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Background: The oral cavity is the gateway to the bacteria community in the lung. Disruption of the symbiotic balance of the oral microbiota has been associated with respiratory diseases. However, little is known about the relationship between oral bacteria and respiratory outcomes in the general population. We aimed to describe the associations between oral bacteria, lung function, and lung inflammation in a community-based population. Methods: Oral (gingival) samples were collected concurrently with spirometry tests in 477 adults (47% males, median age 28 years) from the RHINESSA study in Bergen, Norway. Bacterial DNA from the 16S rRNA gene from gingival fluid were sequenced by Illumina®MiSeq. Lung function was measured using spirometry and measurement of fractional exhaled nitric oxide (FeNO) were performed to examine airway inflammation. Differential abundance analysis was performed using ANCOM-BC, adjusting for weight, education, and smoking. Results: The abundance of the genera Clostridiales, Achromobacter, Moraxella, Flavitalea and Helicobacter were significantly different among those with low FEV1 (< lower limit of normal (LLN)) as compared to normal FEV1 i.e. ≥ LLN. Twenty-three genera differed in abundance between among those with low FVC < LLN as compared to normal FEV1 ≥ LLN. The abundance of 27 genera from phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Sacchribacteria differed significantly between elevated FeNO levels (≥ 50 ppb) compared to FeNO ≤ 25 ppb. Conclusion: Oral bacterial composition was significantly different for those with low FEV or FVC as compared to those with normal lung function equal to or higher than LLN. Differential bacterial composition was also observed for elevated FeNO levels. [ABSTRACT FROM AUTHOR]

This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1–3.2) for breathlessness score 3 and 2.1 (95% CI 1.7–2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4–7.7) for breathlessness score 3 and 3.0 (2.4–3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4–1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2–1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health. [ABSTRACT FROM AUTHOR]

Objective: Most women live to experience menopause and will spend 4–8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause; categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers. Methods: Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17β-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC). Results: The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90–0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83–0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women. Conclusions: The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials. [ABSTRACT FROM AUTHOR]

Background: Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father's preconception smoking. Methods: We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7–50 years) on father's any preconception smoking (n = 875 offspring) and father's pubertal onset smoking < 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father's smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure. Results: Father's smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) < 0.05) in PRR5 and CENPP. Father's pubertal onset smoking was associated with 19 CpGs (FDR < 0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p < 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father's smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR < 0.05), and all sites remained significant (p < 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure. Conclusion: Father's preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity. [ABSTRACT FROM AUTHOR]

Background: Several epidemiological studies have examined the risk of asthma and respiratory diseases in association with long-term exposure to outdoor air pollution. However, little is known regarding the adverse effects of long-term exposure to outdoor air pollution on the development of these outcomes in low- and middle-income countries (LMICs). Our study aims to investigate the association between long-term exposure to outdoor air pollution and asthma and respiratory diseases in LMICs through a systematic review with meta-analysis. Methods: This systematic review and meta-analysis will follow the PRISMA (Preferred Reporting for Systematic Reviews and Meta-Analyses) checklist and flowchart guidelines. The inclusion criteria that will be used in our study are 1) Original research articles with full text in English; 2) Studies including adult humans; 3) Studies with long-term air pollution assessment in LMICs, air pollutants including nitrogen oxide (NO2), sulfur oxide (SO2), particulate matter (PM2.5 and PM10), carbon monoxide (CO) and ozone (O3); 4) cohort and cross-sectional studies; 5) Studies reporting associations between air pollution and asthma and respiratory symptoms. A comprehensive search strategy will be used to identify studies published up till August 2022 and indexed in Embase, Medline, and Web of Science. Three reviewers will independently screen records retrieved from the database searches. Where there are enough studies with similar exposure and outcomes, we will calculate, and report pooled effect estimates using meta-analysis. Systematic review registration: PROSPERO CRD42022311326. Discussion: Findings from the health effects of long-term exposure to outdoor air pollution may be of importance for policymakers. This review will also identify any gaps in the current literature on this topic in LMICs and provide direction for future research. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) can lead to severe disability as the disease advances. The 6-minute walk test (6MWT) is commonly used to measure functional capacity in COPD patients and has three potential outcomes; walking distance, oxygen desaturation, and self-perceived dyspnea assessed by the Borg scale, all reflecting different aspects of COPD. The aim of this study was to identify predictors of all 3 outcomes of 6MWT in patients with COPD. Methods: 370 COPD patients, aged 40-75 yrs, were included from the first phase of the Bergen COPD cohort study. They were examined with spirometry, bioelectrical impedance measurements, 6MWT, Center for Epidemiologic Studies of Depression (CES-D) Scale, Medical Research Council (MRC) dyspnea scale, Charlson index for co-morbidities, self-reported physical activity questionnaire, plasma levels of C-reactive protein (CRP) and arterial blood gases. Results: Significant predictors in the multivariate analyses were sex, age, FEV1 in% predicted, symptoms of dyspnea (MRC), co-morbidities (Charlson Index) and self-reported physical activity for walking distance, FEV1 in% predicted and PaO2 for oxygen desaturation, and body composition, smoking and co-morbidities for self-perceived dyspnea assessed by the Borg scale. Conclusion: Several COPD characteristics have predictive value for the 6MWT, and some COPD characteristics are more strongly related to specific 6MWT outcomes than others. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Exposure to environmental tobacco smoke (ETS) is associated with impaired lung function in childhood, which in turn, is associated with chronic obstructive pulmonary disease (COPD) in adulthood. However, little is known regarding the direct association between childhood exposure to ETS and the development of COPD. The main objective of the present study was to examine the associations between childhood ETS exposure and adult COPD and respiratory symptoms. Methods: Patients with COPD ( n = 433) and control subjects ( n = 325) participated in the Bergen COPD Cohort Study during 2006-2009. Participants performed spirometry and answered extensive questionnaires. The risk factors for COPD, morning cough, cough with phlegm, chronic cough and dyspnoea were examined using logistic regression analysis. Analyses were stratified by gender. Results: The prevalence of childhood exposure to ETS was 61%. After adjustment, women who were exposed to ETS during childhood had a higher risk of COPD than those who were not exposed: odds ratio 1.9, 95% confidence interval 1.0, 3.7. Other important predictors for COPD and respiratory symptoms among women were occupational dust exposure (COPD), family history of COPD (COPD, all symptoms), current exposure to ETS in the home (morning cough) and education (COPD, dyspnoea). ETS exposure during childhood was associated with respiratory symptoms among males (odds ratios 1.5-1.7). Risk factors for COPD among men were occupational dust exposure, family history of COPD and level of education. Occupational dust exposure and family history of COPD also predicted dyspnoea among males. Conclusions: Exposure to ETS during childhood was associated with COPD and respiratory symptoms in adulthood. Although active smoking is still the most important risk factor for COPD, reduction of childhood ETS exposure could contribute to the prevention of COPD and respiratory symptoms. [ABSTRACT FROM AUTHOR]

