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BACKGROUND The tuberculin skin test (TST) is often used to screen for latent tuberculosis infection (LTBI) in school children, many of whom were bacille Calmette-Guerin (BCG)-vaccinated in infancy. The reliability of the TST in such children is unknown. METHODS TSTs performed in low-risk BCG-vaccinated and -nonvaccinated grade 1 and grade 6 First Nations (North American Indian) school children in the province of Alberta, Canada, were evaluated retrospectively. To further assess the specificity of the TST, BCG-vaccinated children with a positive TST (≥10 mm of induration) and no treatment of LTBI were administered a QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis International). RESULTS A total of 3996 children, 2063 (51.6%) BCG-vaccinated and 1933 (48.4%) BCG-nonvaccinated, were screened for LTBI. Vaccinated children were more likely than nonvaccinated children to be TST positive (5.7% vs. 0.2%, P < 0.001). Vaccinated children with a positive TST were more likely to have a recent past TST as compared with those with a negative TST (6.8% versus 2.8%, P = 0.01). Among 65 BCG-vaccinated TST-positive children who underwent a QFT-GIT, only 5 (7.7%; 95% CI: 2.5%, 17.0%) were QFT-GIT positive. A TST of ≥15 mm was more likely to be associated with a positive QFT-GIT than a TST of 10 to 14 mm, 16.0% (95% CI: 4.5%, 36.1%) versus 2.5% (95% CI: 0.1%, 13.2%), P = 0.047. CONCLUSION The TST is unreliable in school children, BCG-vaccinated in infancy, and who are at low risk of infection. The QFT-GIT is a useful confirmatory test for LTBI in BCG-vaccinated TST-positive school children.

BACKGROUND: Currently, no reference or normative values for spirometry based on a randomly selected Canadian population exist.OBJECTIVE: The aim of the present analysis was to construct spirometric reference values for Canadian adults 20 to 90 years of age by combining data collected from healthy lifelong nonsmokers in two population-based studies.METHOD: Both studies similarly used random population sampling, conducted using validated epidemiological protocols in the Canadian Obstructive Lung Disease study, and the Lung Health Canadian Environment study. Spirometric lung function data were available from 3042 subjects in the COLD study, which was completed in 2009, and from 2571 subjects in the LHCE study completed in 1995. A total of 844 subjects 40 to 90 years of age, and 812 subjects 20 to 44 years of age, were identified as healthy, asymptomatic, lifelong nonsmokers, and provided normative reference values for spirometry. Multiple regression models were constructed separately for Caucasian men and women for the following spirometric parameters: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio, with covariates of height, sex and age. Comparison with published regression equations showed that the best agreement was obtained from data derived from random populations.RESULTS: The best-fitting regression models for healthy, never-smoking, asymptomatic European-Canadian men and women 20 to 90 years of age were constructed. When age- and height-corrected FEV1, FVC and FEV1/FVC ratio were compared with other spirometry reference studies, mean values were similar, with the closest being derived from population-based studies.CONCLUSION: These spirometry reference equations, derived from randomly selected population-based cohorts with stringently monitored lung function measurements, provide data currently lacking in Canada.

To cite this article: Chan-Yeung M, Anthonisen NR, Becklake MR, Bowie D, Sonia Buist A, Dimich-Ward H, Ernst P, Sears MR, Siersted HC, Sweet L, Van Til L, Manfreda J. Geographical variations in the prevalence of atopic sensitization in six study sites across Canada. Allergy 2010; 65: 1404–1413. Abstract Background: Geographical variations in atopic sensitization in Canada have not been described previously. This study used the standardized protocol of the European Community Respiratory Health Survey-1 (ECRHS-1) to investigate the distribution and predictors of atopic sensitization in six sites across Canada and to compare the results with some ECRHS-1 centers. Methods: Adults aged 20–44 years in six study sites across Canada underwent allergy skin testing using 14 allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae) cat, cockroach, grasses (Timothy grass, Kentucky grass), molds (Cladosporium herbarium, Alternaria alternata, Aspergillus fumigatus, Penicillium), trees (tree mix, birch, Olea europea), and common ragweed. Results: The overall prevalence of atopy (skin test over 0 mm to any allergen) was 62.7%. There was significant geographical variation in the prevalence of atopy in the six study sites (lowest 55.6% [95% C.I.51.3–59.9] in Prince Edward Island, highest 66.0 [61.7–70.3] in Montreal) and of sensitization to each of the allergens tested even after adjustment for confounders. When the first eight of the nine allergens in the ECRHS were used to estimate the prevalence of atopic sensitization, the prevalence of atopy in Canada was 57% compared with 35.2% overall for centers in the ECRHS. The prevalence of atopy in Vancouver (57% [52.3–61.8]) was close to that of Portland, Oregon (52.1% [46.2–58.0]). Conclusion: There was a significant variation in atopic sensitization among different study sites across Canada. The prevalence of atopic sensitization is relatively high in Canada compared with sites in the ECRHS and this may, in part, account for the high prevalence of asthma and asthma symptoms in Canada.

Christine Macie, Kate Wooldrage, Jure Manfreda, Nicholas AnthonisenDepartment of Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaAbstract: We used the Manitoba Health database to examine the relationship between use of inhaled respiratory drugs in people with chronic obstructive respiratory diseases and cardiovascular hospitalizations from 1996 through 2000. The drugs examined were beta agonists [BA], ipratropium bromide IB, and inhaled steroids (ICS). End points were first hospitalizations for supraventricular tachycardia, myocardial infarction, heart failure or stroke. A nested case control analysis was employed comparing people with and without cardiovascular events. Cases and controls were matched for gender and age, and conditional logistic regression was used in multivariate analysis considering other respiratory drugs, respiratory diagnosis and visit frequency, non-respiratory, non-cardiac comorbidities, and receipt of drugs for cardiovascular disease. In univariate analyses, BA, IB and ICS were all associated with hospitalizations for cardiovascular disease, but in multivariate analyses ICS did not increase risk while both BA and IB did. There were interactions between respiratory and cardiac drugs receipt in that bronchodilator associated risks were higher in people not taking cardiac drugs; this was especially true for stroke. There were strong interactions with specific cardiac drugs; for example, both BA and IB substantially increased the risk of supraventricular tachycardia in patients not anti-arryhthmic agents, but not in the presence of such agents. We conclude that bronchodilator therapy for chronic obstructive diseases is associated with increased cardiovascular risk, especially in patients without previous cardiovascular diagnoses, and that this is unlikely due to the severity of the respiratory disease, since risk was not increased with ICS.Keywords: bronchodilator therapy, inhaled corticosteroids, nested case control study

BACKGROUND: Pediatric tuberculosis (TB) is important medically and indicative of a public health problem. An understanding of the epidemiology and case characteristics of pediatric TB, in a province that accepts large numbers of immigrants, can inform TB elimination strategy. METHODS: All cases of pediatric TB notified in Alberta between 1990 and 2004 were identified in the TB Registry. Individual diagnostic criteria were reviewed and case patients were related to a population grid derived from Statistics Canada censuses and population estimates of Status Indians from the Department of Indian and Northern Affairs, Canada. Incidence rates were determined by ethnic group and gender. Clinical/mycobacteriologic case characteristics were compared by ethnic group and birth country. RESULTS: Among 124 notified cases, 95 (96 episodes) met strict diagnostic criteria: 45 Status Indians, 30 Canadian-born ‘other’ and 21 foreign-born. Incidence rates were much higher in Status Indians and the foreign-born compared to the Canadian-born ‘other’; 10.7, 5.4, and 0.4 per 100,000 person-years, respectively. Among Canadian-born ‘other’ cases, 12 were Métis and 11 were Canadian-born children of foreign-born parents. Compared to foreign-born cases, Canadian-born cases were more likely to have a source case in Alberta, to be detected through contact tracing, to have primary pulmonary TB, and to have a rural address. CONCLUSION: Pediatric TB in Alberta is mainly the result of ongoing transmission in Aboriginal peoples and immigration to Canada of persons with latent TB infection. The elimination of pediatric TB will require interruption of transmission in Aboriginal peoples and prevention of disease in immigrants.

