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1.  Norovirus GII.4 Detection in Environmental Samples from Patient Rooms during Nosocomial Outbreaks 
Journal of Clinical Microbiology  2014;52(7):2352-2358.
Norovirus (NoV) is an important cause of nosocomial gastroenteric outbreaks. This 5-month study was designed to characterize NoV contamination and airborne dispersal in patient rooms during hospital outbreaks. Air vents, overbed tables, washbasins, dust, and virus traps designed to collect charged particles from the air were swabbed to investigate the possibility of NoV contamination in patient rooms during outbreaks in seven wards and in an outbreak-free ward. Symptomatic inpatients were also sampled. Nucleic acid extracts of the samples were examined for NoV RNA using genogroup I (GI) and GII real-time reverse transcription-PCR (RT-PCR). The NoV strains were characterized by RT-PCR, sequencing, and phylogenetic analysis of the RNA-dependent RNA-polymerase-N/S capsid-coding region (1,040 nucleotides [nt]). Patient strains from two outbreaks in one ward were sequenced across the RNA-dependent-RNA-polymerase major capsid-coding region (2.5 kb), including the hypervariable P2 domain. In the outbreak wards, NoV GII was detected in 48 of 101 (47%) environmental swabs and 63 of 108 patients (58%); NoV genotype II.4 was sequenced from 18 environmental samples, dust (n = 8), virus traps (n = 4), surfaces (n = 6), and 56 patients. In contrast, NoV GII was detected in 2 (GII.4) of 28 (7%) environmental samples and in 2 (GII.6 and GII.4) of 17 patients in the outbreak-free ward. Sequence analyses revealed a high degree of similarity (>99.5%, 1,040 nt) between NoV GII.4 environmental and patient strains from a given ward at a given time. The strains clustered on 11 subbranches of the phylogenetic tree, with strong correlations to time and place. The high nucleotide similarity between the NoV GII.4 strains from patients and their hospital room environment provided molecular evidence of GII.4 dispersal in the air and dust; therefore, interventional cleaning studies are justified.
PMCID: PMC4097690  PMID: 24759712
2.  Hymenoptera venom allergy: work disability and occupational impact of venom immunotherapy 
BMJ Open  2014;4(8):e005593.
Little is known about the Hymenoptera venom allergy impact on work ability and the effect of venom immunotherapy (VIT) on work. The objective of this study was to evaluate the prevalence and predictors of work disability in patients treated with VIT and the effects of VIT on occupational functioning.
181 patients, aged 18–71 years, treated with VIT while working, were investigated by questionnaire. Participants were classified into employed and self-employed and, based on work exposure to Hymenoptera, into three risk categories: high risk, occasionally high risk and low risk. Work disability was defined as having to have changed jobs/tasks and/or suffered economic loss because of Hymenoptera venom allergy. Predictors of work disability were assessed in logistic regression models.
31 (17%) patients reported work disability. Being self-employed and having the severe reaction at work were associated with work disability (p<0.01). Having a high-risk job for exposure to Hymenoptera was a significant predictor of work disability (OR 2.66, 95% CI 1.04 to 6.75). 24% of patients referred a positive effect of VIT on work. Determinants of the positive effect of VIT on work were having a high-risk job for exposure to hymenoptera (OR 3.60, 95% CI 1.52 to 8.51) and having already concluded VIT (OR 2.82, 95% CI 1.30 to 6.14).
Hymenoptera venom allergy could determine work disability. Patients with Hymenoptera venom allergy having a high-risk job for exposure to Hymenoptera seem to have higher risk of work disability and refer more frequently a positive effect of VIT on work.
PMCID: PMC4127938  PMID: 25099935
Epidemiology; Occupational & Industrial Medicine
3.  Psychosocial work environment, job mobility and gender differences in turnover behaviour: a prospective study among the Swedish general population 
BMC Public Health  2014;14:605.
Throughout the literature, substantial evidence supports associations between poor psychosocial work characteristics and a variety of ill-health outcomes. Yet, few reports strategies workers carry out to improve detrimental work conditions and consequently their health, such as changing jobs. The aim of this study was to examine if adverse psychosocial work exposure, as measured with the job demand-control and effort-reward imbalance models, could predict job mobility over a 5 years observation period.
