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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]

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]

Rationale: Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause.Objectives: To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause.Methods: The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect.Measurements and Main Results: Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women.Conclusions: Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging. [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]

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: 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]

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]

Background: Prolonged exposure to air pollution has been linked to adverse respiratory health, yet the evidence concerning its association with chronic obstructive pulmonary disease (COPD) is inconsistent. The evidence of a greenness effect on chronic respiratory diseases is limited., Objective: This study aimed to investigate the association between long-term exposure to particulate matter (PM 2.5 and PM 10 ), black carbon (BC), nitrogen dioxide (NO 2 ), ozone (O 3 ) and greenness (as measured by the normalized difference vegetation index - NDVI) and incidence of self-reported chronic bronchitis or COPD (CB/COPD)., Methods: We analyzed data from 5355 adults from 7 centers participating in the Respiratory Health in Northern Europe (RHINE) study. Mean exposures to air pollution and greenness were assessed at available residential addresses in 1990, 2000 and 2010 using air dispersion models and satellite data, respectively. Poisson regression with log person-time as an offset was employed to analyze the association between air pollution, greenness, and CB/COPD incidence, adjusting for confounders., Results: Overall, there were 328 incident cases of CB/COPD during 2010-2023. Despite wide statistical uncertainty, we found a trend for a positive association between NO 2 exposure and CB/COPD incidence, with incidence rate ratios (IRRs) per 10 μg/m³ difference ranging between 1.13 (95% CI: 0.90-1.41) in 1990 and 1.18 (95% CI: 0.96-1.45) in 2000. O 3 showed a tendency for inverse association with CB/COPD incidence (IRR from 0.84 (95% CI: 0.66-1.07) in 2000 to 0.88 (95% CI: 0.69-1.14) in 2010. No consistent association was found between PM, BC and greenness with CB/COPD incidence across different exposure time windows., Conclusion: Consistent with prior research, our study suggests that individuals exposed to higher concentrations of NO 2 may face an elevated risk of developing COPD, although evidence remains inconclusive. Greenness was not associated with CB/COPD incidence, while O 3 showed a tendency for an inverse association with the outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: 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., Objective: 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., Methods: 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., Results: 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/m 3 ), 1.33 (95 % CI: 1.02-1.74 per 10 μg/m 3 ), 1.16 (95 % CI: 0.98-1.38 per 0.4 μg/m 3 ) and 1.17 (95 % CI: 0.92-1.50 per 10 μg/m 3 ), 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., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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/m 2 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., (© 2023. The Author(s).)