Sampling is regarded as crucial to the validity of case-control studies. Ideally, cases and controls should be selected from the same source population, but deviations from this approach are often seen. Our objective was to examine how exposure-disease relationships in a study on chronic obstructive pulmonary disease (COPD) were affected by the sampling sources of cases and controls. A Norwegian case-control study on COPD including 1909 subjects used three sources of recruitment for cases (general population, hospital registry and volunteers) and two sources for controls (general population and volunteers). This resulted in six sampling combinations of cases and controls (groups A-F). We examined how the risk factors gender, age, smoking, educational level and comorbidity were associated with COPD in these six sampling groups. Several exposure-disease associations were dependent on variation in sampling source, thereby demonstrating the possibility of selection bias. The theoretically most ideal sampling group is likely group A, where both cases and controls are recruited from a general population. When using group A as a reference, the groups containing either voluntary controls and/or hospital-based cases deviated the most, suggesting higher susceptibility to selection bias in these groups. Recruitment from several sources made our study design vulnerable to selection bias. Our findings should bring about increased awareness to the sampling process, and encourage sampling of cases and controls from the same source population in future studies. Please cite this paper as: Sørheim I-C, Johannessen A, Grydeland TB, Omenaas ER, Gulsvik A and Bakke PS. Case-control studies on risk factors for COPD: how does the sampling of the cases and controls affect the results? The Clinical Respiratory Journal 2010; 4: 89-96. [ABSTRACT FROM AUTHOR]

Utilisation of healthcare resources because of pulmonary diseases have previously been presented according to lung function or symptom severity. We aimed to compare the associations of symptoms and lung function to healthcare and social service utilisation in subjects with self-reported obstructive lung diseases (OLDs) (asthma, chronic obstructive pulmonary disease, chronic bronchitis, emphysema). Of 2819 participants aged 27-82 years in the Hordaland County Respiratory Health Survey, 200 subjects (7.1%) self-reported OLD. They answered 13 questions on respiratory symptoms and 5 questions on use of healthcare and social services. Altogether, 161 participants (81%) completed post-bronchodilation spirometry. Use of anti-asthmatic drugs, regular physician's appointment, sick leave payment for the last 12 months, hospital admission for the last 12 months and disability pension were reported by 68%, 63%, 18%, 8% and 7% of those with self-reported OLD, respectively. Twenty per cent of subjects with self-reported OLD had not received any healthcare or social services. In adjusted multivariate logistic regression analyses, increase in the respiratory symptom score was significantly associated with more healthcare and social services. Lower forced expiratory volume in 1 s in % predicted, however, was not significantly associated with more use of healthcare and social services. The majority (80%) of subjects in a general population with self-reported OLD received healthcare services. The utilisation of healthcare and social services was strongly associated to the burden of respiratory symptoms, and, to a lesser degree, to the level and pattern of lung function. Please cite this paper as: Nielsen R, Johannessen A, Bakke PS, Askildsen JE, Omenaas ER and Gulsvik A. Aspects of healthcare utilisation in self-reported obstructive lung disease. The Clinical Respiratory Journal 2009; 3: 34-41. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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<0.5). 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

This was a validation study of the Norwegian version of The Interprofessional Collaborative Competency Attainment Survey (ICCAS). ICCAS consists of 20 retrospective pre- and post-questions, where respondents rate their agreement with regard to self-assessed competencies after participating in interprofessional education courses. It has been validated across various settings. The questionnaire was translated using the back-translation technique. We investigated evidence of validity regarding content, response process, and internal structure. Data were obtained from health and social care students (n = 1440, response rate 42.8%) participating in 12 different interprofessional courses in seven education institutions in Norway using a cross-sectional design. Exploratory factor analysis indicated one retracted factor for pre-scores and one retracted factor for post-scores. High McDonald's omega values indicated good internal consistency. Item deletion did not improve the scale's overall consistency on pre- or post-scores. We observed higher mean post-scores than pre-scores with moderate-to-large effect sizes, indicating a positive change in self-assessed interprofessional capabilities after training. Our findings indicate that the Norwegian version of ICCAS is a valid tool that may be implemented across a wide range of interprofessional education courses. Finally, our findings support earlier recommendations that ICCAS should be analyzed at an overall level to address change in interprofessional capabilities. [ABSTRACT FROM AUTHOR]

Study Objectives: To analyze the association between sleep-related symptoms and sleep length in parents and their children in relation to other risk factors in both generations.Method: The participants were parents (n = 5,855, age 54.3 ± 6.5 years, 45.2% men) who participated in the community-based Respiratory Health in Northern Europe (RHINE) study and one random member of their adult offspring (n = 5,855, age 30.2 ± 7.7 years, 41.5% men) who participated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study. Both generations responded to identical questionnaires on sleep symptoms, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), snoring, nocturnal sweating, nocturnal gastroesophageal reflux (nGER), sleep time and excessive daytime sleepiness (EDS). Insomnia was defined as either, or both, DIS and DMS in combination with EDS.Results: All sleep variables except nocturnal sweating were more common in offspring whose parents had reported the same symptom. After adjusting for age, gender, BMI, smoking, physical activity, education, center and parents' total number of children, there were independent associations between sleep symptoms in parents and offspring for DIS (adj. OR, 95% CI: 1.52, 1.20-1.93), DMS (1.34, 1.15-1.56), snoring (1.45, 1.15,1.83), nGER (1.65, 1.15-2.37), insomnia (1.39, 1.13-1.73), short sleep time (<6 h/night) (2.51, 1.72-3.68) and EDS (1.48, 1.26,1.72). There were no independent relationships between symptoms in parents and offspring for EMA, nocturnal sweating or long sleep time (>9 h/night).Conclusion: The familiar aggregation of many sleep disturbances was not explained by investigated lifestyle and environmental factors. This supports a heritable factor in sleep problems. [ABSTRACT FROM AUTHOR]

Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma.Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines.Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55).Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception.Funding: European Union (Horizon 2020, GA-633212). [ABSTRACT FROM AUTHOR]

Background: Previous research suggests an association between road traffic noise and obesity, but current evidence is inconclusive. The aim of this study was to assess the association between nocturnal noise exposure and markers of obesity and to assess whether sleep disturbance might be a mediator in this association. Methods: We applied data from the Respiratory Health in Northern Europe (RHINE) cohort. We used self-measured waist circumference (WC) and body mass index (BMI) as outcome values. Noise exposure was assessed as perceived traffic noise in the bedroom and/or the bedroom window's location towards the street. We applied adjusted linear, and logistic regression models, evaluated effect modifications and conducted mediation analysis. Results: Based on fully adjusted models we found that women, who reported very high traffic noise levels in bedroom, had 1.30 (95% CI 0.24–2.37) kg/m2 higher BMI and 3.30 (95% CI 0.39–6.20) cm higher WC compared to women, who reported no traffic noise in the bedroom. Women who reported higher exposure to road traffic noise had statistically significant higher odds of being overweight and have abdominal obesity with OR varying from 1.15 to 1.26 compared to women, who reported no traffic noise in the bedroom. For men, the associations were rather opposite, although mostly statistically insignificant. Furthermore, men, who reported much or very much traffic noise in the bedroom, had a statistically significantly lower risk of abdominal obesity. Sleep disturbance fully or partially mediated the association between noise in bedroom and obesity markers among women. Conclusion: Our results suggest that self-reported traffic noise in the bedroom may be associated to being overweight or obese trough sleep disturbance among women, but associations were inconclusive among men. [ABSTRACT FROM AUTHOR]

