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Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus.

In this study, we attempted to establish the prevalence and nature of pulmonary dysfunction in a cross section of a diabetic population and the relationship of pulmonary dysfunction to diabetic factors and complications. Forty insulin-dependent diabetic patients, 15 to 60 yr of age, and 40 healthy reference subjects, matched for age, sex, and race, were studied. All subjects were lifelong nonsmokers and had no clinical evidence of past or present respiratory disease. Lung function was assessed from the flow-volume curve, single-breath nitrogen washout, static lung elastic recoil, and pulmonary diffusing capacity (DLCO/VA) and its components: membrane diffusing capacity (Dm/VA) and pulmonary capillary blood volume (Qc/VA). The diabetic patients had an increased value for Kst(L) and in Kst(L), the exponential shape constant of the pressure-volume curve compared with that of the reference subjects (Kst(L), 0.184 +/- 0.011 versus 0.135 +/- 0.005; p less than 0.005, mean +/- SEM). The DL/VA was lower in the diabetic subjects (4.62 = 0.12 versus 5.31 +/- 0.10 ml/min/mm Hg/L; p less than 0.001), and this was due to a lower Qc/VA (9.45 +/- 0.43 versus 11.75 +/- 0.35 ml/min; p less than 0.001). The Kst(L) and Qc/VA were correlated with the duration of diabetes. The In Kst(L) was negatively correlated with both DL/VA (r = -0.32, p less than 0.05) and Qc/VA (r = -0.36, p less than 0.05). There was no association between abnormal pulmonary function and the presence of other diabetic complications. It is concluded that there are mild, duration-related abnormalities of lung elastic recoil and pulmonary diffusing capacity and a reduction in pulmonary capillary blood volume in insulin-dependent diabetes mellitus.

Adolescent↗

Pulmonary diffusion-circulation interrelationships two to seven years after pneumonectomy.

Ventilatory function, pulmonary diffusion capacity and right heart catheterization were studied in eight patients 2-7 years after pneumonectomy. The operation had been carried out for bronchial carcinoma. Dependence of pulmonary diffusion capacity on pulmonary perfusion rather than on ventilatory changes was characteristic of the elderly patients in the late post-pneumonectomy state. When decreased pulmonary perfusion, produced by cardiac disease or increased pulmonary vascular resistance, severely affects the pulmonary diffusion capacity, a careful assessment of the cardiac state is very important in the pre-operative evaluation of operability. In the absence of coexisting diseases, the cardiopulmonary state of long-term survivors usually remains good.

Adult↗

Chlorozotocin (DCNU)--induced pulmonary toxicity.

A case of pulmonary toxicity after chlorozotocin (DCNU) is described. This patient developed shortness of breath, nonproductive cough, and interstitial infiltrates after his third dose of DCNU. This was documented on pulmonary function tests which showed a reduction in vital capacity and pulmonary diffusion capacity. Similar findings have been reported in restrictive pulmonary disease associated with other nitrosoureas. This is the first case reported of pulmonary toxicity induced by DCNU.

Fibrosarcoma↗

Pulmonary O2 diffusing capacity at exercise by a modified rebreathing method.

The rebreathing technique for the measurement of the pulmonary O2 diffusing capacity, DO2, previously developed for resting conditions [Cerretelli et al., J. appl. Physiol. 37, 526-532 (1974)] has been modified for application to exercise and simplified to one rebreathing maneuver only. The changes consist: 1) in administering in the course of a normoxic exercise a priming breath of an O2 free mixture just before the onset of rebreathing in order to achieve rapidly the appropriate starting PO2 values on the linear part of the O2 dissociation curve as required by the method; 2) in calculating mixed venous blood O2 tension by extrapolation of the alveolar to mixed venous blood PO2 equilibration curve, instead of determining it separately. While the mean DO2 value of 21 measurements on 5 subjects at rest was 30 ml-min-1 - Torr-1 +/- 3 (S.E.), in 2 subjects exercising on a bicycle ergometer, DO2 was found to increase from a resting value of about 32 ml- min-1 - Torr-1 to 107 ml - min-1 - Torr-1 for an eightfold increase of O2 uptake. The validity and the applicability of the method are critically discussed.

