Associations between symptoms, modern health worries, and somatosensory amplification in patients with building-related symptoms.

OBJECTIVE: The objective of the present study was to investigate the associations between somatosensory amplification, modern health worries (MHWs), and symptoms among patients with building-related symptoms (BRS). METHODS: Patients with self-reported and medically confirmed BRS (n = 83) were included in this cross-sectional study. The Somatosensory Amplification Scale (SSAS) was used to quantify the tendency to amplify somatic sensations and perceive them as unpleasant and dangerous. Concerns about harmful effects of modern technologies were assessed with the Modern Health Worries Scale (MHWS). Symptoms commonly found in different forms of environmental intolerance were assessed with the Environmental Hypersensitivity Symptom Inventory (EHSI). RESULTS: Patients with BRS were characterized by more frequent and more severe environmental hypersensitivity symptoms compared to a reference population. Females and those with co-morbid self-reported chemical intolerance reported even more symptoms. MHWS and SSAS scores showed weak to moderate associations with symptoms, even after adjusting for socio-economic variables. However, neither the mean MHWS score or the SSAS score of our sample differed from normative scores. CONCLUSION: Patients with BRS are not characterized by elevated levels of MHWs and somatosensory amplification, thus other, psychosocial and/or environmental, factors may have contributed to the development of the condition. However, the associations between severity of symptoms and MHWs and somatosensory amplification suggest that psychosocial characteristics may substantially influence symptom experience in this group.

Comparable responses to a wide range of olfactory stimulation in women and men.

The evidence for differences between women and men in terms of olfactory abilities is contradictory. We analyzed women and men's performance and reactions to a wider range of odour exposure outcomes than usually studied, to assess possible differences and similarities between sexes. Measures of sensitivity and sensory decision rule were established in 37 women and 39 men. Perceptual, cognitive, symptom-related and autonomic nervous system (skin conductance level and heart-rate variability) reactions were also assessed during extended ambient odour exposure, as well as participants' self-rated chemical intolerance. Bayesian analyses consistently revealed greater support for sex-related similarities than differences, suggesting that women and men perform and react comparably not only in terms of basic olfactory measures, but also to environmental odour exposure mimicking everyday situations.

Stress and Sleep in Relation to Severity of Building Related Symptoms.

OBJECTIVE: This study investigates different aspects of stress and sleep in medically examined individuals with varying severity of building-related symptoms (BRS). METHODS: Three questionnaires were used to assess acute and long-term stress and sleep (Perceived Stress Scale; Shirom Melamed Burnout Questionnaire, and Karolinska Sleep Questionnaire). RESULTS: Individuals with BRS, regardless of severity, did not differ in level of perceived stress (indicator of short-term stress). The indicators of long-term stress differed between the groups where an increased severity was associated with higher levels of burnout and sleep problems. CONCLUSIONS: The study suggests an association between symptom severity and measures of long-term stress and sleep quality. This has implications for the treatment of persons affected by BRS, because not only the environment needs to be treated, but also the concurrent signs of distress, such as burnout or sleep problems.

Feasibility and reliability of measures of bioactive lipids in human plasma and nasal mucosa.

Analysis of bioactive lipids is increasingly useful in clinical studies, and there is a need for non-invasive and easy-to-use sampling methods that meet the demands of reliability. Samples that can be taken by a non-professional and that can be taken repeatedly so as to provide more detailed information about the inflammatory process are often desired. In this study, the feasibility of non-invasive sampling of nasal mucosa and saliva for the analysis of bioactive lipid mediators (e.g. oxylipins and endocannabinoids) was evaluated in a pilot study (n = 10). In a second study, the reliability (relative and absolute) of sampling of these lipid mediators derived from nasal mucosa and from plasma was assessed by calculation of the intraclass correlation coefficient and Bland-Altman's limit of agreement. Samples were taken at the same time of day on two occasions from a cohort of individuals with and without building-related intolerance (n = 37). Nasal mucosa proved to be a suitable matrix for the analysis of bioactive lipids and was therefore included in the study on reliability together with the plasma samples. Relative reliability varied among the identified oxylipins and endocannabinoids. Arachidonic acid derivatives showed generally better reliability. Absolute reliability measures also varied indicating that only a subset of the oxylipins and endocannabinoids were suitable as biomarkers in either nasal mucosa or plasma and should therefore be used with caution for that purpose.

