Thesis (M.Sc.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Epidemiology, Department of Public Health Sciences. Title from pdf file main screen (viewed on November 6, 2009). Includes bibliographical references.

Per- and polyfluorinated compounds (PFCs) are known to be toxic, bioaccumulative, and persistent. However, exposure routes and toxic effects in humans are still widely unknown. The concentrations of 17 PFCs were measured in newborn cord blood plasma and plasma from pre- and postnatal women from Winnipeg, Manitoba using online solid phase extraction coupled with liquid chromatography mass spectrometry. Median concentrations (with standard deviation) were 2.2 ng/mL (1.8 ng/mL) for perfluorooctanesulfonic acid (PFOS) and 0.89 ng/mL (0.75 ng/mL) for perfluorooctanoic acid (PFOA) in prenatal maternal plasma and 1.8 ng/mL (1.8 ng/mL) for PFOS and 0.55 ng/mL (0.46 ng/mL) for PFOA in postnatal maternal plasma. Multiple linear regression and principal component analysis were used to evaluate possible associations of maternal and infant characteristics with PFC concentrations. In general, concentrations of PFCs in plasma were associated with maternal characteristics, but not home characteristics, wheezing, or developmental effects.

Per- and polyfluorinated compounds (PFCs) are known to be toxic, bioaccumulative, and persistent. However, exposure routes and toxic effects in humans are still widely unknown. The concentrations of 17 PFCs were measured in newborn cord blood plasma and plasma from pre- and postnatal women from Winnipeg, Manitoba using online solid phase extraction coupled with liquid chromatography mass spectrometry. Median concentrations (with standard deviation) were 2.2 ng/mL (1.8 ng/mL) for perfluorooctanesulfonic acid (PFOS) and 0.89 ng/mL (0.75 ng/mL) for perfluorooctanoic acid (PFOA) in prenatal maternal plasma and 1.8 ng/mL (1.8 ng/mL) for PFOS and 0.55 ng/mL (0.46 ng/mL) for PFOA in postnatal maternal plasma. Multiple linear regression and principal component analysis were used to evaluate possible associations of maternal and infant characteristics with PFC concentrations. In general, concentrations of PFCs in plasma were associated with maternal characteristics, but not home characteristics, wheezing, or developmental effects.

This study showed a strong association between asthma, hay fever, and eczema in the same child. The presence of pets outdoors but not indoors appeared to be associated with an increased incidence of wheezing in children. Use of the traditional Gulf incense also appeared to be a precipitating factor for asthma in this study. There were also statistically significant relationships between asthma and exposure to dust at home from air conditioner blasts, which is consistent with studies elsewhere. Moreover, in this study, passive exposure to tobacco smoking at home did not appear to have any significant relationship with asthma. There was, however, a statistically significant relationship between asthma and exposure to pollen from indoor plants, which is also consistent with studies elsewhere. Parental asthma but not parental atopy was a significant risk factor for asthma in offspring, a finding which agrees with other studies that have shown that parental atopy may enhance the likelihood of the expression of asthma, but does not, on its own, impact as a risk factor in the same way as parental asthma. There was a statistically significant difference in the prevalence of asthma and the symptoms of asthma between different areas across the United Arab Emirates, but not for eczema or hay fever. This is most likely attributable to the impact of radically different environmental conditions on the development of allergies in two genetically homogenous populations of United Arab Emirates nationals. Asthma, wheeze, dyspnoea and nocturnal cough were more prevalent in coastal humid Dubai, compared to dry inland Al-Ain. However, there was no statistically significant difference in the prevalence of eczema and hay fever between coastal and inland areas in the United Arab Emirates. An environmental survey carried out in Dubai and Al-Ain to study the effect of air pollution among asthmatic children showed that overall air quality in both Dubai and in Al-Ain is good, except during adverse weather conditions, strong winds and dust storms, in summer time, where the level of Respirable Particulates (PM10) is occasionally high in Dubai. However, a previous study of seasonal trends in hospital admissions for asthmatic children in Dubai showed that the highest numbers of admissions for asthmatic children occurred between the months of October and February. These are the coldest months of the year in the United Arab Emirates. Therefore air pollution from dust storms was not the cause of the high prevalence of asthma in Dubai. Although the prevalence of asthma and wheezing was lower in the United Arab Emirates than in some developed countries, it was still higher than other chronic diseases. This study demonstrated that symptoms suggestive of asthma are quite common and constitute a major health problem in the United Arab Emirates. High rates of consanguineous marriage, a buoyant economy, rapid industrialization, development of the agricultural sector, an increase in the domestication of animals and dairy farms, combined with an emphasis on 'greening' the environment, may have resulted in an increase of the prevalence of asthma. World-wide trends have been in this direction. Therefore, a concentrated effort should be made to implement therapeutic and non-therapeutic programmes for the management of asthma by parents, teachers and physicians.

