Genome-wide association study of preserved ratio impaired spirometry (PRISm).

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.

Social position and functional somatic disorders: The DanFunD study.

BACKGROUND AND AIM: It is generally accepted that functional somatic disorders (FSDs) are a product of biological, psychological, and social factors. Social position might be part of this complex, but the literature on this issue is currently heterogeneous and inconsistent. The aim of the present study was - in a population-based cohort - to test the hypothesis that lower social position would be associated with higher a risk of FSD. METHOD: The association between social position and FSD was examined in a cross-sectional study with various measures of social position (education as measured by vocational training; employment; cohabitation; subjective social status) and delimitations of FSD (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, bodily distress syndrome, and symptom profiles). The associations were analyzed using logistic regressions to calculate odds ratios and 95% confidence intervals. Each social measure was analyzed independently and was adjusted for age and sex. RESULTS: Lower levels of vocational training, being unemployed, and living alone were associated with higher risk of FSD, regardless of the FSD delimitation. There was also a significant negative association between subjective evaluated social status and FSD. The associations remained after multiple adjustments, and seemed to be strongest for the more severe FSD-types. CONCLUSIONS: Lower social position is associated with higher risk of FSD, especially the more severe FSD delimitations, which might constitute an especially vulnerable group. However, the mechanisms behind the relations remain unknown.

Normative values of short-term heart rate variability in a cross-sectional study of a Danish population. The DanFunD study.

AIMS: The autonomic nervous system includes parasympathetic and sympathetic components that monitor and regulate most of the bodily functions and play a central role in the physiology and homeostasis of the human body. Heart rate variability is a non-invasive tool for quantification of rhythmic fluctuations in heart rate that reflects the function of the autonomic nervous system. The study aims to describe the heart rate variability distribution in the general population, stratified in sex and age groups, which is currently insufficiently described. METHODS: A cross-sectional population-based study recruited participants in 10 municipalities in the western part of the greater Copenhagen area in Denmark, including 6891 men and women aged 18-72 years (participation rate was 29.5%). Short-term heart rate variability measures were obtained and related to age and gender. RESULTS: Both time and frequency domain measures showed a huge variation in the different sex and age groups. Women had a higher median heart rate than men, and the association with age was U-shaped. Measures indicating a predominance of the parasympathetic component in relation to the sympathetic component were more frequent in women and younger age groups. CONCLUSIONS: Both sex and age influence the heart rate variability in this adult Danish population. Therefore, our age- and sex-related reference values of heart rate variability in the time and frequency domain should be used in further epidemiological and clinical research.

Examine the public health impacts of functional somatic disorders using the DanFunD study.

Background: Persistent physical symptoms (e.g. pain, fatigue) are prevalent in the population and some persons may develop a functional somatic disorder (FSD). We still need to explore the limits between general bodily sensations and FSD, and great controversies exist as regard delimitation, occurrence, risk factors, prognosis, and costs of FSD in the general population. This is mainly due to the lack of focused, sufficient powered, population-based epidemiological studies. Material and Methods: The DanFunD study is the largest focused population-based study on FSD and has the potential to answer these crucial questions regarding the FSD disorders. DanFunD has its origin in the Copenhagen area of Denmark and was initiated in 2009 by an interdisciplinary team of researchers including basic scientists, clinical researchers, epidemiologists, and public health researchers. A population-based cohort of nearly 10,000 people have filled in detailed questionnaires, gone through a thorough health examination, and a biobank is established. The cohort was re-examined after five years. Results:The prevalence of FSD in the Danish population is about 10-15% and is twice as common in women as in men. Persons with FSD report impaired daily activities and low self-perceived health, which qualifies FSD as a major public health problem. The research plan to unravel the risk factors for FSD employs a bio-psycho-social approach according to a detailed plan. Preliminary results are presented, and work is in progress. Likewise, plans for assessing prognosis and health care costs are provided. Conclusion: We invite researchers in the field to collaborate on this unique data material.

