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Biomedical subjects

M Svartengren

Publications and source records attributed to M Svartengren.

At least 37 records · Page 2Linked to original sources

Short-term exposure to air pollution in a road tunnel enhances the asthmatic response to allergen.

The aim of this study was to assess whether air pollution in road tunnels would promote asthmatic reactions in persons with mild allergic asthma. Twenty volunteers with mild allergic asthma were exposed, inside a car, for 30 min in a Stockholm city road tunnel. As a control, the subjects were exposed to much lower pollution levels in a suburban area. Four hours after the exposure, the subjects inhaled a low dose of allergen. Asthmatic reaction during the early phase was measured as the increase in specific airway resistance 15 min after allergen inhalation and during the late phase as the decrease in lung function forced expiratory volume in one second 3-10 h after allergen inhalation. Asthma symptoms and drug use were monitored up to 18 h after allergen inhalation. The median nitrogen dioxide level during exposure was 313 microg x m-3 (range 203-462). The median levels of particles with 50% cut-off aerodynamic diameters of 10 (PM10) and 2.5 microm (PM2.5) were 170 (range 103-613) and 95 (range 61-218) micro x m-3, respectively. Subjective symptoms during tunnel exposure were not pronounced. However, subjects exposed to tunnel N02 levels of > or = 300 microg x m-3 had a significantly greater early reaction, following allergen exposure, as well as lower lung function and more asthma symptoms during the late phase, compared to control. Also, subjects with PM2.5 exposure > or = 100 microg x m-3 had a slightly increased early reaction compared to control. In conclusion, exposure to air pollution in road tunnels may significantly enhance asthmatic reactions to subsequently inhaled allergens.

Adult↗

Does lung retention of inhaled particles depend on their geometric diameter?

Experiments with a bolus technique suggest that retained fractions in the airways are dependent on the geometric diameter of the particles. This view has been adopted by the International Commission on Radiological Protection (ICRP) in its new human respiratory tract model (HRTM). The aim of the present study was to test this view by the use of an inhalation technique, in which particles with an aerodynamic diameter of about 6 microns are inhaled extremely (0.05 l/s) and as a result, the particles are deposited mainly in small ciliated airways. Nine healthy subjects inhaled on one occasion monodisperse 111In-labelled polystyrene particles (geometric diameter 6.05 microns, aerodynamic diameter 6.2 microns) and on another occasion monodisperse 111In-labelled Teflon particles (geometric diameter 4.47 microns, aerodynamic diameter 6.5 microns). Both particles were inhaled at 0.045 L/s and radioactivity in the body was measured after 0, 24, 48, and 72 hours as well as after 1, 2, and, for some subjects, also 3 weeks. The retention in the lungs at 24 hours was slightly lower for the Teflon particles (47%) than for the polystyrene particles (51%). From earlier experimental data with different particle sizes as well as from predictions with theoretical lung models, this difference is reasonably explained by the somewhat larger aerodynamic diameter of the Teflon particles. Clearance of the 2 particle types between 1 day and 2 weeks was similar within each individual as well as in the whole group. The differences between the clearance of 4.5 microns and 6 microns geometric diameter particles observed in the present experiment are significantly different (P < .01) from the differences seen in earlier shallow bolus experiments as well as from the differences for such particles calculated with the HRTM, i.e., our experiment does not support the hypothesis that the fraction retained after 1 day is dependent on the geometric diameter in the size range studied.

Administration, Inhalation↗

Assessment of long-term bronchiolar clearance of particles from measurements of lung retention and theoretical estimates of regional deposition.

Twelve healthy nonsmokers inhaled monodisperse Teflon particles labelled with 51Cr (half-life 27.8 days) with an aerodynamic diameter (dae) of 6.1 microns, 5 at a normal flow, 0.5 L/s, and 7 at an extremely slow flow, 0.05 L/s. Lung retention after 24 hours was measured for about 6 months and could be well described by a 2-component exponential function. After the normal inhalation, 14% of the particles retained after 24 hours cleared with a half-time of 3.7 days and 86% with a half-time of 217 days. After the slow inhalation, 35% of the particles retained after 24 hours cleared with a half-time of 3.6 days and 65% with a half-time of 170 days. Deposition was calculated using 3 different models including the recent Human Respiratory Tract Model (HRTM), adopted by the International Commission on Radiological Protection (ICRP), and a model based on Monte Carlo particle transport, together with an asymmetric lung model. Generally, the 3 models agreed fairly well and predicted a considerably higher deposition in the bronchiolar region (generations 9-15) at the slow flow than at the normal flow. Together, the experimental data and the predictions of the deposition models indicate that about 40% of the particles deposited in the conducting airways during the slow inhalation were retained after 24 hours. They also strongly indicate that the particles which cleared with a half-time of about 4 days were mainly deposited in the bronchiolar region, and that about 25% of the particles deposited in the bronchiolar region cleared in this phase. The experimental data agreed quite well with the HRTM predictions made using its default parameter values for slow clearance in the bronchial tree.