No description available.

Background: Wheezing disorders have increased worldwide. The respiratory epithelium plays an important role in the pathogenesis of wheeze. Nasal epithelial cells (NEC) are a valid surrogate for bronchial airway epithelial cells, are accessible and could be a valuable tool in translational epidemiological studies. A better understanding of this layer may decrease the burden of wheezing disorders. Objectives: To determine the feasibility of sampling and culturing NEC from children and adults with and without different wheezing conditions in epidemiological studies. To study NEC mediator release in these individuals following different environmental exposures. Methods: NEC were sampled from unsedated children and adults with and without a wheezing condition by brushing. NEC were cultured in media and also exposed to interleukin-1 (IL-1) & tumour necrosis factor alpha (TNF-), house dust mite (HDM) extract, lipopolysaccharide (LPS) and extracted tobacco smoke (ETS) for 24 hours. Resulting supernatants were analysed via Enzyme – linked immunosorbent assay (ELISA) and cytometric bead array (CBA) for mediator release. Results: 287 individuals including 164 children and 123 adults where phenotyped and brushed. 81 samples reached tertiary passage. Decreased release of vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein -1 (MCP-1) was observed in wheezing individuals when compared to healthy controls. These cytokines were increased in individuals with chronic obstructive pulmonary disease (COPD) relative to both asthmatic and healthy adults. Individuals with/without allergic rhinitis demonstrated different mediator release. Conclusions: It is feasible to obtain NEC in adults and children for both epidemiological and translational research, although the presence of allergic rhinitis may act as a potential confounder. Differences are present in adults and children with asthma compared to healthy controls. Contrasting differences between COPD and asthma suggest that these are different conditions.

No description available.

Parental reports are often used in studies of asthma and allergic diseases in children. A change in respondent from parent to index subject usually occurs during adolescence. Little is known about the effects this change in method might have on the outcomes of a longitudinal study. Smoking is a major cause of respiratory symptoms among adults and environmental tobacco smoke (ETS) is a risk factor for asthma among children. Less is known about these associations among teenagers. In order to improve prevention of smoking, it is important to identify populations at risk of becoming smokers.       The aim of this thesis were to 1) evaluate the methodological change from parental to self-completion of a questionnaire about asthma and allergic diseases, and 2) to study determinants for, and respiratory health effects of ETS and personal smoking in teenagers. In 1996, a longitudinal study of asthma and allergic diseases among schoolchildren started within the Obstructive Lung Disease in Northern Sweden (OLIN) studies. All children in first and second grades (aged 7-8 years) in three municipalities, Luleå, Kiruna and Piteå (n=3,525) were invited and 97% participated by parental completion of a questionnaire. The cohort has been followed with annual questionnaires until age 16-17 years and with high participation rates (>91%). From age 12-13 years, the teenagers were the respondents and questions about their tobacco use were included. In addition to the questionnaire completed by the teenagers at age 13-14 years, a questionnaire was also distributed to a random sample of 10% of the parents and 294 participated (84%).   The parents and the teenagers reported a similar prevalence of asthma, respiratory symptoms, rhinitis, eczema and environmental factors. Two statistically significant differences were found: the teenagers reported a higher prevalence of wheezing during or after exercise (14% vs 8%, p<0.05), and having a dog in the home in the last 12 months (42% vs 29%, p<0.001). Answer agreement between parents and teenagers on questions about asthma was almost perfect with kappa values of 0.8-0.9. Corresponding kappa values for questions about respiratory symptoms and rhinitis were 0.3-0.6 and for eczema 0.5-0.6. Agreement about environmental factors varied from 0.2-0.9. Kappa values for parental smoking were 0.8-0.9. The risk factor pattern for allergic diseases was similar regardless of respondent, ie parent or teenager. The prevalence of smoking increased from 3% at 12-13 years to 6% at 14-15 years. Smoking was more common among girls, while the use of snus was more common among boys. Significant risk factors related to smoking among teenagers were smoking family members, female sex and living in an apartment. Having physician-diagnosed asthma did not prevent the teenagers from becoming smokers. Factors related to using snus were a smoking mother and male sex.  Daily smokers aged 16-17 years (9%) reported a significantly higher prevalence of wheezing and physician-diagnosed asthma compared to non-smokers. There was a significant dose-response association with higher prevalence of wheeze among those who smoked ≥11 cigarettes per day compared to those who smoked ≤10 per day. In multivariate analyses, maternal environmental tobacco smoke exposure was a significant risk factor for ever wheeze and physician-diagnosed asthma at age 16-17 years, while daily smoking was a risk factor for current wheeze. In conclusion, the methodological change of questionnaire respondent from parent to index subject did not substantially alter the findings of this longitudinal study. There were significant sex differences in the tobacco use: smoking was more common among girls and snus was more common among boys. The most important factor related to tobacco use was presence of family members who smoke. Both maternal ETS exposure and personal smoking was associated with asthma and wheeze in adolescence. ETS was associated with lifetime symptoms but daily smoking was more strongly associated with current symptoms.

