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1.  Predictors of dyspnea prevalence: Results from the BOLD study 
The European respiratory journal  2013;43(6):1610-1620.
Dyspnea is a cardinal symptom for cardiorespiratory diseases. No study has assessed worldwide variation in dyspnea prevalence or predictors of dyspnea.
We used cross-sectional data from population-based samples in 15 countries of the BOLD study to estimate prevalence of dyspnea in the full sample as well as in an a priori defined low-risk group (few risk factors or dyspnea-associated diseases). Dyspnea was defined by the modified Medical Research Council questions. We used ordered logistic regression analysis to study the association of dyspnea with site, sex, age, education, smoking habits, low/high BMI, self-reported disease, and spirometry results.
Of the 9,484 participants, 27% reported any dyspnea. In the low-risk subsample (N=4,329), 16% reported some dyspnea. In multivariate analyses, all covariates were correlated to dyspnea, but only 13% of dyspnea variation was explained. Women reported more dyspnea than men (odds ratio ≈ 2.1). When forced vital capacity (FVC) fell below 60% of predicted, dyspnea was much more likely.
There was considerable geographical variation in dyspnea, even when we adjusted for known risk factors and spirometry results. We were only able to explain 13% of dyspnea variation.
PMCID: PMC4143752  PMID: 24176991
Dyspnea; Lung function; Epidemiology; Multi-center study
2.  Productivity losses in chronic obstructive pulmonary disease: a population-based survey 
BMJ Open Respiratory Research  2014;1(1):e000049.
We aimed to estimate incremental productivity losses (sick leave and disability) of spirometry-defined chronic obstructive pulmonary disease (COPD) in a population-based sample and in hospital-recruited patients with COPD. Furthermore, we examined predictors of productivity losses by multivariate analyses.
We performed four quarterly telephone interviews of 53 and 107 population-based patients with COPD and controls, as well as 102 hospital-recruited patients with COPD below retirement age. Information was gathered regarding annual productivity loss, exacerbations of respiratory symptoms and comorbidities. Incremental productivity losses were estimated by multivariate quantile median regression according to the human capital approach, adjusting for sex, age, smoking habits, education and lung function. Main effect variables were COPD/control status, number of comorbidities and exacerbations of respiratory symptoms.
Altogether 55%, 87% and 31% of population-based COPD cases, controls and hospital patients, respectively, had a paid job at baseline. The annual incremental productivity losses were 5.8 (95% CI 1.4 to 10.1) and 330.6 (95% CI 327.8 to 333.3) days, comparing population-recruited and hospital-recruited patients with COPD to controls, respectively. There were significantly higher productivity losses associated with female sex and less education. Additional adjustments for comorbidities, exacerbations and FEV1% predicted explained all productivity losses in the population-based sample, as well as nearly 40% of the productivity losses in hospital-recruited patients.
Annual incremental productivity losses were more than 50 times higher in hospital-recruited patients with COPD than that of population-recruited patients with COPD. To ensure a precise estimation of societal burden, studies on patients with COPD should be population-based.
PMCID: PMC4256604  PMID: 25553244
COPD epidemiology; Health Economist
3.  Place of upbringing in early childhood as related to inflammatory bowel diseases in adulthood: a population-based cohort study in Northern Europe 
European Journal of Epidemiology  2014;29(6):429-437.
Background The two inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, has increased rapidly during the twentieth century, but the aetiology is still poorly understood. Impaired immunological competence due to decreasing biodiversity and altered microbial stimulation is a suggested explanation. Objective Place of upbringing was used as a proxy for the level and diversity of microbial stimulation to investigate the effects on the prevalence of IBD in adulthood. Methods Respiratory Health in Northern Europe (RHINE) III is a postal follow-up questionnaire of the European Community Respiratory Health Survey (ECRHS) cohorts established in 1989–1992. The study population was 10,864 subjects born 1945–1971 in Denmark, Norway, Sweden, Iceland and Estonia, who responded to questionnaires in 2000–2002 and 2010–2012. Data were analysed in logistic and Cox regression models taking age, sex, smoking and body mass index into consideration. Results Being born and raised on a livestock farm the first 5 years of life was associated with a lower risk of IBD compared to city living in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95 % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical difference in this association. Furthermore, there was a significant trend comparing livestock farm living, village and city living (p < 0.01). Sub-analyses showed that the protective effect was only present among subjects born after 1952 (OR 0.25, 95 % CI 0.11; 0.61). Conclusion This study suggests a protective effect from livestock farm living in early childhood on the occurrence of IBD in adulthood, however only among subjects born after 1952. We speculate that lower microbial diversity is an explanation for the findings.