Administration, Inhalation↗

Human tracheobronchial deposition and effect of a cholinergic aerosol inhaled by extremely slow inhalations.

Ten subjects inhaled the same amounts of cholinergic aerosol of a mass median diameter (MMD) of 7.7 microns in a normal provocation test and in a test with extremely slow inhalations (ESI). This new technique using ESI and large droplets/particles gives a high degree of deposition in small ciliated airways which cannot be obtained by using small particles. The purpose was to compare measured effects with calculated doses of the aerosol in large and small ciliated airways. The effect on large airways was measured by airway resistance (R(aw)), and the effect on small airways was measured by the phase III slope of single breath nitrogen test (N2-delta). Mouth and throat deposition was calculated from human experimental data, and deposition of the cholinergic aerosol into large and small airways was calculated, using a computerized lung model. The study showed that the extremely slow inhalation caused a larger effect on R(aw) and tendency to a larger effect on N2-delta compared to the effect in the normal provocation. Deposited dose in the large airways, in percent of inhaled dose, was calculated to be 25-33% for normal inhalation and 20-24% for ESI. Calculated deposited dose in the small airways (bronchioles; generations 12-16) was 1.8-3.4% for normal inhalation and 18-25% for ESI. For large airways a stronger effect was induced by ESI, perhaps by the more uniform distribution of particles within each generation, compared to normal inhalations when particles deposit near the bifurcations. Concerning the small airways, N2-delta did not differ significantly between normal and ESI provocations, indicating that they did not react much on cholinergic exposure. We believe that our approach using ESI for small airway deposition of a nebulized aerosol can be of value for estimating the effects of various substances on large and small airways.

Administration, Inhalation↗

Lung deposition and extremely slow inhalations of particles. Limited effect of induced airway obstruction.

Studies of lung deposition and clearance have focused on the large airways. Still, lung diseases affect also the small airways. We have developed a method for selective particle deposition in the smallest ciliated airways. Eight healthy subject inhaled 6-micron radiolabelled test particles on 3 occasions at 0.05 L/s and retention was measured for 72 hours. At one occasion, the subjects inhaled the particles at a normal airway resistance. At a second occasion, a 2-3-fold increase in airway resistance was induced by a cholinergic provocation before inhalation of the particles. At a third occasion, a corresponding provocation was induced after inhalation of the particles. The percentage lung depositions were 76 +/- 7, 68 +/- 7, and 73 +/- 8 (mean +/- SD) for "normal airway resistance," "provocation before," and "provocation after" exposures, respectively. The lower value for the "provocation before" exposure was probably a result of increased mucociliary clearance, due to cholinergic stimulation, before the first measurements of radioactivity. The retentions at 24 hours were 51 +/- 7, 52 +/- 9, and 51 +/- 8 in percent of initial lung deposition for "normal airway resistance," "provocation before," and "provocation after" exposures, respectively. We conclude that our inhalation technique is useful in studying conditions in the bronchioles, as deposition is rather independent of airway resistance.

Administration, Inhalation↗

Clearance in small ciliated airways in allergic asthmatics after bronchial allergen provocation.

BACKGROUND: Asthma tends to affect mucociliary clearance, as assessed from measurements in large airways. However, there is no knowledge about clearance in the smallest airways of the tracheobronchial region in acute exacerbation of asthma. OBJECTIVE: The aim of the study was to investigate clearance from the bronchiolar region in patients with allergic asthma in a situation resembling a mild acute exacerbation of the disease. We also aimed to compare clearance data with corresponding data found for healthy subjects and asthmatics on therapy. METHODS: Tracheobronchial clearance was studied twice in 9 patients with mild asthma of the allergic type after inhalation of 6 microm (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. At one exposure, inhalation was performed 4 h after bronchial provocation with an allergen the patients were allergic to. The second exposure was a control measurement. The particles were inhaled at an extremely slow flow, 0.05 liter/s, which gives deposition mainly in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h. RESULTS: All patients demonstrated an early asthmatic reaction of varying degree after bronchial provocation. There was significant clearance of radioaerosol in each 24-hour period for both exposures, with the possible exception of the period between 24 and 48 h for the provocation exposure, with similar fractions of retained particles at all points of time. The retained fractions were significantly larger compared to a group of healthy subjects and asthmatics on regular treatment with anti-inflammatory drugs. CONCLUSIONS: Our results indicate that in allergic asthmatics a bronchial allergen provocation with an early asthmatic reaction does not significantly influence overall clearance from the bronchiolar region. However, in the present group of patients, retention in small ciliated airways was significantly higher compared to healthy subjects and asthmatics on regular treatment.

