Carbon monoxide diffusing capacity.
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Carbon Monoxide↗
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Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity.
PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance.
Adult↗
Fibrosing alveolitis in systemic sclerosis: indices of lung function in relation to extent of disease on computed tomography.
OBJECTIVE: Thin-section computed tomography (CT) provides a sensitive and reproducible method of quantifying the morphologic extent of disease in the clinical management of fibrosing alveolitis associated with systemic sclerosis (FASSc). The aim of this study was to determine which indices of lung function best reflect the extent of disease on CT in FASSc, and to determine the independent influences of smoking history, extent of fibrosing alveolitis, demographic features, and concurrent treatment upon functional impairment in FASSc. METHODS: Sixty-four patients with FASSc were studied using CT and static and exercise lung function testing. Statistical relationships were determined by multiple regression analyses. RESULTS: Five patients with overt pulmonary hypertension were characterized by severe impairment in 3 indices of lung function: diffusing capacity for carbon monoxide (DLCO), DLCO adjusted for alveolar volume (KCO), and arterial partial pressure of oxygen. On multiple regression analysis, the major determinant of functional impairment was the extent of fibrosing alveolitis on CT. A history of smoking was independently associated with preservation of total lung capacity and depression of KCO, but did not otherwise influence functional-morphologic correlations. The percent predicted DLCO correlated better with extent of disease on CT (r = -0.70) than did oxygen desaturation on exercise (r = 0.55), the physiologic component of the clinical-radiographic-physiologic score (CRP index) (r = 0.52), or other indices of lung function. Lung volume measures correlated poorly with disease extent on CT. CONCLUSION: The percent predicted DLCO best reflects the extent of fibrosing alveolitis in FASSc, and therefore should be measured in routine evaluations. Exercise testing may also have a useful role in staging the severity of pulmonary fibrosis, but the CRP index offers no additional advantage over the DLCO and exercise testing.
Carbon Monoxide↗
Fall in diffusing capacity associated with induction therapy for lung cancer: a predictor of postoperative complication?
BACKGROUND: Pulmonary resection after induction therapy is associated with high rates of pulmonary morbidity and mortality. However, the impact of induction therapy on the pulmonary toxicity and associated pulmonary complications has not been fully investigated in the setting of lung cancer surgery. METHODS: We assessed the 66 consecutive patients who underwent a pulmonary resection after induction therapy, 48 of whom received chemoradiotherapy and 18, chemotherapy alone. Results of pulmonary function before and after induction therapy were compared, and logistic regression analyses utilized to explore the risk factors of pulmonary morbidity. RESULTS: After induction therapy, forced expiratory volume in 1 second (FEV1) was increased significantly (from 2.28 +/- 0.61 L to 2.40 +/- 0.62 L; p < 0.05); however, percent vital capacity (%VC) and FEV1/FVC did not change significantly. The diffusing capacity of lung for carbon monoxide (D(LCO)) was decreased significantly by 21% (from 90.3% +/- 18.3% to 71.1% +/- 12.5%; p < 0.0005). Patients with respiratory complication showed lower predicted postoperative %FEV1 (49.5% +/- 11.1% versus 57.2% +/- 14.2%; p = 0.031) and predicted postoperative %Dlco (41.9% +/- 8.0% versus 55.4% +/- 10.1%; p < 0.0001) results than those without complications. Univariate and multivariate analyses revealed that predicted postoperative %D(LCO) alone was an independent factor to predict postoperative pulmonary morbidity. CONCLUSIONS: For patients who undergo a pulmonary resection after induction therapy, predicted postoperative %D(LCO) is more important to predict pulmonary morbidity rather than static pulmonary function (predicted postoperative %VC or %FEV1). The decrease in D(LCO) is thought to reflect a limited gas exchange reserve, caused by the potential toxicity of chemotherapy or chemoradiotherapy. We believe that the impact of diffusion limitation after induction therapy should to be emphasized to decrease the pulmonary morbidity.
