A population-based study of tuberculosis epidemiology and innovative service delivery in Canada.

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.

Piecing the puzzle together: foreign-born tuberculosis in an immigrant-receiving country.

In major immigrant-receiving countries, annual foreign-born tuberculosis (TB) case counts and rates are relatively constant. Why this is so, and who might be a high-yield target for screening for latent TB infection, remain open questions. Foreign-born TB in Canada during 1986-2002 was retrospectively examined using national TB and immigration data as well as census data. Case counts and rates were analysed in relation to demographics, immigration period and time since arrival. Pre-1986 immigrants (n=3,860,853) and 1986-2002 immigrants (n=3,463,283) contributed 8,662 and 9,613 TB cases, respectively. Immigrants arriving ≤ 5 yrs ago and those arriving >10 yrs ago contributed almost equally to the annual foreign-born TB case count despite a 3.5-fold difference in in-country person-yrs. Remarkably stable and relatively low TB incidence was observed among immigrants >10 yrs post-arrival. Conversely, TB incidence within 5 yrs of arrival was dynamic, demonstrating a strong inverse association with time since arrival and higher sensitivity to changes in immigration level than shifts toward higher incidence source countries. Relative constancy in foreign-born TB incidence is explained by a complex convergence of several factors. Immigrants born in high-incidence countries who arrived ≤ 2 yrs ago and were aged 15-34 yrs upon arrival constitute high-yield targets for preventive therapy.

Geographical variations in the prevalence of atopic sensitization in six study sites across Canada.

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.

Introduction of leukotriene receptor antagonists in Manitoba.

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.

Use of spirometry and respiratory drugs in Manitobans over 35 years of age with obstructive lung diseases.

BACKGROUND: Previous data indicated that spirometry was underused in people with obstructive disease, especially those with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To examine the use of respiratory drugs in patients with COPD and asthma, and to relate drug use to spirometry. METHODS: Manitoba Health maintains a database of physician services remunerated by fees that includes spirometry. The database contains the diagnosis and patient identifiers, as well as sex, date of birth and residential postal code. Similar identifiers are used in the provincial pharmacare program that records prescriptions dispensed at retail pharmacies. These databases were examined for the time period between 1996 to 2000, and people over 35 years of age diagnosed with asthma, COPD or both were identified. The frequency of spirometry in these patients and their use of respiratory drugs was determined. RESULTS: Spirometry and drug prescription frequencies increased with the number of physician visits (including those for bronchitis), but their patterns differed. Patients with asthma or asthma plus COPD had considerably higher rates of drug prescription and slightly higher spirometry rates than did those with COPD. Patients with asthma and asthma plus COPD who underwent spirometry were slightly more likely to receive drugs than those who did not undergo spirometry; this trend was more striking in patients with COPD. However, approximately 30% of patients with COPD who had five physician visits and who underwent spirometry did not receive drugs; this was true for approximately 10% of similar patients with asthma. Patients with asthma generally received beta-agonists and inhaled steroids; these agents were less commonly given to patients with COPD, who instead were given anticholinergics much more often than were asthmatics. Patients who were diagnosed with asthma plus COPD had beta-agonist and inhaled corticosteroid prescription rates similar to asthmatics, and anticholinergic prescription rates similar to patients with COPD. Theophylline and antileukotriene drugs were used less often than were inhaled agents. In patients with asthma, drugs were frequently discontinued, and during drug use, prescription refills were consistent with an intake of 30.9% of the prescribed doses. In patients with COPD, discontinuing drugs early was uncommon, and refills were consistent with the use of 54% of the prescribed amounts. The same was true of patients with both COPD and asthma. DISCUSSION: Drug prescription was considerably more common in patients labelled with asthma or COPD plus asthma than in patients with COPD. Spirometry was also less common in patients with COPD but had a distinct influence on the frequency of drug prescription. Patterns of drug prescription were predictable, and patterns of drug use indicated poor compliance, in agreement with other data. The results suggest that COPD symptoms may be discounted and patients systematically undertreated or the diagnosis could frequently be applied to people with trivial disease or both.

