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1.  Comparison of parental reports of smoking and residential air nicotine concentrations in children 
Using questionnaires to assess children's residential exposure to environmental tobacco smoke (ETS) may result in misclassification from recall and response bias. Questionnaire data have frequently been validated against urinary cotinine measurements, but rarely against actual measurements of residential air nicotine.
To compare questionnaire reported smoking with air nicotine concentrations in a large population of children and with urinary cotinine levels in a subpopulation; and to assess the potential impact of the symptom status of the children on the agreement between different measures of exposure.
The authors assessed residential exposure to ETS in 347 German, 335 Dutch, and 354 Swedish preschool and schoolchildren by questionnaire and air nicotine measurements, and in a subset of 307 German children by urinary cotinine measurements. They then compared the different measures of ETS exposure.
In all countries, air nicotine concentrations increased with increasing questionnaire reported smoking in a dose‐response fashion. Specificity and negative predictive values of questionnaire reports for nicotine concentrations were excellent. Sensitivity and positive predictive values were moderate to good. Excluding occasional smokers, the overall percentage of homes misclassified was 6.9%, 6.7%, and 5.1% in Germany, the Netherlands, and Sweden, respectively. Similar results were found for the agreement of urinary cotinine concentrations with questionnaire reports and air nicotine levels. There was no indication of underreporting by parents of symptomatic children.
Despite some misclassification, questionnaire reports are an inexpensive and valid estimate of residential ETS exposure among preschool and school children.
PMCID: PMC2077986  PMID: 16912089
environmental tobacco smoke; questionnaire; air nicotine; urinary cotinine
2.  Diet and asthma in Dutch school children (ISAAC‐2) 
Thorax  2005;61(12):1048-1053.
The rise in the prevalence of asthma in western societies may be related to changed dietary habits. Epidemiological studies in children have shown inverse associations of asthma related outcomes with intake of fruits, vegetables, dairy and whole grain products, and fish. In contrast to most previous studies, we used both questionnaire and clinical data to define asthma.
Intake of the abovementioned foods was studied in relation to asthma in 598 Dutch children aged 8–13 years. Dietary intake was estimated using a parent completed semi‐quantitative food frequency questionnaire. Current wheeze and current asthma were defined based on questionnaire data. More complex end points were defined using information on bronchial hyperresponsiveness (BHR) and atopic sensitisation as well. Linear associations were studied using logistic regression analysis and odds ratios presented for the highest versus the lowest tertile of intake. In the final models, adjustments were made for maternal educational level, foreign descent, and total energy intake.
The intake of whole grain products and of fish was inversely associated with asthma. Adjusted odds ratios for the independent associations with whole grains and fish were 0.46 (95% CI 0.19 to 1.10) and 0.34 (95% CI 0.13 to 0.85) for current asthma and 0.28 (95% CI 0.08 to 0.99) and 0.12 (95% CI 0.02 to 0.66) for atopic asthma with BHR. Similar results were observed for current wheeze and atopic wheeze with BHR. Intake of (citrus) fruits, vegetables, and dairy products showed no clear associations with asthma end points.
Our findings suggest that a high intake of whole grain products and fish may have a protective effect against asthma in children.
PMCID: PMC2117046  PMID: 16244092
diet; asthma; children; fish; whole grains
3.  Associations between ambient, personal, and indoor exposure to fine particulate matter constituents in Dutch and Finnish panels of cardiovascular patients 
Aims: To assess the relation between ambient, indoor, and personal levels of PM2.5 and its elemental composition for elderly subjects with cardiovascular disease.
Methods: In the framework of a European Union funded study, panel studies were conducted in Amsterdam, the Netherlands and Helsinki, Finland. Outdoor PM2.5 concentrations were measured at a fixed site. Each subject's indoor and personal PM2.5 exposure was measured biweekly for six months, during the 24 hour period preceding intensive health measurements. The absorbance of PM2.5 filters was measured as a marker for diesel exhaust. The elemental content of more than 50% of the personal and indoor samples and all corresponding outdoor samples was measured using energy dispersive x ray fluorescence.
