Metagenomic gut microbiome analysis of Japanese patients with multiple chemical sensitivity/idiopathic environmental intolerance.

BACKGROUND: Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship　between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples. METHODS: We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC). RESULTS: We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively). CONCLUSIONS: The gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018.

Impact of comorbidity on symptomatology in various types of environmental intolerance in a general Swedish and Finnish adult population.

Comorbidity with various health conditions is common in environmental intolerances (EIs), which restricts understanding for what symptoms that are associated with the intolerance per se. The present objectives were to study (i) prevalence of a broad range of specific symptoms in chemical, building-related, electromagnetic field- (EMF) related, and sound EI, irrespective of comorbidity, (ii) prevalence of symptoms in body systems in exclusive EIs, and (iii) increased risk of symptoms in body systems in exclusive EIs that cannot be referred to functional somatic syndromes, inflammatory diseases or mental disorders. Cross-sectional data (n = 4941) were used from two combined population-based surveys, the Västerbotten (Sweden) and Österbotten (Finland) Environmental Health Studies. Categorization of EI cases and controls were based on self-reports. Symptoms were assessed with the Environmental Hypersensitivity Symptom Inventory, and these were converted to 27 symptoms of the International Classification of Primary Care, 2nd edition, in eight chapters of body systems. The results showed, with few exceptions, that all assessed specific symptoms were significantly more prevalent in all four EIs than in referents. Although a large overlap between EIs, characteristic body system symptoms were eye and respiratory symptoms in chemical and building-related intolerance, skin symptoms in EMF-related intolerance, and general and unspecified, digestive, eye, cardiovascular, neurological, and psychological symptoms in sound intolerance. After controlling for various comorbidities, all studied body system symptoms were positively associated with chemical intolerance, fewer with sound intolerance, only one with building-related intolerance, and none with EMF-related EI. In conclusion, a broad range of symptoms are reported in all four EIs implying common mechanisms, but symptoms of certain body systems are more likely to be reported in a certain EI that cannot be explained by comorbidity.

Prevalence and correlation of multiple chemical sensitivity and electromagnetic hypersensitivity with age, sex, and depression in the Japanese population: a retrospective study.

BACKGROUND: In Japan, there are currently no definitive conclusions regarding the characteristics of multiple chemical sensitivity (MCS) and electromagnetic hypersensitivity (EHS). This study aimed to determine the prevalence and correlation of MCS and EHS with age, sex, and depression in the Japanese population. METHODS: An anonymous self-report questionnaire was distributed to 2,007 participants. Variables such as MCS, EHS, depression score, and demographic characteristics were individually evaluated using the U-test, chi-squared test, and correlation analyses. Moreover, we performed a covariance structure analysis to build a structural equation model. RESULTS: Older individuals and women were more likely to exhibit MCS and EHS symptoms. Moreover, depression was correlated with MCS and EHS. CONCLUSIONS: Although MCS and EHS are strongly correlated, they exhibit distinct characteristics and symptoms, indicating that they can be regarded as separate conditions.

Irritant-induced Asthma Caused by Aerotoxic Syndrome.

PURPOSE: Case series on respiratory features of Aerotoxic Syndrome (AS). The term AS has been coined to describe the spectrum of clinical manifestations after aircraft fume events. Among these manifestations, neurological and respiratory symptoms are the most frequently reported complaints. METHODS: Three cases of AS with relevant respiratory features are presented. RESULTS: Cough and shortness of breath for 6 to12 months were the predominant symptoms in the first two cases. The first case also developed neurological symptoms affecting his central nervous system. In the third case, the patient complained for nine years about an unbearable cough triggered by odors, smells, and a variety of indoor and outdoor irritants, among other symptoms of multiple chemical sensitivity. In all three cases, the respiratory symptoms resolved after appropriate treatment. CONCLUSION: Our report aims at raising awareness on AS and calls for actions to improve the management of patients suffering from this syndrome.

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.

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity.

