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Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3,176). We show that: 1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, 2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns towards a younger profile, and 3) muscle disuse “ages” the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted towards a younger state after exercise training interventions, while the transcriptome shifted towards an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

A modified Fontan procedure is performed to palliate single ventricle malformations. This hemodynamic arrangement sets systemic venous pressure unphysiologically high which predisposes the patient to severe long-term complications. As a means of self-care, exercise may ease transpulmonary flow. We investigated the effects of 6-month exercise prescription on pediatric Fontan patients. Eighteen stable Fontan patients (14 ± 2.6 years, 160.4 ± 11.3 cm, and 51.4 ± 14.4 kg) were recruited. Baseline fitness was assessed by physical activity questionnaire, body composition, cardiorespiratory performance, and muscle fitness tests. Exercise prescription was individually tailored for a 6-month training period at home. At entrance to the study, Fontan patients had lower than normal maximal oxygen uptake (VO2max) of 28. ± 5.9 ml/kg/min (61 ± 11% of normal). VO2max significantly correlated with weekly amount of habitual exercise and muscle mass of the lower limbs (p p = 0.007, and workload tolerance of 119 ± 39 vs 132.4 ± 44 W, p = 0.001. At EUROFIT tests, the patient muscle fitness was below age-matched reference, but correlations existed between VO2max and lower limb muscle tests. Our patients with Fontan hemodynamics were able to positively respond to an exercise program by enhancing submaximal performance which should be beneficial for getting through daily activities. Future studies should correlate whether hemodynamic findings at Fontan completion influence physical activity and exercise reserves, and whether these predict predisposition to chronic complications.

Objectives Our objective was to study mortality related to different obstructive lung diseases, occupational exposure, and their potential joint effect in a large, randomized population-based cohort. Methods We divided the participants based on the answers to asthma and chronic obstructive pulmonary disease (COPD) diagnoses and occupational exposure and used a combined effects model and compared the results to no asthma or COPD with no occupational exposure. Results High exposure had a hazards ratio (HR) of 1.34 (1.11-1.62) and asthma and COPD coexistence of 1.58 (1.10-2.27). The combined effects of intermediate exposure and coexistence had an HR of 2.20 (1.18-4.09), high exposure with coexistence of 1.94 (1.10-3.42) for overall mortality, and sub-HR for respiratory-related mortality of 3.21 (1.87-5.50). Conclusions High occupational exposure increased overall but not respiratory-related mortality hazards, while coexisting asthma and COPD overall and respiratory-related hazards of mortality. publishedVersion

Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijarvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijarvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV1)%/mg): Sovijarvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijarvi (PD15) and Nieminen (PD20) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.

Background: Chronic nonrespiratory diseases are seemingly more prevalent in subjects with than without asthma, and asthma seems to differentiate by age of onset. However, studies with comparison of nonrespiratory diseases in subjects with and without asthma, considering asthma age of onset, are scarce. Objective: To compare the quantity and type of chronic nonrespiratory diseases in adults with and without asthma considering age at asthma diagnosis. Methods: In 2016, a FinEsS questionnaire was sent to 16,000 20- to 69-year-old adults randomly selected in Helsinki and Western Finland populations. Physician-diagnosed asthma was categorized to early (0-11), intermediate (12-39), and late-diagnosed (40-69 years). Results: A total of 8199 (51.5%) responded, and 842 (10.3%) reported asthma and age at diagnosis. In age and sex-adjusted binary logistic regression model, the most represented nonrespiratory disease was treated gastroesophageal reflux disease in early-diagnosed (odds ratio, 1.93; 95% CI, 1.17-3.19; P =.011) and osteoporosis in both intermediate-diagnosed (odds ratio, 3.45; 95% CI, 2.01-5.91; P

Objective: Low socioeconomic status based both on educational level and income has been associated with asthma and respiratory symptoms, but changes over time in these associations have rarely been studied. The aim was to study the associations between educational or income inequality and asthma and respiratory symptoms among women and men over a 20-year period in northern Sweden. Methods: The study was performed within the Obstructive Lung disease in Northern Sweden (OLIN) research program. Mailed questionnaire surveys were administered to a random sample of adults (20-69 years of age) living in Sweden, in 1996, 2006 and 2016. Data on educational level and income were collected from the national integrated database for labor market research. Results: The educational inequality associated with asthma and asthmatic wheeze tended to decrease from 1996 to 2016, while it increased for productive cough, the latter among men not among women. The income inequality decreased for productive cough, especially for women, while no clear overall trends were found for asthmatic wheeze and asthma, apart from a decrease in income inequality regarding asthma among men. Conclusion: The patterns for socioeconomic inequality differed for asthma and wheeze compared to productive cough, and the results emphasize that education and income do not mirror the same aspects of socioeconomic inequality in a high-income country. Our findings are important for decision makers, not the least on a political level, as reduced inequality, e.g. through education, could lead to reduced morbidity.