BACKGROUND: On April 1, 2004, BCG (bacille Calmette-Guérin), a tuberculosis (TB) control vaccine, was discontinued in all but four high-risk communities in Alberta. To confirm the safety of vaccine withdrawal, and for future planning, the annual risk of infection (ARI) was determined in preschool First Nations children. METHODS: First Nations children born into reserve communities in Alberta between April 1, 1998 and March 31, 2004, and still living on reserve in 2004–2005, were identified. Health centre TB histories were validated by cross-referencing the birth cohort with the provincial TB Registry. Children that were not BCG vaccinated and not known to be tuberculin skin test (TST) positive underwent a TST. Birth cohort children were grouped as follows: (i) BCG vaccinated; (ii) BCG non-vaccinated, no TST; (iii) BCG non-vaccinated, TST; (iv) BCG vaccination status unknown. The ARI was calculated and the age and community characteristics of the groups were compared. RESULTS: There were 8,447 children in the 6-year birth cohort, 4,699 (55.6%) vaccinated, 2,696 (31.9%) non-vaccinated, and 1,052 (12.5%) whose vaccination status was unknown. Of the non-vaccinated children, 1,921 (71.3%) were tested and only 2 were TST positive. No other TST positive, BCG non-vaccinated children were identified in the TB Registry cross-match. The prevalence of infection in 2004–2005 was 0.1% and the ARI was 0.03%. The community risk of TB exposure was comparable in tuberculin-tested and non-tested BCG non-vaccinated children. CONCLUSION: In low BCG-uptake First Nations communities in Alberta, the ARI is low and it is safe to withdraw BCG.

SUBJECTIVE OBJECTIVES: To document healthcare utilization 2 years after diagnosis in women with obstructive sleep apnea syndrome (OSAS).Retrospective observational cohort study.Tertiary university-based medical center.Four hundred and fourteen women with OSAS were matched with 1404 women from the general population who served as controls.Patients were treated with continuous positive airway pressure (CPAP) or were recommended weight loss alone.There were 231 treatment compliant (TC) patients, 91 patients not using CPAP (NCU), and 92 patients who were only recommended weight loss (WL). In the entire group, there was increase in fees of $123.43+/-$25.01 in the 2 years before diagnosis and a reduction of fees of $37.96+/-$21.35 in the 2 years after diagnosis (p.0001). Physician claims increased in the 2 years before diagnosis by $111.22+/-31.35 in TC and by $152.77+/-59.55 in the NCU groups and then decreased in TC by $20.96+/-$26.60 (p.01) and NCU by $72.20 +/-45.91 in the 2 years after diagnosis (p.01). The fees in WL group did not change significantly. The number of clinic visits of the entire group increased in the 2 years before diagnosis by 2.32+/-0.43 and decreased over the next 2 years by 1.48+/-0.42 visits (p.0001). There was an increase of clinic visits in the 3 subgroups in the 2 years before diagnosis (2.30+/-0.57 in TC, 2.55+/-0.99 in NCU, and 2.18+/-0.82 in WL groups) followed by a reduction of clinic visits over the next 2 years (1.56+/-0.55 fewer visits in TC [p.0001], 1.70+/-0.90 in NCU [p.01], and 1.04+/-0.90 in the WL group [p.05] ).Healthcare utilization in women with OSAS increased in the years before sleep-clinic evaluation and then decreased in the following 2 years.

Study objectives To assess the influence of inhaled corticosteroids (ICSs) on mortality in COPD patients, which is currently a controversial topic. Setting Manitoba Health maintains a population-wide research database that includes pharmaceutical information. Design and patients We examined mortality in people 90 to 365 days after hospital discharge for COPD, comparing those persons who received inhaled steroids within 90 days of hospital discharge with those who did not. Cox proportional hazards models were used with adjustments for other respiratory drugs, comorbidities, and physician visits before and after hospital discharge. We also compared mortality in patients who received inhaled steroids with those who received other respiratory drugs, but not inhaled steroids, and those who received neither. Using nested case control analysis, we examined the time of receipt of inhaled steroids in relation to fatal events. Results In people > 65 years of age, inhaled steroids were associated with a 25% reduction in mortality between 90 and 365 days after hospital discharge, while mortality increased with bronchodilator use, physician visits, age, and comorbidities. The exclusion of people who had also received a diagnosis of asthma or had received inhaled steroids before hospitalization did not change the result. Inhaled steroids were associated with an even larger mortality reduction in people aged 35 to 64 years. People who received bronchodilators but no steroids had higher mortality than people who received no bronchodilators or received both bronchodilators and inhaled steroids. The reduction in all-cause mortality was largely due to the decreased number of cardiovascular deaths. The receipt of inhaled steroids within 30 days of death was protective, but this was not the case for greater time intervals. Conclusions Therapy with ICSs reduced mortality in COPD patients; the effect was particularly notable for cardiovascular death and was short term in that it was dependent on recent exposure.

Purpose To estimate incidence rates for dementia and the impact of subject attrition on these rates. Methods Crude, age- and gender-specific incidence rates of dementia and Alzheimer's disease were calculated using person-years analysis and Cox proportional hazard models in a population-based cohort study of 1952 adults aged 65+ years in Manitoba, Canada. Rates were standardized to the nondemented population using the direct method. Ratios of incidence rates comparing completers to subjects who had died, refused, or were unavailable for follow up were based on health care utilization data (available for all subject groups) and used to adjust rates for attrition. Results Decedents had a significantly higher incidence of dementia than did subjects who completed the follow-up assessment. The incidence in subjects who refused or were unavailable at follow up was intermediate between decedents and completers. Adjusted for attrition, the standardized dementia incidence rate for community and institutional subjects was 25.3/1000 person-years, significantly higher than that based on follow-up assessments only (17.8/1000 person-years; 95% confidence interval: 14.3–21.4). Conclusions The impact of loss to follow up on incidence rates varies depending on the reason for subject attrition. Incidence studies of dementia should develop strategies to characterize and address subject attrition to avoid underestimating disease incidence.

Background A worldwide increase has been noted in the prevalence of asthma, but the data for other allergic disorders are less consistent. Objective To study 14-year trends in utilization of physician resources for asthma and compare them to trends for allergic rhinitis. Methods We studied visits to physicians by Manitoba residents for asthma ( International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD-9-CM ] code 493) and allergic rhinitis ( ICD-9 code 477) between 1985 and 1998. Prevalence and incidence of physician resources utilization were calculated annually for the total population and by age groups. Aggregate statistics and frequency of physician resources utilization were also analyzed. Results The prevalence and incidence of physician resources utilization for asthma increased more than for allergic rhinitis; differences were most striking in the youngest age groups. In adults, the differences were smaller and changed little with time. Most of the increase in asthma care occurred in children and in people without allergic rhinitis. Overall, 17% of Manitobans were diagnosed as having asthma, and the average asthmatic patient made 6 visits. Approximately 14% had an allergic rhinitis diagnosis, each person being seen twice on average. Coexistence of asthma and allergic rhinitis led to increased physician resources utilization for each of the conditions. Conclusions Trends in utilization of physician resources for allergic rhinitis differed strikingly from trends for asthma, particularly in the youngest age group. Asthma and allergic rhinitis affected comparable proportions of the population, but a diagnosis of asthma resulted in much higher utilization of physician resources. The relationship of physician-diagnosed asthma and atopy, as indicated by the diagnosis of allergic rhinitis, appears to have weakened with time in children but not in adults.