Adenocarcinoma↗
In vivo estimation of septal lung tissue volume and correlation with diffusing capacity in lung volume reduction surgery.
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Animals↗
Ventilatory and diffusion abnormalities in potential heart transplant recipients.
Few data are available concerning pulmonary function in patients with severe chronic congestive heart failure. Of 315 patients evaluated for potential cardiac transplantation at UCLA, 132 underwent pulmonary function tests. The latter patients had severe heart failure with a mean left ventricular ejection fraction of 19 percent and mean cardiac index of 2.1 L/min/m2. Diffusion impairment either alone or combined with restrictive and/or obstructive ventilatory defects occurred in 67 percent of the patients evaluated. Diffusion impairment occurred as the sole abnormality in 31 percent of the patients and in combination with a restrictive ventilatory defect in 21 percent. A reduction in diffusing capacity has not been previously described as a frequent finding in patients with chronic congestive heart failure. In contrast to other studies involving patients with acute heart failure, obstructive ventilatory defects were uncommon. None of the lung function abnormalities was associated with smoking status, prior drug use, chest roentgenographic changes, hemodynamic findings, or clinical features, including duration of congestive heart failure. The mechanism for the diffusion impairment is unclear but could be due to chronic passive congestion with pulmonary fibrosis and/or recurrent pulmonary emboli. Recognition of diffusion impairment as a common finding in patients with severe chronic congestive heart failure who are candidates for heart transplantation is important for proper interpretation of possible post-transplant changes in diffusing capacity due to other causes.
Adult↗
[Factors in the development of arterial hypoxemia in middle-aged and elderly people].
Partial pressure of oxygen and carbon dioxide in alveolar air and arterial blood, lung diffusion capacity and its components, ventilation parameters, ventilation-perfusion ratio were determined in healthy people aged 60-89 (45 subjects) and aged 20-31 (19 subjects, controls). In elderly and old people PO2 in arterial blood was found to decrease with increasing alveolar-arterial PO2 gradient. In other words, arterial hypoxemia was determined by the disturbance in gas exchange between alveolar air and blood of lung capillaries. The diffusion capacity of lung decreased at the expense of membrane factor. Its age-related dynamics was mainly due to a decrease in the pulmonary diffusion surface occurring because of improper coordination of ventilation and perfusion in the lungs. The discrepancy of pulmonary ventilation and perfusion proved to be the leading factor of arterial hypoxemia in late ontogenesis.
Adult↗
Pulmonary capillary blood volume in emphysema.
We determined single breath diffusing capacity (DLCO) and pulmonary capillary blood volume (Vc) in a total of 110 patients, who were being evaluated for resectional lung surgery for a localized tumor or lesion. Pathologic assessment of emphysema was obtained in 55 cases who had resection of a lung or an upper lobe, based on a standard reference panel for emphysema grading. In 86 cases, the extent of emphysema was quantitated by computed tomography (CT) of the chest. There was a significant negative correlation between Vc and emphysema assessed by either pathology or CT (r = about -0.5, p less than 0.001) similar to the correlation between DLCO and the extent of emphysema. Results of Vc were significantly lower in cases with moderate emphysema (pathologic grade greater than or equal to 30) than those with no emphysema (grade less than or equal to 5) (p less than 0.001) or mild emphysema (grade 10 to 25) (p less than 0.05), and they were significantly lower (p less than 0.05) in the group with mild emphysema compared with the group with no emphysema on pathologic assessment similar to DLCO results. Although Vc was reduced in emphysema, determination of Vc did not result in improved discrimination in separating cases with emphysema from those without emphysema when compared with DLCO.
Adult↗
Peripheral muscle weakness contributes to exercise limitation in COPD.