Background: Although asthma may begin at any age, knowledge about relationship between asthma age of onset and the prevalence and character of different symptoms is scarce. Objectives: The aim of this study was to investigate if adult-diagnosed asthma is associated with more symptoms and different symptom profiles than child-diagnosed asthma. Methods: A FinEsS postal survey was conducted in a random sample of 16 000 20-69-year-old Finnish adults in 2016. Those reporting physician-diagnosed asthma and age at asthma diagnosis were included. Age 18 years was chosen to delineate child- and adult-diagnosed asthma. Results: Of responders (N = 8199, 51.5%), 842 (10.3%) reported asthma diagnosis. Adult-diagnosed asthma was reported by 499 (59.3%) and child-diagnosed by 343 (40.7%). Of responders with adult-diagnosed and child-diagnosed asthma, 81.8% versus 60.6% used asthma medication (p < 0.001), respectively. Current asthma was also more prevalent in adult-diagnosed asthma (89.2% versus 72.0%, p < 0.001). Risk factors of attacks of breathlessness during the last 12 months were adult-diagnosis (OR = 2.41, 95% CI 1.64–3.54, p < 0.001), female gender (OR = 1.49, 1.07–2.08, p = 0.018), family history of asthma (OR = 1.48, 1.07–2.04, p = 0.018) and allergic rhinitis (OR = 1.49, 1.07–2.09, p = 0.019). All the analysed asthma symptoms, except dyspnea in exercise, were more prevalent in adult-diagnosed asthma in age- and gender-adjusted analyses (p = 0.032

Background Smoking and occupational airborne exposures are known to increase asthma symptoms, but less is known about their influence by the age of asthma diagnosis. Objective To evaluate the effect of exposures to VGDF (vapors, gases, dusts and fumes), tobacco smoke and their combination for asthma symptoms comparing subjects with asthma diagnosed in childhood and adulthood. Methods A random sample of 16 000 adults aged 20–69 years were invited to a postal survey on obstructive pulmonary diseases in Finland in 2016. Those reporting physician-diagnosed asthma and age at diagnosis were included in the analysis and their reported VGDF-exposure and smoking habits were analyzed. Age 18 years was chosen to delineate child- and adult-diagnosed asthma. Results 8199 (51.5%) responded. Of the responders, 831 reported physician-diagnosed asthma. 41% of asthmatics reported child-diagnosed and 59% adult-diagnosed asthma. Current smoking was reported by 25.2% and 20.2% and VGDF exposure by 31.3% and 44.7% in child -diagnosed and adult-diagnosed asthma, respectively. Combined VGDF-exposure and current smoking was reported by 9.7% and 10.6%, respectively. Compared to the unexposed, those with asthma diagnosed in childhood and with combined current smoking and VGDF exposure, had higher prevalence of wheeze (69.7% vs 39.5%, p=0.009), sputum production (39.4% vs 11.4%, p=0.001) and morning dyspnea (42.4% vs 21.9%, p=0.002). Corresponding pattern was seen in those with asthma diagnosed in adulthood; for wheeze (78.8% vs 53.6%, p=0.007), sputum production (40.4% vs 25.0%, p=0.014) and morning dyspnea (65.4% vs 42.0%, p=0.008). Child-diagnosed asthmatics both without exposure history (46.5% vs 69.6%, p=0.001) and with combined exposure to smoking and VGDF (66.7% vs 94.2%, p=0.003) reported less often ≥3 symptoms compared to adult-diagnosed asthmatics, even though they reported less frequently use of asthma medication (60.7% vs 82.0%, p>0.001). Smoking asthmatics with adult-diagnosis and exposure to VGDF had the highest prevalence estimates of having multiple symptoms (94.2%) in our study. Conclusion Although asthmatics diagnosed in child- and adulthood reported symptoms related to exposure to smoking and VGDF, symptoms were reported more often by those with adult diagnosis. The results indicate the importance of targeted asthma treatment and follow-up by patient’s exposure history and asthma diagnosis age.

