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Biomedical subjects

M Svartengren

Publications and source records attributed to M Svartengren.

At least 19 recordsLinked to original sources

Negligible clearance of ultrafine particles retained in healthy and affected human lungs.

Ambient particles are believed to be a specific health hazard, although the underlying mechanisms are not fully understood. There are data in the literature indicating fast and substantial systemic uptake of particles from the lung. The present authors have developed an improved method to produce ultrafine particles with more stable radiolabelling and defined particle size range. Fifteen subjects inhaled technetium 99m (99mTc)-labelled carbonaceous particles of 100 nm in size. Radioactivity over the lung was followed for 70 h. The clearance of these ultrafine particles from the lungs and specifically translocation to the circulation was tested. Lung retention for all subjects at 46 h was mean+/-sd 99+/-4.6%. Cumulative leaching of 99mTc activity from the particles was 2.6+/-0.96% at 70 h. The 24-h activity leaching in urine was 1.0+/-0.55%. No evidence of a quantitatively important translocation of 100-nm particles to the systemic circulation from the lungs was found. More research is needed to establish if the approximately 1% cleared activity originates from leached activity or insoluble translocated particles, and whether a few per cent of translocated particles is sufficient to cause harmful effects.

Administration, Inhalation↗

IgE-sensitization to predatory mites and respiratory symptoms in Swedish greenhouse workers.

BACKGROUND: Predatory mites are used as biological pesticides worldwide for control of spider mites and other pests in greenhouses. The aim of this study was to evaluate the impact of occupational exposure to Phytoseiulus persimilis and Hypoaspis miles on IgE sensitization among a large group of Swedish greenhouse workers and to examine the relationship between exposure and allergic asthma and rhinoconjunctivitis. METHODS: A total of 96 greenhouse workers from the southern part of Sweden, who were using the predatory mites for control of pests, were investigated with a questionnaire and a medical examination including lung function test. Blood samples were taken to test for allergen-specific IgE antibodies to Phytoseiulus persimilis and Hypoaspis miles as well as to Tetranychus urticae, Dermatophagoides pteronyssinus/farinae and Tyrophagus putrescentiae. RESULTS: Seventeen of the 96 workers were positive in ImmunoCAP to predatory mites: 17 to P. persimilis (17.7%) and 14 to H. miles (14.6%). Subjects sensitized to predatory mites were significantly more often atopic (13/17), defined as a positive Phadiatop, than those who lacked IgE against these mite species (17/79) (P <0.01). IgE antibodies to the red spider mite T. urticae were present among 23 subjects. Thirty-five of the investigated subjects displayed a positive ImmunoCAP to at least one of the investigated mite species. Furthermore, sensitization to any of the mites tested was significantly associated with asthma (OR=9.3) and rhinoconjunctivitis (OR=4.3). CONCLUSIONS: IgE sensitization to predatory mites, P. persimilis and H. miles, is common among greenhouse workers. The findings stress the importance of improved allergen avoidance in greenhouse environments.

Adult↗

Long-term clearance from small airways decreases with age.

The prevalence of respiratory symptoms increases with age. Age has been found to be negatively associated with large airway clearance. The small airways region is considered important for development of airway disease. Clearance after the first 24 h was studied in 46 healthy subjects with a wide age distribution, (mean 42, range 19-81 yrs). All subjects inhaled monodisperse 6 microm Teflon particles labelled with 111In, with an extremely slow inhalation flow (0.05 L.s-1). The particles were mainly deposited in the small conducting airways. Lung retention was measured at 0 and 24 h, and at 7, 14 and 21 days after inhalation. Significant relationships were found for the individual 24 h "large" airway clearance in per cent of initial lung deposition with age, forced expiratory volume in one second and forced vital capacity. Age was negatively associated with "small" airway clearance after 24 h as estimated at 2, 7, 14 and 21 days. Using stepwise linear regression only age remained significantly associated to clearance. In conclusion, small airway clearance over 21 days was found to decrease with age. This might be one factor associated with the high prevalence of respiratory symptoms associated among the elderly.

Administration, Inhalation↗

Long-term clearance from small airways in patients with cystic fibrosis.

Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways. Radiolabelled Teflon particles (6 microm) were inhaled with an extremely slow inhalation flow, 0.05 L x s(-1). Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects. The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12-16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase. The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.

Administration, Inhalation↗

Building characteristics, indoor air quality and recurrent wheezing in very young children (BAMSE).

This study was conducted to examine the impact of building characteristics and indoor air quality on recurrent wheezing in infants. We followed a birth cohort (BAMSE) comprising 4089 children, born in predefined areas of Stockholm, during their first 2 years of life. Information on exposures was obtained from parental questionnaires when the children were 2 months and on symptoms and diseases when the children were 1 and 2 years old. Children with recurrent wheezing, and two age-matched controls per case, were identified and enrolled in a nested case-control study. The homes were investigated and ventilation rate, humidity, temperature and NO2 measured. We found that living in an apartment erected after 1939, or in a private home with crawl space/concrete slab foundation were associated with an increased risk of recurrent wheezing, odds ratio (OR) 2.5 (1.3-4.8) and 2.5 (1.1-5.4), respectively. The same was true for living in homes with absolute indoor humidity >5.8 g/kg, OR 1.7 (1.0-2.9) and in homes where windowpane condensation was consistently reported over several years, OR 2.2 (1.1-4.5). However, air change rate and type of ventilation system did not seem to affect the risk. In conclusion, relatively new apartment buildings, single-family homes with crawl space/concrete slab foundation, elevated indoor humidity, and reported wintertime windowpane condensation were associated with recurrent wheezing in infants. Thus, improvements of the building quality may have potential to prevent infant wheezing.

Air Pollutants↗

Radionuclide biokinetics database (RBDATA-EULEP): an update.

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.

Body Burden↗

Influence of male sex and parental allergic disease on childhood wheezing: role of interactions.

BACKGROUND: Boys have been reported to be more susceptible to childhood wheezing, whereas girls are more susceptible later in life. This difference might be related to both genetic and environmental factors. OBJECTIVE: To investigate the influence of male sex and parental allergic disease on the development of childhood wheezing. METHODS: Infants (n=4089) born in Stockholm were recruited in a prospective study, BAMSE. Data on parental allergic diseases were obtained from questionnaires answered at the children's birth and on symptoms of wheezing at 1, 2 and 4 years of age. Sensitization to inhalant allergens and lung function was investigated at the age of 4 years. RESULTS: Children were classified as having recurrent, transient (n=266), early-onset persistent (n=319) and late-onset wheezing (n=195). Boys were over-represented in all groups of wheezing (odds ratio, OR=1.4-1.5) and both maternal and paternal allergic disease was of importance for the wheezing outcomes. A dominating influence from maternal allergic disease was only seen in children with persistent wheezing. An interaction exceeding additivity was found between male sex and parental allergic disease, particularly in children with persistent wheezing (OR=2.9 and 95% confidence interval, CI 95% 2.1-4.0 for boys with any parental history vs. OR=1.4, CI 95% 1.0-2.1 for girls). Interaction between male sex and parental allergic disease was also observed in children who wheezed at the age of 4 years and were sensitized to inhalant allergens. CONCLUSION: Our data suggest an interaction between male sex and parental allergic disease in childhood wheezing, which may represent a sex-specific genetic influence.

Child, Preschool↗

Indoor exposures and recurrent wheezing in infants: a study in the BAMSE cohort.

AIM: The aim of this study was to examine the relationship between indoor exposures and the home environment, and the development of recurrent wheezing during infancy. METHODS: A birth cohort, comprising 4089 children, was followed. Information on exposures was obtained shortly after birth, and episodes of wheezing were recorded when the infants were 1 and 2 y of age. In a nested case-control study, 181 infants were enrolled, who had three or more reported episodes of wheezing after 3 mo of age combined with either use of inhaled steroids or symptoms of bronchial hyper-reactivity, and 359 age-matched controls. Home inspections were performed during the winter following enrolment, and indoor conditions were measured. RESULTS: Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. The OR for recurrent infant wheezing associated with signs of dampness reported prospectively by parents was 1.4 (0.9-2.2), and the OR for observed signs of dampness at home inspections was 1.6 (1.0-2.5). A trend was found in the risk of recurrent wheezing in relation to the number of indicators of dampness: OR 1.3 (0.8-2.2) for one sign of dampness and OR 2.7 (1.3-5.4) for three or more signs of dampness. Newly painted surfaces in the child's bedroom was associated with an increased OR for recurrent wheezing: 1.7 (1.3-2.6). CONCLUSION: Indicators of dampness, as well as recently repainted interior surfaces, appear to be associated with recurrent infant wheezing, with a strengthened effect of combined indoor exposures.

