Time series of daily administrative cardio-respiratory health and environmental information have been extensively used to assess the potential public health impact of ambient air pollution. Both series are subject to strong but unrelated temporal cycles. These cycles must be removed from the time series prior to examining the role air pollution plays in exacerbating cardio-respiratory disease. In this paper, we examine a number of methods of temporal filtering that have been proposed to eliminate such temporal effects. The techniques are illustrated by linking the number of daily admissions to hospital for respiratory diseases in Toronto, Canada for the 11 year period 1981 to 1991 with daily concentrations of ambient ozone. The ozone-hospitalization relationship was found to be highly sensitive to the length of temporal cycle removed from the admission time series, and to day of the week effects, ranging from a relative risk of 0.874 if long wave cycles were not removed at all to 1.020 for models which removed at least cycles greater than or equal to one month based on the interquartile pollutant range. The specific statistical method of adjustment was not a critical factor. The association was not as sensitive to removal of cycles less than one month, except that negative autocorrelation increased for series in which cycles of one week or less were removed. We recommend three criteria in selecting the degree of smoothing in the outcome: removal of temporal cycles, minimizing autocorrelation and optimizing goodness of fit. The association between ambient ozone levels and hospital admissions for respiratory diseases was also sensitive to the season of examination, with weaker associations observed outside the summer months.
Mutations in ABCA1, a member of the ATP-binding cassette family, have been shown to underlie Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA), which are genetic disorders that are characterized by depressed concentrations of plasma high density lipoprotein (HDL) cholesterol. An important question is whether common variants within the coding sequence of ABCA1 can affect plasma HDL cholesterol in the general population. To address this issue, we developed a screening strategy to find common ABCA1 variants. This strategy involved long-range amplification of genomic DNA by using coding sequences only, followed by deep sequencing into the introns. This method helped us to characterize a new set of amplification primers, which permitted amplification of virtually all of the coding sequence of ABCA1 and its intron-exon boundaries with a single DNA amplification program. With these new sequencing primers, we found 3 novel ABCA1 mutations: a frameshift mutation (4570insA, A1484S-->X1492), a missense mutation (A986D) in a TD family, and a missense mutation (R170C) in aboriginal subjects with FHA. We also used these sequencing primers to characterize 4 novel common amino acid variants in ABCA1, in addition to 5 novel common silent variants. We tested for association of the ABCA1 I/M823 variant with plasma HDL cholesterol in Canadian Inuit and found that M823/M823 homozygotes had significantly higher plasma HDL cholesterol compared with subjects with the other genotypes. The results provide proof of principle of the effectiveness of this approach to identify both rare and common ABCA1 genomic variants and also suggest that common amino acid variation in ABCA1 is a determinant of plasma HDL cholesterol in the general population.
A large cross-sectional study provided an opportunity to estimate the prevalence of childhood asthma in several regions across Canada.
In 1988, approximately 18,000 questionnaires were distributed to the families of 5-8 year old children in 30 communities from the following six regions across Canada: the interior of British Columbia, southeastern Saskatchewan, southwestern Ontario, the central region of Ontario, southern Quebec, and the Maritimes (Nova Scotia and Prince Edward Island). These communities were free of point-source air pollutants and selected to represent a range of ambient sulphate concentrations. In all 14,948 questionnaires were returned representing an 83% response rate.
Currently present, physician-diagnosed asthma was reported for 4.7% of children by their parents. Persistent wheezing was reported for 13% and persistent cough for 5.9%. Asthma was most common in the two Maritime provinces (7.4%), and least common in British Columbia (3.3%) and Quebec (3.4%). Similar regional differences were seen for persistent cough, persistent wheeze, and also hospital separation rates for asthma which were approximately 800 per 100,000 for the Maritimes and 396 per 100,000 for British Columbia. Differences persisted despite adjustments for several host and environmental (indoor and outdoor) characteristics.
The east coast of Canada may be an endemic area of asthma in Canada. If confirmed by objective measures of asthma, a detailed aetiologic investigation could enhance understanding of this phenomenon and the major environmental determinants of asthma morbidity in general.
A cross-sectional epidemiological study investigating the respiratory health of children in two Canadian communities was conducted in 1983-1984 in Tillsonburg, Ontario, located in a region of moderately elevated concentrations of transported air pollutants, and in Portage la Prairie, Manitoba, situated in a low pollution area. There were no significant local sources of industrial emissions in either community. Seven hundred and thirty-five children aged 7-12 were studied in the first town and 895 in the second. Respiratory health was assessed by the measurement of the forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1.0) of each child, and by evaluation of the child's respiratory symptoms and illnesses using a parent-completed questionnaire. Sulfur dioxide (SO2), sulfate, and particulate nitrate levels were significantly higher in Tillsonburg than in Portage la Prairie (P less than 0.05), but nitrogen dioxide (NO2) and inhalable particles (PM10) differed little between the communities. Historical data in the vicinity of Tillsonburg indicated that average annual levels of sulfates, total nitrates, and ozone (O3) did not vary markedly in the 9-year period preceding the study. The results show that Tillsonburg children had statistically significant (P less than 0.001) lower levels of 2% for FVC and 1.7% for FEV1.0 as compared with children in Portage la Prairie. These differences could not be explained by parental smoking or education, the use of gas cooking or wood heating fuels, pollution levels on the day of testing, or differences in age, sex, height, or weight. The differences persisted when children with cough with phlegm, asthma, wheeze, inhalant allergies, or hospitalization before age 2 for a chest illness were excluded from analysis. With the exception of inhalant allergies, which occurred more frequently in Tillsonburg children, the prevalence of chronic respiratory symptoms and illnesses was similar in the two communities.
In 1988, the authors conducted a questionnaire-based study on the health effects of the indoor environment in 30 Canadian communities. This paper focuses on the association between the respiratory health of young children and home dampness and molds. A total of 17,962 parents or guardians of schoolchildren received a questionnaire, and 14,948 (83.2%) questionnaires were returned. Children living in mobile homes, tents, and boats were excluded as were those with cystic fibrosis, leaving 13,495 children included in the study group. The housing stock was distributed as follows: 81% were one-family detached homes, 6% were one-family attached homes, and 13% were buildings for two or more families. Molds were reported in 32.4%, flooding in 24.1%, and moisture in 14.1% of the homes. Prevalences of all respiratory symptoms were consistently higher in homes with reported molds or dampness; i.e., adjusted odds ratios ranged from 1.32 (95% confidence interval 1.06-1.39) for bronchitis to 1.89 (95% confidence interval 1.58-2.26) for cough. The prevalence of home dampness or molds, 37.8%, indicates that it is an important public health issue. Further studies are required to elucidate the pathogenesis.