SPET of a computerised model of diffuse lung disease.

Emphysema is a common and debilitating disease that is the commonest cause of end-stage respiratory failure. Treatment is either by lung transplantation or by lung volume reduction surgery (LVRS) that improves the biomechanics of respiration. Patient selection for LVRS hinges on the demonstration of heterogeneous disease, predominantly involving the upper lobes, as a good surgical outcome is most likely in these patients. We used a virtual model of lung scintigraphy to compare planar with tomographic scintigraphy for the detection of diffuse lung disease. Lesions of the magnitude of the lung acinus, as well as larger and smaller lesions, were distributed throughout the lungs in volumes from 2% to 50%. Single-photon emission tomography does not add incremental value to planar images for the detection of diffuse lung disease.

Single-photon emission tomography of a computerised model of pulmonary embolism.

Planar pulmonary scintigraphy is currently the standard investigation for the diagnosis of pulmonary embolism. There are a number of problems with the technique, particularly in patients with an intermediate scan report under the PIOPED criteria. The technique is also under threat from the increasing use of spiral CT angiography. A putative improvement may be gained by use of tomography. The incremental value of tomography over planar studies was therefore evaluated in a virtual model of pulmonary scintigraphy. A model of the segmental anatomy of the lungs was developed from computed tomography, cadaveric human lungs and available anatomical texts. Counts were generated within the phantom by Monte Carlo simulation of photon emission. Eighteen single segmental lesions were interspersed with 47 subsegmental defects and displayed on an Icon reporting station. These were presented in the transaxial, sagittal and coronal planes to four experienced reporters to obtain assessment of defect size. Planar studies of the same defects were displayed to the same observers in the standard eight views with a normal study for comparison. With planar studies, the accuracy of estimation of defect size was 51% compared with 97% using tomographic studies. Defects in the medial basal segment of the right lower lobe were not identified in planar studies but were easily seen by all observers in the tomographic study. It is concluded that there is marked improvement in the accuracy of determination of defect size for tomographic studies over the planar equivalents. This is especially important in the lung bases, the most common reported site of pulmonary emboli. Tomography permits visualisation of defects in the medial basal segment of the right lung, which are not seen in planar studies.

Inhalation of dry powder mannitol improves clearance of mucus in patients with bronchiectasis.

Bronchiectasis is a disease characterized by hypersecretion and retention of mucus requiring physical and pharmacologic treatment. Recently we reported that inhalation of dry powder mannitol markedly increases mucociliary clearance (MCC) in asthmatic and in healthy subjects (Daviskas, E., S. D. Anderson, J. D. Brannan, H. K. Chan, S. Eberl, and G. Bautovich. 1997. Inhalation of dry-powder mannitol increases mucociliary clearance. Eur. Respir. J. 10:2449-2454). In this study we investigated the effect of mannitol on MCC in patients with bronchiectasis. Eleven patients 40 to 62 yr of age inhaled mannitol (approximately 300 mg) from a Dinkihaler. MCC was measured over 90 min, in the supine position, on three occasions involving: mannitol or control or baseline, using a radioaerosol technique. On the control day patients reproduced the breathing maneuvers and the number of coughs induced by the mannitol. Mannitol significantly increased MCC over the 75 min from the start of the intervention compared with control and baseline in the whole right lung, central, and intermediate region. Mean (+/- SEM) clearance with mannitol was 34.0 +/- 5.0% versus 17.4 +/- 3.8% with control and 11.7 +/- 4.4% with baseline in the whole right lung (p < 0.0001). The mean number of coughs induced by mannitol was 49 +/- 11. In conclusion, inhalation of dry powder mannitol increased clearance of mucus and thus has the potential to benefit patients with bronchiectasis.

Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic acid generated and delivered by a novel system (AERx) in healthy subjects.

Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous radioaerosols generated by a novel aerosol delivery system (AERx) was studied in six healthy subjects using both planar and single-photon emission tomography (SPET) imaging. AERx is a microprocessor-controlled, bolus inhalation device that is actuated at pre-programmed values of inspiratory flow rate and volume. The aims of the study were to determine the effects of posture and inhaled volume upon deposition of the aerosol in the lungs. Each subject inhaled the radioaerosol in two positions (supine vs sitting) and with two inspiratory manoeuvres [vital capacity (VC) vs "fixed volume" of 1 l above functional residual capacity]. Simultaneous transmission-emission planar and tomographic images were acquired. The results showed diffuse deposition of the aerosol in the lung. Neither the breathing manoeuvre nor the posture was found to affect the distribution of the aerosol as measured by the ratio of the activity (counts per pixel) in the peripheral:central (penetration index, PI) or in the apex:base regions of the planar lung images (P>0.1). A small, albeit statistically significant, difference in PI (P<0.03) was found between VC and fixed volume sitting manoeuvres with SPET only. The PI values themselves indicate that the radioaerosol was well distributed in the lung, with the periphery having 45%-64% of the activity of the central region. Superposition of transmission SPET lung outline on emission SPET visually confirmed the excellent peripheral deposition of the aerosol. The AERx system showed high efficiency of delivery, with approximately 50% of the extruded dose in the device depositing in the lung. The uniformity of radioactivity distributed throughout the lung is attributed to the fine particle size (mass median aerodynamic diameter of 2 microm) of the aerosol and the electronic control of aerosol inhalation by the device. In conclusion, the AERx system can be ideal for diffuse aerosol deposition of therapeutic or diagnostic agents and is largely unaffected by inhaled volume and posture. The efficiency of the device device can limit the total radiation exposure of patients and staff administering the radioaerosols, and can make it suitable for delivery of expensive drugs.

Optimized acquisition time and image sampling for dynamic SPECT of Tl-201.

With the recent development in scatter and attenuation correction algorithms, dynamic single photon emission computerized tomography (SPECT) can potentially yield physiological parameters, with tracers exhibiting suitable kinetics such as thallium-201 (Tl-201). A systematic way is proposed to investigate the minimum data acquisition times and sampling requirements for estimating physiological parameters with quantitative dynamic SPECT. Two different sampling schemes were investigated with Monte Carlo simulations: 1) Continuous data collection for total study duration ranging from 30-240 min. 2) Continuous data collection for first 10-45 min followed by a delayed study at approximately 3 h. Tissue time activity curves with realistic noise were generated from a mean plasma time activity curve and rate constants (K1 - k4) derived from Tl-201 kinetic studies in 16 dogs. Full dynamic sampling schedules (DynSS) were compared to optimum sampling schedules (OSS). We found that OSS can reliably estimate the blood flow related K1 and Vd comparable to DynSS. A 30-min continuous collection was sufficient if only K1 was of interest. A split session schedule of a 30-min dynamic followed by a static study at 3 h allowed reliable estimation of both K1 and Vd avoiding the need for a prolonged (>60-min) continuous dynamic acquisition. The methodology developed should also be applicable to optimizing sampling schedules for other SPECT tracers.

Enhanced accuracy and reproducibility in reporting of lung scintigrams by a segmental reference chart.

UNLABELLED: The diagnostic probability of pulmonary embolic disease is based on the recognition of unmatched segmental perfusion defects. Although interobserver and intraobserver reproducibility have been studied, accuracy has been an elusive goal due to the lack of a gold standard. We investigated the accuracy and reproducibility of reporting in a virtual scintigraphic model of the lungs, with and without the use of a lung segmental reference chart. METHODS: A Monte Carlo package was used to model lung scintigraphy from a digital phantom of the human lungs. An ideal lung segmental reference chart was created from the phantom. Five experienced nuclear medicine physicians reported a set of all possible defects involving 100% of a segment, without and with the chart. A further set of defects involving 45%-55% of a segment in the lower lobes was investigated using the chart. RESULTS: There was a significant improvement in accuracy (from 48% to 72%) and intraobserver agreement (from 61% to 77%) with the chart. The accuracy of reporting defects in the upper and middle lobes was consistently better than that in the lower lobes. There was no significant difference between the accuracy of reporting large defects and that of reporting moderate defects in the lower lobes. CONCLUSION: The lung segmental reference chart significantly improves both the accuracy and reproducibility of reporting lung scintigrams; however, although reporting in the lung bases is improved, absolute accuracy is substantially less than that in the upper and middle lobes. This emphasizes the need for caution because the lung bases are the most common site of embolic disease.

Variability of perceived defect size in virtual lung scintigraphy.