Air Pollution, Indoor↗

Strategies for preventing wheezing and asthma in small children.

OBJECTIVE: To assess the effects of living in agreement with allergy preventive guidelines on wheezing and asthma at 2 years of age. DESIGN: Prospective birth cohort study (BAMSE). Questionnaires on heredity and environmental factors were answered when the child was 2 months, and detailed questionnaires on symptoms at 1 and 2 years of age. PARTICIPANTS: 4089 children, born during 1994-1996. SETTING: Child Health Centres in central and north-western parts of Stockholm, Sweden. MAIN OUTCOME MEASURES: Wheezing and asthma up to the age of 2. RESULTS: The effects of preventive guidelines regarding breastfeeding, maternal tobacco smoke and home dampness on wheezing and asthma were assessed in multiple logistic regression models. The cumulative incidence of recurrent wheezing at 2 years of age was 12.6% and of asthma 6.8% among those with a lifestyle in agreement with all guidelines and 24.1 and 17.9%, respectively, in families exposed to at least two of the three risk factors. Among children with no heredity, family lifestyle according to the guidelines gave a twofold reduction of asthma (5.3 vs. 10.5%), while the group with heredity had a threefold reduction (9.1 vs. 27.3%). The attributable fraction for asthma associated with the guidelines was 23% in total and 33% among those with heredity. CONCLUSION: In this observational study, family lifestyle according to preventive guidelines is associated with an important reduction of recurrent wheezing and asthma at 2 years of age, especially among children with allergic heredity. A follow-up will determine whether there still a risk reduction of both symptoms and disease.

Asthma↗

Family history and risk of atopic dermatitis in children up to 4 years.

BACKGROUND: The aetiology of atopic dermatitis (AD) is presumably multi-factorial, with interactions between genetic and environmental factors. OBJECTIVE: To investigate the relation between atopic family history and development of AD up to 4 years. METHODS: Using annual questionnaires, we studied the cumulative incidence of AD in 0-4-year-olds in a prospective birth cohort of 4089. Atopic diseases in parents and siblings were recorded at birth. The occurrence of serum immunoglobulin E (IgE) antibodies to inhalant and food allergens was analysed in 2614 4-year-olds, and AD was divided into non-IgE-associated and IgE-associated. RESULTS: Of the children without atopic parents, 27.1% developed AD; of those with single or double parental atopic history, 37.9% and 50.0%, respectively, did so. The effects of parental history of eczema and of atopic respiratory disease (ARD) did not differ significantly, nor did those of maternal and paternal history. Parental history of ARD increased the risk significantly more for IgE-associated AD than for non-IgE-associated AD (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.5-2.8 vs. OR 1.3; 95% CI 1.0-1.8), whereas the two forms lacked major differences in the effect of parental eczema. A history of eczema in older siblings was a risk indicator for both forms of AD (OR 2.1; 95% CI 1.4-3.3 vs. OR 1.8; 95% CI 1.2-2.6). CONCLUSIONS: We found no difference between the effects of maternal and paternal atopic history. Parental eczema was a risk factor for AD irrespective of its association with IgE, but parental history of ARD mainly increased the risk of IgE-associated AD.

Child, Preschool↗

Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort.

INTRODUCTION: There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results. OBJECTIVE: To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study. METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders. RESULTS: A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38). CONCLUSION: Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.

Adult↗

The need for a focus on air pollution research in the elderly.