Systemic inflammation and immune activation are striking features of multiple chemical sensitivity (MCS). The rs2298383 SNP of ADORA2A gene, coding for adenosine receptor type 2A (A2AR), has been involved in aberrant immune activation. Here we aimed to assess the prevalence of this SNP in 279 MCS patients and 238 healthy subjects, and its influence on ADORA2A, IFNG and IL4 transcript amounts in peripheral blood mononuclear cells of randomly selected patients (n = 70) and controls (n = 66) having different ADORA2A genotypes. The ADORA2A rs2298383 TT mutated genotype, significantly more frequent in MCS patients than in controls, was associated with a three-fold increased risk for MCS (O.R. = 2.86; C.I. 95% 1.99-4.12, p < 0.0001), while the CT genotype, highly prevalent among controls, resulted to be protective (O.R. = 0.33; C.I. 95% 0.224-0.475, p < 0.0001). Notably, ADORA2A mRNA levels were significantly lower, while IFNG, but not IL4, mRNA levels were significantly higher in TT MCS patients compared with controls. A significant negative correlation was found between ADORA2A and both IFNG and IL4, while a significant positive correlation was found between IFNG and IL4. These findings suggest that A2AR defective signaling may play a relevant role in PBMC shift towards a pro-inflammatory phenotype in MCS patients.

Electrohypersensitivity as a Newly Identified and Characterized Neurologic Pathological Disorder: How to Diagnose, Treat, and Prevent It.

Since 2009, we built up a database which presently includes more than 2000 electrohypersensitivity (EHS) and/or multiple chemical sensitivity (MCS) self-reported cases. This database shows that EHS is associated in 30% of the cases with MCS, and that MCS precedes the occurrence of EHS in 37% of these EHS/MCS-associated cases. EHS and MCS can be characterized clinically by a similar symptomatic picture, and biologically by low-grade inflammation and an autoimmune response involving autoantibodies against O-myelin. Moreover, 80% of the patients with EHS present with one, two, or three detectable oxidative stress biomarkers in their peripheral blood, meaning that overall these patients present with a true objective somatic disorder. Moreover, by using ultrasonic cerebral tomosphygmography and transcranial Doppler ultrasonography, we showed that cases have a defect in the middle cerebral artery hemodynamics, and we localized a tissue pulsometric index deficiency in the capsulo-thalamic area of the temporal lobes, suggesting the involvement of the limbic system and the thalamus. Altogether, these data strongly suggest that EHS is a neurologic pathological disorder which can be diagnosed, treated, and prevented. Because EHS is becoming a new insidious worldwide plague involving millions of people, we ask the World Health Organization (WHO) to include EHS as a neurologic disorder in the international classification of diseases.

Polyallergy (Multiple Chemical Sensitivity) is Associated with Excessive Healthcare Utilization, Greater Psychotropic Use, and Greater Mental Health/Functional Somatic Syndrome Disorder Diagnoses: A Large Cohort Retrospective Study.

BACKGROUND: Associations between the crude capture of polyallergy-also known as multiple chemical sensitivity or multiple drug intolerance syndrome-and mental health/functional somatic syndrome disorders, healthcare utilization, or other clinical phenomenon have not been examined extensively. METHODS: An IRB-approved retrospective chart review of all patients between age 18 and 70 who had a clinical encounter at a large medical center between 2009 and 2014. Patients were stratified into 4 categories based on the absolute number of chart-documented allergies: (1) no allergies; (2) normal allergy (1-4 allergies); (3) polyallergy (5-9 allergies); and (4) "ultrapolyallergy," (≥10 allergies), which were corroborated through a sensitivity analysis. Demographics, comorbidities, and medications were clustered per allergy grouping. Analysis of variance, chi-square, and multivariable logistic regression analyses were employed to test for associations. RESULTS: 2,007,434 patients were examined ("no allergy" group, n = 1,423,631, 70.9%; "normal allergy" group: n = 549,927, 27.4%; "polyallergy" group n = 29,453, 1.5%; "ultrapolyallergy" group, n = 4,423, 0.22%). Proportion of females increased from 51% in the "no allergy" group to 89.6% in the "ultrapolyallergy" group (p < 0.001). Rates of mental health and functional somatic syndrome disorder diagnoses increased significantly across allergy groups (p < 0.001). All psychotropic medication classes were increased significantly across allergy groups (p < 0.001). Healthcare utilization was also significantly elevated across allergy cohorts (p <0.001). CONCLUSIONS: This study demonstrates that polyallergy/multiple chemical sensitivity may serve as a crude yet meaningful indicator of comorbid psychopathology. Drug intolerance mechanisms are reviewed, and both clinical and investigational implications are examined.

Olfactory-Related Quality of Life in Multiple Chemical Sensitivity: A Genetic-Acquired Factors Model.