Background: Endotoxin is a lipopolysaccharide located on the outer membrane of the cell wall of Gram-negative bacteria that is widespread in the environment. Although domestic endotoxin has been found to be associated with asthma and wheeze, its association with chronic obstructive pulmonary disease (COPD) is unclear. It is also unknown how environmental exposures influence the relationship between endotoxin and asthma and very few studies have investigated the effectiveness of interventions in reducing endotoxin in the homes of people with asthma. Goals: The goals of this dissertation were to examine 1) the association of house dust endotoxin with chronic bronchitis or emphysema, two phenotypes of COPD, 2) the influence on the relationship between endotoxin and asthma outcomes of environmental factors such as exposure to dog and cat in homes, climate regions, as well as co-exposure to ambient air pollution, and 3) the effectiveness of an environmental intervention in reducing home endotoxin and asthma symptoms in rural Iowa children with asthma. Methods: For the first two goals of this dissertation, data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) was used. Dust sampled from the bedroom floor and bedding of 6,963 children and adult participants was evaluated for endotoxin at the University of Iowa Pulmonary Toxicology facility using a kinetic chromogenic Limulus amebocyte lysate assay. Data on asthma outcomes and chronic bronchitis or emphysema (CBE) was collected using questionnaires. Home exposure to dog and cat was considered by pet ownership and levels of dog (Canis familiaris 1) and cat (Feline domesticus 1) allergens in house dust. Annual average particulate matter ≤2.5 µm (PM2.5), ozone (O3), and nitrogen dioxide (NO2) concentrations at participants’ residential location were estimated using the Community Multiscale Air Quality (CMAQ) and Downscaler (DS) models. In the third goal, data from the Louisa Environmental Intervention Project (LEIP) study which included schoolchildren 5-14 years-old with active asthma from Louisa and Keokuk counties in rural Iowa was analyzed. The households were block-randomized to receive extensive (education + professional cleaning) or educational intervention. Environmental sampling and questionnaire administration were done at baseline and during three follow-up visits. Results: In the NHANES, the median concentration of endotoxin in house dust was 16.2 EU/mg. In adjusted analysis, house dust endotoxin (log10-endotoxin) was associated with increased odds of CBE diagnosis (OR: 1.27, 95% CI: 1.00-1.61) and chronic bronchitis symptoms (OR: 1.78, 95% CI: 1.01-3.12). Sensitization to inhalant allergens modified the relationship between log10-endotoxin and CBE diagnosis (P(interaction)=0.001), with stronger associations observed in sensitized participants (OR: 2.46, 95% CI: 1.72-3.50). The association of endotoxin with asthma outcomes was different with climate regions of the U.S. Endotoxin was associated with higher prevalence of wheeze outcomes in the past 12 months in subarctic/very cold/cold regions (OR: 1.48, 95% CI:1.19-1.85) and in hot-humid regions (OR: 1.66, 95% CI:1.04-2.65). In hot-humid regions, endotoxin was positively associated with current asthma (OR: 1.56, 95% CI:1.11-2.18), but negatively with sensitization to any inhalant allergens (OR: 0.83, 95% CI:0.74-0.92). Exposure to dog and cat allergens enhanced endotoxin association with current asthma (OR: 2.00, 95% CI: 1.04-3.83, P(interaction)=0.012) and wheeze in the past 12 months (OR: 1.88, 95% CI: 1.32-2.66, P(interaction)=0.016). House dust endotoxin co-exposure with PM2.5 (CMAQ) was synergistically associated with emergency room visits for asthma in the past 12 months (OR: 5.01, 95% CI: 2.54-9.87) in general. In children, a synergistic association was found for co-exposure to house dust endotoxin and NO2 with the outcome (OR: 3.45, 95% CI: 1.65-7.18). In LEIP, 104 asthmatic children from 89 homes were included in the study. In the main analysis, extensive compared to the educational intervention was associated with decreased endotoxin load in farm homes (P-value of main effect for intervention <0.0001) and with less frequent nighttime asthma symptoms (Intervention x visit interaction P-value = 0.044). In exploratory analysis, endotoxin load reduction from baseline was associated with less daytime wheeze (OR: 0.59, 95%CI: 0.38-0.91) and daytime cough (OR: 0.62, 95% CI: 0.40-0.97). Conclusions: House dust endotoxin is associated with obstructive pulmonary diseases. The association of endotoxin with asthma outcomes is stronger in cold regions of the U.S. and is enhanced by exposure to pet allergens and co-exposure to ambient air pollutants such as PM2.5 and NO2 in children. The LEIP study demonstrated that extensive cleaning interventions can be effective at reducing endotoxin in the homes children with asthma and can alleviate their symptoms.