In clinical practice, assessment of expiratory nitric oxide (F-ENO) may reveal eosinophilic airway inflammation in asthmatic and other pulmonary diseases. Currently, measuring of F-ENO is standardized to exhaled flow level of 50 ml s(-1), since the expiratory flow rate affects the F-ENO results. To enable the comparison of F-ENO measured with different expiratory flows, we firstly aimed to establish a conversion model to estimate F-ENO at the standard flow level, and secondly, validate it in five external populations. F-ENO measurements were obtained from 30 volunteers (mixed adult population) at the following multiple expiratory flow rates: 50, 30, 100 and 300 ml s(-1), after different mouthwash settings, and a conversion model was developed. We tested the conversion model in five populations: healthy adults, healthy children, and patients with COPD, asthma and alveolitis. F-ENO conversions in the mixed adult population, in healthy adults and in children, showed the lowest deviation between estimated FENO from 100 ml s(-1) and measured F-ENO at 50 mL s(-1): -0 center dot 28 ppb, -0 center dot 44 ppb and 0 center dot 27 ppb, respectively. In patients with COPD, asthma and alveolitis, the deviation was -1 center dot 16 ppb, -1 center dot 68 ppb and 1 center dot 47 ppb, respectively. We proposed a valid model to convert F-ENO in healthy or mixed populations, as well as in subjects with obstructive pulmonary diseases and found it suitable for converting F-ENO measured with different expiratory flows to the standard flow in large epidemiological data, but not on individual level. In conclusion, a model to convert F-ENO from different flows to the standard flow was established and validated.

Objective: Education in itself and as a proxy for socioeconomic status, may influence asthma control, but remains poorly studied in adult-onset asthma. Our aim was to study the association between the level of education and asthma control in adult-onset asthma. Methods: Subjects with current asthma with onset >15 years were examined within the Obstructive Lung Disease in Northern Sweden study (OLIN, n = 593), Seinäjoki Adult Asthma Study (SAAS, n = 200), and West Sweden Asthma Study (WSAS, n = 301) in 2009–2014 in a cross-sectional setting. Educational level was classified as primary, secondary and tertiary. Uncontrolled asthma was defined as Asthma Control Test (ACT) score ≤19. Altogether, 896 subjects with complete data on ACT and education were included (OLIN n = 511, SAAS n = 200 and WSAS n = 185). Results: In each cohort and in pooled data of all cohorts, median ACT score was lower among those with primary education than in those with secondary and tertiary education. Uncontrolled asthma was most common among those with primary education, especially among daily ICS users (42.6% primary, 28.6% secondary and 24.2% tertiary; p = 0.001). In adjusted analysis, primary education was associated with uncontrolled asthma in daily ICS users (OR 1.92, 95% CI 1.15–3.20). When stratified by atopy, the association between primary education and uncontrolled asthma was seen in non-atopic (OR 3.42, 95% CI 1.30–8.96) but not in atopic subjects. Conclusions: In high-income Nordic countries, lower educational level was a risk factor for uncontrolled asthma in subjects with adult-onset asthma. Educational level should be considered in the management of adult-onset asthma. publishedVersion

Background: Difference in dyspnea mMRC >= 2 between Finnish speaking and Swedish-speaking populations in Finland has not been previously studied. Methods: In February 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland with a response rate of 52.3%. The registered native language of each subject determined whether questionnaire in Finnish or Swedish was applied. Multiple logistic regression was performed to calculate Odds Ratios (OR) with 95% CI for the simultaneous effects of independent variables on dyspnea mMRC >= 2. Results: Of all participants, 2780 (71.9%) were Finnish speakers and 1084 (28.1%) were Swedish speakers. Finnish speakers had a higher prevalence of dyspnea mMRC >= 2 (11.1% vs 6.5% p < 0.001) when compared to Swedish speakers. Finnish speakers smoked more often, had higher BMI, spent less time moving during the day, had more often occupational exposure to vapours, gases, dusts or fumes (VGDF), and had lower socioeconomic status based on occupation. Significant risk factors for dyspnea mMRC >= 2 were COPD (OR = 10.94), BMI >35 (OR = 9.74), asthma (OR = 4.78), female gender (OR = 2.38), older age (OR = 2.20), current smoking (OR = 1.59), and occupational exposure to VGDF (OR = 1.47). Conclusions: Swedish speakers had less dyspnea mMRC >= 2 which is explained by a healthier lifestyle. Smoking, obesity, and occupational exposures should be in focus to improve respiratory health.