Introduction: Previous studies on the association between abdominal and general obesity and respiratory disease have provided conflicting results., Aims and Objectives: We aimed to explore the associations of abdominal obesity with respiratory symptoms, asthma, and chronic obstructive pulmonary disease independently from general obesity in women and men., Methods: This cross-sectional study was based on the Respiratory Health in Northern Europe (RHINE) III questionnaire (n = 12 290) conducted in 2010-2012. Abdominal obesity was self-measured waist circumference using a sex-specific standard cut-off point: ≥102 cm in males and ≥88 cm in females. General obesity was defined as self-reported BMI ≥30.0 kg/m 2 ., Results: There were 4261 subjects (63% women) with abdominal obesity and 1837 subjects (50% women) with general obesity. Both abdominal and general obesity was independent of each other and associated with respiratory symptoms (odds ratio (OR) from 1.25 to 2.00)). Asthma was significantly associated with abdominal and general obesity in women, OR (95% CI) 1.56 (1.30-1.87) and 1.95 (1.56-2.43), respectively, but not in men, OR 1.22 (0.97-3.17) and 1.28 (0.97-1.68) respectively. A similar sex difference was found for self-reported chronic obstructive pulmonary disease., Conclusions: General and abdominal obesity were independent factors associated with respiratory symptoms in adults. Asthma and chronic obstructive pulmonary disease were independently linked to abdominal and general obesity in women but not men., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We studied home environment exposures in relation to asthma, allergic rhinitis and atopic dermatitis among offspring of participants (parents) in the Respiratory Health in Northern Europe (RHINE) study (age ≤ 30 y). Totally 17,881 offspring from Iceland, Norway, Sweden, Denmark and Estonia were included. Home environment exposures, including dampness and mold, type of dwelling, construction year and indoor painting were registered through a questionnaire answered by parents in the first follow up (RHINE II). The parents reported ten years later with in the frame of RHINE III offspring's birth year and offspring's asthma, allergic rhinitis, atopic dermatitis. They also reported dampness and mold at home from RHINE II to RHINE III. The prevalence of offspring's asthma before 10 y, asthma after 10 y, allergic rhinitis at any age and atopic dermatitis at any age were 9.7 %, 4.3 %, 15.6 % and 17.3 %, respectively. Asthma before 10 y was related to any indoor painting at RHINE II (OR = 1.14, 95%CI (1.02, 1.29)). Asthma after 10 y was associated with dampness/mold at home (OR = 1.33-1.62) and living in the newest buildings (constructed in 1986-2001) (OR = 1.30, 95%CI (1.02, 1.66)). Allergic rhinitis was associated with living in newer buildings (constructed in 1961-2001) (OR = 1.16-1.24). Atopic dermatitis was associated with visible mold (OR = 1.35, 95%CI(1.12, 1.62)), dampness/mold at home (OR = 1.18-1.38), living in apartments (OR = 1.22, 95%CI(1.10, 1.35)) and living in newer buildings (constructed in 1961-2001) (OR = 1.14-1.25). There were dose-response effects of dampness and mold on offspring's asthma after 10 y and atopic dermatitis (20 years exposure vs. 10 years exposure). Older offspring had increased risk of developing asthma after 10 y and atopic dermatitis. In conclusion, home dampness and mold, living in apartments, living in newer buildings and indoor painting were associated with offspring's asthma or allergic diseases. Stronger health effects were found among offspring with prolonged exposure of dampness/mold., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort was established to (1) investigate how exposures before conception and in previous generations influence health and disease, particularly allergies and respiratory health, (2) identify susceptible time windows and (3) explore underlying mechanisms. The ultimate aim is to facilitate efficient intervention strategies targeting multiple generations., Participants: RHINESSA includes study participants of multiple generations from ten study centres in Norway (1), Denmark (1), Sweden (3), Iceland (1), Estonia (1), Spain (2) and Australia (1). The RHINESSA core cohort, adult offspring generation 3 (G3), was first investigated in 2014-17 in a questionnaire study (N=8818, age 18-53 years) and a clinical study (subsample, n=1405). Their G2 parents participated in the population-based cohorts, European Community Respiratory Heath Survey and Respiratory Health In Northern Europe, followed since the early 1990s when they were 20-44 years old, at 8-10 years intervals. Study protocols are harmonised across generations., Findings to Date: Collected data include spirometry, skin prick tests, exhaled nitric oxide, anthropometrics, bioimpedance, blood pressure; questionnaire/interview data on respiratory/general/reproductive health, indoor/outdoor environment, smoking, occupation, general characteristics and lifestyle; biobanked blood, urine, gingival fluid, skin swabs; measured specific and total IgE, DNA methylation, sex hormones and oral microbiome. Research results suggest that parental environment years before conception, in particular, father's exposures such as smoking and overweight, may be of key importance for asthma and lung function, and that there is an important susceptibility window in male prepuberty. Statistical analyses developed to approach causal inference suggest that these associations may be causal. DNA methylation studies suggest a mechanism for transfer of father's exposures to offspring health and disease through impact on offspring DNA methylation., Future Plans: Follow-up is planned at 5-8 years intervals, first in 2021-2023. Linkage with health registries contributes to follow-up of the cohort., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Breathlessness is a major cause of suffering and disability globally. The symptom relates to multiple factors including asthma and lung function, which are influenced by hereditary factors. No study has evaluated potential inheritance of breathlessness itself across generations., Methods: We analysed the association between breathlessness in parents and their offspring in the Respiratory Health in Northern Europe, Spain and Australia generation study. Data on parents and offspring aged ≥18 years across 10 study centres in seven countries included demographics, self-reported breathlessness, asthma, depression, smoking, physical activity level, measured Body Mass Index and spirometry. Data were analysed using multivariable logistic regression accounting for clustering within centres and between siblings., Results: A total of 1720 parents (mean age at assessment 36 years, 55% mothers) and 2476 offspring (mean 30 years, 55% daughters) were included. Breathlessness was reported by 809 (32.7%) parents and 363 (14.7%) offspring. Factors independently associated with breathlessness in parents and offspring included obesity, current smoking, asthma, depression, lower lung function and female sex. After adjusting for potential confounders, parents with breathlessness were more likely to have offspring with breathlessness, adjusted OR 1.8 (95% CI 1.1 to 2.9). The association was not modified by sex of the parent or offspring., Conclusion: Parents with breathlessness were more likely to have children who developed breathlessness, after adjusting for asthma, lung function, obesity, smoking, depression and female sex in both generations. The hereditary components of breathlessness need to be further explored., Competing Interests: Competing interests: MJA reports grants from Pfizer, grants from Boehringer-Ingelheim, personal fees from Sanofi, other from Sanofi and personal fees from GSK, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