Transmission characteristics of tuberculosis in the foreign-born and the Canadian-born populations of Alberta, Canada.

SETTING: All notified cases of tuberculosis in the province of Alberta, Canada, 1994-1998. OBJECTIVE: To compare the transmission characteristics of tuberculosis among foreign-born and Canadian-born cases. DESIGN: Retrospective analysis using DNA fingerprinting (IS6110 restriction fragment length polymorphism and spoligotyping) and patient information from the Alberta Tuberculosis Registry. Transmission indexes were determined by calculating the average number of culture-positive pulmonary cases generated by a single source case. RESULTS: Of the 750 cases of active tuberculosis, 437 (58.3%) were in the foreign-born. DNA fingerprinting of Mycobacterium tuberculosis isolates from all 573 culture-positive cases over the 5 years from 1994 to 1998 showed that there was significantly less clustering among foreign-born isolates (9.8%) compared to Canadian-born non-Aboriginal (28.8%) and Aboriginal (44.7%) isolates. The transmission index was significantly higher for males, lower for those > or =65 years of age, and higher for Aboriginals. CONCLUSION: Although cases of tuberculosis in the foreign-born constitute the majority in Alberta, there is little transmission to other foreign-born or to Canadian-born individuals. Transmission of tuberculosis among the Aboriginal population remains a significant problem in Alberta.

Genetic variants of the IL13 and IL4 genes and atopic diseases in at-risk children.

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.

The epidemiology of tuberculosis among foreign-born persons in Alberta, Canada, 1989-1998: identification of high risk groups.

BACKGROUND: To date, there have been no comprehensive epidemiological studies in Canada of the incidence rates of tuberculosis among foreign-born persons. Accurate rate estimates are needed to develop cost-effective strategies for the prevention, control, and ultimate elimination of tuberculosis. METHODS: Most new immigrants to Canada settle in one of four provinces: Ontario, British Columbia, Quebec and Alberta. Data from the provincial reporting system for tuberculosis, from Statistics Canada censuses and population estimates of Treaty Status Indians provided by the Department of Indian and Northern Affairs Canada, were used to estimate the rate of tuberculosis in Alberta's Canadian-born and foreign-born population between 1989 and 1998. RESULTS: Age-adjusted tuberculosis case rates per 100,000 person-years were 19.4 and 61.9 in the foreign-born and Canadian-born Treaty Indians-approximately 10 times and 30 times, respectively, higher than the rate in the remainder of the Canadian-born population (2.1/100,000 person-years). Age-specific rates in male and female foreign-born persons were highest at ages 15-34 and > or = 65 years, whereas rates in Canadian-born non-Treaty and Treaty males and females increased incrementally, with a single peak at > or = 65 years. Tuberculosis case rates in the foreign-born varied significantly according to World Bank region and country of birth. By far the highest rates were seen in immigrants to Canada from Asia, in particular Vietnam, the Philippines, China, Hong Kong and India. Most (90%) tuberculosis patients from these countries had not been identified as requiring medical surveillance in Canada after arrival. CONCLUSION: Immigrants to Alberta from Asia and Treaty Status Indians are at high risk for tuberculosis. Physicians in Alberta who care for foreign-born persons should be aware that their patients are at increased risk for tuberculosis, even if they have been medically cleared during the legal immigration process.

The emergency department is a determinant point of contact of tuberculosis patients prior to diagnosis.

SETTING: Metropolitan Edmonton, Canada. OBJECTIVES: To determine 1) the pre-diagnosis emergency department utilization history of urban tuberculosis patients, and 2) the resource and outcome implications of emergency department utilization by tuberculosis patients pre-diagnosis. DESIGN: Nested case (emergency department attendee) control (non-emergency department attendee) study of a retrospective cohort of tuberculosis patients. PATIENTS: All tuberculosis notifications, 1994 through 1998. MAIN OUTCOME MEASURES: Emergency department utilization during the 6 months antedating the diagnosis and emergency department attendee characteristics; for those notified in 1997 and 1998, hospitalizations, nosocomial infectiousness time, and health care costs. RESULTS: Of 250 cases of tuberculosis, 117 (47%) made a total of 258 pre-diagnosis emergency department visits. Emergency department use increased the nearer the patient was to diagnosis. Emergency department attendees were more likely to be older, to have smear and/or culture positive respiratory disease, to have a risk factor for progression of infection to disease, and to have a fatal outcome. In 1997 and 1998, emergency department throughput accounted for 70% of all hospitalization days, 95% of all source case nosocomial infectiousness time, and most health care costs of tuberculosis patients pre-diagnosis. CONCLUSIONS: The emergency department is heavily utilized by urban tuberculosis patients pre-diagnosis. Emergency department throughput of tuberculosis patients pre-diagnosis has major resource and outcome implications. The emergency department may present an opportunity for earlier diagnosis.

Cardiovascular medication use in patients with undiagnosed obstructive sleep apnoea.

BACKGROUND: A study was undertaken in patients with undiagnosed sleep apnoea/hypopnoea syndrome (OSAS) to document the use of prescribed medications, especially those used in cardiovascular diseases, in the year before the OSAS diagnosis was confirmed. METHODS: A total of 549 patients with OSAS (401 men of mean age 47.2 years, mean body mass index (BMI) 35.5 kg/m(2), mean apnoea/hypopnoea index (AHI) 47.2 and148 women of mean age 50.2 years, BMI 39.6 kg/m(2), AHI 32.6) were each matched to one general population control by age, sex, geographical location, and family physician. Medication use was evaluated for patients and controls using a database containing information about all prescriptions completed in the province of Manitoba, Canada. RESULTS: In the year before OSAS was diagnosed, prescribed medication costs were $155.91 (Canadian dollars) (95% CI $91.34 to $220.49) greater for cases than for controls. Cases were dispensed 3.3 (95% CI 1.5 to 5.2) more prescriptions, were on 1.2 (95% CI 0.8 to 1.6) more medications, and were supplied with 157.4 (95% CI 95.9 to 218.8) more daily doses of medication. The odds ratio of OSAS cases being on a prescribed medication was 1.88 relative to controls (95% CI 1.38 to 2.54, p<0.0001). In the same year 36.6% of cases and 19.7% of controls were using medications for cardiovascular disease (OR 2.82, 95% CI 2.05 to 3.89, p<0.0001), consuming 79.4 (95% CI 48.9 to 109.8) more daily doses of medication, having been dispensed 1.7 (95% CI 1.0 to 2.4) more prescriptions, and at a $75.26 (95% CI $44.03 to $106.50) greater cost. The odds ratio of patients with OSAS being on medications indicated for the treatment of systemic hypertension was 2.71 (95% CI 1.96 to 3.77) relative to controls; however, such medications might also be prescribed for other indications such as angina pectoris and congestive heart failure, and for the secondary prevention of myocardial infarction. The use of medications indicated for the treatment of systemic hypertension was predicted significantly by age (odds ratio (OR) 1.10 per year), BMI (OR 1.05 per unit), and AHI (OR 1.01 per unit). CONCLUSIONS: In the year before OSAS was diagnosed, patients with OSAS were heavy users of medications, particularly those used to treat cardiovascular diseases.

Spirometry and obstructive lung disease in Manitoba.

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 renumerated 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.

The use of health-care resources in obesity-hypoventilation syndrome.

