The SAPALDIA Cohort - 30 Years of Research for Better Health

21.7% of participants in the SAPALDIA4 health survey met the Swiss physical activity recommendations (2½ hours per week of moderate-intensity physical activity in the form of everyday activities or sport, or 1¼ hours of vigorous-intensity sport or physical activity). People who were severely overweight, over 75 years of age, smokers, and participants who lived alone spent more time sitting and less time doing light, moderate, and vigorous physical activity than participants who were of normal weight, between 52 and 64 years of age, non-smokers, and married. Participants living in French-speaking Switzerland were less likely to engage in intense physical activity than participants from German-speaking Switzerland. These results show that physical activity needs to be promoted among older people and specific subgroups in Switzerland (Aebi et al. 2020. Swiss Med Wkly).

Using SAPALDIA4 data, researchers were able to divide participants into three groups based on criteria relating to cardiovascular health, metabolism and physical activity: 30% of participants were classified as ‘in good health’, 29% as ‘in poor health’ and the third group as ‘at risk of poor health’. Participants classified as ‘in poor health’ have a lower health-related quality of life than participants ‘in good health’. This was particularly evident in the area of physical functioning. The results suggest that people with cardiovascular and metabolic problems, as well as those who are physically inactive, are an important target group for health promotion and maintaining well-being (Cerletti et al. 2020, Health Qual Life Outcomes).

Together with the European Community Respiratory Health Survey (ECRHS), it was shown that physical activity is associated with a reduced risk of developing lung impairment over a 10-year period. This finding underscores the importance of promoting physical activity among the population in order to improve long-term health and prevent disease (Carsin et al. 2020. Am J Epidemiol).

A dietary pattern that includes a high proportion of fruit, vegetables, nuts and fish, as well as the consumption of soups, water, tea and coffee, is associated with better lung function in SAPALDIA participants than a dietary pattern with a high proportion of proteins (such as meat, sausage, eggs), salty snacks and alcohol (Steinemann et al 2018. Respiration).

A healthy lifestyle (plenty of exercise, weight control, not smoking and low alcohol consumption) not only protects against chronic diseases, but also has a positive effect on the course of an existing chronic disease. However, the SAPALDIA data showed no improvement in lifestyle among men despite known hypertension or diabetes diagnoses. Recommendations for a healthy lifestyle are an important component of any treatment for diabetes and hypertension and must be emphasised, especially among men (Walther et al. 2017. Prev Med).

SAPALDIA also provided evidence that physical activity can alter the effect of air pollution on cardiovascular risk, which is determined by the stiffness of the arteries, in areas with low air pollution. Even a small amount of physical activity can reduce the negative effects of air pollution on vascular health (Endes et al. 2017. Int J Hyg Environ Health).

Not all exercise is the same, as the SAPALDIA data show. Leisure-time physical activity has a stronger effect on body weight than physical activity at work. This means that sport and regular running in your free time are good ways to keep weight gain in check (Wanner et al 2016. Prevent Med Rep).

The wall of the carotid artery tends to thicken with age and the arteries become stiffer. This ageing process cannot be completely prevented, even with regular exercise, but it can be slowed down (Caviezel et al. 2015. PLOSone; Endes et al. 2016. Eur J Epidemiol).

New research findings from SAPALDIA suggest that noise sensitivity is negatively associated with physical and psychological aspects of health-related quality of life. How sensitive people are to noise or disturbing sounds seems to be more relevant to the results than traffic noise pollution itself. This suggests that other sources of noise may also play a role in quality of life. In addition, personality traits appear to influence the impact of noise pollution on health-related quality of life. Traffic noise pollution itself appears to affect quality of life primarily in psychological aspects (Cerletti et al., 2020. Environ Int).

SAPALDIA researchers showed that both traffic noise levels and noise pollution are associated with the risk of developing depression, especially in people who do not get much exercise. The observed link between noise exposure and the associated annoyance, as well as the greater impact of noise annoyance on people with insufficient physical activity or excessive daytime sleepiness, shed light on the possible links between traffic noise, noise annoyance and mental health problems (Eze et al. 2020. Environ Int).