Results: For Amsterdam and Helsinki respectively, a total of 225 and 238 personal, and 220 and 233 indoor measurements, were analysed from 36 and 46 subjects. For most elements, personal and indoor concentrations were lower than and highly correlated with outdoor concentrations. The highest correlations (median r>0.9) were found for sulfur and particle absorbance, which both represent fine mode particles from outdoor origin. Low correlations were observed for elements that represent the coarser part of the PM2.5 particles (Ca, Cu, Si, Cl).
Conclusions: The findings of this study provide support for using fixed site measurements as a measure of exposure to particulate matter in time series studies linking the day to day variation in particulate matter to the day to day variation in health endpoints, especially for components of particulate matter that are generally associated with fine particles and have few indoor sources. The high correlation for absorbance of PM2.5 documents that this applies to particulate matter from combustion sources, such as diesel vehicles, as well.
PMCID: PMC1740941  PMID: 16299096
4.  Exposure to traffic related air pollutants: self reported traffic intensity versus GIS modelled exposure 
Background: In epidemiological studies of the potential health effects of traffic related air pollution, self reported traffic intensity is a commonly used, but rarely validated, exposure variable.
Methods: As part of a study on the impact of Traffic Related Air Pollution on Childhood Asthma (TRAPCA), data from 2633 and 673 infants from the Dutch and the German-Munich cohorts, respectively, were available. Parents subjectively assessed traffic intensity at the home address. Objective exposures were estimated by a combination of spatial air pollution measurements and geographic information system (GIS) based modelling using an identical method for both cohorts.
Results: The agreement rates between self reported and GIS modelled exposure—accumulated over the three strata of self assessed traffic intensity—were 55–58% for PM2.5, filter absorbance (PM2.5 abs), and nitrogen dioxide in Munich and 39–40% in the Netherlands. Of the self reported low traffic exposed group, 71–73% in Munich and 45–47% in the Netherlands had low modelled exposure to these three air pollutants. Of the self assessed high exposed subgroups in Munich (15% of the total population) and the Netherlands (22% of the total population), only 22–33% and 30–32% respectively had high modelled exposure to the three air pollutants. The subjective assessments tend to overestimate the modelled estimates for PM2.5 and NO2 in both study areas. When analysis was restricted to the portion of the Dutch cohort living in non-urban areas, the agreement rates were even lower.
Conclusions: Self reported and modelled assessment of exposure to air pollutants are only weakly associated.
PMCID: PMC1741068  PMID: 16046603
5.  Out of Africa 
PMCID: PMC1741042  PMID: 15901878
6.  Daily variation in fine and ultrafine particulate air pollution and urinary concentrations of lung Clara cell protein CC16 
Background: Daily variations in ambient particulate air pollution have been associated with respiratory mortality and morbidity.
Aims: To assess the associations between urinary concentration of lung Clara cell protein CC16, a marker for lung damage, and daily variation in fine and ultrafine particulate air pollution.
Methods: Spot urinary samples (n = 1249) were collected biweekly for six months in subjects with coronary heart disease in Amsterdam, Netherlands (n = 37), Erfurt, Germany (n = 47), and Helsinki, Finland (n = 47). Ambient particulate air pollution was monitored at a central site in each city.
Results: The mean 24 hour number concentration of ultrafine particles was 17.3x103 cm–3 in Amsterdam, 21.1x103 cm–3 in Erfurt, and 17.0x103 cm–3 in Helsinki. The mean 24 hour PM2.5 concentrations were 20, 23, and 13 µg/m3, respectively. Daily variation in ultrafine particle levels was not associated with CC16. In contrast, CC16 concentration seemed to increase with increasing levels of PM2.5 in Helsinki, especially among subjects with lung disorders. No clear associations were observed in Amsterdam and Erfurt. In Helsinki, the CC16 concentration increased by 20.2% (95% CI 6.9 to 33.5) per 10 µg/m3 increase in PM2.5 concentration (lag 2). The respective pooled effect estimate was 2.1% (95% CI –1.3 to 5.6).
Conclusion: The results suggest that exposure to particulate air pollution may lead to increased epithelial barrier permeability in lungs.