STUDY OBJECTIVES Patients with untreated obstructive sleep apnea syndrome (OSAS) have higher healthcare utilization than matched controls. However, the long-term impact of continuous positive airway pressure (CPAP) use on healthcare utilization is unknown. DESIGN Retrospective observational cohort study. SUBJECTS There were 342 eligible men with OSAS and matched controls on whom there were utilization data for 5 years prior to initial OSAS diagnosis and for the 5 years on CPAP treatment of the cases. INTERVENTIONS Patients were treated with CPAP. RESULTS Patients with OSAS were typical cases (mean +/- SD): age, 48.2 +/- 0.6 years; body mass index, 35.6 +/- 0.4 kg/m2; Epworth Sleepiness Scale score, 14.2 +/- 0.3; apnea-hypopnea index, 47.1 +/- 1.8 events per hour. The number of physician visits were higher by 3.46 +/- 0.2 (95% confidence interval [CI]: 2.57 to 4.36) in cases in the year before diagnosis, compared with the fifth year before diagnosis, then decreased over the next 5 years by 1.03 +/- 0.49 (95% CI: -1.99 to -0.07)(P

Objective: The objective of this cohort study was to determine if complications of pregnancy and labor, characteristics at birth, and exposure to infections influence the incidence of asthma in the first 6 years of life. Design: We identified all children born between 1980 and 1990 in the Province of Manitoba, Canada. We used records of physician contacts (inpatient and outpatient) and services of the universal provincial health insurance plan to follow up 170,960 children from birth to the age of 6 years to identify the first diagnosis of asthma. Information on mothers and siblings was also obtained to determine family history of disease and exposure to infections. Results: During the study period, a diagnosis of asthma was made in 14.1% of children by the age of 6 years. The incidence was higher in boys than in girls, in those with family history of allergic diseases. It was higher in urban than in rural areas, and lowest in those born in winter. Asthma was more likely in those with low birth weight and premature birth. Certain congenital abnormalities and complications of pregnancy and labor also increased the risk of asthma. The risk of asthma increased with maternal age. Both upper and lower respiratory infections increased the risk of subsequent asthma, and this effect was more important than exposure to familial respiratory infections, which also tended to increase asthma risk. The risk of asthma decreased with the number of siblings when siblings had a history of allergic disorders. Conclusions: In addition to genetic influences, intrauterine and labor conditions are determinants of asthma. Exposure to both upper and lower respiratory tract infections increases the risk; these infections do not explain the protective effect associated with the increasing number of siblings.

Objectives Geographic variability in reported prevalences of asthma worldwide could in part relate to interpretation of symptoms and diagnostic biases. Bronchial responsiveness measurements provide objective evidence of a common physiologic characteristic of asthma. We measured bronchial responsiveness using the standardized protocol of the European Community Respiratory Health Survey (ECRHS) in six sites in Canada, and compared prevalences across Canada with international sites. Design Samples of 3,000 to 4,000 adults aged 20 to 44 years were randomly selected in Vancouver, Winnipeg, Hamilton, Montreal, Halifax, and Prince Edward Island, and a mail questionnaire was completed by 18,616 individuals (86.5%). Preselected random subsamples (n = 2,962) attended a research laboratory for examination including more detailed questionnaires, lung function testing including methacholine challenge, and skin testing with 14 allergens. Results Prevalences of bronchial hyperresponsiveness, measured as cumulative dose of methacholine required to produce a 20% fall from the post-saline solution FEV 1 ≤ 1 mg, ranged from 4.9% (95% confidence interval [CI], 1.6 to 8.5) in Halifax to 22.0% (95% CI, 18.1 to 26.0) in Hamilton (median, 10.7%). In all Canadian sites, bronchial hyperresponsiveness was more prevalent in women than in men. Neither the geographic nor gender differences were accounted for by differences in age, smoking, skin test reactivity, or baseline FEV 1. Geographic- and gender-related variability changed little when only bronchial hyperresponsiveness associated with asthma-like symptoms was considered. Conclusions A wide variability in bronchial responsiveness can occur within one country, almost as wide as the range found across all international sites participating in the ECRHS study and not explained by differences in gender, smoking, skin test reactivity, and FEV 1 . While gender variability in the prevalence of bronchial responsiveness is likely due to hormonal and immunologic factors, geographic variability is likely to result from environmental factors.

Background Allergic sensitization is a major risk factor in asthma. Objective To evaluate the effectiveness of and compliance to intervention measures in reducing levels of house-dust mite and cat allergen in the context of a randomized, controlled study in the primary prevention of asthma. Methods A total of 545 high-risk families were recruited prenatally and randomly assigned into the intervention group (n = 278) and the control group (n = 267). Intervention measures were instituted before birth of the infants and maintained for 12 months afterward in the intervention group and the control group received the usual care from their family physician. Dust samples were collected at six sites in the homes before birth and at specific intervals up to 24 months after birth for analysis of allergens. At 24 months, there were 244 families in the intervention group and 228 in the control group available for followup examination. Results House-dust mite avoidance measures, consisting of encasement of mattresses, pillows, and duvets, and hot-water washing of bedding were effective in reducing mite allergen in parents' mattresses to one-third from baseline, significantly lower than the control group, even at 24 months. The use of an acaricide did not reduce mite allergen levels in carpets and upholstered furniture. Seventeen intervention families gave up their cats but six families acquired a new one over a period of 24 months, similar to control families. Cat allergen levels decreased in all sites in the homes of those who removed the cat, similar in both groups. Conclusions House-dust mite avoidance measures were effective in reducing house-dust mite allergen in mattresses, but not on floors. Reduction in cat allergen levels were evident for those families who got rid of their cats, but the advice to remove pets was not adhered to by most families.

Background Patients with obstructive sleep apnea syndrome (OSAS) use health-care resources at higher rates than control subjects for years prior to diagnosis. Although obesity and certain cardiovascular disorders are more common in OSAS patients, the precise cause of increased health-care utilization is unclear. Objectives To examine the causes of increased utilization, and what patients with OSAS were being treated for prior to this diagnosis. Methods We compared the records of 773 patients with OSAS to those of age-, gender-, geographic-, and physician-matched control subjects from the general population. Results We found that sleep apnea patients used 23 to 50% more resources (defined by physician fees, physician visits, and hospital nights) in the 5 years prior to diagnosis than did control subjects. We examined the diagnoses made and found that apnea patients are at higher risk for hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.0 to 3.3), congestive heart failure (OR, 3.9; 95% CI, 1.7 to 8.9), cardiac arrhythmias (OR, 2.2; 95% CI, 1.2 to 4.0), cardiovascular disease (OR, 2.6; 95% CI, 2.0 to 3.3), chronic obstructive airways disease (OR, 1.6; 95% CI, 1.2 to 2.0), and depression (OR, 1.4; 95% CI, 1.0 to 1.9). To control for the confounding effects of obesity and to determine the independent effects of body mass index (BMI), gender, age, degree of hypoxemia, apnea-hypopnea index, and sleepiness in the 773 patients, we performed a logistic regression analysis with the dependent variable being diagnosis, and a linear regression analysis with the dependent variable being measures of health-care utilization. Age and BMI were significant independent predictors of most cardiovascular diagnoses and arthropathy. Male gender predicted ischemic heart disease (OR, 2.98; 95% CI, 1.36 to 6.54), and female gender was predictive of chronic obstructive airways disease (OR, 2.63; 95% CI, 1.85 to 3.72) and depression (OR, 2.24; 95% CI, 1.45 to 3.44). The best model predicting health-care utilization measures was comprised of age, gender, and BMI, and explained 9%, 14%, and 8% of the variability in physician fees, number of physician claims, and number of physician visits, respectively. Conclusion Of all comorbid diagnoses, significantly increased utilization was found for cardiovascular disease and especially hypertension in the OSAS patients.

