The effect of airway deposition on the assessment of lung injury by 99mTc-DTPA clearance--lung injury in interstitial lung diseases assessed by using the duplicated 99mTc-DTPA aerosol inhalation method

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.     

A comparison of 99mTc-DTPA and 113mIn-DTPA aerosol clearances in humans. Effects of smoking, hyperinflation, and in vitro oxidation

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)     

Assessment of pulmonary epithelial permeability in interstitial lung diseases]

The pulmonary epithelial permeability of 99mTc-DTPA (diethylene triamine penta acetate) was assessed in patients with interstitial lung diseases including radiation pneumonitis, idiopathic interstitial pneumonia/pulmonary fibrosis, sarcoidosis, unclassified interstitial pneumonia, and in healthy subjects. Pulmonary epithelial permeability was estimated by the rate constant (kep) of inhaled 99mTc-DTPA 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 an increase in kep. This increase correlated with their cigarette consumption per day, but was reversible after cessation of smoking. The provocative concentration of histamine to decrease FEV 1.0 by more than 20% caused an increase in epithelial permeability. However, its effect on permeability was transient, limited, and not dose-dependent. During lung inflation by continuous external negative pressure or by positive end-expiratory pressure, pulmonary 99mTc-DTPA clearance was increased, suggesting changes in epithelial permeability. The patients with diffuse interstitial lung diseases also showed increased permeability compared with healthy nonsmokers. In the patients with pre-existing radiation pneumonitis, the mean kep value obtained from the area with infiltration on chest X-ray films was significantly higher than that from the opposite lung. In the prospective study, 3 of 11 patients developed radiation pneumonitis during the course of radiation therapy. The mean kep value obtained in the 3 patients who developed radiation pneumonitis increased just before onset, and further increased when the disease manifested clinically. We believe that 99mTc-DTPA aerosol inhalation is a sensitive test for the detection of inflammatory changes in the bronchioalveolar epithelium.     

Effect of pattern of aerosol inhalation on clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid from the lungs of normal humans.

The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of 99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (Vtidal) or multiple vital capacity maneuvers (VVC). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following VVC at 30 min equaled 1.36 +/- 0.55%/min compared with 0.83 +/- 0.25%/min for Vtidal (p less than 0.025). VVC inhalations resulted in a larger fast compartment of 16 +/- 12% compared with 3 +/- 2% with tidal breathing (p less than 0.01). The least intrasubject variability with coefficient of variation (CV) of +/- 18% was obtained with monoexponential analyses after Vtidal during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with Vtidal gave the least scatter between subjects, with CV of +/- 30%. These data show that simple tidal inhalations of 99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 +/- 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery VVC suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of 99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing.     

Pulmonary epithelial permeability in ARDS and cardiogenic pulmonary oedema

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.     

Increased airway mucosal permeability of smokers. Relationship to airway reactivity

We studied pulmonary epithelial permeability and bronchial reactivity in 10 smoking and 8 nonsmoking adults. Permeability was measured as the disappearance half-life (T 1/2) of aerosolized 99mTc-DTPA from the lungs, and a permeability index (PI) calculated that reflected the appearance of the tracer in the blood. Smokers had increased permeability with a T 1/2 of 44.6 +/- 12.2 min and PI values at 10, 25, and 60 min of 27.3 +/- 13.2, 32.5 +/- 10.2, and 34.3 +/- 9.9, compared with those in nonsmokers with a T 1/2 of 110.0 +/- 62.7 min and PI values of 9.4 +/- 5.7, 14.9 +/- 8.3, and 23.1 +/- 9.0. Bronchial reactivity to histamine was measured with and without prior exposure to aerosolized propranolol (to achieve beta-blockade of airway smooth muscle). Reactivity increased significantly (p less than 0.001) in both groups after beta-blockade, but no difference was found between smokers and nonsmokers. Despite the increased permeability in smokers, there was no evidence of increased reactivity.     

Permeability changes in bronchiolo-alveolar epithelium

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.     

Lung inflammation in coal miners assessed by uptake of 67Ga-citrate and clearance of inhaled 99mTc-labeled diethylenetriamine pentaacetate aerosol.

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)     

Ozone exposure increases respiratory epithelial permeability in humans

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.     

Assessment of alveolar epithelial permeability in progressive systemic sclerosis (PSS) using 99mTc-DTPA (diethylene triamine penta acetate) aerosol inhalation]

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.     

Fibrinogen depletion and control of permeability in oleic acid lung injury

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.     

Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to 99mTc-DTPA

Respiratory epithelial clearance of 99mTc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of 113mIn-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stable during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.     

Comparison of lung vascular and epithelial permeability indices in the adult respiratory distress syndrome

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.     

Pulmonary epithelial clearance of 99mTc-DTPA after thrombin-induced pulmonary microembolism

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.     

Increased lung clearance of 99mTcDTPA in allograft lung rejection. The Paris-Sud Lung Transplant Group.

