Effect of bronchodilation on the deposition and clearance of radioaerosol in bronchial asthma in remission.

Radioaerosol inhalation lung cine-scintigraphy and lung function tests were performed on ten patients with bronchial asthma in remission before and after inhalation of salbutamol following intravenously administered aminophylline. Radioaerosol inhalation lung cine-scintigraphy was very useful in revealing the changes not only in the deposition patterns of inhaled aerosol in the lungs but also in the dynamic transport of mucus on the airways. The bronchodilating effect of the combined treatment was significant; the inhaled aerosol deposited more homogeneously and less centrally in the lungs, the "penetration index" and the alveolar deposition ratio (ALDR) increased from 31 +/- 3 to 49 +/- 7%, and from 29 +/- 2% to 39 +/- 1%, respectively, while the airway deposition ratio (ADR) decreased from 72 +/- 2 to 61 +/- 1% immediately after the treatment. Lung function data including FVC, FEV 1.0, FEV 1.0%, MMF, V50 and Vp significantly improved after the treatment. There was, however, little visual or quantitative improvement in mucociliary clearance after the treatment.

Mucociliary clearance and transport in bronchiectasis: global and regional assessment.

Global and regional mucociliary clearance and transport in the lungs was studied in 20 patients with bronchiectasis by radioaerosol inhalation lung cine-scintigraphy and the quantitative analysis following inhalation of ultrasonically-generated 99mTc-tagged human serum albumin aerosol (mass median diameter; 1.93 microns with geometric s.d. of 1.52). In bronchiectatic lung regions, deposition of inhaled aerosol was diminished or inhomogeneous. Transport of inhaled radioactivity from the bronchiectatic regions was deranged in 95% of the patients (19/20). The following abnormal mucous transport patterns were regionally observed; stasis in 12 of the 20 patients (12/20), regurgitation or reversed transport in 14/20, straying in 8/20, spiral or zigzag transport in 1/20, and/or various combinations of these four abnormal transport patterns. When coughs occurred, regurgitation and stray became more marked in the bronchiectatic regions. These regional abnormalities in mucociliary transport seem to be responsible for the development of infections and hemoptysis in the bronchiectatic regions.

Radionuclide venography and its functional analysis in superior vena cava syndrome.

UNLABELLED: In addition to imaging, radionuclide venography maybe used for the functional assessment of superior vena cava (SVC) syndrome by applying the indices of transit time (TT), time of half-peak count (TH) and peak count ratio (PC ratio). METHODS: Ten healthy subjects (Group N) and 107 patients with SVC syndrome (64 symptomatic and 43 asymptomatic) were studied. Images were visually assessed for collaterals or jugular venous reflux and values of the indices were calculated. RESULTS: The 107 patients were subclassified into three groups according to the images obtained. Collateral circulation was seen in 37 patients (Group C). In 20 patients, jugular venous reflux was observed (Group J). Fifty patients who showed neither collaterals nor reflux were included in Group P. In comparison to Group N [3.6 +/- 0.56 see (sem)], TT values were significantly higher (p < 0.05) for Group J (7.13 +/- 1.16 sec) and Group C (7.00 +/- 0.87 sec). Values of TH were significantly prolonged (p < 0.05) for Group J (23.6 +/- 4.8 sec) and Group C (18.8 +/- 2.2 sec) in comparison to Group N (9.2 +/- 1.5 sec). PC ratio values were higher in all patient groups in comparison to Group N (3.4 +/- 0.57). CONCLUSION: These indices are potentially useful in the initial diagnosis and post-therapeutic evaluation of SVC syndrome. In the absence of other causes, appearance of jugular venous reflux may be considered a sign of SVC syndrome.

Difference in inhaled aerosol deposition patterns in the lungs due to three different sized aerosols.