OBJECTIVE: 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. DESIGN: Retrospective observational cohort study. SETTING: University-based sleep disorders center in Manitoba, Canada. PATIENTS AND CONTROL SUBJECTS: 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. MEASUREMENTS AND RESULTS: 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 (p < 0.01) visits for OBCs and 4.5 +/- 0.4 (p < 0.001) 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 (p < 0.001) for OBCs and $236 +/- 25 (p < 0.001) 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]). CONCLUSIONS: 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.

The role of symptomatic colds in asthma exacerbations: Influence of outdoor allergens and air pollutants.

BACKGROUND: 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. OBJECTIVE: In this study, we aimed to assess the possible associations of symptomatic colds with outdoor allergens and air pollutants in exacerbating asthma. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Risk factors for Alzheimer's disease: a population-based, longitudinal study in Manitoba, Canada.

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.

The association between respiratory viruses and symptoms in 2-week-old infants at high risk for asthma and allergy.

OBJECTIVES: The role of viral respiratory tract infections in the onset of childhood asthma and allergy is controversial, partly because of limited understanding about postnatal viral exposures. We investigated the prevalence of 3 common respiratory viruses and associated respiratory symptoms in 2-week-old infants at high risk for having asthma and allergy. STUDY DESIGN: Frozen nasal specimens from 2-week-old children at high risk (n = 495) underwent reverse transcription-polymerase chain reaction (RT-PCR) for picornavirus-, parainfluenza-, and respiratory syncytial virus-specific nucleic acid. RT-PCR findings were related to respiratory symptoms (cold, cough, and wheeze) and to characteristics implicated with increased risk for asthma and allergy. RESULTS: Viral RT-PCR was positive in 199 (40.2%) of 495 specimens examined, with picornavirus and parainfluenza significantly associated with respiratory symptoms. Viral prevalence was significantly higher in children born during the winter and summer months. CONCLUSIONS: A high percentage (40.2%) of infants at high risk for asthma and allergy had been exposed to common respiratory viruses at 2 weeks of age. RT-PCR is a powerful diagnostic method that can be used in epidemiologic studies examining the role of viral respiratory tract infections in the pathogenesis of pediatric asthma and allergy.

Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of prematurity.

Apnea of prematurity is common and none of the treatments being used are fully effective and free of significant adverse side effects. We hypothesized that low concentrations of CO2 (< or = 1.5%) may reduce apnea without causing discomfort from an increase in ventilation. We studied 10 preterm infants at a gestational age of 32+/-1 wk (mean +/- SEM) and birthweight 1.8+/-0.2 kg. After a control period of 1 hour, concentrations of CO2 were given (0.5%, 1%, and 1.5%) for 1 hour each, followed by a recovery period of 1 hour. Apnea number significantly decreased from 2.0+/-0.3 apneas/min during control to 1.0+/-0.1 apneas/min (0.5% CO2; P < .05), 1.1+/-0.2 (1% CO2; P < .05), and to 0.7+/-0.2 (1.5% CO2; P < .01). The apnea time significantly decreased from 14.2+/-2.5 s/min during control to 5.2+/-0.8 (0.5% CO2; P < .01), 5.8+/-0.7 (1% CO2; P < .01), and to 3.7+/-0.9 (1.5% CO2; P < .01). Minute ventilation significantly increased with CO2 without evidence of respiratory discomfort. TcPCO2 did not change and TcPO2 increased slightly. These findings suggest that inhalation of low concentrations of CO2 in preterm infants with apnea 1) decreases the number and time of apneas, 2) improves oxygenation, 3) increases ventilation, and 4) is effective even in such low concentrations as 0.5%. We speculate that inhalation of CO2 (< 1%) is more effective and safer than methylxanthines for the treatment of apnea of prematurity.

Prevalence of asthma symptoms among adults aged 20-44 years in Canada.