Genetic polymorphisms as well as environmental exposures to chemical compounds, iatrogenic, psychological, and physical trauma may play a pathophysiological role in multiple chemical sensitivity (MCS) olfactory complaints, given that xenobiotic metabolism is influenced by sequence variations in genes of metabolizing enzymes. Thus, the aim of the present study was to depict-by means of multiple regression analysis-how different genetic conditions, grouped according to their function as well as clinical background and environmental exposure may interfere with those olfactory complaints referred by MCS patients. Therefore, MCS patients after gene polymorphism sequencing, the olfactory-related quality of life score-calculated by means of the Questionnaire of Olfactory Disorder in forty-six MCS patients-have been found to significantly rely on the phase I and II enzymes score and exposure to previous compounds and surgical treatments. The present work-implementing for the first time a genetic-acquired factors model on a regression analysis-further reinforces those theories, positing MCS as a complex, multifactorial, disease in which the genetic risk related to phase I and II enzymes involved in xenobiotic detoxification, olfactory, and neurodegenerative diseases play a necessary, but probably not sufficient role, along the pathophysiological route of the disease.

Chemical intolerance: involvement of brain function and networks after exposure to extrinsic stimuli perceived as hazardous.

BACKGROUND: Chemical intolerance (CI) is a chronic condition characterized by recurring and severe symptoms triggered by exposure to low levels of odorous or pungent substances. The etiology of CI has been a controversial subject for a long time. The aim of this review is to summarize findings on the neurological processing of sensory information during and after exposure to low levels of odorous or pungent substances in individuals with CI, focusing on the brain function and networks. METHODS: Scientific studies on CI published between 2000 and 2019 in academic peer-reviewed journals were systematically searched using medical and scientific literature databases. Only peer-reviewed articles reporting original research from experimental human studies directly associated with CI, and involving related neurological responses or brain imaging after exposure to odorous or pungent substances (i.e., in chemical provocation tests), were considered. RESULTS: Forty-seven studies were found to be eligible for a full-text review. Twenty-three studies met the selection criteria and were included in this review. Evidence indicated that differences between subjects with CI and healthy controls were observed by brain imaging during and after exposure to odorous or pungent substances. Differences in brain imaging were also observed between initial exposure and after exposure to these substances. Neurological processing of sensory information after exposure to extrinsic stimuli in the limbic system and related cortices were altered in subjects with CI. A previous documentable exposure event was likely to be involved in this alteration. CONCLUSIONS: This review documents consistent evidence for the altered neurological processing of sensory information in individuals with CI. Further neurophysiological research exploring the processing of extrinsic stimuli and cognition of sensation through the limbic system and related cortices in CI, and the appearance of symptoms in individuals with CI, are required.

Prevalence of various environmental intolerances in a Swedish and Finnish general population.

OBJECTIVE: To determine the prevalence of various environmental intolerances (EIs), using several criteria in a Swedish and a Finnish general population. Ill-health attributed to low-level environmental exposures is a commonly encountered challenge in occupational and environmental medicine. METHODS: In population-based questionnaire surveys, the Västerbotten Environmental Health Study (Sweden) and the Österbotten Environmental Health Study (Finland), EI was inquired by one-item questions on symptom attribution to chemicals, certain buildings, or electromagnetic fields (EMFs), and difficulties tolerating sounds. The respondents were asked whether they react with central nervous system (CNS) symptoms or have a physician-diagnosed EI attributed to the corresponding exposures. Prevalence rates were determined for different age and sex groups and the Swedish and Finnish samples in general. RESULTS: In the Swedish sample (n = 3406), 12.2% had self-reported intolerance to chemicals, 4.8% to certain buildings, 2.7% to EMFs, and 9.2% to sounds. The prevalence rates for the Finnish sample (n = 1535) were 15.2%, 7.2%, 1.6%, and 5.4%, respectively, differing statistically significantly from the Swedish. EI to chemicals and certain buildings was more prevalent in Finland, while EI to EMFs and sounds more prevalent in Sweden. The prevalence rates for EI with CNS-symptoms were lower and physician-diagnosed EIs considerably lower than self-reported EIs. Women reported EI more often than men and the young (18-39 years) to a lesser degree than middle-aged and elderly. CONCLUSIONS: The findings reflect the heterogeneous nature of EI. The differences in EI prevalence between the countries might reflect disparities concerning which exposures people perceive harmful and focus their attention to.