Adult↗

Longitudinal and genetic effects in the relationship between pulmonary function and cognitive performance.

Previous studies have found cognitive deficits in patients with impaired pulmonary function, and recent data from healthy older adults suggest an association of pulmonary function with cognitive function. This 6-year longitudinal study evaluated genetic and environmental sources of covariation in the association of pulmonary function and cognitive performance. The sample included 222 Swedish twin pairs (60% women) with a mean age of 62.3 (+/- 7.7) years (age range: 40-84). Hierarchical multiple regression analyses, controlling for the effects of age, gender, and height, were employed to predict performance on cognitive tests of fluid intelligence (Digit Symbol, Block Design, Digit Span-Backward) and crystallized intelligence (Information) from forced expiratory volume in one second (FEV1). Bivariate cross-twin correlations were used to evaluate the contribution of genetic and environmental factors in the association of pulmonary function and cognitive performance. Results indicated that FEV1 predicted performance on tests of fluid intelligence but not crystallized intelligence at the initial assessment and at the 6-year follow-up. Cross-twin correlational analyses indicated that genetic effects accounted for a greater share of the association of pulmonary function and cognitive performance than environmental effects, but environment also accounted for a substantial share of the covariance.

Adult↗

Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose.

We investigated the effects of NO2 and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 microg x m(-3) NO2 for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO2 and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO2 was at EP -25% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO2 exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO2 plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO2 enhances the airway response to a nonsymptomatic allergen dose.

Adult↗

Description and primary results from an audiometric study of male twins.

OBJECTIVE: The purpose of this study is to present descriptive results from an audiometric examination of a male twin sample, compare the values with normative databases, and explore whether there are age differences in genetic and environmental contributions to variation in hearing. DESIGN: Audiometric and questionnaire data were collected on a subsample of male twins who were identified through the population-based Swedish Twin Registry. Hearing examinations were completed for a total of 557 intact pairs, comprised of 250 identical (monozygotic [MZ] pairs and 307 fraternal (dizygotic [DZ] pairs aged 36 to 80 yr. A scale measuring hearing in the high-tone ranges was constructed by calculating the mean for the hearing threshold values obtained for both ears combined at 3000, 4000, 6000, and 8000 Hz for air conduction. RESULTS: To assess whether the twin values are representative of genera hearing function, the hearing thresholds were compared with values from two normative databases. Results suggest that these twin data provide a valid representation of hearing function in a cross-section of the Swedish male population, aged 35 and older. The mean values for hearing ability decreased across age, and variation increased. Twin similarity, estimated across four age groups using intraclass correlations, decreased from 0.716 to 0.516 for the MZ pairs and increased from 0.131 to 0.279 for the DZ pairs. These results suggest that variation in hearing ability in the high ranges is due to genetic and environmental factors and that environmental effects become more important with age. CONCLUSIONS: These data reflect typical age-related deterioration in hearing ability accompanied by greater individual differences in hearing function with age. Across all ages, genetic and environmental effects are important sources of variation in hearing. However, preliminary analyses suggest that the relative influence of environment increases with age. These environmental effects are of the nonshared type that are not associated with shared family environments but rather are explained by unique exposures.

Adult↗

Residential radon and lung cancer in Sweden: risk analysis accounting for random error in the exposure assessment.

A large epidemiologic study on residential radon exposure and lung cancer has been conducted in Sweden. An attempt is now made to quantify the impact of random error in the exposure assessment on the risk estimate for lung cancer in this study. The study included 1,360 lung cancer cases, diagnosed from 1980 to 1984, and 2,847 population controls. Radon measurements were performed in 8,992 dwellings occupied by the study subjects some time since 1947. Questionnaires provided information on smoking and other risk factors. Imprecision in the retrospective exposure assessment for radon was estimated from a Monte Carlo technique modeling Swedish conditions. Adjusted risk estimates were obtained from regression analyses based on expected values for true time-weighted average residential radon concentration (TWA), conditional on observed TWA. Without adjustment for random error in the TWA estimates, the linear excess relative risk coefficient was 0.10 per 100 Bq m(-3), but an excess relative risk of about 0.15 to 0.20 per 100 Bq m(-3) was suggested following adjustment. The potentially significant consequences of errors in the retrospective radon exposure assessment should be taken into consideration in the risk estimation as well as in comparisons of results of different studies and in future pooled analyses.