PMCID: PMC1757829  PMID: 15477284
7.  The great indoors 
Thorax  2004;59(9):729-730.
PMCID: PMC1747139  PMID: 15333842
9.  Short and long term variability of the interrupter technique under field and standardised conditions in 3–6 year old children 
Thorax  2003;58(9):761-764.
Methods: The interrupter technique was studied under field and standardised conditions in children aged 3–6 years. Under field conditions, five investigators performed the measurements using two different measurement devices in random sequence. Both short term (20–30 minutes) and long term variability (median 38 days) were assessed in 32 children. Under standardised conditions, a single investigator conducted all measurements using a single device; the repeated measurements were conducted at the same time of day in a familiar quiet classroom. Long term variability (median 11 days) was estimated in 15 children. Within-subject standard deviations were estimated by analysis of variance with adjustment for the effects of different investigators and measurement devices on within-subject variability under field conditions.
Results: Under field conditions within-subject standard deviations for short and long term variability were 0.10 kPa/l/s (adjusted 0.10 kPa/l/s) and 0.13 kPa/l/s (adjusted 0.14 kPa/l/s), respectively. Under standardised conditions the within-subject standard deviation for long term variability was 0.10 kPa/l/s.
Conclusions: Measurement of interrupter resistance under field conditions only slightly increased the within-subject variability compared with standardised conditions. The results indicate that interrupter resistance is a stable individual characteristic over a period of some weeks.
PMCID: PMC1746802  PMID: 12947133
10.  Association of consumption of products containing milk fat with reduced asthma risk in pre-school children: the PIAMA birth cohort study 
Thorax  2003;58(7):567-572.
Background: Environment and lifestyle contribute to the development of asthma in children. Understanding the relevant factors in this relationship may provide methods of prevention. The role of diet in the development of asthma in pre-school children was investigated.
Methods: Data from 2978 children participating in a prospective birth cohort study were used. Food frequency data were collected at the age of 2 years and related to asthma symptoms reported at the age of 3 years.
Results: The prevalence of recent asthma at age 3 was lower in children who consumed (at age 2) full cream milk daily (3.4%) than in those who did not (5.6%) and in those who consumed butter daily (1.5%) than in those who did not (5.1%). The prevalence of recent wheeze was lower in children who consumed milk products daily (13.7%) than in those who did not (18.4%) and in children who consumed butter daily (7.7%) than in those who did not (15.4%). These effects remained in a logistic regression model including different foods and confounders (adjusted odds ratio (CI) for recent asthma: full cream milk daily v rarely 0.59 (0.40 to 0.88), butter daily v rarely 0.28 (0.09 to 0.88)). Daily consumption of brown bread was also associated with lower rates of asthma and wheeze, whereas no associations were observed with the consumption of fruits, vegetables, margarine, and fish.
Conclusions: In pre-school children, frequent consumption of products containing milk fat is associated with a reduced risk of asthma symptoms.
PMCID: PMC1746729  PMID: 12832666
11.  Nutrition and respiratory health in children in six Central and Eastern European countries 
Thorax  2003;58(3):231-236.
Method: A total of 20 271 children aged 7–11 were surveyed in six European countries. Respiratory health and food intake were assessed using questionnaires. Associations between four symptoms and nutritional factors were evaluated using logistic regression, controlling for area plus other potential confounders.
Results: All symptoms showed initial associations with nutritional factors. Low consumption of fish and of summer and winter fruit were the most consistent predictors. In a fully adjusted model low fish intake remained a significant independent predictor of persistent cough (OR=1.18; 95% CI 1.04 to 1.34), wheeze ever (OR=1.14; 95% CI 1.03 to 1.25) and current wheeze (OR=1.21; 95% CI 1.06 to 1.39) and a weaker predictor of winter cough (OR=1.10; 95% CI 0.99 to 1.23). Low summer fruit intake was a predictor of winter cough (OR=1.40; 95% CI 1.10 to 1.79) and persistent cough (OR=1.35; 95% CI 1.01 to 1.82). Low winter fruit intake was associated with winter cough (OR=1.28; 95% CI 1.09 to 1.51). Associations between symptoms and vegetable intake were inconsistent. Low summer intake was significantly associated with winter cough (OR=1.23; 95% CI 1.03 to 1.47) but, overall, winter intake had inverse associations with both coughs. Associations between winter vegetable intake and wheeze varied considerably between countries.