Use of register- and survey-based measures of anxiety in a population-based Danish cohort.

OBJECTIVE: We explored the comparability of anxiety measures from register- and survey-based data including analyses of prevalence and associations with selected psychiatric and somatic diseases. METHODS: We measured anxiety using Danish registers (hospital diagnosis and anxiolytic drug prescriptions), self-reports, symptom checklist (SCL) scores, and a clinical interview in 7493 adults with mean age 52 (SD 13.3) years who participated in a health survey between 2012 and 2015. We estimated the prevalence of anxiety, agreement between different measures and performed quantitative bias analysis. RESULTS: The lifetime prevalence of hospital diagnosed anxiety, anxiolytic drug prescriptions, and self-reported anxiety were 4.4%, 6.2%, and 5.1%, respectively, after adjusting for selective participation. The agreement between the different anxiety measures was low. Thus, 25% with an anxiety diagnosis and 20% with anxiolytic drug prescriptions also had a high SCL score. Anxiolytic drugs were the only measure significantly associated with higher odds of heart disease. Hospital diagnosis and self-reported anxiety were associated with depression with odds ratio (OR) above 15, whereas anxiolytic drug prescriptions were less strongly associated (OR = 2.2(95% confidence interval: 1.26-3.91)). The risk estimates attenuated considerably when correcting for measurement error, whereas the ORs became slightly higher when the selective participation in the survey was accounted for. CONCLUSION: Anxiety diagnosed in hospitals and self-reported anxiety showed low level of agreement but provide comparable results regarding frequency measures and associations with disease outcomes.

The impact of the Covid-19 pandemic on mental and physical health in Denmark - a longitudinal population-based study before and during the first wave.

BACKGROUND: In the continuation of the first wave of the Covid-19 outbreak in Denmark, unprecedented restrictions with great impact on the citizen's everyday life were implemented. The objectives of this study were to investigate the influence of the Covid-19 pandemic on mental and physical health in the Danish population during the spring 2020 first wave outbreak and lockdown. METHODS: A sample from the adult Danish population (n = 2190) were included. Self-reported measures of illness worry (Whiteley-6-R), emotional distress (SCL-90), and physical symptom load (SLC-90) were obtained before and during the first wave of the pandemic and compared with Wilcoxon signed-rank tests. Impact of covariates on physical and mental health was evaluated with ordinal regression analyses. Results from a tailored questionnaire regarding the Covid-19 pandemic were presented to explore the direct impact of the pandemic. RESULTS: We only found minor increases in illness worry, emotional distress and physical symptom load (0-1 points difference, p ≤ 0.007) during the Covid-19 pandemic compared to before the pandemic. Sex, age, education, and physical disease were not associated with illness worry, emotional distress, or physical symptom load. Overall, the participants were trustful in the authorities' recommendations and felt that they managed the pandemic and the restrictions to a great extent despite that some expected great/major future consequences of the pandemic. CONCLUSIONS: This study suggested that the first wave of the Covid-19 pandemic only had minor impact on mental and physical health in the Danish general population. Future studies should address the impact of the second wave of the pandemic and the renewed implementation of the concomitant restrictions.

Prevalence of functional somatic syndromes and bodily distress syndrome in the Danish population: the DanFunD study.

