Describing the status of reproductive ageing simply and precisely: A reproductive ageing score based on three questions and validated with hormone levels

Equation 6. Quadratic logistic function approximating the function mu(B)(with age in years). Equation 1. Proportion of women who have regular menstruation for each number of reported menstruations in the last year(with period = number of periods per year, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months" and z = number of women answering "No, my periods have stopped", e.g. x(11) = number of women reporting regular menstruation among those who report 11 menstruations in the last 12 months). Equation 5. Biquadratic exponential function mu(A)depending of the number of periods. Equation 3. Age modification by smoking and oophorectomy. Equation 2. Proportion of women whose menstruations have already stopped, for each reported year of age(with age = age in years, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months", z = number of women answering "No, my periods have stopped", e.g. x(40) = number of women reporting regular menstruations among those who are 40 years old). Equation 7. Final formula to calculate the reproductive ageing score (RAS)(with period being the number of periods per year and age as the age in years, modified according to smoking status and oophorectomy). Objective Most women live to experience menopause and will spend 4-8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause;categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers. Methods Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17 beta-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC). Results The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90-0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83-0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women. Conclusions: The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials. Equation 4. The reproductive ageing score as an aggregation function of mu(A)and mu(B)

Early life exposures contributing to accelerated lung function decline in adulthood – a follow-up study of 11,000 adults from the general population

Background We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods Participants (20–68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991–2013 and 1997–2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation Mothers’ smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding 10.13039/501100007601European Union's Horizon 2020; 10.13039/501100005416Research Council of Norway; 10.13039/501100002341Academy of Finland; University Hospital Oulu; 10.13039/501100008530European Regional Development Fund; 10.13039/501100004837Spanish Ministry of Science and Innovation; 10.13039/501100002809Generalitat de Catalunya

A three-generation study on the association of tobacco smoking with asthma

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

The Exposome Approach in Allergies and Lung Diseases: Is It Time to Define a Preconception Exposome?

Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept

The epidemiology of breathlessness

Breathlessness is a prevalent issue reported in the general population, increasing with advancing age. A variety of analyses have been undertaken to characterise the epidemiological characteristics and demographic patterns of this important symptom. There are several methodological factors that should be considered when assessing the available data in this area, and overall, there remains a paucity of high-quality and robust data. The aim of this chapter is to describe findings from the available published work in this field and to highlight the different approaches that have been used to assess this issue. The chapter addresses differences among populations, risk factors and changes in breathlessness across the lifespan. The chapter also covers health-related events that are associated with breathlessness and concludes by addressing unmet needs and future research priorities

Influence of farm environment on asthma during the life course:a population-based birth cohort study in Northern Finland

Abstract We investigated the influence of a farming environment on asthma at three time points from birth to 46 years using the Northern Finland Birth Cohort 1966 (n = 10,926). The prevalence of asthma was investigated by postal questionnaires at 14, 31 and 46 years of age. Exposure to a farming environment was assessed by a postal questionnaire at birth and at 31 and 46 years of age. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) for the prevalence of asthma were obtained from multinomial logistic regression, stratified by sex. Being born in a farmer family was potentially causally associated with lower risk of asthma in males at 31 years of age (OR 0.56, 95% CI 0.37, 0.85) and in females at 46 years of age (OR 0.64, 95% CI 0.44, 0.95). Working as a farmer was not associated with asthma. Exposure to a farming environment in childhood may have a lifelong impact on developing asthma from birth through young adulthood and until middle age, indicating that ‘immune deviation’ may persist throughout life

Interaction between asthma and smoking increases the risk of adult airway obstruction

The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy. In the European Community Respiratory Health Survey, 15 668 persons aged 20-56 years underwent spirometry in 1991-1993 and 9 years later (n=8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (>10 years of age) and late-onset (<10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates. Interaction of asthma with smoking was expressed as relative excess risk due to interaction (RERI). A 20-fold increase in adult airway obstruction was found among those with early-onset asthma independently of smoking status (never-smokers: OR 21.0, 95% CI 12.7-35; current smokers: OR 23.7, 95% CI 13.9-40.6). Late-onset asthma was associated with airway obstruction, with a stronger association among current smokers (OR 25.6, 95% CI 15.6-41.9) than among never-smokers (OR 11.2, 95% CI 6.8-18.6) (RERI 12.02, 95% CI 1.96-22.07). Stratifying by atopy, the association between smoking and asthma was most pronounced among nonatopics. Early- and late-onset asthma were associated with 10-20-fold increased risk of adult airway obstruction. Smoking increased the risk of adult airway obstruction in subjects with asthma onset after age 10 years. Investigation of measures potentially preventive of chronic obstructive pulmonary disease development following asthma is urgently needed