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.

High-sensitive C-reactive protein is associated with reduced lung function in young adults.

Systemic inflammation has been associated with reduced lung function. However, data on the interrelationships between lung function and inflammation are sparse, and it is not clear if low-grade inflammation leads to reduced lung function. Associations between high-sensitive C-reactive protein (CRP) and spirometric lung function were assessed in a population-based cohort of approximately 1,000 Danes aged 20 yrs. In males, the average decline in forced expiratory volume in one second (FEV(1)) in the highest CRP quintile was 23 mL.yr(-1) versus 1.6 mL.yr(-1) in the lowest quintile. In females, the average decline was 6.2 mL.yr(-1) in the highest CRP quintile versus an increase of 1.8 mL.yr(-1) in the lowest CRP quintile. In a multiple regression analysis adjusted for sex, body mass index, cardiorespiratory fitness, smoking, asthma, airway hyperresponsiveness and serum eosinophil cationic protein, higher levels of CRP at age 20 yrs were associated with a greater reduction in both FEV(1) and forced vital capacity between ages 20 and 29 yrs. The findings show that higher levels of C-reactive protein in young adults are associated with subsequent decline in lung function, suggesting that low-grade systemic inflammation in young adulthood may lead to impaired lung function independently of the effects of smoking, obesity, cardiorespiratory fitness, asthma and eosinophilic inflammation.

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.

Impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic teenagers.

AIM: To investigate the impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic subjects. METHODS: In this prospective, community-based study, 271 asymptomatic adolescents with an average age at inclusion of 13.9 years were followed for 6.4 years. Airway lability was assessed at baseline by three tests, including exercise challenge, airway provocation with methacholine, and monitoring of peak expiratory flow. Atopy was defined by one or more positive reactions (> or = 3-mm weal) to 10 common aeroallergens by skin prick testing. The influence of airway lability, atopy, and smoking on the development of asthma-like symptoms was assessed by logistic regression. RESULTS: During the 6-year study period, 68 of the previously asymptomatic teenagers (25%) developed asthma-like symptoms. Among those, 50% reported cough only, 29% reported wheezing only, and 21% reported both wheezing and coughing. Hyperresponsiveness to methacholine (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.1 to 11.6), smoking (OR, 2.1; 95% CI, 1. 2 to 3.8), and atopy (OR, 3.5; 95% CI, 1.8 to 6.8) each contributed independently to explain symptom development (wheezing and cough together). Girls, but not boys, with airway lability were less likely to take up smoking, compared with subjects of that set with no airway lability (32% vs 51%; p < 0.05). No effect of airway lability on the likelihood of giving up smoking could be demonstrated, nor did the presence of atopy have any significant impact on smoking behavior. CONCLUSION: Hyperresponsiveness to methacholine, atopy, and smoking were independent risk factors for the development of asthma-like symptoms during adolescence. The presence of airway lability may prevent girls from taking up smoking.

Increased eosinophil cation protein level in sensitized nonasthmatics is linked to subsequent hyperresponsiveness to methacholine. The Odense Schoolchild Study.

