[Radon in dwellings and lung cancer. Smoking is more than an additional risk increasing factor].
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Adult↗
Biomedical subjects
M Svartengren
Publications and source records attributed to M Svartengren.
Residential radon exposure and lung cancer in Sweden.
BACKGROUND: Residential radon is the principal source of exposure to ionizing radiation in most countries. To determine the implications for the risk of lung cancer, we performed a nationwide case-control study in Sweden. METHODS: The study included 586 women and 774 men 35 to 74 years of age with lung cancer that was diagnosed between 1980 and 1984. For comparison, 1380 female and 1467 male controls were studied. Radon was measured in 8992 dwellings occupied by the study subjects at some time since 1947. Information on smoking habits and other risk factors for lung cancer was obtained from questionnaires. RESULTS: Radon levels followed a log-normal distribution, with geometric and arithmetic means of 1.6 and 2.9 pCi per liter (60.5 and 106.5 Bq per cubic meter), respectively. The risk of lung cancer increased in relation to both estimated cumulative and time-weighted exposure to radon. In comparison with time-weighted average radon concentrations up to 1.4 pCi per liter (50 Bq per cubic meter), the relative risk was 1.3 (95 percent confidence interval, 1.1 to 1.6) for average radon concentrations of 3.8 to 10.8 pCi per liter (140 to 400 Bq per cubic meter), and it was 1.8 (95 percent confidence interval, 1.1 to 2.9) at concentrations exceeding 10.8 pCi per liter. The estimates of risk were in the same range as those projected from data in miners. The interaction between radon exposure and smoking with regard to lung cancer exceeded additivity and was closer to a multiplicative effect. CONCLUSIONS: Residential exposure to radon is an important cause of lung cancer in the general population. The risks appear consistent with earlier estimates based on data in miners.
Adult↗
Genetic and environmental influences on pulmonary function in aging Swedish twins.
BACKGROUND: In addition to their value in assessing pulmonary health and disease, spirometric variables have been shown to be powerful predictors of time until death in aging populations. The sources of variability in these spirometric values are consequently of relevance to basic gerontological research, and also of potential value in clinical application. The objective of this study was to estimate genetic and environmental sources of variance in pulmonary function. METHODS: The study involved 230 Swedish twin pairs (mean age = 64.9 years), of which number 37 monozygotic (MZ) pairs and 72 dizygotic (DZ) pairs had been separated and reared apart. Comparing these groups to the 57 MZ and 64 DZ pairs reared together permits stronger interpretation than that of conventional twin studies. Measures of vital capacity (VC) and forced expiratory volume in one second (FEV1) were residualized for height, age, sex, and tobacco consumption in pack-years. RESULTS: Maximum likelihood analyses of VC and FEV1 gave heritability estimates of .48 and .67, respectively. Age effects were explored both by dividing the sample into two cohorts, respectively above and below 65 years, and by moving interval analysis. In the two-cohort analysis, heritabilities were somewhat higher for the older cohort than the younger cohort for FEV1. The opposite was true for VC: heritability was lower in the older cohort, and there was evidence for a shared rearing environmental effect for this group. Moving interval analysis suggests these differences are gradual rather than saltatory. There were no gender differences in parameter estimates. CONCLUSION: Genetic factors account for between one-half and two-thirds of the variability in pulmonary function. There is a suggestion of age differences in the relative importance of genetic and environmental influences.
Adult↗
Deposition of inhaled particles in the mouth and throat of asthmatic subjects.
We previously studied the deposition of inhaled particles in the mouth and throat of asthmatic patients, and found large, reproducible differences among subjects. In the present study, we examined whether anatomical and/or functional differences in the pharynx and larynx could underlie this interindividual variation. Deposition in the mouth and throat, and in the lung was estimated in 16 asthmatic subjects after inhalation of 3.6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at a flow rate of 0.5 l.s-1 with maximally deep breaths. Radioactivity was measured by external scanning over head and neck, lungs and stomach, immediately after the inhalation. Radioactivity in the lungs was also measured 24 h later. A measure of the total amount of particles deposited in the mouth and throat was obtained from the added activities in mouthwash, head and neck, and stomach, immediately after the inhalation of the test particles. Pharynx and larynx function was examined by fibreoptic laryngoscopy performed during a corresponding inhalation procedure. Deposition in the mouth and throat varied widely among the subjects, ranging 9-76% (median 12%). We found two subpopulations, 13 subjects in the range 9-34%, and 3 subjects with > 70% deposition. Deviations in pharyngeal configuration during inhalation were significantly related to high mouth and throat deposition, whereas functional differences in the larynx were not. Our study shows that mouth and throat deposition may be extremely high in some asthmatics, and that pharyngeal configuration affects deposition of particles in the mouth and throat.
