +/- 12% versus 23 +/- 8%, p < 0.05) in patients with an LIP than in patients without an LIP. Lung density histograms of patients with an LIP showed a unimodal distribution with a peak at 7 Hounsfield units (HU). Lung density histograms of patients without an LIP had a bimodal distribution, with a first peak at -727 HU and a second peak at 27 HU. Total respiratory system and lung compliances were lower in patients with an LIP whereas all other cardiorespiratory parameters were similar in the two groups. In both groups, PEEP induced an alveolar recruitment that was associated with lung overdistension only in patients without an LIP. The amount of lung overdistension was related to the volume of lung parenchyma, characterized by a CT number less than -800 HU before PEEP implementation (y = 0.52x + 4, R = 0.87, and p < 0.0001). This study shows that the presence or the absence of an LIP on the lung P-V curve is associated with differences in lung morphology. In patients without an LIP on the lung P-V curve, normally aerated lung areas coexist with nonaerated lung areas and increasing levels of PEEP result in lung overdistension rather than in additional alveolar recruitment. In patients with an LIP, air and tissue are more homogeneously distributed within the lungs and increasing levels of PEEP result in additional alveolar recruitment without lung overdistention.

Acute Disease↗

Effect of lung volume on lung resistance and elastance in awake subjects measured during sinusoidal forcing.

BACKGROUND: Although lung volume may be changed by certain procedures during anesthesia and mechanical ventilation, dependence of the dynamic mechanical properties of the lungs on lung volume are not clear. Based on studies in dogs, the authors hypothesized that changes in lung mechanics caused by anesthesia in healthy humans could be accounted for by immediate changes in lung volume and that lung resistance will not be decreased by positive end-expiratory airway pressure if tidal volume and respiratory frequency are in the normal ranges. METHODS: Lung resistance and dynamic lung elastance were measured in six healthy, relaxed, seated subjects during sinusoidal volume oscillations at the mouth (5 mL/kg; 0.4 Hz) delivered at mean airway pressure from -9 to +25 cmH2O. Changes in lung volume from functional residual capacity were measured with inductance plethysmographic belts. RESULTS: Decreases in mean mean airway pressure that caused decreases in lung volume from functional residual capacity comparable to those typically observed during anesthesia were associated with significant increases in both dynamic lung elastance and lung resistance. Increases in mean mean airway pressure that caused increases in lung volume from functional residual capacity did not increase lung resistance and increased dynamic lung elastance only above about 15 cmH2O. CONCLUSIONS: Increases in dynamic lung elastance and lung resistance with anesthesia can be explained by the accompanying, acute decreases in lung volume, although other factors may be involved. Increasing lung volume by increasing mean airway pressure with positive end-expiratory pressure will decrease lung resistance only if the original lung volume is low compared to awake, seated functional residual capacity.

Adult↗

Role of open lung biopsy in lung transplant recipients in a single children's hospital: a 13-year experience.

BACKGROUND: There are few data in the literature regarding the utility of open lung biopsy for the assessment of graft dysfunction after pediatric lung transplantation. The aim of this study is to review our experience with diagnostic open lung biopsy in lung transplant recipients in a children's hospital. METHODS: Records of lung transplant recipients from January 1990 through December 2002 were reviewed to identify the indications, outcomes, and complications of open lung biopsy. RESULTS: Two hundred twenty-four patients (mean age, 9.9 +/- 6.2 years; median age, 11 years; age range, 0.01-19.6 years) underwent 249 lung transplantations: 231 bilateral, 8 single, and 10 heart-lung transplantations. Mean follow-up was 3.4 years. One hundred three open lung biopsies were performed in 89 (40% of all recipients) patients. Thirteen recipients underwent open lung biopsy twice, and 1 recipient had 3 open lung biopsies. The indications for open lung biopsy were suspicion of bronchiolitis obliterans (n = 70), posttransplantation lymphoproliferative disorder (n = 15), infection (n = 8), and unexplained respiratory failure (n = 10). A new diagnosis was made in 49 biopsies (48%), 50 biopsies (49%) confirmed the preoperative clinical diagnosis, and 4 biopsies (3%) were nondiagnostic. Bronchiolitis obliterans was confirmed in 40 (57%) of 70 open lung biopsies, posttransplantation lymphoproliferative disorder was confirmed in 4 (27%) of 15 open lung biopsies, and infection was confirmed in 6 (75%) of 8 open lung biopsies. A change in therapy occurred in 69% of the cases as a result of the diagnosis made from open lung biopsy. There was no mortality as a direct result of open lung biopsy. Eleven major complications and 22 minor complications occurred in 103 procedures. CONCLUSION: Open lung biopsy can be performed safely, and established or confirmed a diagnosis in 97% of the cases. A change in therapy occurred in 69% of the cases as a result of the diagnosis made from open lung biopsy. In our experience open lung biopsy appears to be a useful tool.