To document health-care utilization (ie, physician claims and hospitalizations) in patients with obesity-hypoventilation syndrome (OHS), for 5 years prior to the diagnosis and for 2 years after the diagnosis and initiation of treatment.Retrospective observational cohort study.University-based sleep disorders center in Manitoba, Canada.Twenty OHS patients (mean [+/- SD] age, 52.7 +/- 9.5 years; body mass index [BMI], 47.3 +/- 11.0 kg/m(2); PaCO(2), 59.7 +/- 13.8 mm Hg; PaO(2), 51.6 +/- 12.4 mm Hg) were matched to two sets of control subjects. First, each case was matched to 15 general population control subjects (GPCs) by age, gender, and geographic location, and, second, each case was matched to a single obese control subject (OBC) who was matched using the same criteria as for the GPCs, plus the measurement of BMI.In the 5 years before diagnosis, the 20 OHS patients had (mean +/- SE) 11.2 +/- 1.8 physician visits per patient per year vs 5.7 +/- 0.8 (p0.01) visits for OBCs and 4.5 +/- 0.4 (p0.001) visits for GPCs. OHS patients generated higher fees, $623 +/- 96 per patient per year for the 5 years prior to diagnosis compared to $252 +/- 34 (p0.001) for OBCs and $236 +/- 25 (p0.001) for GPCs. OHS patients were much more likely to be hospitalized than were subjects in either control group in the 5 years prior to diagnosis (odds ratio [OR] vs GPCs, 8.6) (95% confidence interval [CI], 5.9 to 12.7); OR vs OBCs, 4.9 (95% CI, 2.3 to 10.1). In the 2 years after diagnosis and the initiation of treatment (usually continuous positive airway pressure or bilevel positive airway pressure), there was a significant linear reduction in physician fees. In the 2 years after the initiation of treatment, there was a 68.4% decrease in days hospitalized per year (5 years before treatment, 7.9 days per patient per year; after 2 years of treatment, 2.5 days per patient per year [p = 0.01]).OHS patients are heavy users of health care for several years prior to evaluation and treatment of their sleep breathing disorder; there is a substantial reduction in days hospitalized once the diagnosis is made and treatment is instituted.

Background Current knowledge of risk factors for Alzheimer’s disease (AD) is limited. Data from a longitudinal, population-based study of dementia in Manitoba, Canada were used to investigate risk factors for AD. Methods Cognitively intact subjects completed a risk factor questionnaire assessing sociodemographic, genetic, environmental, medical and lifestyle exposures. Five years later, 36 subjects had developed AD and 658 remained cognitively intact. Results Older subjects or those who had fewer years of education were at greater risk of AD. After adjusting for age, education and sex, occupational exposure to fumigants/ defoliants was a significant risk factor for AD (relative risk [RR] = 4.35; 95% CI : 1.05‐17.90). A history of migraines increased the risk of AD (RR = 3.49; 95% CI : 1.39‐8.77); an even stronger effect was noted among women. Self-reported memory loss at baseline was associated with subsequent development of AD (RR = 5.15; 95% CI : 2.36‐11.27). Vaccinations and occupational exposure to excessive noise reduced the risk of AD. Conclusions Some well-known risk factors for AD were confirmed in this study and potential new risk factors were identified. The association of AD with a history of migraines and occupational exposure to defoliants/fumigants is of particular interest because these are biologically plausible risk factors.

BACKGROUND: Spirometry, the measurement of forced expiratory volume in 1 s and forced vital capacity, is recommended in the diagnosis and management of the obstructive lung diseases asthma and chronic obstructive pulmonary disease (COPD). The present report describes spirometry use in Manitoba and tests the hypothesis that regional spirometry use correlates with the prevalence of physician-diagnosed obstructive lung diseases.METHODS: Spirometry is remunerated on a fee-for-service basis by Manitoba Health. Like other physician services, billing data include a diagnosis, patient identifiers, as well as the patient’s sex, date of birth and residential postal code. Physician billings for spirometry for 1991 to 1998 were analyzed, comparing data with billings for physician visits for obstructive diseases. Four age groups were examined, as were income quintiles in Winnipeg, Manitoba. In addition, the prevalence of physician-diagnosed obstructive diseases were compared with spirometry rates in 49 service use areas of the province.RESULTS: Annually, about 3% of the Manitoba population underwent spirometry, and in aggregate, about 14% underwent spirometry during the eight years of the study. Rates in Winnipeg were higher than in the remainder of the province. Spirometry rates did not increase with time, and people who underwent spirometry had 1.4 to 1.7 tests/year. In children, higher income quintiles were tested more than lower income quintiles, while in adults, income quintiles were tested with equal frequency. People with obstructive lung disease accounted for about 75% of those tested, and in people with these diagnoses, the likelihood of testing increased approximately linearly with the number of physician visits for asthma or COPD. Children with asthma were tested less often than adults, and adults with asthma or both asthma and COPD were tested more often than those with COPD alone. In adults with asthma or asthma and COPD who had more than 10 physician visits for these diagnoses, testing rates were more than 70%, and multiple tests were common. In patients labelled with COPD only and with more than 20 physician visits, about one-third did not undergo spirometry. In children aged five to 14 years and in adults 15 to 44 years old, regional spirometry rates correlated well with regional asthma rates. Regional spirometry rates also correlated significantly with regional rates of asthma and/or COPD in people older than 34 years old.INTERPRETATION: Spirometry use is considerably higher in patients with asthma than in patients with COPD, suggesting that guidelines are followed more closely in patients with asthma, and that many patients are labelled with COPD without appropriate documentation. Spirometry use is apparently indicative of physician interest in the problem of obstructive lung diseases.

Polymorphisms in the TNF- α (A–308G), IL-4 (C–589T), and Fc α RI β (E237G) genes have been associated with asthma and related phenotypes. To determine the predictive value of these polymorphisms we have assessed their relative risk (RR) for the development of atopy, asthma, and rhinitis in a high-risk infant population that is being followed longitudinally from birth. DNA was extracted and genotyped for 373 infants and 572 parents for each polymorphism. Phenotypic data were collected for atopy and allergic diseases in the infants at 12 mo of age. The prevalence of these phenotypes in the 281 white infants was compared in each genotypic group. There were no differences in the prevalence of any phenotype between genotypes of the TNF- α and Fc α RI β polymorphisms. However, we found that the IL4-589*T allele was associated with “probable” asthma (RR = 4.1) and that homozygotes for the IL4-589*T allele had an increased risk for the development of rhinitis (RR = 2.4). Using the transmission disequilibrium test...

Background The value of cord blood IgE in predicting the development of asthma and other IgE-mediated allergic diseases is unclear. Objective The purpose of this study is twofold: (1) to determine factors affecting cord blood IgE level and (2) to determine whether cord blood IgE predicts the development of asthma and other IgE-mediated allergic diseases in high risk (defined as those with at least one first degree relative with asthma or 2 first degree relatives with other IgE-mediated allergic diseases) infants at 12 months. Methods The study utilized cord blood obtained from a group of high risk infants who took part in a randomized controlled trial to assess the effectiveness of an intervention program in the primary prevention of asthma and other IgE-mediated allergic diseases. Total IgE and cotinine in the cord blood were measured. Assessment of the infants was done at 12 months for these diseases. Results Sixty-four (17.8%) infants had detectable total IgE in cord blood >0.5 kU/L. The proportion of infants with elevated cord blood IgE was significantly higher among nonwhites, birth during winter months, and those with a maternal history of asthma. There was no correlation between cord blood IgE and cord blood cotinine level. Cord blood IgE was found to be a significant predictor for the development of urticaria due to food allergy but not for other outcomes. Conclusion Both genetic and environmental risk factors play a role in determining the level of IgE in cord blood. Cord blood IgE was a significant risk factor for the development of urticaria due to food allergy at 12 months of life. As urticaria due to food allergy is a prodrome for anaphylaxis, measurement of IgE in cord blood may be indicated in infants at high risk for developing allergic diseases so that preventive measures can be applied.