Epidemiological association between multiple chemical sensitivity and birth by caesarean section: a nationwide case-control study.

INTRODUCTION: Multiple chemical sensitivity (MCS) is characterized by recurrent nonspecific symptoms that are attributed to exposure to trace levels of environmental agents. Although the clinical symptoms of MCS have been described in several studies, the risk factors for this condition remain unclear. Our aim was to clarify the risk factors for MCS and the association between MCS and birth by caesarean section. METHODS: We conducted a nationwide case-control study of Japanese individuals (aged 20-65 years) with physician-diagnosed MCS (183 cases) and without MCS (345 controls). The study participants were selected from among 150,000 people in a web-based research panel with approximately 1,000,000 registrants. They completed an online survey including questions on their sociodemographic characteristics, birth history (i.e., birth by caesarean section), and other potential risk factors for MCS. Multivariate logistic regression analysis was employed to determine the association between sociodemographic characteristics and the risk of MCS. RESULTS: The proportions of case and control subjects who were born by caesarean section were 39.9 and 7.0%, respectively. The association between birth by caesarean section and MCS was significant even after adjusting for potential confounders (adjusted odds ratio: 6.15; 95% confidence interval: 3.13-12.1). A history of agricultural work, mouth breathing, ≥11 vaccinations in the past 10 years, and residing in a new home (< 1 year-old) ≥3 times were also significantly associated with MCS. CONCLUSION: Our data indicate an epidemiological link between MCS and birth by caesarean section. Moreover, we show that factors other than chemical exposure may be associated with the development of MCS.

Psychological and cognitive effects of laser printer emissions: A controlled exposure study.

The possible impact of ultrafine particles from laser printers on human health is controversially discussed although there are persons reporting substantial symptoms in relation to these emissions. A randomized, single-blinded, cross-over experimental design with two exposure conditions (high-level and low-level exposure) was conducted with 23 healthy subjects, 14 subjects with mild asthma, and 15 persons reporting symptoms associated with laser printer emissions. To separate physiological and psychological effects, a secondary physiologically based categorization of susceptibility to particle effects was used. In line with results from physiological and biochemical assessments, we found no coherent, differential, or clinically relevant effects of different exposure conditions on subjective complaints and cognitive performance in terms of attention, short-term memory, and psychomotor performance. However, results regarding the psychological characteristics of participants and their situational perception confirm differences between the participants groups: Subjects reporting symptoms associated with laser printer emissions showed a higher psychological susceptibility for adverse reactions in line with previous results on persons with multiple chemical sensitivity or idiopathic environmental intolerance. In conclusion, acute psychological and cognitive effects of laser printer emissions were small and could be attributed only to different participant groups but not to differences in exposure conditions in terms of particle number concentrations.

Perspectives on multisensory perception disruption in idiopathic environmental intolerance: a systematic review.

PURPOSE: Multiple chemical sensitivity (MCS) also known as idiopathic environmental intolerance/illness (IEI) encompasses a cohort of subjective symptoms characterized by susceptibility to a wide spectrum of environmental compounds, causing symptoms involving various organs and a decrease in quality of life. The aim of this systematic review is to summarize evidence about MCS, with focus on indexed studies analyzing sensory pathway-related disorders. METHODS: Medical databases were searched for English language articles related to the topic, published between 1965 and 2017 in academic, peer-reviewed journals. Particular focus was concentrated on articles depicting disturbances involving sensory organs. References of the relevant articles were examined to identify additional significant documents. RESULTS: Fifty-eight studies were eligible for full text review. Of these, 34 studies met the selection criteria and were included in this analysis. Many variables, such as different diagnostic criteria, lack of homogeneous symptom questionnaires and the general incidence of personality traits in control subjects, biased studies as confounding factors. However, moderate evidences show that sensory pathways are somewhat altered, especially with respect to information processing in the limbic system and related cortical areas. Recent studies suggested the presence, in MCS cohorts, of attention bias, sensitization and limbic kindling, as well as recently revealed subclinical organic alterations along sensory pathways. CONCLUSIONS: Evidences are consistent with MCS/IEI to be the result of a neural altered processing of sensorial ascending pathways, which combined with peculiar personality traits constitutes the underpinning of a multisensory condition needing multidisciplinary clinical approach.