Odor perception and symptoms during acrolein exposure in individuals with and without building-related symptoms.

Building-related symptoms (BRS) is a significant work-related and public health problem, characterized by non-specific symptoms occurring in a particular building. The cause of BRS is unknown, but certain reactive compounds are suggested risk factors. The aim of this controlled exposure study was to investigate whether BRS cases report more odor annoyance and symptoms and show altered autonomous nervous system (ANS) response during exposure to the reactive aldehyde, acrolein in comparison with referents. Individuals with BRS (n = 18) and referents (n = 14) took part in two exposure sessions (80 min). One session contained heptane alone, and the other heptane and acrolein. Perceived odor annoyance; eye, nose, and throat symptoms; and ANS response were measured continuously. BRS cases did not experience more odor annoyance; eye, nose, and throat symptoms; or altered ANS response in comparison with referents during the exposures. Supplementary analyses revealed that BRS cases that also reported chemical intolerance perceived more symptoms than referents during acrolein exposure. Acrolein exposure at a concentration below previously reported sensory irritation detection thresholds is perceived as more irritating by a subgroup of BRS individuals compared with referents. The results of this study indicate that a subset of individuals with building related symptoms (BRS) has a lowered sensory irritation threshold towards acrolein exposure. Future guidelines on chemical exposures to acrolein should take time and individual sensitivity into account.

The relation of neuroticism to physiological and behavioral stress responses induced by auditory startle.

INTRODUCTION: The negative cognitive effects of the startle response are not yet fully understood. Ecological observations in the aviation field indicate risk for severe outcomes in complex or pressured situations, while sparse previous research suggests milder negative effects on simple cognitive tasks. Neuroticism is proposed as a factor related to the level of negative effects following startle. METHODS: This study examined the effects of startle on performance in a choice reaction time task and analyzed relations between performance, neuroticism, and physiological stress. RESULTS: Our results indicate that reaction time directly following startle was not affected, but reaction time in subsequent trials was significantly slower. Neuroticism and physiological stress were both unrelated to this performance effect. DISCUSSION: We argue that higher complexity/demand tasks are necessary to complement the research on base cognitive functioning in relation to startle. If neuroticism is related to startle effects, this is more likely to be found in these higher demand situations.

Symptoms and oxylipins in plasma before and after exposure to rooms in which individuals have both experienced and not experienced building-related symptoms - an exploratory study.

The aim of this study was to investigate if there are differences in symptom ratings and plasma concentrations of oxylipins as a measure of acute inflammation between individuals with building-related symptoms (BRS) and referents during exposure to rooms where people experienced BRS and rooms where they did not experience BRS. Medically examined individuals with BRS and healthy, age and sex matched referents working in the same building were exposed for 60 min. Ratings of symptoms and collection of blood to measure oxylipins in plasma were performed before and after each exposure. Individuals with BRS reported more symptoms (mostly mucosal) than the referents in the problem rooms and there was a tendency towards a difference between the groups in concentration of metabolites from the cyclooxygenase pathway (COX). The mean reported intensity of symptoms among all participants was also found to be positively correlated with both COX and lipoxygenase (LOX-15) oxylipins in problem rooms.

Skin sensitivity to capsaicin, perceived stress and burn out among patients with building-related symptoms.

OBJECTIVE: The mechanisms behind building-related symptoms have remained unknown despite many years of research. It is known that environmental and psychosocial factors are of importance. Some receptors in the Transient Receptor Potential family elicit the same symptoms when stimulated, as reported by those suffering from building-related symptoms. The aim of this study was to compare capsaicin sensitivity between people with and without skin symptoms. A second aim was to investigate perceived stress among individuals with different levels of capsaicin sensitivity. METHODS: People referred to an occupational health care unit and judged to have building-related symptoms by a physician answered a questionnaire regarding their symptoms. Solutions with different capsaicin concentrations were applied to participants' nasolabial folds. Self-reported stress and burnout were assessed using two questionnaires: the Perceived Stress Scale (PSS) and the Shirom-Melamed Burnout Questionnaire (SMBQ). RESULTS: We found that people who reported facial erythema or itching, stinging, tight or burning facial skin were more sensitive than those without symptoms and similarities with Sensitive Skin are discussed. We also found that participants who reacted to the lowest capsaicin concentrations scored significantly higher on scales for stress and burnout. CONCLUSIONS: We found associations between sensitivity to capsaicin and skin symptoms among people with building-related symptoms, as well as associations between capsaicin sensitivity and perceived stress/burnout.