Background The prevalence of asthma has increased both among children and adults during the latter half of the 20th century. The prevalence among adults is affected by the incidence of asthma not only in childhood but also in adulthood. Time trends in asthma incidence have been poorly studied. Aims The aim of this study was to review the incidence of adult-onset asthma from 1996 to 2006 and 2006 to 2016 and compare the risk factor patterns. Methods In the Obstructive Lung Disease in Northern Sweden (OLIN) studies, two randomly selected population-based samples in the 20–69-year age group participated in postal questionnaire surveys about asthma in 1996 (n=7104, 85%) and 2006 (n=6165, 77%). A 10-year follow-up of the two cohorts with the same validated questionnaire was performed, and 5709 and 4552 responded, respectively. Different definitions of population at risk were used in the calculations of asthma incidence. The protocol followed a study performed between 1986 and 1996 in the same area. Results The crude incidence rate of physician-diagnosed asthma was 4.4 per 1000 person-years (men 3.8, women 5.5) from 1996 to 2006, and 4.8 per 1000 person-years (men 3.7, women 6.2) from 2006 to 2016. When correcting for possible under-diagnosis at study entry, the incidence rate was 2.4 per 1000 person-years from 1996 to 2006 and 2.6 per 1000 person-years from 2006 to 2016. The incidence rates were similar across age groups. Allergic rhino-conjunctivitis was the main risk factor for incident asthma in both observation periods (risk ratio 2.4–2.6). Conclusions The incidence of adult-onset asthma has been stable over the last two decades and has remained at a similar level since the 1980s. The high incidence contributes to the increase in asthma prevalence., The incidence of adult-onset asthma in adults has been stable in Sweden over the last 30 years but the relatively high incidence rate in combination with low remission rate in adulthood contributes to the reported increase in asthma prevalence among adults https://bit.ly/2QP0AF4

BACKGROUND: Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seem-ingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce. OBJECTIVE: To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission. METHODS: In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was catego-rized by age at diagnosis to early-(0-11 years), intermediate-(12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months. RESULTS: Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, signifi-cant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.373.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD. CONCLUSION: Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission. (C) 2020 American Academy of Allergy, Asthma & Immunology

Objective: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. Method: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. Results: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7–8.2% versus 6.3–6.7%) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7 and 2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. Conclusion: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex. Accepted author version posted online: 30 May 2020Published online: 13 Jun 2020

Multimorbidity is an emerging public health priority. This study aims to assess the role of lifestyle and socioeconomic status in the prevalence of multimorbidity and chronic diseases by using two language groups that are part of the same genetic subgroup but differ by daily habits. We conducted a cross-sectional survey in 2016 with randomly selected population sample with 4173 responders (52.3%) aged 20–69 years in Western Finland. We included 3864 Finnish participants with Swedish (28.1%) or Finnish (71.9%) as a native language. We used a questionnaire to assess participants' chronic diseases and lifestyle. We determined multimorbidity as a disease count ≥ 2. Finnish speakers were more likely to have a diagnosis of COPD, heart failure, diabetes, reflux disease, chronic kidney failure, and painful conditions than Swedish speakers. The prevalence of multimorbidity was higher for Finnish speakers in the age group of 60–69 years (41.0% vs. 32.0%, p = 0.018) than Swedish speakers. A higher proportion of Finnish speakers smoked, were obese, inactive, and had lower socioeconomic status compared to Swedish speakers. All these factors, in addition to age and female sex, were significant risk factors for multimorbidity. Prevalence of multimorbidity was different in two language groups living in the same area and was associated with differences in lifestyle factors such as smoking, physical inactivity and obesity. publishedVersion

Vertaisarvioitu. Epästabiilissa sepelvaltimotaudissa lepo-EKG:n muutos voi olla kivuttomalla potilaalla ainoa viite uhkaavasta sydäntapahtumasta. Kuvaamme tapauksen, jossa hyvävointisen potilaan EKG-löydös oli ratkaiseva vihje uhkaavasta sydäninfarktista.