Symptoms related to new flight attendant uniforms.

BACKGROUND: Flight attendants at Alaska Airlines reported health symptoms after the introduction of new uniforms in 2011. The airline replaced the uniforms in 2014 without acknowledging harm. To understand possible uniform-related health effects, we analyzed self-reported health symptoms in crew who participated in the Harvard Flight Attendant Health Study between 2007 and 2015, the period before, during, and after the introduction of new uniforms. METHODS: We calculated a standardized prevalence of respiratory, dermatological and allergic symptoms at baseline, as well as during and after uniform changes in 684 flight attendants with a varying number of surveys completed across each time point. We used Generalized Estimating Equations (GEE) to model the association between symptoms at baseline versus the exposure period after adjusting for age, gender and smoking status and weighting respondents for the likelihood of attrition over the course of the study period. RESULTS: We found the following symptom prevalence (per 100) increased after the introduction of new uniforms: multiple chemical sensitivity (10 vs 5), itchy/irritated skin (25 vs 13), rash/hives (23 vs 13), itchy eyes (24 vs 14), blurred vision (14 vs 6), sinus congestion (28 vs 24), ear pain (15 vs 12), sore throat (9 vs 5), cough (17 vs 7), hoarseness/loss of voice (12 vs 3), and shortness of breath (8 vs 3). The odds of several symptoms significantly increased compared to baseline after adjusting for potential confounders. CONCLUSION: This study found a relationship between health complaints and the introduction of new uniforms in this longitudinal occupational cohort.

(In)Visibility Online: The Benefits of Online Patient Forums for People with a Hidden Illness: The Case of Multiple Chemical Sensitivity (MCS).

Sufferers of medically unexplained conditions that are not observable in the clinic can experience multiple layers of invisibility: a lack of biomedical diagnosis; legal skepticism; political disinterest; and a loss of their prior social identity. For those with environmental sensitivities, this is compounded by literal hiddenness due to often being housebound. Drawing on an online survey of people with multiple chemical sensitivity, this article examines how the everyday experience of invisibility is mitigated by engaging with other patients online. Respondents used online forums to undertake various forms of "visibility work," including attempts to crystallize their suffering into something recognizable medically, legally, and politically, and to reconstruct an identity considered valid and deserving-although the therapeutic potential of online support was contingent on intra-group politics. This study demonstrates that online forums allow biomedicine's "invisible others" to struggle for alternative forms of recognition beyond the clinical gaze.

Expert clinician's perspectives on environmental medicine and toxicant assessment in clinical practice.

BACKGROUND: Most clinicians feel ill-equipped to assess or educate patients about toxicant exposures, and it is unclear how expert environmental medicine clinicians assess these exposures or treat exposure-related conditions. We aimed to explore expert clinicians' perspectives on their practice of environmental medicine to determine the populations and toxicants that receive the most attention, identify how they deal with toxicant exposures and identify the challenges they face and where they obtain their knowledge. METHODS: A qualitative study involving semi-structured interviews with expert environmental clinicians in Australia and New Zealand was conducted. Interviews were recorded and transcribed, and themes were identified and collated until no new themes emerged. RESULTS: Five dominant themes emerged from 16 interviews: (1) environmental medicine is a divided profession based on type of practice, patient cohort seen and attitudes towards nutrition and exposure sources; (2) clinical assessment of toxicant exposures is challenging; (3) the environmental exposure history is the most important clinical tool; (4) patients with environmental sensitivities are increasing, have unique phenotypes, are complex to treat and rarely regain full health; and (5) educational and clinical resources on environmental medicine are lacking. CONCLUSIONS: Environmental medicine is divided between integrative clinicians and occupational and environmental physicians based on their practice dynamics. All clinicians face challenges in assessing toxicant loads, and an exposure history is seen as the most useful tool. Standardised exposure assessment tools have the potential to significantly advance the clinical practice of environmental medicine and expand its reach across other clinical disciplines.

Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study.