Aims: Little is known about the prevalence and characteristics of functional somatic syndromes (FSS) such as irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), whiplash associated disorders (WAD), multiple chemical sensitivity (MCS), and bodily distress syndrome (BDS) in the general population when they are investigated simultaneously. Method: This cross-sectional study is based on the Danish Study of Functional Disorders (DanFunD) cohort consisting of 9656 adults from the general population. FSS and BDS were identified by questionnaires and characterized by age, sex, vocational training, physical health and comorbidity with physical and psychiatric disease. Results: In total, 16.3% (95% CI: 15.6-17.1) of the participants fulfilled the criteria for at least one FSS, ranging from 1.7% for WAD to 8.6% for CFS, and 16.1% (95% CI: 15.4-16.9) fulfilled the criteria for BDS. Cases had a high risk of poor self-perceived health, limitations in daily activities, and a high psychiatric comorbidity, all increasing with the number of syndromes in each individual. However, the associations differed across the various FSS. Mutual overlaps of IBS, FM and CFS were greater than could be expected by chance. Conclusions: FSS and BDS are prevalent in the adult Danish population, and cases have high risk of poor self-perceived health, limitation in daily activities, and psychiatric comorbidity. These associations were particularly strong for cases with multiple FSS and multi-organ BDS.

Irritable bowel symptoms, use of healthcare, costs, sickness and disability pension benefits: A long-term population-based study.

Objectives: Irritable bowel syndrome (IBS) is associated with increased healthcare use and work absenteeism. We aimed to investigate long-term use of healthcare services and social benefits across IBS symptom groups. Additionally, we estimated excess healthcare costs. Methods: A longitudinal population-based study comprising two 5-year follow-up studies: The Danish part of the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (Dan-MONICA) 1 (1982-1987) and Inter99 (1999-2004) recruited from the western part of Copenhagen County. The total study population (n = 7278) was divided into symptom groups according to degree of IBS definition fulfillment at baseline and/or 5-year follow-up and was followed until 31 December 2013 in Danish central registries. Poisson regression was used for the analyses adjusting for age, sex, length of education, comorbidity, cohort membership and mental vulnerability. Results: IBS symptom groups compared to no IBS symptoms were associated with an increased number of contacts with primary and secondary healthcare, as well as weeks on sickness and disability benefits. Accounting for mental vulnerability decreased the estimates and all but two associations between IBS symptom groups and outcomes remained statistically significant. The two associations that became insignificant were contacts with psychiatric hospitals and weeks on disability pension. The excess unadjusted healthcare costs for IBS were 680 Euros per year and the overall association between symptom groups and total healthcare costs were statistically significant. Conclusions: IBS symptoms influence the long-term use and costs of healthcare, as well as the use of social benefits in the general population. Mental vulnerability explained some, but not all, of the use of healthcare and social benefits.

Aberrant intestinal microbiota in individuals with prediabetes.

AIMS/HYPOTHESIS: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0 mmol/l or HbA1c of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers of poor metabolic health. METHODS: In the present case-control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age- and sex-matched individuals with normal glucose regulation. RESULTS: We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change -0.64 (SEM 0.23), p adj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), p adj = 5 × 10-4; 0.51 (SEM 0.11), p adj = 1 × 10-4; 0.60 (SEM 0.21), p adj = 0.0497; and 0.92 (SEM 0.21), p adj = 4 × 10-4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log2 fold change -1.74 (SEM 0.41), p adj = 2 × 10-3 and -1.65 (SEM 0.34), p adj = 4 × 10-4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice. CONCLUSIONS/INTERPRETATION: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

Chemosensory perception, symptoms and autonomic responses during chemical exposure in multiple chemical sensitivity.

PURPOSE: Multiple chemical sensitivity (MCS) is a prevalent medically unexplained symptom characterized by symptom reactions to everyday chemical exposure below hygienic thresholds. The aim of this study was to investigate the expressions of hyper-reactivity in MCS during whole-body exposure to low concentrations of the odorant n-butanol. METHODS: We exposed 18 participants with MCS and 18 non-ill controls to a low concentration of the odorant n-butanol using an exposure chamber. The first 10 min constituted blank exposure, after which the n-butanol concentration increased and reached a plateau at 11.5 mg/m(3). RESULTS: MCS participants, compared with controls, reported greater perceived odor intensities, more unpleasantness to the exposure and increasing symptoms over time. MCS participants also expressed higher pulse rate and lower pulse rate variability than controls did. No group differences were found for breathing rate or tonic electrodermal activity responses. CONCLUSIONS: We conclude that MCS sufferers differ from healthy controls in terms of autonomic responses, symptoms and chemosensory perception during chemical exposure.

