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.

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.

Parental Prepuberty Overweight and Offspring Lung Function.

In a recent study we found that fathers' but not mothers' onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring's adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents' overweight on adult offspring's lung function within the paternal and maternal lines. We included 929 offspring (aged 18-54, 54% daughters) of 308 fathers and 388 mothers (aged 40-66). Counterfactual-based multi-group mediation analyses by offspring's sex (potential moderator) were used, with offspring's prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers' overweight before puberty had a negative indirect effect, mediated through sons' height, on sons' forced expiratory volume in one second (FEV1) (beta (95% CI): -144 (-272, -23) mL) and forced vital capacity (FVC) (beta (95% CI): -210 (-380, -34) mL), and a negative direct effect on sons' FVC (beta (95% CI): -262 (-501, -9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers' overweight before puberty had neither direct nor indirect effects on offspring's lung function. Fathers' overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons' adult height but not through sons' prepubertal overweight.

Does parental farm upbringing influence the risk of asthma in offspring? A three-generation study.

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.

FEV1 decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort.

BACKGROUND: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies. OBJECTIVE: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort. METHODS: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline. RESULTS: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.

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.

Asthma and selective migration from farming environments in a three-generation cohort study.

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.

Critical age windows in the impact of lifetime smoking exposure on respiratory symptoms and disease among ever smokers.

BACKGROUND: Despite extensive knowledge of smoking effects on respiratory disease, there is no study including all age windows of exposure among ever smokers. The objective of this study was to assess the effects from smoking exposure in utero, early childhood, adolescence and adulthood on respiratory health outcomes in adult male and female ever smokers. METHODS: Respiratory health outcomes were assessed in 10,610 participants of the European Community Respiratory Health Survey (ECRHS) I who reported a history of ever smoking by questionnaire. The associations of maternal smoking in utero, maternal smoking during childhood, age of smoking debut and pack-years of smoking with respiratory symptoms, obstructive diseases and bronchial hyperreactivity were analysed using generalized linear regression, non-linearity between age of smoking debut and outcomes were assessed by Generalized additive mixed models. RESULTS: Respiratory symptoms and asthma were more frequent in adults if their mother smoked during pregnancy, and, in men, also if mother smoked in childhood. Wheeze and ≥3 respiratory symptoms declined with later smoking debut among women [≤10 years: OR = 3.51, 95% CI 1.26, 9.73; 11-12 years: 1.57[1.01-2.44]; 13-15 years: 1.11[0.94-1.32] and ≤10 years: 3.74[1.56-8.83]; 11-12 years: 1.76[1.19-2.56]; 13-15 years: 1.12[0.94-1.35], respectively]. Effects of increasing number of packyears were pronounced in women (Chronic Obstructive Pulmonary Disease (COPD): OR/10 packyears women: 1.33 [1.18, 1.50], men: 1.14 [1.04, 1.26] pinteraction = 0.01). CONCLUSIONS: Among ever smokers, smoking exposure in each stage of the lifespan show persistent harmful effects for adult respiratory health, while women appeared to be more vulnerable to an early age of smoking debut and amount of smoking in adulthood.

Zoonotic helminth exposure and risk of allergic diseases: A study of two generations in Norway.

BACKGROUND: Animal and human studies indicate that definitive host helminth infections may confer protection from allergies. However, zoonotic helminths, such as Toxocara species (spp.), have been associated with increased allergies. OBJECTIVE: We describe the prevalence of Toxocara spp. and Ascaris spp. seropositivity and associations with allergic diseases and sensitization, in 2 generations in Bergen, Norway. METHODS: Serum levels of total IgG4, anti-Toxocara spp. IgG4 and Ascaris spp. IgG4 were established by ELISA in 2 cohorts: parents born 1945-1972 (n = 171) and their offspring born 1969-2003 (n = 264). Allergic outcomes and covariates were recorded through interviews and clinical examinations including serum IgEs and skin prick tests. RESULTS: Anti-Ascaris spp. IgG4 was detected in 29.2% of parents and 10.3% of offspring, and anti-Toxocara spp. IgG4 in 17.5% and 8.0% of parents and offspring, respectively. Among offspring, anti-Toxocara spp. IgG4 was associated with pet keeping before age 15 (OR = 6.15; 95% CI = 1.37-27.5) and increasing BMI (1.16[1.06-1.25] per kg/m2 ). Toxocara spp. seropositivity was associated with wheeze (2.97[1.45- 7.76]), hayfever (4.03[1.63-9.95]), eczema (2.89[1.08-7.76]) and cat sensitization (5.65[1.92-16.6]) among offspring, but was not associated with allergic outcomes among parents. Adjustment for childhood or current pet keeping did not alter associations with allergies. Parental Toxocara spp. seropositivity was associated with increased offspring allergies following a sex-specific pattern. CONCLUSIONS & CLINICAL RELEVANCE: Zoonotic helminth exposure in Norway was less frequent in offspring than parents; however, Toxocara spp. seropositivity was associated with increased risk of allergic manifestations in the offspring generation, but not among parents. Changes in response to helminth exposure may provide insights into the increase in allergy incidence in affluent countries.

Functional Gastrointestinal Symptoms Are Associated with Higher Serum Total IgE Levels, but Less Atopic Sensitization.

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

Asthma and Wheeze Prevalence among Nursing Professionals in Western Japan: A Cross-Sectional Study.