Background: Cord blood mononuclear cells (CBMNCs) have been found to proliferate when stimulated with food or inhalant allergens. The significance of this finding is not known. Objectives: We sought to determine the factors associated with proliferation of CBMNCs when stimulated with house dust mite (HDM) allergen and to determine whether proliferation of CBMNCs is associated with subsequent development of HDM sensitization and development of allergic rhinitis and asthma. Methods: Cord blood was taken from infants at high risk for having asthma and allergic diseases who were recruited for a primary prevention study in which infants were randomized into the intervention or the control group. CBMNCs were stimulated with HDM allergen and PHA as a positive control. Infants were assessed at 12 and 24 months for health outcome. Results: When stimulated with HDM allergen, 29.7% of infants had a stimulation index (SI) of 2 or greater. There were no differences in the levels of cord blood IgE and cotinine, maternal smoking, immediate skin test reactivity, maternal IgE, and maternal exposure to HDM allergen between those with an SI of 2 or greater and those with an SI of less than 2. Infants with an SI of less than 2 had a significantly higher proportion of mothers with a history of asthma. No differences in the incidence of "asthma" and rhinitis without cold at 12 months and cumulative prevalence at 24 months were seen between the 2 groups. None of the infants had skin test reactions to HDM allergen. Conclusion: The negative association between HDM allergen–induced proliferation of CBMNCs and maternal mite allergen exposure and health outcomes at 12 and 24 months raises the issue of the significance of CBMNC proliferation. (J Allergy Clin Immunol 1999;104:317-21.)

Background: Several pets, such as cats, dogs, and rodents, are known to produce allergens. Despite the clinical and laboratory evidence that exposure to pets can cause bronchoconstriction in sensitized subjects, the results of population studies have been contradictory. Objectives: The purpose of this study was to investigate the relationship between cat ownership and the prevalence of asthma, asthma-like symptoms, and bronchitic symptoms among subjects 20 to 44 years of age in Vancouver, Canada and to determine whether sensitization is responsible for such an association. Methods: Two thousand nine hundred ninety-nine (88%) randomly selected subjects responded to a mail questionnaire. Of these, 504 participated in laboratory examination, including allergy skin testing. Results: One thousand nineteen study responders (34%) were pet owners at the time of the study (current owners). Current pet owners were found to have a higher prevalence of current asthma, asthma-like symptoms, and bronchitic symptoms compared with those without pets. Cat owners had significantly higher risk of having current asthma and asthma-like symptoms. In the subset who had allergic skin tests, we found that those who were allergic to cat dander had a significantly higher risk of current asthma than those not allergic to cat dander and not owning a cat. Conclusion: This study provides evidence that sensitization to cat dander is a more important risk factor for current asthma and asthma-like symptoms than cat ownership itself. (J Allergy Clin Immunol 1999;103:60-5.)

Objectives (1) To correlate structure (CT) with function in pulmonary tuberculosis (TB), and (2) to describe the evolution of structural and functional abnormalities when pulmonary TB is treated with directly observed therapy. Subjects and methods Twenty-five patients with drug-susceptible pulmonary TB, 15 cavitary and 10 noncavitary, were studied prospectively. Conventional CT and pulmonary function testing (spirometry, diffusing capacity, and arterial blood gases) were performed at baseline, and after 1 and 6 months of directly observed therapy. Results All but one patient with noncavitary miliary TB had CT evidence of endobronchial disease, and all patients with cavitary disease had coexistent reduced lung attenuation, the latter presumably a result of gas trapping, hypoxic vasoconstriction, and vascular injury. Functional impairment was minimal and in proportion to the number of diseased segments and cavitary volume. Bronchiectasis was significantly more likely to complicate cavitary than noncavitary disease (64 vs 11%; p Conclusions CT findings correlate well with function in pulmonary TB. Physiologic data were consistent with the concept that pulmonary TB is an endobronchial disease that causes parallel reductions in ventilation and perfusion. This concurrent involvement of both airways and contiguous pulmonary blood supply offers an explanation for the minimal respiratory limitation experienced by these patients despite often extensive lung disease. Supervised therapy of drug-susceptible disease results in minimal structural and functional residua.

Background Several acaricides have become available for reducing house dust mite allergen levels. Objective The purpose of this study was to assess whether the use of benzyl benzoate (Acarosan) provides additional benefit to the usual mite control measures including encasement of mattress and pillows with vinyl covers. Methods A randomized controlled trial was carried out in 26 homes (14 control versus 12 treatment) of asthmatic patients in two cities (Vancouver and Winnipeg). The control group had the usual house dust mite control measures including the use of vinyl covers for mattresses and pillows while the treatment group had application of benzyl benzoate to mattresses and carpets in the bedroom and the most commonly used room, in addition to the above control measures. Mite allergen levels were measured 3 months and immediately before, 1 week, and 1 and 3 months after the application of house dust mite control measures. Patients kept diary cards on asthma symptoms and peak expiratory flow rates morning and evening 1 month before and 3 months after the onset of mite allergen control measures. Results A reduction of mite allergen level was found in mattress samples in both groups, statistically significant at all times in the treatment group and at 1 and 3 months in the control group. Mite allergen levels on floor carpets also showed progressive reduction in both groups, but were significantly different in the treatment group (compared with controls) at 1 week, and were lower compared with baseline in the treatment group up to 3 months. No significant changes in asthma symptoms, peak expiratory flow rates, spirometric measurements, or bronchial hyperresponsiveness were observed among treatment or control group subjects. Conclusion The addition of benzyl benzoate to conventional house dust mite control measures resulted in a significant reduction in floor carpet dust mite levels that persisted for 3 months. The results of this study should be confirmed in a larger and longer study.

High blood pressure is a well-recognized, modifiable, cardiovascular disease risk factor. Tracking of blood pressure was examined in the University of Manitoba Follow-up Study, a cohort of 3,983 men followed over a 40-year period, between 1948 and 1988. Blood pressure measurements recorded over time in these men, prior to the development of ischemic heart disease, were used in this analysis. Two approaches to tracking were used ; correlation analysis and the quantification of the likelihood for a man whose blood pressure was in either the top or bottom quintile to remain in the extreme end of the distribution at later measurement. For ages 25-75 years and for intervals between blood pressure measurement ranging from 5 to 35 years, significant evidence for tracking was found. The strongest evidence for tracking was in middle age, 45-55 years. Strength of tracking decreased with increasing time between measurements. This analysis suggests that men at highest risk for hypertension can be identified at a young age. Hence, strategies for prevention of cardiovascular complications can be targeted in early adulthood.

To determine the epidemiology and clinical features of disease due to nontuberculous mycobacteria (NTM) in our institution, we reviewed the medical records of all patients from whom NTM isolates were recovered from 1988 to 1990 to extract selected clinical and laboratory data. On the basis of the likelihood of infection, patients were classified as having definite, probable, or unlikely NTM disease as defined by published guidelines. Of 80 patients who met the inclusion criteria, 17 had definite NTM disease, and 23 had probable NTM disease. No differences in age, sex, presence of underlying pulmonary or nonpulmonary disease, or chest radiographic abnormalities were noted between patients with and without NTM disease. More than 85% of all definite or probable cases were caused by Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium fortuitum complex. The diagnosis of NTM disease was often delayed or missed, which resulted in unsatisfactory management of patients. There is a need to educate physicians about the diagnosis and management of NTM infections.