Conclusion: A number of associations were found between respiratory symptoms and low intake of fish, fruit and vegetables in children. Low fish intake was the most consistent predictor of poor respiratory health. Fruit and vegetable intake showed stronger associations with cough than with wheeze.
PMCID: PMC1746605  PMID: 12612301
12.  Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children 
Thorax  2003;58(3):242-245.
Methods: Levels of eNO in a sample of 450 children aged 7–12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV1 and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing.
Results: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV1 and MMEF were not associated with eNO levels.
Conclusions: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.
PMCID: PMC1746591  PMID: 12612304
13.  Early respiratory and skin symptoms in relation to ethnic background: the importance of socioeconomic status; the PIAMA study 
Archives of Disease in Childhood  2002;87(6):482-488.
Aims: To evaluate ethnic differences in the prevalence of respiratory and skin symptoms in the first two years of life.
Methods: A total of 4146 children participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study. Parents completed questionnaires on respiratory and skin symptoms, ethnic background, and other potential confounders during pregnancy, and at 3 months, 1 year, and 2 years of age.
Results: In the first year, "non-Dutch" children (compared with "Dutch" children) had a higher prevalence of runny nose with itchy/watery eyes (11.0% versus 5.0%). In the second year, a higher prevalence of wheeze at least once (26.7% versus 18.5%), night cough without a cold (24.6% versus 15.5%), runny nose without a cold (34.1% versus 21.3%), and runny nose with itchy/watery eyes (13.7% versus 4.6%) was found. Adjustment for various confounders, especially adjustment for socioeconomic factors, reduced most associations between ethnicity and respiratory symptoms. Only runny nose with itchy/watery eyes in the second year of life was independently associated with non-Dutch ethnicity (adjusted odds ratio 2.89, 95% CI 1.3–6.4).
Conclusions: Non-Dutch children more often had respiratory symptoms in the first two years of life than Dutch children. This could largely be explained by differences in socioeconomic status. Follow up of the cohort will determine whether this higher prevalence of respiratory symptoms in children with non-Dutch ethnicity represents an increased risk of developing allergic disease rather than non-specific or infection related respiratory symptoms.
PMCID: PMC1755839  PMID: 12456544
14.  The effect of brief neonatal exposure to cows' milk on atopic symptoms up to age 5 
Archives of Disease in Childhood  2002;86(5):365-369.
Aims: To determine the effect of brief early exposure to cows' milk on the expression of atopy during the first five years of life.
Methods: Follow up analysis of a double blind, placebo controlled, randomised feeding intervention trial (BOKAAL study). Subjects were 1108 children from 1533 initially randomised breast fed neonates in the Netherlands. Atopic disease and prevalence of allergic symptoms at age 1, 2, and 5, and specific IgE at age 1 and 5 were determined.
Results: Atopic disease in the first year was found in 10.0% (cows' milk) versus 9.3% (placebo) of the children, with a relative risk (RR) of 1.07. No differences were found in the second year either. At age 5, atopic disease was found in 26.3% (cows' milk) versus 25.0% (placebo), RR 1.05. There was no difference in the prevalence of allergic symptoms. Specific IgE to cows' milk (RAST positive 2+ or more) was 5.8% (cows' milk) versus 4.1% (placebo) at age 1 (RR 1.43), and 5.3% versus 3.0% at age 5 (RR 1.77). There was no difference in sensitisation to other common allergens between the two groups.
Conclusion: Early, brief exposure to cows' milk in breast fed children is not associated with atopic disease or allergic symptoms up to age 5.
PMCID: PMC1751102  PMID: 11970933
15.  Repeatability of bronchial hyperresponsiveness to adenosine-5'-monophosphate (AMP) by a short dosimeter protocol 
Thorax  2001;56(5):362-365.