Background: Lipid A is the primary immunostimulatory part of the lipopolysaccharide (LPS) molecule. The inflammatory response of LPS varies and depends upon the number of acyl chains and phosphate groups in lipid A which is specific for a bacterial species or strain. Traditional LPS quantification assays cannot distinguish between the acylation degree of lipid A molecules, and therefore little is known about how bacteria with different inflammation-inducing potencies affect fractional exhaled nitric oxide (FeNO). We aimed to explore the association between pro-inflammatory hexa- and less inflammatory penta-acylated LPS-producing oral bacteria and FeNO as a marker of airway inflammation. Methods: We used data from a population-based adult cohort from Norway (n = 477), a study center of the RHINESSA multi-center generation study. We applied statistical methods on the bacterial community- (prediction with MiRKAT) and genus-level (differential abundance analysis with ANCOM-BC) to investigate the association between the oral microbiota composition and FeNO. Results: We found the overall composition to be significantly associated with increasing FeNO levels independent of covariate adjustment, and abundances of 27 bacterial genera to differ in individuals with high FeNO vs. low FeNO levels. Hexa- and penta-acylated LPS producers made up 2.4% and 40.8% of the oral bacterial genera, respectively. The Bray–Curtis dissimilarity within hexa- and penta-acylated LPS-producing oral bacteria was associated with increasing FeNO levels independent of covariate adjustment. A few single penta-acylated LPS producers were more abundant in individuals with low FeNO vs. high FeNO, while hexa-acylated LPS producers were found not to be enriched. Conclusions: In a population-based adult cohort, FeNO was observed to be associated with the overall oral bacterial community composition. The effect of hexa- and penta-acylated LPS-producing oral bacteria was overall significant when focusing on Bray–Curtis dissimilarity within each of the two communities and FeNO levels, but only penta-acylated LPS producers appeared to be reduced or absent in individuals with high FeNO. It is likely that the pro-inflammatory effect of hexa-acylated LPS producers is counteracted by the dominance of the more abundant penta-acylated LPS producers in this population-based adult cohort involving mainly healthy individuals. [ABSTRACT FROM AUTHOR]

Studies using mothers’ self-reported information on birth and pregnancy characteristics are common, but the validity of such data is uncertain. We evaluated questionnaire data from the RHINE III study on reproductive health provided by 715 mothers from Bergen, Norway, about their 1629 births between 1967 and 2010, using the Medical Birth Registry of Norway (MBRN) as gold standard. Validity of dichotomous variables (gender, preterm birth [<37 weeks’ gestation], postterm birth [>42 weeks’ gestation], induction of labour, forceps delivery, vacuum delivery, caesarean section, were assessed by sensitivity, specificity, positive and negative predictive values (PPV and NPV) and Cohen’s kappa. Paired t-test, Pearson’s correlation coefficient and Bland-Altman plots were used to validate birthweight, stratified by mother’s level of education, parity, birth year and child’s asthma status. Child’s gender and caesarean section showed high degree of validity (kappa = 0.99, sensitivity and specificity 100%). Instrumental delivery and extremely preterm birth showed good agreement with sensitivity 75–92%. Preterm birth and induction of labour showed moderate agreement. Post-term delivery was poorly reported. The validity appeared to be independent of recall time over 45 years, and of the child’s asthma status. Maternally reported birth and pregnancy information is feasible and cheap, showed high validity for important birth and pregnancy parameters, and showed similar risk-associations compared to registry data. [ABSTRACT FROM AUTHOR]

Rationale: There is some evidence that maternal smoking increases susceptibility to personal smoking’s detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure. Objectives: In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning’s unhealthy effects. Methods: The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent´s educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection <5 years, born during winter months, maternal age at birth >35 years) was investigated. Main Results: Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3–1.6), adult-onset asthma (1.5 [1.2–1.8]) and self-reported COPD (1.7 [1.3–2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: ≤1 year 0.9 [0.7–1.3]; 1–4 years 1.5 [1.1–2.0]; ≥4 years 1.6 [1.2–2.1]). The association of wheeze with cleaning activity ≥4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5–2.3] vs. 1.3 [0.96–1.8]; pinteraction 0.035). Conclusions: Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life. [ABSTRACT FROM AUTHOR]

Background: Fractional exhaled nitric oxide (FeNO) is a well‐known marker of type‐2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant. Objective: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi‐centre population‐based study. Methods: A total of 741 subjects with current asthma and 4155 non‐asthmatic subjects participating in the second follow‐up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview‐led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made. Results: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9–7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7–9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p =.03) and between rhinoconjunctivitis and FeNO (p =.03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non‐asthmatic subjects with perennial sensitization, with 12.1 (0.2–25.5) % higher FeNO in subjects with current rhinitis than in those without. Conclusions & Clinical Relevance: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis. [ABSTRACT FROM AUTHOR]

• Long-term exposure to low-level air pollution is associated with increased mortality. • Effects of air pollution persist decades after exposure. • Air pollution over time may be more harmful than anticipated. • No interaction between air pollution and greenness on mortality was observed. Air pollution has been linked to mortality, but there are few studies examining the association with different exposure time windows spanning across several decades. The evidence for the effects of green space and mortality is contradictory. We investigated all-cause mortality in relation to exposure to particulate matter (PM 2.5 and PM 10), black carbon (BC), nitrogen dioxide (NO 2), ozone (O 3) and greenness (normalized difference vegetation index - NDVI) across different exposure time windows. The exposure assessment was based on a combination of the Danish Eulerian Hemispheric Model and the Urban Background Model for the years 1990, 2000 and 2010. The analysis included a complete case dataset with 9,135 participants from the third Respiratory Health in Northern Europe study (RHINE III), aged 40–65 years in 2010, with mortality follow-up to 2021. We performed Cox proportional hazard models, adjusting for potential confounders. Altogether, 327 (3.6 %) persons died in the period 2010–2021. Increased exposures in 1990 of PM 2.5 , PM 10 , BC and NO 2 were associated with increased all-cause mortality hazard ratios of 1.40 (95 % CI1.04–1.87 per 5 μg/m3), 1.33 (95 % CI: 1.02–1.74 per 10 μg/m3), 1.16 (95 % CI: 0.98–1.38 per 0.4 μg/m3) and 1.17 (95 % CI: 0.92–1.50 per 10 μg/m3), respectively. No statistically significant associations were observed between air pollution and mortality in other time windows. O 3 showed an inverse association with mortality, while no association was observed between greenness and mortality. Adjusting for NDVI increased the hazard ratios for PM 2.5 , PM 10 , BC and NO 2 exposures in 1990. We did not find significant interactions between greenness and air pollution metrics. Long term exposure to even low levels of air pollution is associated with mortality. Opening up for a long latency period, our findings indicate that air pollution exposures over time may be even more harmful than anticipated. [ABSTRACT FROM AUTHOR]

