Decrease of diffusing capacity and pulmonary blood flow during passive lung inflation.
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Animals↗
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Hypothermic lung preservation functions, six or more years later.
The functions of each lung were measured 41 and 79 months following hypothermic twenty-four four lung preservation and autotransplantation in six and four dogs respectively. Functional results were compared with long-term autotransplanted canine lungs. Compliance, total lung capacity, functional reserve capacity and ventilation of preserved lungs were similar to autotransplanted lungs, and only slightly decreased as compared with normal animals. There was no statistically significant difference between the pulmonary diffusion capacity and oxygen uptake of the preserved and autotransplanted lungs group and autotransplants alone. However, in both groups, diffusion capacity and oxygen uptake were decreased as compared with intact animals. Pulmonary hypertension was found on occlusion of the contralateral lung's artery: it was due to increased pulmonary vascular resistance. No gross narrowing of the pulmonary artery or venous anastomosis was found that could explain the increased resistance. Diffuse emphysema of various degrees was observed in all animals. This study seems to indicate that hypothermic preservation of the lung does not affect significantly the long-term functional ability of the organ, and probably will have practical value in future clinical lung transplantation.
Animals↗
Effects of increasing metabolism by 2,4-dinitrophenol on respiration and pulmonary gas exchange in the duck.
The effects of pharmacologically elevated metabolism on respiration and parabronchial gas exchange were studied in the anesthetized, spontaneously breathing duck using 2,4-dinitrophenol (DNP), injected in successive single doses of 1.2-2.5 mg per kg body mass. Oxygen uptake, MO2, increased with the cumulative amount of DNP, reaching a sevenfold resting level at the highest DNP level tolerated, 15 mg/kg. Ventilation increased nearly as much as MO2, mainly by an increase in respiratory frequency, fresp. Cardiac output increased somewhat less than MO2, mediated by increases in both cardiac frequency and stroke volume. Arterial blood-gases showed little change; however, mixed venous PO2 dropped significantly, and PCO2 increased significantly, with stimulated metabolism. Pulmonary diffusing capacity, DO2, showed a significant rise with MO2, beyond that expected from a reduction of functional lung heterogeneity. The results show that pharmacological stimulation of metabolism can evoke responses in the respiratory and circulatory systems that are comparable to those observed with exercise. The mechanism by which parabronchial diffusing capacity increases during elevated metabolism remains to be investigated.
2,4-Dinitrophenol↗
Modeling carbon monoxide uptake during work.
Acute carbon monoxide poisoning is the result of a diminished capacity of the blood to transport oxygen and sustain a level of metabolic activity. The diminished capacity is expressed in terms of the carboxyhemoglobin (COHb) level in the blood which is dependent upon the concentration of CO in the inhaled air. The rate of CO uptake or elimination is dependent upon the concentration of CO in the air as well as pulmonary diffusion capacity and alveolar ventilation which change with different metabolic rates. Coburn, Forster and Kane (CFK) developed a mathematical model to describe the uptake and elimination kinetics of CO in sedentary individuals. The CFK model was used in a mathematical simulation of CO uptake and elimination where the independent variables were inhaled CO concentration and metabolic rate. The metabolic rate was used to specify pulmonary diffusing capacity and alveolar ventilation. As the level of COHb increased the metabolic rate was decreased to a level compatible with the impaired oxygen transport. A physical fatigue limit was also included. The theoretical model was used to simulate conditions beyond the range of exposures permissible under experimental laboratory conditions.
Carbon Monoxide↗
Prediction of peak exercise oxygen uptake by cardiopulmonary measurements at rest in heart transplant candidates.