We investigated the prevalence of chronic cough and its association with work ability and sick leave in the general population.Data were analysed from the Respiratory Health In Northern Europe (RHINE) III cohort (n=13 500), of which 11 252 participants had also participated in RHINE II 10 years earlier, a multicentre study in Northern Europe. Participants answered a questionnaire on chronic cough, employment factors, smoking and respiratory comorbidities.Nonproductive chronic cough was found in 7% and productive chronic cough in 9% of the participants. Participants with nonproductive cough were more often female and participants with productive cough were more often smokers and had a higher body mass index (BMI) than those without cough. Participants with chronic cough more often reported >7 days of sick leave in the preceding year than those without cough ("nonproductive cough" 21% and "productive cough" 24%; p<0.001 for comparisons with "no cough" 13%). This pattern was consistent after adjusting for age, sex, BMI, education level, smoking status and comorbidities. Participants with chronic cough at baseline reported lower work ability and more often had >7 days of sick leave at follow-up than those without cough. These associations remained significant after adjusting for cough at follow-up and other confounding factors.Chronic cough was found in around one in six participants and was associated with more sick leave. Chronic cough 10 years earlier was associated with lower work ability and sick leave at follow-up. These associations were not explained by studied comorbidities. This indication of negative effects on employment from chronic cough needs to be recognised., Competing Interests: Conflict of interest: A. Johannessen has nothing to disclose. Conflict of interest: M. Holm has nothing to disclose. Conflict of interest: B. Forsberg has nothing to disclose. Conflict of interest: V. Schlünssen has nothing to disclose. Conflict of interest: R. Jõgi has nothing to disclose. Conflict of interest: M. Clausen has nothing to disclose. Conflict of interest: E. Lindberg has nothing to disclose. Conflict of interest: A. Malinovschi has nothing to disclose. Conflict of interest: Ö.I. Emilsson has nothing to disclose. Conflict of interest: H. Johansson has nothing to disclose., (Copyright ©ERS 2021.)

Background: While direct effects of occupational exposures on an individual's respiratory health are evident, a new paradigm is emerging on the possible effects of pre-conception occupational exposure on respiratory health in offspring. We aimed to study the association between parental occupational exposure starting before conception and asthma in their offspring (at 0-15 years of age)., Methods: We studied 3985 offspring participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Their mothers or fathers (n = 2931) previously participated in the European Community Respiratory Health Survey (ECRHS). Information was obtained from questionnaires on parental job history pre- and post-conception which was linked to an asthma-specific job-exposure matrix (JEM). We assessed the association between parental occupational exposure and offspring asthma, applying logistic regression models, clustered by family and adjusted for study centre, offspring sex, parental characteristics (age, asthma onset, place of upbringing, smoking) and grandparents' level of education., Results: Parental occupational exposure to microorganisms, pesticides, allergens or reactive chemicals pre-conception or both pre- and post-conception was not related to offspring asthma; in general, subgroup analyses confirmed this result. However, maternal exposure both pre- and post-conception to allergens and reactive chemicals was associated with increased odds for early-onset asthma in offspring (0-3 years of age); odds ratio 1.70 (95% CI: 1.02-2.84) and 1.65 (95% CI: 0.98-2.77), respectively., Conclusions: This study did not find evidence that parental occupational exposure, defined by an asthma JEM before conception only or during pre- and post-conception vs non-exposed, was associated with offspring asthma., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigated if greenness and air pollution exposure in parents' childhood affect offspring asthma and hay fever, and if effects were mediated through parental asthma, pregnancy greenness/pollution exposure, and offspring exposure. We analysed 1106 parents with 1949 offspring (mean age 35 and 6) from the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Mean particulate matter (PM 2.5 and PM 10 ), nitrogen dioxide (NO 2 ), black carbon (BC), ozone (O 3 ) (µg/m 3 ) and greenness (normalized difference vegetation index (NDVI)) were calculated for parents 0-18 years old and offspring 0-10 years old, and were categorised in tertiles. We performed logistic regression and mediation analyses for two-pollutant models (clustered by family and centre, stratified by parental lines, and adjusted for grandparental asthma and education). Maternal medium PM 2.5 and PM 10 exposure was associated with higher offspring asthma risk (odds ratio (OR) 2.23, 95%CI 1.32-3.78, OR 2.27, 95%CI 1.36-3.80), and paternal high BC exposure with lower asthma risk (OR 0.31, 95%CI 0.11-0.87). Hay fever risk increased for offspring of fathers with medium O 3 exposure (OR 4.15, 95%CI 1.28-13.50) and mothers with high PM 10 exposure (OR 2.66, 95%CI 1.19-5.91). The effect of maternal PM 10 exposure on offspring asthma was direct, while for hay fever, it was mediated through exposures in pregnancy and offspring's own exposures. Paternal O 3 exposure had a direct effect on offspring hay fever. To conclude, parental exposure to air pollution appears to influence the risk of asthma and allergies in future offspring.

