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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.

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.

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.

OBJECTIVES: To compare the prevalence of different insomnia subtypes among middle-aged adults from Europe and Australia and to explore the cross-sectional relationship between insomnia subtypes, respiratory symptoms and lung function. DESIGN: Cross-sectional population-based, multicentre cohort study. SETTING: 23 centres in 10 European countries and Australia. METHODS: We included 5800 participants in the third follow-up of the European Community Respiratory Health Survey III (ECRHS III) who answered three questions on insomnia symptoms: difficulties falling asleep (initial insomnia), waking up often during the night (middle insomnia) and waking up early in the morning and not being able to fall back asleep (late insomnia). They also answered questions on smoking, general health and chronic diseases and had the following lung function measurements: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio. Changes in lung function since ECRHS I about 20 years earlier were also analysed. MAIN OUTCOME MEASURES: Prevalence of insomnia subtypes and relationship to respiratory symptoms and function. RESULTS: Overall, middle insomnia (31.2%) was the most common subtype followed by late insomnia (14.2%) and initial insomnia (11.2%). The highest reported prevalence of middle insomnia was found in Iceland (37.2%) and the lowest in Australia (22.7%), while the prevalence of initial and late insomnia was highest in Spain (16.0% and 19.7%, respectively) and lowest in Denmark (4.6% and 9.2%, respectively). All subtypes of insomnia were associated with significantly higher reported prevalence of respiratory symptoms. Only isolated initial insomnia was associated with lower FEV1, whereas no association was found between insomnia and low FEV1/FVC ratio or decline in lung function. CONCLUSION: There is considerable geographical variation in the prevalence of insomnia symptoms. Middle insomnia is most common especially in Iceland. Initial and late ins

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

BACKGROUND: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). METHODS: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. RESULTS: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV1 declines. We found no association between weight change profiles and FEV1/FVC decline. CONCLUSION: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life.

BACKGROUND: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. OBJECTIVE: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. METHODS: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. RESULTS: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. CONCLUSION: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health.

Supplement: 63. Meeting Abstract: PA1978.

BACKGROUND: Smoking is the main risk factor for most of the leading causes of death. Cessation is the single most important step that smokers can take to improve their health. With the aim of informing policy makers about decisions on future tobacco control strategies, we estimated time and age trends in smoking cessation in Europe between 1980 and 2010. METHODS: Data on the smoking history of 50,228 lifetime smokers from 17 European countries were obtained from six large population-based studies included in the Ageing Lungs in European Cohorts (ALEC) consortium. Smoking cessation rates were assessed retrospectively, and age trends were estimated for three decades (1980-1989, 1990-1999, 2000-2010). The analyses were stratified by sex and region (North, East, South, West Europe). RESULTS: Overall, 21,735 subjects (43.3%) quit smoking over a total time-at-risk of 803,031 years. Cessation rates increased between 1980 and 2010 in young adults (16-40 years), especially females, from all the regions, and in older adults (41-60 years) from North Europe, while they were stable in older adults from East, South and West Europe. In the 2000s, the cessation rates for men and women combined were highest in North Europe (49.9 per 1,000/year) compared to the other regions (range: 26.5-32.7 per 1,000/year). A sharp peak in rates was observed for women around the age of 30, possibly as a consequence of pregnancy-related smoking cessation. In most regions, subjects who started smoking before the age of 16 were less likely to quit than those who started later. CONCLUSIONS: Our findings suggest an increasing awareness on the detrimental effects of smoking across Europe. However, East, South and West European countries are lagging behind North Europe, suggesting the need to intensify tobacco control strategies in these regions. Additional efforts should be made to keep young adolescents away from taking up smoking, as early initiation could make quitting more challenging during later li

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

BACKGROUND: Self-report questionnaires are commonly used in epidemiology, but may be susceptible to misclassification, especially if answers are given on behalf of others, e.g. children or parents. The aim was to determine agreement and analyse predictors of disagreement in parents' reports of offspring asthma, and in offspring reports of parents' asthma. METHODS: In the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study, 6752 offspring (age range 18-51 years) and their parents (age range 39-66 years) reported their own and each other's asthma status. Agreement between asthma reports from offspring and parents was determined by calculating sensitivity, specificity, positive and negative predictive value and Cohen's kappa. The participants' own answers regarding themselves were defined as the gold standard. To investigate predictors for disagreement logistic regression analyses were performed to obtain odds ratios (OR) with 95% confidence intervals (CI) for sex, smoking status, education, comorbidity and severity of asthma. RESULTS: Agreement was good for parental report of offspring early onset asthma (< 10 years, Cohen's kappa 0.72) and moderate for offspring later onset asthma (Cohen's kappa 0.46). Specificity was 0.99 for both, and sensitivity was 0.68 and 0.36, respectively. For offspring report of maternal and paternal asthma the agreement was good (Cohen's kappa 0.69 and 0.68), specificity was 0.96 and 0.97, and sensitivity was 0.72 and 0.68, respectively. The positive predictive value (PPV) was lowest for offspring report of maternal asthma (0.75), and highest for parents' report of early onset asthma in the offspring (0.83). The negative predictive value (NPV) was high for all four groups (0.94-0.97). In multivariate analyses current smokers (OR = 1.46 [95% CI 1.05, 2.02]) and fathers (OR = 1.31 [95% CI 1.08, 1.59]) were more likely to report offspring asthma incorrectly. Offspring wheeze was associated with reporting pare

Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

The early life environment appears to have a persistent impact on asthma risk. We hypothesize that environmental factors related to rural life mediate lower asthma prevalence in rural populations, and aimed to investigate an urban-rural gradient, assessed by place of upbringing, for asthma. The population-based Respiratory Health In Northern Europe (RHINE) study includes subjects from Denmark, Norway, Sweden, Iceland and Estonia born 1945-1973. The present analysis encompasses questionnaire data on 11,123 RHINE subjects. Six categories of place of upbringing were defined: farm with livestock, farm without livestock, village in rural area, small town, city suburb and inner city. The association of place of upbringing with asthma onset was analysed with Cox regression adjusted for relevant confounders. Subjects growing up on livestock farms had less asthma (8%) than subjects growing up in inner cities (11%) (hazard ratio 0.72 95% CI 0.57-0.91), and a significant urban-rural gradient was observed across six urbanisation levels (p = 0.02). An urban-rural gradient was only evident among women, smokers and for late-onset asthma. Analyses on wheeze and place of upbringing revealed similar results. In conclusion, this study suggests a protective effect of livestock farm upbringing on asthma development and an urban-rural gradient in a Northern European population.

BackgroundIt has been suggested that gastroesophageal reflux disease (GERD) is a risk factor for developing rhinitis/rhinosinusitis, but data are lacking. This is a prospective 10-year follow-up study of a large multicenter cohort from Northern Europe, evaluating the relationship between nocturnal GERD and noninfectious rhinitis (NIR). MethodsThe study comprised 5417 subjects born between 1945 and 1973, who answered a questionnaire in 1999-2001 and again in 2010-2012. Noninfectious rhinitis was defined as having nasal obstruction, secretion, and/or sneezing without having the common cold. Odds ratios for developing NIR in relation to age, gender, BMI, smoking, asthma, and nocturnal GERD were calculated. ResultsDuring the 10-year observation period, 1034 subjects (19.1%) developed NIR. Subjects reporting nocturnal gastroesophageal reflux in both 1999 and 2010 had more NIR in 2010 (2.8% vs 1.2%, P<0.001). There was a significant dose-response relationship between the number of reflux episodes/week in 1999 and the risk of having NIR in 2010, P=0.02. In the multiple regression adjusted for age, gender, BMI, tobacco smoke, and asthma, those with nocturnal GERD in 1999 (3 episodes of nocturnal gastroesophageal reflux symptoms per week) had an OR of 1.6 (95% CI 1.0-2.5, P=0.03) to develop NIR in 2010. Smoking was associated both with an increased risk of developing NIR (30.7% vs 24.0%, P<0.001) and with the development of nocturnal GERD. ConclusionThis large, population-based, 10-year study indicates that nocturnal GERD was a risk factor for noninfectious rhinitis/rhinosinusitis. GERD should therefore be considered in patients with rhinitis of known and unknown origin.

Investigations on bioefficacy of parasitoids and microbial agents against potato tubermoth (PTM), Phthorimaea operculella (Zeller) (Lepidoptcra: Gelechiidae) were carried out under field and storage conditions of potato during 1996-1997. The results showed that three sprays of endosulfan 0.05 per cent at 10 days interval proved to be the most effective and on par with four releases of Chelonus blackburni Cameron @ 15000 adults/ha/release at weekly interval,Copidosoma koehleri Blanchard @ 50000 adults/ha/lrelcase and Trichogramma chilonis Ishii @ 50000 adults/ha/releasc at weekly interval, and three sprays of Bacillus Thuringiensis Berliner @ 1 kg/ha at 10 days interval. Amongst the parasitoids, maximum parasitism was recovered through retrieval with C. blackburni (71.78 %), followed bye C. koehleri (69.39%) and T. chilonis (61.33%). Under storage conditions (Arnies), initial release of C. blackburni @ 2 adults/kg tubers recorded minimum tuber infestation (7.21 %) after 60 days.

Investigations on bioefficacy of parasitoids and microbial agents against potato tubermoth (PTM), Phthorimaea operculella (Zeller) (Lepidoptcra: Gelechiidae) were carried out under field and storage conditions of potato during 1996-1997. The results showed that three sprays of endosulfan 0.05 per cent at 10 days interval proved to be the most effective and on par with four releases of Chelonus blackburni Cameron @ 15000 adults/ha/release at weekly interval,Copidosoma koehleri Blanchard @ 50000 adults/ha/lrelcase and Trichogramma chilonis Ishii @ 50000 adults/ha/releasc at weekly interval, and three sprays of Bacillus Thuringiensis Berliner @ 1 kg/ha at 10 days interval. Amongst the parasitoids, maximum parasitism was recovered through retrieval with C. blackburni (71.78 %), followed bye C. koehleri (69.39%) and T. chilonis (61.33%). Under storage conditions (Arnies), initial release of C. blackburni @ 2 adults/kg tubers recorded minimum tuber infestation (7.21 %) after 60 days.