Adolescent↗

Lung transplant waiting list: differential outcome of type of end-stage lung disease, one year after registration.

BACKGROUND: Donor lung scarcity, distinct natural courses of the different types of end-stage lung diseases, and lung allocation schemes demand appropriate candidate acceptance for a lung transplant and time of listing. This study was undertaken to investigate the association between type of end-stage lung disease and outcome, 1 year after a lung transplant candidate was put on the waiting list. METHODS: From 1990 to 1995, 1376 adult patients were registered for a first lung (n = 1006) or heart-lung (n = 370) transplantation in Eurotransplant. All patients were followed for at least 1 year. For each type of end-stage lung disease (cystic fibrosis, pulmonary fibrosis, emphysema, pulmonary hypertension, congenital heart disease, and other), chances of transplantation, of death on the waiting list, and of removal for other reasons, 1 year after listing, were calculated with the competing risks method. A multivariate Cox regression model was used to assess the influence of the type of end-stage lung disease on the waiting list outflow among other prognostic variables. RESULTS: Lung transplant candidates with emphysema and with pulmonary fibrosis had the highest chance of a transplant; however, patients with pulmonary fibrosis had also the highest probability of dying while waiting, while the emphysema patients and those with the type "other" had the lowest probability. In the multivariate analysis, the type of end-stage lung disease appeared as an independent prognostic factor for both outcomes. Compared to the patients with cystic fibrosis (reference group), only patients with pulmonary fibrosis had a significantly higher chance of a transplant (RR = 1.50); the lowest chance of death for the emphysema and the "other" patients was confirmed (RR = 0.53 and RR = 0.51, respectively). Recipient size, ABO blood group, country and epoch of listing also had a significant impact on the transplant chance, while country of listing and recipient age were the other factors independently influencing the chance of dying on the waiting list. On the heart-lung waiting list, the type of end-stage lung disease solely affected the chance of death prior to transplant. Compared with cystic fibrosis, pulmonary fibrosis had a significantly higher risk (RR = 2.93), closely followed by pulmonary hypertension (RR = 2.57). Factors crucial for the chance of a heart-lung transplant were recipient size, ABO blood group and country of listing. CONCLUSIONS: The type of end-stage lung disease is a distinctive factor for predicting survival on the lung and heart-lung transplant waiting list, and should be taken into account whenever assessing waiting list outcomes. When developing lung allocation schemes, it is medically justified to incorporate the type of end-stage lung disease.

Adolescent↗

[Utility of SPECT lung perfusion scans in assessing early changes in pulmonary function of patients with lung cancer after radiotherapy].

BACKGROUND & OBJECTIVE: Radiation-induced lung injury is commonly following radiotherapy (RT)for tumors in,and around the thorax. Lung function is usually assessed by pulmonary function tests (PFTs), but RT-induced regional changes of pulmonary function cannot be accurately evaluated by PFTs. Lung perfusion scintigraphy compared with other radiographic methods can well assess the regional pulmonary physiological function,and 3-dimension conformal radiotherapy (3D-CRT) planning system can quantitatively calculate irradiation dosage. This study was to assess early changes in the pulmonary function of patients with lung cancer receiving thoracic 3D-CRT by lung perfusion scintigraphy. METHODS: Nineteen patients receiving thoracic 3D-CRT for lung cancer were studied. Single photon emission computed tomography (SPECT) lung perfusion scan,and X-ray or CT scan before RT, and after 40-50 Gy radiation were performed. Pre-RT SPECT lung perfusion images were classified by comparing lung perfusion defect with area of radiological abnormality before RT. Grade 0: no lung perfusion defect in the area of radiological abnormality. Grade 1: the size of radiological abnormality is similar to the area of lung perfusion defect. Grade 2: the area of lung perfusion defect is bigger than that of radiological abnormality,and extend to 1 pulmonary lobe. Grade 3: the area of lung perfusion defect exceed 1 pulmonary lobe. The radiation field with more than 20 Gy was drawn as a region of interest (ROI). The proportion of radioactive count within this ROI to total lung count in one slice was calculated to assess changes in pulmonary function after RT. Student's t test was used for statistical analyses. RESULTS: All patients had lung perfusion defect, 9 patients with grade 1 damage, 5 patients with grade 2 damage, and 5 patients with grade 3 damage. All tumors in the 19 patients were reduced with variant degree after 40-50 Gy radiation in CT or X-ray images. The mean radioactive proportions of ROI in 19 patients were (53.7+/-29.8)% before radiation,and (57.6+/-22.6)% during RT, the difference wasn't significant (P=0.280). The relatively decreased post-RT lung perfusion was observed in 6 patients, whereas the relatively increased post-RT lung perfusion was observed in 13 patients. CONCLUSION: SPECT lung perfusion scans is a simple, convenient, and useful method for assessing pre-RT regional lung function,and monitoring the changes in regional lung function after irradiation.

Adult↗

Evaluation of the long-term results of single lung versus heart-lung transplantation for emphysema.

BACKGROUND: Heart and lung transplantation used to be the standard operation for patients with emphysema. Because of the shortage of donors, more patients are having single lung transplantation with satisfactory short-term results. METHODS: This study was performed to evaluate the long-term results of both groups. During the period between December 1985 and December 1993, 89 patients underwent lung transplantation, and 68 patients (43 male and 25 female) underwent single lung transplantation. There were 31 right and 37 left single lung transplantations with 24 bronchial revascularization procedures. RESULTS: The actuarial 5-year survival was 67% +/- 0.3% in single lung and 60% +/- 0.2% in heart-lung groups (p = 0.947). In the single lung group, two patients required a second single lung for air trapping and 11 patients (16%) had obliterative bronchiolitis, two of whom required retransplantation. In the heart-lung group, four patients (19%) had obliterative bronchiolitis, two of whom required retransplantation. The cumulative probability of developing obliterative brochiolitis at 3 and 5 years was 17% and 38% in the heart-lung transplantation group and 23% and 48% in the single lung transplantation group, respectively. The average forced expiratory volumes in 1 second at 3 and 5 years were 1.6 and 1.4 (L/min) (standard error +/- L/min) for single lung and 3 and 2.9 (L/min) standard error +/- 0.25) for heart-lung transplant recipients, respectively. The percentage of the predicted maximum oxygen consumption was 42% and 58% in single lung and heart lung groups, respectively. CONCLUSIONS: The long-term results in respiratory function, exercise capacity, and the quality of life of heart-lung transplant recipients are significantly better with survival compared with single lung transplant recipients. Although single lung transplantation for patients with emphysema makes better use of organs, the long-term results when compared with those of the heart-lung group needs to be evaluated further.

Adult↗

Retinoic acid rescues lung hypoplasia in nitrofen-induced hypoplastic foetal rat lung explants.

There is increasing evidence to suggest that the retinoid pathway is involved in the pathogenesis of congenital diaphragmatic hernia (CDH). We hypothesised that retinoids are involved in the pathogenesis of associated pulmonary hypoplasia in CDH and therefore designed this study to investigate the effects of retinoid acid on nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9.5 of gestation. Foetal lungs were harvested on embryonic day 13.5 and were cultured for 96 h with or without exogenous retinoic acid (RA) (1 muM) added daily to the culture medium. Lungs were divided into four study groups: control (n=31); control + RA (n=19); nitrofen (n=19); and nitrofen + RA (n=12). Lung growth was assessed in each group by measuring branching morphogenesis, total DNA content and the proportion of proliferating cells stained by immunohistochemistry. One-way ANOVA test was used for statistical analysis. Retinoic acid significantly increased the growth of nitrofen-induced hypoplastic lungs, whilst growth of control lungs did not change. The number of lung buds and lung area of nitrofen-exposed hypoplastic lungs after 96 h of culture significantly increased after the addition of RA compared to the non-treated hypoplastic lungs (25.75+/-6.47 vs 15.11+/-3.29 and 0.98+/-0.18 mm(2) vs 0.65+/-0.13 mm(2), respectively; P<0.0001). Lung perimeter was also higher when RA was added to hypoplastic lungs compared to the non-treated ones, although it did not reach significance (12.51+/-2.53 mm vs 11.19+/-2.56 mm; P=0.17). Conversely, the addition of RA to control lungs did not affect the number of lung buds, lung area or lung perimeter after 96 h in culture compared to the non-treated ones (31.28+/-4.66 vs 31.81+/-6.67; 1.29+/-0.18(2) vs 1.29+/-0.23 mm(2) and 18.47+/-3.47 mm vs 17.89+/-2.94 mm, respectively; P=NS). Retinoic acid also increased the total DNA content and the proportion of proliferating cells in hypoplastic lungs compared to the non-treated ones (2.59+/-0.58 mug vs 1.96+/-0.31 mug and 57.89+/-9.46% vs 36.76+/-8.15%, respectively; P<0.001). The addition of RA did not affect either total DNA content or the proportion of proliferating cells in control lungs compared to the non-treated ones (4.04+/-0.64 mug vs 3.79+/-0.85 mug and 58.67+/-11.23% vs 56.03+/-10.36%, respectively; P=NS). This study demonstrates for the first time that RA rescues lung hypoplasia in nitrofen-induced hypoplastic lungs. These results suggest that retinoid pathway may be involved in the pathogenesis of associated pulmonary hypoplasia in CDH.

Analysis of Variance↗

The effects of prenatal intraamniotic surfactant or dexamethasone administration on lung development are comparable to changes induced by tracheal ligation in an animal model of congenital diaphragmatic hernia: studies of lung glycogen content, elastic fiber density, and collagen content.

BACKGROUND/PURPOSE: A new noninvasive therapeutic strategy, which consisted of prenatal intraamniotic administration of porcine surfactant or dexamethasone, was previously used to prevent the functional and structural immaturity of lungs associated with congenital diaphragmatic hernia (CDH), and its effects on lung development were comparable with the changes induced by tracheal ligation (TL). The purpose of this study is to verify if this novel therapeutic modality has any effect in the elevated concentration of lung glycogen and altered contents of lung elastic fiber and collagen promoted by CDH. METHODS: A pilot study was performed to investigate in the rabbit model if the infused drugs in the amniotic cavity were aspirated by the CDH and non-CDH fetuses, and if there was correspondence between lung immaturity and high glycogen concentration in lung tissue. Experimental groups consisted of 50 pregnant rabbits that underwent surgery on gestational day 24 or 25 to create left-sided diaphragmatic hernias in 56 fetuses, which were divided in groups according to the procedures: CDH (n = 12), CDH plus TL (n = 16), CDH plus intraamniotic administration of Curosurf (40 mg, n = 12), and CDH plus intraamniotic administration of dexamethasone (n = 16). On gestational day 30, the fetuses were delivered by cesarean section, and 28 normal unoperated fetuses served as controls. The lungs were weighed and submitted to biochemical determination of glycogen, morphometric evaluation of elastic fibers, and colorimetric analysis of collagen. RESULTS: In all CDH and non-CDH fetuses of the pilot study, the amniotic content was massively aspirated into the lungs and trachea. There was an increase in lung glycogen content of fetuses at 24 days' gestation in comparison with 20-day gestational age fetuses, followed by a decrease in the near full-term fetuses. In the fetuses of the experimental groups, CDH decreased the lung weight to body weight ratios of lungs ipsilateral to the hernia. These changes were reversed by TL but not by intraamniotic administration of surfactant or dexamethasone. Lung glycogen concentrations in the lungs of CDH fetuses were significantly higher than those in the control group. These changes were reversed by intraamniotic administration of surfactant but not by dexamethasone administration or TL. In the lungs ipsilateral to the hernia, surfactant administration promoted a significant decrease in glycogen content to levels lower than control lungs. CDH promoted a decrease in the linear density of elastic fibers in both lungs, ipsilateral and contralateral to the hernia. This alteration was partially corrected by TL and surfactant administration, although dexamethasone administration had no effect. The concentrations of collagen in both lungs were increased significantly by CDH, and these alterations could not be reversed by TL. In the lungs ipsilateral to the hernia, intraamniotic administration of surfactant or dexamethasone promoted a significant decrease in the lung concentration of collagen but not to control levels. CONCLUSIONS: The positive effects of intraamniotic surfactant or dexamethasone administration on lung maturity of fetuses with CDH were observed. This therapy may be a substitute for TL.

Animals↗

Aryl hydrocarbon hydroxylase activity in human lung tissue: in relation to cigarette smoking and lung cancer.

In order to investigate the relationship between aryl hydrocarbon hydroxylase (AHH) activity and smoking or lung cancer, AHH activities in fresh lungs (normal tissue, tumorous tissue, and surrounding tissue of tumor) obtained from lung cancer patients and non-lung cancer patients were measured. There were no differences in lung AHH activity in the lung lobes. In the non-lung cancer patients, AHH activities ranged from 0.13 to 2.37 (pmol 3 hydroxybenzo[a]pyrene/20 min/mg protein), and whereas in the normal tissues of the lung cancer patients they ranged from 0.19 to 5.05. Lung AHH activities showed normal distribution, and a large variation (26 times) was observed in normal tissues in the lung cancer patients. In most cases, AHH activities in the tumorous tissues and the surrounding tissue of the tumor were lower than those in the normal tissues of the lung cancer patients. In the non-lung cancer group, the means of AHH activity of the nonsmoker subgroup (NN) and the smoker subgroup (SN) were 0.62 and 0.96, respectively. On the other hand, in the lung cancer group the means of AHH activity of the nonsmoker subgroup (NC) and smoker subgroup (SC) were 0.85 and 1.05, respectively. Statistically significant differences were observed between NN and SN, NN and NC, and NN and SC. These results suggest that human lung AHH activity was increased by cigarette smoke as in rodent lungs, and the distribution of basal AHH activity in lung tissue of the nonsmokers group in the lung cancer patients shifted toward high levels compared to the nonsmokers group in the non-lung cancer group. The effect of the histological cell types of the lung cancer on the AHH activity was not observed in this study.

Adenocarcinoma↗

Modeling and remodeling of the lung in neonatal chronic lung disease: implications for therapy.

Neonatal chronic lung disease (CLD) is the major long-term pulmonary complication of preterm birth affecting about 20% of infants who need mechanical ventilation. CLD is the result of abnormal repair processes following inflammatory lung injury that lead to remodeling of the lung. Inflammation may be initiated by a variety of stimuli including mechanical ventilation, oxygen toxicity and infection. The resultant neutrophil chemotaxis and degranulation leads to the release of enzymes such as matrix metalloproteinases that can cause proteolysis of the lung extracellular matrix. Abnormal healing with remodeling leads to poorly compliant lungs with reduced capacity for gas exchange. Drugs can influence the normal process of lung modeling or remodeling. Fetal lung development can be influenced by glucocorticosteroids and inflammation. Both can cause abnormal lung modeling with fewer, larger alveoli and accelerated lung maturation, which confers benefits in terms of reduced morbidity and mortality from respiratory distress syndrome but potentially increases the risk of subsequent lung injury. Antioxidants, such as retinol (vitamin A), administered post-natally may reduce the effects of oxidative stress leading to a modest reduction in CLD but they require repeated intramuscular injections. Postnatal glucocorticosteroid therapy can modify the lung inflammatory response and reduce CLD but it can also have detrimental effects on the developing brain and lung, thereby creating a clinical dilemma for neonatologists. Proteinase inhibitors may be a rational therapy but more research is needed before they can be accepted as a treatment for preterm neonates.'Modeling' is defined as planning or forming that follows a set pattern. The term is used to describe the normal process of lung growth and development that culminates in mature branching alveolar air spaces surrounded by a network of capillaries. Normal lung modeling occurs under a variety of genetic and hormonal influences that can be altered, leading to abnormal patterns of growth. 'Remodeling' is defined as altering the structure of or re-making and, in the case of the lung, is used to describe the abnormal patterns of lung growth that occur after lung injury. Modeling and remodeling of the lungs occur to an extent throughout life but never more rapidly than during the fetal and early neonatal periods, and factors that influence this process may lead to development of neonatal CLD. Some of the factors involved in normal and abnormal lung modeling and inflammation and glucocorticosteroid-induced remodeling in the perinatal period, in the context of neonatal CLD, are reviewed with considerations of how various drugs may influence these processes.

Chronic Disease↗

Lung mechanical behavior during one-lung ventilation.

OBJECTIVE: Switching from two-lung to one-lung ventilation would be expected to have large effects on lung mechanical properties, and these effects may depend on tidal volume and respiratory frequency. These changes in lung mechanics with one-lung ventilation may be similar to pulmonary edema. Deteriorating lung mechanics during pulmonary edema have been attributed to a loss of ventilated lung units. Therefore, changes in lung mechanics caused by one-lung ventilation were measured and compared with those previously seen during pulmonary edema. DESIGN: Prospective study. SETTING: Research laboratory. INTERVENTIONS: After induction of anesthesia, beagle dogs' tracheas were intubated with an endotracheal tube with a bronchial blocker (Univent System Corp, Tokyo, Japan) to apply one-lung ventilation. The proper position of the bronchial blocker during one-lung ventilation was confirmed with a fiberoptic bronchoscope. MEASUREMENTS AND MAIN RESULTS: Lung elastance (EL) and resistance (RL) were calculated from measurements of airway pressure, esophageal pressure, and airway flow in five anesthetized, paralyzed dogs during sinusoidal forcing at a constant mean airway pressure of 10 cmH2O in a wide range of breathing frequencies (0.2 to 1.0 Hz in intervals of 0.2) and tidal volumes (50, 100, 200, and to 300 mL). Measurements were made before and after the left mainstem bronchus was occluded with the bronchial blocker. During ventilation of both lungs, EL and RL depended relatively little on frequency, and both EL and RL were independent of tidal volume. During one-lung ventilation, EL doubled and, at most frequencies, RL increased; frequency dependences were not increased, and no dependence on tidal volume was observed. CONCLUSIONS: The lack of tidal volume dependence in EL and lack of large-frequency dependence in RL during one-lung ventilation are inconsistent with changes induced by severe pulmonary edema. Although decreases in ventilatable lung volume may contribute to increases in lung elastance, other characteristics of mechanical behavior during one-lung ventilation differ from those of pulmonary edema; therefore, other additional mechanisms must be involved in determining lung mechanical properties during severe pulmonary edema.

Airway Resistance↗

Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema.

BACKGROUND: Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. METHODS: We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. RESULTS: Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with alpha1-antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P = 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/F(I)O2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9+/-14.6 hours vs 40.4+/-3.9, P = 0.02, ANOVA) and longer lengths of stay (19.3+/-2.1 days vs 13.7+/-1.3, P = 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. CONCLUSION: Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation.

Acute Disease↗

Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury.

INTRODUCTION: Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange METHODS: In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung. RESULTS: Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve. CONCLUSION: A recruitment maneuver by repeatedly hyperinflating the lungs led to an increase of poorly aerated and a decrease of nonaerated lung mainly. Changes in aerated and nonaerated lung volumes were adequately represented by respiratory compliance but not by changes in oxygenation or shunt.

Animals↗

The Washington University-Barnes Hospital experience with lung transplantation. Washington University Lung Transplantation Group.

OBJECTIVE: --To review our experience with lung transplantation, emphasizing recipient selection, choice of procedure, functional results, and outcome. DESIGN: --Retrospective review of patients who received lung transplants at Barnes Hospital, St Louis, Mo, between July 1, 1988, and January 31, 1991. SETTING: --Washington University School of Medicine, St Louis, Mo, and Barnes Hospital, a medical school and its affiliated referral hospital, respectively. PATIENTS: --Sixty-nine lung transplant procedures were performed in 66 recipients. Patients with clinically and physiologically severe lung disease were selected according to predetermined guidelines. Underlying diseases in the recipients included chronic obstructive pulmonary disease, alpha 1-antitrypsin deficiency emphysema, cystic fibrosis, pulmonary fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome associated with an atrial septal defect, bronchiectasis, eosinophilic granuloma, and lymphangiomyomatosis. INTERVENTION: --Double-lung, bilateral sequential, and single-lung transplantations were performed. Eight patients underwent en bloc double-lung transplantations or a modification of this procedure with separate bronchial anastomoses. Thereafter, the bilateral sequential approach to replacement of both lungs was performed in 26 patients. Thirty-two patients underwent single-lung transplantations. MAIN OUTCOME MEASURES: --Pulmonary function tests, arterial blood gas levels, pulmonary artery pressure, pulmonary vascular resistance, and actuarial survival. RESULTS: --Actuarial survival at 1 year for the 66 lung transplant recipients was 79%. Actuarial survival at 1 year was 82% for the bilateral lung transplant recipients and was 90% for the single-lung transplant recipients. In patients with either restrictive or obstructive lung disease, pulmonary function tests and arterial blood gas levels improved markedly after lung transplantation. In patients with primary pulmonary hypertension or Eisenmenger's syndrome, the pulmonary artery pressure decreased and the cardiac index increased into the normal range after single-lung transplantation. CONCLUSIONS: --In carefully selected patients with end-stage lung disease, single-lung and bilateral lung transplantations can significantly improve functional capacity, with promising early actuarial survival statistics after 1 year.

Actuarial Analysis↗