Factors associated with having previously received a diagnosis of fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome: A cross sectional DanFunD study.

OBJECTIVES: Fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome are highly prevalent conditions and part of the functional somatic syndromes (FSS) diagnosis, that are classified under the unifying umbrella term functional somatic disorder (FSD). Multiple factors are associated with FSD symptom development; However, few studies have explored these associations in relation to the diagnosis status. This study aims to examine associations with a previously received FSS diagnosis from a physician in participants fulfilling the FSD diagnostic criteria in a population-based sample. METHODS: This research employs a comprehensive observational approach using a cross sectional design with data from the DanFunD part two cohort. Information about received FSS diagnoses was obtained from self-reported questionnaires. Participants fulfilling the FSD diagnostic criteria were identified with both self-reported questionnaires and diagnostic interviews. Validated questionnaires were used to assess the examined factors. RESULTS: 1704 cases fulfilled the diagnostic criteria for an FSD according to questionnaires or interviews in the DanFunD study. In participants fulfilling the diagnostic criteria, having previously received an FSS diagnosis by a physician was strongly associated with female sex, negative illness perceptions and poor health-related quality of life for questionnaire and interview-based diagnoses. Less consistent associations were observed for lower socioeconomic status, anxiety, and adverse life events. CONCLUSION: Previously received FSS diagnoses showed associations with multiple factors with a particular strong association with female sex and poor health related quality of life.

Neuroticism, perceived stress, adverse life events and self-efficacy as predictors of the development of functional somatic disorders: longitudinal population-based study (DanFunD).

BACKGROUND: Functional somatic disorder (FSD) is a unifying diagnosis that includes functional somatic syndromes such as irritable bowel, chronic widespread pain (CWP) and chronic fatigue. Several psychological factors are associated with FSD. However, longitudinal population-based studies elucidating the causal relationship are scarce. AIMS: To explore if neuroticism, perceived stress, adverse life events (ALEs) and self-efficacy can predict the development of FSD over a 5-year period. METHOD: A total of 4288 individuals who participated in the DanFunD baseline and 5-year follow-up investigations were included. FSD was established at both baseline and follow-up, with symptom questionnaires and diagnostic interviews. Neuroticism was measured with the short-form NEO Personality Inventory, perceived stress with the Cohen's Perceived Stress Scale, ALEs with the Danish version of the Cumulative Lifetime Adversity Measure and self-efficacy with the General Self-Efficacy Scale. Associations were investigated with multiple logistic regression models. RESULTS: Perceived stress predicted incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.04-1.17). Neuroticism predicted incident FSD and chronic fatigue (odds ratios: 1.03-1.16). ALEs predicted incident FSD, CWP and chronic fatigue (odds ratios: 1.06-1.18). An increase in perceived stress from baseline to follow-up was associated with incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.05-1.22). Contrary, an increase in self-efficacy seemed to be a protective factor (odds ratios: 0.89-0.99). CONCLUSIONS: High neuroticism, high perceived stress and a high number of ALEs are risk factors for the development of FSD. Particularly perceived stress seems to be an important contributor to the onset of FSD.

Lipid metabolism and functional somatic disorders in the general population. The DanFunD study.

OBJECTIVES: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark. PARTICIPANTS: A total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots. RESULTS: We found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles. CONCLUSION: This is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sectional design, it cannot be determined whether the findings are consequences or determinants of FSD. Further studies-preferable prospective studies-are needed.

Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD.