During recent years an increasing focus has been directed towards the adverse health effects associated with ambient air pollution. Elderly people appear to be particularly susceptible to the adverse effects involving the respiratory and cardiovascular systems, resulting in symptoms, exacerbations of disease and even mortality. From an epidemiological point of view it is essential to obtain a more detailed description and identification of factors associated with these health effects. Novel study designs are needed with complementary exposure and biomedical characterisation. Long-term prospective studies are required. A better understanding of the pathophysiological mechanisms is considered important and requires an interaction between epidemiological and mechanistic studies in elderly individuals with or without complementary diseases that put in them especially at risk. Generally a synergy between complementary disciplines is warranted to move this important research area forward, also including in vitro models of cell responses in the elderly, animal models of diseases of the elderly, together with controlled air pollution exposure studies identifying health-related events and mechanisms. The generation of an understanding of air pollution effects in the elderly, at an elevated level, is a prerequisite to substantially reducing the adverse health effects of this population group. At local, national and European Union levels, some steps have been taken to support the research in this area. A major focus on the adverse air pollution effects in the elderly requires a long-term commitment that still remains to be established.

Aged↗

Inhalation and deposition of nebulized sodium cromoglycate in two different particle size distributions in children with asthma.

The relative deposition of two inhaled droplet size distributions of sodium cromoglycate produced by a Hudson Updraft II nebulizer was evaluated, using a setup modified from the proposed Comité Européen Normalisé (CEN) standard prEN 13544-1. The modified setup comprised an Andersen 296 impactor and a Spira Electro 2 dosimeter. The setup was characterized prior to use in children with sodium cromoglycate (SCG) and sodium fluoride as tracer aerosol. The main in vivo study was designed to allow nine children with a mean age of 10 years to inhale SCG aerosol at two different relative humidities (RH), a high RH (> 90%) and a low RH (13%), which in turn resulted in two different droplet size distributions. The nebulizer/dosimeter was set to provide 1-sec nebulization during 50 inhalations. Throughout the exposures, the children were instructed to inhale in a consistent manner with target tidal volumes (0.5 L) and inhalation flows (0.4 L/sec). Blood samples were taken at predefined time intervals, and the area under the curve (AUC) was calculated. A lung deposition program, TGLD2, was used to calculate the expected deposition, using the droplet sizes and inhalation parameters obtained during in vivo exposures. The in vivo monitoring of droplet size distribution during the exposure showed that the low, intermediate (room air), and high RHs gave a mean droplet size distribution with a mass median aerosol diameter (MMAD) of 1.2, 1.7, and 2.0 microm, respectively. The average tidal volume over all exposures was 0.51 +/- 0.12 L. The total deposition fraction was 33.4% of the estimated nebulizer output. A correlation was found between tidal volume and the calculated deposited fraction. The results indicate that there is a difference in total deposition, depending on the size of the droplet size distribution, with the larger droplet size distribution (MMAD, 2.0 microm) having a higher total deposition than the smaller droplet size distribution (MMAD, 1.2 microm). The deposition results were in good agreement with the deposition fractions estimated using the TGLD2 software for the inhalation parameters found in the study. The obtained study results can arise from differences in regional deposition, but may also be explained by differences in extrathoracic deposition.

Administration, Inhalation↗

The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies.

The Swedish Twin Registry (STR), which today has developed into a unique resource, was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases whilst controlling for genetic propensity to disease. Since that time, the Registry has been expanded and updated on several occasions, and the focus has similarly broadened to most common complex diseases. In the following, we will summarize the content of the database, describe for the first time recent data collection efforts and review some of the principal findings that have come from the Registry.

Cohort Studies↗

Ambient level of NO2 augments the inflammatory response to inhaled allergen in asthmatics.

Air pollution constitutes an important factor for asthma aggravation, and there is increased concern about respiratory health effects of common air pollutants. The purpose of this study was to examine how exposure to a high ambient concentration nitrogen dioxide (NO2) prior to a bronchial allergen challenge modulated the inflammatory response in the bronchi. Thirteen subjects with mild asthma and allergy were exposed at rest to either purified air or 500 microg x m 3 NO2 for 30 min, followed 4 h later by an allergen inhalation challenge. The exposures (NO2 or air) were performed in random order and at least 4 weeks apart. Lung function during NO2/air exposure and allergen challenge was measured by plethysmography, and then hourly by portable spirometry after exposures. Subjective symptoms were recorded during and after exposure. Bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 19 h after allergen challenge. NO2+allergen enhanced the percentage of neutrophils in both BW and BAL compared to air+allergen (BW 19 vs. 11, P=0.05; BAL 3 vs. 1, P=0.02 median values). The levels of eosinophil cationic protein (ECP) in BW was higher after NO2+allergen compared to air+allergen (90 vs. 3.6 microg/l; P=0.02, median values). There was no NO2-associated effect on symptoms or pulmonary function. These data suggest that ambient NO2 can enhance allergic inflammatory reaction in the airways without causing symptoms or pulmonary dysfunction.