Humans↗

Measurement of functional residual capacity and pulmonary carbon monoxide diffusing capacity during mechanical ventilation with PEEP.

First, our new simplified method to measure FRC and DLCO simultaneously during mechanical ventilation was described in detail. Secondly, we applied the method to ARDS patients and observed the effects of PEEP on arterial blood gases (ABGs), FRC and DLCO of these patients. As reported hitherto, FRC was consistently increased by PEEP, whereas ABGs in some cases were not necessarily improved with increase in FRC. DLCO/FRC remained unchanged, although DLCO increased with PEEP. We concluded that the dissociation of FRC and ABG data in a group of patients could be caused by wasted ventilation which might be attributed to VA/Q unevenness.

Adult↗

Analysis of factors determining the resistance to diffusion in patients with liver cirrhosis.

In 5 patients with liver cirrhosis the measured pulmonary diffusing capacity for oxygen (DLo2) was related to the diffusing capacity of the pulmonary membrane (DM) and to the volume of blood in the pulmonary capillary bed (Vc) as estimated from the measured pulmonary blood flow (Qc) and the value of the presumptive transit time. DL and DM were found to be diminished in 4 of the 5 cases, DM being only once 1,7 times greater than DL. The relationship between the resistance of the red blood cells to diffusion and the resistance of the pulmonary membrane to diffusion (see journal for formula) ranged between 5 and 35% indicating that the resistance of the pulmonary membrane to the uptake of O2 was of greater importance than the resistance of the red cells. A correlation was found to exist between D/Q and DM/ThetaVc (diffusing capacity/blood flow and membrane diffusing capacity/diffusing capacity of the red cells in the pulmonary capillary bed). The possible site and nature of the diffusion defect is discussed.

Adult↗

Single-breath diffusing capacity of NO independent of inspiratory NO concentration in rabbits.

Pulmonary diffusing capacity of NO (DLNO) was determined by performing single-breath experiments on six anesthetized paralyzed supine rabbits, applying inspiratory concentrations of NO (FINO) within a range of 10 parts per million (ppm) < or = FINO < or = 800 ppm. Starting from residual volume, the rabbit lungs were inflated by 50 ml of a NO-nitrogen-containing indicator gas mixture. Breath-holding time was set at 0.1, 1, 3, 5, and 7 s. Alveolar partial pressure of NO was determined by analyzing the end-tidal portion from expirates, with the use of respiratory mass spectrometry. In the six animals, pulmonary diffusing capacity of NO averaged DLNO = 1.92 +/- 0.21 ml.mmHg-1.min-1 (mean +/- SD value). Despite extreme variations in FINO, we found very similar DLNO values, and in three rabbits we found identical values even at such different FINO levels of 80 ppm or 500, 20, or 200 ppm as well as 10 or 800 ppm. There was also no dependence of DLNO on the respective duration of the single-breath maneuvers. In addition, the time course of NO removal from alveolar space was independent of applied FINO levels. These results suggest that DLNO determinations are neither affected by chemical reactions of NO in alveolar gas phase as well as in lung tissue nor biased by endogenous release of NO from pulmonary tissue. It is our conclusion that the single-breath diffusing capacity of NO is able to provide a measure of alveolar-capillary gas conductance that is not influenced by the biochemical reactions of NO.

Administration, Inhalation↗

Postnatal development of respiratory function in lambs studied serially between birth and 8 weeks.

We have quantified developmental changes in major aspects of respiratory function in 12 pentobarbitone-sedated lambs by making repeated measurements during the first 8 postnatal weeks, between term birth and post-weaning. Pulmonary diffusing capacity for CO increased with age due to increases in both the diffusing capacity of the alveolar capillary membrane (Dm) and pulmonary capillary blood volume (Vc). Total lung capacity measured at a lung inflation pressure of 30 cmH2O decreased from 74.4 +/- 3.2 ml/kg at 3 days to 47.2 +/- 2.9 ml/kg at 8 weeks. Static respiratory system compliance, measured between FRC and TLC fell rapidly during the first 3 weeks, then remained unchanged; the early postnatal fall was largely due to a reduction in chest wall compliance as lung compliance was constant. FRC declined from 32.3 +/- 1.7 ml/kg at 3 days to 25.1 +/- 1.5 ml/kg at 2 weeks, then fell to 21.4 +/- 1.2 ml/kg by 8 weeks. Specific pulmonary conductance (conductance/FRC) during mid-inspiration and mid-expiration did not change with age (0.195 +/- 0.012 and 0.194 +/- 0.019 L x sec(-1) x cmH2O(-1) x L(-1)-FRC, respectively). Breathing frequency, and weight-adjusted tidal volume and minute ventilation declined after birth until 4 weeks after which they did not change. This study has shown that, using basic methodology, serial assessments of respiratory function can be obtained in sedated lambs from soon after birth. The age-related increase seen in pulmonary diffusing capacity is due to increases in both Dm and Vc, which are consistent with continuing alveolarisation. Our data on age-related changes in pulmonary function and volumes provide a reference for future studies on the effect of altered prenatal lung development on postnatal lung function in sheep.

Aging↗

Lung membrane diffusing capacity, heart failure, and heart transplantation.

The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure and remains decreased after heart transplantation. This decrease in DLCO may depend on a permanent alteration after transplantation of one or the other of its components: diffusion of the alveolar capillary membrane or the pulmonary capillary blood volume (Vc). Therefore, we measured DLCO, the membrane conductance, and Vc before and after heart transplantation. At the time of hemodynamic measurements, the Roughton and Forster method of measuring DLCO at varying alveolar oxygen concentrations was used to determine the membrane conductance, Vc, DLCO/alveolar volume (VA), the membrane conductance/VA and thetaVc/VA (theta = carbon monoxide conductance of blood, VA = alveolar volume) in 21 patients with class III to IV heart failure before and after transplantation, and in 21 healthy controls. Transplantation normalized pulmonary capillary pressure and increased cardiac index. DLCO was decreased before transplantation (7.11 vs 10.0 mmol/min/kPa in controls), but DLCO/VA was normal (1.67+/-0.44 vs 1.71+/-0.26 mmol/min/kPa/L in controls). DLCO/VA remained unchanged after transplantation, because the decrease in Vc (82+/-30 vs 65+/-18 ml before and after transplantation) and thetaVc/VA was not compensated by the changes in membrane conductance (11+/-4 vs 12+/-5 mmol/min/kPa before and after transplantation, respectively) and membrane conductance/VA. We conclude that the decrease in DLCO in patients with chronic heart failure is due to a restrictive ventilatory pattern because their DLCO/VA remains normal; the decrease in the membrane conductance is compensated by the increase in Vc. After transplantation, the decrease in Vc due to normalization of pulmonary hemodynamics is not completely compensated for by an increase in membrane conductance. Because the membrane conductances, measured before and after transplantation, are negatively correlated with duration of heart failure, its abnormal pulmonary hemodynamics may have irreversibly altered the alveolar capillary membrane.

Adult↗

Standardized quantitative 67Ga scintigraphy in relation to carbon monoxide diffusion capacity in pulmonary sarcoidosis.

67Ga lung uptake, obtained by a standardized computer-assisted quantitative method of 67Ga scintigraphy, was compared to carbon monoxide diffusion capacity (DLCO) in 45 patients with biopsy proven pulmonary sarcoidosis. Increased 67Ga lung uptake was found in 24 (53%) patients and DLCO was decreased in only 16 (36%) patients. An inverse relationship (r = -0.53; p < 0.001) was demonstrated between 67Ga lung uptake and DLCO. Eleven patients had an increased 67Ga lung uptake whereas the DLCO values were normal. There was no correlation between 67Ga lung uptake or DLCO and either chest radiographic stage or mode of clinical presentation. On the basis of the normal limits for 67Ga lung uptake and DLCO, 4 subgroups of patients could be identified. The use of the combined investigations may open an opportunity for an early identification of those patients who require therapy. An increased 67Ga accumulation within the lung seems to be considered as a factor indicating risk for pulmonary disability, which is supported by the follow-up of the 4 subgroups of patients.