OBJECTIVES: It has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case-control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders conducted 2013-2015 in 10 municipalities in the western part of Greater Copenhagen, Denmark. PARTICIPANTS: A total of 6891 men and women aged 18-72 years were included in the analyses after exclusion of 602 persons with missing HRV data. Various delimitations of FSD (chronic fatigue, chronic widespread pain, irritable bowel and bodily distress syndrome) were identified by validated questionnaires and diagnostic interviews. HRV parameters in time and frequency domains were calculated from successive beat-to-beat heart rate (HR) data using the 'E-motion' HR monitor device during 7 min of supine rest. Chronic stress was assessed by Cohen's self-perceived stress scale. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between the various delimitations of FSD and HRV adjusting for chronic stress. RESULTS: Persons with FSD had a slightly higher mean HR and lower HRV as measured by time domain parameters, whereas associations with frequency domain parameters were not consistent. Adjusting for chronic stress attenuated associations slightly. CONCLUSION: The study supports a sympathetic predominance in persons with FSD, which could not be entirely explained by chronic stress. However, it is not possible to conclude whether the association is a causal factor to or a consequence of FSD.

The association of vitamin K status with lung function and disease in a general population.

Introduction: Matrix Gla protein (MGP) is an inhibitor of lung tissue calcification. The plasma level of dephosphorylated-uncarboxylated MGP (dp-ucMGP) is a biomarker of vitamin K status. The present study assessed whether lower vitamin K status (reflected by higher dp-ucMGP) was associated with lung function and lung disease/symptoms. Methods: A general population sample of 4092 individuals, aged 24 to 77 years, underwent a health examination including questionnaires, spirometry and measurements of plasma dp-ucMGP. Associations of dp-ucMGP with lung function and self-reported disease/symptoms were estimated using regression models adjusted for age, sex and height. Associations were expressed as ß-estimates or odds ratios (ORs) per doubling in dp-ucMGP. Results: Lower vitamin K status (higher dp-ucMGP) was associated with lower forced expiratory volume in 1 s (FEV1) (98 mL; 95% CI: 54-141 mL) and lower forced vital capacity (FVC) (136 mL; 95% CI: 85-187 mL). Dp-ucMGP was not associated with the FEV1/FVC ratio (0.0 percentage points higher than the expected value; 95% CI: -1.0-1.0). Furthermore, lower vitamin K status was associated with COPD (OR 2.24, 95% CI: 1.53-3.27), wheezing (OR 1.81, 95% CI: 1.44-2.28) and asthma (OR 1.44, 95% CI: 1.12-1.83). Conclusion: Lower vitamin K status was associated with lower ventilatory capacity (lower FEV1 and FVC), and with higher risk of self-reported asthma, COPD and wheezing. Vitamin K status was not associated with airflow obstruction (FEV1/FVC ratio).

High Perceived Stress and Low Self-Efficacy are Associated with Functional Somatic Disorders: The DanFunD Study.

Objective: Several psychological factors have been proposed to be associated with functional somatic disorders (FSD) including functional somatic syndromes, such as irritable bowel, chronic widespread pain, and chronic fatigue. However, large randomly selected population-based studies of this association are sparse. This study aimed to investigate the association between FSD and perceived stress and self-efficacy, respectively, and to investigate if FSD differed from severe physical diseases on these aspects. Methods: This cross-sectional study included a random sample of the adult Danish population (n = 9656). FSD were established using self-reported questionnaires and diagnostic interviews. Perceived stress was measured with Cohen's Perceived Stress Scale and self-efficacy with the General Self-Efficacy Scale. Data were analysed with generalized linear models and linear regression models. Results: FSD were associated with higher perceived stress and lower self-efficacy, especially for the multi-organ and the general symptoms/fatigue FSD types and for chronic fatigue. However, controlling for the personality trait neuroticism altered the associations with self-efficacy so it became insignificant. The analysis did not support an important interaction between perceived stress and self-efficacy on the likelihood of having FSD. Individuals with FSD presented levels of perceived stress that were not equal, ie higher, to those in individuals with severe physical diseases. Conclusion: FSD were positively associated with perceived stress and negatively associated with self-efficacy. Our study may point to stress being part of the symptomatology of FSD. This underlines the severity of having FSD and stresses the relevance of the resilience theory in the understanding of the condition.