Deposition patterns of inhaled aerosol in the lungs were studied in five normal subjects and 20 patients with lung disease by inhaling radioaerosols with three different particle size distributions. These aerosols were generated from BARC, UltraVent, and Mistogen-EN-142. Particle size distributions generated by these three nebulizers were 0.84, 1.04 and 1.93 microns in activity median aerodynamic diameter (AMAD) with its geometric standard deviation (sigma g) of 1.73, 1.71 and 1.52, respectively. Deposition patterns of inhaled aerosols were compared qualitatively and quantitatively by studying six different parameters: alveolar deposition ratio (ALDR), Xmax, Xmean, standard deviation (S.D.), skewness and kurtosis of the radioactive distribution in the lungs following inhalation. It has been found that aerosol deposition patterns varied with particle size. The unevenness of aerosol deposition, Xmax, Xmean and the number of 'hot spots' became more prominent with the increase in particle size, whereas values of ALDR and S.D. decreased as particle size increased. Knowing these deposition characteristics would facilitate a judicious application of aerosol inhalation to medical use.

Technegas for inhalation lung imaging.

Technegas, an aerosol generator recently devised in Australia, produces aerosol particulates called 'technegas' which have characteristics of both an aerosol and a gas. The majority of the particulate is below 200 nm in size as measured by electron microscopy. Four normal subjects and 31 patients with various lung diseases were studied by imaging the lungs following inhalation of technegas. The penetration of inhaled technegas to the lung periphery was excellent; the average alveolar deposition ratio (ALDR) was 85%. Comparative studies with lung images obtained either with an ultrasonic nebulizer or jet nebulizers also confirmed better penetration of inhaled technegas to the lung periphery. There was no significant statistical difference in the ALDRs between normals and patients. Aerosol studies were comparable to perfusion counterparts, and evaluation of regional ventilatory status was greatly facilitated. Because of the large ALDR and the low airway deposition ratio (ADR), actual imaging could be done not only immediately after aerosol inhalation but also some time later without losing too much radioactivity from the lungs. One disadvantage was that technegas immediately after generation was anoxic.

Inhalation of pertechnegas: similar clearance from the lungs to that of inhaled pertechnetate aerosol.

It has been reported that the inhalation of pertechnegas (TGO3) generated under an atmosphere of 3% oxygen (O2) in argon (Ar) instead of 100% Ar without O2 in the technegas generator, offers a simple but accurate quantification of clearance from the lungs, permitting it to be used in place of 99Tcm-diethylenetriamine pentaacetic acid (DTPA). The disappearance from the lungs of inhaled TGO3 was so similar to that of inhaled pertechnetate aerosol (TcO4) in this study, that there was neither a statistically significant difference in the clearance half-time (t1/2), nor a difference in the lung images between them. Neither TGO3 nor TcO4 inhalation could distinguish smokers from non-smokers using t1/2. When inhaled, TGO3 appears to behave in a similar manner to TcO4 in the lungs and hence cannot be used in place of 99Tcm-DTPA in clinical practice.

Incidence of pulmonary embolism in a chest hospital in Japan and importance of preoperative perfusion lung imaging in the diagnosis of postoperative pulmonary embolism.

The incidence of pulmonary embolism was retrospectively studied in a University Chest Institute and its affiliated hospital in Sendai, Japan, whose annual numbers of discharged patients from chest medical wards and lung operations as a whole are about 600 and 400, respectively. Before 1975 there was no documented patient with pulmonary embolism. Since then 70 patients had been clinically suspected of having pulmonary embolism and 31 of the 70 were diagnosed as having pulmonary embolism; 15 without and 16 with surgical operations in the immediate past. Fourteen of the 31 patients required combined perfusion and aerosol inhalation lung imaging for diagnosis. Twelve postoperative patients could be diagnosed as pulmonary embolism by comparing postoperative perfusion lung images taken at the time of suspicion with preoperative perfusion counterparts. Although it is said to be rising, the incidence of pulmonary embolism in a chest hospital still seems to remain low compared with that in western countries. For postoperative patients, comparison with preoperative studies was found very useful in diagnosing postoperative pulmonary embolism. The importance of preoperative perfusion lung imaging cannot be overstressed not only as a preoperative lung function test but as a baseline study to be compared with postoperative perfusion images when pulmonary embolism is clinically suspected in postoperative patients.

