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Biomedical subjects

K Philipson

Publications and source records attributed to K Philipson.

At least 37 records · Page 2Linked to original sources

Human lung deposition of particles suspended in air or in helium/oxygen mixture.

Deposition in mouth and throat and the fraction of alveolarly deposited particles in the lung of 3.6- to 3.8-microns Teflon particles labeled with 99mTc were estimated in nine healthy subjects. The particles were inhaled in air or helium/oxygen mixture with a flow of 0.5 l/s by subjects with or without induced bronchoconstriction. The bronchoconstriction (two- to threefold increase in airway resistance) was induced by an aerosol of methacholine bromide. As the Reynolds number is three times lower for the helium/oxygen mixture than for air, and the sedimentation rate of the particles is about the same in both, a different regional deposition between particles suspended in air and helium/oxygen mixture should be due to turbulence. Deposition in mouth and throat did not differ significantly between air and the helium/oxygen mixture. The alveolarly deposited fraction tended to be larger for unconstricted airways and was significantly larger for constricted airways for inhalations in the helium/oxygen mixture compared to air. In real life, air pollutants and therapeutic aerosols may be inhaled with larger flow rates and broncho-constriction may be more pronounced in patients, so that deposition of particles due to turbulence can be important.

Administration, Inhalation↗

Regional deposition in human lung of 2.5 microM particles.

Regional deposition in the lung of 111In-labelled Teflon particles with an aerodynamic diameter of 2.5 micron was studied in eight healthy nonsmokers. The particles were inhaled at 0.5 l/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholine bromide aerosol, for one exposure series before (provocation experiment) and for one exposure series after (control experiment) inhalation of the Teflon particles. Airway resistance (Raw) was measured with a whole-body plethysmograph before and after the induction of bronchoconstriction and increased on an average by a factor of 3-4. The total lung deposition, in percent of the inhaled radioactivity, was 83 +/- 6% (mean +/- SD) for the control experiment and 84 +/- 5% for the provocation experiment. Alveolar deposition, estimated as the percentage retention of lung deposition after 24 hrs (Ret24), was significantly lower in the provocation experiment than in the control experiment, 42 +/- 10% and 77 +/- 12%, respectively. Ret24 varied greatly among the subjects in the control experiment; for example, individual tracheobronchial deposition varied by a factor of 5. Ret24 was not related to FEV1, FVC or Raw. The Ret24 values in the two exposure series correlated significantly indicating an individual factor. Retention at 3 and 24 hrs correlated strongly, r = 0.94. This implies that radionuclides with half-lives of a few hours, e.g., 99mTc, can be used in studies of regional lung deposition when mucociliary transport system has been stimulated.

Adult↗

Deposition of large particles in human lung.

Twenty-four nonsmoking males, all without history of pulmonary disease, were randomly divided into four groups of six subjects each. The subjects in each group inhaled monodisperse Teflon particles labelled with 111In (half-life 2.83 days); 8.2, 11.5, 13.7 and 16.4 micron aerodynamic diameter, respectively. Radioactivity in head and throat, lung and stomach was determined after 0, 3 and 24 hrs using a profile scanner. For some subjects radioactivity was also determined using a whole-body scanner at 3.5 and 24 hrs. After the 24-hr determination the subjects inhaled labelled Teflon particles again, this time with a filter in front of the mouth. Average values for total deposition in the body, obtained using a profile scanner, whole-body scanner and filter measurements, agreed fairly well. Lung retention values obtained by whole-body and profile scanning also agreed well. The average deposition in the lung, expressed as a percentage of total deposition, was 49, 31, 21 and 13% for the four particle sizes (8.2-16.4 micron). Alveolar deposition, determined as retention at 24 hrs and expressed in percent of total deposition, was 15, 4, 4 and 1%. For the smallest particle sizes the deposition values agreed with earlier investigations. However, for the larger particles the two deposition values were higher than expected when compared to earlier studies.

Administration, Inhalation↗

Influence of ambroxol on tracheobronchial clearance in simple chronic bronchitis.

