Background:

Chemical intolerance is a prevalent, medically unexplained symptom characterized by diverse symptoms following weak chemical exposure. The symptom-eliciting exposures are often odorous, and include perfume, fabric softeners and fragrant flowers. Several explanatory mechanisms have been proposed, but empirical data is scarce. By reanalyzing data from previous studies, we aimed to find a criterion for chemical intolerance based on reactions to actual chemical exposure.

Method:

We grouped participants from six previous studies based on their pattern of habituation to weak olfactory (amylacetate and n-butanol) and trigeminal (CO2 and acrolein) compounds. In two studies utilizing event-related potentials, and one functional magnetic resonance imaging study, stimuli were presented intranasally using a dynamic olfactometer. An exposure chamber that allowed full body exposure was used in the remaining three studies.

Results:

Individuals who did not habituate to weak chemical exposure, compared with those who did, reported (1) increasing symptoms during the course of the exposure, (2) greater problems with odors in everyday life, and (3) greater levels of everyday distress. They (4) performed worse on cognitively demanding tasks during exposure, and differed in measures of (5) the autonomic nervoussystem(respiratoryrateandpulseratevariability),(6)low-level inflammation and oxidative stress, and (7) the so called pain matrix of the brain.

Discussion:

Lack of habituation to weak chemical exposure may be a fruitful method of defining a sub-group of chemical intolerance.

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.

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.

Individuals differ considerably when rating the perceived properties of odors, especially over time. A second glance at previously published data-sets from our laboratory revealed that the same invariant exposure often produced both floor and roof effects. An odor that at the end of the exposure ses-sion was regarded as non-existent by one participant, could border the “absoulte maximum” rating category in another. We provide re-analyses from four exposure studies where we illustrate the perceptual variability over time, and outcomes associated with such ratings. We note that high, compared with low ratings of odor intensity over time is associated with ratings of unpleasantness and symptoms, but also with everyday distress, cognitive performance, autonomous nerv-ous system activity and deviating responses in the so-called pain or saliency matrix of the brain. We bring an open ques-tion to ECRO regarding how this considerable variability should be interpreted, and what the consequenced are for research and for setting exposure limits.

A widely held view is that top-down modulation of sensory information relies on an amodal control network that acts through the thalamus to regulate incoming signals. Olfaction lacks a direct thalamic projection, which suggests that it may differ from other modalities in this regard. We investigated the late positive complex (LPC) amplitudes of event-related potentials (ERP) from 28 participants, elicited by intensity-matched olfactory, auditory and visual stimuli, during a condition of focused attention, a neutral condition, and a condition in which stimuli were to be actively ignored. Amplitudes were largest during the attend condition, lowest during the ignore condition, with the neutral condition in between. A Bayesian analysis resulted in strong evidence for similar effects of task across sensory modalities. We conclude that olfaction, despite its unique neural projections, does not differ from audition and vision in terms of task-dependent neural modulation of the LPC.

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 60 min. 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.

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.

Objectives: We tested the hypothesis of high comorbidity between asthma/allergy and chemical intolerance (CI) and between asthma/allergy and building intolerance (BI), and high multimorbidity between asthma/allergy, CI, and BI.

Methods: Population-based questionnaire data were used from 530 participants with asthma/allergy (allergic asthma, nonallergic asthma, allergic rhinitis, and/or atopic dermatitis), 414 with self-reported and 112 with physician-diagnosed CI, and 165 with self-reported and 47 with physician-diagnosed BI. Separate reference groups were formed for each of the five case groups.

Results: Adjusted odds ratios varied from 4.6 to 13.1 for comorbidity, and from 6.6 to 46.4 for multimorbidity.

Conclusion: The large comorbidity and multimorbidity between asthma/allergy, CI, and BI evokes the question as to whether there are similarities in underlying mechanisms between these conditions.

Chemical intolerance (CI) is a term used to describe a condition in which the sufferer experiences a complex array of recurrent unspecific symptoms attributed to low-level chemical exposure that most people regard as unproblematic. Severe CI constitutes the distinguishing feature of multiple chemical sensitivity (MCS). The symptoms reported by CI subjects are manifold, involving symptoms from multiple organs systems. In severe cases of CI, the condition can cause considerable life-style limitations with severe social, occupational and economic consequences. As no diagnostic tools for CI are available, the presence of the condition can only be established in accordance to criteria definitions. Numerous modes of action have been suggested to explain CI, with the most commonly discussed theories involving the immune system, central nervous system, olfactory and respiratory systems as well as altered metabolic capacity, behavioral conditioning and emotional regulation. However, in spite of more than 50 years of research, there is still a great deal of uncertainties regarding the event(s) and underlying mechanism(s) behind symptom elicitation. As a result, patients are often misdiagnosed or offered health care solutions with limited or no effect, and they experience being met with mistrust and doubt by health care professionals, the social care system and by friends and relatives. Evidence-based treatment options are currently unavailable, however, a person-centered care model based on a multidisciplinary treatment approach and individualized care plans have shown promising results. With this in mind, further research studies and health care solutions should be based on a multifactorial and interdisciplinary approach.

BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology.

OBJECTIVES: The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls.

METHOD: Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained.

RESULTS: The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences.

CONCLUSION: We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

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

There is a need for better understanding of various characteristics in hyperacusis in the general population. The objectives of the present study were to investigate individuals in the general population with hyperacusis regarding demographics, lifestyle, perceived general health and hearing ability, hyperacusis-specific characteristics and behavior, and comorbidity. Using data from a large-scale population-based questionnaire study, we investigated individuals with physician-diagnosed (n = 66) and self-reported (n = 313) hyperacusis in comparison to individuals without hyperacusis (n = 2995). High age, female sex, and high education were associated with hyperacusis, and that trying to avoid sound sources, being able to affect the sound environment, and having sough medical attention were common reactions and behaviors. Posttraumatic stress disorder, chronic fatigue syndrome, generalized anxiety disorder, depression, exhaustion, fibromyalgia, irritable bowel syndrome, migraine, hearing impairment, tinnitus, and back/joint/muscle disorders were comorbid with hyperacusis. The results provide ground for future study of these characteristic features being risk factors for development of hyperacusis and/or consequences of hyperacusis.