Objectives: Smoking is associated with sleep disturbances. The aim of this study was to analyze whether sleep disturbances are predictors of smoking cessation and whether continued smoking is associated with the development of sleep disturbances., Methods: A questionnaire was sent to randomly selected men and women in Northern Europe in 1999-2001 (RHINE II) and was followed up by a questionnaire in 2010-2012 (RHINE III). The study population consisted of 2568 participants who were smokers at baseline and provided data on smoking at follow-up. Insomnia symptoms were defined as having difficulty initiating and/or maintaining sleep and/or early morning awakening ≥3 nights/week. Multiple logistic regression analyses were performed to calculate odds ratios (OR)., Results: Subjects with difficulty initiating sleep (adjusted odds ratio; 95% confidence interval: 0.6; 0.4-0.8), difficulty maintaining sleep (0.7; 0.5-0.9), early morning awakening (0.6; 0.4-0.8), any insomnia symptom (0.6; 0.5-0.8) or excessive daytime sleepiness (0.7; 0.5-0.8) were less likely to achieve long-term smoking cessation after adjustment for age, BMI, pack-years, hypertension, diabetes, chronic bronchitis, rhinitis, asthma, gender and BMI difference. There was no significant association between snoring and smoking cessation. In subjects without sleep disturbance at baseline, continued smoking increased the risk of developing difficulty initiating sleep during the follow-up period compared with those that had quit smoking (adj. OR 1.7, 95% CI 1.2-2.3)., Conclusions: Insomnia symptoms and excessive daytime sleepiness negatively predict smoking cessation. Smoking is a risk factor for the development of difficulty initiating sleep. Treatment for sleep disturbances should be included in smoking-cessation programs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Study Objectives: Exposure to traffic noise increases the risk of sleeping disturbance, but little is known about the effect of traffic-related air pollution on insomnia symptoms. We aimed to investigate the separate associations of self-reported proximity to traffic and traffic noise with insomnia., Methods: This is a cross-sectional study of the population included in the Respiratory Health in Northern Europe study, consisting of randomly selected men and women born between 1945 and 1973, from 7 Northern European centers. Hearing traffic noise in the bedroom, bedroom window proximity to traffic, and insomnia symptoms were self-reported. Bedroom window proximity to traffic was used as a surrogate for exposure to traffic-related air pollution. The following insomnia symptoms were assessed: difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening., Results: A total of 12,963 individuals was included. Traffic noise was positively associated with all three insomnia symptoms: difficulty initiating sleep (odds ratio [OR] = 3.54; 95% confidence interval [CI]: 1.85, 6.76), difficulty maintaining sleep (OR = 2.95; 95% CI: 1.62, 5.37), and early morning awakening (OR = 3.25; 95% CI: 1.97, 5.37). Proximity to traffic without disturbing noise was associated with difficulty initiating sleep (OR = 1.62; 95% CI: 1.45, 1.82)., Conclusions: This study adds further support to the identification of traffic noise as a risk factor for insomnia. Proximity to traffic without being exposed to noise was associated with an increased risk of difficulty initiating sleep. Our findings indicate that insomnia may be associated with both traffic noise and traffic-related air pollution., (© 2020 American Academy of Sleep Medicine.)

Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945-1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963-1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010-2012 and by G2 in 2013-2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0-G1 and G1-G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1-G2 (RR 1.11, 95% CI 0.81-1.52) or in G0-G1 (RR 0.99, 0.85-1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12-3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11-1.06). This pattern was not observed in analyses of G0-G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.

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.