The influence on tracheobronchial clearance of ambroxol, a metabolite of bromhexine, was investigated by measuring the lung retention of inhaled 6 micron monodisperse Teflon particles labelled with 99mTc. Fourteen subjects with simple chronic bronchitis, who belonged to a "responder" group in an earlier study on the subjective effects of ambroxol, were examined using a double-blind cross-over design comparing 120 mg ambroxol daily and placebo. On commencing the study and after each 2-week treatment period, the subjects were examined for mucociliary clearance and clearance by voluntary coughing. Treatment did not influence mucociliary clearance or clearance by cough. There is still a possibility that phlegm loosening by cough is enhanced in situations with more hypersecretion.

Adult↗

Spirometric data and penetration of particles to the alveoli.

The percentage retention at 24 hours of 4 micron Teflon particles, aerodynamic diameter about 6 micron, was studied in 29 healthy male volunteers. The particles were inhaled at 0.5l/s with maximally deep breaths. The 24 hour retention correlated significantly with FEV1 and FVC and persisted when the subjects were divided into different categories according to profession and smoking habits. The results suggest that for exposure to metal particles at a size where impaction is an important deposition mechanism--that is, particles larger than a few microns--workers with large FEV1 values may run a greater risk of receiving systemic toxic effects than those with small FEV1 values.

Adult↗

Regional deposition of particles in human lung after induced bronchoconstriction.

The percentage 24-hr lung retention (Ret24), a measure of penetration to the aveoli, of 4 micron monodispersed Teflon particles, aerodynamic diameter 6 micron, was studied in 8 healthy nonsmokers. The particles were inhaled at 0.2 1/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholinebromide aerosol for one exposure before and for one exposure after inhalation of the Teflon particles. Airway resistance (Raw) was measured using a whole body pletysmograph before and after the induction of bronchoconstriction and increased on an average by a factor 2-3. Ret24 was significantly lower when the Teflon particles were inhaled during bronchoconstriction than when bronchoconstriction was induced after inhalation of the Teflon particles, 26 +/- 12% and 48 +/- 6% (mean +/- SD), respectively. These experimental data agree fairly well with data on deposition due to impaction and sedimentation using a lung model where the diameters of the airways were varied so that an increase in airway resistance occurs similar to that produced in our experimental subjects. However, the experimental data tended to be lower than the theoretical ones when the particles were inhaled during the induced bronchoconstriction. In this study, where the mucociliary transport system was stimulated by methacholinebromide, the percentage 3-hr retention (Ret3) was highly correlated with Ret24, r = 0.97, i.e., Ret3 can be used instead of the Ret24. This implies that radionuclides with shorter half-lives which give lower radiation doses, can be used, and that subjects can be studied within shorter periods of time.

Adult↗

Mucociliary clearance in relation to clinical features in patients with bronchiectasis.

Patients with bronchiectasis collected from a register covering all hospital stays within the county of Stockholm were asked to participate in a study of lung mucociliary clearance. Twenty-one patients inhaled 6 um Teflon particles labelled with 99mTc and radioactivity was measured externally. The patients were also clinically classified. Clearance varied from normal to extremely slow. The average retention at 2 hours was significantly higher in the patients, 65+27%, (mean +/- SD) than in healthy nonsmokers, 36+22%. Clearance was more impaired the more generalized the airway symptoms were, the more continuous they were, and the earlier in life they had started, all features which indicate a coherence with the immotile cilia syndrome, an obvious "model disease" in this context. Clearance was studied separately in two lungs in 18 patients and was similar in both lungs with one exception. A full presentation of this investigation is submitted to Eur. J. Respir. Dis.

Adult↗

Mucociliary clearance in relation to clinical features in patients with bronchiectasis.

Patients with bronchiectasis were collected from a register covering all hospital stays within the county of Stockholm. They were asked to come for an interview, a clinical examination and to participate in a study of lung mucociliary clearance. The subjects inhaled 6 microns Teflon particles labelled with 99mTc and radioactivity was measured externally. Clearance varied from normal to extremely slow. The average retention of the Teflon particles at 2 h was significantly higher in the 21 patients, 65 +/- 27% (mean +/- SD), than in healthy nonsmokers, 36 +/- 22%. Clearance was more impaired the more generalized the airway symptoms were, the more continuous they were, and the earlier in life they had started; all features which indicate a coherence with the immotile cilia syndrome, an obvious "model disease" in this context. Clearance was studied separately in the two lungs in 18 patients and was similar in both lungs, with one exception.