Participants were working men and women (n = 940; 54.3% women), aged 24–60 years from the population of Gothenburg and surrounding metropolitan area. Job demand-control and effort-reward variables were compared with independent t-tests and chi2-test in persons with and without job mobility. Multivariate logistic regression was used to analyse whether psychosocial factors could predict job mobility. All regression analyses were stratified by gender.
Exposure to a combination of high demands-low control or high imbalance between effort and reward was related to increased odds of changing jobs (OR 1.63; CI 1.03-2.59 and OR 1.46; CI 1.13-1.89 respectively). When analysing men and women separately, men had a higher OR of changing jobs when exposed to either high demands-low control (OR 2.72; CI 1.24-5.98) or high effort-reward imbalance (OR 1.74; CI 1.11-2.72) compared to reference values. The only significant associations for women was slightly decreased odds for turnover in high reward jobs (OR 0.96; CI 0.92-0.99).
The results indicate that workers will seek to improve poor work environment by changing jobs. There were notable gender differences, where men tended to engage in job mobility when exposed to adverse psychosocial factors, while women did not. The lack of measures for mechanisms driving job mobility was a limitation of this study, thus preventing conclusions regarding psychosocial factors as the primary source for job mobility.
PMCID: PMC4073185  PMID: 24927628
Job demand-control; Effort-reward imbalance; Job mobility
4.  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
5.  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
6.  Validity of a questionnaire-based diagnosis of chronic obstructive pulmonary disease in a general population-based study 
The diagnosis of chronic obstructive pulmonary disease (COPD) is based on airflow obstruction. In epidemiological studies, spirometric data have often been lacking and researchers have had to rely almost solely on questionnaire answers. The aim of this study is to assess the diagnostic accuracy of questionnaire answers to detect COPD.
A sample of the Swedish general population without physician-diagnosed asthma was randomly selected and interviewed using a respiratory questionnaire. All eligible subjects aged 25–75 years (n = 3892) performed spirometry for detection of airflow obstruction using Global Initiative for Chronic Obstructive Lung Disease (GOLD) or American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria. Sensitivity, specificity, positive likelihood ratio (LR+), positive predictive values (PPVs), and negative predictive values (NPVs) were calculated to define diagnostic accuracy of questionnaire answers.
The sensitivity of the question “Have you been diagnosed by a physician as having COPD or emphysema?” in detecting airflow obstruction was 5.7% using GOLD, and 9.8% using ATS/ERS, criteria; specificity was 99.7% for GOLD and 99.5% for ATS/ERS. Sensitivity, specificity, and PPV were higher for the question compared to self-reported symptoms of chronic bronchitis in identifying subjects with airflow obstruction.
The high specificity and good PPV suggest that the question “Have you been diagnosed by a physician as having COPD or emphysema?” is more likely to identify those who do not have airflow obstruction, whereas the low sensitivity of this question could underestimate the real burden of COPD in the general population.
PMCID: PMC3994476  PMID: 24650114
Airway obstruction; Spirometry; Sensitivity; Accuracy; ATS/ERS; GOLD
7.  A longitudinal general population-based study of job strain and risk for coronary heart disease and stroke in Swedish men 
BMJ Open  2014;4(3):e004355.
The aim was to investigate whether psychosocial stress based on the job-demand-control (JDC) model increased the risk for coronary heart disease (CHD) and stroke.
Swedish men.
The Primary Prevention Study (PPS) comprises 6070 men born between 1915 and 1925 free from previous history of CHD and stroke at baseline (1974–1977). Psychosocial workplace exposure was assessed using a job-exposure matrix (JEM) for the JDC model based on occupation at baseline. The participants were followed from baseline examination, until death, until hospital discharge or until 75 years of age, whichever occurred first, using the Swedish national register on cause of death and the Swedish hospital discharge register for non-fatal and fatal stroke and CHD events. Cox regression models were used with stroke or CHD as the outcome, using JDC model and age as explanatory variables, as well as stratified models with regard to smoking, self-reported stress, socioeconomic status, obesity, hypertension and diabetes.
Primary and secondary outcome measures
Risk for stroke and CHD.