Adult↗
Bronchial reactivity, lung function, and serum immunoglobulin E in smoking-discordant monozygotic twins.
Smokers with chronic bronchitis and/or chronic obstructive pulmonary disease (COPD) have been reported to have an increased bronchial reactivity (BR). It has been discussed whether increased BR is a risk factor for the development of COPD in smokers. We studied 10 monozygotic twin pairs who were discordant for tobacco smoking by means of histamine provocation tests, lung function tests, and serum samples for total IgE. The smokers had a mild obstructive ventilatory impairment, with FEV1 significantly lower than that of the partner both when it was determined from the flow-volume loops (3.2 +/- 1.0 L for smokers and 3.4 +/- 0.8 L for nonsmokers) and by the Vitalograph spirometer (3.5 +/- 1.0 L for smokers and 3.8 +/- 0.8 L for nonsmokers). Forced midexpiratory flow (FEF25-75%) and forced expiratory flow at 75 to 85% of vital capacity (FEF75-85%) were both significantly lower in the smokers (p < 0.05). The alveolar plateau phase N2-delta test and lung clearing index in the multibreath nitrogen washout test were both significantly affected in the smokers (p < 0.05 and p < 0.01, respectively). We found no significant difference in histamine reactivity between smokers and nonsmokers and no correlation between differences in reactivity and differences in lung function within pairs. Total serum IgE was significantly higher in the smokers than in their nonsmoking siblings. These data suggest that obstructive ventilatory impairment and raised serum IgE are earlier and more constant manifestations of tobacco smoking than increased bronchial reactivity. Thus, bronchial hyperreactivity does not seem to be a major risk factor for the development of early airways obstruction in smokers.
Adult↗
Deposition in asthmatics of particles inhaled in air or in helium-oxygen.
Ten subjects with asthma inhaled 3.6 micron particles labeled with 111In in air and in a helium-oxygen mixture (He-O2) at 0.5 and at 1.2 L/s. Lung retention was measured after zero and after 24 h, and the percentage 24-h retention (Ret24) was taken to represent the fraction deposited in the alveolar part of the lung. For both inhalation rates, Ret24 was significantly higher when particles were inhaled with He-O2 than with air. The increase in Ret24 seemed to be larger in subjects with asthma than in healthy persons earlier studied. Ret24 was correlated with changes in both large and small airways, especially when the particles were inhaled with He-O2. Our data suggest that inhalation of drugs in He-O2 might be of therapeutic value when treating patients with severely obstructed airways.
Administration, Inhalation↗
Methylations in hemoglobin from monozygotic twins discordant for cigarette smoking: hereditary and tobacco-related factors.
Dose monitoring of exogenous methylators by measurement of N-methylvaline in hemoglobin (Hb) is rendered difficult due to a relatively high, variable background in unexposed persons. A kinetic study indicates intracellular S-adenosylmethionine to be a main source of these background methylations. A comparison of twin pairs indicates that the variation in methylvaline levels is partly hereditary (P less than 0.001). Therefore, in a study of monozygotic twin pairs discordant for tobacco smoking the resolving power of the monitoring was increased and in vivo doses of methylators from the smoke could be more easily monitored through their adducts to Hb. Probably, twin studies offer a useful tool for the identification and quantification of electrophiles of endogenous and exogenous origin.
Adult↗
Individual differences in activity of glutathione peroxidase and catalase studied in monozygotic twins discordant for smoking.
1. Cigarette smoke contains free radicals. The enzymes glutathione peroxidase (GSH-px) and catalase are important parts of the anti-oxidative protecting system. 2. Ten pairs of monozygotic twins, who were discordant for smoking, were analysed in order to determine their erythrocyte glutathione peroxidase and catalase activities and their plasma concentrations of selenium. 3. Analysis of variance (ANOVA) revealed that the difference in activities of catalase and glutathione peroxidase was much less within pairs than between pairs, indicating a large individual variation due to genetic expression or shared environment and no major effect from smoking. 4. The plasma selenium levels of the investigated twins revealed sufficient intake of selenium to maintain maximal activity of GSH-px in erythrocytes. The mean +/- s.d. selenium concentration in plasma for smokers was 98 +/- 16 micrograms l-1 and for non-smokers 111 +/- 16 micrograms l-1. There was no correlation between plasma selenium and glutathione peroxidase in erythrocytes.