Thanks to calculation models, exposure to aircraft, rail and road traffic noise can be estimated for all addresses in Switzerland. SAPALDIA data has shown that increased traffic noise exposure at home is associated with an increased risk of obesity and a larger waist circumference. This could not be proven for other noise sources such as aircraft or railway noise (Foraster et al., 2018. Environ. Int.).

Results from the SAPALDIA study suggest that noise pollution can also influence the occurrence of respiratory symptoms. Noise levels and noise pollution both appear to exacerbate asthma in adults independently of each other. The physical and psychological effects of noise can thus have an impact on the respiratory tract and therefore appear to be relevant for the management of asthma (Eze et al. 2018. Environ. Int.).

Long-term exposure to railway noise, especially recurring night-time noise pollution, mainly associated with road noise, can affect arterial stiffness, as measured in the carotid artery. Arterial stiffness is an important indicator of cardiovascular disease (Foraster et al. 2017. Environ Health Perspect).

Traffic noise, especially road and aircraft noise, may be associated with an increased risk of developing type 2 diabetes mellitus. Researchers were able to demonstrate this using SAPALDIA data (Eze et al. 2017. Int J Epidemiol). Researchers also showed that long-term traffic noise at night has an effect on blood sugar control, especially in diabetics. This means that a doctor's recommendation to diabetics could be: close the window at night or sleep on the quieter side of your home (Eze et al. 2017. Int J Environ Res Public Health).

People who feel disturbed by aircraft, train and road noise at home exercise less regularly or go running less often. This observation can probably be explained by the fact that they sleep less well (Foraster et al., 2016. Environ Int).

Railway noise has an impact on blood pressure, especially when exposed to noise at night. Researchers demonstrated this in the SAPALDIA study. The effects of railway and traffic noise were particularly pronounced in people diagnosed with high blood pressure, cardiovascular disease or diabetes (Dratva et al. 2012. Environ Health Perspect).

In a SAPALDIA study, our researchers were able to show that noise pollution is linked to health-related quality of life. These findings underscore the importance of the environment for mental and physical health (Dratva et al. 2010. Qual Life Res).

Lung function is influenced by the environment and lifestyle. We were able to show that tobacco-related DNA methylation patterns in particular influence lung function. This demonstrates once again the harmfulness of smoking. The results will also be important for assessing the harmfulness of e-cigarettes (Imboden et al. 2019. Eur Respir J).

Does smoking play a role in the development of asthma in adults? Researchers were able to provide evidence for this as part of the GABRIEL project. Six studies participated in this project, and SAPALDIA was of course also involved. Through a genome-wide association study, researchers were able to show that there are gene variants on chromosomes 9 and 12 that are associated with both tobacco smoking and the development of asthma in adults (Vonk et al. 2017. Int J Hyg Environ Health).

It takes years for all traces of smoking to disappear completely and for the ECG profile of a person who has stopped smoking to resemble that of a person who has never smoked (Girard et al., 2016. Environ Res).

As part of the European EXPOsOMICS study, in which SAPALDIA participated, air pollution at home and in personalised environments (at work, on the move, etc.) was repeatedly measured in a group of SAPALDIA participants from Basel, among others. Researchers found that short-term personal exposure to PM2.5 and smoke was associated with blood pressure, but not with lung function (van Nunen et al. 2021. Environ Res).

Using SAPALDIA data as part of the European Community Respiratory Health Survey (ECRHS), it was shown that participants with COPD and asthma reported maternal smoking more frequently and already had impaired lung function at the age of 20. In more than half of the participants, asthma began in childhood. Participants with COPD alone had been exposed to the highest levels of tobacco smoke and occupational pollutants throughout their lives and showed an accelerated decline in lung function in adulthood. The coexistence of asthma and COPD appears to have its origins early in life. Preventive measures for these diseases, which typically occur in older age, should therefore begin in childhood (Marcon et al. 2021. Eur Respir J).

