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.     

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.     

Usefulness of Technetium-99m Hexamethylpropylene Amine Oxime Lung Scan to Detect Subclinical Lung Injury in Patients with Chronic Renal Failure

We used technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) lung scan to detect subclinical lung injury in patients with chronic renal failure (CRF), on regular hemodialysis (HD), who had normal chest X-ray findings (CXR) and pulmonary function test (PFT). The degree of pulmonary vascular endothelium damage was represented as lung/liver uptake ratios (L/L ratios) calculated by Tc-99m HMPAO lung scan. The L/L ratios of the 20 male CRF patients on HD with normal CXR and PFT were compared with those of the 20 male normal controls. The results show that the L/L ratios on Tc-99m HMPAO lung scans were significantly higher in CRF patients on HD (1.06 ± 0.55) than those in normal controls (0.34 ± 0.09). Using a cut-off value of 0.50, 18/20 [90%] CRF patients had abnormally increased L/L ratios. Our findings concluded that the pulmonary vascular endothelium damage represented as significantly increased L/L ratios on Tc-99m HMPAO lung scan in CRF patients on HD with normal CXR and PFT. In addition, Tc-99m HMPAO lung scan has the potential to be a sensitive, objective and noninvasive method to detect subclinical lung injury of CRF patients on HD, which is different from the traditional studies such as CXR or PFT.     

Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

Pulmonary radioaerosol clearance rate of 99mTc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with 67Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (including 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).     

Mixed infiltrative and obstructive disease on high-resolution CT: differential diagnosis and functional correlates in a consecutive series

Fourteen of 400 consecutive patients having high-resolution computed tomography (HRCT) with expiratory images showed findings of infiltrative lung disease on inspiratory HRCT and air trapping on expiratory CT. Diagnoses included hypersensitivity pneumonitis, sarcoidosis, atypical infection, and pulmonary edema. The extent of infiltrative abnormalities and air trapping were correlated with pulmonary function tests (PFT) in 11 patients. PFT indicated a mixed pattern in five, an obstructive pattern in three, and a restrictive pattern in three. Forced expiratory volume (FEV) in 1 second/forced vital capacity (FVC) correlated significantly with the extent of air-trapping (r = 0.60; p = 0.05). The extent of infiltrative abnormalities correlated significantly and negatively with forced vital capacity (r = -0.82, p = 0.002), FEV1 (r = -0.59, p = 0.05), total lung capacity (TLC) (r = -0.67, p = 0.05), and DLCO (r = -0.75, p = 0.02). Findings of lung infiltration on inspiratory HRCT scans and air trapping on expiratory CT correlated respectively with PFT measures of restrictive and obstructive lung disease.     

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)     

Usefulness of techntium-99m hexamethylpropylene amine oxime lung scan to detect subclinical lung injury in patients with noninsulin-dependent diabetes mellitus

In this study, we employed techntium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) lung scan to detect subclinical lung injury of patients with noninsulin-dependent diabetes mellitus (NIDDM) who had normal chest X-ray findings (CXR) and pulmonary function test (PFT). The degree of pulmonary vascular endothelium damage was represented as lung/liver uptake ratios (L/L ratios) calculated by Tc-99m HMPAO lung scan. The L/L ratios of the 20 male NIDDM patients with normal CXR and PFT were compared with those of the 20 male normal controls. The results show that the L/L ratios on Tc-99m HMPAO lung scan were significantly higher in NIDDM patients than those in normal controls. Using a cutoff value of 0.50, 17 of the 20 (85%) NIDDM patients had abnormally increased L/L ratios. Our findings concluded that the pulmonary vascular endothelium damage represented as significantly increased L/L ratios on Tc-99m HMPAO lung scan in NIDDM patients with normal CXR and PFT. In addition, Tc-99m HMPAO lung scan has the potential to be a sensitive, objective, and noninvasive method to detect subclinical lung injury of patients with NIDDN, which are different from the traditional studies such as CXR or CFT.     

Bosentan in pulmonary arterial hypertension secondary to scleroderma

OBJECTIVE:. To assess the efficacy and tolerability of bosentan in pulmonary arterial hypertension secondary to systemic sclerosis (SSc-PAH) including patients with restrictive lung disease. METHODS: We retrospectively reviewed 23 SSc-PAH patients with PAH at baseline [PA systolic pressure (PASP) >or= 45 mm Hg by echocardiogram or mean PA pressure > 25 mm Hg at rest by cardiac catheterization], World Health Organization (WHO) functional classes II-IV, and with data available for 18 months. Bosentan dose was 62.5 mg twice daily for 1 month then 125 mg twice daily. Outcomes were WHO functional class, PASP, and pulmonary function tests (PFT) at 3-month intervals for 18 months. RESULTS: WHO class at baseline 3.1 +/- 0.1 (mean +/- SE); 3 months, 2.5 +/- 0.2*; 6 months, 2.4 +/- 0.2*; 9 months, 2.5 +/- 0.2* (*p < 0.02 vs baseline, n = 21 to 23), indicating clinical improvement at 9 months. After 9 months, results were not significant versus baseline. Reduction in WHO class by at least one rank was 57% at 3 months; none worsened. After 9 months, WHO class tended to worsen compared to baseline. Baseline PASP was 54 +/- 2 mm Hg (n = 23) and did not change significantly with therapy. Restriction (total lung capacity 76% +/- 4% of predicted) and reduced diffusing capacity (39% +/- 3% of predicted) were unchanged during therapy. Abnormal transaminases in 2 patients (9%) necessitated discontinuing drug in both. CONCLUSION: Bosentan is clinically beneficial in patients with SSc-PAH including patients with restrictive lung disease, but pulmonary hemodynamics and PFT results remained stable during treatment.     