BACKGROUND: Reported prevalence rates of asthma vary within and between countries around the world. These differences suggest environmental factors in addition to genetic factors in the cause of the disease and may provide clues for preventive strategies. We examined the variability of asthma-related symptoms and medication use among adults in 6 sites across Canada (Vancouver, Winnipeg, Hamilton, Montreal, Halifax and Prince Edward Island) and compared our findings with those from sites that had participated in a recent European survey. METHODS: We used the same sampling strategy and standardized questionnaire as those used in the European Community Respiratory Health Survey (ECRHS). The 6 Canadian sites were selected to represent different environments with respect to climate, air pollution and occupational exposure. Community-based samples of 3000 to 4000 people aged 20-44 years were randomly selected in each site. Subjects were asked to complete the questionnaire by mail between March 1993 and November 1994. Prevalence rates (and 95% confidence intervals [CIs]) of asthma symptoms, self-reported asthma attacks and use of asthma medication were compared across the Canadian sites and with sites that had participated in the ECRHS. RESULTS: The overall response rate of those selected to receive the questionnaire was 86.5% (range 74.5%-92.8%). The prevalence rates of most asthma symptoms varied significantly among the Canadian sites. For instance, 21.9% (Montreal) to 30.4% (Halifax) of the men and 24.0% (Vancouver) to 35.2% (Halifax) of the women reported wheezing in the year before the survey. Depending on the site, 4.4% to 6.3% of the men and 5.2% to 9.5% of the women reported an asthma attack in the last year, and 4.0% to 6.1% of the men and 4.9% to 9.7% of the women were currently using asthma medication. Prevalence rates of symptoms, asthma attacks and medication use did not change with age, but they were higher among women than among men. Compared with the results from the ECRHS sites, those from the Canadian sites were among the highest. INTERPRETATION: Significant variation in the prevalence of asthma symptoms, asthma attacks and use of asthma medication between Canadian sites and international sites suggests environmental influences. Different combinations of factors in different sites may be responsible for the high prevalence rates and should be the subject of further research to guide clinical management and public health intervention.

Occupational asthma in adults in six Canadian communities.

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.

A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants.

BACKGROUND: The prevalence of asthma has increased in developed countries in the past 2 decades. The effectiveness of intervention measures on the primary prevention of asthma has not been well studied. OBJECTIVE: To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants (in this study, infants are defined as persons from birth to the age of 1 year). DESIGN: Prospective, prenatally randomized, controlled study with follow-up through the age of 1 year. SETTING: University hospital-based settings at 2 Canadian centers: Vancouver, British Columbia, and Winnipeg, Manitoba. PARTICIPANTS: A total of 545 high-risk infants (at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases) identified before birth. INTERVENTIONS: Avoidance of house dust mite and pet allergens and environmental tobacco smoke, encouragement of breastfeeding, and supplementation with a partially hydrolyzed formula. MAIN OUTCOME MEASURES: Probable or possible asthma, rhinitis without apparent colds, and a prick skin test result positive for common inhalant allergens. RESULTS: Thirty-eight (15.1%) of the 251 infants available for assessment in the intervention group and 49 (20.2%) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma (adjusted relative risk, 0.66; 90% confidence interval, 0.44-0.98). Also, 16.7% of the infants in the intervention group and 27.3% of the infants in the control group developed rhinitis without colds (adjusted relative risk, 0.51; 90% confidence interval, 0.35-0.74). The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups (4.4% in the intervention group and 4.6% in the control group). CONCLUSIONS: Our multifaceted intervention program resulted in a modest but significant (P= .04) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants. In the absence of a validated definition of asthma at the age of 12 months, follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants.

Polymorphisms of the IL-4, TNF-alpha, and Fcepsilon RIbeta genes and the risk of allergic disorders in at-risk infants.

Polymorphisms in the TNF-alpha (A-308G), IL-4 (C-589T), and Fcalpha RIbeta (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-alpha and Fcalpha RIbeta 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, an association of IL4-589*T with atopy was found. We conclude that IL-4-589*T, but not TNF-alpha-308*2 or Fcalpha RIbeta*G, is a risk factor for the development of atopy, asthma, and rhinitis by 12 mo of age.