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1.
The pathophysiology in the bronchiolo-alveolar region in healthy smokers and patients with interstitial lung diseases was assessed in terms of changes in epithelial permeability. The pulmonary epithelial permeability was estimated by the rate constant (referred to as "kep") of inhaled 99mTc-DTPA (diethylene triamine penta acetate) clearance from the lungs. Healthy nonsmokers had a mean kep value of 0.82 +/- 0.26%/min, and their kep values were constant irrespective of age or sex. Of healthy smokers 53% showed increased permeability. Young smoking males, whose lung injury was supposed to be limited mainly to respiratory bronchioles, showed increased permeability. This increase was correlated with their cigarette consumption per day and was reversible after stopping smoking. The patients with interstitial lung diseases also showed increased permeability as compared with healthy non-smokers. We believe that the method is a sensitive test to detect inflammatory changes in the bronchiolo-alveolar epithelium.  相似文献   

2.
To evaluate alveolar epithelial damage in PSS, we studied pulmonary epithelial permeability by measuring the clearance of inhaled 99mTc-DTPA aerosol and performing thin slice CT scan, pulmonary function tests and right heart catheterization in 28 patients with PSS. The 99mTc-DTPA clearance rate (kep value) in PSS was greater than in 11 non-smoking normal subjects (18.2 +/- 7.63 x 10(-3)/min vs. 9.12 +/- 0.77 x 10(-3)/min, p less than 0.01). In PSS, the kep value did not correlate with age, sex, duration of illness, dermal lesions, % vital capacity, or PaO2. In contrast, the kep value showed significant correlations with %DLco (diffusing capacity for carbon monoxide), extent of interstitial lesions evaluated by CT scan (CT score), and mean pulmonary artery pressure. On the other hand, the kep value was high in some patients with normal CT scan and normal %DLco. These findings indicate that pulmonary interstitial lesions in PSS are accompanied by alveolar epithelial damage, and that the clearance of 99mTc-DTPA may be an early predictor of interstitial change.  相似文献   

3.
The 99mTc-DTPA aerosol inhalation method permits detection of pulmonary epithelial damage. We investigated one of several problems, airway deposition of inhaled aerosol, on the assessment of pulmonary epithelial permeability in healthy nonsmokers and patients with interstitial lung diseases. We used the rate constant of pulmonary 99mTc-DTPA clearance curve, k, as a parameter of the epithelial permeability. The alveolar-peripheral airway deposition of aerosol was estimated by the duplicated inhalation method, which we newly developed. The mean k in patients with interstitial lung diseases (2.52 +/- 0.72%/min, n = 8; p less than 0.01) was significantly greater than that in healthy nonsmokers (0.92 +/- 0.20%/min, n = 4). The alveolar-peripheral airway deposition was similar in both healthy nonsmokers and interstitial lung diseases (73.5 +/- 7.8% and 75.5 +/- 9.2%, respectively). The mean k corrected for alveolar-peripheral airway deposition (corrected k; kc) was higher in patients with interstitial lung diseases (4.08 +/- 1.63%/min; p less than 0.01) as compared with healthy nonsmokers (1.36 +/- 0.47%/min). The mean k was significantly greater than the mean kc in both groups (p less than 0.01, p less than 0.01). However, there was a significant correlation between the k and kc obtained among the subjects (r = 0.951; p less than 0.01). We, therefore, conclude that correction for alveolar-peripheral airway deposition was not necessary to distinguish the patients with interstitial lung diseases from the healthy nonsmokers using 99mTc-DTPA aerosol inhalation method although the correction was significant in the individual subjects.  相似文献   

4.
99mTc-DTPA clearance was studied in 11 healthy nonsmokers, 20 patients with simple or complicated silicosis (5 of simple, 15 of complicated). The results indicated that both the patients with simple silicosis (T1/2 32.8 +/- 14.4min) and complicated silicosis (T1/2 26.6 +/- 8.5min) showed faster clearance of inhaled 99mTc-DTPA than observed in healthy nonsmokers (77.9 +/- 11.7min, p < 0.01). Regional clearance apico-basal difference was found in patients with silicosis. This study presents evidence of increased pulmonary epithelial permeability and regional distribution of pulmonary epithelial permeability in silicosis.  相似文献   

5.
The changes in pulmonary epithelial permeability during and following radiation therapy were studied in 10 patients with malignant diseases of the chest; 9 patients with bronchogenic carcinoma and one with thymoma. 99mTc-DTPA aerosol was inhaled during tidal breathing with the patient in supine position, and radioactivity was measured anteriorly by a gamma camera and recorded on a computer. Half time clearance (t1/2) was calculated from exponential fitting of time activity curves by regression analysis in various regions of interest in the initial 7 min following completion of aerosol inhalation. Studies were made every two weeks. In patients who developed radiation pneumonitis, t1/2 values decreased and reached the nadir at the time of manifest pneumonitis, indicating increased pulmonary epithelial permeability. Increased pulmonary epithelial permeability was observed not only in the pneumonic regions but also in the contralateral normal lung regions. Steroid therapy reversed these changes. Increased pulmonary epithelial permeability was observed in 2 out of 5 patients who did not develop radiation pneumonitis. In summary, pulmonary epithelial permeability changes occur not only in regions of radiation pneumonitis but also in non-irradiated lung regions following radiation therapy. We consider that the judicious use of this method enables detection of changes in pulmonary epithelial permeability prior to the development of clinical manifestations of radiation pneumonitis.  相似文献   

6.
The application of 99mTc-DTPA radioaerosols to a variety of clinical disorders is described. With the development of simple equipment that can deliver very small droplets, this approach has become increasingly popular for measurements of the distribution of ventilation in patients with obstructive lung disease and suspected pulmonary embolism. In addition, by determining the rate at which the radionuclide is cleared from the lung, information has been obtained concerning the permeability of the pulmonary epithelium to extracellular indicators. Accelerated clearance rates have been found in patients with a variety of chronic interstitial lung diseases indicating that epithelial permeability is increased. Accelerated clearance rates have also been found with acute inflammation of the lung such as the adult respiratory distress syndrome and pneumocystis pneumonia. Furthermore, rapidly reversible increases in 99mTc-DTPA clearance occur in smokers and may be related to the inflammatory changes that contribute to the development of emphysema.  相似文献   

7.
Clearance of inhaled 99mTechnetium-labelled diethylene triamine pentacetate (99mTc-DTPA) from the lung, an index of pulmonary alveolar epithelial permeability (PAEP), was measured in 13 patients with cardiogenic interstitial pulmonary oedema (CIPO) and in 7 patients with adult respiratory distress syndrome (ARDS). Thirty-five normal subjects (22 nonsmokers and 13 smokers) were evaluated as controls. Half-time clearance (t0.5) values in ARDS patients (mean +/- SD: 15 +/- 2 min) were significantly lower than in CIPO patients (62 +/- 9 min). This PAEP increase in ARDS was impressive, even in comparison to heavy smokers. Loss of the PAEP vertical gradient (apical PAEP greater than base PAEP) was observed in both cardiogenic and ARDS lungs and among smokers.  相似文献   

8.
99mTc-DTPA is a low molecular weight substance which is believed to pass through the pulmonary epithelium when it is inhaled as an aerosol. We performed 99mTc-DTPA inhalation studies in 10 nonsmoking normal subjects and 10 patients with biopsy proven idiopathic interstitial pneumonia prior to therapy. 99mTc-DTPA aerosol was inhaled for 3 min with the subject in the supine position and radioactivity was measured anteriorly with a gamma camera and recorded on a computer. Measurements were performed for 3 min with the subject inhaling aerosol and for the subsequent 30 min with the subject in the same position. Time activity curves from the five regions of interest (ROIs) including the entire left lung, the entire right lung, and the upper, middle and lower third of the right lung were separately fitted to a single exponential function for the initial 7 min following cessation of inhalation, and the respective clearance half life (t1/2) in min was calculated. Lung function data, arterial blood gas tensions and blood chemistry were also obtained for comparison with the t1/2 values. The t1/2 values were significantly smaller in all ROIs in patients with idiopathic interstitial pneumonia than in normal subjects, indicating a increased pulmonary epithelial permeability in these patients. There was no relationship between t1/2 and %DLco, %DLco/VA, PaO2, or LDH. Although the true pathophysiologic significance of t1/2 measured using 99mTc-DTPA aerosol is still not known, we consider that this measurement may be an important indicator of nonrespiratory lung function, in particular the degree of alveolar epithelial damage.  相似文献   

9.
G R Mason  R M Effros  J M Uszler  I Mena 《Chest》1985,88(3):327-334
The regional clearance of 99mTc-diethylenetriamine penta-acetate (99mTc-DTPA) from the lungs was measured in 14 patients with noncardiogenic pulmonary edema, six patients with acute pulmonary edema secondary to heart failure, and 29 normal subjects. The radionuclide was delivered in an aerosol which was inhaled for 120 seconds, and the subsequent decline of radioactivity from the lungs was monitored for seven minutes over each of six peripheral regions of interest with a computerized scintillation camera. The average 99mTc-DTPA clearance of these regions was accelerated above the 98 percent confidence limits in all but three of the patients with noncardiogenic edema. The mean clearance value in this group of patients was significantly greater than those in normal subjects or patients with cardiogenic pulmonary edema. Clearances returned toward normal in each of seven subjects who improved clinically. Only one of the patients with cardiogenic pulmonary edema had an elevated average clearance rate, and the mean clearance for this population was not statistically greater than normal. This procedure appears to detect increased epithelial permeability caused by lung injury and may help distinguish between cardiogenic and noncardiogenic pulmonary edema.  相似文献   

10.
A radioaerosol procedure using 99mcTc-DTPA (diethylene triamine penta acetate) was used to evaluate the permeability of the pulmonary epithelium in smokers and nonsmokers. The average clearance of this indicator from the lungs of smokers without significant airway obstruction exceeded that found in normal subjects by an average factor of more than five. This abnormality was observed throughout all lung regions. 99mTc-DTPA clearance decreased rapidly during the week after smoking was discontinued. It is concluded that smoking results in a rapidly reversible increase in pulmonary epithelial permeability.  相似文献   

11.
Ozone exposure increases respiratory epithelial permeability in humans   总被引:4,自引:0,他引:4  
Ozone is a respiratory irritant that has been shown to cause an increase in the permeability of the respiratory epithelium in animals. We used inhaled aerosolized 99mTc-labeled diethylene triamine pentacetic acid (99mTc-DTPA) to investigate whether human respiratory epithelial permeability is similarly affected by exposure to ozone. In a randomized, crossover double-blinded study, 8 healthy, nonsmoking young men were exposed for 2 h to purified air and 0.4 ppm ozone while performing intermittent high intensity treadmill exercise (minute ventilation = 66.8 L/min). SRaw and FVC were measured before and at the end of exposures. Seventy-five minutes after the exposures, the pulmonary clearance of 99mTc-DTPA was measured by sequential posterior lung imaging with a computer-assisted gamma camera. Ozone exposure caused respiratory symptoms in all 8 subjects and was associated with a 14 +/- 2.8% (mean +/- SEM) decrement in FVC (p less than 0.001) and a 71 +/- 22% increase in SRaw (p = 0.04). Compared with the air exposure day, 7 of the 8 subjects showed increased 99mTc-DTPA clearance after the ozone exposure, with the mean value increasing from 0.59 +/- 0.08 to 1.75 +/- 0.43%/min (p = 0.03). These data show that ozone exposure sufficient to produce decrements in the pulmonary function of human subjects also causes an increase in 99mTc-DTPA clearance.  相似文献   

12.
As an index of permeability of the alveolar epithelium, the clearance of an inhaled aerosol of 99mTc-DTPA is increased in several disease states. However, the usefulness of the test to assess the severity of disease is limited because healthy smokers also have abnormally rapid rates of clearance. Because the stability of the 99mTc-DTPA bond might be a contributory factor, we tested the affinity of 99mTc for DTPA in vitro, and in groups of healthy smokers (n = 13) and nonsmokers (n = 7) we measured the clearances of 99mTc-DTPA and 113mIn-DTPA, which have a similar molecular shape and charge. In vitro, sodium hypochlorite or hydrogen peroxide released as much as 98% of free 99mTc from the 99mTc-DTPA complex. When incubated with human neutrophils stimulated with phorbol myristate acetate, between 4 and 7% of free 99mTc-DTPA was released after 30 min, and 12% was released after 60 min. In vivo, the clearances of both 99mTc-DTPA and 113mIn-DTPA in the smokers (n = 13) were faster than in the nonsmokers (n = 7) (p less than 0.05). Within the smokers, the mean 99mTc-DTPA clearance (T1/2 25 +/- 4 min) was faster than the mean 113mIn-DTPA clearance (34 +/- 6 min), (p less than 0.05). For nonsmokers, the difference was smaller (T1/2 99mTc-DTPA, 56 +/- 6; T1/2 113mIn-DTPA, 62 +/- 6) and not significant. During hyperinflation, smokers (n = 8) and nonsmokers (n = 8) both demonstrated an increase in 113mIn-DTPA clearance.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

13.
This study was performed to investigate the mechanism by which 99mTc-DTPA molecules pass through the pulmonary epithelium following inhalation of 99mTc-DTPA aerosol. Interstitial pneumonitis was induced in 6-week-old male rats by instilling 1 mg/kg of bleomycin into the trachea. Disappearance of radioactivity from the lungs was measured with a gamma camera every 2 weeks to estimate pulmonary epithelial permeability, and light- and electron-microscopic histopathologic examinations were performed at the same intervals. There was a statistically significant increase in the pulmonary epithelial permeability at 2 weeks after the instillation of bleomycin. However, subsequent changes in pulmonary epithelial permeability were not uniform; some animals showed recovery and some showed further increase and/or partial recovery. Microscopically, increase in the capillary bed, round cell infiltration, and widening of the interstitial space were observed in addition to the presence of macrophages in the alveolar spaces at 2 weeks. Electron microscopic examination revealed vacuolization, thinning and detachment of the alveolar epithelium, and denudation of the basement membrane. Prominent fibrosis, honeycombing, thinning of the pulmonary epithelium, and increase in collagen fibers were observed after 18 weeks. We consider that vacuolization, thinning, and detachment of the pulmonary epithelium and denudation of the basement membrane are related to the increase in pulmonary epithelial permeability in bleomycin-induced interstitial pneumonitis.  相似文献   

14.
In two patients with chronic unilateral massive pulmonary embolism, we studied the pulmonary epithelial permeability by measuring the clearance of inhaled and deposited 99mTc-DTPA aerosol. The clearances from the embolized lungs with complete or almost complete occlusion of a main pulmonary artery were more rapid than the clearances from the normal lung, which had an increased blood flow. This suggests that in chronic, embolized lung (1) the bronchial flow clears the inhaled solutes, and (2) there is an increase of epithelial permeability.  相似文献   

15.
The rate of clearance of inhaled 99mTc-DTPA was measured in 20 nonsmoking pigeon fanciers and 7 control subjects. The degree of their avian contact and pigeon-related symptoms were noted, humoral immune response in the form of IgG antibody to pigeon gamma globulin was quantified, and diffusing capacity and total lung capacity were measured. Thirteen fanciers who had a high level of antibody had increased rates of clearance of 99mTc-DTPA (mean half-time clearance of 16.8 [+/- SEM 2.02] min [p = 0.001]) even if they were asymptomatic and even if their diffusing capacity and total lung capacity were normal. Seven control subjects without exposure to pigeon-derived antigens had normal clearance (mean 72.6 [+/- 5.98] min), and seven fanciers with antigen exposure but without an antibody response had intermediate rates of clearance (mean 42.57 [+/- 5.11] min). Clearance was not directly related to the indices of intensity and duration of antigen exposure. The measurement of rate of clearance of 99mTc-DTPA in pigeon fanciers can identify an alteration in pulmonary integrity more subtle than found with conventional pulmonary function tests and may therefore be a useful test for studying the pulmonary response to inhaled antigen and for detecting the earliest stages in the evolution of hypersensitivity pneumonitis.  相似文献   

16.
Measurements of pulmonary clearance of inhaled 99mTc-DTPA and transvascular 113mIntransferrin flux were made in 12 patients with established ARDS and 14 volunteer control subjects (7 smokers and 7 nonsmokers). Smokers had significantly increased 99mTc-DTPA clearance (clearance rate constant, 3.6 +/- 0.8; mean +/- SEM) compared with nonsmokers (1.2 +/- 0.1). All patients with ARDS had increased clearance of 99mTc-DTPA (5.2 +/- 0.9), but the finding was nonspecific in that increased clearance overlapped with the findings in normal smokers. Protein flux in smokers (protein flux units, 0.0 +/- 0.2) was similar to that in nonsmokers (0.3 +/- 0.2). In 9 of the 12 patients with ARDS, protein flux was increased, and as a group (3.2 +/- 1.0) they differed significantly (p less than 0.01) from the combined smoking and nonsmoking control subjects (0.2 +/- 0.1, n = 14). The parameters of DTPA clearance and transvascular protein flux correlated well in the patients with ARDS (Spearman's rank correlation = 0.71, p less than 0.01). Although 99mTc-DTPA clearance is a sensitive technique in ARDS, a single study in this context does not allow a diagnostic conclusion because of its non-specificity. Abnormal protein flux appears to be more specific for ARDS but was not a universal finding in the patients studied.  相似文献   

17.
To determine if the biphasic pulmonary clearance of aerosolized 99mTc diethylene penta acetate (99mTc-DTPA) observed in oleic acid lung injury represents acute epithelial damage followed by sealing as a result of intra-alveolar fibrin deposition, we examined the effect of fibrinogen depletion. 99mTc-DTPA clearance was assessed in three groups of rabbits: Group 1, normal fibrinogen + oleic acid injury; Group 2, fibrinogen-depleted + oleic acid injury; Group 3, fibrinogen-depleted with no oleic acid injury. In Group 3 animals with no lung injury, the 99mTc-DTPA clearance rate, expressed as k, the percent decrease in thoracic radioactivity, was similar to that previously reported for healthy rabbits (k = 1.16 +/- 0.57%/min, mean +/- SD). Oleic acid administration to Groups 1 and 2 resulted in significantly faster clearance rates, with identical biphasic curves in all animals, irrespective of fibrinogen status. There were no significant differences between either the initial fast phase (k, Group 1 = 5.26 +/- 1.83%/min, Group 2 = 5.70 +/- 1.77%/min) or the subsequent slow phase (k, Group 1 = 1.67 +/- 0.63%/min, Group 2 = 1.57 +/- 0.55%/min, p greater than 0.05). On histologic examination, Groups 1 and 2 showed greater cellular interstitial infiltrate, alveolar edema, and hemorrhage than did Group 3. Fibrinogen depletion plus oleic acid injury resulted in greater alveolar cellular exudate, edema, and hemorrhage than did either oleic acid or fibrinogen depletion alone. We conclude that fibrinogen is not necessary to produce biphasic 99mTc-DTPA clearance in oleic acid lung injury.  相似文献   

18.
We compared the diffuse lung uptake of 67Ga-citrate, an index of inflammatory lung activity, with the lung clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate (DTPA) aerosol, an index of pulmonary epithelial permeability, in a group of 19 West Virginia coal miners whose pulmonary status was compatible with coal worker's pneumoconiosis. 99mTc-DTPA clearance alone and 67Ga-citrate uptake alone were measured in nine and five additional subjects, respectively. The objective of this study was to determine if increased 99mTc-DTPA lung clearance was caused by inflammation at the lung epithelial surfaces. Subjects inhaled approximately 150 microCi (approximately 5.6 MBq) of 99mTc-DTPA aerosol, and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 min. Regions of interest (ROI) were selected to include (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc-DTPA clearance was determined from the slopes of the respective time-activity plots for the different ROI. Each subject was intravenously administered 50 miCroCk (1.9 MBq)/kg 67Ga-citrate 48 to 72 h before imaging the body between neck and pelvis. The extent of 67Ga-citrate lung uptake was expressed as the gallium index (GI). Mean radioaerosol clearance half-time (T1/2) for the six nonsmoking coal miners (60.6 +/- 16.0 min) was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 min). T1/2 for the 12 smoking miners (18.4 +/- 10.2 min) was shorter than for the smoking control group (33.1 +/- 17.8 min), but the difference did not attain statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

19.
We investigated the effect of thrombin-induced pulmonary microembolism on the pulmonary clearance rate of aerosolized 99mTc diethylenetriamine pentaacetic acid (99mTc-DTPA) in awake, chronically prepared sheep. Chest activity was recorded after administration of a 0.44 micron aerosol of 99mTc-DTPA. Decay-corrected data were fit to an exponential and expressed as percent decrease per min (%/min). Sheep were given alpha-thrombin intravenously (80 U/kg for 10 min) 60 min after the aerosol administration. The clearance rate prior to alpha-thrombin was 0.35 +/- 0.05 %/min (mean +/- SEM). During alpha-thrombin administration, the clearance rate increased to 5.84 +/- 0.70 %/min (p less than 0.001 from baseline), but returned to 0.41 +/- 0.06 %/min within 30 min after the end of the thrombin infusion. The increased clearance rate during alpha-thrombin administration was not due to increased lung volume since alpha-thrombin did not change functional residual capacity. Moreover, the clearance rate was unchanged during gamma-thrombin administration, which does not induce coagulation, or during alpha-thrombin challenge in defibrinogenated animals. alpha-thrombin administration in neutrophil-depleted sheep caused a transient increase in DTPA clearance similar to that in control sheep, suggesting that the increase occurred independently of neutrophils. The results indicate that alpha-thrombin causes a large, transient increase in 99mTc-DTPA clearance, which may be the result of increased epithelial permeability. This response is dependent on the activation of intravascular coagulation.  相似文献   

20.
Systemic thickening of capillary endothelial basement membrane underlies the chronic complications of human diabetic microangiopathy. Since 99mTc-DTPA aerosol scintigraphy is a sensitive, non-invasive test of membrane permeability, we decided to study the effect of diabetes on the permeability of lung epithelium in diabetic patients using this test. Fifty (NIDDM) patients, aged 40-70 years, with or without complications, and who were non-smokers, were subjected to evaluation using 99mTc-DTPA aerosol. At the same time, pulmonary function tests, including carbon monoxide diffusion capacity, were done. Normal non-smoking subjects with no history of cardio-respiratory disease, who underwent 99mTc-DTPA and pulmonary function tests, served as controls. The risk factors which included age, sex, degree of control and presence of complications were noted. Twenty-nine (58%) of the patients had abnormal 99mTc-DTPA clearance. Thirty-four percent of the patients with complications and 24% of those without complications had abnormal clearance. Complications recorded included retinopathy, neuropathy and nephropathy. Fifty-five percent of patients with abnormal 99mTc-DTPA had suffered from diabetes for longer than 10 years. Sixty-two percent of patients with poor glycaemic control had abnormal 99mTc-DTPA. Diffusion capacity was not significantly affected in patients with complicated diabetes. Our preliminary results suggest that 99mTc-DTPA is a potentially sensitive test in assessing the degree of lung affection in diabetic patients. No significant correlation exists between diffusion capacity and 99mTc-DTPA. The risk factors did not affect the 99mTc-DTPA clearance, probably due to the small sample size.  相似文献   

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