A Europe-wide study involving SAPALDIA showed that social status is an important factor that must be included in the analysis to determine the health effect of air pollution, e.g. from NO2 (nitrogen dioxide), on lung function. (Keidel et al. 2019. Int J Environ Res Public Health).

A SAPALDIA study showed that long-term exposure to air pollution can have a negative effect on heart rate variability, especially in people who lack the GSTM1 gene. This correlation was only apparent in healthy individuals (Meier-Girard et al. 2019. Environ Int).

There is growing evidence that air pollution plays a role in the development of asthma. A study involving SAPALDIA showed that certain biomarkers of the immune system play a role in this (Mostafavi et al. 2019. Sci. Rep.).

Air pollution is associated with cerebrovascular disease. The results of a SAPALDIA study point to the role of oxidative stress and activated inflammatory responses as the primary pathway. The results of this study contribute to unravelling the link between air pollution and the increased risk of brain/cardiovascular disease by demonstrating a change in the methylation of DNA of key inflammatory genes over several years (Fiorito et al. 2018. Environ Mol Mutagen).

Arteriosclerosis has been linked to long-term exposure to particulate matter. SAPALDIA was able to show that the thickness of the carotid artery wall is related to PM10, PM 2.5 and ultrafine particulate matter (Aguilera et al. 2016. Environ Health Perspect).

Air pollution, especially fine dust smaller than 10 micrometres (PM10), is associated with type 2 diabetes. In SAPALDIA, we were able to show that people with a certain expression of the interleukin 6 gene are more susceptible to the risk of developing type 2 diabetes due to fine dust. Interleukin 6 is involved in inflammatory processes, thus demonstrating the relevance of inflammatory processes in the relationship between type 2 diabetes and air pollution from fine particulate matter (Eze et al. 2016. Environ Health). A follow-up study then provided evidence that the effect of air pollutants on diabetes risk could be attributed to changes in insulin sensitivity in people with existing inflammation (Eze, et al. 2016. Environ Int).

High blood pressure, obesity and, above all, abdominal fat, as well as elevated blood sugar and blood lipid levels, are referred to by doctors as ‘metabolic syndrome’. In SAPALDIA, we were able to show that exposure to particulate matter also increases the risk of metabolic syndrome (Eze et al. 2015. PLOS One).

Living in areas with heavy traffic is associated with elevated blood levels of C-reactive protein. This blood value is a marker of inflammation in the body and a known risk factor for cardiovascular disease. However, it remains unclear which air pollutant is responsible for this association (Lanki et al. 2015. Environ Health Perspect).

SAPALDIA is part of the European multicentre ESCAPE project (European Study of Cohorts for Air Pollution Effects). The ESCAPE study investigated the association between mortality from natural causes and long-term exposure to various air pollutants. The study showed that long-term exposure to particulate matter correlates with natural mortality. This was also demonstrated at low particulate matter concentrations, which are well below the current European annual average limit value (Beelen et al. 2014. Lancet). Long-term exposure to particulate matter smaller than 2.5 micrometres (PM₂.₅), especially sulphur, was also associated with increased natural mortality (Beelen et al. 2015. Environ Health Perspect).

One of the largest European research collaborations (ESCAPE) on air pollution and health has shown that even very low levels of air pollution impair the average lung function of the population. Interestingly, the lungs of severely obese individuals are more sensitive to air pollution (Adam et al. 2015. Eur. Resp. J.).

In Switzerland, air pollution from traffic caused an estimated 14,000 lost years of life in 2010, and 8,700 cardiorespiratory days of hospitalisation were attributed to traffic-related air pollution. Air pollution and noise caused costs in the order of CHF 1,700 to 1,800 million in 2010. In the case of air pollution, the effects on mortality are the most important cost factors (Vienneau et al. 2015. Int J Hyg Environ Health).