There was an increased risk (HR) for CHD in relation to high strain (HR 1.31, 95% CI 1.01 to 1.70). The risk was further increased among ever-smokers and among blue-collar workers. There was a relation between low control and increased risk for CHD (HR 1.19, 95% CI 1.06 to 1.35). There was no increased risk for stroke in any of the JDC categories.
Exposure to occupational psychosocial stress defined as job strain or low control increased the risk for CHD, especially among smokers and blue-collar workers. There was no increased risk for stroke in any of the JDC categories.
PMCID: PMC3948640  PMID: 24589825
8.  Natural History of Perceived Food Hypersensitivity and IgE Sensitisation to Food Allergens in a Cohort of Adults 
PLoS ONE  2014;9(1):e85333.
No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults.
To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity.
Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20–45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation.
Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (p<0.001) and IgE sensitisation to peanut decreased in particular by 67% (p = 0.003). The prevalence of timothy grass IgE sensitisation decreased by 15% (p = 0.003) while cat, mite and birch IgE sensitisation did not decrease significantly. Female sex, rhinitis, eczema and presence of IgE sensitisation to aeroallergens were independently associated with new onset food hypersensitivity.
The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens.
PMCID: PMC3888405  PMID: 24427301
9.  Effects of smoking, gender and occupational exposure on the risk of severe pulmonary fibrosis: a population-based case-control study 
BMJ Open  2014;4(1):e004018.
To estimate the effects of smoking, gender and occupational exposure on the risk of developing severe pulmonary fibrosis (PF), including dose-response and interaction effects.
National case–control study of 171 patients (cases) who had started a long-term oxygen therapy for PF in Sweden between February 1997 and April 2000, and 719 random control participants from the general population. Of these cases, 137 had probable idiopathic PF (IPF). The ORs for smoking, gender and occupational exposure were estimated using Mantel-Haenszel analysis and conditional logistic regression, controlling for age and year of diagnosis.
The adverse effect of smoking was amplified by male gender and occupational exposure, OR 4.6 (95% CI 2.1 to 10.3) for PF, and OR 3.0 (1.3 to 6.5) for IPF, compared with in non-exposed women. Higher cumulative smoking exposure was linearly associated with increased risks. Compared with smoking less than 10 pack-years, smoking ≥20 pack-years was associated with increased risk of PF and IPF, OR 2.6 (1.4 to 4.9) and OR 2.5 (1.3 to 5.0), respectively.
Smoking has a dose-related association with increased risk of severe PF. Men with a history of smoking and occupational exposure is a particular risk group for developing severe PF.
PMCID: PMC3902328  PMID: 24413348
10.  Incidence of chronic bronchitis in a cohort of pulp mill workers with repeated gassings to sulphur dioxide and other irritant gases 
Environmental Health  2013;12:113.
Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis.
The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970–2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated.
The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22).
Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.
PMCID: PMC3882105  PMID: 24354705
(MeSH); Bronchitis; Chronic; Irritants; Sulphur dioxide; Paper
11.  Explaining the social gradient in sickness absence: a study of a general working population in Sweden 
BMC Public Health  2013;13:545.
Some previous studies have proposed potential explanatory factors for the social gradient in sickness absence. Yet, this research area is still in its infancy and in order to comprise the full range of socioeconomic positions there is a need for studies conducted on random population samples. The main aim of the present study was to investigate if somatic and mental symptoms, mental wellbeing, job strain, and physical work environment could explain the association between low socioeconomic position and belonging to a sample of new cases of sick-listed employees.
This study was conducted on one random working population sample (n = 2763) and one sample of newly sick-listed cases of employees (n = 3044), drawn from the same random general population in western Sweden. Explanatory factors were self-rated 'Somatic and mental symptoms', 'Mental well-being', 'job strain', and 'physical work conditions' (i.e. heavy lifting and awkward work postures). Multiple logistic regression analyses were used.
Somatic and mental symptoms, mental well-being, and job strain, could not explain the association between socioeconomic position and sickness absence in both women and men. However, physical work conditions explained the total association in women and much of this association in men. In men the gradient between Non-skilled manual OR 1.76 (1.24;2.48) and Skilled manual OR 1.59 (1.10;2.20), both in relation to Higher non-manual, remained unexplained.
The present study strengthens the scientific evidence that social differences in physical work conditions seem to comprise a key element of the social gradient in sickness absence, particularly in women. Future studies should try to identify further predictors for this gradient in men.
PMCID: PMC3683342  PMID: 23738703
13.  Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA2LEN Study 
PLoS ONE  2013;8(1):e54137.
Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders.
In 2008 the Global Allergy and Asthma European Network (GA2LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds.
Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years.
In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
PMCID: PMC3554721  PMID: 23357876
14.  Stroke and coronary heart disease: predictive power of standard risk factors into old age—long-term cumulative risk study among men in Gothenburg, Sweden 
European Heart Journal  2013;34(14):1068-1074.
The aim of this study was to examine the short-term and long-term cumulative risk of coronary heart disease (CHD) and stroke separately based on age, sex, smoking status, systolic blood pressure, and total serum cholesterol.
Methods and results
The Primary Prevention Study comprising 7174 men aged between 47 and 55 free from a previous history of CHD, stroke, and diabetes at baseline examination (1970–73) was followed up for 35 years. To estimate the cumulative effect of CHD and stroke, all participants were stratified into one of five risk groups, defined by their number of risk factors. The estimated 10-year risk for high-risk individuals when adjusted for age and competing risk was 18.1% for CHD and 3.2% for stroke which increased to 47.8 and 19.6%, respectively, after 35 years. The estimates based on risk factors performed well throughout the period for CHD but less well for stroke.
The prediction of traditional risk factors (systolic blood pressure, total serum cholesterol, and smoking status) on short-term risk (0–10 years) and long-term risk (0–35 years) of CHD of stroke differs substantially. This indicates that the cumulative risk in middle-aged men based on these traditional risk factors can effectively be used to predict CHD but not stroke to the same extent.
PMCID: PMC3618888  PMID: 23303661
Score models; Stroke; CHD; Risk prediction; Risk factors
15.  A cross-sectional study of the relationship between job demand-control, effort-reward imbalance and cardiovascular heart disease risk factors 
BMC Public Health  2012;12:1102.
This cross-sectional study explored relationships between psychosocial work environment, captured by job demand-control (JDC) and effort-reward imbalance (ERI), and seven cardiovascular heart disease (CHD) risk factors in a general population.
The sampled consists of randomly-selected men and women from Gothenburg, Sweden and the city’s surrounding metropolitan areas. Associations between psychosocial variables and biomarkers were analysed with multiple linear regression adjusted for age, smoking, education and occupational status.
The study included 638 men and 668 women aged 24–71. Analysis between JDC and CHD risk factors illustrated that, for men, JDC was associated with impaired scores in several biomarkers, especially among those in high strain jobs. For women, there were no relationships between JDC and biomarkers. In the analysis of links between ERI and CHD risk factors, most associations tested null. The only findings were raised triglycerides and BMI among men in the fourth quartile of the ERI-ratio distribution, and lowered LDL-cholesterol for women. An complementary ERI analysis, combining high/low effort and reward into categories, illustrated lowered triglycerides and elevated HDL-cholesterol values among women reporting high efforts and high rewards, compared to women experiencing low effort and high reward.
There were some associations between psychosocial stressors and CHD risk factors. The cross-sectional design did not allow conclusions about causality but some results indicated gender differences regarding sensitivity to work stressors and also how the models might capture different psychosocial dimensions.
PMCID: PMC3541343  PMID: 23259757
Psychosocial work environment; Cardiovascular heart disease risk factors; Job demand-control; Effort-reward imbalance; Gender
16.  Occupational Exposure and New-onset Asthma in a Population-based Study in Northern Europe (RHINE) 
Annals of Occupational Hygiene  2012;57(4):482-492.
In a large population-based study among adults in northern Europe the relation between occupational exposure and new-onset asthma was studied.
The study comprised 13 284 subjects born between 1945 and 1973, who answered a questionnaire 1989–1992 and again 1999–2001. Asthma was defined as ‘Asthma diagnosed by a physician’ with reported year of diagnose. Hazard ratios (HR), for new-onset adult asthma during 1980–2000, were calculated using a modified job-exposure matrix as well as high-risk occupations in Cox regression models. The analyses were made separately for men and women and were also stratified for atopy.