Although adult asthma is attributable to occupational factors, few reports are available on asthma prevalence among health care workers in Japan. The objective of this study was to estimate the prevalence of asthma and wheeze among Japanese nursing professionals. A cross-sectional study was conducted by postal survey using a translated version of the European Community Respiratory Health Survey questionnaire from April to June 2013. The analysis included 4634 nursing professionals (257 men and 4377 women) and the overall response rate was 84.8%. The prevalence of current asthma and wheeze were 10.7% (95% confidence interval (CI), 9.9%-11.7%) and 15.6% (95% CI, 14.5%-16.6%), respectively. More than one year of work experience as a nursing professional and more than one year of experience with bed-making tasks were associated with odds ratios (ORs) of 1.95 (95% CI, 1.12-3.39) and 1.64 (95% CI, 1.15-2.23) for wheeze, respectively. Current smoking was significantly associated with the presence of wheeze, with ORs of 2.27 for men (95% CI, 1.11-4.64) and 2.01 for women (95% CI, 1.54-2.64). Among female nurses, latex allergy was associated with wheeze (OR, 1.87; 95% CI, 1.56-2.23), as was body mass index ≥30 (OR, 2.76; 95% CI, 1.65-4.62). This study has provided the prevalence of asthma and wheeze among Japanese nursing professionals. Employment period, bed-making tasks, latex allergy, obesity, and smoking may be risk factors for prevalent wheeze among nursing professionals.

Asthma under/misdiagnosis in primary care setting: an observational community-based study in Italy.

BACKGROUND: Published data suggest that asthma is significantly under/misdiagnosed. The present community-based study performed in Italy aims at investigating the level of asthma under/misdiagnosis among patients referring to the General Practitioner (GP) for respiratory symptoms and undergoing Inhaled corticosteroids. METHODS: A sub-analysis of a previously published observational cross-sectional study has been provided. It included subjects registered in the GP databases with at least three prescriptions of inhaled or nebulised corticosteroids during the 12 months preceding the start of the study. All subjects, independently of the diagnosis, were invited to visit their GP's office for a standardised interview and to fill the European Community Respiratory Health Survey (ECRHS) questionnaire. RESULTS: The studies involved 540 GPs in most of the Italian regions and 2090 subjects (mean age 54.9 years, 54.1 % females) were enrolled. Among them 991 cases of physician-diagnosed asthma were observed while 1099 subjects received a diagnosis other than asthma (chronic obstructive pulmonary disease, chronic upper respiratory tract infections etc.). Among the lasts, the ECRHS questionnaire was suggestive for asthma diagnosis in 365 subjects (33.2 %). CONCLUSIONS: The data suggest that there is still a large under/misdiagnosis of asthma in the Italian primary care setting, despite the spread of GINA guidelines nearly 20 years before this study. A validated tool like the ECRHS questionnaire has detected a considerable proportion of potentially asthmatic patients who should be addressed to lung function assessment to confirm the diagnosis. Further educational efforts directed to the GPs are needed to improve their diagnosis of asthma (SAM104964).

House dust-mite allergen exposure is associated with serum specific IgE but not with respiratory outcomes.

Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunologic response to dust-mite allergens in those who are IgE sensitized to house dust-mite. Mattress house dust-mite concentrations were measured in a population-based sample of 2890 adults aged between 27 and 56 years living in 22 centers in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust-mite concentrations, adjusting for individual and household confounders. There was no overall association of respiratory outcomes with measured house dust-mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician-diagnosed asthma. However, there was a positive association of high serum specific IgE levels to HDM (>3.5 kUA /l) with mattress house dust-mite concentrations and a negative association of sensitization to cat with increasing house dust-mite concentrations. In conclusion, there was no evidence that respiratory symptoms in adults were associated with exposure to house dust-mite allergen in the mattress, but an association of house mite with strong sensitization was observed.

Can an airway challenge test predict respiratory diseases? A population-based international study.

BACKGROUND: Evidence on the longitudinal association of airway responsiveness with respiratory diseases is scarce. The best indicator of responsiveness is still undetermined. OBJECTIVE: We investigated the association of airway responsiveness with the incidence of asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis. METHODS: We studied 3851 subjects who underwent spirometry and methacholine challenge tests both at baseline (1991-1993), when they were 20 to 44 years old, and at follow-up (1999-2002) in the European Community Respiratory Health Survey. Airway responsiveness was defined based on the methacholine dose-response slope on both occasions. Incidence rate ratios for the association of airway responsiveness with disease occurrence were computed by using Poisson regression. RESULTS: With respect to reference (slope of the fourth quintile or greater), subjects with the greatest degree of airway responsiveness (slope less than the first quintile) showed the greatest risk of developing asthma, COPD, and allergic rhinitis (incidence rate ratios of 10.82, 5.53, and 4.84, respectively; all P < .01). A low slope predicted disease occurrence, even in subjects who did not reach a 20% decrease in FEV1 at the cumulative dose of 1 mg of methacholine (PD20 >1 mg). A decrease in slope over time was an independent predictor of disease risk. CONCLUSION: Airway responsiveness predicted new-onset asthma, COPD, and allergic rhinitis. Our study supports the use of a continuous noncensored indicator of airway responsiveness, such as the slope of the methacholine dose-response curve, in clinical practice and research because it showed clear advantages over PD20.