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., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of this investigation was to study change in adults over a 20 year period in the prevalence of respiratory symptoms and disorders and its association to year of birth, life style and sleep related variables., Method: Adults 20-44 years of age, 6085 women and 5184 men, were randomly selected from seven centres in Northern Europe and followed for 20 years. The number of participants in the first survey was 21,595 and 11,269 participated in all three surveys. The participants were divided into three birth cohorts: 1944-1955, 1956-1965 and 1966-1975., Results: During the 20 year period the prevalence of wheeze decreased (- 2%) and the prevalence of asthma (+ 4%) and allergic rhinitis (+ 5%) increased, whereas the prevalence of nocturnal respiratory symptoms was relatively unchanged. The increase in allergic rhinitis was largest in those born 1966 to 1975 except in Estonia. There was large decrease in smoking (- 20%), increase in obesity (+ 7%) and snoring (+ 6%) during the study period. Smoking, obesity, snoring and nocturnal gastroesophageal reflux (nGER) were related to a higher risk of all symptoms. Obesity, snoring and nGER were also independently related to asthma., Conclusion: We conclude that as our participants got older there was a decrease in wheeze, no change in nocturnal symptoms and an increase in reported asthma and allergic rhinitis. These changes in prevalence are probably related to a decrease in smoking being counteracted by an increase in allergy, obesity and sleep related disorders.

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 (p(heterogeneity) = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (p(interaction) = 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.

Background: There is limited and conflicting evidence on the effect of menopause on asthma., Objectives: We sought to study whether the incidence of asthma and respiratory symptoms differ by menopausal status in a longitudinal population-based study with an average follow-up of 12 years., Methods: The Respiratory Health in Northern Europe study provided questionnaire data pertaining to respiratory and reproductive health at baseline (1999-2001) and follow-up (2010-2012). The study cohort included women aged 45 to 65 years at follow-up, without asthma at baseline, and not using exogenous hormones (n = 2322). Menopausal status was defined as nonmenopausal, transitional, early postmenopausal, and late postmenopausal. Associations with asthma (defined by the use of asthma medication, having asthma attacks, or both) and respiratory symptoms scores were analyzed by using logistic (asthma) and negative binomial (respiratory symptoms) regressions, adjusting for age, body mass index, physical activity, smoking, education, and study center., Results: The odds of new-onset asthma were increased in women who were transitional (odds ratio, 2.40; 95% CI, 1.09-5.30), early postmenopausal (odds ratio, 2.11; 95% CI, 1.06-4.20), and late postmenopausal (odds ratio, 3.44; 95% CI, 1.31-9.05) at follow-up compared with nonmenopausal women. The risk of respiratory symptoms increased in early postmenopausal (coefficient, 0.40; 95% CI, 0.06-0.75) and late postmenopausal (coefficient, 0.69; 95% CI, 0.15-1.23) women. These findings were consistent irrespective of smoking status and across study centers., Conclusions: New-onset asthma and respiratory symptoms increased in women becoming postmenopausal in a longitudinal population-based study. Clinicians should be aware that respiratory health might deteriorate in women during reproductive aging., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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.

Background: 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)., Methods: 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)., Results: 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))., Conclusions: 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.

Rationale: There is little knowledge of variations in respiratory symptoms during the menstrual cycle in a general population, and potential modifying factors are not investigated., Objectives: To investigate menstrual cycle variation in respiratory symptoms in a large general population, using chronobiology methodology, and stratifying by body mass index (BMI), smoking, and asthma status., Methods: A total of 3,926 women with regular cycles less than or equal to 28 days and not taking exogenous sex hormones answered a postal questionnaire regarding the first day of their last menstruation and respiratory symptoms in the last 3 days. Moving 4-day means were computed to smooth uneven records of daily sampling; best-fitting 28-day composite cosine curves were applied to each time series to describe rhythmicity., Measurements and Main Results: Significant rhythmic variations over the menstrual cycle were found in each symptom for all subjects and subgroups. Wheezing was higher on cycle Days 10-22, with a midcycle dip near the time of putative ovulation (approximately Days 14-16) in most subgroups. Shortness of breath was higher on days 7-21, with a dip just before midcycle in many subgroups. Cough was higher just after putative ovulation for subjects with asthma, BMI greater than or equal to 23 kg/m(2), and smokers, or just before ovulation and menses onset for low symptomatic subgroups., Conclusions: Respiratory symptoms varied significantly during the menstrual cycle and were most frequent from the midluteal to midfollicular stages, often with a dip near the time of ovulation. The patterns varied by BMI, smoking, and asthma status. These relations link respiratory symptoms with hormonal changes through the menstrual cycle and imply a potential for individualized chronotherapy for respiratory diseases.

Background: Severe α₁-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α₁-antitrypsin, but whether they have an increased risk of COPD is uncertain., Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease., Results: PI MZ was associated with a 3.5% lower FEV₁/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV₁/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies., Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV₁/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.