One in 20 people who participated in SAPALDIA3 in 2010 has type 2 diabetes mellitus. And: the higher the level of particulate matter pollution at the place of residence, the greater the risk of type 2 diabetes. (Eze et al. 2014. Environ Int).

As part of the European ESCAPE project, 15 cohorts, including SAPALDIA, were used to investigate the influence of air pollution on blood pressure. It was found that participants who do not take antihypertensive medication and who are exposed to high levels of traffic-related air pollution at their place of residence are more likely to have elevated arterial blood pressure. This suggests that there is also a risk of high blood pressure. However, the relationship between individual air pollutants and blood pressure was not clear (Fuks et al. 2014. Environ Health Perspect).

Genetic variations in one of the most important pro-inflammatory cytokines, interleukin 6, can alter heart rate variability, and this is associated with long-term exposure to traffic-related particulate matter (Adam, et al. 2014. PLoS One).

SAPALDIA found evidence that long-term exposure to nitrogen dioxide (NO₂) could have a negative effect on the autonomic function of the heart in older and middle-aged women (Felber, Dietrich, et al. 2008. Environ Health Perspect).

Please also read the article ‘Air hygiene as a success factor’, which appeared in the VSAO Journal in April 2022.

There is growing evidence that sex hormones play a role in lung health. Dehydroepiandrosterone sulphate (DHEA-S) is a precursor of both female and male sex hormones and was measured in the blood. Researchers have shown that low levels of dehydroepiandrosterone sulphate (DHEA-S) in the blood are associated with impaired lung function and an increased risk of developing respiratory restriction in later adulthood in women. These findings suggest that sex hormones, in this case DHEA-S, play a role in respiratory health (Pesce et al., 2020, EClinicalMedicine).

Moderate and high weight gain over 20 years is associated with an accelerated decline in lung function. Weight loss, on the other hand, counteracts this. Weight control is therefore an important factor in maintaining good lung function in adulthood (Peralta et al. 2020. Thorax).

Estimating how the number of COPD patients will develop is important for determining the future burden of disease. The long-term ECRHS and SAPALDIA studies showed that the incidence (number of new cases) of airway obstruction (also known as airway narrowing) over 20 years was considerable in adults without asthma who were examined between the ages of 25 and 64. The age-related increase in the number of cases of airway obstruction among participants who had never smoked was strongly associated with cumulative exposure to tobacco, which seems to largely explain the different age trends in men and women. Although the increase in respiratory obstruction cases remained relatively unchanged with age, it was also high among lifelong non-smokers, supporting the fact that COPD is also a significant burden in the non-active smoking population (Accordini et al. 2020. Sci Rep).

The European ECRHS project, in which SAPALDIA has been involved since the beginning, investigated whether smoking bans have reduced exposure to second-hand smoke. The study showed that after the introduction of smoking bans, the likelihood of being exposed to second-hand smoke at work decreased significantly. Smoking bans in public and private workplaces have therefore effectively reduced harmful passive smoking (Olivieri et al. 2019. Indoor Air).

In SAPALDIA, 4% of participants have impaired lung function. There can be many reasons for this. However, the SAPALDIA data show that people with reduced lung function engage in physical activity less frequently and less intensively, and that they also suffer more frequently from other diseases such as high blood pressure, diabetes, cardiovascular disease and depression (Carsin et al. 2019. Respir Med).

A SAPALDIA study showed that the risk of developing asthma in late adulthood increases if participants reported an increase in body size (weight gain) between different stages of life (childhood, puberty, young adulthood, etc.). In women, this was particularly the case between the ages of 45 and menopause (Hansen et al. 2019. Respiratory Medicine).