Background: A farm upbringing has been associated with lower risk of asthma and methylation of asthma-related genes. As such, a farm upbringing has the potential to transfer asthma risk across generations, but this has never been investigated. We aimed to study the generational effects from a parental farm upbringing on offspring asthma.Methods: Our study involved three generations: 5759 participants from the European Community Respiratory Health Survey (ECRHS) study (born 1945-1971, denoted G1), their 9991 parents (G0) and their 8260 offspring (G2) participating in RHINESSA (Respiratory Health In Northern Europe, Spain and Australia). Questionnaire data were collected on G0 and G1 from G1 in 2010 and on G2 from themselves in 2013. The parental/grandparental place of upbringing was categorized: (i) both parents from farm; (ii) mother from farm, father from village/city; (iii) father from farm, mother from village/city; (iv) both parents from village or one parent from village and one from city; (v) both parents from city (reference group). Grandparental upbringing was equivalently categorized. Offspring asthma was self-reported and data were analysed using Cox-regression models with G2 age as the time scale.Results: A parental farm upbringing was not associated with offspring asthma when compared with city upbringing [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.74-1.69]. Findings remained similar when stratified by offspring upbringing and asthma phenotypes. Quantitative bias analyses showed similar estimates for alternative data sources. A grandparental farm upbringing was not associated with offspring asthma in either the maternal (HR 1.05, 95% CI 0.67-1.65) or paternal line (HR 1.02, 95% CI 0.62-1.68).Conclusions: This multigenerational analysis suggests no evidence of an association between parental/grandparental farm upbringing and offspring asthma. [ABSTRACT FROM AUTHOR]

Six-minute walk test (6MWT) measures walking distance (6MWD) and desaturation status in chronic obstructive pulmonary disease (COPD) patients. This study aimed to examine whether change in 6MWD and desaturation in 1 year were risk factors for later mortality, lung function decline and number of exacerbations. A total of 295 COPD patients performed 6MWT at baseline and 1 year later in the Bergen COPD cohort study 2006–2011. They were clinically examined and interviewed at annual visits. Mortality information was collected from the Norwegian Cause of Death Registry in 2015. We performed cox regression for mortality outcomes, linear mixed effect models for lung function, and negative binomial regression for exacerbations. Patients who desaturated in both 6MWTs had increased risk of all-cause and respiratory mortality, hazard ratio (HR) 2.7 (95% confidence interval [CI] 1.5–5.0) and 3.6 (95% CI 1.7–7.6), respectively, compared to non-desaturators. Patients who desaturated only at second 6MWT were at risk for all-cause mortality (HR 2.0, 95% CI 1.0–3.8). There were no apparent association between 6MWD and mortality. Desaturation in second 6MWT was associated with later increased rate of decline in forced vital capacity (FVC) % predicted (after 1 year predicted mean 4.2% above non-desaturators, after 5 years 0.7% below). Decline in 6MWD ≥ 30m was borderline (p = 0.06) associated with later decline in forced expiratory volume in 1 second % predicted, and with exacerbations (p = 0.07). Repeated desaturation in the 6MWT over time in COPD patients is a risk factor for all-cause and respiratory mortality, while onset of desaturation is associated with future FVC decline. [ABSTRACT FROM AUTHOR]

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991–1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999–2003, and ECRHS III in 2010–2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean β (95% CI), comparing active versus non-active individuals: 58 mL (21–95) for forced expiratory volume in one second and 83 mL (36–130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that parents' preconception exposures may influence offspring health. We aimed to investigate maternal and paternal smoking onset in specific time windows in relation to offspring body mass index (BMI) and fat mass index (FMI). We investigated fathers (n = 2111) and mothers (n = 2569) aged 39–65 years, of the population based RHINE and ECRHS studies, and their offspring aged 18–49 years (n = 6487, mean age 29.6 years) who participated in the RHINESSA study. BMI was calculated from self-reported height and weight, and FMI was estimated from bioelectrical impedance measures in a subsample. Associations with parental smoking were analysed with generalized linear regression adjusting for parental education and clustering by study centre and family. Interactions between offspring sex were analysed, as was mediation by parental pack years, parental BMI, offspring smoking and offspring birthweight. Fathers' smoking onset before conception of the offspring (onset ≥15 years) was associated with higher BMI in the offspring when adult (β 0.551, 95%CI: 0.174–0.929, p = 0.004). Mothers' preconception and postnatal smoking onset was associated with higher offspring BMI (onset <15 years: β1.161, 95%CI 0.378–1.944; onset ≥15 years: β0.720, 95%CI 0.293–1.147; onset after offspring birth: β2.257, 95%CI 1.220–3.294). However, mediation analysis indicated that these effects were fully mediated by parents' postnatal pack years, and partially mediated by parents' BMI and offspring smoking. Regarding FMI, sons of smoking fathers also had higher fat mass (onset <15 years β1.604, 95%CI 0.269–2.939; onset ≥15 years β2.590, 95%CI 0.544–4.636; and onset after birth β2.736, 95%CI 0.621–4.851). There was no association between maternal smoking and offspring fat mass. We found that parents' smoking before conception was associated with higher BMI in offspring when they reached adulthood, but that these effects were mediated through parents' pack years, suggesting that cumulative smoking exposure during offspring's childhood may elicit long lasting effects on offspring BMI. [ABSTRACT FROM AUTHOR]

Background: Chronic systemic inflammation accelerates early vascular ageing. Atopic sensitization and allergic diseases may involve increased inflammatory activity. This study aimed to assess whether atopic sensitization and allergic diseases were associated with altered vascular biomarkers in Norwegian adolescents. Methods: Distensibility coefficient of the common carotid arteries, carotid intima-media thickness and atopic sensitization (serum total and specific IgEs) were assessed in 95 Norwegian adolescents, who participated in the RHINESSA generation study. Symptoms of allergic disease were assessed by an interviewer-led questionnaire. Results: Atopic sensitization was found in 33 (34.7%) of the adolescents. Symptomatic allergic disease was found in 11 (33.3%) of those with atopic sensitization. Distensibility coefficient of the common carotid arteries appeared to be lower in participants with atopic sensitization than in those without (46.99±8.07*10−3/kPa versus 51.50±11.46*10−3/kPa; p>0.05), while carotid intima-media thickness did not differ between these groups (0.50±0.04mm versus 0.50±0.04mm; p>0.05). Crude, as well as age- and sex-adjusted multiple regression, revealed no significant association, neither of atopic sensitization nor of allergic disease, with distensibility coefficient of the common carotid arteries and carotid intima-media thickness. Conclusions: Our results do not support the assumption of an adverse impact of atopic sensitization and/or allergic disease on distensibility coefficient of the common carotid arteries and carotid intima-media thickness in Norwegian adolescents. Further research is necessary to study whether the clinical severity of allergic diseases might be more important than the status of allergic disease or atopic sensitization. [ABSTRACT FROM AUTHOR]