Recently, it was suggested that fatigue of peripheral muscles could contribute to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). In order to quantify the role of peripheral muscle force, we restudied potential determinants of exercise capacity (6-min walking distance [6 MWD] and maximal oxygen consumption [V02max]) in 41 consecutive COPD patients (FEV1, 43 +/- 19% of predicted, TLCO, 56 +/- 25% of predicted) admitted to our pulmonary rehabilitation program. VO2max (incremental cycle ergometer test), 6 MWD (best of three), lung function (FEV1, FVC, TLC, FRC), diffusing capacity (TLCO), isometric quadriceps force (QF), hand grip force (HF), and maximal inspiratory (PImax) and expiratory (PEmax) pressures were measured. Patients had a poor 6 MWD (372 +/- 136 m) and VO2max (1.35 +/- 0.60 L, 71%), reduced respiratory (PImax 65 +/- 27%) and peripheral muscle force (QF 74 +/- 27%, HF 82 +/- 23%). In single regression analysis, significant correlations (r) were found for VO2max and TLCO (0.68), FEV1 (0.64), QF (0.55), HF (0.53), and body weight (0.49). Walking distance was significantly correlated with QF (0.63), HF (0.61), PImax (0.49), and TLCO (0.38). In stepwise multiple regression analysis, the variables significantly contributing to 6 MWD were QF and Plmax. For VO2max, variables significantly contributing were TLCO, QF, and FEV1. We conclude that lung function and peripheral muscle force are important determinants of exercise capacity in COPD.
Body Weight↗
[Determination of diffusing capacity in 66 cases of chronic bronchitis (author's transl)].
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Adult↗
The single breath transfer factor (Tl,co) and the transfer coefficient (Kco): a window onto the pulmonary microcirculation.
The transfer factor, Tl,co (with the transfer coefficient, Kco, also known as the transfer factor per unit alveolar volume, [Tl/Va]), is one of the most useful clinical tests of pulmonary function, the only one which specifically focuses on pulmonary microcirculation. It was originally devised in 1909 as a physiological tool to assess the diffusive capacity of the lung as a gas exchanger. It was subsequently developed as a clinical tool, but cumbersome analytical techniques delayed its introduction into clinical medicine until 1950s. The physiology of the carbon monoxide transfer factor (also called the diffusing capacity Dl,co) is based on the Roughton-Forster equation which partitions Dl,co, a conductance, into membrane (Dm) and red cell (thetaVc) diffusion conductances. Recent work (1987-2001) suggests that 70-80% of the resistance to CO (and O2) diffusion may reside in the red cell fraction. The clinical implication is that Tl,co and Kco are 'windows' onto the pulmonary microcirculation. As regards reference values for clinical use, Tl,co depends on age, height and gender. Kco, which is actually a rate constant, is independent of gender, and is affected principally by age. A schema is presented for the clinical interpretation of Tl,co. As Tl,co is derived from the product of Kco and the accessible alveolar volume (Va), examination of these two components (Kco and Va) will usually suggest a specific pathophysiological mechanism as the explanation for a reduction in Tl,co.
Humans↗
Cardiorespiratory responses to incremental exercise in patients with systemic sclerosis.
Patients with systemic sclerosis are known to have histologic pulmonary abnormalities despite normal chest radiograph or conventional pulmonary function or both. In an attempt to detect early features of lung involvement in progressive systemic sclerosis, we investigated patients with systemic sclerosis using cardiopulmonary exercise testing. We have studied 78 patients who fulfilled the American Rheumatism Association criteria for the classification of systemic sclerosis, and according to the classification of LeRoy, 44 had limited cutaneous systemic sclerosis and 34 had diffuse cutaneous systemic sclerosis. A significantly decreased diffusing capacity (65 +/- 3% of that predicted) was present only in the group with diffuse cutaneous systemic sclerosis. The patients with lung involvement showed a significant reduction in exercise capacity (54 +/- 3% of that predicted) and in oxygen uptake (70 +/- 3% of that predicted). Additionally, we could demonstrate an increased functional dead space ventilation (0.34 +/- 0.02) and widened alveolar-arterial oxygen difference during exercise (44 +/- 3 mm Hg). By cardiopulmonary exercise testing, 12 of the 78 patients (15%) with normal single-breath diffusing capacity for carbon monoxide had increased dead space to tidal volume ratio. Our results suggest that occult pulmonary impairment may be present in patients with normal pulmonary function and that cardiopulmonary exercise testing enables detection of such impairment. Our study results show the limitations of resting data in predicting abnormalities during exercise in patients with systemic sclerosis.