BACKGROUND—To study bronchial responsiveness to adenosine 5'-monophosphate (AMP) in population surveys, repeatability of a rapid dosimetric method with quadrupling doses was evaluated.
METHODS—Volunteers with symptoms of airway respiratory allergy or asthma were invited for AMP challenges on two occasions. After each dose the fall in forced expiratory volume in one second (FEV1) compared with the post-saline value was determined. The cumulative doses of AMP needed to cause a fall in FEV1 of 20% (PD20), 15% (PD15), and 10% (PD10) were calculated. Agreement was evaluated by means of kappa values. After excluding systematic differences in PD values on two occasions (t test), repeatability of a single estimation of the chosen PD values was calculated and expressed in doubling doses (DD).
RESULTS—In 28 of 76 subjects a PD20 was estimated on the two visits, in 29 subjects a PD15 was estimated, and in 32 a PD10 was obtained. Kappa values for a positive threshold were 0.89 for a cut off level for a 20% fall in FEV1, 0.78 for a 15% fall in FEV1, and 0.76 for a fall in FEV1 of 10%. The PD values did not differ between the two visits and 95% repeatability of a single estimation was ±1.7 DD for PD20, ±2.2 DD for PD15, and ±2.4 DD for PD10. The quadrupling dose method reduced time by 40% in non-hyperresponsive subjects and no adverse effects were observed.
CONCLUSION—The short dosimeter protocol with quadrupling doses for AMP challenges is a rapid, reproducible tool for estimating bronchial responsiveness in population surveys.

PMCID: PMC1746039  PMID: 11312404
16.  Acute effects of urban air pollution on respiratory health of children with and without chronic respiratory symptoms 
OBJECTIVES: To investigate to what extent different components of air pollution are associated with acute respiratory health effects in children with and without chronic respiratory symptoms. METHODS: During three consecutive winters starting in 1992-3, peak expiratory flow (PEF) and respiratory symptoms were registered daily in panels of children of 7-11 years old with and without symptoms, living in urban areas with high traffic intensity in The Netherlands. Simultaneously, panels of children living in non-urban areas were studied. Daily measurements of particles with aerodynamic diameter < 10 microns (PM10), black smoke (BS), sulphate, SO2, and NO2 were performed in both areas. RESULTS: The contrast in particle concentrations (PM10, BS, and sulphate) between urban and non-urban areas was small, but there was more contrast in the concentrations of SO2 and NO2. In children with symptoms from both areas, significant associations were found between PM10, BS, and sulphate concentrations and the prevalence of symptoms of the lower respiratory tract (LRS) and decrements in PEF. Particle concentrations were also associated with use of bronchodilators in the urban areas, but not in the non-urban areas. After stratification by use of medication, stronger associations were found in children who used medication than in children who did not use medication. The magnitude of the estimated effects was in the order of a twofold increase in the use of bronchodilators, a 50% increase in LRS, and an 80% increase in decrements in PEF for a 100 micrograms/m3 increase in the 5 day mean PM10 concentration. In children without symptoms, significant associations were found between concentrations of PM10 and BS and decrements in PEF in both areas, but these associations were smaller than those for children with symptoms. No associations with respiratory symptoms were found. CONCLUSIONS: The results suggest that children with symptoms are more susceptible to the effects of particulate air pollution than children without symptoms, and that use of medication for asthma does not prevent the adverse effects of particulate air pollution in children with symptoms.
