Outcome-based Definition of the Lower Limit of Normal in Spirometry: A Study of 26,000 Young Adult Men.

Rationale The definition of the lower limit of normal (LLN) of spirometric variables is not well established. Objectives To investigate the relationship between spirometric abnormalities defined with different thresholds of the LLN and clinical outcomes, and to explore the possibility of using different LLN thresholds according to the pre-test probability of disease. Methods We studied the associations between pre-bronchodilator spirometric abnormalities (FEV1 < LLN, FVC < LLN, airflow obstruction, spirometric restriction) defined with different thresholds of the LLN (10th, 5th, 2.5th, 1st percentile) and multiple outcomes (prevalence of spirometric abnormalities, respiratory symptoms, all-cause and respiratory mortality) in 26,091 30-46 years old men who participated in a general population survey in Norway in 1988-1990 and were followed for 26 years. Analyses were performed with both local and GLI-2012 reference equations, stratified by pre-test risk (presence or absence of respiratory symptoms), and adjusted for age, BMI, smoking, and education. Results In the total population, the prevalence of airflow obstruction was 11.6% with GLI-LLN10, 11.0% with Local-LLN5, 6.1% with GLI-LLN5, 7.6% with Local-LLN2.5, and 3.5% with GLI-LLN2.5. The prevalence of spirometric restriction was 5.9% with GLI-LLN10, 5.2% with Local-LLN5, and 2.8% with GLI-LLN5. Increasingly lower thresholds of the LLN were associated with increasingly higher odds of respiratory symptoms and hazard of mortality for all spirometric abnormalities with both reference equations. Spirometric abnormalities defined with Local-LLN2.5 in asymptomatic subjects were associated with lower hazard of all-cause mortality (hazard ratio 1.50 (1.15, 1.95, 95% confidence intervals) for FEV1 < LLN) than those defined with Local-LLN5 in the general population (1.67 (1.50, 1.87) for FEV1 < LLN) and symptomatic subjects (1.67 (1.46, 1.91) for FEV1 < LLN). Overall, prevalence of spirometric abnormalities and associations with outcomes obtained with Local-LLN5 were comparable to those obtained with GLI-LLN10, and those obtained with Local-LLN2.5 to GLI-LLN5. Conclusions There is a relationship between statistically-based thresholds of the LLN of spirometric variables and clinical outcomes. Different thresholds of the LLN may be used in different risk subgroups of subjects, but the choice of the threshold needs to be evaluated together with the choice of reference equations.

Gastroesophageal reflux and snoring are related to asthma and respiratory symptoms: Results from a Nordic longitudinal population survey.

AIM: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive. METHODS: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: "never"; "former"; "incident"; "persistent". Incident respiratory symptoms were analyzed among participants without respective symptom at baseline. RESULTS: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21-1.72)), nGER (2.18 (1.60-2.98)) and in those with both snoring and nGER (2.59 (1.83-3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15-1.82)), nGER (1.99 (1.35-2.93)) and in those with both snoring and nGER (1.72 (1.06-2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring. CONCLUSION: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms.

Long-term exposure to low-level air pollution and greenness and mortality in Northern Europe. The Life-GAP project.

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 (PM2.5 and PM10), black carbon (BC), nitrogen dioxide (NO2), ozone (O3) 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 PM2.5, PM10, BC and NO2 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. O3 showed an inverse association with mortality, while no association was observed between greenness and mortality. Adjusting for NDVI increased the hazard ratios for PM2.5, PM10, BC and NO2 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.

Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study): a prospective cohort study in adults.

Background: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults. Methods: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age. Findings: Mean ambient ozone concentrations were approximately 65 µg/m³. A one interquartile range increase of 7 µg/m³ in ozone was associated with a faster decline in FEV1 of -2.08 mL/year (95% confidence interval: -2.79, -1.36) and in FVC of -2.86 mL/year (-3.73, -1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio. Interpretation: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period. Funding: German Research Foundation.

Reduced lung function and cause-specific mortality: A population-based study of Norwegian men followed for 26 years.

BACKGROUND AND AIM: Reduced lung function is associated with increased mortality, but it is unclear how different spirometric patterns are related to specific deaths. Aim of this study was to investigate these associations in a large general population cohort. METHODS: The study population consisted of 26,091 men aged 30-46 years from the Pneumoconiosis Survey of Western Norway conducted in 1988-1990 with follow-up on date and cause of death for 26 years. Cox proportional hazard models were used to estimate the association between baseline FEV1, FVC, obstructive (OSP) and restrictive spirometric pattern (RSP) (z-scores calculated according to GLI-2012 equations) and mortality (European 2012 shortlist classification (E-2012)), after adjustment for age, body mass index, smoking habits, and education. RESULTS: In total, 2462 (9%) subjects died. A predominant reduction of FEV1 (and OSP) were associated with respiratory non-cancer (E-8) (HR for one unit FEV1 z-score decrease 2.29 (95% CI 1.90, 2.77) and lung cancer mortality (E-2.1.8) (1.27(1.12, 1.44)). A similar reduction of FEV1 and FVC (and RSP) were associated with diabetes (E-4.1) (FEV1 2.21(1.67, 2.92), FVC 2.41(1.75, 3.32)), cerebrovascular (E-7.3) (1.52(1.21, 1.91), 1.54(1.19, 1.98)), ischemic heart disease (E-7.1) (1.22(1.10, 1.35), 1.21(1.08, 1.36)), neurological (E-6.3) (1.56(1.21, 2.01), 1.61(1.22, 2.13)), suicide (E-17.2) (1.37(1.13, 1.65), 1.29(1.04, 1.59)) and hematological cancer mortality (E-2.1.19-21) (1.29(1.05, 1.58), (1.26(1.00, 1.58)). No association was found between reduced lung function and mortality due to accidents, alcohol abuse, digestive and genitourinary cancer. CONCLUSIONS: Spirometric obstruction was mainly related to pulmonary mortality. Spirometric restriction was mainly related to extra-pulmonary mortality.