Epidemiological studies show that air pollution is a common risk factor for lung and brain/cardiovascular diseases. As part of the European EXPOsOMICS project, in which SAPALDIA is participating, researchers have shown that certain metabolic processes in the body (e.g. linoleate metabolism) are disrupted by long-term air pollution, especially by particulate matter. They were also able to show that linoleate metabolism plays a role in asthma in adults and in brain/cardiovascular diseases. These results suggest that air pollution disrupts metabolic processes that are common to many chronic diseases and can thus increase the risk of diseases such as asthma and brain/cardiovascular diseases (Jeong et al. 2018. Environ Int). (Linoleate is a salt of the unsaturated fatty acid linoleic acid).

Lung diseases are associated with an increased risk of cardiovascular disease in adults, but little is known about early effects in adolescence. In the SAPALDIA youth study, 257 children of SAPALDIA participants were examined during SAPALDIA3. It was shown that asthmatic boys already have an increased risk of early blood vessel changes in the cardiovascular system during adolescence. These results suggest that asthma in childhood could increase the risk of cardiovascular disease in later adulthood (Dratva et al. 2018. Eur J Pediatr).

Asthma is a complex lung disease. It may not be a single disease at all, but rather a group of different diseases, all of which can lead to asthma attacks. Based on information about the frequency of asthma attacks, whether asthma occurs together with allergies, whether asthma medication is taken, and at what age asthma was diagnosed, we were able to identify different types of asthma in the SAPALDIA data. It is believed that severe obesity is a risk factor for asthma. In fact, there were differences in whether and to what extent obesity influences the different types of asthma. (Jeong et al. 2017. Respir Med.).

Asthma and allergic symptoms become less common with age, but still occur frequently. People who have asthma themselves or who have a family history of allergies are at increased risk of suffering from an allergic form of rhinitis. People who grew up on a farm, have older siblings or currently live in the countryside are less likely to suffer from allergic rhinitis (Abramson et al. 2016. Allergol Int).

The lung protein CC16 is produced in the lungs and can be measured in the blood. The more CC16 is produced by the lungs, the better they are able to combat inflammatory and oxidative attacks from environmental influences. This protective effect of CC16 was also demonstrated in blood samples from SAPALDIA participants. The higher the CC16 value in the blood, the more stable lung function remained over the years. This result points the way to possible new drugs for lung diseases (Guerra et al. 2015. Lancet Resp Med).

Also within the framework of ECRHS, researchers were able to show that occupational exposure to pollutants such as dust, mineral dust and metals is a risk factor for deterioration in lung function. Occupational activity appears to be a risk factor independent of smoking, underscoring the need to prevent and better control these exposures in the workplace (Lytras et al. 2021. Ann Am Thorac Soc).

People who are exposed to metals or mineral dust in the workplace are more likely to suffer from chronic bronchitis and have more frequent problems with sputum production. These are the results of an analysis conducted as part of the ECRHS project (Lytras et al. 2019. Occup. Environ. Med.).

When cleaning with chemical cleaning agents (e.g. cleaning sprays), the respiratory tract is exposed to the chemical vapours of the agents. ECRHS researchers have shown that women who regularly clean their homes or work as cleaners experience a more rapid decline in lung function. This means that the long-term use of chemical cleaning agents when cleaning could pose a long-term health risk to the respiratory tract (Svanes et al., 2018. Am J Respir Crit Care Med.).

Biological processes in the body are influenced by the environment and lifestyle. This happens through epigenetics, because epigenetic changes in DNA, methylation patterns, regulate biological processes. Epigenetic patterns associated with air pollution and traffic noise could lead to physiological and biochemical changes in the body. SAPALDIA has shown that DNA methylation is specifically linked to traffic noise and exposure to air pollution. The areas most strongly affected by the changes were inflammatory responses, cell development and immune responses (Eze et al., 2020. Environ Health Perspect).

Changes in DNA methylation can provide information about age, regardless of a person's actual age. There may be a difference between a person's estimated age, based on DNA methylation, and their actual age. If the estimated age is higher than the actual age, this is also referred to as epigenetic age acceleration. This difference is used to study ageing more closely. In SAPALDIA and ECRHS, it was shown that age acceleration, based on epigenetic patterns, is significantly related to the lung function of women over the age of 50. It is thought that this could be due to the menopause. This could be used to determine the lung health of older women more accurately and could be an important factor in determining lung health in adults in general (Rezwan et al., 2020. Aging).