To investigate whether lung 99mTc-DTPA clearance is altered during allograft lung rejection, a group of four double lung and 24 heart-lung transplant patients was studied using serial measurement of the clearance rate of aerosolized 99mTc-DTPA (DTPA-Cl), in association with pulmonary function tests, bronchoalveolar lavage, and transbronchial lung biopsies. Using histologic diagnosis as a standard, we compared 56 episodes with normal lung histology to 32 episodes with allograft lung rejection. A control group of 20 healthy nonsmokers was used to define normal DTPA-Cl. In patients with normal lung histology, DTPA-Cl was higher than in control subjects (2.62 +/- 0.25 versus 1.20 +/- 0.12 %/min; p less than 0.001). In the episodes of allograft lung rejection, DTPA-Cl increased to 3.65 +/- 0.41 %/min (p less than 0.02) as compared with episodes of normal lung histology. The change in DTPA-Cl during allograft lung rejection was correlated (r = 0.3, p less than 0.01) with the increased percentage of lymphocytes in bronchoalveolar lavage (27.8 +/- 3.5% in rejection versus 19.9 +/- 2.2% in normal histology; p less than 0.02). Sensitivity and specificity of DTPA-Cl measurement in detecting lung rejection were 69 and 82%, respectively, versus 45 and 85% for FEV1 measurement. These results suggest that DTPA-Cl monitoring could be used in conjunction with pulmonary function testing as a noninvasive approach for the detection of lung rejection.     

Permeability of the bronchial mucosa to 99mTc-DTPA in asthma

Previous investigators, using 99mTc-DTPA aerosol as a marker to assess epithelial permeability in asthma, did not find an increased permeability in this group. However, they either failed to deliver the aerosol to the optimal site (bronchial mucosa, not alveoli) or failed to account for mucociliary clearance in analyzing their results. We studied 10 asthmatics and eight age-matched control subjects using a dosimeter (Spira-Elektra 2) and a carefully controlled breathing pattern to deliver aerosol to the subjects' airways. Two aerosols were delivered on separate days in each patient; 99mTc-DTPA aerosol, and 99mTc-HSA (human serum albumin), using similar breathing patterns to ensure reproducibility of the deposition pattern with the two aerosols. From measurements of retention versus time over a 1-h period, rate constants Ktot and Km were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modelling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. There was no significant difference between Ktot in normal subjects and asthmatics; however, because of the slower mucociliary clearance in the asthmatic group, and the relative importance of mucociliary clearance in determining the washout of 99mTc-DTPA aerosol, there was a significant difference in airway permeability between the normal subjects and the asthmatics (t1/2 = 296 min +/- 141 SD and 126 min +/- 58, p less than 0.01, in normal subjects and asthmatics, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of 99mTc-DTPA and urea for measuring cefepime concentrations in epithelial lining fluid.

The efficacy of antimicrobial agents against pulmonary infections depends on their local concentrations in the lung. The aims of the present study were to: 1) compare technetium-99m diethylenetriaminepenta-acetic acid (99mTc-DTPA) and urea as markers of epithelial lining fluid (ELF) dilution for measuring ELF concentrations of pharmaceuticals; 2) quantify ELF cefepime concentrations in normal and injured lung; and 3) measure the increase in permeability to cefepime following oleic acid-induced acute lung injury. A modified bronchoalveolar lavage technique, based on equilibration of infused 99mTc-DTPA, was used to measure ELF volume. Cefepime was administered intravenously at steady plasma levels. Six serial bronchoalveolar lavages were performed 5 h after the beginning of infusion. ELF to plasma cefepime concentration ratios were 95 +/- 17 and 100 +/- 14.5% in normal and injured lung respectively. When urea was used as marker, cefepime concentration ratios were underestimated at 16.4 +/- 2.7 and 73.9 +/- 8.4% respectively. Cefepime blood/ airspace clearance increased from 3.8 +/- 0.7 micro x min(-1) in controls to 39.8 +/- 4.9 microL x min(-1) in acute lung injury. It was concluded that: 1) cefepime concentrations in epithelial lining fluid were in equilibrium with those in plasma in both normal and injured lung after 5 h at steady plasma concentrations; 2) epithelial lining fluid cefepime concentration by the urea method was much less underestimated in injured versus normal lung; and 3) acute lung injury induces a 10-fold elevation of cefepime blood/airspace clearance.     

Pulmonary epithelial permeability in normal subjects and patients with idiopathic interstitial pneumonia]

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.     

Respiratory clearance of 99mTc-DTPA and pulmonary involvement in sarcoidosis

To investigate the relationships between the respiratory epithelial clearance of micronic aerosolized 99mTc-DTPA (RC-DTPA) and pulmonary function, serum angiotensin-converting enzyme (SACE), and lymphocytic alveolitis in patients with sarcoidosis, RC-DTPA was measured in 49 nonsmokers with pulmonary sarcoidosis and 38 normal nonsmokers. Pulmonary involvement was evaluated on chest roentgenograms (type O = normal, type I = hilar adenopathies, type II = hilar adenopathies associated with parenchymal shadows, type III = parenchymal shadows without adenopathy) and by pulmonary function tests. Serum angiotensin-converting enzyme was determined, and a bronchoalveolar lavage was performed for alveolar lymphocyte differential counting (Ly%). RC-DTPA was increased (greater than or equal to 1.96%/min) in 12 of 31 patients with type II or III involvement but was normal in all 18 patients with type O or I involvement (p = 0.002). Patients with increased RC-DTPA had low FVC, TLC, FEV1, and resting Pao2 (p less than 0.05); resting and exercise AaPo2 were increased (p less than 0.05), but RC-DTPA correlated negatively with FEV1 (p less than 0.01), Pao2 at rest (p less than 0.005), and DLCO (p less than 0.05) and positively with resting and exercise AaPO2 (p less than 0.01). In patients with increased RC-DTPA (42 +/- 17%), Ly% did not differ from Ly% in patients with normal RC-DTPA (34 +/- 16%). SACE was increased in patients with increased RC-DTPA (56 +/- 26 U/ml versus 38 +/- 16 U/ml; p = 0.007) and correlated positively with RC-DTPA (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapidly reversible alterations of pulmonary epithelial permeability induced by smoking

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.