Adult↗
Routine pulmonary function tests during bleomycin therapy. Tests may be ineffective and potentially misleading.
Forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) studies in two patients with proved interstitial fibrosis after low doses of bleomycin were contrasted with these measurements in 21 patients who received bleomycin without toxicity. The FVC decreased significantly (20% or more) in both fibrosis patients and in seven others. In one fibrosis patient and in three others the results could be explained by weakness. The DLco fell in both patients with fibrosis and in 12 others. Correction for decrease in hemoglobin level accounted for the change in one of the toxic patients and seven of the others, but hemoglobin correction made two insignificant changes significant and increased therapy values above control four times. Since these tests have many false-positive results and can be affected by weakness and anemia leading to false-negative results their use is ineffective and may be misleading.
Bleomycin↗
Serial pulmonary function testing in patients with systemic lupus erythematosus.
Previous studies have documented the pulmonary function abnormalities associated with systemic lupus erythematosus (SLE). There are very few data, however, regarding the progression of such changes. To study this question, we evaluated the pulmonary function of a group of 25 patients with SLE from two to seven years after a set of pulmonary function tests had been performed as part of their overall initial assessment. Reductions in diffusing capacity, FVC, and total lung capacity did not change significantly for the group over the period of our study. The mean FEF25-75%, which was initially low, and the mean FEV1/FVC ratio, which was initially normal, both decreased significantly. The observed abnormalities in airway function were not related to smoking history. Other aspects of lupus activity, as measured by serum creatinine levels and clinical activity, did not appear related to progression of lung disease.
Adult↗
Almost simultaneous measurement of cardiovascular and gas exchange variables during maximal exercise.
We measured gas exchange variables such as oxygen uptake, carbon dioxide output, and lung diffusing capacity using noninvasive techniques almost simultaneous with assessment of cardiovascular variables such as pulmonary blood flow at several levels of treadmill exercise up to and including maximal capacity. We utilized a single breath exhalation technique for measurement of diffusing capacity and cardiac output and breath by breath methodology for evaluating oxygen uptake. The equipment required for these measurements--rapid gas analyzers, oximeters, on-line computation, and pneumatic valves--are well within the capabilities of many exercise laboratories and are not difficult to use with subjects even at the heaviest levels of exercise. The results agreed well with values reported in the literature. From these entirely noninvasive measures, we calculated mixed venous oxygen saturation and maximal tissue oxygen diffusing capacity.
Adult↗
Diffusing capacity for carbon monoxide as a predictor of gas exchange during exercise.
In patients with pulmonary disease, the diffusing capacity for carbon monoxide has been used to predict abnormal gas exchange in the lung. However, abnormal values for arterial blood gases during exercise are likely to be the most sensitive manifestations of lung disease. We compared the single-breath diffusing capacity for carbon monoxide at rest with measurements of gas exchange during exercise, including arterial oxygen tension, the alveolar-arterial difference in oxygen tension, the arterial-end-tidal difference in carbon dioxide tension, and the dead-space/tidal-volume ratio in 276 current and former shipyard workers. Sixteen workers had a diffusing capacity for carbon monoxide below 70 percent of predicted; one or more measurements of gas exchange during exercise were abnormal in 14. In contrast, of 96 men who had abnormal gas exchange during exercise, only 14 had a diffusing capacity for carbon monoxide below 70 percent of predicted. Neither the type nor the degree of abnormality in gas exchange could be predicted from the diffusing capacity. We conclude that diffusing capacity for carbon monoxide at rest is a specific but insensitive predictor of abnormal gas exchange during exercise and that, if indicated, measurements of arterial blood gases should be obtained during exercise.