During the observation period there were 429 subjects with new-onset asthma with an asthma incidence of 1.3 cases per 1000 person-years for men and 2.4 for women. A significant increase in new-onset asthma was seen for men exposed to plant-associated antigens (HR = 3.6; 95% CI [confidence interval] = 1.4–9.0), epoxy (HR = 2.4; 95% CI = 1.3–4.5), diisocyanates (HR = 2.1; 95% CI = 1.2–3.7) and accidental peak exposures to irritants (HR = 2.4; 95% CI = 1.3–4.7). Both men and women exposed to cleaning agents had an increased asthma risk. When stratifying for atopy an increased asthma risk were seen in non-atopic men exposed to acrylates (HR = 3.3; 95% CI = 1.4–7.5), epoxy compounds (HR = 3.6; 95% CI = 1.6–7.9), diisocyanates and accidental peak exposures to irritants (HR = 3.0; 95% CI = 1.2–7.2). Population attributable risk for occupational asthma was 14% for men and 7% for women.
This population-based study showed that men exposed to epoxy, diisocyanates and acrylates had an increased risk of new-onset asthma. Non-atopics seemed to be at higher risk than atopics, except for exposure to high molecular weight agents. Increased asthma risks among cleaners, spray painters, plumbers, and hairdressers were confirmed.
PMCID: PMC3622438  PMID: 23204511
Atopics and non-atopics; high molecular weight agent; high-risk occupations; irritating agents;  job-exposure matrix; low molecualr weight agent; occupational asthma;  population attributable risk
17.  Nasal nitric oxide in a random sample of adults and its relationship to sensitization, cat allergen, rhinitis, and ambient nitric oxide 
There is conflicting evidence whether nasal nitric oxide (NO) is associated with current rhinitis and with other possible predictors. Most studies have been performed in clinical cohorts and there is a lack of studies based on a general population sample. The aim of the present study was to investigate predictors for levels of nasal nitric oxide (NO) in a general population.
The population consisted of 357 subjects from Gothenburg participating in the follow-up of the European Respiratory Health Survey in 1999–2001. All subjects completed an extensive respiratory questionnaire. Nasal NO was measured from one nostril at a time with a sampling rate of 50 mL/s for 16 seconds and the nasal NO concentration was determined as the mean value within the plateau phase. Mattress dust samples were collected for cats and mites in a subsample of subjects. Ambient and exhaled NO was also measured. The predictors for nasal NO were analyzed in multiple linear regression models.
There was no relation between the levels of nasal NO and reporting current rhinitis. Nasal NO was significantly increased among those with high levels of IgE against cats and current smokers had significantly lower nasal NO. There was also a positive association between ambient NO and nasal NO. There were no significant associations between nasal NO and sex, age, or height, or between nasal NO and measured levels of cat antigen.
In this general population sample we found no relation between current rhinitis and nasal NO levels. There was a clear association between sensitization to cat and nasal NO, but there was no relation to current exposure to cat allergen. Our data support that nasal NO has a limited value in monitoring upper airway inflammation.
PMCID: PMC3906512  PMID: 22643936
Allergic rhinitis; epidemiology; FENO; nasal nitric oxide; nNO; rhinitis; sensitization
18.  Bronchial Responsiveness Is Related to Increased Exhaled NO (FENO) in Non-Smokers and Decreased FENO in Smokers 
PLoS ONE  2012;7(4):e35725.
Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FENO), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role.
To investigate how the relation between FENO and bronchial responsiveness is modulated by atopy and smoking habits.
Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed.
Main Results
Increased bronchial responsiveness was associated with increased FENO levels in non-smokers (p = 0.02) and decreased FENO levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FENO was seen only in the group smoking less <10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FENO in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FENO and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values<0.05).
The present study highlights the interactions of the relationship between FENO and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness.
PMCID: PMC3338521  PMID: 22563393
19.  Can work ability explain the social gradient in sickness absence: a study of a general population in Sweden 
BMC Public Health  2012;12:163.
