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CT scores of emphysema and oxygen desaturation during low-grade exercise in patients with emphysema.

PURPOSE: We evaluated the usefulness of CT for assessing oxygen desaturation during walking in patients with emphysema. MATERIAL AND METHODS: The study comprised 32 patients with emphysema (mean age 67+/-6 years). Serial CT images of 5 mm were obtained from the apex to the basal regions of the lung during deep inspiration. The severity of emphysema was scored by four physicians according to a visual method. A six-minute walking test and oxygen desaturation (pSO2) measurements were performed. RESULTS AND CONCLUSION: The mean CT score of the four observers was significantly correlated with the nadir pSO2 and deltapSO2, but did not correlate with the total distance walked. These results suggest that CT may be used for the assessment of oxygen desaturation during low-grade exercise in patients with emphysema.

Aged↗

Functional MR imaging of pulmonary ventilation using hyperpolarized noble gases.

The current status of experimental and clinical applications for functional MR imaging of pulmonary ventilation using hyperpolarized noble gases are reviewed. 3-helium (3He) and 129-xenon (129Xe) can be hyperpolarized by optical pumping techniques such as spin exchange or metastability exchange in sufficient amounts. This process leads to an artificial, non-equilibrium increase of the density of excited nuclei which represents the source of the MR signal. Those hyperpolarized gases are administered mostly via inhalation, and will fill airways and airspaces allowing for ventilation imaging. Recent human studies concentrate on imaging the airways and airspaces with high spatial resolution. Normal ventilation is reflected by an almost complete and homogeneous distribution of the hyperpolarized gas represented by the signal detected. Loss of signal or inhomogeneous signal distribution represent mass effects and ventilatory abnormalities. Even healthy subjects with seasonal allergies without pulmonary symptoms have been observed to exhibit transient ventilation defects. Real-time imaging of ventilation has become feasible for 3He MR imaging and allows for assessment of ventilation-distribution. Furthermore, functional oxygen-sensitive 3He MR imaging opens the field of non-invasive assessment of regional intrapulmonary oxygen concentrations in vivo. Knowing that the diffusion of gas is affected by the geometry and nature of its environment, diffusion measurements are under investigation as a sensitive marker of diseases that involve structural changes of lung parenchyma, such as emphysema and fibrosis. Whereas 3He is not absorbed and is restricted to the airspaces, 129Xe is soluble in blood and lipid-rich tissue. This presents the opportunity for additional dissolved-phase imaging, providing a step towards simultaneous ventilation-perfusion studies.

Helium↗

Volume adjustment of lung density by computed tomography scans in patients with emphysema.

PURPOSE: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema. MATERIAL AND METHODS: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA. RESULTS: The coefficients for volume adjustment for PD were relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema. CONCLUSION: Volume adjustment is mandatory in repeated CT densitometry and is more robust for PD than for RA. Therefore, PD seems more suitable for monitoring the progression of emphysema.

Absorptiometry, Photon↗

Short-term reproducibility of computed tomography-based lung density measurements in alpha-1 antitrypsin deficiency and smokers with emphysema.

PURPOSE: To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms. MATERIAL AND METHODS: Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed. RESULTS: The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema. CONCLUSION: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.

Absorptiometry, Photon↗

Numerical simulation of the transient transport of inert gases in lung tissue.

A numerical simulation of the transport of xenon gas into healthy and oedematous lung tissue is described. The lung is modelled as four parallel tissue layers; alveolar membrane, interstitial fluid, capillary membrane, and blood, surrounded by a uniform air space. Using a finite difference representation of the governing diffusion equations, the concentration distribution of Xe gas in each of the layers of tissue is obtained for a step change in the Xe concentration in the air space. The effect of a thickening of the interstitial fluid layer, found in pulmonary oedema, on the kinetics of Xe transport is also considered. Computational findings indicate that a good approximation to the steady state profiles for Xe in the layers of tissue can be obtained simply by assuming that instantaneous equilibrium exists (as described by Henry's Law) between the lung tissue and surrounding air space. This same finding is documented even when the thickness of the interstitial fluid layer is increased by a factor of 40 above baseline values. The results suggest that the reduction in gas exchange which occurs in pulmonary oedema is caused by fluid flow into the alveoli, rather than a true diffusion deficit caused by a thicker alveolar-capillary barrier. The relationship of the present findings to those which would be obtained for more physiological input functions of Xe gas into the air space in also discussed.

