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PubMed1999

Intrapulmonary gas mixing and the sloping alveolar plateau in COPD patients with macroscopic emphysema.

Chronic obstructive pulmonary disease patients, especially those with emphysema, show steep slopes of the alveolar plateau (S). This study tested the hypothesis that continued gas exchange between poorly and well-ventilated lung units by means of collateral ventilation would contribute to S in these patients. Nine young volunteers, nine older volunteers and 11 patients with macroscopic emphysema performed wash-out tests with helium (He) and sulphur hexafluoride (SF6). S was determined for breaths 1-5 (range 1), and for breaths between 95% and 98% of complete wash-out (range 2). An unequal ventilation index (UVI) was defined as the ratio between the estimated mean alveolar pressure and the end tidal pressure (PET) of each tracer gas, calculated over range 2. Over the same range, a phase III ratio was calculated by dividing PET by the estimated pressure at Fowler dead space. In all groups of subjects, the S for He and SF6 were greater for range 2 than for range 1 (p< or =0.012). In the emphysema patients, the correlations between S and UVI were 0.72 for He (p=0.012) and 0.81 for SF6 (p=0.002), while the mean phase III ratios were 1.7 for He and 2.4 for SF6, much less than their theoretical maxima. It was concluded that in patients collateral ventilation may account for only a small part of the increase in the alveolar plateau slope between ranges 1 and 2, and that this increase was mainly caused by unequal ventilation in combination with sequential emptying of lung units. The degree of sequential emptying, however, was modest compared with its full potential.

Adult↗
PubMed2000

Lung function measured by the oscillometric method in prematurely born children with chronic lung disease.

Premature birth is related to a chronic respiratory morbidity, which may persist until school-age. In these children, the forced oscillation technique would be suitable for evaluation of lung function even at preschool age, since it requires only minimal patient cooperation. In order to investigate the oscillometric findings related to premature birth, using the oscillation technique and conventional lung function methods 49 school-aged children born prematurely with (n=15) or without (n=34) chronic lung disease (CLD), and 18 healthy children born at full term were studied. Children with CLD had higher respiratory resistance (Rrs,5) and lower reactance (Xrs,5) than prematurely born children without CLD or healthy controls. Both Rrs,5 (r=-0.55, p<0.0001) and Xrs,5 (r=0.76, p<0.0001) were significantly associated with forced expiratory volume in one second (FEV1), the agreement with spirometry being better in Xrs,5 than in Rrs,5 (p=0.02). Rrs,5 was significantly related to airway resistance (Raw) measured by body plethysmography (r=0.63, p<0.0001), but underestimated resistance at high values of Raw. There was no significant relationship between the pulmonary diffusing capacity and the oscillometric findings. Compared to conventional methods, the oscillometric method yields concordant information on the severity of lung function deficit in children born prematurely, with or without chronic lung disease. In these children, the oscillometric findings are probably due to peripheral or more widespread airway obstruction. As conventional methods are not usually suitable for preschool children, oscillometry may serve as an alternative for early evaluation of chronic lung disease among children with premature birth in clinical or research settings.

Analysis of Variance↗
PubMed2000

Exhaled nitric oxide and its long-term variation in healthy non-smoking subjects.

Exhaled nitric oxide (NOexp) is an indicator of inflammation in the airways. Reference values obtained from healthy adults or information on long-term variation of NOexp are not yet available. The aims of this pilot study were to collect values of NOexp from a selected group of healthy adults and to assess their long-term variation. We studied 26 healthy subjects (age 21-48, 16 male, 10 female) with normal findings in flow-volume spirometry, pulmonary diffusing capacity, relative amount of blood eosinophils, chest X-ray and ECG at rest. NOexp was determined according to the European Respiratory Society guidelines during slow expiration against an airflow resistance. The measurements were repeated after 7 (n = 13) and 23 days (n = 17). The mean value of NOexp (n = 26) was 6.9 ng g-1 (95% confidence interval, 6.0-7.9 ng g-1). The upper limit of intra-individual variation (+2 SD) was 11.9 ng g-1 and the lower limit (-2 SD) 1.9 ng g-1, respectively. The mean (SD) value of NO production (NO output) was 39.1 pmol s-1 (20 pmol s-1). We found no correlation between NOexp and age (r = -0.06, P = 0.78) and no association of NOexp with the gender (male vs. female, P = 0.40). The intraindividual coefficient of variation (CoV) was 15.8% of NOexp and 20.7% of NO output within the interval of 7 days. CoV was 16.8% of NOexp and 18% of NO output within the interval 23 days. The results suggest that NOexp values over 12 ng g-1 are abnormally high in healthy subjects. According to the results the change of NOexp by 30-35% or more within the interval of 1-3 weeks would be abnormal.