Lung function is hereditary and differs between the sexes throughout life. However, little is known about gender-specific genetic effects on lung function. Researchers have found that genetic variants associated with HHIP (Hedgehog-Interacting Protein) have gender-specific effects on lung function (Fawcett et al. 2020. Wellcome Open Res).

In an epigenetic analysis, researchers found that BMI (body mass index) is unlikely to influence lung function via DNA methylation (Amaral et al. 2020. BMC Pulm Med).

A combination of many studies involving SAPALDIA showed that epigenetic patterns can be used to identify the biological processes through which social inequalities can affect healthy ageing (Fiorito et al. 2019. Aging).

Obesity has been repeatedly linked to non-allergic asthma. In mouse models, there was evidence that inflammatory mechanisms play a significant role. SAPALDIA data was used to investigate the biological mechanisms behind this. SAPALDIA researchers were able to confirm that the increased risk of non-allergic asthma associated with obesity is influenced by epigenetic changes in pro-inflammatory genes (Jeong et al. 2019. Int J Environ Res Public Health).

Large international studies involving data from more than 400,000 participants have identified over 270 genetic risk factors for lung function. Knowledge of genetic factors can improve the long-term treatment of COPD (chronic obstructive pulmonary disease) by providing a better understanding of the mechanisms of the disease. This can even contribute to the prevention of this serious disease (Shirane et al. 2019. Nature Genetics; Wain et al. 2018. Nature Genetics; Jackson et al. 2018. Wellcome Open Research).

Asthma is a chronic, treatable lung disease. In some cases, asthma can disappear (remission). In collaboration with other cohort studies, genes have been identified that are likely to play a role in the remission of asthma (Vonk et al., 2018. Clin. Exp. Allergy).

Allergic hay fever is more common in certain families than in others, and a large international study of almost 60,000 people with hay fever, to which SAPALDIA analyses also contributed, identified 20 new genes that increase the risk of developing hay fever (Waage et al. 2018, Nature Genetics).

The protein alpha-1 antitrypsin (AAT) circulates in the blood and protects the lungs from attacks, which are exacerbated by smoking. It is known that a genetic deficiency of AAT protein in the blood combined with smoking can lead to chronic lung disease as early as middle age. SAPALDIA researchers have recently shown that AAT can protect not only the lungs but also the blood vessels. Whether it is clinically relevant to consider this traditional lung risk factor for cardiovascular disease must first be confirmed by further studies (Curjuric et al. 2018. Arteriosclerosis). Furthermore, using SAPALDIA data, we were able to analyse epigenetic patterns (analysis of DNA methylation) and show that, contrary to expectations, epigenetic regulation of the AAT gene region does not influence lung function in the general population (Beckmeyer-Borowko et al., 2018, Resp. Res.).

Analysis of SAPALDIA data on genes, air pollution and lung function allowed us to identify the Cadherin13 gene. Depending on the Cadherin13 gene variant, the lungs react more strongly or less strongly to particulate matter. Cadherin13 probably amplifies the effect of air pollutants on the lungs by reducing the availability of adiponectin, an inflammation-regulating messenger substance. Adiponectin is also important in connection with weight loss (Imboden et al. 2015. Environ Health Perspect).

The dental health of the Swiss population was examined as part of the SAPALDIA4 health survey. This was the first time that nationwide examinations had been carried out to collect data on dental health in the population. It was shown that participants had an average of five missing teeth, 74.8% had dentures and 21.1% had pocket depths of more than 4 mm, which is an indication of periodontitis. The average number of missing teeth and the presence of tooth loss, fixed dentures and removable dentures are related to age, level of education, smoking status and the time since the last visit to the dentist (Schmidt JC et al. 2020. Eur J Oral Sci).