Background: Child-onset asthma is known to remit with high probability but remission in adult-onset asthma seems to be less common. Reports of association between remission and asthma onset age in adulthood are scarce. Objectives: To study if age at asthma diagnosis and gender are associated to remission rate in adult asthma population. Methods: In 2016, a random sample of 16 000 subjects aged 20-69 years from Helsinki and Western Finland were sent a FinEsS-questionnaire. Asthma was categorized by reported age when diagnosed with asthma by a physician: child (0-11 years) adolescent-young-adult (12-39 years) and late-adult-diagnosed (40-69 years). Remission was defined as a physician diagnosed asthma but not having had asthma symptoms, wheezing or use of asthma medication in the past 12 months. Results: 8199 subjects (51.5%) responded to the postal questionnaire. Remission was most common in child-diagnosed (30.2%), followed by adolescent-young-adult-diagnosed (17.9%) and least common in late-adult-diagnosed asthma (5.0%) (p Conclusion: Remission was rare (5%) in adults diagnosed with asthma after age 40 years in both sexes. Causes of poor prognosis in adult-onset asthma need to be further elucidated.

Background: During the second half of the 20th century the prevalence of asthma has increased and smoking habits and socioeconomy has changed in Sweden. Aim: To analyze risk factor patterns for current asthma in 1996, 2006 and 2016. Methods: Three cross-sectional random samples from the same area of Sweden, 20-69 years, participated in population surveys with the same validated questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%). Current asthma was defined as physician-diagnosed asthma with symptoms common in asthma and/or asthma medication use during the last 12 months. Socioeconomic classification was based on occupation. Risk factors for current asthma were analyzed by multivariable logistic regression. Results: A family history of asthma yielded the highest odds ratios (OR) all three years with ORs 3.19-3.66. Data on occupational exposure to gas, dust or fumes (GDF) was not available in 1996, but associated with current asthma in both 2006 (1.86, 1.51-2.30) and 2016 (1.70, 1.37-2.10). Ex-smoking was a risk factor in 1996 (1.39, 1-12-1.73) and 2006 (1.38, 1.11-1.71) but not in 2016 (1.15, 0.92-1.44). Manual workers in service and industry, non-manual employees and self-employed had increased risk for current asthma in 2016, but not in 1996 or 2006, compared to professionals and executives. Conclusion: The risk factor pattern for asthma among adults has changed in Sweden from 1996 to 2016. While occupational exposure to GDF was a prominent and constant risk factor for asthma, ex-smoking lost significance in 2016, and socioeconomic differences with regard to occupation emerged.

Background: Multimorbidity is an emerging public health priority. This study aims to assess the role of lifestyle and socioeconomic status in the prevalence of multimorbidity and chronic diseases by using two language groups that are genetically similar but differ by daily habits. Methods: In 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in Western Finland. After two reminders, 4173 (52.3%) subjects responded, including 3864 persons with Swedish or Finnish as a native language. The questionnaire was used to assess participants9 chronic diseases and lifestyle. Multimorbidity was determined as a disease count ≥2. Results: Of the participants, 2780 (71.9%) were Finnish speaking and 1084 (28.1%) Swedish speaking Finns. Finnish speakers were more likely to have a diagnosis of COPD, heart failure, diabetes, reflux disease, chronic kidney failure, and painful conditions than Swedish speakers. More Finnish speakers smoked, were obese, inactive and had lower socioeconomic status compared to Swedish speakers. All these factors, in addition to age and female gender, were significant risk factors for multimorbidity, but not the native language. The prevalence of multimorbidity was higher for Finnish speakers, in the age group of 60-69 years (41.0% vs 32.0%, p=0.018). Conclusions: This study in genetically similar populations having different lifestyles suggests the connection of unhealthy lifestyle to multimorbidity and gives population-based insight that with a healthier lifestyle including non-smoking, healthy weight, and active lifestyle, it is possible to reduce multimorbidity at an older age.

Low socioeconomic status (SES) has been associated with asthma and wheezing. Occupational group, educational level and income are commonly used indicators for SES, but no single indicator can illustrate the entire complexity of SES. The aim was to investigate how different indicators of SES associate with current asthma, allergic and nonallergic, and asthmatic wheeze. In 2016, a random sample of the population aged 20–79 years in Northern Sweden were invited to a postal questionnaire survey, with 58% participating (n=6854). The survey data were linked to the national Integrated Database for Labour Market Research by Statistics Sweden for the previous calendar year, 2015. Included SES indicators were occupation, educational level and income. Manual workers had increased risk for asthmatic wheeze, and manual workers in service for current asthma, especially allergic asthma. Primary school education associated with nonallergic asthma, whereas it tended to be inversely associated with allergic asthma. Low income was associated with asthmatic wheeze. Overall, the findings were more prominent among women, and interaction analyses between sex and income revealed that women, but not men, with low income had an increased risk both for asthmatic wheeze and current asthma, especially allergic asthma. To summarise, the different indicators of socioeconomic status illustrated various aspects of associations between low SES and asthma and wheeze, and the most prominent associations were found among women., Occupation, educational level and income each mirror different aspects of the association between socioeconomic status and asthma and asthmatic wheeze. This is most pronounced among women. Health-related social inequities should not be underestimated. https://bit.ly/2ByuFRz