Biological Transport↗

Growth and development of Andean high altitude residents.

Growth and development under conditions of chronic hypoxia result in a different pattern of growth in Andean highlanders than in lowlanders. Growth at high altitude results in a small (1 to 4 cm) delay in linear growth, with most, if not all, of the delay probably established at or soon after birth. It also results in an enhancement of lung volumes, particularly residual volume, which is 70%-80% larger in highland than lowland children, on average, with the magnitude of the increase being positively related to age. In addition, growth and development under conditions of chronic hypoxia result in a blunted ventilatory response to hypoxia, a 4% to 5% reduction in Sa(O2), and a substantial increase in pulmonary diffusing capacity. Andean highlanders have V(O2 max) similar to that of lowlanders at low altitude, suggesting that they have successfully adapted to their hypoxic environment. It is likely that both developmental and genetic factors influence most, if not all, components of the cardiorespiratory system of Andean highlanders, but the relative importance of each is not clear.

Acclimatization↗

Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients.

A retrospective chart review was carried out on 344 patients with systemic sclerosis (SSc) followed prospectively for the occurrence of pulmonary hypertension (PHT). Seventeen patients (4.9%) were found to have PHT. Eight patients had isolated PHT, while in nine PHT was associated with restrictive lung disease (RLD). The subset with RLD developed PHT earlier, but had longer survival than patients with isolated PHT. Patients with limited scleroderma tend to develop isolated PHT, while in those with diffuse disease PHT is associated with RLD. Irrespective of disease type, PHT in SSc has an extremely poor prognosis with a median survival of 12 months following diagnosis.

Adult↗

Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVE: A prospective study to evaluate echocardiography and gas transfer (DLCO) by comparison with cardiac catheterization in discriminating between patients with and without systemic sclerosis-associated pulmonary arterial hypertension (SScPAH). METHOD: A total of 137 (52 with and 85 without pulmonary fibrosis) had echocardiography and lung function tests within 3 months of their definitive invasive study. RESULTS: At cardiac catheterization 99 of these patients were found to have PAH, while PAH was excluded in 38. Echocardiographically estimated tricuspid gradient (TG) showed a moderate positive correlation (r(2) = 0.44, P<0.005) with both mean pulmonary pressure and invasively determined tricuspid gradient. DLCO showed a weak correlation (r(2 )= 0.09, P = 0.006), when compared with mean pulmonary arterial pressure. In total, 97% of patients with an echocardiographically determined TG of > 45 mmHg were found to have pulmonary hypertension at catheterization. However, no threshold could be defined with either screening test that safely excluded PAH. CONCLUSIONS: The positive predictive accuracy of currently used non-invasive tests are adequate for the diagnosis of advanced PAH provided sufficiently high thresholds (TG > 45 mmHg or DLCO < 55% predicted) are used. These tests cannot be relied upon to exclude pulmonary hypertension where pre-test probability is high.

Aged↗

The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome.

Prone positioning improves gas exchange in some patients with adult respiratory distress syndrome (ARDS), but the effects of repeated, long-term prone positioning (20 h duration) have never been evaluated systemically. We therefore investigated 20 patients with ARDS after multiple trauma (Injury Severity Score [ISS] 27.3 +/- 10, ARDS score 2.84 +/- 0.42). Patients who fulfilled the entry criteria (bilateral diffuse infiltrates, severe hypoxemia, pulmonary artery occlusion pressure [PAOP] < 18 mm Hg, and PaO2/fraction of inspired oxygen [FIO2] < 200 mm Hg at inverse ratio ventilation with positive end-expiratory pressure [PEEP] > 8 mm Hg for more than 24 h) were turned to the prone position at noon and were turned back to the supine position at 8:00 AM on the next day. Thus only two turns per day were necessary, and the risk of disconnecting airways or medical lines was minimized. Prone positioning was repeated for another 20 h if the patients fulfilled the entry criteria. Except for FIO2, the ventilator settings remained unchanged during the study period. All patients were sedated and, if needed paralyzed to minimize patient discomfort. One hour before and after each position change, ventilator settings and pulmonary and systemic hemodynamics were recorded and blood was obtained for blood gas analysis. Derived cardiopulmonary and ventilatory variables were calculated using standard formulas. Overall mortality was 10%. Oxygenation variables improved significantly each time the patients were placed prone. Immediately after the first turn from the supine to the prone position the following changes were observed: PaO2 increased from 97 +/- 4 to 152 +/- 15 mm Hg, intrapulmonary shunt (Qva/Qt) decreased from 30.3 +/- 2.3 to 25.5 +/- 1.8, and the alveolar-arterial oxygen difference decreased from 424 +/- 24 to 339 +/- 25 mm Hg. All these changes were statistically significant. Most of these improvements were lost when the patients were turned supine, but could be reproduced when prone positioning was repeated after a short period (4 h) in the supine position. Short periods in the supine position were necessary to allow for nursing care, medical evaluation, and interventions such as placement of central lines. No position-dependent changes of systemic hemodynamic variables were observed. We conclude that, in trauma patients with ARDS undergoing long-term positioning treatment, lung function improves significantly during prone position compared to short phases of conventional supine position during which the beneficial effects are partly lost.

Adult↗

A comparison in vivo dacron wool (Swank) and polyester mesh (Pall) micropore blood transfusion filters in the prevention of pulmonary microembolism associated with massive transfusion.

Experiments were performed to compare the effectiveness in vivo of the two most widely used micropore blood transfusion filters in preventing detrimental physiologic changes associated with transfusion of microaggregate-containing blood. Exchange transfusion with stored blood having an elevated screen filtration pressure (SFP) through polyester mesh (Pall) filters (Group PM) was followed by decreases in arterial blood pH and O2 consumption, increases in arterial blood pyruvate and lactate concentrations, and a decrease in pulmonary DO2. The lungs of 5 of 6 animals revealed emboli far out in the pulmonary microcirculation. These changes did not occur in animals transfused through dacron wool (Swank) filters (Group DW). Even though an increase after transfusion in pulmonary Qs/Qt in Group PM did not achieve statistical significance when compared to pretransfusion Qs/Qt, it was significantly higher than that in animals in Group DW. Both filters removed considerable quantities of microaggregates; however, the polyester mesh (Pall) filters permitted passage of small microaggregates and development of ditrimental physiologic changes. Dacron wool (Swank) filters completely removed measurable microaggregates and detrimental changes did not occur.

Animals↗

Progression and resolution of changes in pulmonary function and structure due to pulmonary microembolism and blood transfusion.

It was the purpose of this research to define the progression over several days of changes in pulmonary function and structure and to document the phases of recovery following transfusions to dogs of sublethal quantities of stored blood containing microaggregates. Ten dogs underwent partial exchange transfusions averaging 60% of blood volume through standard blood transfusion filters. Average screen filtration pressure (SFP) of the blood was 85 mm Hg. Pulmonary hypertension did not develop, but there were striking decreases in O2 consumption, increases in Qs/Qt and decreases in Do2. Changes became progressively more marked over the first 48 to 72 hours after the transfusions. Pulmonary function of surviving animals returned nearly to normal by the sixth day after transfusions. Pathologic examinations of the lungs of animals sequentially sacrificed over 6 days showed intravascular microemboli, alveolar cell hyperplasia and interstitial and alveolar pulmonary edema. Progressive recovery was associated with progressive resolution of all detrimental changes. In 6 animals exchange transfused 100% of their blood volumes through dacron wool (Swank) filters and in three control animals that were not transfused, there were no significant changes in pulmonary function or structure. These experiments define the progression of deterioration and recovery over 6 days of pulmonary function in dogs after sublethal pulmonary microembolism occurring during blood transfusion.

Animals↗

Phase I trial of ImmTher, a new liposome-incorporated lipophilic disaccharide tripeptide.

A phase I clinical trial was conducted to evaluate the toxicology and biological activity of a new liposome-incorporated lipophilic disaccharide tripeptide, ImmTher. Twelve patients with advanced nonhematological malignant disease received 13 courses of therapy at dose levels of 200-1,200 micrograms/m2. A course of therapy consisted of once-weekly administration of the drug for 2-12 weeks. The major clinical toxicities observed were chills and hypotension. No renal, hepatic, cardiac, or hematological toxicity was observed. A small decrease in pulmonary diffusion capacity was observed. Biological activity was demonstrated by changes in plasma cytokine levels, changes in in vitro monocyte cytotoxicity, and by a decrease in tumor size. Improvement was observed in three of three patients with metastatic disease to the liver. Response in these three patients correlated with an increase in their tumor necrosis factor and neopterin levels compared with nonresponders. These preliminary indications of biological and clinical activity of a liposome-incorporated lipophilic disaccharide tripeptide in patients with advanced metastatic hepatic disease suggest a potential new therapeutic approach to this common problem.

Acetylmuramyl-Alanyl-Isoglutamine↗

Implications of liver activity associated with 133Xe ventilation lung scans.

A series of 35 xenon-133 (133Xe) ventilation studies yielded nine cases demonstrating accumulation of activity in the liver. Maximum intrahepatic deposition of radioxenon occurred during the washout phase of the study. In addition to those clinical instances which make this phenomenon possible, i.e., obesity, alcoholic-induced liver steatosis and diabetes mellitus, we found that hyperlipidemia and coronary artery disease also favor xenon-133 localization into the hepatic parenchyma. It is concluded that the lipid avidity of 133Xe facilitates its liver accumulation hyperlipidemic patients and in patients with coronary artery disease, and that this action may be explored to further understand deranged metabolic pathways in the liver of these patients. Hepatic accumulation of 133Xe during ventilation studies must be considered when assessing regional ventilation/perfusion relationships.

Adult↗

Abnormal uptake of Tc-99m MIBI, a novel myocardial imaging agent, in the lungs of patients with systemic sclerosis.

OBJECTIVE: Fibrosing alveolitis is a prominent feature of systemic sclerosis (SSc), and accounts for much of the morbidity and mortality of this disease. Sensitive techniques for the detection and monitoring of fibrosing alveolitis could target patients for early therapeutic intervention. The objective of this small pilot study was to assess the frequency and clinical significance of abnormal lung uptake of Tc-99m MIBI, a novel radionuclide imaging agent that selectively accumulates in cells rich in mitochondria. METHODS: Sixteen patients with SSc and evidence of pulmonary involvement were studied. The uptake of radionuclide in the lungs, and the ratio of pulmonary to cardiac uptake were evaluated after intravenous injection of Tc-99m MIBI. Results were correlated with clinical and laboratory parameters. RESULTS: Lung uptake of Tc-99m MIBI was increased in all 16 SSc patients compared to control patients with coronary heart disease but no evidence of pulmonary abnormality. The degree of isotope uptake in the lungs was correlated with the extent of maximal skin induration and with radiologic evidence of interstitial lung disease, but not with other clinical or laboratory parameters of disease activity or extent of pulmonary involvement. The ratio of pulmonary to cardiac uptake of isotope was also increased in patients with SSc compared to controls. CONCLUSION: Accumulation of Tc-99m MIBI is abnormally elevated in the lungs of SSc patients with pulmonary involvement. Isotope accumulation in the lungs may be related to activation of fibroblasts or endothelial cells. The specificity and sensitivity of Tc-99m MIBI scanning in the detection and monitoring of pulmonary involvement, and its potential role in the management of SSc, deserve further investigation.

Coronary Disease↗

Unusual case of diagnosis of pigeon breeder's hypersensitivity pneumonitis with ventilation-perfusion lung scan.

The authors describe a patient thought to have pulmonary embolism. Results of a perfusion scan were normal, but Tc-99m DTPA aerosol ventilation lung scan showed, in successive views, decreased activity of the deposited aerosol. The lung Tc-99m DTPA clearance was measured and was markedly increased. This suggested possible hypersensitivity pneumonitis, which was later confirmed as pigeon breeder's disease. The decreased activity observed on the DTPA ventilation scan must be directed toward increased lung clearance and its measurement.

Administration, Inhalation↗