OBJECTIVE: Peak oxygen uptake (VO2) is a powerful prognostic index, but maximal exercise testing in heart transplant candidates has a number of disadvantages. It is unknown whether it is possible to predict peak VO2 from a comprehensive dataset with parameters of heart and lung function at rest. METHODS: One hundred adult patients in sinus rhythm and with either idiopathic or ischaemic heart failure performed a graded cycle ergometer test until volitional fatigue and underwent radionuclide ventriculography, heart catheterization, and lung function measurements at rest. RESULTS: Weight, height, age, gender and aetiology of heart failure explained 48% of the variance of peak VO2. On top of these anthropometric, demographic and clinical patient characteristics, 12% of the variance of peak VO2 was additionally explained by all resting measurements combined, i.e. radionuclide left ventricular ejection fraction, peak ejection rate, peak filling rate, cardiac frequency, mean right atrial pressure, pulmonary capillary wedge pressure, pulmonary artery pressures, cardiac output, forced vital capacity, forced expiratory volume in one second, and pulmonary diffusing capacity (cumulative R2 = 0.60); among these, pulmonary vascular resistance was the most important predictor (+6%; P < 0.001). Analyses in a subset of 43 male patients pointed out that systemic pressures and vascular resistance were not related to peak VO2. CONCLUSION: On the basis of resting left ventricular function, haemodynamics, and routine pulmonary measurements, it is unlikely to accurately predict exercise tolerance in the majority of heart transplant candidates, i.e. patients with either idiopathic or ischaemic heart failure and able to exercise until exhaustion.
Adult↗
Pulmonary calcification in hemodialyzed patients detected by technetium-99m diphosphonate scanning.
Metastatic pulmonary calcification, a well-known complication in patients with chronic disease, has been demonstrated postmortem in patients with a negative chest X-ray. Recently, scintigrams with bone-seeking radionuclides have been used to detect such subclinical pulmonary calcium deposits. We describe 23 patients on maintenance hemodialysis with no evidence of pulmonary calcification on chest X-ray who were prospectively studied by lung scanning with a bone-seeking radionuclide and pulmonary function testing. Of the 23 patients, 14 (61%) had a positive technetium-99m diphosphonate (99mTc-DP) scan (group 1). These patients were on dialysis 38 +/- 5 months compared with 12 +/- 4 months in 9 patients with a negative scan (group 2) (P less than 0.01). Age, sex, blood pressure, hematocrit, serum calcium, phosphorous, bicarbonate, magnesium, and calcium X phosphorus product, as well as parathyroid hormone level did not differ between the two groups. Of 10 group-1 patients tested, 7 had abnormal pulmonary diffusion capacity compared with non in 5 group-2 patients tested (P = 0.014). Histologic examination of the lung in 1 group-1 patients who expired revealed calcification (amorphous on X-ray diffraction), whereas none was found in 1 group-2 patients autopsied. These observations suggest that in patients on maintenance hemodialysis, pulmonary scanning with 99mTc-DP is a sensitive method for detecting pulmonary metastatic calcification, which may be associated with an abnormality in pulmonary diffusion capacity.
Adult↗
The pathophysiology of pulmonary diffusion impairment in human immunodeficiency virus infection.
Numerous reports have demonstrated that prior to the development of acquired immunodeficiency syndrome (AIDS)-related pulmonary complications, human immunodeficiency virus-positive (HIV+) individuals commonly develop unexplained reductions in pulmonary diffusing capacity (DLCO). The potential relevance of this observation is underscored by recent data demonstrating that reductions in DLCO independently predict the subsequent development of opportunistic pneumonia. To delineate the alterations in gas exchange associated with HIV, we investigated a group of HIV+ subjects with unexplained reductions in DLCO, using high-resolution computed tomography (HRCT) of the chest and a separation of diffusing capacity into its membrane (Dm) and capillary blood volume (Vc) components. We compared this abnormal group with HIV+ subjects with more normal gas exchange and also with a group of HIV- volunteers matched for age and smoking history. Compared with other groups, the HIV+ group with diffusion impairment demonstrated prominent reductions in Vc, despite a well-preserved total lung capacity (TLC). HRCT demonstrated virtually no evidence of interstitial fibrosis in any HIV+ subject, but evidence of early emphysema that significantly correlated with DLCO. Our results suggest that the previously reported impairment in pulmonary gas exchange in the HIV+ population involves loss of Vc and likely represents the development of early emphysema.
AIDS-Related Opportunistic Infections↗
Morphometrics of the avian lung. 3. The structural design of the passerine lung.