BACKGROUND: Previous studies have shown evidence of comorbid conditions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). OBJECTIVE: To estimate the prevalence of comorbidities and assess their associations using a nationwide population-based database of a Spanish CFS/ME cohort. METHOD: A nationally representative, retrospective, cross-sectional cohort study (2008-2015) assessed 1757 Spanish subjects who met both the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian Criteria for CFS/ME. Sociodemographic and clinical data, comorbidities, and patient-reported outcome measures at baseline were recorded. A cluster analysis based on baseline clinical variables was performed to classify patients with CFS/ME into 5 categories according to comorbidities. A multivariate logistic regression analysis was conducted adjusting for potential confounding effects such as age and sex; response and categorical predictor variables were also assessed. RESULTS: A total of 1757 CFS/ME patients completed surveys were collected. We identified 5 CFS/ME clusters: group 1-fibromyalgia, myofascial pain, multiple chemical hypersensitivity, sicca syndrome, epicondylitis, and thyroiditis; group 2-alterations of ligaments and subcutaneous tissue, hypovitaminosis D, psychopathology, ligamentous hyperlaxity, and endometriosis. These 2 subgroups comprised mainly older women, with low educational level, unemployment, high levels of fatigue, and poor quality of life; group 3-with hardly any comorbidities, comprising mainly younger women, university students or those already employed, with lower levels of fatigue, and better quality of life; group 4-poorly defined comorbidities; and group 5-hypercholesterolemia. CONCLUSION: Over 80% of a large population-based cohort of Spanish patients with CFS/ME presented comorbidities. Among the 5 subgroups created, the most interesting were groups 1-3. Future research should consider multidisciplinary approaches for the management and treatment of CFS/ME with comorbid conditions.

Noise sensitivity and hyperacusis in patients affected by multiple chemical sensitivity.

PURPOSE: The aim of this study was to investigate the presence of noise sensitivity and hyperacusis in patients suffering from multiple chemical sensitivity (MCS), a chronic condition characterized by several symptoms following low-level chemical exposure. Moreover, distortion product otoacoustic emissions (DPOAE) were performed to further study cochlear function. METHODS: A questionnaire-based survey was performed. Eighteen MCS patients, selected with strict diagnostic criteria, and 20 healthy age- and gender-matched subjects filled Weinstein's Noise Sensitivity Questionnaire (WNS) and Khalfa's Hyperacusis Questionnaire (HQ). Results were compared with scores from the quick Environmental Exposure Sensitivity Index (qEESI), a routinarily used questionnaire to screen MCS symptoms, and with DPOAE values. An analysis of variance (ANOVA) was performed between MCS and control subjects scores; moreover, Spearman's rank correlation test was performed between questionnaire results. RESULTS: ANOVA testing on DPOAE values showed any significant difference between groups, while WNS, HQ and qEESI scores were significantly higher in MCS group compared to controls. Correlation analysis showed strong positive correlation between WNS, HQ and qEESI in MCS subjects. CONCLUSIONS: For the first time, auditory-related perceptual disorders were studied in MCS. A strong association between WNS, HQ results and MCS symptoms severity has been highlighted. These findings suggest that decreased sound tolerance and noise sensitivity could be considered as possible new aspects of this syndrome, contributing to its peculiar phenotype. Furthermore, as DPOAE values did not differ from healthy subjects, present findings might suggest a 'central' source for such disorders in this group of patients.

A randomised, placebo-controlled trial of transcranial pulsed electromagnetic fields in patients with multiple chemical sensitivity.

OBJECTIVE: To evaluate the efficacy of transcranially applied pulsed electromagnetic fields (PEMF) on functional impairments and symptom severity in multiple chemical sensitivity (MCS) patients. METHODS: The study was conducted as a nationwide trial in Denmark using a randomised, parallel-group, double-blind and placebo-controlled design. Sample size was estimated at 40 participants. Eligibility criteria were age 18-75 years and fulfilment of the MCS case criteria. Participants received either PEMF or placebo PEMF (no stimulation) applied transcranially for 6 weeks. The primary outcome was the Life Impact Scale (LIS) of the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Secondary outcomes were the Symptom Severity Scale (SSS) and the Chemical Intolerance Scale of QEESI. RESULTS: A total of 39 participants were randomised to PEMF or placebo treatment. No significant difference was observed on QEESI LIS between groups with a mean change score of -5.9 in the PEMF group compared with -1.5 in the placebo group (p=0.35, effect size=-0.31). However, a significant decrease was detected on QEESI SSS within and between groups with a mean change score of -11.3 in the PEMF group compared with -3.2 in the placebo group (p=0.03, effect size=-0.60). CONCLUSION: PEMF treatment of 6 weeks showed no effect on functional impairments in MCS. However, a significant decrease in symptom severity was observed.