Understanding the reasons for the social gradient in sickness absence might provide an opportunity to reduce the general rates of sickness absence. The complete explanation for this social gradient still remains unclear and there is a need for studies using randomized working population samples. The main aim of the present study was to investigate if self-reported work ability could explain the association between low socioeconomic position and belonging to a sample of new cases of sick-listed employees.
The two study samples consisted of a randomized working population (n = 2,763) and a sample of new cases of sick-listed employees (n = 3,044), 19-64 years old. Both samples were drawn from the same randomized general population. Socioeconomic status was measured with occupational position and physical and mental work ability was measured with two items extracted from the work ability index.
There was an association between lower socioeconomic status and belonging to the sick-listed sample among both women and men. In men the crude Odds ratios increased for each downwards step in socioeconomic status, OR 1.32 (95% CI 0.98-1.78), OR 1.53 (1.05-2.24), OR 2.80 (2.11-3.72), and OR 2.98 (2.27-3.90). Among women this gradient was not as pronounced. Physical work ability constituted the strongest explanatory factor explaining the total association between socioeconomic status and being sick-listed in women. However, among men, the association between skilled non-manual, OR 2.07 (1.54-2.78), and non-skilled manual, OR 2.03 (1.53-2.71) positions in relation to being sick-listed remained. The explanatory effect of mental work ability was small. Surprisingly, even in the sick-listed sample most respondents had high mental and physical work ability.
These results suggest that physical work ability may be an important key in explaining the social gradient in sickness absence, particularly in women. Hence, it is possible that the factors associated with the social gradient in sickness absence may differ, to some extent, between women and men.
PMCID: PMC3311564  PMID: 22397520
20.  Risk factors for respiratory work disability in a cohort of pulp mill workers exposed to irritant gases 
BMC Public Health  2011;11:689.
The association between chronic respiratory diseases and work disability has been demonstrated a number of times over the past 20 years, but still little is known about work disability in occupational cohorts of workers exposed to respiratory irritants. This study investigated job or task changes due to respiratory problems as an indicator of work disability in pulp mill workers occupationally exposed to irritants.
Data about respiratory symptoms and disease diagnoses, socio-demographic variables, occupational exposures, gassing episodes, and reported work changes due to respiratory problems were collected using a questionnaire answered by 3226 pulp mill workers. Information about work history and departments was obtained from personnel files. Incidence and hazard ratios for respiratory work disability were calculated with 95% confidence intervals (CI).
The incidence of respiratory work disability among these pulp mill workers was 1.6/1000 person-years. The hazard ratios for respiratory work disability were increased for workers reporting gassings (HR 5.3, 95% CI 2.7-10.5) and for those reporting physician-diagnosed asthma, chronic bronchitis, and chronic rhinitis, when analyzed in the same model.
This cohort study of pulp mill workers found that irritant peak exposure during gassing episodes was a strong predictor of changing work due to respiratory problems, even after adjustment for asthma, chronic bronchitis, and chronic rhinitis.
PMCID: PMC3178494  PMID: 21896193
21.  Respiratory health effects and exposure to superabsorbent polymer and paper dust - an epidemiological study 
BMC Public Health  2011;11:557.
The primary aim of the present study was to investigate if exposure to dust from absorbent hygiene products containing superabsorbent polymer is related to symptoms from the airways and from the eyes. The secondary aim was to estimate the current exposure to superabsorbent polymer among production and maintenance workers in a plant producing hygiene products.
The cohort comprised 1043 workers of whom 689 were exposed to super absorbent polymer and 804 were exposed to paper dust (overlapping groups). There was 186 workers not exposed to either superabsorbent polymer or to paper dust They were investigated with a comprehensive questionnaire about exposure, asthma, rhinitis and symptoms from eyes and airways. The results were analyzed with logistic regression models adjusting for sex, age, atopy and smoking habits. An aerosol sampler equipped with a polytetrafluoroethylene filter with 1 μm pore size was used for personal samplings in order to measure inhalable dust and superabsorbent polymer.
The prevalence of nasal crusts (OR 1.4, 95% CI 1.01-2.0) and nose-bleeding (OR 1.7, 95% CI 1.2-2.4) was increased among the paper dust exposed workers (adjusted for superabsorbent polymer exposure). There were no significant effects associated with exposure to superabsorbent polymer (adjusted for paper dust exposure). The average exposure to inhalable levels of total dust (paper dust) varied between 0.40 and 1.37 mg/m3. For superabsorbent polymer dust the average exposure varied between 0.02 and 0.81 mg/m3.