BACKGROUND: Increased levels of eosinophil cation protein (ECP) in sensitized subjects may reflect early stages of an ongoing inflammatory process and therefore precede asthma and bronchial hyperreactivity. AIM: To study whether nonasthmatic subjects with sensitization to allergens and increased ECP levels are at a higher risk for subsequent increased bronchial reactivity compared with sensitized nonasthmatics with normal ECP levels. METHODS: A prospective study of 240 schoolchildren with a mean age of 13.9 years (range: 12.6-15.9) who were followed up after 6.3 years. Bronchial reactivity was assessed by methacholine provocation testing. Sensitization was defined by one or more positive reactions (>3 mm wheal) to 10 common aeroallergens by skin prick testing. Increased ECP was defined as values above 20 microg/l. This separated the subjects into four categories: group 1: healthy controls without sensitization (n = 147); group 2: sensitized subjects with a serum ECP below 20 microg/l (n = 55); group 3: sensitized subjects with an ECP level at or above 20 microg/l (n = 16), and group 4: all asthmatics (n = 22). RESULTS: Bronchial reactivity was similar in subjects of groups 2 and 3 at baseline (p = 0.8). Six years later, subjects from group 3 were more responsive to methacholine compared with subjects from group 2 (median: 12.7 versus 20.5 micromol; p < 0.05). In a logistic regression with hyperresponsiveness to methacholine at follow-up as dependent variable, the odds ratios (OR) for the groups were, with group 1 as reference: group 2: OR = 2.2 (0.8-6.6: p = 0.2), group 3: 5.9 (1. 6-21.7: p < 0.01). CONCLUSION: Subjects with sensitization and increased ECP levels are subsequently more airway-responsive to methacholine compared with sensitized subjects with normal ECP levels. This supports the hypothesis that sensitization is linked to increased bronchial reactivity through a process in which markers of inflammation are involved.

Comparison of two standardized methods of methacholine inhalation challenge in young adults.

In the European Community Respiratory Health Study (ECRHS), airway responsiveness to methacholine was determined using the Mefar dosimeter protocol. Elsewhere, the 2-min tidal breathing method has become the preferred standardized method. The relationship between measurements of responsiveness by these two methods is not well established. This study measured airway responsiveness to methacholine by dosimeter and tidal breathing methods in 47 healthy asthmatic subjects aged 20-44 yrs. Tests were performed within 1 week and in random order. Baseline forced expiratory volume in one second (FEV1) varied by <10% between tests in 42/47 subjects. There was a close association between responsiveness determined by the two methods. A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) value of < or =8.0 mg x mL(-1) (tidal method) used to categorize airway hyperresponsiveness agreed most closely with a provocative dose of methacholine causing a 20% fall in FEV1 (PD20) value of < or =0.5 mg (dosimeter method) (kappa statistic 0.78). Each doubling or halving of PC20 to define a level of hyperresponsiveness agreed closely with a doubling or halving of PD20. Assessment of airway responsiveness as provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second by the Mefar dosimeter protocol gave a close and predictable relationship with provocative concentration of methacholine causing a 20% fall in expiratory volume in one second assessed using the tidal breathing method. Airway hyperresponsiveness as determined by the accepted criterion of provocative concentration of methacholine causing a 20% fall in expiratory volume in one second < or =8 mg x mL(-1) was best correlated with provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second <0.5 mg by Mefar dosimeter.

Low physical fitness in childhood is associated with the development of asthma in young adulthood: the Odense schoolchild study.

Intense physical activity in children may either improve fitness and protect against asthma, or may trigger symptoms. The aim of this study was to determine whether physical fitness in childhood has an impact on the development of asthma. In this prospective, community-based study, 757 (84%) asymptomatic children with an average age at inclusion of 9.7 yrs were followed for 10.5 yrs. In both surveys a maximal progressive exercise test on a bicycle ergometer was used to measure physical fitness (maximal workload) and to induce airway narrowing. A methacholine provocation test was performed in the subjects at follow-up. During the 10-yr study period, 51 (6.7%) of the previously asymptomatic children developed asthma. These subjects had a lower mean physical fitness in 1985 than their peers: (3.63 versus 3.89 W x kg(-1); p=0.02) in boys and (3.17 versus 3.33 W x kg(-1); p=0.02) in girls. A weak correlation was found between physical fitness in childhood and airway responsiveness to methacholine at follow-up when adjusted for body mass index, age and sex (r=0.11; p<0.01). In a multiple regression analysis, physical fitness was inversely related to the development of physician diagnosed asthma, odds ratio=0.93 (0.87-0.99). Thus, the risk for the development of asthma during adolescence is reduced 7% by increasing the maximal workload 1 W x kg(-1). In conclusion, this study showed that physical fitness in childhood is weakly correlated with the development of asthma during adolescence and that high physical fitness seems to be associated with a reduced risk for the development of asthma.

Asymptomatic bronchial hyperresponsiveness to exercise in childhood and the development of asthma related symptoms in young adulthood: the Odense Schoolchild Study.

BACKGROUND: Exercise testing may be of value in identifying a group of children at high risk of subsequently developing respiratory symptoms. As few longitudinal studies have investigated this issue, the bronchial hyperresponsiveness to exercise in asymptomatic children was evaluated as a risk factor for developing asthma related symptoms in young adulthood. METHODS: A community based sample of 1369 schoolchildren, first investigated in 1985 at a mean age of 9.7 years, was followed up after a mean of 10.5 years. Nine hundred and twenty children (67%) were asymptomatic in childhood and 777 (84.9%) of these were re-investigated at follow up. At the first examination a maximum progressive exercise test on a bicycle ergometer was used to induce airway narrowing. The forced expiratory volume in one second (FEV1) after exercise was considered abnormal if the percentage fall in FEV1 was more than 5% of the highest fall in the reference subjects characterised by having no previous history of asthma or asthma related symptoms. The threshold for a positive test was 8.6% of pre-exercise FEV1. RESULTS: One hundred and three subjects (13%) had wheeze within the last year at follow up and, of these, nine (9%) had been hyperresponsive to exercise in 1985. One hundred and seventy subjects (22%) had non-infectious cough within the previous year, 11 of whom (6%) had been hyperresponsive to exercise in 1985. Multiple regression analysis showed that subjects with hyperresponsiveness to exercise had an increased risk of developing wheeze compared with subjects with a normal response to exercise when the fall in FEV1 after exercise was included as a variable (threshold odds ratio (OR) 2.3 (95% CI 1.1 to 5.5)). The trend was not significant when exercise induced bronchospasm was included as a continuous variable (OR 1.02 (95% CI 0.97 to 1.06)). CONCLUSIONS: Asymptomatic children who are hyperresponsive to exercise are at increased risk of developing new symptoms related to wheezing but the predictive value of exercise testing for individuals is low.

Population based study of risk factors for underdiagnosis of asthma in adolescence: Odense schoolchild study.

OBJECTIVE: To describe factors related to underdiagnosis of asthma in adolescence. DESIGN: Subgroup analysis in a population based cohort study. SETTING: Odense municipality, Denmark. SUBJECTS: 495 schoolchildren aged 12 to 15 years were selected from a cohort of 1369 children investigated 3 years earlier. Selection was done by randomisation (n = 292) and by a history indicating allergy or asthma-like symptoms in subject or family (n = 203). MAIN OUTCOME MEASURES: Undiagnosed asthma defined as coexistence of asthma-like symptoms and one or more obstructive airway abnormalities (low ratio of forced expiratory volume in 1 second to forced vital capacity, hyperresponsiveness to methacholine or exercise, or peak flow hypervariability) in the absence of physician diagnosed asthma. Risk factors (odds ratios) for underdiagnosis. RESULTS: Undiagnosed asthma comprised about one third of all asthma identified. Underdiagnosis was independently associated with low physical activity, high body mass, serious family problems, passive smoking, and the absence of rhinitis. Girls were overrepresented among undiagnosed patients with asthma (69%) and underrepresented among diagnosed patients (33%). Among the risk factors identified, low physical activity and problems in the family were independently associated with female sex. The major symptom among those undiagnosed was cough (58%), whereas wheezing (35%) or breathing trouble (50%) was reported less frequently than among those diagnosed. Less than one third of those undiagnosed had reported their symptoms to a doctor. CONCLUSIONS: Asthma, as defined by combined symptoms and test criteria, was seriously underdiagnosed among adolescents. Underdiagnosis was most prevalent among girls and was associated with a low tendency to report symptoms and with several independent risk factors that may help identification of previously undiagnosed asthmatic patients.

Reduced forced expiratory flow in schoolchildren with respiratory symptoms: the Odense Schoolchild Study.