Adult↗

Genes, environments, and sex: factors of importance in atopic diseases in 7-9-year-old Swedish twins.

Various atopic manifestations among adults have been shown to be influenced mainly by genetic factors. With the increase in prevalence of atopic diseases in recent years, especially among children, a great deal of attention has been given to environmental causes. In a study of 1480 Swedish twin pairs, 7-9 years old, we examined the importance of genetic and environmental factors in asthma, hay fever, eczema, and urticaria. Structural equation model fitting showed 33-76% of the variation in liability to the diseases to be due to genetic effects. Shared environmental effects were also important for hay fever and urticaria in both sexes and for eczema among girls. The clustering of atopic disease in families was almost entirely due to a common set of genes, but each disease manifestation also seemed to have specific genes of importance. Investigation of unlike-sex twins showed that boys had a higher cumulative incidence of asthma and hay fever than girls, whereas girls had a higher incidence of eczema. Thus, it may be concluded that although genetic factors are of major importance in atopic manifestation in children, both environmental and sex-related factors play a role.

Asthma↗

Nitrogen dioxide exposure enhances asthmatic reaction to inhaled allergen in subjects with asthma.

We investigated whether exposure to a low level (490 micrograms/m3) of nitrogen dioxide (NO2) affects bronchial responsiveness to allergen and enhances allergen-induced increase in airway responsiveness to histamine. Eighteen subjects with asthma and allergy to pollen were exposed at rest to either purified air or NO2 for 30 min followed 4 h later by an allergen inhalation challenge. Responsiveness to histamine was measured the day after. Lung function during NO2 exposure and allergen challenge was measured by plethysmography and after exposure by a portable spirometer hourly. The order of exposure to NO2 and air was randomized and separated by at least 2 wk. The asthmatic reaction during the late phase was enhanced by NO2, and peak expiratory flow after allergen challenge was on average 6.6% lower (p = 0.02) after NO2 than after air exposure. The number of subjects having a late asthmatic reaction (fall in FEV1 > 15%) was seven after air and 10 after NO2 (NS). Peripheral blood samples were analyzed for differential cell counts before and after NO2/allergen and serum levels of eosinophil cationic protein (ECP). NO2 effect on lung function was neither associated with an increase in eosinophil numbers nor with ECP levels. NO2 did not affect lung function before allergen challenge, early asthmatic reaction, and allergen-induced increase in responsiveness to histamine. These results indicate that short exposure to an ambient level of NO2 followed several hours later by allergen inhalation enhances allergen-induced late asthmatic reaction.

Administration, Inhalation↗

Tracheobronchial deposition and clearance in small airways in asthmatic subjects.

Asthma tends to impair mucociliary clearance, as assessed from measurements in large airways. However, very little is known about clearance in the smallest airways of the tracheobronchial region. Deposition and clearance was estimated in 11 subjects with stable asymptomatic asthma and 10 healthy subjects after inhalation of 6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at an extremely slow flow, 0.05 L.s-1. Theoretical calculations and experimental data in healthy subjects using this slow flow support an enhanced deposition in the tracheobronchial region, in particular in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h. Clearance was significant every 24 h both for asthmatic and healthy subjects, with similar fractions of retained particles at all time-points. The fractions of tracheobronchially-deposited particles were on average 41 and 47% for asthmatic and healthy subjects, respectively, as compared to a maximal deposition of 30% using a normal inhalation flow (0.5 L.s-1). No significant correlation was found between lung retention and lung function, either in asthmatics or in healthy subjects. Our results indicate that particles clear equally well from small ciliated airways in asthmatic and healthy subjects, maybe as a consequence of an optimal asthma therapy. Furthermore, our results show that it is possible to enhance tracheobronchial deposition both in healthy and asthmatic subjects, i.e. practically independent of airway dimensions, by inhaling rather large aerosol particles extremely slowly. This may be a useful therapeutic approach.

Administration, Inhalation↗

Oropharyngeal deposition of 3.5 microns particles inhaled through an elongated mouthpiece.