Adult↗
PubMed2001

Postnatal outcomes in term and preterm lambs following fetal growth restriction.

1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm birth following intra-uterine growth restriction (IUGR) are unknown. Thus, our objectives were: (i) to identify prenatal factors associated with preterm birth in IUGR fetuses; and (ii) to characterize postnatal effects of preterm birth following IUGR. 2. We studied pregnant sheep and their offspring, in which fetal growth was restricted by umbilico-placental embolization during late gestation. Some of these animals were born at term (146 +/- 1 days) and some were born prematurely (139 +/- 1 days). In both groups, we have conducted longitudinal studies of postnatal respiratory function, cardiovascular function and learning ability up to 6-8 weeks of age. 3. Before birth, IUGR fetuses born prematurely (P-IUGR) were more hypoxaemic and acidaemic and had higher haemoglobin concentrations than both control fetuses and IUGR fetuses born at term (T-IUGR). In P-IUGR fetuses, plasma cortisol concentrations increased earlier than in the two other groups. The P-IUGR lambs had lower birthweights than T-IUGR lambs and both groups of IUGR lambs remained lighter than controls for 8 weeks. 4. After birth, P-IUGR lambs were hypoxaemic compared with T-IUGR and control lambs. Pulmonary diffusing capacity (adjusted for lung volume) was significantly lower in both groups of IUGR lambs than in controls, with P-IUGR lambs having lower values than T-IUGR lambs. Lung compliance (adjusted for lung volume), was not different between P-IUGR and control lambs, but values were higher in T-IUGR lambs than in control and P-IUGR lambs. Chest wall compliance (adjusted for lung volume) was higher in both groups of IUGR lambs than in controls. 5. During the 8 week postnatal study period, both groups of IUGR lambs had lower mean arterial pressures than control lambs; this relative hypotension was greatest in P-IUGR lambs. 6. In tests of learning ability, P-IUGR lambs took longer to complete a simple maze task at all ages and, in the second postnatal week, made a greater number of errors compared with controls. In an obstacle course, P-IUGR lambs recorded longer trial durations; they also made more errors than control lambs. 7. We conclude that preterm birth in the presence of late- gestational placental insufficiency and IUGR can result in specific effects on respiratory and cardiovascular development after birth, in addition to the effects of IUGR alone.

Animals↗
PubMed2006

Physiology of fetal lung fluid clearance and the effect of labor.

Respiratory morbidity in near term (> or =34 and <37 weeks) infants delivered spontaneously or by elective cesarean section (ECS) has been well documented in the literature, and accounts for a significant number of admissions to intensive care units among these neonates. Given the high rates of near-term deliveries in the USA and worldwide, the public health and economic impact of morbidity in this subgroup is considerable. Causes of respiratory distress include transient tachypnea of the newborn (TTNB), surfactant deficiency, pneumonia, and pulmonary hypertension. There is considerable evidence that physiologic events in the last few weeks of pregnancy coupled with the onset of spontaneous labor are accompanied by changes in the hormonal milieu of the fetus and its mother, resulting in rapid maturation and preparation of the fetus for delivery and neonatal transition. A surge in endogenous steroids and catecholamines accompanies term gestation and spontaneous vaginal delivery, and is responsible for some of the maturational effects. Rapid clearance of fetal lung fluid clearance plays a key role in the transition to air breathing. The bulk of this fluid clearance is mediated by transepithelial sodium reabsorption through amiloride-sensitive sodium channels in the alveolar epithelial cells with only a limited contribution from mechanical factors and Starling forces. Disruption of this process can lead to retention of fluid in air spaces, setting the stage for alveolar hypoventilation. When infants are delivered near-term, especially by cesarean section (repeat or primary) before the onset of spontaneous labor, the fetus is often deprived of these hormonal changes, making the neonatal transition more difficult. This chapter discusses the physiologic mechanisms underlying fetal lung fluid absorption and explores potential strategies for facilitating neonatal transition.

Animals↗
PubMedDate not supplied

Blood rheological responses to running and cycling: a potential effect on the arterial hypoxemia of highly trained athletes?