Social economic factors and the risk of multiple chemical sensitivity in a Danish population-based cross-sectional study: Danish Study of Functional Disorders (DanFunD).

OBJECTIVES: Multiple chemical sensitivity (MCS) is a rare multisystem and poly-symptomatic disease characterised by a report of various somatic symptoms attributed to inhalation of volatile chemicals in usually harmless doses. The aim was to explore four selected social factors and the risk of MCS in the general Danish population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Disorders was conducted from 2011 to 2015 which included 9656 participants. PARTICIPANTS: A total of 8800 participants were included in analyses after observations with missing data on exposure and/or outcome were excluded. A total of 164 cases fulfilled the questionnaire criteria for MCS. Of the 164 MCS cases, 101 reported no comorbid functional somatic disorder (FSD) and were included in a subgroup analysis. A total of 63 MCS cases fulfilled the criteria for at least one additional FSD, this subgroup was not included in further analysis. The remaining study population without MCS or any FSD were regarded as controls. OUTCOME MEASURES: We used adjusted logistic regression to calculate OR and 95% CIs of MCS and MCS without FSD comorbidities for each social variable separately including education, employment, cohabitation and subjective social status. RESULTS: We found an increased risk of MCS among the unemployed (OR: 2.95, 95% CI: 1.75 to 4.97), and a twofold increased risk of MCS among individuals with low subjective social status (OR: 2.00, 95% CI: 1.08 to 3.70). At the same time, 4 years or more of vocational training were protective of MCS. No significant associations were observed among MCS cases with no comorbid FSD. CONCLUSION: Lower socioeconomic status was found to be associated with a higher risk of having MCS but not with MCS without FSD comorbidities. Due to the cross-sectional design of the study, we cannot determine whether social status is a determinant or a consequence of MCS.

Are Sexual Assaults Related to Functional Somatic Disorders? A Cross-Sectional Study.

An increasing number of sexual assaults (SAs) are being reported. This study investigated associations between SA and FSD, conceptualized as bodily distress syndrome (BDS), and five functional somatic syndromes (FSSs): chronic widespread pain (CWP), irritable bowel (IB), chronic fatigue (CF), multiple chemical sensitivity (MCS), and whiplash-associated disorder (WAD). Participants (n = 7493) from the population-based cohort Danish Study of Functional Disorders (DanFunD) completed questionnaires on FSD, emotional distress, SA, and sociodemographics. Risk ratios (RRs) for each FSD and emotional distress were calculated in nine models with SA as the primary exposure using generalized linear models with binomial family and log link and were adjusted for other potential risk factors. The results showed that SA was associated with single-organ FSD (RR = 1.51; 95% CI = 1.22-1.87), multi-organ FSD (RR = 3.51; 95% CI = 1.89-6.49), CWP (RR = 1.28; 95% CI = 0.83-1.98), IB (RR = 2.00; 95% CI = 1.30-3.07), CF (RR = 1.81; 95% CI = 1.42-2.32), WAD (RR = 2.62; 95% CI = 1.37-5.03), MCS (RR = 3.04; 95% CI = 1.79-5.17), emotional distress (RR = 1.75; 95% CI = 1.21-2.54), and health anxiety (RR = 1.65; 95% CI = 1.10-2.46). Overall, SA victims experienced significantly more somatic symptoms than individuals not exposed to SA. Adjusting for physical and emotional abuse did not change the observed associations. Our results suggest a large impact of SA on the overall somatic and mental health of SA victims. Due to the cross-sectional study design, further studies are required.

The gut microbiota in multiple sclerosis varies with disease activity.

BACKGROUND: Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known. METHODS: Here, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity. RESULTS: We found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-ß, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages. CONCLUSIONS: Considerable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials.