Hans Christian Siersted

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

Abstract 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. Key messages One third of young people with asthma are not diagnosed; most are girls Undiagnosed asthma is associated with low physical activity, high body mass index, serious family problems, passive smoking, and the absence of symptoms of rhinitis Cough is the most common symptom among those with undiagnosed asthma Two thirds of those with undiagnosed asthma do not report their symptoms to a doctor, suggesting a need for targeted asthma campaigns

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.

Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

BackgroundBronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure.MethodsPatients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT.Results45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group.ConclusionsThe absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years.

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 ∼1,000 Danes aged 20 yrs. In males, the average decline in forced expiratory volume in one second (FEV1) 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 FEV1 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.

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.

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.

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.

Increased use of inhaled corticosteroids among young Danish adult asthmatics: An observational study

OBJECTIVE This population-based longitudinal study aimed to investigate trends in use of inhaled corticosteroids (ICS) and determinants of ICS use in young Danish adults with asthma. METHODS 106 757 users, aged 18-44 years, of anti-asthmatic drugs were identified in the Danish Register of Medical Product Statistics during 1997-2006. One year prevalences of ICS use were calculated in categories of gender, age, and annual consumption of inhaled beta-2-agonists (IBA) in defined daily doses (DDD) per year. Determinants of ICS use were estimated by logistic regression models. RESULTS The one year prevalence of ICS use was constant, approximately 64%, during 1997-2000. An annual increase was observed from 67% in 2001 to 77% in 2006. This trend also existed when stratifying on gender, age and IBA use. Using 1997 as baseline, the adjusted odds ratios (ORs) of ICS use in 2000 was 0.98 (95% CI 0.96-1.01) compared to 1.12 (95% CI 1.09-1.15) in 2001, and 1.81 (95% CI 1.75-1.87) in 2006. Other determinants of high ICS use were female gender, young age, and high annual IBA consumption. Among those using at least 400 DDD of IBA per year (corresponding to 4.4 powder inhalations daily), nearly 20% had no ICS prescriptions in 2006. CONCLUSION Treatment with ICS among young Danish adult asthmatics has increased since 2001. This apparent improvement was associated with the introduction of fixed dose combination inhalers with ICS and inhaled long-acting beta-2-agonists. However, there is still room for improvement.

Associations between airway hyperresponsiveness, obesity and lipoproteins in a longitudinal cohort.

Epidemiological data have linked obesity with an increased risk of asthma, but the mechanisms responsible for this relationship remain unknown. One possible mechanism, which has received little attention, could be the effect of cholesterol metabolism on airway smooth muscle function. The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low‐density lipoprotein (LDL), high‐density lipoprotein (HDL) and total cholesterol].

Impact of socioeconomic status on the use of inhaled corticosteroids in young adult asthmatics

OBJECTIVE The aim of this population-based longitudinal study was to examine the associations between socioeconomic status (SES) and anti-asthmatic treatment with inhaled corticosteroids (ICS) among young Danish adult asthmatics, and to investigate whether these associations were consistent over time. METHODS We extracted data on prescription drug use, education, and income in 97 665 users of anti-asthmatic drugs, aged 18-44 years, identified in Statistics Denmark during 1997-2005. Individual information on education and income was used as measures of SES. Education was categorised into basic school/high school, vocational training, and higher education, and income was categorised into low, middle, and high income. Associations between ICS use and SES were estimated by logistic regression models. RESULTS High levels of education and income were independently associated with ICS use, education demonstrating the strongest association. Using basic school/high school and low income as baselines, the adjusted odds ratios (ORs) of ICS use for higher education were 1.46 (95% CI 1.40-1.51) and 1.10 (95% CI 1.06-1.14) for high income. Higher education was a nearly constant factor associated with ICS use throughout the observation period, but high income did not demonstrate any association before 2001 with increasing ORs observed each year hereafter. All associations became more pronounced when restricting to 35-44 year-olds. CONCLUSION High levels of SES were positively associated with ICS use in young adult asthmatics. To encourage ICS use, special attention should be paid to asthmatics with low educational level and low income. Further studies are needed to elucidate underlying mechanisms for this socioeconomic inequality.