Gas cooking indoors and respiratory symptoms in the ECRHS cohort.

BACKGROUND: Gas cooking is an important source of indoor air pollutants, and there is some limited evidence that it might adversely be associated with respiratory health. Using repeated cross-sectional data from the multi-centre international European Community Respiratory Health Survey, we assessed whether adults using gas cookers have increased risk of respiratory symptoms compared to those using electric cookers and tested whether there was effect modification by a priori selected factors. METHODS: Data on respiratory symptoms and gas cooking were collected from participants at 26-55 and 38-67 years (median time between examinations 11.4 years) from interviewer-led questionnaires. Repeated associations between gas cooking (versus electric) and respiratory symptoms were estimated using multivariable mixed-effects logistic regression models adjusted for age, sex, study arm, smoking status, education level, and included random intercepts for participants within study centres. Analyses were repeated using a 3-level variable for type of cooker and gas source. Effect modification by ventilation habits, cooking duration, sex, age atopy, asthma, and study arm were examined. RESULTS: The sample included 4337 adults (43.7% males) from 19 centres in 9 countries. Gas cooking increased the risk of "shortness of breath whilst at rest" (OR = 1.38; 95%CI: 1.06-1.79) and "wheeze with breathlessness" (1.32; 1.00-1.74). For several other symptoms, effect estimates were larger in those who used both gas hobs and ovens, had a bottled gas source and cooked for over 60 min per day. Stratifying results by sex and age found stronger associations in females and younger adults. CONCLUSION: This multi-centre international study, using repeat data, suggested using gas cookers in the home was more strongly associated than electric cookers with certain respiratory symptoms in adults. As gas cooking is common, these results may play an important role in population respiratory health.

Spirometric patterns in young and middle-aged adults: a 20-year European study.

BACKGROUND: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). METHODS: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/FVC≥LLN and FVC<10th percentile, obstructive if FEV1/FVC

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.

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.

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.

Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort.

BACKGROUND: The prevalence of obstructive sleep apnea is higher in women after menopause. This is suggested to be a result of an altered sex hormone balance but has so far not been confirmed in a population-based study. OBJECTIVE: To investigate whether serum concentration of estrogens and progesterone are associated with the prevalence of sleep apnea symptoms in middle-aged women of the general population. METHODS: We analyzed data from 774 women (40-67 years) from 15 study centers in seven countries participating in the second follow-up of the European Community Respiratory Health Survey (2010-2012). Multiple logistic regression models were fitted with self-reported symptoms of sleep apnea as outcomes and serum concentrations of various estrogens and progesterone as predictors. All analyses were adjusted for relevant covariates including age, BMI, education, study center, smoking habits, and reproductive age. RESULTS: Among all included women, a doubling of serum concentrations of estrone and progesterone was associated with 19% respectively 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of 17ß-estradiol, estrone and estrone 3-sulfate was associated with 18%, 23% and 17% decreased odds of breathing irregularly, and a doubling of the progesterone concentration was further associated with 12% decreased odds of waking up suddenly with a chocking sensation. Other evaluated associations were not statistically significant. CONCLUSIONS: Middle-aged women with low serum estrogen and progesterone levels are more likely to snore and report symptoms of obstructive sleep apnea.

Breathlessness across generations: results from the RHINESSA generation study.

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.

Ultraviolet radiation as a predictor of sex hormone levels in postmenopausal women: A European multi-center study (ECRHS).

BACKGROUND: Solar ultraviolet radiation (UVR) affects the body through pathways that exhibit positive as well as negative health effects such as immunoregulation and vitamin D production. Different vitamin D metabolites are associated with higher or lower concentrations of estrogens and may thus alter the female sex hormone balance. OBJECTIVE: To study whether exposure to UVR, as a modifiable lifestyle factor, is associated with levels of sex hormones (17ß-estradiol, estrone, estrone 3-sulfate, testosterone, dehydroepiandrosterone sulfate), gonadotropins (follicle stimulating hormone, luteinizing hormone) as well as sex hormone binding globulin in postmenopausal women, and thus investigate whether managing UVR exposure can influence the hormone balance, with potential benefits for the biological aging process. METHODS: The study included 580 postmenopausal women from six European countries, participating in the European Community Respiratory Health Survey (2010-2014). Average UVR exposure during the month before blood sampling was estimated based on personal sun behavior and ambient levels. Hormone concentrations were measured in serum using state-of-the-art methods. Subsequently we applied linear mixed-effects models, including center as random intercept, hormone concentrations (one at a time) as outcome and UVR, age, skin type, body mass index, vitamin D from dietary sources, smoking, age at completed full-time education and season of blood sampling as fixed-effect predictors. RESULTS: One interquartile range increase in UVR exposure was associated with decreased levels of 17ß-estradiol (-15.6 pmol/L, 95 % Confidence Interval (CI): -27.69, -3.51) and estrone (-13.36 pmol/L, 95 % CI: -26.04, -0.68) and increased levels of follicle stimulating hormone (9.34IU/L, 95 % CI: 2.91, 15.77) and luteinizing hormone (13.86 IU/daL, 95 % CI: 2.48, 25.25). CONCLUSIONS: Exposure to UVR is associated with decreased estrogens and increased gonadotropins in postmenopausal women, a status associated with osteoporosis, lung function decline and other adverse health effects. This study indicates that managing UVR exposure has potential to influence the hormone balance and counteract adverse health conditions after menopause.

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

Low serum DHEA-S is associated with impaired lung function in women.

BACKGROUND: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS). METHODS: Lung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999-2002 and in 2010-2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999-2002 with incidence of restrictive pattern and airflow limitation in 2010-2013 were also assessed. FINDINGS: Women with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14). INTERPRETATION: Low DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health. FUNDING: EU H2020, grant agreement no.633212.

Residential surrounding greenspace and age at menopause: A 20-year European study (ECRHS).

BACKGROUND: Menopause is associated with a number of adverse health effects and its timing has been reported to be influenced by several lifestyle factors. Whether greenspace exposure is associated with age at menopause has not yet been investigated. OBJECTIVE: To investigate whether residential surrounding greenspace is associated with age at menopause and thus reproductive aging. METHODS: This longitudinal study was based on the 20-year follow-up of 1955 aging women from a large, population-based European cohort (ECRHS). Residential surrounding greenspace was abstracted as the average of satellite-based Normalized Difference Vegetation Index (NDVI) across a circular buffer of 300 m around the residential addresses of each participant during the course of the study. We applied mixed effects Cox models with centre as random effect, menopause as the survival object, age as time indicator and residential surrounding greenspace as time-varying predictor. All models were adjusted for smoking habit, body mass index, parity, age at menarche, ever-use of contraception and age at completed full-time education as socio-economic proxy. RESULTS: An increase of one interquartile range of residential surrounding greenspace was associated with a 13% lower risk of being menopausal (Hazard Ratio: 0.87, 95% Confidence Interval: 0.79-0.95). Correspondingly the predicted median age at menopause was 1.4 years older in the highest compared to the lowest NDVI quartile. Results remained stable after additional adjustment for air pollution and traffic related noise amongst others. CONCLUSIONS: Living in greener neighbourhoods is associated with older age at menopause and might slow reproductive aging. These are novel findings with broad implications. Further studies are needed to see whether our findings can be replicated in different populations and to explore the potential mechanisms underlying this association.

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.

Second-hand smoke exposure in adulthood and lower respiratory health during 20 year follow up in the European Community Respiratory Health Survey.

BACKGROUND: Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. METHODS: We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. RESULTS: Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (ß: - 49 ml; 95%-CI: -132, 35 for FEV1 and ß: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. CONCLUSION: Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.

Exogenous female sex steroids may reduce lung ageing after menopause: A 20-year follow-up study of a general population sample (ECRHS).

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

Leisure-time vigorous physical activity is associated with better lung function: the prospective ECRHS study.

OBJECTIVE: We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort. METHODS: FEV1 and FVC were measured in 3912 participants at 27-57 years and 39-67 years (mean time between examinations=11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity ≥2 times and ≥1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV1 and FVC. RESULTS: Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline. CONCLUSION: Leisure-time vigorous physical activity was associated with higher FEV1 and FVC over a 10-year period among current smokers, but not with FEV1 and FVC decline.

Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study.

BACKGROUND: Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population. METHODS: We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow-up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4-6 years in the Tucson Children's Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function. FINDINGS: After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV1 at baseline, we found an inverse association between CC16 concentration and decline in FEV1 in adults in TESAOD (4·4 mL/year additional FEV1 decline for each SD decrease in baseline CC16 concentration, p=0·0014) and ECRHS-Sp (2·4 mL/year, p=0·023); the effect in SAPALDIA was marginal (4·5 mL/year, p=0·052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV1 to forced expiratory volume [FEV1/FVC] less than 70% plus FEV1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV1 deficit of 68 mL up to age 16 years (p=0·0001), which was confirmed in children who had never smoked by age 16 years (-71 mL, p<0·0001). INTERPRETATION: Low concentrations of CC16 in serum are associated with reduced lung function in childhood, accelerated lung function decline in adulthood, and development of moderate airflow limitation in the general adult population. FUNDING: National Heart, Lung, and Blood Institute and European Union Seventh Framework Programme.