Adult↗

Evaluation of lung diffusing capacity by physiological and morphometric techniques.

Determinations of pulmonary diffusing capacity for CO (DLCO) by physiological and morphometric techniques have resulted in substantially different values for both DLCO and its major components. To evaluate the differences in these methods of measurement of DLCO, measurements were made under controlled conditions on isolated perfused dog lungs. Multiple gas-rebreathing techniques were used to measure DLCO, the membrane component of the diffusing capacity for CO (DmCO), and pulmonary capillary blood volume (Vc) in both anesthetized dogs and after isolation and perfusion of their lungs. The isolated perfused lungs were than perfusion fixed for morphometric analysis of the components of DLCO. The values obtained morphometrically for Vc were similar to those measured by physiological techniques. Perfusion fixation did not substantially alter the morphometric estimate of DmCO when compared with previous values obtained on inflation fixed lungs. However, the morphometric estimate of DmCO was over 10 times higher than that estimated physiologically. Analysis of the potential errors in the techniques suggests that the correct value for DmCO is substantially higher than that commonly estimated by use of physiological techniques and that the explanation for the difference is due to a number of factors that can influence the binding of CO to hemoglobin under in vivo conditions. The net effect of these factors can be represented by an unknown in each component of the Roughton-Forster relationship so that 1/DL = 1/(U1.Dm) + 1/(U2.theta Vc), where theta is the binding rate for CO to hemoglobin. Because the magnitudes of the unknown terms (U1 and U2) in the Roughton-Forster relationship are likely to be large, this relationship cannot be reliably used to determine Dm and Vc.

Animals↗

Demand vs. capacity in the healthy pulmonary system.

This review examines the lung and chest wall adaptation to exercise in health in persons of widely varying degrees of fitness. First we examine the regulation of breathing and gas exchange in the sedentary young adult who shows a near perfect regulation of alveolar gases, ventilation to perfusion distribution, diffusion equilibrium in the lung during all levels of exercise. This individual's respiratory muscles are also ideally recruited both tonically and phasically so as to meet multi-faceted postural, locomotory and respiratory demands. The topic of plasticity in the pulmonary system is discussed with specific reference to the effects of physical training and athleticism. The key point made here is that both homeostasis of gas transport and mechanical efficiency, with which the pulmonary system meets the demands of muscular exercise will depend upon the ability to maintain a significant margin between demand vs. structural capacity. Pulmonary diffusion capacity and at least some aspects of respiratory muscle function seem to be "overbuilt" in the young untrained adult. This margin of safety no longer prevails as the athlete becomes fitter. The cause is to be found in the relative lack of adaptability of the lung and chest wall to the training stimulus. Examples of demand coming very close or exceeding the capacity of the pulmonary system include the highly trained young endurance athlete and the aged athlete. Examples of "failure" or near failure in the pulmonary system's response to exercise include: a) exercise induced arterial hypoxemia via diffusion limitation; b) diaphragmatic fatigue in endurance exercise; c) expiratory flow limitation at VO2max.; d) achieving the capacity of inspiratory muscles for pressure generation at VO2max. and e) oxygen cost of breathing which is in excess of 15% of VO2max. in those athletes who experience the most mechanical limitation.

Adaptation, Physiological↗

Pulmonary O2 diffusing capacity estimates from assumed log-normal VA/Q distributions.