In conclusion, our study shows that workers manufacturing diapers in the hygiene industry have an increased prevalence of symptoms from the nose, especially nose-bleeding. There was no relation between exposure to superabsorbent polymer and symptoms from eyes, nose or respiratory tract, but exposure to paper dust was associated with nose-bleeding and nasal crusts. This group of workers had also a considerable exposure to superabsorbent polymer dust.
PMCID: PMC3155498  PMID: 21752269
22.  Subjects in a Population Study with High Levels of FENO Have Associated Eosinophil Airway Inflammation 
ISRN Allergy  2011;2011:792613.
Background. Measurement of fraction of exhaled nitric oxide (FENO) is a promising tool to increase validity in epidemiological studies of asthma. The association between airway inflammation and FENO has, however, only been examined in clinical settings and may be biased by selection of patients with asthma. Methods. In a population study with FENO registrations on 370 individuals, we identified nine subjects out of thirty subjects with high levels of FENO (>85th percentile, 30.3 ppb), irrespective of presence of respiratory symptoms, and 21 control subjects with FENO at median levels (11.1–16.4 ppb) willing to undergo bronchoscopy and bronchoalveolar lavage (BAL), all nonsmokers. FENO was measured in accordance with ATS criteria, and the examination also included spirometry, methacholine challenge test, and sampling of exhaled breath condensate (EBC). Results. Subjects with high FENO levels had significantly higher median the percentage of eosinophils in BAL than controls (2.1 versus 0.6, P < .006), and there was a significant association between FENO and the percentage of eosinophils in BAL (ρ=0.6, P < .002) and ECP in BAL (ρ=0.65, P < .05) examining the whole group, but no association with gender, FEV1, or degree of metacholine sensitivity or any of the biomarkers in EBC. All subjects with high FENO had respiratory symptoms, but only three had diagnosed asthma. There were a significant association between hydrogen peroxide in EBC and the percentage of neutrophils in bronchial wash. Conclusion. High FENO levels signal asthmatic or allergic respiratory disease in a population-based study. FENO levels are associated with degree of eosinophil airway inflammation as measured by the percentage of eosinophils and ECP in BAL.
PMCID: PMC4058119  PMID: 24977053
23.  Increased Prevalence of Symptoms of Rhinitis but Not of Asthma between 1990 and 2008 in Swedish Adults: Comparisons of the ECRHS and GA2LEN Surveys 
PLoS ONE  2011;6(2):e16082.
The increase in asthma prevalence until 1990 has been well described. Thereafter, time trends are poorly known, due to the low number of high quality studies. The preferred method for studying time trends in prevalence is repeated surveys of similar populations. This study aimed to compare the prevalence of asthma symptoms and their major determinants, rhinitis and smoking, in Swedish young adults in 1990 and 2008.
In 1990 the European Community Respiratory Health Survey (ECRHS) studied respiratory symptoms, asthma, rhinitis and smoking in a population-based sample (86% participation) in Sweden. In 2008 the same symptom questions were included in the Global Allergy and Asthma European Network (GA2LEN) survey (60% participation). Smoking questions were however differently worded. The regions (Gothenburg, Uppsala, Umeå) and age interval (20–44 years) surveyed both in 1990 (n = 8,982) and 2008 (n = 9,156) were analysed.
The prevalence of any wheeze last 12 months decreased from 20% to 16% (p<0.001), and the prevalence of “asthma-related symptoms” was unchanged at 7%. However, either having asthma attacks or using asthma medications increased from 6% to 8% (p<0.001), and their major risk factor, rhinitis, increased from 22% to 31%. Past and present smoking decreased.
From 1990 to 2008 the prevalence of obstructive airway symptoms common in asthma did not increase in Swedish young adults. This supports the few available international findings suggesting the previous upward trend in asthma has recently reached a plateau. The fact that wheeze did not increase despite the significant increment in rhinitis, may at least in part be due to the decrease in smoking.