Differences in chemical composition of indoor air in rooms associated/not associated with building related symptoms.

Building related health effects or symptoms (BRS), known also as sick-building syndrome (SBS), are a phenomenon that is not well understood. In this study, air samples from 51 rooms associated with BRS and 34 control rooms were collected on multi-sorbent tubes and analyzed by a non-target approach using comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry techniques. The large amount of data gathered was analyzed using multivariate statistics (principle component analysis (PCA) and partial least squares (PLS)). This new analysis approach revealed that in rooms where people experienced BRS, petrochemicals and chemicals emitted from plastics were abundant, whereas in rooms where people did not experience BRS, flavor and fragrance compounds were abundant. Among the petrochemicals benzene and 2-butoxyethanol were found in higher levels in rooms where people experienced BRS. The levels of limonene were sometimes in the range of reported odor thresholds, and similarly 3-carene and beta-myrcene were found in higher concentrations in indoor air of rooms where people did not experience BRS. It cannot be ruled out that these compounds may have influenced the perceived air quality. However, the overall variability in air concentrations was large and it was not possible to accurately predict if the air in a particular room could cause BRS or not.

Chemical Intolerance Is Associated With Altered Response Bias, not Greater Sensory Sensitivity.

Chemical intolerance is a surprisingly prevalent condition or affliction characterized by adverse reactions to low levels of chemical, often odorous stimulation. Sufferers often assume that their plight is due to an uncommon sensory acuteness, yet studies repeatedly fail to reveal altered detection thresholds. Here, we investigated whether self-reported chemical intolerance is associated with altered sensory sensitivity or response bias. The sensory acuity (sensitivity; A) and sensory decision rule (criterion; B) to n-butanol was assessed using the method of constant stimuli in 82 participants with different degrees of chemical intolerance (low to high). Higher self-reported chemical intolerance was associated with a lower criterion, but not with sensitivity.

A standardized protocol for comparable analysis of GSH/GSSG by UHPLC-ESI-MSMS for human plasma.

Variability in the levels of GSH and GSSG in plasma is suggested to derive from inadequate pre-processing methods. The aim of this study was to develop a protocol for comparable and reliable measurements of GSH/GSSG. Venous blood from 8 healthy individuals were collected and divided into 7 different pre-processing procedures. For three of the samples an extraction mixture was added after 0 (baseline), 4 and 8 min and for three of the samples the extraction mixture was added at different times during defrost. A worst case scenario where a sample was left in a cool box during 6 h was also included. The samples were analyzed with UHPLC-ESI-MSMS. A large difference in the levels of GSH and GSSG were identified and it was clearly associated with the sample handling procedures. A sample left untreated for 4 min will have significantly reduced amount of GSH. Stability tests showed that the level of GSH was reduced after 3 months in -80 °C.

Building-Related Environmental Intolerance and Associated Health in the General Population.

People frequently attribute adverse symptoms to particular buildings when exposure to pollutants is low, within nonhazardous levels. Our aim was to characterize building-related intolerance (BRI) in the general population. Data were derived from two population-based questionnaire surveys, the Västerbotten and Österbotten Environmental Health Study. We identified cases of BRI if respondents reported symptoms emerging from residing in certain buildings, when most other people had none. The questionnaires covered lifestyle factors, perceived general health, BRI duration and symptom frequency, the emotional and behavioral impact of BRI, coping strategies, and physician-diagnosed diseases. From the total of 4941 participants, we formed two case groups, 275 (5.6%) fulfilled criteria for self-reported BRI, and 123 (2.5%) for BRI with wide-ranging symptoms. Individuals in both case groups were significantly more often female, single, and perceived their general health as poorer than the referents, i.e., those reporting no BRI symptoms. The mean duration of BRI was 12 years. In both case groups, avoidance behavior was found in over 60%, and nearly half of the sample had sought medical care. BRI with wide-ranging symptoms was associated with elevated odds for all studied comorbidities (somatic and psychiatric diseases and functional somatic syndromes). The perceived health of individuals with BRI is poorer and comorbidities are more frequent than among referents. BRI seems to be similar to other environmental intolerances and shares features with functional somatic syndromes.

Physical and chemical trigger factors in environmental intolerance.

BACKGROUND: Individuals with environmental intolerance (EI) react to exposure from different environmental sources at levels tolerated by most people and that are below established toxicological and hazardous thresholds. The main aim of this study was to determine the prevalence of attributing symptoms to chemical and physical sources in the environment among individuals with different forms of self-reported EI and in referents. METHODS: Cross-sectional data from a population-based study, the Västerbotten Environmental Health Study (n = 3406), were used and individuals with self-reported EI to chemicals, buildings, electromagnetic fields and sounds as well as a group with multiple EIs were identified. The Environmental-Symptom Attribution Scale was used to quantify degree to which health symptoms are attributed to 40 specific environmental exposures and sources, with subscales referring to the four types of EI. RESULTS: All EI groups, except the group with building related intolerance (BRI), reported more symptoms from the expected sources compared to the referents. In addition, individuals with chemical and sound intolerance reported symptoms from building related trigger factors, and individuals with electromagnetic hypersensitivity reported symptoms from chemical trigger factors. CONCLUSIONS: The study suggests that individuals with BRI react to fewer and more specific trigger factors than do individuals with other EIs, and that it is important to ask about different sources since three of the EI groups attribute their symptoms to a wide variety of sources in addition to the sources to which their EI implicates.

Comorbidity of Airway Inflammatory Diseases in Chemical and Building-Related Intolerance.

OBJECTIVES: This study investigated comorbidity in chemical intolerance (CI) and building- related intolerance (BRI) with (i) chronic sinusitis, chronic obstructive pulmonary disease, allergic and nonallergic asthma and allergic rhinitis, and (ii) airway inflammatory symptoms. METHODS: Data from two population-based questionnaire surveys, the Västerbotten and Österbotten Environmental Health Studies, were used. The participants were categorized as CI or BRI and referents, and binary logistic regression analysis was applied. RESULTS: Prevalence rates for the case groups were 7.2% to 40.0% for diseases and 24.3% to 68.9% for symptoms, whereas adjusted odds ratios (ORs) were 3.4 to 26.1 for diseases and 3.3 to 17.0 for symptoms, all being significantly higher than unity. Prevalence rates and ORs were in general higher in BRI than in CI. CONCLUSION: Inflammatory airway diseases and symptoms are associated with CI and BRI, which encourages further research regarding underlying mechanisms and treatments.

Levels of oxylipins, endocannabinoids and related lipids in plasma before and after low-level exposure to acrolein in healthy individuals and individuals with chemical intolerance.

Oxylipins and endocannabinoids play important biological roles, including effects upon inflammation. It is not known whether the circulating levels of these lipids are affected by inhalation of the environmental pollutant acrolein. In the present study, we have investigated the consequences of low-level exposure to acrolein on oxylipin, endocannabinoid and related lipid levels in the plasma of healthy individuals and individuals with chemical intolerance (CI), an affliction with a suggested inflammatory origin. Participants were exposed twice (60min) to heptane and a mixture of heptane and acrolein. Blood samples were collected before exposure, after and 24h post-exposure. There were no overt effects of acrolein exposure on the oxylipin lipidome or endocannibinoids detectable in the bloodstream at the time points investigated. No relationship between basal levels or levels after exposure to acrolein and CI could be identified. This implicates a minor role of inflammatory mediators on the systemic level in CI.

Symptoms from masked acrolein exposure suggest altered trigeminal reactivity in chemical intolerance.