PMCID: PMC1757690  PMID: 10658536
17.  Mass concentration and elemental composition of PM10 in classrooms 
OBJECTIVES: To investigate the sources of high concentrations of particles of < 10 microns diameter (PM10) in classrooms, observed in a previous study on childhood exposure to PM10, and to study the correlation between classroom and outdoor concentrations of mass and elements of PM10. METHODS: Measurements of PM10 were conducted in two schools and outdoors in Amsterdam, the Netherlands. Averaging time was 24 hours for the outdoor measurements and both 8 hours (school time) and 24 hours for the classroom measurements. Analysis by x ray fluorescence was used to measure the elemental composition of 55 samples from the 11 days when measurements were conducted simultaneously in both classrooms and outdoors. RESULTS: For most elements, classroom concentrations were considerably higher than outdoor concentrations, especially during school hours. The highest classroom/outdoor ratios were found for the elements from soils Si, Ca, and Ti. The only measured elements that were not increased were S, Br, Pb, and Cl, which are dominated by non-crustal sources. For S, Br, and Pb, which are generally associated with particles < 1 micron, significant correlations between classroom and outdoor concentrations and between the two classrooms were found. The other elements generally had low correlations. CONCLUSIONS: The results show that the high PM10 concentrations found in our classrooms are probably due to resuspension of coarse particles or suspension of soil material. Due to these excess coarse particles, the correlation between classroom and outdoor concentrations is lower for elements associated with coarse particles than for elements associated with fine particles. As the general composition of PM10 in classrooms differs from the composition of PM10 in ambient air, the high PM10 mass concentrations in classrooms can probably not be directly compared with ambient air quality guidelines.
PMCID: PMC1757765  PMID: 10472320
18.  Inhomogeneity in response to air pollution in European children (PEACE project) 
OBJECTIVES: The PEACE study is a multicentre panel study of the acute effects of particles with a 50% cut off aerodynamic diameter of 10 microns (PM10), black smoke (BS), sulphur dioxide (SO2), and nitrogen dioxide (NO2) on respiratory health of children with chronic respiratory symptoms. In the complete panels no consistent association between air pollution and respiratory health was found. The study evaluated whether potentially more sensitive subgroups in the panels did show effects of air pollution. METHODS: To evaluate heterogeneity in response to air pollution, effect estimates of air pollution on peak expiratory flow (PEF) and respiratory symptoms were calculated in subgroups based on presence of chronic respiratory symptoms, use of respiratory medication, atopy, sex, and baseline lung function. RESULTS: The association between PEF and air pollution was positive in asthmatic children who used respiratory medication whereas the associations tended to be negative in children who did not use respiratory medication selected only on cough. No consistent association was found among asthmatic children who did not use medication. The association between daily prevalence of symptoms and concentrations of air pollution was not different between these subgroups. CONCLUSION: None of the predefined potentially more sensitive subgroups showed a consistent association between air pollution, PEF, and respiratory symptoms.
PMCID: PMC1757699  PMID: 10448312
19.  Personal and outdoor nitrogen dioxide concentrations in relation to degree of urbanization and traffic density. 
Environmental Health Perspectives  2001;109(Suppl 3):411-417.
To assess differences in exposure to air pollution from traffic in relation to degree of urbanization and traffic density, we measured personal and home outdoor nitrogen dioxide (NO(2)) concentrations for 241 children from six different primary schools in the Netherlands. Three schools were situated in areas with varying degrees of urbanization (very urban, fairly urban, and nonurban) and three other schools were located near highways with varying traffic density (very busy, fairly busy, and not busy). Weekly averaged measurements were conducted during four different seasons. Simultaneously, indoor and outdoor measurements were conducted at the schools. Personal and outdoor NO(2) concentrations differed significantly among children attending schools in areas with different degrees of urbanization and among children attending schools in areas close to highways with different traffic densities. For the children living near highways, personal and outdoor NO(2) concentrations also significantly decreased with increasing distance of the home address to the highway. Differences in personal exposures between children from the different schools remained present and significant after adjusting for indoor sources of NO(2). This study has shown that personal and outdoor NO(2) concentrations are influenced significantly by the degree of urbanization of the city district and by the traffic density of and distance to a nearby highway. Because NO(2) can be considered a marker for air pollution from traffic, the more easily measured variables degree of urbanization, traffic density, and distance to a nearby highway can all be used to estimate exposure to traffic-related air pollution.