Objective: To assess changes in the severity of physician-diagnosed asthma between 1983 and 1988. Design: Cross-sectional studies examining the frequency of markers of asthma severity: hospitalizations, ICU admissions, hospital emergency department visits, multiple physician contacts, and referrals to specialists in patients aged 0 to 14 years, 14 to 34 years, and ≥35 years separately. Setting: Physicians' claims data from the universal Provincial Health Insurance Plan for fiscal years 1983 and 1988. Patients: All patients with the diagnosis of asthma, bronchitis, and COPD identified from the Manitoba Health database. Measurements: The markers of severity were related to the prevalence of patients seeing a physician and receiving a diagnostic label of asthma, COPD, or bronchitis. Results: The number of patients with physician-diagnosed asthma increased by 36.4% over the 5 years. In 1983, 11% of asthmatics were hospitalized during the year and 8% were hospitalized in 1988 (–2.5%; 95% confidence interval [CI], –3.2 to –1.8%). During both years, about 75% of the patients hospitalized were in hospital once only. Mean and median duration of hospital stay declined. The percentage of asthmatics seen in the hospital emergency departments declined slightly in all age groups, the total being 21% in 1983 and 18% in 1988 (–3.5%; 95% CI, –4.5 to –2.5%). About one third of the patients with asthma were seen only once by a physician during both of the years examined, 43 to 45% of them being seen on three or more occasions during both years. Referrals to specialists for all asthmatics increased from 12 to 14% (1.9%; 95% CI, 1.0 to 2.8%) from 1983 to 1988. This was almost entirely due to an increase from 11 to 16% (5.1%; 95% CI, 4.0 to 6.2%) in the youngest age group, an increase not accompanied by an increase in any other marker of severity. Changes in asthma severity were similar to changes in the severity in patients with bronchitis and COPD. Conclusion: No increase in severity of asthma was seen between 1983 and 1988, but the prevalence of the diagnostic label of asthma increased substantially.

Purpose Atrial fibrillation is a common arrhythmia associated with increased cardiovascular morbidity and mortality. This study was undertaken to identify the natural history of this condition, including risk factors for its development, and outcome. Patients and methods The incidence of atrial fibrillation among 3,983 male air crew recruits observed continuously for 44 years was calculated based on person-years of observation. Age and 23 variables were examined to identify risk factors for atrial fibrillation. Controlling for age and 9 prognostic variables, the effect of atrial fibrillation on 8 outcomes was examined. Analysis of risk factors for atrial fibrillation and outcome after atrial fibrillation was based on a Cox proportional hazard model using time-dependent covariates. Results Of the 3,983 study members, 299 (7.5%) developed atrial fibrillation during 154,131 person-years of observation. The incidence rose with age from less than 0.5 per 1,000 person-years before age 50 to 9.7 per 1,000 person-years after age 70. Risk for atrial fibrillation was increased with myocardial infarction (relative risk [RR]3.62), angina (RR 2.84), and ST-T wave abnormalities in the absence of ischemic heart disease (RR 2.21). The RR for atrial fibrillation was strongest at the onset of ischemic heart disease and diminished over time. The rate of atrial fibrillation was 1.42 times increased in men with a history of hypertension. Congestive heart failure, valvular heart disease, and cardiomyopathy were important but uncommon risk factors. Atrial fibrillation independently increased the risk for stroke (RR 2.07) and congestive heart failure (RR 2.98). Total mortality rate was increased 1.31 times; cardiovascular mortality including and excluding fatal stroke were also increased (RR 1.41 and 1.37, respectively). Conclusions The incidence of atrial fibrillation in men increases with advancing age. Clinical cardiac abnormalities, particularly recent ischemic heart disease and hypertension, are strongly associated with increased risk for atrial fibrillation. Atrial fibrillation increases morbidity and mortality, but the magnitude of the increase may be less than previously reported.

Summary The homes of 120 patients with asthma, 57 in Vancouver and 63 in Winnipeg, were studied. The characteristics of the homes were assessed by a questionnaire. Dust samples were collected and the indoor relative humidity was measured four times during the year covering all four seasons in both cities. Mite allergen levels were determined using monoclonal antibodies against Der p I and Der f I by the ELISA method. The mean levels of both mite allergens in mattress and floor samples in the homes in Vancouver and in Winnipeg were relatively low for all seasons. Mite allergen levels were found to be associated with city, season and individual home differences. They were significantly higher in Vancouver than in Winnipeg. Der p I and Der f I in mattress samples in both cities and Der f I in floor samples in Vancouver, varied by season. The indoor relative humidity level in the homes in Vancouver were also significantly higher than those in Winnipeg. There was, however, no significant association between the levels of indoor relative humidity and the levels of mite allergens after adjusting for variations in city, season and individual home. Although individual home differences were highly associated with mite allergen levels, only a few home characteristics were found to be related to mite allergen levels such as the type and the age of the home, the type of heating, the use of feather pillows and the number of occupants in the homes. Whether low levels of mite allergens are partially responsible for the relatively low prevalence of childhood asthma in Canada remains to be investigated.

Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation (TBMV) is an uncommon occurrence. Over a 10 yr period in the province of Manitoba, Canada (population 1,091,942 in 1991), 13 patients with TBMV were identified. Non-drug-resistant M. tuberculosis was isolated from each case. The patients fell into two categories: miliary or disseminated tuberculosis (n = 7) and tuberculous pneumonia (n = 6); eight developed ARDS (adult respiratory distress syndrome) and another two probable ARDS. The hospital mortality for TBMV was compared with that for mechanically ventilated nontuberculous pneumonia and ARDS patients. Hospital mortality for patients with TBMV (69%, nine of 13) was significantly worse than hospital mortality for patients with nontuberculous pneumonia requiring mechanical ventilation (36%, 34 of 94; p0.025) and similar to the hospital mortality for patients with ARDS of any cause (56%, 15 of 27; p0.10). APACHE II scores for all groups of patients were similar. Compared with patients with tuberculous pneumonia, patients with miliary or disseminated tuberculosis were significantly more likely to develop TBMV (18.9 versus 0.8%, p0.0001). Despite the availability of effective antituberculous drugs, TBMV is often associated with ARDS and carries a similarly high mortality rate. Among patients with pulmonary tuberculosis, those with miliary or disseminated disease are especially prone to develop TBMV.

Objective To compare and interpret tuberculosis (TB) incidence rates in a Canadian population across two decennials (1989-1998 and 1999-2008) as a benchmark for World Health Organization targets and the long-term goal of TB elimination. The population under study was served by two urban clinics in the first decennial and two urban and one provincial clinic in the second. Methods TB rates among Status Indians, Canadian-born 'others' and the foreign-born were estimated using provincial and national databases. Program performance was measured in on-reserve Status Indians in each decennial. Results In each decennial, the incidence rate in Status Indians and the foreign-born was greater than that in the Canadian-born 'others'; respectively 27.7 and 33.0 times in Status Indians, and 8.0 and 20.9 times in the foreign-born. Between decennials, the rate fell by 56% in Status Indians, 58% in Canadian-born 'others', and 18% in the foreign-born. On-reserve Status Indians had higher rates than off-reserve Status Indians, and the three-clinic model out-performed the two-clinic model among those on-reserve. Rates in the foreign-born varied by World Bank region, and were highest among those from Africa and Asia. Conclusion Status Indians and the foreign-born are at increased risk of TB in Canada. Significant progress towards TB elimination has been made in Status Indians but not in the foreign-born.

This study examined the prevalence and determinants of tuberculin reactors and the booster response in 272 (97%) residents and 218 (69%) staff of an urban nursing home where a case of miliary TB was being investigated. Many subjects were foreign born (56%), and 15% had a history of BCG vaccination (34% of staff). Testing was done with 5 TU PPD-S (Connaught). Those with10 mm induration at 48 h were retested at 1 wk. Test sizes9 mm were classified positive (reactors). A questionnaire was given to collect information on risk factors for a positive test. Results showed that 28% (36% staff and 22% of residents) of subjects were reactors at the initial test, 6% at the booster test (staff and residents), and 32% at either test (40% staff and 26% residents). BCG (OR 4.8) and foreign birth (OR 1.7) were significantly associated with total reactors. The association with foreign birth was inversely related to the time since immigration. Only BCG was associated with a positive booster test (OR 6.7). Of positive tuberculin reactions in individuals with a history of BCG, 72% were attributed to the vaccine. We concluded that (1) staff as well as residents should be two-step tested when retesting is anticipated; (2) the prevalence of tuberculin reactors is highly related to the prevalence of BCG vaccinees and foreign birth; and (3) chemoprophylaxis is probably not indicated for isolated tuberculin reactors with a history of BCG.