PMCID: PMC4065648  PMID: 24916994
Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Microbial exposure; Rural/urban environments; Hygiene hypothesis
4.  Longterm follow-up in European respiratory health studies – patterns and implications 
Selection bias is a systematic error in epidemiologic studies that may seriously distort true measures of associations between exposure and disease. Observational studies are highly susceptible to selection bias, and researchers should therefore always examine to what extent selection bias may be present in their material and what characterizes the bias in their material. In the present study we examined long-term participation and consequences of loss to follow-up in the studies Respiratory Health in Northern Europe (RHINE), Italian centers of European Community Respiratory Health Survey (I-ECRHS), and the Italian Study on Asthma in Young Adults (ISAYA).
Logistic regression identified predictors for follow-up participation. Baseline prevalence of 9 respiratory symptoms (asthma attack, asthma medication, combined variable with asthma attack and/or asthma medication, wheeze, rhinitis, wheeze with dyspnea, wheeze without cold, waking with chest tightness, waking with dyspnea) and 9 exposure-outcome associations (predictors sex, age and smoking; outcomes wheeze, asthma and rhinitis) were compared between all baseline participants and long-term participants. Bias was measured as ratios of relative frequencies and ratios of odds ratios (ROR).
Follow-up response rates after 10 years were 75% in RHINE, 64% in I-ECRHS and 53% in ISAYA. After 20 years of follow-up, response was 53% in RHINE and 49% in I-ECRHS. Female sex predicted long-term participation (in RHINE OR (95% CI) 1.30(1.22, 1.38); in I-ECRHS 1.29 (1.11, 1.50); and in ISAYA 1.42 (1.25, 1.61)), as did increasing age. Baseline prevalence of respiratory symptoms were lower among long-term participants (relative deviations compared to total baseline population 0-15% (RHINE), 0-48% (I-ECRHS), 3-20% (ISAYA)), except rhinitis which had a slightly higher prevalence. Most exposure-outcome associations did not differ between long-term participants and all baseline participants, except lower OR for rhinitis among ISAYA long-term participating smokers (relative deviation 17% (smokers) and 44% (10–20 pack years)).
We found comparable patterns of long-term participation and loss to follow-up in RHINE, I-ECRHS and ISAYA. Baseline prevalence estimates for long-term participants were slightly lower than for the total baseline population, while exposure-outcome associations were mainly unchanged by loss to follow-up.
PMCID: PMC4021078  PMID: 24739530
5.  Feasible and simple exclusion criteria for pulmonary reference populations 
Thorax  2007;62(9):792-798.
International guidelines recommend that pulmonary reference populations consist of never‐smokers without respiratory diseases or symptoms, but the diseases and symptoms are not clearly specified. The present study aimed to identify simple exclusion criteria for defining pulmonary reference populations.
Based on a random sample from a general population (the parent population), 2358 subjects aged 26–82 years performed spirometric tests. From this sample, subjects were stepwise excluded according to self‐reported obstructive lung diseases, symptoms and smoking history. Four increasingly more healthy respiratory reference populations were formed. Prediction equations for the median and lower limit of normal lung function were derived using quantile regression analysis.
Subjects without self‐reported obstructive lung diseases or the cardinal respiratory symptoms of breathlessness, cough or wheeze (population B), never‐smokers without cardinal symptoms (population C) and never‐smokers without any respiratory symptoms (population D) constituted 50% (n = 1184), 23% (n = 539) and 14% (n = 331) of the parent population (population A), respectively. The largest discrepancy between prediction equations was found between the parent population and the population without cardinal respiratory symptoms (population B) (p<0.05). Minor changes in the reference equations were also seen when excluding ever‐smokers (population C). There was no additional change with exclusion of other respiratory symptoms (population D). Age‐related decline in lung function was steepest in the parent population.
Obstructive lung diseases, smoking history, breathlessness, cough and wheeze are optimal exclusion criteria for a pulmonary reference population. Further validation of the exclusion criteria identified in this study is recommended with identical wording in other and larger multinational populations.
PMCID: PMC2117321  PMID: 17389756

Results 1-5 (5)