Asbestosis↗
Transpleural CO2 diffusion in excised dog lungs.
Previous studies of transpleural gas diffusion have reported both linear and nonlinear relationships between total gas transfer and the transpleural driving gradient estimated as the difference between pleural and end-tidal gas tensions. The present studies were undertaken to explain these conflicting results by examining the role of convective mixing as well as the validity of using measurements of end-tidal gas to estimate subpleural gas tensions and calculate the transpleural partial pressure gradient. Nine excised nonperfused dog lungs were ventilated with room air under varying conditions of frequency (f), tidal volume (VT) and pleural CO2 concentration (FplCO2). The relationship between CO2 elimination (VCO2) and the transpleural CO2 concentration gradient estimated by (FplCO2-FETCO2) was found to be linear for every level of ventilation (constant convective mixing) studied. The slope of this relationship, equal to the pleural CO2 diffusing capacity (DplCO2) was found to decrease as ventilation was decreased whether achieved by reductions in f or VT. Because changes in membrane geometry were insufficient to explain the differences in DplCO2, seven additional excised dog lungs were studied ultrastructurally following 4 h of ventilation with room air at a pleural CO2 concentration of 6%. Previous studies under similar conditions have shown that changes in type II pneumocyte lamellar body volume density Vv(LB/cyto) are related to the alveolar concentration of CO2. The results indicated that the concentration of CO2 in alveoli located within 1 mm of the pleural surface was substantially greater than the value estimated by FETCO2. Consequently, (FplCO2-FETCO2) over-estimates the transpleural concentration gradient and produces erroneously low estimates of the diffusing capacity of the pleural membrane.
Animals↗
[Impairment of gas exchange in acute lung injury].
To demonstrate the characteristics of impaired gas exchange in acute respiratory distress syndrome (ARDS), an experimental model of lung injury was produced in 24 mongrel dogs by intravenously injecting 0.07 ml/kg of oleic acid. While allowing the animal to breathe a mixture of 0.1% CO in air, normal saline, which contained appropriate amounts of six inert gases such as SF6, ethane, cyclopropane, halothane, ether and acetone, was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were taken simultaneously. The concentrations of the nine indicator gases (O2, CO2, CO and six inert gases) in the samples were measured in terms of a gas chromatograph, permitting analysis of the distribution of ventilation to perfusion (VA/Q) as well as the diffusing capacity to perfusion (G/Q) in injured lungs. To determine the role of hypoxic pulmonary vasoconstriction (HPV) in maintaining gas exchange in ARDS, hemodynamic and gas-exchange parameters were investigated at inspired O2 concentrations (FIO2) of either 21 or 60%. The impairment of gas exchange was examined by measuring the fractional retention (R) of the inert gases in arterial blood. Furthermore, to assess the possible contribution of vasoactive prostanoids in regulating vascular reactivity in ARDS, observations at FIO2 of 60% were repeated after administered indomethacin at a dose of 5 mg/kg. Analytical results revealed that shunt flow in experimental dogs with lung damage caused by oleic acid averaged 17%. Furthermore, widening of VA/Q distribution was found accompanied with significant contribution of extremely low VA/Q areas. In addition, most of the lung was operating in G/Q units with values ranging from 10(-3) to 10(-2) but 9.8% of total Q(QT) was received by the area with G/Q less than 10(-3), which might limit O2 exchange between the alveolar gas phase and capillary blood. Although pulmonary vascular resistance (PVR) in injured lungs observed at FIO2 of 60% was significantly smaller than the value obtained at FIO2 of 21%, QT as well as extravascular lung water did not differ in the two conditions. The R value for the indicator gas was consistently lower at FIO2 of irrespective of gas species. Administration of indomethacin caused a considerable diminution of the R value for inert gas but a rise in PVR without an appreciable change of either QT or extravascular lung water. This was followed by a significant rise in arterial PO2 from 84 to 99 Torr.(ABSTRACT TRUNCATED AT 400 WORDS)
Acute Disease↗