We attempted to assess recent changes in the prevalence of physician-diagnosed asthma and the possible influence of diagnostic exchange on these trends. The routinely collected data of the provincial Health Insurance Plan (physicians' claims) were used to determine the annual prevalence of physician-diagnosed asthma in Manitoba. Results indicate that the prevalence of physician-diagnosed asthma increased for all age groups in both male and female subjects between 1980 and 1990. The average increases were the highest in the age group 5 to 14 years for both sexes. The average increases varied with age and there were significant differences between the two sexes. There was evidence of increasing diagnostic exchange, that is, a tendency to label patients with asthma instead of alternative diagnoses. This was particularly prominent in those younger than 35 years of age. However, the increased prevalence of physician-diagnosed asthma, even for the younger population, cannot be fully explained by diagnostic exchange.

UNLABELLED BACKGROUND" Fluoroquinolone (FLQ) antibiotics are not uncommonly prescribed for community-acquired pneumonia that is later proven to be pulmonary tuberculosis (TB). Such FLQ monotherapy may result in FLQ-resistant pulmonary TB. METHODS To assess outpatient FLQ use by patients with culture-proven pulmonary TB before diagnosis, TB registries in Alberta and Saskatchewan, Canada, were linked with provincial and federal drug benefit plans. To assess FLQ resistance, a case-control study was performed. RESULTS Of 428 patients with pulmonary TB who were covered by a drug benefit plan, 74 (17.3%) had received > or = 1 FLQ prescription during the 6 months immediately before receipt of the diagnosis. Older patients (age, >64 years) were more likely than younger patients (age, 15-64 years) to be prescribed an FLQ (P < .05). Patients who were prescribed an FLQ received a total of 103 prescriptions. Most (54 [73.0%] of 74) patients who were prescribed an FLQ received a single prescription. Most (69 [67.0%] of 103) FLQ prescriptions were written within 90 days before the diagnosis of pulmonary TB. Patients who were prescribed an FLQ were not statistically significantly more likely than matched patients who were not prescribed an FLQ (control subjects) to be infected with FLQ-resistant Mycobacterium tuberculosis. Of 148 isolates of M. tuberculosis from patients and control subjects, 3 were FLQ resistant; all of these isolates were from patients who had received multiple FLQ prescriptions. Patients who had received multiple FLQ prescriptions were more likely than patients who had received a single FLQ prescription to be infected with FLQ-resistant M. tuberculosis (15.0% vs. 0.0%; odds ratio, 11.4; P = .04). CONCLUSIONS Outpatient FLQ use, ostensibly for community-acquired pneumonia, is not uncommon among patients with pulmonary TB, especially older patients. Single FLQ prescriptions were not associated with FLQ-resistant M. tuberculosis, whereas multiple FLQ prescriptions were associated with FLQ resistance.

We estimated the prevalence of asthma related symptoms in grade 7 and 8 students in a rural region in India. Method. An International Study of Asthma and Allergies in Childhood (ISAAC), questionnaire with added questions related to environmental and familial exposures, was administered to 3668 students from 48 rural schools near Malegaon, India. Results. A history of asthma was present in 10.7% students and 7.3% wheezed in the past 12 months, with about one-third having at least four attacks. Boys had the higher prevalence of all asthma-related symptoms than girls did, and symptom frequency was generally above the median reported for urban Indian ISAAC centers. Asthma and wheeze were associated with a family history of asthma, smoking, and frequent chest colds. Significant environmental factors included parental occupation and smoking and poor water sources. Increased odds of asthma occurred in students working for wages, exposed to animals, or eating in the kitchen. Relationships were similar for wheezing. Both asthma and wheeze were higher in the Scheduled Tribe (ST) group. Most markers of socioeconomic status and environmental exposure were not significant in multivariate analysis. Conclusion. The prevalence of asthma and wheeze in a rural region in India was similar to that found in the urban ISAAC study; it was higher in students from lower socioeconomic groups with poorer environmental conditions.

OBJECTIVE: Airflow obstruction is relatively uncommon in young adults, and may indicate potential for the development of progressive disease. The objective of the present study was to enumerate and characterize airflow obstruction in a random sample of Canadians aged 20 to 44 years.SETTING: The sample (n=2962) was drawn from six Canadian sites.DESIGN: A prevalence study using the European Community Respiratory Health Survey protocol was conducted. Airflow obstruction was assessed by spirometry. Bronchial responsiveness, skin reactivity to allergens and total serum immunoglobulin E were also measured. Logistic regression was used for analysis.RESULTS: Airflow obstruction was observed in 6.4% of the sample, not associated with sex or age. The risk of airflow obstruction increased in patients who had smoked and in patients who had lung trouble during childhood. Adjusted for smoking, the risk of airflow obstruction was elevated for subjects with past and current asthma, skin reactivity to allergens, elevated levels of total immunoglobulin E and bronchial hyper-responsiveness. Of the subjects with airflow obstruction, 21% were smokers with a history of asthma, 50% were smokers without asthma, 12% were nonsmokers with asthma and 17% were nonsmokers with no history of asthma. Bronchial hyper-responsiveness increased the prevalence of airflow obstruction in each of these groups.CONCLUSION: Smoking and asthma, jointly and individually, are major determinants of obstructive disorders in young adults. Bronchial hyper-responsiveness contributes to obstruction in both groups.

The contribution of respiratory viral infections to the onset of asthma and atopy is controversial. In "high risk" children (n = 455) born into asthmatic/atopic families, we determined the relationship of exposures to common respiratory viruses and concomitant respiratory symptoms, and to subsequent possible asthma and atopy at ages 1 and 2 years. Frozen nasal specimens, obtained when children were 2 weeks, 4, 8, and 12 months old, underwent reverse transcription-polymerase chain reaction (RT-PCR) testing for parainfluenza virus (PIV), respiratory syncytial virus (RSV), and picornavirus (rhinovirus/enterovirus). Odds ratios of viral RT-PCR results to respiratory symptoms ("cold," rhinitis, cough, wheezing) and to possible asthma or atopy at 1 and 2 years of age were calculated. Positive viral RT-PCR was associated with increased odds of "cold" and cough; PIV and picornavirus were associated with rhinitis, and RSV was associated with wheezing. PIV was associated with increased odds of atopy at 1 year of age in the control group; PIV and RSV were associated with possible asthma at 2 years of age. We conclude that in high-risk children, viral exposures documented by RT-PCR are associated with respiratory symptoms, and exposures to PIV and RSV during the first year of life are associated with the initial onset of possible asthma.

Patient characteristics and prescribing patterns during the introduction of leukotriene receptor antagonists (LTRA) in Manitoba are described using the provincial health database. Residents of Manitoba with asthma, chronic obstructive pulmonary disease, bronchitis or claims for respiratory medications were identified. Six thousand forty-one of 160,626 (3.8%) patients received LTRA; the likelihood of receiving LTRA increased if a patient was younger than 15 years, lived in a rural locale, had asthma, had frequent physician visits or used inhaled corticosteroids. Subsequent prescriptions (68%) were associated with the number of physician visits and inhaled corticosteroid use, which were thought to be indexes of severity. Patients, especially children, who received more than five prescriptions showed evidence of increased asthma control, but there was little evidence of benefit in less selected patient groups due, at least in part, to poor compliance with all respiratory drugs.