Adult↗

Comparison of clearance of particles inhaled with bolus and extremely slow inhalation techniques.

Ten healthy nonsmokers inhaled 6-microm (aerodynamic diameter) Teflon particles labelled with 111In twice, once with the shallow bolus technique (volumetic lung depth 76+/-20 mL ([+/- SD]) and once with the extremely slow inhalation technique (0.05 L/s). The radioactivity in the lungs was measured at 1 and 24 hours as well as at 1, 2, and 3 weeks after both inhalations. The 24-hour lung retention a percentage of lung deposition was significantly lower for the bolus inhalation, 46%+/-9% (+/- SD) than for the extremely slow inhalation, 56%+/-11%. The retention after 21 days as a percentage of the 24-hour retention was 55%+/-9% for the shallow bolus inhalation and 56%+/-10% for the extremely slow inhalation. Also within the subjects, clearance was similar for the 2 modes of inhalation. Deposition of particles inhaled with the 2 modes of inhalation was calculated with 2 model, one being based on Monte (Carlo particle transport together with an asymmetric lung model. Deposition predicted with this model agreed well with the experimental data under the assumption that there are large retained fractions only in small ciliated airways (bronchioli) and not in large ones. For the bolus inhalation, the model predicted 43% to 50% deposition in the bronchial (BB) region of initial lung deposition, 33% to 38% in the bronchiolar (bb) region, and 16% to 22% in the alveolar region. For the extremely slow inhalation, the model predicted 31% to 34% deposition in the BB region, 45% to 47% in the bb region, and 21% to 22% in the alveolar region. In addition, it predicted about the same ratio between bb and alveolar depositions for the 2 modes of inhalation. Thus, both the experimental and theoretical data indicate that the shallow bolus particles to a considerable extent reach both the bb and the alveolar regions and that they do that at about the same extent as the particles inhaled extremely slow. This conclusion is concerning the experimental data based on the assumption that there are no large retained fractions in the BB region. Another interpretation of the similar clearance for the two modes of inhalation is that there are large retained fractions in both the BB and the bb regions and that individual charactristics of clearance of these fractions are of importance rather than the site of deposition.

Administration, Inhalation↗

Lung clearance in children with Duchenne muscular dystrophy or spinal muscular atrophy with and without CPAP (continuous positive airway pressure).

Bronchiolar clearance was studied in 7 boys in the age range of 8 to 17 years, 6 with Duchenne muscular dystrophy (DMD) and 1 with spinal muscular atrophy type II (SMA-II). These boys had healthy lungs but a severely reduced muscular strength (wheelchair dependent). In 6 of the boys, clearance was studied twice, at one occasion as a control and at the other occasion following treatment with continuous positive airway pressure (CPAP). A control group of healthy adults was used. In the clearance examinations, 6-microm Teflon particles, labeled with III In was inhaled extremely slowly, 0.05 L/s. This gives a deposition mainly in the bronchioles. Lung retention was measured after 0,24,48, and 72 hours. A model for deposition of particles in the adult lung was scaled down to represent the children in this study. Deposition in various airway generations was calculated to be similar in children and adults. Also the measured retentions were similar in the boys and the adults. In the clearance experiments during CPAP treatment, there was a significantly lower retention after 72 hours (but not after 24 and 48 hours) than in the control experiments. Theresults indicate that a severe reduction of muscular strength, and thereby a reduction of mechanical movement of the lung, does not affect clearance from large and small airways. However, some effect of clearance from small airways cannot be excluded due to the short measuring period. The small but significant effect of the CPAP treatment might have potential clinical importance and suggest that bronchiolar clearance can be affected by some form of mechanical force.

Adolescent↗