We previously studied the deposition of inhaled particles in the oropharynx of asthmatic patients, and found that a pharyngeal narrowing during inhalation seems to be one reason for high oropharyngeal deposition. In the present study, we investigated whether by-passing a larger part of the oral cavity by using an elongated mouthpiece would reduce deposition in the oropharynx, and increase deposition in the lungs. Deposition in the oropharynx and in the lungs was estimated in nine patients with obstructive airway diseases. In earlier investigations, three of these patients had repeatedly shown extremely high oropharyngeal deposition (> 70%). In the present study, the patients inhaled 3.5 microns (aerodynamic diameter) radiolabelled Teflon particles at 0.5 L.s-1, with and without an individually adapted elongated mouthpiece. Radioactivity was measured using a profile scanner. On average, oropharyngeal deposition was 27% (range 12-45%) and 30% (range 11-77%) of the total amount of particles deposited in the body, with and without elongated mouthpiece, respectively. There was no significant difference between these values (p > 0.05), nor between the values of lung deposition. However, oropharyngeal deposition was markedly reduced, with a corresponding increase in lung deposition, by the elongated mouthpiece in the one and only patient who still showed extremely high oropharyngeal deposition (> 70%). Our study shows that lengthening of the mouthpiece is not sufficient to reduce average deposition of aerosol particles in the oropharynx in patients with comparatively normal deposition values. This result, however, does not exclude a beneficial effect in patients with extremely high oropharyngeal deposition.

Administration, Inhalation↗

Added external resistance reduces oropharyngeal deposition and increases lung deposition of aerosol particles in asthmatics.

Mouth and throat, and regional lung deposition was estimated in fifteen asthmatic subjects for 3.6-microns (aerodynamic diameter) radiolabeled polytetrafluoroethylene (Teflon) particles inhaled at 0.5 L/s with and without added external resistance. Radioactivity was measured by a profile scanner. Behavior of the pharynx and larynx was assessed by fiberoptic laryngoscopy. Mean mouth and throat deposition was 22% (range, 13 to 47%) and 33% (range, 12 to 84%) with and without resistance (p < 0.05), respectively. A marked reduction in mouth and throat deposition (range, 20 to 44%), with a corresponding increase in lung deposition, was observed especially in the six subjects with mouth and throat deposition values > 30% at inhalation without resistance. Furthermore, a small (mean 8%) but significant (p < 0.05) increase in peripheral lung deposition, estimated as retention at 24 h, was found at inhalation with increased resistance. The fiberoptic examination showed wide intersubject variability in the pharynx and larynx, with tendencies toward higher mouth and throat deposition with pharyngeal narrowing, and significantly (p < 0.05) lower lung retention with laryngeal narrowing. Our results show that an external resistance reduces mouth and throat deposition and increases deposition and retention of aerosol particles in the lungs in asthmatic individuals.

Adult↗

Repeatability of airway deposition and tracheobronchial clearance rate over three days in chronic bronchitis.

Previous investigations on tracheobronchial clearance in chronic bronchitis or chronic obstructive pulmonary disease (COPD) have usually referred to measurements during a short time-period, i.e. a few hours. The purpose of this study, therefore, was to study regional particle deposition and tracheobronchial clearance during 72 h. In 14 patients with chronic bronchitis clearance of 111In-labelled 3.6 micrograms Teflon particles and lung function were measured on two occasions, with an interval of 2 weeks. Lung retention of test particles was measured at 0, 24, 48 and 72 h using a profile scanner. The weight of expectorated sputum samples was measured after the two clearance measurements. The particle retentions at all time-points were reproducible, as seen from the two measurements ( r > 0.90). The fast clearance phase was completed within 72 h. No correlation between sputum volume and clearance was seen. There was a significant negative correlation between airway resistance and the 72 h retention (r= -0.66), and an even better correlation between specific airway resistance and the 72 h retention (r = -0.82), indicating more central deposition in obstructed airways. There was no significant correlation between lung function tests reflecting smaller airways and the 72 h retentions. Deposition data agreed well with theoretical calculations and experimental data in healthy subjects. In spite of earlier findings that mucociliary transport is usually severely impaired in chronic bronchitis and COPD, the present results indicate that overall tracheobronchial mucus clearance in these patients is fairly effective, probably due to a productive cough. Alveolar deposition may be estimated by measurements of the 72 h retention in subjects with chronic obstructive pulmonary disease. The 72 h retention is dependent mainly on the calibre of larger airways. The present method of studying airway clearance during 3 days is highly reproducible.

Adult↗