Mucociliary clearance in pulmonary vascular disease.

The mucociliary clearance function was studied by radioaerosol inhalation lung cinescintigraphy and its quantification in 8 patients with pulmonary vascular diseases; pulmonary embolism, 5 cases, and right pulmonary artery hypoplasia, pulmonary arteriovenous fistulas, aortitis syndrome, 1 case each. The mucociliary clearance function was found to be well maintained in pulmonary vascular diseases unless ventilation was disturbed. There was no difference in the mucociliary clearance function between pulmonary embolism and other pulmonary vascular diseases.

Technegas versus krypton-81m gas as an inhalation agent. Comparison of pulmonary distribution at total lung capacity.

Exactly how the pulmonary distribution of inhaled radioactive gas and Technegas, or ultra-small aerosol particulates, differs from each other, is still uncertain. The authors compared the distribution of inhaled Kr-81 m gas and Technegas in the lungs at total lung capacity in 13 control subjects with no clinical conditions and 13 patients with various chest diseases. In normal lungs, there was no difference in the distribution ratios in the right and left lungs between inhaled Kr-81m gas and Technegas. However, there was a significant difference in the lungs of patients with pulmonary disease. Technegas tended to deposit more in the lung bases than did Kr-81m gas. Despite these statistical differences, they were visually, or qualitatively, similar. From a practical and clinical standpoint, Technegas seems to be useful as an inhalation agent, unless quantitative analyses are required.

[Radioaerosol inhalation lung imaging using technegas].

Technegas generator using 99mTc-pertechnetate was tested on 4 normal subjects and 31 patients with various chest diseases including bronchogenic carcinoma, pneumonia, pulmonary tuberculosis, sarcoidosis, and so on. Technegas was inhaled from the RV to the TLC levels through the mouth with the nose clipped followed by breath-holding. Three deep breaths were enough to deposit 37-55.5 MBq (1 to 1.5 mCi) of technegas in the lungs. The average alveolar deposition ratio (ALDR) was 85% and penetration of inhaled technegas to the lung periphery was excellent. "Hot spots" or excessive radioactive deposition were also seen when there was airway obstruction. The former indicated the characteristic as gas and the latter, that as aerosol particles. Because of the large ALDR's the timing for imaging lungs after inhalation of technegas most likely indicated the intrapulmonary sites of effective ventilation, because respective inhalation and perfusion lung images resembled each other very much. The disadvantage of technegas was that it was anoxic right after generation.

Does a beta 2-stimulator really facilitate mucociliary transport in the human lungs in vivo? A study with procaterol.

The purpose was to study whether procaterol, a beta 2-stimulator, facilitated mucociliary transport on the ciliated airways in the human lungs. From immediately after inhalation of [99mTc]albumin aerosol, radioactivity of the thorax was continuously measured anteriorly by a gamma camera with the examinee in the supine position; the data were sequentially stored in a computer in 10-s frame mode. Three puffs (30 micrograms) of procaterol were inhaled from a metered dose inhaler at 60 min in the same supine position, and measurement of radioactivity was continued for 30 min more. Spirometry was performed before and after the measurement of radioactivity. A group of 8 normal subjects and 34 patients with various lung diseases, including 6 with bronchial asthma in remission, were studied. In addition to observation of mucus transport on the large airways by radioaerosol inhalation lung cinescintigraphy, the time-activity curve from the right lung was evaluated and the quantitative parameters for evaluating mucociliary clearance were calculated for the right lung. Following inhalation of procaterol, there were neither significant acceleration in mucus transport on the large airways by cinescintigraphy nor significant changes in the slope of time-activity curves. Quantitative parameters did not show any significant changes either, although spirometry indicated significant bronchodilation. We conclude that three puffs of inhaled procaterol neither necessarily accelerate mucus transport nor facilitate mucociliary clearance in the human lung.

[Pulmonary epithelial permeability in rats with bleomycin-induced pneumonitis].

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.

A case of pulmonary hyalinizing granuloma.