Adult↗

Long-term lung clearance in humans studied with Teflon particles labeled with chromium-51.

Six healthy nonsmoking males inhaled 4-micron diameter Teflon particles labeled with chromium-51. Lung retention was measured for approximately 300 days. Three subjects inhaled "high-leaching" particles and three "low-leaching" particles. The high-leaching leaching particles leached 0.26%/day in water at 37 degrees C for the first 100 days and the low-leaching particles 0.065%/day. On an average, urine sampled for 24 h contained 0.13% of the lung burden for the high-leaching particles and 0.02% for the low-leaching particles. Thirty percent of the long-term clearance occurred with a fast phase, with half-times ranging from 4.5-45 days, and 70% with a slow phase, with half-times ranging from 200-2500 days. The fast phase was similar for the high-leaching and low-leaching groups. The slow phase varied widely among the subjects. There was no clear-cut relationship between half-time and type of particle. However, it seems probable that the slow phase was dependent on the degree of leaching, i.e., the half-times for elimination of intact particles from the lung are even slower. The large differences in long-term clearance among subjects indicate that long-term exposure to highly insoluble particles will result in large differences in lung burden. Subjects with a low capacity to eliminate alveolarly deposited particles are thus expected to be more susceptible to diseases in the alveolar part of the lung, i.e., diseases caused by certain insoluble particles.

Adult↗

Airway resistance and deposition of particles in the lung.

The percentage 24-h lung retention of 4-micrometers monodispersed Teflon particles, aerodynamic diameter about 6 micrometers, was studied twice in 8 healthy nonsmokers. The particles were inhaled at 0.5 liter/sec with maximally deep breaths. Bronchoconstriction was induced by inhalation of a methacholine-bromide aerosol for one exposure before and for the other 20-30 min after the inhalation of the Teflon particles. For both exposures, airway resistance (Raw) was measured with a whole body plethysmograph before and after the induction of the bronchoconstriction and was found on an average to increase with a factor of 2-3. For the exposure when bronchoconstriction was induced after the inhalation of the Teflon particles, Raw and 24-h lung retention correlated significantly. Retention at 24 h was markedly lower when bronchoconstriction was induced before inhalation of the Teflon particles than when bronchoconstriction was induced after, the ranges being 13-24% and 38-68%, respectively. The experimental data agreed well with theoretical data from a lung model wherein the diameters of the airways were varied. The results indicate that the magnitude of bronchoconstriction occurring in real life can protect the alveolar part of the lung by reducing the amount of inhaled particles that deposit there.

Adult↗

Tracheobronchial clearance after flexible fiberoptic bronchoscopy.

As the tracheobronchial mucosa is vulnerable to mechanical trauma it is important to investigate whether examination with a flexible fiberoptic bronchoscope (FFB) damages the respiratory mucosa. In 12 subjects, tracheobronchial clearance was measured 1 day before and 1 day after FFB performed under topical anaesthesia. Mucociliary transport was studied by having the patients inhale 6 micron teflon particles tagged with 99mTc, and by external measurements of the radioactivity retained in the lungs. Most of the patients had a similar clearance on both days. A marked impairment after FFB was only seen in one patient. This study suggests that the tracheobronchial clearance system has a large reserve against mechanical trauma. FFB may possibly change mucociliary clearance in some patients, and this can be of practical significance in patients unable to cough.

Adult↗

Intercomparison of regional deposition of aerosol particles in the human respiratory tract and their long-term elimination.

Human chest clearance of Teflon particles with an aerodynamic diameter of 4.7 micrometers tagged with 198Au or 111In was studied with two apparatuses and two gamma-ray spectrometers for the external detection of the activity deposited in the respiratory tract. Approximately the same chest retention function was measured with two gamma-ray spectrometers when the subjects inhaled equal aerosols under equal breathing conditions. The long-term clearance rate following the short-term elimination of particles from ciliated airways was slower for Teflon particles (mean half-time 105 days for 111In-labeled particles and 128 days for 198Au-labeled particles) than for iron oxide particles of the same size (mean half-time about 60 days). It is suggested that insoluble particles of this size studied are cleared with a half-time of about 120 days within the first 2 weeks after completion of mucociliary clearance. Regional deposition did not differ between the iron oxide and Teflon particles.