Introduction: The fractional exhaled nitric oxide (FENO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FENO as a reliable biomarker, it is important to investigate factors that influence FENO in healthy individuals. Men have higher levels of FENO than women, but it is unclear whether determinants of FENO differ by sex. Objective: To identify determinants of FENO in men and women without lung diseases. Method: Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. Results: Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3‐67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FENO than subjects in the lowest age quartile (39.7‐48.3 years) P = 0.02. Women in the two highest age quartiles (54.6‐60.2 and 60.3‐67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = <0.001 higher FENO, compared with the lowest age quartile. Height was related to 8% higher FENO level in men (P < 0.001) and 5% higher FENO levels in women (P = 0.008). Men who smoked had 37% lower FENO levels and women had 30% lower levels compared with never‐smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FENO levels compared with non‐sensitized subjects 26% and 29%, P < 0.001 for both. Conclusion and Clinical Relevance: Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FENO started increasing at lower age in women than in men, suggesting that interpretation of FENO levels in adults aged over 50 years should take into account age and sex. [ABSTRACT FROM AUTHOR]

Objectives: Menopause involves hypoestrogenism, which is associated with numerous detrimental effects, including on respiratory health. Hormone replacement therapy (HRT) is often used to improve symptoms of menopause. The effects of HRT on lung function decline, hence lung ageing, have not yet been investigated despite the recognized effects of HRT on other health outcomes.Study Design: The population-based multi-centre European Community Respiratory Health Survey provided complete data for 275 oral HRT users at two time points, who were matched with 383 nonusers and analysed with a two-level linear mixed effects regression model.Main Outcome Measures: We studied whether HRT use was associated with the annual decline in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1).Results: Lung function of women using oral HRT for more than five years declined less rapidly than that of nonusers. The adjusted difference in FVC decline was 5.6 mL/y (95%CI: 1.8 to 9.3, p = 0.01) for women who had taken HRT for six to ten years and 8.9 mL/y (3.5 to 14.2, p = 0.003) for those who had taken it for more than ten years. The adjusted difference in FEV1 decline was 4.4 mL/y (0.9 to 8.0, p = 0.02) with treatment from six to ten years and 5.3 mL/y (0.4 to 10.2, p = 0.048) with treatment for over ten years.Conclusions: In this longitudinal population-based study, the decline in lung function was less rapid in women who used HRT, following a dose-response pattern, and consistent when adjusting for potential confounding factors. This may signify that female sex hormones are of importance for lung ageing. [ABSTRACT FROM AUTHOR]

Abstract Background Very few studies have examined whether a long-term beneficial effect of physical activity on lung function can be influenced by living in polluted urban areas. Objective We assessed whether annual average residential concentrations of nitrogen dioxide (NO 2) and particulate matter with aerodynamic diameters < 2.5 μm (PM 2.5) and <10 μm (PM 10) modify the effect of physical activity on lung function among never- (N = 2801) and current (N = 1719) smokers in the multi-center European Community Respiratory Health Survey. Methods Associations between repeated assessments (at 27–57 and 39–67 years) of being physically active (physical activity: ≥2 times and ≥1 h per week) and forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) were evaluated using adjusted mixed linear regression models. Models were conducted separately for never- and current smokers and stratified by residential long-term NO 2 , PM 2.5 mass and PM 10 mass concentrations (≤75th percentile (low/medium) versus >75th percentile (high)). Results Among current smokers, physical activity and lung function were positively associated regardless of air pollution levels. Among never-smokers, physical activity was associated with lung function in areas with low/medium NO 2 , PM 2.5 mass and PM 10 mass concentrations (e.g. mean difference in FVC between active and non-active subjects was 43.0 mL (13.6, 72.5), 49.5 mL (20.1, 78.8) and 49.7 mL (18.6, 80.7), respectively), but these associations were attenuated in high air pollution areas. Only the interaction term of physical activity and PM 10 mass for FEV 1 among never-smokers was significant (p-value = 0.03). Conclusions Physical activity has beneficial effects on adult lung function in current smokers, irrespective of residential air pollution levels in Western Europe. Trends among never-smokers living in high air pollution areas are less clear. Highlights • Air pollution may modify associations between physical activity and lung function. • Physical activity was positively associated with lung function in current smokers regardless of air pollution levels. • Results in never smokers were less clear. • Air pollution control policies would ensure maximal benefit of physical activity promotion policies. [ABSTRACT FROM AUTHOR]

Background: The term Asthma and COPD Overlap (ACO) describes a condition where asthma and COPD overlap. We aimed to investigate associations between ACO and insomnia and respiratory symptoms, and to investigate the prevalence of ACO and the characteristics of subjects with ACO in two Northern European population studies. Methods: The study comprised 25 429 subjects aged ≥ 40 years who participated in one of two Northern European general population surveys. Both surveys included questions on asthma, COPD, respiratory and sleep-related symptoms, including difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening, and excessive daytime sleepiness. ACO was defined as having both self-reported asthma and COPD. Results: The prevalence of ACO was 1.0%. The group with ACO had a higher prevalence of both insomnia and respiratory symptoms than subjects with only asthma or COPD. Having ACO was independently associated with a 2–3 times higher probability of having sleep-related symptoms as compared with the group without asthma or COPD, after adjustment for age, sex, BMI, smoking history and educational level (adjusted odds ratio 2.14–3.36, 95% CI). Conclusion: Subjects with ACO have a high prevalence of insomnia and respiratory symptoms. To our knowledge, this is the first study to assess the association between sleep-related symptoms and ACO. [ABSTRACT FROM AUTHOR]

Rationale and objectives: The oral cavity is united with the airways, and thus poor oral health may affect respiratory health. However, data on the interaction of periodontal and respiratory health is limited. We aimed to evaluate whether periodontal health status, assessed by the Community Periodontal Index (CPI), was related to lung function among young and middle-aged adults in two Norwegian cohorts. Methods: Periodontal health status and lung function were measured among 656 participants in the Norwegian part of the European Community Respiratory Health Survey (ECHRS III) and the RHINESSA offspring study. Each participant was given a CPI-index from 0 to 4 where higher values reflect poorer periodontal status. The association between CPI and lung function was estimated with linear regression adjusting for age, gender, smoking, body mass index, exercise, education, use of antibiotics, inhaled medication and corrected for clustering within families. Main results: Participants with CPI 3–4 had significantly lower FEV1/FVC ratio compared to participants with CPI 0, b (95% CI) = -0.032 (-0.055, -0.009). Poorer periodontal health was associated with a significant decrease in the FEV1/FVC ratio with an adjusted regression coefficient for linear trend b (95% CI) = -0.009 (-0.015, -0.004) per unit increase in CPI. This negative association remained when excluding asthmatics and smokers (-0.014 (-0.022, -0,006)). Conclusions: Poorer periodontal health was associated with increasing airways obstruction in a relatively young, healthy population. The oral cavity is united with the airways and our findings indicate an opportunity to influence respiratory health by improving oral health. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of physical activity on asthma in middle-aged adults, in one longitudinal analysis, and one multi-centre cross-sectional analysis. Methods: The Respiratory Health in Northern Europe (RHINE) is a population-based postal questionnaire cohort study. Physical activity, height and weight were self-reported in Bergen, Norway, at RHINE II (1999–2001) and all centres at RHINE III (2010–2012). A longitudinal analysis of Bergen data investigated the association of baseline physical activity with follow-up asthma, incident asthma and symptoms, using logistic and zero-inflated Poisson regression (n = 1782). A cross-sectional analysis of all RHINE III centres investigated the association of physical activity with concurrent asthma and symptoms (n = 13,542) using mixed-effects models. Body mass index (BMI) was categorised (<20, 20–24.99, 25–29.99, 30+ kg/m2) and physical activity grouped by amount and frequency of lighter (no sweating/heavy breathing) and vigorous (sweating/heavy breathing) activity. Results: In the Bergen longitudinal analysis, undertaking light activity 3+ times/week at baseline was associated with less follow-up asthma (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.22, 0.89), whilst an effect from undertaking vigorous activity 3+ times/week was not detected (OR 1.22, 95% CI 0.44, 2.76). The associations were attenuated with BMI adjustment. In the all-centre cross-sectional analysis an interaction was found, with the association between physical activity and asthma varying across BMI categories. Conclusion: These findings suggest potential longer-term benefit from lighter physical activity, whilst improvement in asthma outcomes from increasing activity intensity was not evident. Additionally, it appears the benefit from physical activity may differ according to BMI. [ABSTRACT FROM AUTHOR]