BACKGROUND: Chemical intolerance (CI) is a widespread occupational and public health problem characterized by symptoms that reportedly result from low-levels of chemical exposure. The mechanisms behind CI are unknown, however modifications of the chemical senses (rather than toxic processes) have been suggested as key components. The aim of this study was to investigate whether individuals with self-reported CI report more sensory irritation during masked acrolein exposure compared to controls without CI. METHODS: Individuals with CI (n=18) and controls without CI (n=19) were exposed in an exposure chamber. Each participant took part in two exposure conditions - one with heptane (the masking compound), and one with heptane and acrolein at a dose below previously reported sensory irritation thresholds. The exposures lasted for 60min. Symptoms and confidence ratings were measured continuously throughout the exposure as were measurements of electrodermal activity and self-reported tear-film break-up time. Participants were blind to exposure condition. RESULTS: Individuals with CI, compared with controls reported greater sensory irritation in the eyes, nose and throat when exposed to acrolein masked with heptane. There was no difference during exposure to heptane. CONCLUSIONS: Masked exposure to acrolein at a concentration below the previously reported detection threshold is perceived as more irritating by individuals with CI compared with controls. The results indicate that there is altered trigeminal reactivity in those with CI compared to controls.

Short-term olfactory sensitization involves brain networks relevant for pain, and indicates chemical intolerance.

Chemical intolerance is a medically unexplained affliction that implies deleterious reactions to non-toxic everyday chemical exposure. Sensitization (i.e. increased reactivity to repeated, invariant stimulation) to odorous stimulation is an important component in theoretical explanations of chemical intolerance, but empirical evidence is scarce. We hypothesized that (1) individuals who sensitize to repeated olfactory stimulation, compared with those who habituate, would express a lower blood oxygenated level dependent (BOLD) response in key inhibitory areas such as the rACC, and higher signal in pain/saliency detection regions, as well as primary and/or secondary olfactory projection areas; and (2) olfactory sensitization, compared with habituation, would be associated with greater self-reported chemical intolerance. Moreover, we assessed whether olfactory sensitization was paralleled by comparable trigeminal processing - in terms of perceptual ratings and BOLD responses. We grouped women from a previous functional magnetic imaging study based on intensity ratings of repeated amyl acetate exposure over time. Fourteen women sensitized to the exposure, 15 habituated, and 20 were considered "intermediate" (i.e. neither sensitizers nor habituaters). Olfactory sensitizers, compared with habituaters, displayed a BOLD-pattern in line with the hypothesis, and reported greater problems with odours in everyday life. They also expressed greater reactions to CO2 in terms of both perceived intensity and BOLD signal. The similarities with pain are discussed.

Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session.

OBJECTIVES: To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure. DESIGN: Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure. SETTINGS: Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper. PARTICIPANTS: 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls. OUTCOME MEASURES: 17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels. RESULTS: MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls. CONCLUSIONS: MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.

Effects of Negative Affectivity and Odor Valence on Chemosensory and Symptom Perception and Perceived Ability to Focus on a Cognitive Task.

The aim was to gain understanding for the impact of negative affectivity (NA) and odor valance on perceptual aspects during low-level odorous exposure. Fifty-five young adults who were either relatively low or high in NA (anxiety, depression, and somatization) were randomized for exposure to either limonene (pleasant odor) or pyridine (unpleasant odor). In an exposure chamber, they took part in baseline, blank and stable exposure sessions, during which they rated odor intensity, impact on ability to focus on an imagined cognitive task, and intensity of symptoms. The results showed higher ratings of negative impact on ability to focus during exposure to the unpleasant odor compared with the pleasant odor, and an association between NA and symptom intensity, with 18% of the variance in symptom intensity explained by somatization. The association between NA and symptom intensity was found to be driven by the factor sex. These results imply (a) that prior findings of odorous exposure that interfere negatively with work performance may be due to impact of an unpleasant odor on ability to focus on cognitive tasks and (b) that there are associations between NA, sex, and symptoms that may partly be referred to attentiveness to and interpretation of bodily sensations.

Human exposure to acrolein: Time-dependence and individual variation in eye irritation.

The aim of the study was to examine the time dependence on sensory irritation detection following exposure to threshold levels of acrolein, in humans. The exposures occurred in an exposure chamber and the subjects were breathing fresh air through a mask that covered the nose and mouth. All participants participated in four exposure conditions, of which three consisted of a mixture of acrolein and heptane and one of only heptane. Exposure to acrolein at a concentration half of the TLV-C lead to sensory irritation. The perceived sensory irritation resulted in both increased detectability and sensory irritation after about 6.8min of exposure in 58% of the participants. The study confirm the previously suggested LOAEL of about 0.34mg/m(3) for eye irritation due to acrolein exposure. The sensory irritation was still significant 10min after exposure. These results have implications for risk assessment and limit setting in occupational hygiene.