The lungs of 46 adult, wild passerine birds belonging to 8 species have been analysed morphometrically, both by light and electron microscope. Volumes were estimated by point counting, surface areas by intersection counting, and thicknesses by intercept length measurements. The mean values obtained for these passerine species appertaining to both lungs together were: volume of the lung per kilogram body weight 25 cm3/kg, volume density of the exchange tissue 52%, surface area of the blood-gas (tissue) barrier per gram body weight 47.48 cm2/g, surface density of the blood-gas (tissue) barrier 323.8 mm2/mm3, capillary loading 1.15 cm3/m2, harmonic mean thickness of the blood-gas (tissue) barrier 0.127 micron, arithmetic mean thickness 0.745 micron and the total morphometric pulmonary diffusion capacity 7.08 ml O2/min/mm Hg/kg. These values indicate that the passerine lung is specially well adapted for gas exchange, mainly by having a thin and extensive blood-gas (tissue) barrier, in response to the high oxygen demand by this group of bird.
Animals↗
Blood gas tension and development of lung damage in mice exposed to oxygen at 1 ATA.
Oxygen and carbon dioxide tension in arterial blood were studied in mice breathing 100% oxygen at ambient pressure. The lungs were simultaneously investigated in order to relate the oxygen-induced pulmonary alterations to the altered pulmonary function. The development of an impairment in pulmonary diffusing capacity is initiated after 30 h of oxygen exposure, at which time the increase in lung weight is associated with beginning lung edema and beginning accumulation of carbon dioxide in the blood. Red spots or areas on the lung surface, which merged together to large streaks or areas after 20 h of exposure, preceded the measurable diffusing impairment noted at 30 h. Light microscope preparations revealed intraalveolar hemorrhagic exudation and proliferative changes in the alveolar walls. After 50 h, the development of severe pulmonary dysfunction is mainly due to an intense parenchymal reaction in the alveolo-capillary region with thickening in the alveolar walls, dystelectasis in the corresponding parenchyma, and further development of pulmonary edema. The resulting impairment in pulmonary diffusing capacity causes a steep decrease in oxygen tension and an accentuated increase in carbon dioxide accumulation. The present results are discussed in relation to the previous findings of oxygen-induced alterations in brain glutamate, GABA, and glutamine concentration.
Animals↗
Short-term pulmonary effects of total parenteral nutrition in children with cystic fibrosis.
Indices of respiratory muscle strength, pulmonary function, and pulmonary diffusing capacity were measured in 11 malnourished children (age 10 to 17 years) with cystic fibrosis, before and after improvement of nutritional status with supplemental parenteral nutrients for 1 month. During this time, the children received 120% of estimated energy requirements (either 3.75% or 22.5% as lipid) and amino acids 2.5 gm/120 kcal by central venous catheter, plus as much of their usual diet as desired. With nutritional supplementation, body weight, triceps skinfold thickness, and mid-arm muscle circumference increased (mean 15%, 62%, and 95%, respectively). Maximum inspiratory airway pressure also increased (mean 29%; P less than 0.01), suggesting improvement in respiratory muscle strength. However, none of the indices of pulmonary function improved. Pulmonary diffusing capacity did not change during parenteral nutrition regardless of the amount of parenteral energy intake supplied by lipid, but arterial oxygen saturation decreased (mean of 93.5% to 91.5%; P less than 0.005). During the month following parenteral nutrition, weight, skinfold thickness, and mid-arm muscle circumference, but not MIP, decreased and arterial oxygen saturation returned to the initial value (P less than 0.01).
Adolescent↗
One-sampling rebreathing method to measure diffusing capacity for CO.
To simplify the rebreathing method to obtain the pulmonary diffusing capacity for CO (DLCO), a one-sampling method was developed, combined with a simulation technique. The change in CO fraction in rebreathing air depends on the rebreathing volume (VRB), the dead space volume (VD), the gas volume in the lung-bag-system (VS) as well as the DLCO: Using the measured VRB, VD, and VS, the changes in CO fraction in bag and alveolar air were simulated by varying the DLCO, where the expired and inspired gas volumes were represented by a sinusoidal function of time. The DLCO was determined by checking the similarity between the simulated and measured CO fractions at the 7th expiratory period. To confirm the validity of the simulation method, two-sampling rebreathing and single breath methods were additionally carried out in 6 normal subjects in the sitting position. The DLCO measured by the simulation agreed well with that measured simultaneously by the two-sampling method. The DLCO measured by this method was also compatible with that obtained from the single breath method, when the dead space was excluded from the measured lung gas volume.
Adult↗
Alveolar-arterial equilibration in the lung of sheep.