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.     

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.     

Pulmonary permeability in coeliac disease and inflammatory bowel disease

Respiratory disease and subclinical pulmonary abnormalities are recognised complications of both coeliac disease (CD) and inflammatory bowel disease (IBD) but the pathogenesis of the lung disease remains uncertain. We have studied lung function, including permeability measured by clearance of inhaled technetium-99m diethylene triamine pentaacetic acid in 25 patients with IBD, 18 patients with CD on a gluten-free diet, and in 20 normal controls, all without respiratory symptoms. In IBD there was evidence of obstruction to airflow (mean forced expiratory volume in 1 s/forced vital capacity equals 75.8%, control 81%; p less than 0.05) but no change in pulmonary permeability (half-time clearance equals 70.3 vs. 69.2 min). In CD airflow was not significantly different from control (forced expiratory volume in 1 s/forced vital capacity equals 80%) but there was an increase in pulmonary permeability (half-time clearance equals 48.9 min; p less than 0.01). These findings suggest that the mechanisms of lung disease in CD differs from that in IBD and supports the hypothesis of a common mucosal defect in lung and small intestine in CD allowing increased permeability.     

Pulmonary clearance of 99mTC-DTPA aerosol in patients with silicosis]

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.     

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.     

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.     

Clearance of 99mTc-DTPA in pigeon fancier's hypersensitivity pneumonitis.

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.     

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 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)     

Membrane and capillary blood components of diffusion capacity of the lung for carbon monoxide in pulmonary sarcoidosis: relation to exercise gas exchange

BACKGROUND: Resting pulmonary diffusing capacity of the lung for carbon monoxide (DLCO) is known to be the best predictor of arterial desaturation during exercise in patients with sarcoidosis. However, the relative contribution of each of the two components of DLCO-alveolar membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc)-remains unclear. STUDY OBJECTIVES: To evaluate which component is responsible for the decrease of resting DLCO in patients with sarcoidosis, and to determine which resting pulmonary function test, including Dm and Vc, is the best predictor of gas exchange abnormalities during submaximal exercise. DESIGN: Prospective analysis of patients referred to our department of respiratory medicine. PATIENTS: Twenty four patients with pulmonary sarcoidosis were separated into two groups according to chest radiographic findings: group 1, stages 2 and 3 (n = 15); group 2, stage 4 (n = 9). All the patients completed pulmonary function tests (flows, volumes, single-breath DLCO, transfer coefficient [Ka], Dm, Vc) and submaximal exercise (two steady-state levels of mild and moderate exercise corresponding respectively to a target oxygen consumption of approximately 10 to 15 mL/min/kg). RESULTS: DLCO was reduced in the two groups (group 1, 63 +/- 16% of predicted; group 2, 64 +/- 16% of predicted). Dm was severely decreased (group 1, 58 +/- 24% of predicted; group 2, 51 +/- 15% of predicted), whereas Vc was unchanged or only mildly decreased (group 1, 81 +/- 18% of predicted; group 2, 85 +/- 28% of predicted). Whatever the group of patients and the exercise level, Dm and DLCO were the strongest predictors (p < 0.001) of gas exchange abnormalities. Ka or volumes were weak predictors, and Vc or flows were not related with exercise gas exchange. CONCLUSIONS: This study demonstrates that a decrease in Dm mostly accounts for resting DLCO reduction, and that Dm as well as DLCO are highly predictive of gas exchange abnormalities at exercise in patients with sarcoidosis.     

Technetium 99m-diethylene triamine penta-acetic acid aerosol clearance in the evaluation of pulmonary involvement in sickle cell disease

BACKGROUND: Pulmonary clearance of inhaled technetium (Tc) 99m-labeled diethylene triamine penta-acetic acid (DTPA) aerosol is a sensitive non-invasive marker of alveolar permeability and patients with interstitial lung diseases show enhanced clearance. However, a previous study in adult patients with diabetes mellitus showed delayed clearance. OBJECTIVES: To investigate DTPA clearance in steady-state, otherwise healthy adult sickle cell disease (SCD) patients and correlate it with pulmonary function tests (PFTs), hematologic and clinical parameters. MATERIALS AND METHODS: The subjects were randomly selected from the Hematology Clinic of Mubarak Hospital, Kuwait. Hematologic and pulmonary function data were collected with standard methods. DTPA radio-aerosol clearance studies were performed using ultrafine nebulizer containing 35 mCi (1295 MBq) of Tc 99m-DTPA in its reservoir and t(1/2) clearance in minutes was determined. Average values for both lungs were calculated and compared with normal values for our population. RESULTS: Forty-three subjects (24 SS and 19 S-beta(0)thal) aged between 16 and 45 yr (mean of 27.1 +/- 9.7) were studied. Twenty-two subjects (51.2%) had delayed, while only 10 (23.3%) showed enhanced DTPA clearance. Patients with enhanced clearance showed better PFTs than those with normal or delayed clearance. There was significant negative correlation of DTPA clearance with forced expiratory volume in 1 s, forced vital capacity and total lung capacity and significant positive correlation with age. CONCLUSIONS: Majority of adult SCD patients have delayed DTPA clearance unlike in inflammatory lung diseases, but similar to diabetes mellitus. DTPA clearance may be a useful modality for monitoring pulmonary involvement in SCD.