Background In the past half-century, the prevalence of asthma among children and adolescents has risen and asthma has become an important public health challenge in Sweden as well as in many other countries, necessitating further studies on this complex disease and its risk factor pattern. The studies included in this thesis aimed to investigate the clinical expression of childhood asthma over time, to describe the determinants of new-onset and remission of asthma, and to evaluate possible environmental risk factors in northern Sweden. Methods As the result of a repeated questionnaire survey among primary school children aged 7-8 years in three municipalities in the north of Sweden, two pediatric cohorts were formed, one in 1996 (n=3430) and one in 2006 (n=2585). The cohort created in 1996 was followed annually until the age of 19 years. Skin prick testing was performed on children in both cohorts. Lung function and bronchial hyperreactivity testing were carried out in children with asthma in the first cohort. The study participation and retention rates were very high in both cohorts. Among children in the second cohort living in Luleå, the home addresses were assigned to coordinates in a geographical information system (GIS) to evaluate the impact on respiratory health of living near roads with much traffic, which was measured as the number of vehicles daily. We used a validated reported diagnosis of asthma and International Study of Asthma and Allergies in Childhood (ISAAC) questions were incorporated into the questionnaire. A cross-sectional study of children of the same age ten years apart, longitudinal studies on asthma incidence and remission as well as a cross-sectional study on vehicle traffic were performed. Results While children aged 7-8 years in 2006 more often had a physician-diagnosed asthma compared to children of the same age in 1996 (7.4% vs 5.7%, p&lt;0.001), they had less asthma symptoms, especially severe symptoms. In parallel, a more beneficial environment and a more intense treatment with inhaled corticosteroids (ICS) were observed. The explanation for this change in clinical expression probably includes also an increased awareness and diagnosing of asthma. From age 12 years to age 19 years, the cumulative incidence of physician-diagnosed asthma was 7.2% and of current wheeze 22.0%. The risk of new-onset asthma in adolescence was increased among girls, sensitized and those with heredity for asthma. Smoking and home dampness increased the risk for incident wheeze. The risk for both incident asthma and wheeze was inversely related to number of siblings. Among children with current asthma at age 7-8 years, 21% were in remission, 38% had periodic asthma and 41% had persistent asthma at a follow-up at age 19 years. Subjects in remission and with periodic asthma had significantly less airway obstruction and showed less bronchial hyperreactivity compared to subjects with persistent asthma. The probability of asthma remission from childhood to early adulthood was significantly increased by absence of allergic sensitization, male gender and a low asthma severity scoring at age 7-8 years. Sensitization to furred animals was more important as a determinant of both incidence and remission than sensitization to pollen. Living close to roads with high traffic flows, especially with heavy vehicles, was associated with an increased risk for current wheeze. Stratified analyses showed that the effect of traffic on asthma and wheeze was restricted to non-sensitized subjects. Conclusion Asthma onset in adolescence was more common among girls and remission was more common among boys. Children sensitized to furred animals and children with a more severe asthma were risk groups for persistence of asthma. Environmental factors such as smoking and dampness were associated to onset of asthma symptoms during adolescence, and vehicle traffic was associated with asthma symptoms among children also in a small city with relatively low traffic flows. Preventive measures like smoking reduction programs, improvement of damp housing conditions and separation of areas where many children live from heavily trafficked roads could prove to be beneficial. / OLIN-studierna