Few studies have investigated associations between self-reported and modelled exposure to traffic pollution. The objective of this study was to examine correlations between self-reported traffic exposure and modelled (a) NO X and (b) traffic proximity in seven different northern European cities; Aarhus (Denmark), Bergen (Norway), Gothenburg, Umeå, and Uppsala (Sweden), Reykjavik (Iceland), and Tartu (Estonia). We analysed data from the RHINE III (Respiratory Health in Northern Europe, www.rhine.nu ) cohorts of the seven study cities. Traffic proximity (distance to the nearest road with >10,000 vehicles per day) was calculated and vehicle exhaust (NO X ) was modelled using dispersion models and land-use regression (LUR) data from 2011. Participants were asked a question about self-reported traffic intensity near bedroom window and another about traffic noise exposure at the residence. The data were analysed using rank correlation (Kendall's tau) and inter-rater agreement (Cohen's Kappa) between tertiles of modelled NO X and traffic proximity tertile and traffic proximity categories (0–150 metres (m), 150–200 m, >300 m) in each centre. Data on variables of interest were available for 50–99% of study participants per each cohort. Mean modelled NO X levels were between 6.5 and 16.0 μg/m 3 ; median traffic intensity was between 303 and 10,750 m in each centre. In each centre, 7.7–18.7% of respondents reported exposure to high traffic intensity and 3.6–16.3% of respondents reported high exposure to traffic noise. Self-reported residential traffic exposure had low or no correlation with modelled exposure and traffic proximity in all centres, although results were statistically significant (tau = 0.057–0.305). Self-reported residential traffic noise correlated weakly (tau = 0.090–0.255), with modelled exposure in all centres except Reykjavik. Modelled NO X had the highest correlations between self-reported and modelled traffic exposure in five of seven centres, traffic noise exposure had the highest correlation with traffic proximity in tertiles in three centres. Self-reported exposure to high traffic intensity and traffic noise at each participant's residence had low or weak although statistically significant correlations with modelled vehicle exhaust pollution levels and traffic proximity. [ABSTRACT FROM AUTHOR]

Background: Women are often underrepresented at sleep clinics evaluating sleep-disordered breathing (SDB). The aim of the present study was to analyze gender differences in sleep apnea diagnosis and treatment in men and women with similar symptoms of SDB.Methods: Respiratory Health in Northern Europe (RHINE) provided information about snoring, excessive daytime sleepiness (EDS), BMI and somatic diseases at baseline (1999-2001) and follow-up (2010-2012) from 4962 men and 5892 women. At follow-up participants were asked whether they had a diagnosis of and/or treatment for sleep apnea.Results: Among those with symptoms of SDB (snoring and EDS), more men than women had been given the diagnosis of sleep apnea (25% vs. 14%, p < 0.001), any treatment (17% vs. 11%, p = 0.05) and CPAP (6% vs. 3%, p = 0.04) at follow-up. Predictors of receiving treatment were age, BMI, SDB symptoms at baseline and weight gain, while female gender was related to a lower probability of receiving treatment (adj. OR 0.3, 95% CI 0.3-0.5). In both genders, the symptoms of SDB increased the risk of developing hypertension (adj OR, 95% CI: 1.5, 1.2-1.8) and diabetes (1.5, 1.05-2.3), independent of age, BMI, smoking and weight gain.Conclusions: Snoring females with daytime sleepiness may be under-diagnosed and under-treated for sleep apnea compared with males, despite running a similar risk of developing hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Background: Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity, and severity of respiratory impairment.Methods: BDR test data were available from clinical patients in the Netherlands, New Zealand, and the United States (n = 15,278; female subjects, 51.7%) and from surveys in Canada, Norway, and five Latin-American countries (n = 16,250; female subjects, 54.7%). BDR calculated according to FEV1, FVC, and FEV1/FVC was expressed as absolute change, a percentage of the baseline level (% baseline), a percentage of the predicted value (% predicted), and z score.Results: Change (Δ) in FEV1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; ΔFEV1 was significantly lower in African Americans. In 1,106 subjects with low FEV1 (200-1,621 mL) the FEV1 increased by 12% to 44.7% relative to baseline but < 200 mL. Expressing BDR as a percentage of the predicted value or as a z score attenuated the bias and made the 200-mL criterion redundant, but reduced positive responses by half. ΔFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z scores or % predicted; ΔFVC, however expressed, increased with the level of airflow obstruction.Conclusions: Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or as z scores eliminates this artifact and renders the required 200-mL minimum increase redundant. In severe airways obstruction ΔFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials. [ABSTRACT FROM AUTHOR]

Background: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception.Methods: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family.Results: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries.Conclusions: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations. [ABSTRACT FROM AUTHOR]

Objective/background: Little is known about associations between traffic exposure and sleep disturbances. We examined if self-reported exposure to traffic is associated with habitual snoring and daytime sleepiness in a general population.Methods: In the RHINE III study, 12184 adults answered questions on sleep disturbances and traffic exposure. We analysed bedrooms near roads with traffic, bedrooms with traffic noise, and travelling regularly along busy roads as proxies for traffic exposures, using logistic regression. Adjustment factors were study centre, gender, age, smoking habits, educational level, body mass index, physical activity, obstructive sleep apnoea, and sleep duration.Results: One in ten lived near a busy road, 6% slept in a bedroom with traffic noise, and 11% travelled regularly along busy roads. Habitual snoring affected 25% and daytime sleepiness 21%. More men reported snoring and more women reported daytime sleepiness. Having a bedroom with traffic noise was associated with snoring (adjusted OR 1.29, [95% CI 1.12, 1.48]). For daytime sleepiness, on the other hand, bedroom with traffic noise and high exposure to traffic pollution have significant risk factors (adjusted ORs 1.46 [1.11, 1.92] and 1.65 [1.11, 2.45]). Results were consistent across study centres.Conclusions: Daytime sleepiness is associated with traffic pollution and traffic noise, while habitual snoring is only associated with traffic noise. Self-reported traffic exposure should be taken into account when diagnosing and planning treatment for patients with sleep disturbances, because reducing noise and pollution exposure in the bedroom may have a beneficial effect. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to validate figural drawing scales depicting extremely lean to extremely obese subjects to obtain proxies for BMI and waist circumference in postal surveys.Design: Reported figural scales and anthropometric data from a large population-based postal survey were validated with measured anthropometric data from the same individuals by means of receiver-operating characteristic curves and a BMI prediction model.Setting: Adult participants in a Scandinavian cohort study first recruited in 1990 and followed up twice since.Subjects: Individuals aged 38-66 years with complete data for BMI (n 1580) and waist circumference (n 1017).Results: Median BMI and waist circumference increased exponentially with increasing figural scales. Receiver-operating characteristic curve analyses showed a high predictive ability to identify individuals with BMI > 25·0 kg/m2 in both sexes. The optimal figural scales for identifying overweight or obese individuals with a correct detection rate were 4 and 5 in women, and 5 and 6 in men, respectively. The prediction model explained 74 % of the variance among women and 62 % among men. Predicted BMI differed only marginally from objectively measured BMI.Conclusions: Figural drawing scales explained a large part of the anthropometric variance in this population and showed a high predictive ability for identifying overweight/obese subjects. These figural scales can be used with confidence as proxies of BMI and waist circumference in settings where objective measures are not feasible. [ABSTRACT FROM AUTHOR]

Background: There is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar. Aims: To investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD. Methods: A postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed. Results: Gum bleeding always/often was significantly associated with ≥3 asthma symptoms (OR 2.58, 95% CI 2.10–3.18), asthma (1.62 [1.23–2.14]) and self-reported COPD (2.02 [1.28–3.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (≥3 symptoms: gum bleeding sometimes 1.42 [1.25–1.60], often/always 2.58 [2.10–3.18]), and there was no heterogeneity between centres (pheterogeneity = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (pinteraction = 0.004). Conclusions: A consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions. [ABSTRACT FROM AUTHOR]

Background: The relation of gastrointestinal (GI) complaints to IgE-mediated allergy is not well understood. Increased numbers of "IgE-armed" mast cells have been observed in duodenal mucosa of patients with functional GI complaints.Aims: To explore whether total IgE and atopic sensitization were associated with functional GI complaints.Methods: Levels of serum total and specific IgE and GI complaints were measured in 161 patients and in a general population sample of 478 persons. Standard inhalant allergens were measured in the patient group, and selected inhalant allergens in the general population. GI complaints were assessed by two standardized questionnaires. The associations between GI complaints and total IgE were analyzed in multiple regression models.Results: GI complaints were positively associated with higher total IgE levels (all: b = 0.028, p = 0.012; patient group: b = 0.038, p = 0.072; general population: b = 0.038, p = 0.005), but negatively associated with atopic sensitization (all: b = -11.256, p = 0.181; patient group: b = -85.667, p < 0.001; general population: b = -14.394, p = 0.083). The relationship between total IgE and GI complaints was consistent among sensitized and non-sensitized persons, among men and women, and across age groups.Conclusion: Serum total IgE was positively associated with GI complaints, while atopic sensitization was inversely associated with GI complaints. This suggests that IgE-mediated immunology plays a role in the pathophysiology of functional GI complaints. The biological mechanisms reflected in higher total IgE levels, but less atopic sensitization, warrant further studies. [ABSTRACT FROM AUTHOR]

Background: It is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma. Objective: To evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010. Methods: The subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20–84 and born between 1925–1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models. Results: The average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1–4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease. Conclusions: After 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias. [ABSTRACT FROM AUTHOR]

Background Maternal folic acid supplementation between subsequent pregnancies may be important to reduce the risk of low folate status associated with short interpregnancy intervals. We examined how the prevalence of preconception folic acid use for a given pregnancy in Norwegian women varied according to the time interval from the previous pregnancy. Methods Analysis was based on 48 855 pairs of pregnancies with the second pregnancy included in the Norwegian Mother and Child Cohort Study (birth years 1999-2009). Interpregnancy interval was defined as the time from birth of a child to the conception of the subsequent sibling. Preconception folic acid use was defined as any use of folic acid-containing supplements within the last 4 weeks before the second pregnancy. Results The prevalence of preconception folic acid use was 31%. Among women with a term birth (≥37 weeks) in the previous pregnancy (92%), those with interpregnancy intervals ≤12 and ≥49 months were associated with up to 35% lower prevalence of preconception folic acid use for the second pregnancy, relative to the reference group (13-24 months). The low use in short intervals was mainly attributable to lower proportion of planned pregnancies and fewer women with higher education. Among women with a preterm birth (<37 weeks) in the previous pregnancy (8%), preconception folic acid use significantly decreased with increasing pregnancy spacing. Conclusions Our finding of a lower preconception folic acid use in women with both short and long interpregnancy intervals might help identifying those with higher risk of folate deficiency and preventing unwanted pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a study to determine if those with heterozygous (protease inhibitor [PI] MZ) who have low serum levels of alpha1-antitrypsin are more likely to develop chronic obstructive pulmonary disease (COPD). It states that researchers compared those with PI MZ and PI MM, dividing them into two groups, a control group in Norway composed of 1,669 people, and 2,707 from the rest of Europe and North America. A technical discussion of the study parameters are described, concluding that PI MZ heterozygotes had less FEV1/(F)VC than those with PI MM.

We studied associations between tobacco smoke, home environment and respiratory health in a 10 year follow up of a cohort of 11,506 adults in Northern Europe. Multilevel logistic regression models were applied to estimate onset and remission of symptoms. Current smokers at baseline developed more respiratory symptoms (OR = 1.39–4.43) and rhinitis symptoms (OR = 1.35). Starting smoking during follow up increased the risk of new respiratory symptoms (OR = 1.54–1.97) and quitting smoking decreased the risk (OR = 0.34–0.60). ETS at baseline increased the risk of wheeze (OR = 1.26). Combined ETS at baseline or follow up increased the risk of wheeze (OR = 1.27) and nocturnal cough (OR = 1.22). Wood painting at baseline reduced remission of asthma (OR 95%CI: 0.61, 0.38–0.99). Floor painting at home increased productive cough (OR 95%CI: 1.64, 1.15–2.34) and decreased remission of wheeze (OR 95%CI: 0.63, 0.40–0.996). Indoor painting (OR 95%CI: 1.43, 1.16–1.75) and floor painting (OR 95%CI: 1.77, 1.11–2.82) increased remission of allergic rhinitis. Living in the oldest buildings (constructed before 1960) was associated with higher onset of nocturnal cough and doctor diagnosed asthma. Living in the newest buildings (constructed 1986–2001) was associated with higher onset of nocturnal breathlessness (OR = 1.39) and rhinitis (OR = 1.34). In conclusion, smoking, ETS and painting indoor can be risk factors for respiratory symptoms. Wood painting and floor painting can reduce remission of respiratory symptoms. Smoking can increase rhinitis. Living in older buildings can be a risk factor for nocturnal cough and doctor diagnosed asthma. Living in new buildings can increase nocturnal dyspnoea and rhinitis. • Smoking and ETS can be risk factors for adult respiratory symptoms. • Indoor painting can increase respiratory symptoms. • Wood painting and floor painting can reduce remission of respiratory symptoms. • Living in older buildings can increase nocturnal cough and doctor diagnosed asthma. • Living in new buildings can increase nocturnal dyspnoea and rhinitis. [ABSTRACT FROM AUTHOR]