UNLABELLED: The diagnosis of pulmonary embolism is based on the presence of mismatched segmental or subsegmental defects. An important axiom is the classification of defect sizes into small, moderate and large. Little information about the recognition and classification of such defects has been published. We undertook a study of the perception of defect size using a model of the virtual scintigraphic anatomy of the lungs to address this issue. METHODS: Segmental anatomy of the lungs was modeled with CT, cadaveric lungs and standard anatomical tests. The emission, scatter and attenuation of photons were modeled within these virtual lungs and the surrounding tissues. Single segmental lesions, each 100% of a segment, were created in eight projections and submitted for blinded reporting by four experienced nuclear medicine physicians to obtain their assessment of the size of each defect on two occasions. RESULTS: Of the 144 defects submitted for reporting, 15% were reported as <25% of a segment, 35% were reported as 25%-75% and 50% were reported as 75%-100%. The accuracy of each reporter and the intraobserver agreement were calculated; the weighted kappa value ranged from 0.34 to 0.60. The segmental defects that were most likely to be underestimated in size were in the right lower lobe. CONCLUSION: It is clear that segmental defect sizes were underestimated, particularly in the right lower lobe. Although the intraobserver agreement in reporting was fair, the accuracy of estimation was only 50%. The variability and inaccuracy might be reduced by the use of a guide to segmental anatomy.

Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline. METHODS: Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl. RESULTS: There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1. CONCLUSIONS: Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.

Inhalation of dry-powder mannitol increases mucociliary clearance.

Inhalation of hypertonic saline stimulates mucociliary clearance (MCC) in healthy subjects and those with obstructive lung disease. We investigated the effect of inhaling the osmotic agent mannitol on MCC. We used a dry-powder preparation of mannitol British Pharmacopea (BP) which was encapsulated and delivered using a Dinkihaler. MCC was measured for 75 min in six asthmatic and six healthy subjects on two occasions before and after the mannitol inhalation or its control, using 99mTc-sulphur colloid and a gamma camera. The inhaled dose of mannitol was 267+/-171 mg (mean+/-SD) and 400 mg and the percentage fall in forced expiratory volume in one second (FEV1) was 22+/-3 and 4+/-2% in the asthmatic and healthy subjects, respectively. The total clearance in the whole right lung for the 60 min from the start of inhalation of mannitol was greater by 263+/-11.9% in the asthmatic and 18.1+/-4.9% in the healthy subjects compared to the control. The total clearance over 75 min was 54.7+/-9.6% and 33.6+/-9.4% on the mannitol and control day (p<0.002), respectively, in the asthmatic subjects and 40.5+/-7.1% and 24.8+/-7.8% (p<0.002) in the healthy subjects. In conclusion, inhalation of dry-powder mannitol increases mucociliary clearance in asthmatic and healthy subjects and may benefit patients with abnormal mucociliary clearance.

Optimization of the scintigraphic segmental anatomy of the lungs.

UNLABELLED: Accurate and reproducible reporting of lung scintigraphy is predicated on a sound knowledge of the segmental anatomy of the lungs. A limited amount of hard data exists about the true segmental anatomy of the lungs. A virtual model of human lungs was created using a CT-based dataset and a Monte Carlo simulation technique to examine the optimal projections for the visualization of each segment in the lungs. METHODS: Segmental anatomy of the lungs was modeled using CT, cadaveric lungs and standard anatomical texts. The emission, scatter and attenuation of photons was modeled within these virtual lungs and the surrounding tissues. Single segmental lesions were created in eight projections and submitted for blinded reporting to four experienced nuclear medicine physicians to obtain the best views for each segment. RESULTS: The anterior and posterior oblique projections yielded the best views for 10 of 18 segments, with the laterals contributing four views, the anterior contributing two views and the posterior contributing one view. The majority of basal segments (six of nine) were best seen in the anterior and posterior oblique projections. CONCLUSION: This model overcomes the major problems associated with experimentation in the normal human and has the potential to provide answers to the major problems of scatter, attenuation and "shine-through" in lung scintigraphy.

Monte Carlo and experimental evaluation of accuracy and noise properties of two scatter correction methods for SPECT.