Adult↗

Clearance by voluntary coughing and its relationship to subjective assessment and effect of intravenous bromhexine.

The elimination of 6 micrometers radioactively tagged teflon particles by 1-2 min of voluntary coughing was studied by profile scanning in 12 patients with tracheobronchial hypersecretion. The patients were tested on 2 different days 40-50 min after receiving 8 mg bromhexine (4 mg in two patients) and placebo intravenously according to a double blind cross-over design. Bromhexine did not influence the elimination of test particles in the nine patients in whom the measurements were technically satisfactory. When asked to identify the day they received bromhexine, the patients failed to do so. However, eight of the nine patients, in whom clearance measurements could be performed, believed they had received bromhexine on the day when most particles were eliminated (P less than 0.01), which coincided with the day on which coughing was easiest. It is suggested that self-assessment of the efficacy of coughing might be a simple, yet reliable technique for studying the short-term influence of drugs on tracheobronchial clearance by coughing.

Adult↗

Elimination of test particles from the human tracheobronchial tract by voluntary coughing.

The effect of coughing on the elimination of inhaled 6 micrometer radioactively tagged teflon particles in humans was studied by external measurements of the radioactivity retained in the lungs before and after 1--2 min of voluntary coughing. In six healthy subjects coughing produced no substantial elimination of the particles. Six out of eight patients with lung disease produced expectorate and also eliminated particles from the lungs by coughing. The other two patients had no phlegm, did not produce any expectorate and did not eliminate particles by coughing. An increased amount of tracheobronchial secretion thus seems to be necessary for coughing to be effective. In the patients, the elimination of particles by coughing was fairly reproducible, suggesting that the test model may be useful for investigation of the influence of physiological and pharmacological factors on the elimination process.

Adult↗

Tracheobronchial clearance 5-15 months after infection with Mycoplasma pneumoniae.

Tracheobronchial clearance was studied in 17 non-smokers who had suffered from a serologically verified Mycoplasma pneumoniae pneumonia 5-15 months earlier. The subjects inhaled 6 micron teflon particles tagged with 99mTc. The retention of the particles in the lungs was measured for 2 h. The retention after 2 h in this group was significantly higher than in a control group of healthy non-smokers. The results suggest that some impairment persists 5-15 months after the infection or that persons with slow clearance contract a mycoplasma pneumonia more easily than do those with fast clearance.

Adolescent↗

Tracheobronchial clearance in patients with emphysema associated with alpha1-antitrypsin deficiency.

Tracheobronchial clearance was studied in five patients who had emphysema associated with deficiency of serum alpha1-antitrypsin but no history of chronic bronchitis. After the patients had inhaled an aerosol of 6 micrometer teflon particles tagged with 99mTc, the radioactivity in the lungs was followed externally during 2 h. Clearance in the emphysematous patients was normal or even rapid as compared with clearance in healthy subjects, and was significantly more rapid than clearance in patients with a history of chronic bronchitis. The results indicate that emphysema can develop in patients with alpha1-antitrypsin deficiency without their having an impairment of mucociliary transport.

Aged↗

Cystic fibrosis compared with the immotile-cilia syndrome. A study of mucociliary clearance, ciliary ultrastructure, clinical picture and ventilatory function.

Patients with cystic fibrosis (CF) were investigated for mucociliary clearance (with and without stimulation by terbutaline), clinical picture, ventilatory function and ultrastructure of cilia. The results were compared with those of patients with congenitally immotile cilia (immotile-cilia syndrome). Mucociliary clearance could be demonstrated in all the seven CF patients who succeeded in inhaling the test aerosol. Ciliary ultrastructure from a deceased CF patient was normal. Patients with the immotile cilia syndrome had no substantial clearance and defective cilia. The CF patients coughed more during the clearance measurements than any other group studied earlier, and their coughing was effective. One patient succeeded in avoiding coughing in both measurements and had faster clearance when he got terbutaline than when he got the vehicle. Although younger, the CF patients tended to be more obstructed in their lungs and more handicapped than the patients suffering from the immotile-cilia syndrome. The latter patients had more discomfort from rhinitis, sinusitis and otitis than had the CF patients. An impairment of the mucociliary transport rate is hence unlikely to be a primary pathogenic factor for the respiratory tract disease in CF patients.

Adult↗