• Our results confirm that short-term exposures are associated with lung health outcomes. • This study extends our knowledge that lifelong exposure increase the risk of poor lung health. • Lifelong exposure to air pollution impact asthma attacks, rhinitis and low lung function. • Lifelong exposure to greenness increased the risk of low lung function in adulthood. To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function. Methods: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO 2), particulate matter (PM 10 and PM 2.5), black carbon (BC), ozone (O 3) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0–10 years, 10–18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and FEV 1 /FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education. Results: Childhood, adolescence and adult exposure to NO 2 , PM 10 and O 3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM 2.5 and O 3 were associated with lower lung function, in particular FEV 1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV 1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74). Conclusions: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function. [ABSTRACT FROM AUTHOR]

• Dampness/mould at home can be risk factors for adult onset of sleep disturbances. • Dampness/mould at work can increase adult onset of sleep disturbances. • Combined dampness at home and at work can further increase the onset. To investigate whether exposure to dampness and mold at home and at work induce sleep disturbances and daytime sleepiness among adults. Associations between onset of sleep disturbances and dampness, mold and mold odor at home and at work were investigated in a cohort of 11,318 adults from the population in Iceland, Norway, Sweden, Denmark and Estonia. The participants answered a questionnaire at baseline and 10 years later, with questions on sleep disturbances, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), insomnia symptoms, snoring and excessive daytime sleepiness (EDS). Multiple logistic regression models were applied to estimate associations adjusting for potential confounders including gender, age, smoking habit at baseline, change of smoking habit from baseline to follow up, BMI at baseline, change of BMI from baseline to follow up, education level at follow up, allergic rhinitis at baseline, doctor diagnosed asthma at baseline and chronic bronchitis at baseline. Baseline floor dampness, visible mold and mold odor at home increased onset of DIS, DMS, EMA, insomnia symptoms and snoring during follow up (OR 1.29–1.87). Any sign of dampness at baseline increased onset of DIS (OR 1.28, 95%CI 1.06–1.55), DMS (OR 1.17, 95%CI 1.02–1.34) and insomnia symptoms (OR 1.18, 95%CI 1.03–1.36). Dampness at home during follow up increased onset of DIS, DMS, EMA, insomnia symptoms and EDS (OR 1.17–1.36). Dampness at work during follow up increased onset of DIS, EMA, insomnia symptoms and EDS (OR 1.16–1.34). Combined dampness at home and at work during follow up increased the risk of onset of DIS, DMS, EMA, insomnia symptoms and EDS (OR 1.29–1.74). Dampness and mold at home and at work can increase the development of insomnia symptoms, snoring and EDS among adults. [ABSTRACT FROM AUTHOR]

Background: With increasing interest in exposure effects across generations, it is crucial to assess the validity of information given on behalf of others.Aims: To compare adult's report of their parent's smoking status against parent's own report and examine predictors for discrepant answers.Methods: We studied 7185 offspring (18-51 years) and one of their parents, n = 5307 (27-67 years) participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Information about parent's smoking status during offspring's childhood and mother's smoking status during pregnancy was obtained by questionnaires from parents and their offspring. We calculated sensitivity, specificity and Cohen's Kappa [κ] for agreement using parent's own report as the gold standard. We performed logistic regression to examine if offspring's sex, age, educational level, asthma status, own smoking status or parental status, as well as the parent's sex and amount of smoking during childhood predicted disagreement.Results: The sensitivity for offspring's correct report of parent's smoking status during childhood (0-10 years) was 0.82 (95% CI 0.81-0.84), specificity was 0.95 (95% CI 0.95-0.96) and a good agreement was observed, κ = 0.79 (95% CI 0.78-0.80). Offspring's report of mothers' smoking status during pregnancy showed a lower sensitivity, 0.66 (95% CI 0.60-0.71), a slightly lower specificity, 0.92 (95% CI 0.90-0.95) and a good agreement, κ = 0.61 (95% CI 0.55-0.67). In multivariate logistic regression analysis, offspring not having children was a predictor for discrepant answers (odds ratio [OR] 2.11 [95% CI 1.21-3.69]). Low amount of parents' tobacco consumption, < 10 cigarettes/day (OR 2.72 [95% CI 1.71-4.31]) also predicted disagreement compared to ≥10 cigarettes per day, and so did offspring's reports of fathers' smoking status (OR 1.73 [95% CI 1.09-2.74]) compared to mothers' smoking status. Offspring's sex, asthma status, educational level, smoking status or age was not related to discrepant answers.Conclusions: Adults report their parent's smoking status during their childhood, as well as their mother' smoking status when pregnant with them, quite accurately. In the absence of parents' direct report, offspring's reports could be valuable. [ABSTRACT FROM AUTHOR]

Introduction: Epidemiological studies have reported adverse health effects at levels even below recommended air quality limits, but the associations at low levels are uncertain. The Nordic region represents low exposure levels adding challenges on study power, especially for susceptible subgroups. Aims: We aim to study health effects of air pollution on (i) birth outcomes and (ii) childhood asthma to evaluate (iii) the concentration-response relationships at Nordic levels. Methods: In Denmark and Sweden we will make use of the National Population Register, Medical Birth Register, Prescribed Drug Register and Patient Register. These will be linked together giving study samples of 3 mill and 250.000 participants, respectively. Norway will use the Norwegian mother and child study (MoBa) with 100.000 participants linked to the same registers, whereas Finland will link the Population Register and Medical Birth Register to their Social Security Institution Register, Hospital Discharge Register and Register of Primary Health Care providing 1,75 mill participants. Through combining modelled air pollutants (PM10, PM2.5, PM10-2.5, NO2, ozone and black carbon) with residential address history we will link exposures with birth outcomes and childhood asthma. Susceptible populations will be defined by low socioeconomic status, lifestyle factors and gender. Results: Annual modelled population weighted means (SD) of PM2.5 levels in 2015 have been reported to be 9.2 µg/m³ (0.7 µg/m³) in Denmark, 6.2 (1.7) in Norway, 5.9 (1.5) in Sweden and 5.1 µg/m³ (1.2 µg/m³) in Finland. The levels in rural areas are generally lower. Conclusions: The Nordic registers provide an excellent platform for cross-border Nordic co-operation and sufficient study size to investigate health effects of low exposure levels in early life, also among susceptible subgroups. [ABSTRACT FROM AUTHOR]