PMCID: PMC3040758  PMID: 21379386
24.  Respiratory Health among Korean Pupils in Relation to Home, School and Outdoor Environment 
Journal of Korean Medical Science  2011;26(2):166-173.
There are few studies about school-environment in relation to pupils' respiratory health, and Korean school-environment has not been characterized. All pupils in 4th grade in 12 selected schools in three urban cities in Korea received a questionnaire (n = 2,453), 96% participated. Gaseous pollutants and ultrafine particles (UFPs) were measured indoors (n = 34) and outdoors (n = 12) during winter, 2004. Indoor dampness at home was investigated by the questionnaire. To evaluate associations between respiratory health and environment, multiple logistic- and multi-level regression models were applied adjusting for potential confounders. The mean age of pupils was 10 yr and 49% were boys. No school had mechanical ventilation and CO2-levels exceeded 1,000 ppm in all except one of the classrooms. The indoor mean concentrations of SO2, NO2, O3 and formaldehyde were 0.6 µg/m3, 19 µg/m3, 8 µg/m3 and 28 µg/m3, respectively. The average level of UFPs was 18,230 pt/cm3 in the classrooms and 16,480 pt/cm3 outdoors. There were positive associations between wheeze and outdoor NO2, and between current asthma and outdoor UFPs. With dampness at home, pupils had more wheeze. In conclusion, outdoor UFPs and even low levels of NO2 may adversely contribute to respiratory health in children. High CO2-levels in classrooms and indoor dampness/mold at home should be reduced.
PMCID: PMC3030998  PMID: 21286005
Asthma; Indoor Dampness; Mold Nitrogen Dioxide; Ultrafine Particles
25.  Mapping Snakebite Epidemiology in Nicaragua – Pitfalls and Possible Solutions 
Snakebites are a public health problem in Nicaragua: it is a tropical developing country, venomous snakes are present and there are reports of snakebites treated both in the formal and informal health care system. We aimed to produce an incidence map using data reported by the health care system that would be used to allocate resources. However, this map may suffer from case detection bias and decisions based on this map will neglect snakebite victims who do not receive healthcare. To avoid this error, we try to identify where underreporting is likely based on available information.
Method and Findings
The Nicaraguan municipalities are categorized by precipitation, altitude and geographical location into regions of assumed homogenous snake prevalence. Socio-economic and healthcare variables hypothesized to be related to underreporting of snakebites are aggregated into an index. The environmental region variable, the underreporting index and three demographic variables (rurality, sex and age distribution) are entered in a Poisson regression model of municipality-level snakebite incidence. In this model, the underreporting index is non-linearly associated with snakebite incidence, a finding we attribute to underreporting in the most deprived municipalities. The municipalities with the worst scoring on the underreporting index and those with combined low reported incidence and large rural population are identified as likely underreporting. 3,286 snakebite cases were reported in 2005–2009, corresponding to a 5-year incidence of 56 bites per 100,000 inhabitants (municipality range: 0–600 cases per 100,000 inhabitants).
Using publicly available data, we identified areas likely to be underreporting snakebites and highlighted these areas instead of leaving them “white” on the incidence map. The effects of the case detection bias on the distribution of resources against snakebites could decrease. Although not yet verified empirically, our study provides an example of how snake bite epidemiology may be investigated in similar settings worldwide at a low cost.
Author Summary
Snakebites have recently been recognized as a neglected cause of human suffering and death worldwide. Many bites are treated by traditional practitioners and thereby not recorded by the health care system. This leads to a lack of reliable epidemiological data and is identified as a major obstacle in dealing with this health problem. Household surveys are recommended for finding the true snakebite incidence, but the countries where snakebites are frequent are usually poor, meaning that this method is often too expensive. The usage of data reported by the health care system could then provide a necessary option when locating and estimating the snakebite problem. However, this data could be biased and lead to implementation of unfair policies. In this study, we use publicly available data about environmental, socioeconomic and health-care related variables and incidence reported from health care facilities to create a map of where underreporting could be suspected, either because of the presence of factors favouring underreporting or by a comparatively low reported incidence. By high-lighting these areas, the reported statistics are put into a context and the decision-maker is able to make a less biased decision on where to locate research, preventive and therapeutic resources.
PMCID: PMC2990701  PMID: 21124884

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