PMCID: PMC1240559  PMID: 11429326
20.  Acute effects of ozone on pulmonary function of cyclists receiving antioxidant supplements 
OBJECTIVES: To identify whether acute lung function effects of ozone can be modulated by antioxidant vitamin supplementation. METHODS: Amateur cyclists (n = 26) were studied in the summer of 1994 in The Netherlands. Repeated lung function measurements were performed with a rolling seal spirometer after training sessions or competitive races on four to 14 occasions. The cyclists were assigned to two study groups. The supplementation group (n = 12) received antioxidant supplements (15 mg beta-carotene, 75 mg vitamin E, and 650 mg vitamin C) once a day for three months. The control group did not receive supplementation. For each subject, lung function after exercise was regressed on the previous eight hour mean ozone concentration. The individual regression coefficients were pooled for each study group and weighted with the inverse of the variance. RESULTS: The eight hour mean ozone concentration was 101 micrograms/m3 (30 to 205 micrograms/m3). For the supplementation group, there was no effect of ozone on FVC, FEV1, peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF). For the control group the mean coefficients were negative, except for MMEF. The difference between the groups was 2.08 (95% confidence interval (95% CI) 1.31 to 2.85) ml/microgram/m3 for FVC, 1.66 (95% CI 0.62 to 2.70) for FEV1, 6.83 (95% CI 3.17 to 10.49) for PEF, and 0.42 (95% CI -1.38 to 2.22) for MMEF. CONCLUSION: The results suggest that antioxidant vitamin supplementation protects against acute effects of ozone on lung function in heavily exercising amateur cyclists.
PMCID: PMC1757500  PMID: 9536157
21.  Childhood exposure to PM10: relation between personal, classroom, and outdoor concentrations. 
OBJECTIVES: To investigate the validity of outdoor concentrations of particulate matter < 10 microns diameter (PM10) as a measure of exposure in time series studies, and to study the extent to which differences between personal and outdoor PM10 concentrations can be explained. METHODS: Four to eight repeated measurements of personal and outdoor PM10 concentrations were conducted for 45 children, aged 10-12 years, from four schools in Wageningen and Amsterdam, The Netherlands. Repeated PM10 measurements in the classrooms were conducted in three of the schools. Averaging time was 24 hours for the personal and outdoor measurements, and eight hours (daytime) and 24 hours for the classroom measurements. For each child separately, personal exposures were related to outdoor concentrations in a regression analysis. The distribution of the individual correlation and regression coefficients was investigated. Information about factors that might influence personal exposures was obtained by questionnaire. RESULTS: Median Pearson's correlations between personal and outdoor concentrations were 0.63 for children with parents who did not smoke and 0.59 for children with parents who smoked. For children with parents who did not smoke, excluding days with exposure to environmental tobacco smoke (ETS) improved the correlation to a median R of 0.73. The mean personal PM10 concentration was 105 micrograms/m3; on average 67 micrograms/m3 higher than the corresponding outdoor concentrations. The main part of this difference could be attributed to exposure to ETS, to high PM10 concentrations in the classrooms, and to (indoor) physical activity. CONCLUSIONS: The results show a reasonably high correlation between repeated personal and outdoor PM10 measurements within children, providing support for the use of fixed site measurements as a measure of exposure to PM10 in epidemiological time series studies. The large differences between personal and outdoor PM10 concentrations probably result from a child's proximity to particle generating sources and particles resuspended by personal activities.