In the present population-based study, spirometric lung function was assessed in symptomatic schoolchildren with and without asthma as compared to an asymptomatic reference group. The primary aim was to investigate if impaired lung function could be demonstrated in symptomatic schoolchildren, even in the absence of diagnosed asthma. Spirometry [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), 50% of forced expiratory flow (FEF 50%) and 75% of forced expiratory flow (FEF 75%)] and anthropometric measures (standing height, weight, skin fold thickness, and length and circumference of the upper arm) were obtained from 1369 8-10-year-old children (81.5% of the eligible population) during the school year 1985-86. In 1321 of those subjects (96.5% of those examined), a self-administered questionnaire was completed. Thirty-five children belonging to ethnic minorities were excluded, thus 1286 subjects were included for further analysis. Point prevalences concerning asthma and respiratory symptoms (wheeze, cough and shortness of breath) were obtained. Thirty-seven children reported asthma and one or more asthma-like symptoms (symptomatic asthmatics), whereas 40 children denied having asthma, although claiming one or more asthma-like symptoms (symptomatic non-asthmatics). In both symptomatic groups, FEF 50% and FEF 75% were reduced relative to the reference group, the deficit being larger in the symptomatic asthmatics. FEF 75% was found to be more reduced than FEF 50%. FEV1 and FVC did not differ significantly between groups. It is concluded that only half of the schoolchildren with respiratory symptoms usually associated with the presence of asthma actually reported having this disease. These results demonstrate the presence of reduced lung function in symptomatic, reportedly non-asthmatic, children, suggesting clinically important underdiagnosis of asthma. More severe impairment of lung function was found in known asthmatics, also implying some degree of undertreatment.

[Discrepancies between diagnosed asthma, asthma-like symptoms and a test for abnormal lung function]. / Manglende overensstemmelse mellem diagnosticeret asthma, asthmalignende symptomer og test for abnorm luftvejsfunktion.

For the diagnosis of asthma, it is neither clear to which degree various tests and symptoms identify the same subjects nor how these characteristics are best combined. We assessed the interrelationship between physician-diagnosed asthma, asthma-like symptoms and abnormal airway function in a population based sample of 495 12-15 year old schoolchildren. Participants filled in a questionnaire and underwent baseline spirometry (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. Most symptomatic subjects with any test positive were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). Although interest agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, between PEF and EXE and between FEV1% and PD15. However, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology, and the combined use of the two tests may be helpful as an epidemiological screening tool for asthma.

Interrelationships between diagnosed asthma, asthma-like symptoms, and abnormal airway behaviour in adolescence: the Odense Schoolchild Study.

BACKGROUND: The diagnosis of asthma is based on several characteristics including symptoms and suitable tests of airway lability. However, it is neither clear to what degree various tests and symptoms identify the same subjects, nor how these characteristics are best combined to diagnose asthma. The interrelationships between physician-diagnosed asthma, asthma-like symptoms, and abnormal airway function, as defined by four commonly used tests, have therefore been assessed. METHODS: A population based sample of 495 Danish schoolchildren aged 12-15 years, comprising 292 randomly selected subjects and 203 subjects considered at risk of having or developing asthma, was examined. Symptoms and background information were recorded by questionnaire. The test panel consisted of baseline forced expiratory volume in one second (FEV1%), provocation with treadmill exercise (EXE) and with inhaled methacholine (PD15), and monitoring of peak expiratory flow (PEF) twice daily for two weeks. RESULTS: The sensitivity for diagnosed asthma was highest for PD15 followed by PEF monitoring, whereas specificity for asthma or asthma-like symptoms was marginally higher with the other two tests. Most symptomatic subjects with any positive test were identified by PD15 alone (75%) or in combination with PEF monitoring (89%). PEF variability was more susceptible to treatment with inhaled steroids than the PD15 index. Although inter-test agreement was weak (kappa < 0.40 for all pairs), significant associations were found between PD15 and EXE, PEF and EXE, and FEV1% and PD15. CONCLUSIONS: The agreement between the four tests was weak. In particular, PEF variability and methacholine responsiveness seem to identify different varieties of airway pathophysiology. The combined use of methacholine provocation testing and PEF monitoring may be helpful as an epidemiological screening tool for asthma.