The relation of circulating YKL-40 to levels and decline of lung function in adult life.

BACKGROUND: YKL-40 is a chitinase-like protein that, in cross-sectional clinical studies, has been associated with severe asthma and COPD in smokers. AIM: To determine the longitudinal relation of circulating YKL-40 to levels and decline of lung function in the general population. METHODS: We used longitudinal data from up to 13 surveys from the population-based TESAOD study which was conducted in Tucson, Arizona between 1972 and 1996. In cross-sectional analyses, we also used data from 3 Spanish centers of the multicenter ECRHS study (ECRHS-Sp). Serum YKL-40 was measured at baseline in TESAOD and in survey 2 in ECRHS-Sp using ELISAs. Multivariate linear regression was used to test associations of serum YKL-40 to concomitant lung function. In TESAOD, random coefficients models were used to test associations of serum YKL-40 to subsequent decline of lung function. RESULTS: Data on YKL-40 and lung function were available from 1088 TESAOD and 854 ECRHS-Sp adult participants (59% and 51% females; respectively). In adjusted multivariate meta-analyses, being in the highest YKL-40 quartile was associated cross-sectionally with significant deficits in FEV1 and FVC %predicted. In adjusted longitudinal analyses, TESAOD participants in the top YKL-40 quartile had an FEV1 decline that was 5 ml/yr (p = 0.05) faster than subjects in the third quartile, 5 ml/yr (p = 0.02) faster than subjects in the second quartile, and 10 ml/yr (p < 0.001) faster than subjects in the lowest YKL-40 quartile. These longitudinal effects were particularly strong in smokers and absent in never smokers. After adjusting for covariates, as compared with the other three quartiles combined, the top YKL-40 quartile was associated with a 9 ml/yr (p = 0.001) faster FEV1 decline among smokers, while no significant effects were found among never smokers (2 ml/yr, p = 0.35). CONCLUSIONS: Circulating YKL-40 is associated with levels and decline of lung function in the general population and may be a biomarker of susceptibility to the long-term effects of cigarette smoking.

Body mass index, weight gain, and other determinants of lung function decline in adult asthma.

BACKGROUND: Little is known about factors associated with lung function decline in asthma. OBJECTIVE: To identify the determinants of FEV(1) decline in adults with asthma with and without airflow obstruction at baseline. METHODS: An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV(1) decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV(1)/forced vital capacity < 0.70) at baseline. RESULTS: In the group of individuals without airflow obstruction (n = 544), a faster FEV(1) decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV(1) decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV(1) decline, whereas weight gain was not associated with decline. CONCLUSIONS: The detrimental effect of weight gain on FEV(1) decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma.

[Changes in the prevalence of asthma in the Spanish cohort of the European Community Respiratory Health Survey (ECRHS-II)]. / Cambios en la prevalencia de asma en la población española del Estudio de Salud Respiratoria de la Comunidad Europea (ECRHS-II).

OBJECTIVE: The rise in the prevalence of asthma in the second half of the 20th century has not been evenly distributed according to recent surveys. We assessed changes in the prevalence of asthma after a period of 9 to 10 years in a cohort of young adults in the Spanish arm of the European Community Respiratory Health Survey (ECRHS). MATERIAL AND METHODS: The ECRHS-II is a multicenter cohort study taking place in 27 centers around Europe, with Spanish centers located in Albacete, Barcelona, Galdakao, Huelva, and Oviedo. The ECRHS questionnaire was administered to individuals who had participated in the first phase of the survey; spirometry and methacholine challenge tests were also performed according to the published protocol. RESULTS: Among new smokers, the prevalence of wheezing in the last 12 months increased from 10% to 33%, while the frequency of phlegm production rose from 8% to 22% (P< .05). In ex-smokers, the prevalences of wheezing and phlegm production decreased from 21% to 12% and from 15% to 8%, respectively (P< .05). Symptom prevalences remained similar for never smokers, although the frequency of diagnosed asthma rose from 4% to 7% (P< .05). After adjusting for smoking, age, sex, and center, we found no significant differences in the frequency of symptoms or asthma, even when the phrase bronchial hyperreactivity was included in the definition. However, the rate of reported asthma rose annually by 0.34% (95% confidence interval [CI], 0.20%-0.48%), while diagnosed asthma rose by 0.26% (95% CI, 0.13%-0.39%) and treated asthma by 0.16% (95% CI, 0.07%-0.25%). CONCLUSIONS: Increased prevalence rates of asthma diagnosis and treatment have been detected, but the rates of reported symptoms have remained similar, consistent with the assumption that more persons are being classified as asthmatics.