NAD(+) is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD(+) depletion occurs in patients with degenerative disorders and whether NAD(+) repletion improves their symptoms has remained open. Here, we report systemic NAD(+) deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD(+) booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD(+) increased in all subjects, up to 8-fold, and muscle-NAD(+) of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD(+) deficiency and points niacin to be an efficient NAD(+) booster for treating mitochondrial myopathy.

Background: A deficiency of muscle phosphofructokinase (PFKM) causes a rare metabolic muscle disease, the Tarui disease (Glycogen storage disease type VII, GSD VII) characterized by exercise intolerance with myalgia due to an inability to use glucose as an energy resource. No medical treatment for GSD VII currently exists. The aim of this study was to determine whether a dietary intervention with excessive fat intake would benefit GSD VII.Patient and Methods: A ketogenic diet (KD) intervention implemented as a modified Atkins diet was established for one patient with PFKM deficiency, with a low late lactate response and very high ammonia levels associated with exercise. We recorded the KD intervention for a total of 5 years with clinical and physiotherapeutic evaluations and regular laboratory parameters. Cardiopulmonary exercise testing, including breath gas analysis and venous lactate and ammonia measurements, was performed before KD and at 3, 8 months and 5 years after initiation of KD.Results: During the 5 years on KD, the patient's muscle symptoms had alleviated and exercise tolerance had improved. In exercise testing, venous ammonia had normalized, the lactate profile remained similar, but oxygen uptake and mechanical efficiency had increased and parameters showing ventilation had improved.Conclusions: This study is the first to show a long-term effect of KD in GSD VII with an alleviation of muscle symptoms, beneficial effects on breathing, and improvement in exercise performance and oxygen uptake. Based on these findings, KD can be recommended under medical and nutritional supervision for selected patients with GSD VII, although further research of this rare disease is warranted.

Background: Genetic alterations occurring in lung cancer are the basis for defining molecular subtypes and essential for targeted therapies. Exhaled breath condensate (EBC) is a form of non-invasive sample that, amongst components, contains DNA from pulmonary tissue. Nextgeneration sequencing (NGS) was herein used to analyze mutations in EBC from patients with lung cancer. Materials and Methods: EBC was collected from 26 patients with cancer and 20 healthy controls. Amplicon-based sequencing using Ion Ampliseq Colon and Lung Cancer gene panel v2 was applied. Results: The sequencing was successful in 17 patients and 20 controls. EBC from patients revealed 39 hotspot mutations occurring in: adenomatous polyposis coli (APC), v-raf murine sarcoma viral oncogene homolog B (BRAE), discoidin domain receptor tyrosine kinase 2 (DDR2), epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 4 (ERBB4), F-box and WD repeat domain containing 7 (FBXW7), fibroblast growth factor receptor 1 (FGER1), FGFR3 (fibroblast growth factor receptor 3), Kirsten rat sarcoma viral oncogene homolog (KRAS), mitogen-activated protein kinase kinase 1 (MAP2K1), met proto-oncogene (MET), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), ret proto-oncogene (RET), SMAD family member 4 (SMAD4), serine/threonine kinase 11 (STK11), and tumorprotein p53 (TP53) genes. EBC from controls revealed 35 hotspot mutations. The average mutant allele fraction was higher in patients than controls. Conclusion: NGS can identify mutations in EBCs from patients with lung cancer. This could provide a promising non-invasive method for the assessment of gene mutations in lung cancer.

Fractional exhaled nitric oxide (F-ENO) assesses eosinophilic inflammation of the airways, but F-ENO values are also influenced by oral nitric oxide (NO). The aim of this pilot study was to measure F-ENO and compare the effect of two different mouthwashes on F-ENO and analyse the duration of the effect. F-ENO was measured in 12 randomized volunteers (healthy or asthmatic subjects) with a NIOX VERO (R) analyser at an expiratory flow rate of 50mL/s. After a baseline measurement, a mouthwash was performed either with tap water or carbonated water and was measured during 20min in 2min intervals. The procedure was repeated with the other mouthwash. We found that both mouthwashes reduced F-ENO immediately at the beginning compared to the baseline (p