Evaluation of peak expiratory flow variability in an adolescent population sample. The Odense Schoolchild Study.

The validity of peak expiratory flow (PEF) recordings and the sensitivity of PEF variability indices in asthma and asthma-like conditions were examined in an adolescent population. Recordings from 245 randomly selected subjects and from an additional 181 subjects reporting or considered at risk for developing asthma were analyzed. Subjects recorded PEF twice daily for 2 wk using Mini-Wright meters, completed a symptoms questionnaire, and were tested for airway responsiveness to methacholine. The first three recording days showed significant accumulation of lowest PEF values recorded (41%) and were excluded from further analysis. Among nine PEF variability indices, the Two-lowest%mean (the mean of the two lowest PEF values as a percentage of the period mean) had the best sensitivity for physician-diagnosed asthma (28%). The sensitivity of the methacholine dose-response slope (DRS) was 69%. Combining these indices, a sensitivity of 77% for diagnosed asthma was obtained. Among subjects with asthma-like symptoms but no diagnosis of asthma, 14% had increased Two-lowest%mean and the DRS was increased in 17%, but only 3% were identified by both tests. In conclusion, inhomogeneity of PEF data could be corrected by disregarding the first three recording days. PEF variability indices identified some diagnosed asthmatics, and particularly some symptomatic "nonasthmatics," not identified by the DRS, suggesting that the combined use of these indices might be helpful.

Extrinsic allergic alveolitis after exposure to the yeast Rhodotorula rubra.

A case of extrinsic allergic alveolitis following exposure to the red yeast Rhodotorula rubra is reported--to our knowledge, for the first time. Extensive growth of the yeast in the patient's environment was demonstrated, explaining an elevated titer of Rhodotorula-specific precipitating antibodies in his serum. A bronchial provocation test confirmed the diagnosis.

Precipitating antibodies against pigeon bloom antigens as a specific and sensitive measure of pigeon exposure.

Precipitating antibodies against pigeon bloom antigen and pigeon serum were evaluated as a measure of pigeon exposure in 62 male pigeon breeders compared with 40 unexposed control subjects. We found a combination of highly antigenic bloom extract and a sensitive counter current immunoelectrophoresis suitable for clinical estimation of pigeon exposure. The sensitivity of the test was 86% in never-smokers and 73% in smokers at the 98% specificity level. Smoking significantly reduced the humoral immune response to both antigens.

[Allergic alveolitis among pigeon breeders in the county of Funen]. / Allergisk alveolitis blandt fynske dueholdere.

Two hundred pigeon breeders from the county of Funen were invited to participate in the study. No definite cases of allergic alveolitis were found among the 68 participants. 40% had experienced airway and/or general symptoms in connection with pigeon exposure. However, most of these symptoms could be explained as irritation of the airway and chronic bronchitis. Precipitating antibodies to pigeon serum and to an aqueous pigeon bloom extract were determined. The antibody titers did not differ in pigeon breeders with or without symptoms. Smokers had lower antibody titers to pigeon antigens and a lower level of total serum IgG, but reported symptoms in connection with pigeon exposure as often as non smokers.

[Occurrence of the yeast, Cryptococcus (Cr) neoformans, in pigeon droppings]. / Forekomst af gaersvampen Cryptococcus (Cr.) neoformans i duegødning.

Pigeon droppings were collected in Copenhagen and Odense. In samples from pigeon lofts, cryptococci were found in 33% from Copenhagen and in 16% from Odense. All of the species of cryptococci found were Cr. neoformans. These findings are compared with the previous Danish investigations. The frequent occurrence of cryptococci in AIDS patients is mentioned.