A case of pulmonary hyalinizing granuloma was presented. The patient was a 37-year-old male who was found to have abnormal chest roentgenograms showing multiple pulmonary nodules taken at the annual chest mass survey in October 1989. The largest nodule measured 35 mm in diameter. He was asymptomatic. No definite diagnosis was established either by brushing cytology, biopsy through bronchoscopy or percutaneous needle biopsy. No abnormalities were found in the GI tract, the urogenital system or the bone. Brain CT indicated an iso-density area surrounded by low density in the left fronto-parietal region. Two nodules of the lingula removed by open lung biopsy revealed a homogeneous cut surface. Histological diagnosis was pulmonary hyalinizing granuloma, consisting of hyalinized collagen fibers and bundles infiltrated with chronic inflammatory cells. No therapeutic effect was recognized with prednisolone. Craniotomy was performed and the brain lesion was removed. Anaplastic astrocytoma was the diagnosis. The brain lesion had no etiological correlation with pulmonary hyalinizing granuloma. Pulmonary hyalinizing granuloma itself is a rare benign disease with no specific therapy and is important in the differential diagnosis of lung diseases showing multiple pulmonary nodules.

[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.

Effect of respiratory phases and gravity on mucociliary transport in the normal lungs.

Effect of gravity and respiratory phase on mucociliary transport was studied in 11 normal subjects. After inhaling 99mTc-human serum albumin aerosol, each subject was positioned in right lateral decubitus and then supine position before a scintillation camera. Data in list mode and simultaneous respiratory curve were stored in a computer for 15 min each. The respiratory curve was sequentially marked at the beginning of inspiration, expiration and pause of each respiratory cycle and list mode data was converted into frame mode, respectively. The frame mode data was then sequentially connected according to the respective respiratory phase. The data in count-per-second from each lungs versus time was fitted to a straight line by regression analysis and the slope of the line was compared with each other for respective respiratory phase. Slopes of net radioactivity changes in the right and left lungs were compared to evaluate gravity effect. Neither respiratory phases nor gravity had any significant effect on mucociliary transport. Theoretical calculations have also supported the present findings.

Establishment of a cell line from an adenocarcinoma of the lung producing carcinoembryonic antigen (CEA) and CA19-9.

An adenocarcinoma cell line was established from pleural effusion of a 67-year-old woman and designated as TK-SA. The population doubling time of the cells was 100.4 hr. Chromosomal analysis revealed the TK-SA to have human aneuploid chromosomes with a near-triploid mode. Ultrastructurally, the TK-SA was compatible with adenocarcinoma. The cell line was highly tumorigenic. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye assay demonstrated resistance of the cell line to Cis-platin (CDDP), Cyclophosphamide (CPM) and Tegafur/Uracil (UFT). High carcinoembryonic antigen (CEA) and CA19-9 levels were similar in patient's serum and conditioned medium.

Normal values for quantitative parameters for evaluation of mucociliary clearance in lungs.

Twenty-eight normal male subjects (13 nonsmokers and 15 smokers, 25 to 76 years of age) inhaled ultrasonically generated 99mTc-tagged human serum albumin aerosol (mass median diameter: 1.93 microns with geometric standard deviation of 1.52) and radioactivity from the thorax was measured continuously from anteriorly in 10 sec frame mode for 90 to 120 min to evaluate mucociliary clearance function in the lungs. Normal values for lung retention ratio (LRR), airway deposition ratio (ADR), airway retention ratio (ARR), airway clearance efficiency (ACE), alveolar deposition ratio (ALDR), and disappearance rate of radioactivity from the ciliated airways (DR) were presented. ALDR was significantly larger in nonsmokers than in smokers. LRR and ARR were significantly smaller and ACE, significantly larger in smokers at any time intervals than in nonsmokers, while ADR and DR were larger in smokers only in the initial 30 min following radioaerosol inhalation was completed. Thereafter there was little difference in ADR and DR between normal smokers and nonsmokers.

[Changes in pulmonary epithelial permeability due to thoracic irradiation].

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.