Steady-state pulmonary gas exchange has been measured in hypoxia in 33 mongrel dogs with the aim of comparing DLO2 estimates obtained with three procedures differing by the models assumed for functional inhomogeneity. In the first procedure the lung was assumed to be homogeneous and the corresponding DLO2 estimate was 15 mumol . min-1. Torr-1 . kg-1. In the second procedure, which is the one commonly used in respiratory physiology, alveolar dead space was considered as the unique form of functional inhomogeneity and the corresponding DLO2 estimate was 31 mumol . min-1. Torr-1 . kg-1. In the third procedure, which has been specially worked out for this study, functional inhomogeneity was represented by a log-normal distribution of the VA/Q ratios and the corresponding DLO2 estimate was 50 mumol . min-1 . Torr-1 . kg-1. The relation between the DLO2 estimates by the second and by the third procedures was found to depend upon the blood pH. This could be explained on the basis of the effects of acidosis on the blood capacitances for O2 and for CO2. Analysis suggests that in hypoxia where normally the O2 capacitance is about half the CO2 one, the third procedure yields DLO2 estimates about twice as large as those obtained by the second one.

Animals↗

[Differentiated characterization of pulmonary diffusion].

The results of Single-Breath-Test with carbon monoxide offers only a rough estimation of the gas exchange situation in the lung as concerns pulmonary diffusion capacity. This statement is related to overestimation of diffusion capacity and reduced possibility to characterize disturbances of pulmonary diffusion function on the basis of values assessed. The proposed six-array-diagram offers the possibility to characterize the disturbances of diffusion more exactly and to differentiate them simultaneously regarding the values determined. So it is possible, to characterize better structural changes of the blood-gas barrier of the lung and to demonstrate compensatory mechanisms.

Breath Tests↗

Lung diffusing capacity and exercise in subjects with previous high altitude pulmonary oedema.

Subjects with a history of high-altitude pulmonary oedema (HAPE) have increased pulmonary artery pressure and more ventilation-perfusion (V'A/Q') inhomogeneity with hypoxia and exercise. We used noninvasive methods to determine whether there are differences in the pulmonary diffusing capacity for carbon monoxide (DL,CO) and cardiac output (Q') during exercise, indicative of a more restricted pulmonary vascular bed in subjects with a history of HAPE. Eight subjects with radiographically documented HAPE and five controls with good altitude tolerance had standard pulmonary function testing and were studied during exercise at 30 and 50% of normoxic maximal oxygen consumption (V'O2) at an inspiratory oxygen fraction of 0.14 and 0.21. DL,CO and Q' were measured by CO and acetylene rebreathing techniques. HAPE-resistant subjects had 35% greater functional residual capacity than HAPE-susceptible subjects. Vital capacity and total lung capacity were also 7-10% greater. There were no differences in airflow rates or resting diffusing capacity. However, DL,CO in HAPE-susceptible subjects was lower in hypoxia and with exercise, and showed less increase (32 versus 49%) with the combined stimulus of hypoxic exercise. HAPE-susceptible subjects had smaller increases in stroke volume, Q', and ventilation during exercise. The findings are consistent with lower pulmonary vasoconstriction, greater vascular capacitance and greater ventilatory responsiveness during exercise in subjects who are resistant to high-altitude pulmonary oedema. Their larger lung volumes suggest a constitutional difference in pulmonary parenchyma or vasculature, which may be a determinant of high-altitude pulmonary oedema resistance.

Adult↗

The scaling of maximal oxygen consumption and pulmonary dimensions in small mammals.

This report has reexamined the relationship between standard and maximal rates of oxygen consumption (VO2std and VO2max) and pulmonary surface area in mammals whose weights extend over the lower half of the total log weight range in mammals. For combined groups of wild and laboratory animals with body weights of 2--3700 g, the following equations pertain: VO2std (ml . min-1) = 0.0602 . W0.727; VO2std, or the factorial aerobic scope, is nearly constant over this weight range at approximately 6.6 (range 5.8--7.1). In view of this finding, earlier studies relating SA or pulmonary diffusion capacity to VO2std are still appropriate models for pulmonary constraints on metabolic rate. The data summarized here suggest that, at least for wild species of mammals, pulmonary diffusion capacity may limit VO2max.

Animals↗