Scatter correction is a prerequisite for quantitative SPECT, but potentially increases noise. Monte Carlo simulations (EGS4) and physical phantom measurements were used to compare accuracy and noise properties of two scatter correction techniques: the triple-energy window (TEW), and the transmission dependent convolution subtraction (TDCS) techniques. Two scatter functions were investigated for TDCS: (i) the originally proposed mono-exponential function (TDCSmono) and (ii) an exponential plus Gaussian scatter function (TDCSGauss) demonstrated to be superior from our Monte Carlo simulations. Signal to noise ratio (S/N) and accuracy were investigated in cylindrical phantoms and a chest phantom. Results from each method were compared to the true primary counts (simulations), or known activity concentrations (phantom studies). 99mTc was used in all cases. The optimized TDCS(Gauss) method overall performed best, with an accuracy of better than 4% for all simulations and physical phantom studies. Maximum errors for TEW and TDCS(mono) of -30 and -22%, respectively, were observed in the heart chamber of the simulated chest phantom. TEW had the worst S/N ratio of the three techniques. The S/N ratios of the two TDCS methods were similar and only slightly lower than those of simulated true primary data. Thus, accurate quantitation can be obtained with TDCS(Gauss), with a relatively small reduction in S/N ratio.

Effect of hypertonic saline, amiloride, and cough on mucociliary clearance in patients with cystic fibrosis.

In patients with cystic fibrosis (CF), dehydration of airway secretions leads to a decrease in mucociliary clearance (MCC). We examined the acute effect of MCC of a single administration by aerosolization of hypertonic saline (7%) (HS), amiloride (0.3% in 0.12% NaCl) (AML) and a combination of AML and HS (AML + HS) in 12 patients with CF using a radioaerosol technique. Isotonic saline [0.9%] (IS) was used as a control solution. As both the AML and HS solutions induced cough in some patients, the last nine patients studied also underwent a cough clearance day. This was to eliminate the possible confounding effect of cough on MCC measurement. Patients ranged from 18 to 28 yr (mean +/- SD, 22 +/- 3) with an FEV1 of 27 to 112% predicted (61 +/- 30%). Following deposition of the radioaerosol, baseline clearance was assessed for 30 min. This was followed by a 30-min intervention period. Assessment of post-intervention clearance for a further 30 min was then performed. Comparison of the amount of radioaerosol cleared from the right lung was made at 60 min (%C60) and 90 min (%C90) using repeated measures ANOVA. The percent cleared at 60 and 90 min was significantly increased with HS (%C60 = 26.5%, %C90 = 29.4%) and the combination of AML + HS (%C60 = 23.1%, %C90 = 27.4%) compared with both IS (%C60 = 14.7%, %C90 = 17.5%) and COUGH (%C60 = 18.0%, %C90 = 19.5%), p < 0.01. Inhalation of hypertonic saline is a potentially useful treatment in patients with cystic fibrosis.

Correlation between post-ejection shortening and improvement in regional wall motion after revascularization in patients with coronary artery disease.

This study investigates the relationship between regional post-ejection shortening and improvement in wall motion after revascularization in patients with severe regional left ventricular contractile dysfunction. Canine studies have documented the phenomenon of post-systolic shortening during acute ischemia, and this predicted recovery of contractile function when ischemia was relieved. This delayed shortening from the ischemic segment would cause regional emptying while the other normal portion of the left ventricle starts to have diastolic relaxation. This was detectable by standard phase analysis of the radionuclide ventriculogram, the abnormal region with delayed emptying being distinguished from the normal portion of left ventricle as an area with a homogeneous phase delay. Twelve patients with successful revascularization and a pre-operative study demonstrating a single homogeneous area of phase delay were identified. The area was demarcated and the regional volume-time curve constructed. The volume-time curve of the abnormal region is analogous to the myocardial segment length versus time relationship in the canine model. We quantitated the amount of delayed (post-systolic) emptying in the demarcated region as the difference between end-systole counts and post-systolic nadir counts, and this was normalised to left ventricular stroke count. After revascularization, regional ejection fraction improved from 44 +/- 10% to 62 +/- 14% (P < 0.001), representing a 47 +/- 50% improvement over baseline. The percentage improvement in regional ejection fraction correlated with post-systolic emptying (r = 0.74, P < 0.05) but not with initial regional ejection fraction. In conclusion, post-ejection shortening causes regional post-systolic emptying and this correlates with post-revascularization improvement in regional wall motion.

Mucociliary clearance during and after isocapnic hyperventilation with dry air in the presence of frusemide.

We have previously shown that mucociliary clearance (MCC) decreased during and increased after isocapnic hyperventilation (ISH) with dry air, both in asthmatic and healthy subjects. Inhaled frusemide, an inhibitor of the Na+/K+/2Cl- and NaCl co-transporters on the basolateral membrane of the epithelial cell, prevents the airway narrowing provoked by ISH with dry air. The co-transport system controls epithelial cell volume and chloride secretion and, thus, frusemide has the potential to modify the rate of recovery of periciliary fluid volume during and after ISH with dry air, and hence affect MCC. Frusemide also blocks mediator release from mast cells, which may also modify the increase in MCC after ISH. Eleven asthmatic and 11 healthy subjects inhaled frusemide (35.7 +/- 0.44 mg) or its vehicle, from a Fisoneb ultrasonic nebulizer 30 min before ISH with dry air, on two separate occasions. MCC was measured using 99mTc-sulphur colloid and a gamma camera. Frusemide, compared to its vehicle, did not affect MCC during or 45 min after ISH. However, in the presence of frusemide, the onset of the increase of MCC after ISH was significantly delayed for approximately 10 min in the whole right lung (p < 0.002) and central region (p < 0.01) in the asthmatic but not in the healthy subjects. These findings could be explained by frusemide delaying the recovery of the periciliary fluid volume after ISH with dry air and/or interfering with the stimulus that causes the increase in MCC in the asthmatic subjects after ISH.

Inhalation of hypertonic saline aerosol enhances mucociliary clearance in asthmatic and healthy subjects.

Hyperosmolarity of the airway surface liquid (ASL) has been proposed as the stimulus for hyperpnoea-induced asthma. We found previously that mucociliary clearance (MCC) was increased after isocapnic hyperventilation (ISH) with dry air, and we proposed that the increase related to transient hyperosmolarity of the ASL. We investigated the effect of increasing the osmolarity of the ASL on MCC, by administering an aerosol of concentrated salt solution. MCC was measured using 99mTc-sulphur colloid, gamma camera and computer analysis in 12 asthmatic and 10 healthy subjects on three separate days, involving administration of each of the following: 1) ultrasonically nebulized 14.4% saline; 2) ultrasonically nebulized 0.9% saline; and 3) no aerosol intervention (control). The (mean +/- SD) volume of nebulized 14.4% saline was 2.2 +/- 1.2 mL for asthmatics and 3.2 +/- 0.7 mL for healthy subjects. This volume was delivered over a period of 5.4 +/- 1.3 and 6.4 +/- 0.7 min for asthmatic and healthy subjects, respectively. The airway response to 14.4% saline was assessed on a separate visit and the fall in forced expiratory volume in one second (FEV1) was 22 +/- 4% in the asthmatic and 3 +/- 2% in the healthy subjects. Compared to the MCC with the 0.9% saline and control, the hypertonic aerosol increased MCC in both groups. In asthmatic subjects, MCC of the whole right lung in 1 h was 68 +/- 10% with 14.4% saline vs 44 +/- 14% with 0.9% saline and 39 +/- 13% with control. In healthy subjects, MCC of the whole right lung in 1 h was 53 +/- 12% with 14.4% saline vs 41 +/- 15% with 0.9% saline and 36 +/- 13% with control. We conclude that an increase in osmolarity of the airway surface liquid increases mucociliary clearance both in asthmatic and healthy subjects. These findings are in keeping with our previous suggestion that the increase in mucociliary clearance after isotonic hyperventilation with dry air is due to a transient hyperosmolarity of the airway surface liquid.

Detection of malignant tumors using Tc-99m labeled Fab' fragments from a monoclonal antibody with specificity for D-dimer of cross-linked fibrin.

The authors present the case studies of two patients whose malignant tumors were detected with a Tc-99m labeled antifibrin monoclonal antibody (DD-3B6/22), which is specific for cross-linked fibrin. The first case was a malignant fibrous histiocytoma involving the proximal aspect of the left thigh, whereas in the second case, the patient was receiving treatment for a squamous cell carcinoma of the right mainstem bronchus. The results highlight the potential of this anti-D-dimer radiopharmaceutical for noninvasive detection of malignant tumors.

Electrocardiographic measurement of infarct size after thrombolytic therapy.