To investigate 1) the blood rheological responses to high training volume and 2) the potential effect of these responses on arterial hypoxemia induced during submaximal running and cycling, 10 triathletes performed an incremental cycle test, 20 minutes of running (R), and 20 minutes of cycling (C). All trials were performed at nearly 75 % of VO2max. Hematocrit (H), blood viscosity (etab), plasma viscosity (etapl), index of erythrocyte rigidity (Tk), changes in plasma volume (DeltaPV), pulmonary diffusing capacity (DLco), and arteriolized blood gas (PaO2) were measured before and after each trial. Pulse oxymetry (SpO2) and cardioventilatory data were collected continuously. A significant increase in etab, etapl, and H was noted after R and C with respect to pre-exercise, whereas DeltaPV decreased, with a greater decrease after C. Tk was significantly higher after R than after C. A significantly greater drop in DLco was noted after C compared with R. SpO2 decreased significantly more during R, as did PaO2. We conclude that blood rheological responses are specific to running and cycling. Cycling induced a sharp decrease in plasma volume, which could partially explain the greater DLco alteration. Running was characterized by an increase in Tk, which could be implicated in the severity of the drop in arterial oxygenation observed.

Adult↗
PubMed1996

The ex-vivo isolated, perfused human lung model: description and potential applications.

An ex-vivo isolated, perfused, and ventilated human lung (IPHL) model is well suited for many kinds of physiological, pharmacological, and surgical studies, when the physiological and biochemical conditions in the lung can be maintained near to those in vivo. The aim of this work was to develop such a model. The lung preparations used were available after resection because of bronchial carcinoma. Since the tumor remains intact in these anatomical preparations, this model is particularly suitable for investigation of the pharmacokinetics and effects of anticancer agents. Carrying out a series of 52 IPHL experiments (with 11 whole-lung preparations and 41 lobe preparations), we have established an IPHL model which allows extracorporeal perfusion and ventilation of the resected lungs in physiological conditions for 2-3 hours. The net weight gain during the experiment, wet-to-dry weight ratio for lung tissue, angiography of the pulmonary artery, pulmonary vascular resistance, color and fluorescence of the lung surface, and alveolar gas diffusion into the perfusate proved to be useful parameters to assess the stability of the preparations and the quality of the experiments. To confirm that an intraparenchymal tumor was perfused via the pulmonary artery, methods to detect avidin and dextran-biotin in tumor tissue after administration into the perfusion solution were employed. Histological examination of bronchial as well as tumor tissue, a computerized histoanalyzation, and a tumor grading program demonstrated that IPHL experiments did not interfere with the grading and staging of the tumors-an important ethical precondition for the use of human preparations in an extracorporeal perfusion model.

Carcinoma, Bronchogenic↗
PubMed1995

[Pulmonary adaptation of the newborn infant: in relation to respiratory distress syndrome].

At onset of respiration, important changes occur in the pulmonary circulation of the newborn. Pulmonary blood flow increases tenfold and pulmonary arterial pressure decreases quickly, thereby decreasing pulmonary vascular resistance to less than 5% of the prenatal values. Right-to-left shunting through the ductus arteriosus and the foramen ovale ceases concomitantly. About 100 ml of alveolar liquid are removed from the alveolar space by active and passive transport. Most of this fluid is drained by the pulmonary bloodstream. Both, disorders in the circulatory adjustments or a prolonged clearance of alveolar liquid, result in an interstitial oedema and hence can contribute to the development of respiratory failure in the newborn.

Adaptation, Physiological↗
PubMed1986

Acute respiratory failure. Pathophysiology, causes, and clinical manifestations.

Acute respiratory failure is a common life-threatening process with myriad causes. It is characterized by a failure of oxygenation or ventilation, or both. Hypoxemia is common to all causes of respiratory failure, whereas PaCO2 may be normal, decreased, or elevated. These abnormalities result from several pathophysiologic processes, including intrapulmonary venoarterial shunt, alveolar hypoventilation, diffusion impairment, and ventilation-perfusion mismatch. Type I failure results from processes that lead to hypocapnia or normocapnia; type II failure is distinguished by the presence of hypercapnia. The clinical manifestations of acute respiratory failure are nonspecific; for this reason, a high index of suspicion and early examination of arterial blood gases are essential to successful management.

Acidosis, Respiratory↗