In order to compare the efficiency of sheep lung with that of dog, gaseous exchange in hypoxia (FIO2 0.12-0.13) with and without CO in the inspired air ( FICO 0.001) was measured in 12 sheep (mean body weight = 30.4 kg) under pentothal anesthesia and artificial ventilation. Alveolar-arterial pressure difference of O2, % venous admixture and amount of VA/Q inhomogeneity were found to be substantially larger than in dog. Steady-state pulmonary diffusing capacity estimates, computed by three different procedures were, both for O2 and for CO, about 40% smaller than in dog. The DLO2/DLCO ratios were not significantly different from those determined on dog data: thus, the presumed beneficial effect of sheep small erythrocytes on O2 transfer could not be demonstrated. Because its DLO2/MO2 ratio is lower than that of dog, sheep appears to be more adequate than dog as a model for human alveolar-arterial gas exchange.
Animals↗
Pulmonary gas exchange during hypoxic exercise in the rat.
Pulmonary gas exchange and O2 transport were studied at rest and during maximal treadmill exercise in rats in acute hypoxia (PIO2 approximately 71 Torr), and in littermates acclimatized to PB = 380 Torr (PIO2 approximately 71 Torr) for 3 weeks (chronic hypoxia). To obtain valid estimates of blood gas partial pressures, particularly during exercise, the temperature coefficients of blood pH, PO2 and PCO2 were determined (Appendix). In both acute and chronic hypoxia, the following changes were observed: alveolar and arterial PO2 increased considerably, but the difference, A-aPO2, did not change significantly; arterial O2 concentration (CaO2) decreased, and apparent pulmonary diffusing capacity for O2, Dapp, increased. The increase in Dapp, together with hyperventilation, may prevent further drop in CaO2 due to a large rightward shift in the blood-O2 equilibrium curve caused by lactic acidosis in conjunction with a large Bohr coefficient characteristic of this species. Comparison with corresponding results obtained in man reveals that during hypoxic exercise, the rat shows a larger increase in PAO2, an increase, instead of a decrease, in PaO2, and a larger increase in Dapp.
Acclimatization↗
Long-term risk of emphysema in patients with farmer's lung and matched control farmers.
We evaluated the long-term outcome of farmer's lung (FL) patients and matched control farmers using high-resolution computed tomography (HRCT). The study population consisted of 88 FL patients and 83 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yr. The great majority, 82%, of the studied subjects were nonsmokers. Clinical studies included HRCT, spirometry, and pulmonary diffusing capacity. Emphysema was found significantly more often (23%) in FL patients than in control farmers (7%) (p = 0.006). The presence of emphysema was 18% in nonsmoking and 44% in smoking FL patients, the respective values being 4% and 20% in control farmers. Patients with recurrent attacks of FL tended to have emphysema more often (p = 0. 08) than patients who had experienced only a single attack. Fibrosis was observed in 17% of the FL patients and in 10% of the control farmers (p = 0.2). Miliary changes were found in 12% of the FL patients compared with 4% of the control farmers (p = 0.07). Both emphysematous and fibrotic but not miliary changes correlated significantly with impaired pulmonary function. In conclusion, farmer's lung disease seems to be associated with an increased risk of developing emphysema.
Age Factors↗
Pulmonary function levels as predictors of mortality in a national sample of US adults.
Single breath pulmonary diffusing capacity for carbon monoxide (DL(CO)) was examined as a predictor of all-cause mortality among 4,333 subjects who were aged 25-74 years at baseline in the First National Health and Nutrition Examination Survey (NHANES I) conducted from 1971 to 1975. The relation of the percentage of predicted DL(CO) to all-cause mortality was examined in a Cox proportional hazard model that included age, sex, race, current smoking status, systolic blood pressure, serum cholesterol, alcohol consumption, body mass index, percentage of predicted forced vital capacity (FVC), and the ratio of forced expiratory volume at 1 second (FEV1) to FVC. Mortality had a linear association with the percentage of predicted FVC (rate ratio (RR) = 1.12, 95% confidence interval (CI) 1.08-1.17, for a 10% decrement) and a significantly nonlinear association with the percentage of predicted DL(CO) with an adverse effect that was clearly evident for levels below 85% of those predicted (RR = 1.24, 95% CI 1.12-1.37 for a 10% decrement). The relative hazard for the percentage of predicted DL(CO) below 85% was not modified by sex, smoking status, or exclusion of subjects with clinical respiratory disease on the initial examination. This association with the percentage of predicted DL(CO) was present among 3,005 subjects with FEV1 levels above 90% of those predicted. Thus, pulmonary diffusing capacity below 85% of predicted levels is a significant predictor of the all-cause mortality rate within the general US population independent of standard spirometry measures and even in the absence of apparent clinical respiratory disease.