OBJECTIVES: We examined the utility of the 32-point QRS score from the 12-lead electrocardiogram (ECG) for measurement of the ischemic risk region and infarct size in patients receiving thrombolytic therapy. BACKGROUND: The QRS score offers a means of evaluating the therapeutic benefit of thrombolytic therapy by comparing final infarct size with the initial extent of ischemic myocardium. METHODS: The study included 38 patients (34 men, 4 women; mean [+/-SD] age 54 +/- 10 years) with a first infarction (18 anterior, 20 inferior). The maximal potential QRS score (QRS0) was assigned to all leads with >/= 100-microV ST elevation on the initial ECG. The QRS scores were calculated at 7 and 30 days after infarction. Left ventricular ejection fraction was measured by radionuclide ventriculography at 1 month. Twenty-eight patients had thallium (Tl)-201 and technetium (Tc)-99m pyrophosphate tomographic measurement of the ischemic region and infarct size. RESULTS: The QRS0 was 10.3 +/- 3.1 (mean +/- SD) for anterior and 10.4 +/- 3.5 for inferior infarcts. The QRS scores were similar at 7 and 30 days for both anterior (5.6 +/- 3.4 vs. 5.5 +/- 3.4) and inferior infarcts (3.7 +/- 2.6 vs. 2.9 +/- 2.2). The day 7 QRS score and ejection fraction at 1 month were inversely correlated (r = -0.74, p < 0.01). The Tl-201 perfusion defect was 34 +/- 11% of the left ventricle for anterior and 32 +/- 7% for inferior infarcts. Subsequent Tc-99m pyrophosphate infarct size was 15 +/- 9% of the left ventricle for anterior and 17 +/- 9% for inferior infarcts. The QRS0 was correlated with the extent of the Tl-201 perfusion defect (r = 0.79, p < 0.001), and the day 7 QRS score was correlated with Tc-99m pyrophosphate infarct size (r = 0.79, p < 0.005). CONCLUSIONS: The 32-point QRS score can provide useful immediate measurements of the ischemic risk region and subsequent infarct size.

Regional deposition of saline aerosols of different tonicities in normal and asthmatic subjects.

Nonisotonic aerosols are frequently used in the diagnosis and therapy of lung disease. The purpose of this work was to study the difference in the pattern of deposition of aerosols containing aqueous solutions of different tonicities. 99mTechnetium-diethyltriaminepentaacetic acid (99mTc-DTPA)-labelled saline aerosols, with mass median aerodynamic diameter 3.7-3.8 microns and geometric standard deviation 1.4, were inhaled under reproducible breathing conditions on two occasions. Hypotonic and hypertonic solutions were used in 11 normals subjects, isotonic and hypertonic solutions in 9 asthmatics. The regional deposition was quantified by a penetration index measured with the help of a tomographic technique. There was a small but significant increase (6.7%) in the penetration index of the hypotonic as compared to the hypertonic aerosols in the normal subjects. The region that was markedly affected was the trachea. The differences in the penetration of the isotonic and hypertonic aerosols in the asthmatics appeared to be strongly dependent on the state of the airways at the time of the study. These findings can be interpreted in terms of effects of growth or shrinkage of nonisotonic aerosols, as well as of airway narrowing, on regional deposition of aerosols. Tonicity of aerosols appears to affect their deposition both through physical and physiological mechanisms. This should be taken into account when interpreting the effects of inhaled aqueous solutions of various tonicities in patients in vivo.

Regional deposition of nebulized hypodense nonisotonic solutions in the human respiratory tract.

Deposition of nonisotonic therapeutic and diagnosis aerosols can cause changes in airway fluid composition and bronchoconstriction in sensitive subjects. "Hypodense" aerosols containing a relatively low concentration of droplets in the carrier air were used in the studies of regional deposition of radiolabelled nebulized solutions of hypo- and hypertonic saline, in order to investigate whether the number of droplets per volume of carrier can affect deposition. Solutions with and without 0.5% nedocromil sodium were nebulized in order to examine the effects of a potential modifier of the rates of heat and mass transfer. The deposition was quantified using penetration index (PI) calculated from images obtained by single photon emission computerized tomography (SPECT) in 11 healthy volunteers per study. There was an increase in the penetration index (10.9%, for the saline only; 15.5%, for the nedocromil study) of the hypotonic compared to the hypertonic aerosol, although the initial size distribution of both types of aerosols was very similar (mass median aerodynamic diameter (MMAD) 3.7 and 3.8 microns; geometric standard deviation (GSD) 1.8 and 1.5 for the hypo- and hypertonic aerosols, respectively). The present results confirm the effects of tonicity on deposition of aerosols found in a parallel study reported in this issue of the Journal. They also give support to the theory that, in addition to the concentration of the nebulized solutions, the number of droplets per volume of the carrier air is a factor affecting deposition of aqueous aerosols. The presence of 0.5% nedocromil sodium in the solutions did not appear to interfere with the processes of heat and water transfer in the airways.