Adult↗
Regional deposition of 3.6-micron particles and lung function in asthmatic subjects.
In a group of moderately severe asthmatic subjects, regional deposition of 3.6-microns (aerodynamic diameter) monodispersed Teflon particles labeled with 111In was studied twice. The particles were inhaled with maximally deep inhalation at 0.5 l/s. Lung retention was measured at 0, 6, 24, and 48 h by use of a profile scanner equipped with two 13 x 5-cm NaI crystals. The retentions at 24 (Ret24) and 48 h were highly correlated (r = 0.96 with a slope of the regression line close to 1). There was a poor correlation between retention at 6 h and Ret24 (r = 0.54). The Ret24 values at the two exposures were well correlated (r = 0.86). There were significant correlations between airway resistance as well as single-breath nitrogen test phase III and Ret24 (r = 0.70 and 0.67, respectively). The correlation between single-breath nitrogen test phase III and Ret24 persisted also when only subjects within a narrow interval of airway resistance were included. The study indicates that regional deposition can be studied by measurements of Ret24 in subjects with moderately severe asthma and that it is dependent on changes in both large and small airways.
Administration, Inhalation↗
Bronchial reactivity and allergy-promoting factors in monozygotic twins discordant for allergic rhinitis.
Bronchial reactivity was studied twice in eight monozygotic twin pairs discordant for allergic rhinitis with pollen hypersensitivity, during the winter season (all eight pairs) and during the pollen season (seven pairs). On both occasions, the allergic twins showed significantly higher reactivity than their nonallergic siblings. The results indicate that moderate allergic rhinitis is associated with increased bronchial reactivity. This increased reactivity is an acquired trait; however, bronchial reactivity is not constantly increased in pollen rhinitis and may be normal even during the pollen season. The symptoms of allergic rhinitis usually started in childhood before the separation of the siblings. We could not demonstrate any major differences in exposure to allergens or airway irritants between the siblings. The allergic twins tended to have lower birth weight and insufficient weight increase just after birth.
Adult↗
[Occupational and environmental medicine in Estonia--a field for further cooperation].
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Estonia↗
Bronchial reactivity and atopy in asthma discordant monozygotic twins.
Bronchial reactivity was studied in six asthma-discordant monozygotic twin pairs. In four pairs, atopy was confirmed in the asthmatic twin. It was not confirmed in any of the nonasthmatics. In five pairs, the asthmatic twin was markedly more reactive than the nonasthmatic partner. Bronchial reactivity correlated significantly with total IgE. The results indicate that hyperreactivity and atopy were acquired.
Adult↗
Tracheobronchial clearance in asthma-discordant monozygotic twins.
Tracheobronchial clearance and bronchial reactivity were studied in 6 asthma-discordant monozygotic twin pairs, and in 3 concordant pairs as controls. Clearance of 6-microns Teflon particles labeled with 99mTc was followed for 2 h. The results indicate that clearance in the larger airways is usually not severely impaired in mild to moderate asthma, and that it may be increased as well as decreased. Bronchial reactivity correlated with clearance in the nonasthmatics.
Administration, Inhalation↗
Individual differences in regional deposition of 6-micron particles in humans with induced bronchoconstriction.
The effect of induced bronchoconstriction on regional lung deposition of 6 microns aerodynamic diameter 99mTc-labeled Teflon particles was studied in eight healthy non-smokers. The Teflon particles were inhaled at 0.5 l/s from a 25-l glass bulb with 8-12 maximally deep breaths on four consecutive days. For three exposures, various degrees of bronchoconstriction were induced using an aerosol of methacholine bromide before the inhalation of the Teflon particles. For the fourth (control) exposure, bronchoconstriction was induced after the inhalation of the Teflon particles. The degree of bronchoconstriction was quantified by measurements of airway resistance (Raw) using a whole-body plethysmograph. The fraction of alveolarly deposited particles in the lung (FAD) was estimated by measurements of radioactivity in the lung immediately after inhalation of the Teflon particles and 6 h later. Earlier studies have shown that when the mucociliary transport is stimulated with the cholinergic aerosol used in this study, the 6-h retention values (Ret6) are similar to the 24-h values. Within the subjects there was a close relationship between Raw and Ret6 with a decrease of Ret6 with increased Raw. This decrease varied markedly among the subjects. The relationship between Raw and Ret6 calculated from the model by the Task Group on Lung Dynamics, in which the airway diameters were varied, agreed with our experimental data. On an average, airway resistance of 1 and 2 cm H2O.s/l correspond to FAD of about 50% and 25%, respectively.
Administration, Inhalation↗
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↗