Greenness exposure: beneficial but multidimensional.

Many studies have shown that greenness has beneficial health effects, particularly on psychological and cardiovascular outcomes. In this narrative review, we provide a synthesis of knowledge regarding greenness exposure and respiratory health. The following outcomes were reviewed: respiratory mortality, lung cancer mortality, lung cancer incidence, respiratory hospitalisations, lung function, COPD, and asthma. We identified 174 articles through a literature search in PubMed, of which 42 were eligible for inclusion in this review. The most common marker for greenness exposure was the normalised difference vegetation index (NDVI), which was used in 29 out of 42 papers. Other markers used were tree canopy cover, landcover/land-use, plant diversity, density of tall trees and subjectively perceived greenness. We found beneficial effects of greenness in most studies regarding respiratory mortality, lung cancer incidence, respiratory hospitalisations and lung function. For lung cancer mortality, asthma and COPD, the effects of greenness were less clear cut. While many aspects of greenness are beneficial, some aspects may be harmful, and greenness may have different health effects in different population subgroups. Future studies of greenness and respiratory diseases should focus on asthma and COPD, on effects in different population subgroups and on disentangling the health effects of the various greenness dimensions.

Fathers' preconception smoking and offspring DNA methylation.

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.

Oral bacterial composition associated with lung function and lung inflammation in a community-based Norwegian population.

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.

Long-term exposure to outdoor air pollution and asthma in low-and middle-income countries: A systematic review protocol.

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.

Maternal and paternal tuberculosis is associated with increased asthma and respiratory symptoms in their offspring: a study from Northern Europe.

Background: Given the profound impact of tuberculosis (TB) on immunity and given murine studies suggesting that infections may influence immunity across generations, we hypothesize that parental TB might impact health and disease in future offspring. Objective: This study investigated the impact of maternal and paternal TB on offspring asthma and respiratory symptoms. Methods: We included data from the third follow-up of the Respiratory Health in Northern Europe study (RHINE). Information on own asthma status, asthma-like symptoms and other respiratory symptoms, as well as information about parental TB and asthma, were collected using standardized questionnaires. The associations between parental TB and RHINE participants' asthma and respiratory symptoms were analyzed using multiple logistic regression, with adjustment for parental education, smoking habits and asthma. Results: Of 8,323 study participants, 227 (2.7%) reported only paternal TB, 282 (3.4%) only maternal TB, and 33 (0.4%) reported that both parents had TB. We found a higher risk of asthma (aOR: 1.29, 95% CI: 1.05-1.57) in offspring with a history of parental TB as compared to offspring without parental TB., Parental TB was significantly associated with allergic asthma in offspring (aOR: 1.58, 95% CI: 1.29-2.05), while no significant association between parental TB and asthma without allergy (aOR: 1.00, 95% CI: 0.76-1.32) in offspring was observed. Conclusion: Results from this study indicate that parental TB might be a risk factor for offspring's asthma and respiratory symptoms. We raise the hypothesis that the immunological impact of infections might be transmitted to influence offspring phenotype in humans.

Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study.

BACKGROUND: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. OBJECTIVE: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. METHODS: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. RESULTS: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval: -2.18 to -0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. CONCLUSIONS: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.

Traffic noise in the bedroom in association with markers of obesity: a cross-sectional study and mediation analysis of the respiratory health in Northern Europe cohort.

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.

Previous tuberculosis infection associated with increased frequency of asthma and respiratory symptoms in a Nordic-Baltic multicentre population study.