Background The space and time distribution of risk factors for allergic diseases may provide insights into disease mechanisms. Allergy is believed to vary by month of birth, but multinational studies taking into account latitude have not been conducted. Methods and Findings A questionnaire was distributed in 54 centres to a representative sample of 20- to 44-y-old men and women mainly in Europe but also including regions in North Africa, India, North America, Australia, and New Zealand. Data from 200,682 participants were analyzed. The median prevalence of allergic rhinitis was 22%, with a substantial variation across centres. Overall, allergic rhinitis decreased with geographical latitude, but there were many exceptions. No increase in prevalence during certain winters could be observed. Also, no altered risk by birth month was found, except borderline reduced risks in September and October. Effect estimates obtained by a multivariate analysis of total and specific IgE values in 18,085 individuals also excluded major birth month effects and confirmed the independent effect of language grouping. Conclusion Neither time point of first exposure to certain allergens nor early infections during winter months seems to be a major factor for adult allergy. Although there might be effects of climate or environmental UV exposure by latitude, influences within language groups seem to be more important, reflecting so far unknown genetic or cultural risk factors., A large international survey of risk factors associated with allergy refutes previous work suggesting that allergy varies by month of birth

We studied a cohort containing 368 children at high risk of developing atopy and atopic disorders and 540 parents of those children to investigate whether the IL13 Arg130Gln and C-1112 T polymorphisms were associated with these outcomes. We also investigated whether haplotypes consisting of any two polymorphisms of IL13 Arg130Gln, IL13 C-1112 T and IL4 C-589 T were associated with these phenotypes. In 288 white children, the IL13 130Gln allele was associated with atopy (RR=1.9, P=0.047), and with atopic dermatitis (RR=2.5, P=0.014). The associations were confirmed using a family-based test of association (P=0.027 and 0.030, respectively) in all subjects. In white subjects there were associations of haplotypes consisting of IL13 Arg130Gln and IL4 C-589 T with atopic dermatitis (P=0.006) and with atopy (P=0.009). Our data suggest that the IL13 Arg130Gln polymorphism and haplotypes consisting of IL13 Arg130Gln and IL4 C-589 T were associated with the development of atopy and atopic dermatitis at 24 months of age.

This report deals with deaths and hospitalizations during the 5-year Lung Health Study, as documented by examination of appropriate records. There were 149 deaths (2.5%) during the study, caused largely by lung cancer and cardiovascular disease, particularly coronary heart disease. A total of 12.8% of participants were hospitalized, with cancer, cardiovascular disease, and nonmalignant respiratory disease accounting for 75% of hospitalizations. There were no significant differences among the original treatment groups for all-cause mortality, lung cancer, or hospitalizations for respiratory disease. Deaths and hospitalizations for cardiovascular disease and coronary artery disease were more common in the smoking intervention plus Atrovent inhaler (SI-A) group, which received ipratropium bromide, than in the smoking intervention plus placebo inhaler (SI-P) group, which received placebo, and the differences approached statistical significance. However, we were unable to find a dose effect, in that differences were not related to self-reported inhaler compliance. In the SI-A group, nine participants were hospitalized for supraventricular tachycardia as compared with two in the SI-P group, and SI-A participants with this condition were unusually compliant with their inhaled medication. When all participants were considered and smoking status considered as a time-dependent covariate, smoking cessation was associated with significant reductions in fatal or nonfatal cardiovascular disease and coronary artery disease.

Narcolepsy is a neurological disorder whose clinical features include excessive daytime sleepiness, hypnagogic hallucinations, cataplexy, sleep paralysis, and disrupted nocturnal sleep. It has been shown that there may be quite a long interval between the onset of symptoms, and the correct diagnosis. We tested the hypothesis that given their severe symptomatology, these patients would have been diagnosed more often with a variety of psychiatric and neurologic conditions than controls in the year prior to confirmation of their narcolepsy diagnosis.Using the Province of Manitoba Health database, we compared the diagnoses made in the year prior to initial sleep disorder center evaluation of 77 patients with narcolepsy (33 males, 44 females) and 1,155 matched control subjects from the general population.Sleep disorders center in University-based teaching hospitalN/A.N/A.Patients were much more likely than controls to be diagnosed with mental disorders (Odds ratio (OR) = 4.0645; 95% confidence limit (CL) = 2.4671-6.6962; p0.0001) and nervous system disorders (OR= 5.0495; CL = 3.0606 -8.3309; p0.0001) and there was a trend towards more injuries in these patients (OR =1.6316; CL = 0.9857-2.7007; p=0.0514). We found that cases were statistically much more likely than controls to have received a diagnosis for neurotic disorders (17% of cases), depression (16%), personality disorders (3%) and adjustment reaction (4%). Although the cases had twice as many doctor visits as the controls (9.3 +/- 0.97 (sem) vs. 4.8 +/- 0.17 p0.0001), only 38% of them had received a diagnosis of narcolepsy in the year prior to sleep specialist evaluation. Neurologists had the highest "success rate" for correct diagnosis: neurologists diagnosed narcolepsy in 55% of the cases they had seen. The other medical practitioners diagnosed narcolepsy in a much smaller percentage of the cases they had seen: 23.5% for internists (excluding neurologists), 21.9% for general practitioners, 11.1% for psychiatrists, and 0% for pediatricians.In the year prior to documentation of narcolepsy in a sleep disorders center, patients with narcolepsy were diagnosed with a wide variety of mental and neurologic disorders. Our findings are supportive of either the coexistence of these disorders in narcolepsy patients or a high frequency of missed diagnosis by their clinicians. The latter may help explain the very long interval between onset of symptoms and correct diagnosis.

Both air pollutants and respiratory viral infections have been recognized to be important triggers of asthma exacerbations, but the possible interaction of these has not been assessed in an epidemiologic study.In this study, we aimed to assess the possible associations of symptomatic colds with outdoor allergens and air pollutants in exacerbating asthma.A total of 57 adults and children with asthma participated in a 1-year study in Vancouver, British Columbia. Diary cards recording symptoms of asthma and colds, medication usage, and peak expiratory flow rates were completed twice daily. Outdoor air pollutant levels and levels of pollen and fungal spores were measured. Levels were examined for associations with exacerbations of asthma with symptoms of a cold, as compared with asthma exacerbations with no cold symptoms and colds in the absence of asthma exacerbations.Of 130 asthma exacerbations, 47% were associated with cold symptoms (accounting for 44% of episodes of colds). Asthma exacerbations with colds were associated with higher levels of sulfur dioxide, and nitric oxide during March to November in comparison with asthma exacerbations without cold symptoms (P.018). Cold-symptom days overall were more common in winter and were significantly associated with lower temperatures, lower ozone levels, and higher sulfur dioxide, nitrogen dioxide, nitrogen oxide (NO and NO(x)), and carbon monoxide levels.Asthma exacerbations are commonly associated with cold symptoms. These episodes are associated with higher levels of sulfur dioxide and nitrogen oxides from March to November in comparison with asthma exacerbations without cold symptoms.

We examined the prevalence, population attributable risk (PAR), and clinical characteristics of occupational asthma (OA) in a randomly selected population in six communities in Canada. Our study followed the European Community Respiratory Health Survey protocol. A randomly selected population of 18,701 (87% response rate) persons from the study communities, ranging in age from 20 to 44 yr, completed an initial questionnaire, of whom 2,974 (39% response rate) attended the laboratory and completed supplementary questionnaires. Of these latter individuals, 383 had asthma. Asthma was defined as physician-diagnosed asthma, and adult-onset asthma was defined as a first attack at age 15 yr or older. We used several methods for estimating OA as follows: (1) reporting of a high-risk job (occupation and industry) for OA at the time of asthma onset (Probable OA); (2) reporting of exposure to a substance that may cause OA (Possible OA) while not in a high-risk job at the time of asthma onset; and (3) combination of the PAR for high-risk jobs and exposures. The prevalence (95% confidence interval [CI]) of Probable OA and Possible OA combined was 36.1% (31.3 to 41.0%) among subjects with adult-onset asthma. The occupations most commonly reported in association with OA were nursing in the Probable OA group and clerical and food preparation in the Possible OA group. The clinical characteristics and exposures reported by both groups were similar. The PAR for adult-onset asthma in high-risk jobs and exposures was 18.2%. The assessment of occupation and industry alone, rather than of exposures, may underestimate the contribution of occupational exposures to asthma prevalence.