PMCID: PMC1128970  PMID: 9470897
23.  Measurement of beta(1-->3)-glucans in occupational and home environments with an inhibition enzyme immunoassay. 
beta (1-->3)-Glucans are known for their potent ability to induce nonspecific inflammatory reactions and are believed to play a role in bioaerosol-induced respiratory symptoms. An inhibition enzyme immunoassay (EIA) was developed for the quantitation of beta (1-->3)-glucans in dust samples from occupational and residential environments. Immunospecific rabbit antibodies were produced by immunization with bovine serum albumin-conjugated laminarin [beta (1-->3)-glucan] and affinity chromatography on epoxy-Sepharose-coupled beta (1-->3)-glucans. The laminarin-based calibration curve in the inhibition EIA ranged from approximately 40 to 3,000 ng/ml (15 to 85% inhibition). Another beta (1-->3)-glucan (curdlan) showed a similar inhibition curve but was three to five times less reactive on a weight basis. Pustulan, presumed to be a beta (1-->6)-glucan, showed a parallel dose-response curve at concentrations 10 times higher than that of laminarin. Control experiments with NaIO4 and beta (1-->3)-glucanase treatment to destroy beta (1-->6)- and beta (1-->3)-glucan structures, respectively, indicate that the immunoreactivity of pustulan in the assay was due to beta (1-->3)-glucan and not to beta (1-->6)-glucan structures. Other polysaccharides, such as mannan and alpha (1-->6)-glucan, did not react in the inhibition EIA. Beta (1-->3)-Glucan extraction of dust samples in water (with mild detergent) was performed by heat treatment (120 degrees C) because aqueous extracts obtained at room temperature did not contain detectable beta (1-->3)-glucan levels. The assay was shown to detect heat-extractable beta (1-->3)-glucan in dust samples collected in a variety of occupational and environmental settings. On the basis of duplicate analyses of dust samples, a coefficient of variation of approximately 25% was calculated. It was concluded that the new inhibition EIA offers a useful method for indoor beta (1-->3)-glucan exposure assessment.
PMCID: PMC168113  PMID: 8795207
24.  Chronic respiratory symptoms in children and adults living along streets with high traffic density. 
OBJECTIVES: To investigate if the population living along streets with high traffic density has a higher prevalence of chronic respiratory symptoms. METHODS: A sample of 673 adults and 106 children (0-15 years), living along busy traffic streets in the city of Haarlem was compared with a control sample of 812 adults and 185 children living along quiet streets. Exposed and control streets were selected on the basis of model calculations of NO2 concentrations. A postal questionnaire containing questions about respiratory symptoms and several potential confounders was used to collect information from the study subjects. RESULTS: After adjustment for potential confounders, children living along busy streets were found to have a higher prevalence of most respiratory symptoms than children living along quiet streets. Adjusted odds ratios were significant for wheeze and for respiratory medication used. Risk ratios were higher for girls than for boys, with significant adjusted odds ratios between 2.9 and 15.8 for girls. In adults, only mild dyspnoea was more often reported by subjects living along streets with high traffic density. CONCLUSIONS: The results suggest that living along busy streets increases the risk of developing chronic respiratory symptoms in children.
PMCID: PMC1128457  PMID: 8664961
25.  Epidemiologic studies on short-term effects of low levels of major ambient air pollution components. 
Environmental Health Perspectives  1995;103(Suppl 2):3-13.
Since the development of the World Health Organization (WHO) Air Quality Guidelines for Europe, a large number of epidemiologic studies have been published documenting effects of major air pollutants on health at concentrations below existing guidelines and standards. In this review, recent studies are discussed that permit some evaluation of short-term health effects observed at exposure levels lower than the current WHO Guidelines or U.S. Environmental Protection Agency (U.S. EPA) standards. Some studies have been conducted at concentration levels that never exceeded existing guidelines or standards. Other studies have been conducted at exposure levels sometimes exceeding current guidelines or standards. The published analyses of several of these studies permit evaluation of low-level health effects either because analyses were restricted to levels not exceeding the guidelines or graphic analyses were reported suggesting effects at these low levels. For ambient ozone, effects on lung function of subjects exercising outdoors have now been documented at 1-hr maximum levels not exceeding 120 micrograms/m3, i.e., half the current U.S. EPA standard. One study even suggests that such effects occur at levels below 100 micrograms/m3. Several studies are now available documenting effects of particulate air pollution on health in the virtual absence of SO2. Effects on mortality and hospital admissions for asthma have been documented at levels not exceeding 100 micrograms/m3, expressed as 24-hr average inhalable particles PM10 concentration. Effects on lung function, acute respiratory symptoms, and medication use have been found at 24-hr average PM10 levels not exceeding 115 micrograms/m3. When the WHO Air Quality Guidelines and the U.S. EPA standard for PM10 were developed, there were no studies available on health effects of PM10. In this review, we include nine studies documenting health effects of measured PM10 at low levels of exposure, indicating that there is now an entirely new epidemiologic database that can be evaluated in the process of revising current guidelines and standards. The low levels of exposure at which effects on health were seen underscore the urgent need for such reevaluations.
PMCID: PMC1518847  PMID: 7614944

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