Background: Tuberculosis (TB) infection induces profound local and systemic, immunological and inflammatory changes that could influence the development of other respiratory diseases; however, the association between TB and asthma is only partly understood. Our objective was to study the association of TB with asthma and respiratory symptoms in a Nordic-Baltic population-based study. Methods: We included data from the Respiratory Health in Northern Europe (RHINE) study, in which information on general characteristics, TB infection, asthma and asthma-like symptoms were collected using standardised postal questionnaires. Asthma was defined based on asthma medication usage and/or asthma attacks 12 months prior to the study, and/or by a report of ≥three out of five respiratory symptoms in the last 12 months. Allergic/nonallergic asthma were defined as asthma with/without nasal allergy. The associations of TB with asthma outcomes were analysed using logistic regressions with adjustments for age, sex, smoking, body mass index and parental education. Results: We included 8379 study participants aged 50-75 years, 61 of whom reported having had TB. In adjusted analyses, participants with a history of TB had higher odds of asthma (OR 1.99, 95% CI 1.13-3.47). The associations were consistent for nonallergic asthma (OR 2.17, 95% CI 1.16-4.07), but not for allergic asthma (OR 1.20, 95% CI 0.53-2.71). Conclusion: We found that in a large Northern European population-based cohort, persons with a history of TB infection more frequently had asthma and asthma symptoms. We speculate that this may reflect long-term effects of TB, including direct damage to the airways and lungs, as well as inflammatory responses.

Association between lipid-A-producing oral bacteria of different potency and fractional exhaled nitric oxide in a Norwegian population-based adult cohort.

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.

Association between abdominal and general obesity and respiratory symptoms, asthma and COPD. Results from the RHINE study.

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/m2. 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.

Clinical Remission of Asthma and Allergic Rhinitis - in a Longitudinal Population Study.

Background: Although asthma and allergic rhinitis are chronic diseases, some patients experience periods of remission. Information on prognostic factors associated with the remission of asthma and allergic rhinitis is valuable in resource prioritization. This study investigated factors associated with the clinical remission of asthma and allergic rhinitis. Methods: In the Respiratory Health In Northern Europe (RHINE) study, data was collected with questionnaires in stage one (RHINE I, 1989-1992) and two follow-ups (RHINE II, 1999-2001 and RHINE III, 2010-2012) from Sweden, Norway, Denmark, Iceland and Estonia. Clinical remission was defined as having reported asthma or allergic rhinitis in RHINE I or RHINE II but not in RHINE III. Results: Of 13,052 participants, 975 (7.5%) reported asthma in RHINE I or RHINE II, and 3379 (25.9%) allergic rhinitis. Clinical remission of asthma and allergic rhinitis was found in 46.4% and 31.8%, respectively. Living in Estonia (OR (95% CI) 2.44 (1.22-4.85)) and living in an apartment (1.45 (1.06-1.98)) were related to remission of asthma, while subjects reporting allergic rhinitis (0.68 (0.51-0.90)), asthma onset ≤ 12 years of age (0.49 (0.35-0.68)), receiving treatment with antibiotics for respiratory illness (0.64 (0.47-0.87)) were less likely to have asthma remission. Factors related to a higher likelihood of remission of allergic rhinitis were no asthma at baseline, age ≥ 58 years in RHINE III, allergic rhinitis onset after 12 years of age, living in rural areas as a child, having only a primary school education and not being pregnant. Conclusion: Clinical remission was found in almost one-half of those with asthma and one-third of persons with allergic rhinitis. Coexisting allergic symptoms were associated with less clinical asthma remission. Age, asthma symptoms and environmental factors in childhood, such as living in a rural area, were found to influence the clinical remission of allergic rhinitis.

Asthma, allergic rhinitis and atopic dermatitis in association with home environment - The RHINE study.

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.

Long-term air pollution exposure, greenspace and health-related quality of life in the ECRHS study.

BACKGROUND: Associations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status. OBJECTIVE: To assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations. METHODS: The study was based on the participants in the second (2000-2002, n = 6542) and third (2011-2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO2, PM2.5 and PM10 annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status. RESULTS: The mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO2, PM2.5 and PM10 concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were -0.69 [-1.23; -0.15], -1.79 [-2.88; -0.70], -1.80 [-2.98; -0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status. CONCLUSION: European adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations.

The effect of farming environment on asthma; time dependent or universal?

The increasing prevalence of asthma is linked to westernization and urbanization. Farm environments have been associated with a lower risk of asthma development. However, this may not be universal, as the association differs across birth cohorts and farming methods. The aim of this study was to investigate the associations of farm upbringing with asthma in different generations and at different times in history. The study population consisted of three generations: 13,868 subjects participating in the ECRHS in 2010, their 9,638 parents, and their 8,885 offspring participating in RHINESSA in 2013. Information on place of upbringing and self-reported ever asthma was provided via questionnaires. Logistic regression was performed including subgroup analysis stratified by generation and birthyear into ten-year-intervals. The prevalence of asthma increased from 8% among grandparents to 13% among parents and to 18% among offspring. An overall analysis showed an inverse association of farm upbringing on the risk of asthma (OR = 0.64; 95%CI 0.55-0.74). Subgroup analysis stratified into ten-year-intervals showed a tendency towards a more pronounced inverse association between growing up on a farm and asthma among subjects born in the 1940s (0.74; 0.48-1.12), 1950s (0.70; 0.54-0.90) and 1960s (0.70; 0.52-0.93). For subjects born in 1970 and thereafter this association appeared less consistent. While growing up on a farm was associated with a reduced risk of developing asthma in participants born between 1945-1999, this was mainly driven by generations born from 1945 to 1973.

Cohort profile: the multigeneration Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort.

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.