Adult↗
Morphologic changes in the lung during the lifespan of Fischer 344 rats.
Pulmonary structure and function were quantitatively investigated over the lifespan of the Fischer 344 rat by morphometric and physiologic techniques. Male animals 1 week, 6 weeks, 5 months, 14 months, and 26 months of age and female animals 5 months, 14 months, and 26 months of age were studied. All alveolar tissue compartments demonstrated significant increases in volume, surface area, and cell number during the first 5 months of life. From 5 to 26 months of age, remodelling in the epithelial and interstitial compartments continued to take place while the endothelial compartment remained relatively unchanged. In the epithelial compartment the ratio of type II cells to type I cells lining the alveolar surface decreased as age increased. In the interstitial compartment the volume of the noncellular components of the interstitium increased by 39% in males and by 89% in females from 5 to 26 months of age. Physiologic measurements of lung volumes in males at 6 weeks, 14 months, and 26 months demonstrated progressive increases in vital capacity (VC) and total lung capacity (TLC). Morphometric pulmonary-diffusion capacity (DLO2) increased in males from 1 week to 5 months of age and remained relatively unchanged from 5 to 26 months of age in both sexes.
Aging↗
Effect of exercise on dilution estimates of extravascular lung water and on the carbon monoxide diffusing capacity in normal adults.
Previous studies in exercising animals have demonstrated that the extravascular lung water accessible to measurement by dilution methodology increases in the transition from rest to low-level exercise and thereafter does not change with progress to high-level exercise. In normal humans, similar systematic examination is essential to provide a background for the interpretation of changes in measured extravascular lung water in pathophysiological states. Moreover, such an examination might provide new insight into the mechanisms underlying the change in the pulmonary diffusing capacity with exercise. We therefore measured both the pulmonary extravascular lung water (by use of the triple indicator-dilution technique) and the diffusing capacity for carbon monoxide in 11 subjects, seated on an exercise bicycle, at rest and usually during two levels of exercise. The central blood volume increased by 50% with a tripling of the cardiac output. The accessible lung water increased from an average of 2.16 g/kg to 2.55 g/kg in the transition from rest to low-level exercise, but it did not increase further at the higher level of exercise. The simultaneously measured diffusing capacity for carbon monoxide (single breath and steady state) continued to increase over the whole range of cardiac outputs. We infer that the proportion of the pulmonary parenchyma perfused by blood flow increases slightly in the transition from rest to low-level exercise but increases no further at the higher level of exercise. The continued increase in the pulmonary diffusing capacity over the range in which the estimated lung water values do not change appears to imply that part of this increase may be blood flow dependent rather than dependent on the recruitment of additional surface for exchange.
Adult↗
Pulmonary elastic recoil and diffusing capacity in subjects with intermediate concentrations of alpha-1 antitrypsin.
Serum from 224 males investigated in a prospective study of respiratory disorders in a recently established asbestos industry has been estimated for alpha-1 antitrypsin (AAT) concentration by single radial immunodiffusion. Mean AAT concentration was 213-4 mg/dl). No subject with a markedly reduced level was found. A comprehensive range of lung function tests sensitive to changes anticipated in emphysema at a preclinical stage, included measurements of diffusing capacity and pulmonary elastic recoil. The 26 subjects with AAT concentration less than 150 mg/dl, were regarded as likely to comprise a majority of genotypes MZ and SS, and the 19 subjects with AAT concentration greater than 300 mg/dl were considered to comprise mainly MM. No difference in pulmonary function could be demonstrated between these two groups. Evidence of diminished pulmonary elastic recoil was found in nine smoking subjects whose AAT concentrations were normal and also in one young non-smoking subject with moderately severe asthma, whose AAT concentration was 140 mg/dl. It is concluded that in a male working population, evidence of diminished pulmonary elastic recoil is not a function of AAT concentration.
Adult↗