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PubMed1999

Metal-specific lymphocytes: biomarkers of sensitivity in man.

Many patients attribute their health problems to amalgam and other dental metals. In genetically susceptible indviduals, mercury and gold may function as haptens and elicit allergic and autoimmune reactions. The frequency of metal-induced lymphocyte responses was examined in 3,162 patients in three European laboratories using MELISA(R), an optimized lymphocyte proliferation test. The patients suffered from local and systemic symptoms attributed to dental restorations. The effect of dental metal removal was studied in 111 patients with metal hypersensitivity and symptoms resembling Chronic Fatigue Syndrome (CFS). After consultation with a dentist the patients decided to replace their metal restorations with non-metallic materials. The changes in health and in vitro lymphocyte reactivity were studied by inquiries and follow-up MELISA(R). Lymphocyte reactivity was also analyzed in 116 healthy subjects with no complaints of metal allergy. A significant number of patients had metal-specific lymphocytes in the blood. Nickel was the most common sensitizer, followed by inorganic mercury, gold, phenylmercury, cadmium and palladium. As compared to lymphocyte responses in healthy subjects, the CFS group had significantly increased responses to several metals, especially to inorganic mercury, phenylmercury and gold. Following dental metal removal, 83 patients (76%) reported long-term health improvement. Twenty-four patients (22%) reported unchanged health and two (2%) reported worsening of symptoms. Following dental metal replacement, the lymphocyte reactivity to metals decreased as well. We propose that an inflammatory process induced by metals may modulate the hypothalamic-pituitary-adrenal axis (HPA axis) and trigger multiple non-specific symptoms characterizing CFS and other chronic conditions like myalgic encephalitis (ME) and multiple chemical sensitivity (MCS).

Journal Article↗
PubMed1996

Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure.

BACKGROUND: Reactive airways dysfunction syndrome is a chronic asthma-like condition developing after an acute irritant exposure, and chronic inflammation has been seen on endobronchial biopsy. Reactive upper-airways dysfunction syndrome is chronic rhinitis developing in temporal association with a toxic inhalation exposure, but the pathophysiology is unknown. OBJECTIVES: To study biopsies of the nasal mucosa in patients with reactive upper-airways dysfunction syndrome and in some cases reactive airways dysfunction syndrome developing in temporal association with a chlorine dioxide exposure, to see if a histologic basis for the persistent rhinitis and sensitivity to chemical irritants could be determined. METHODS: Specimens were stained with hematoxylin-eosin and immunoperoxidase stains for substance P, vasointestinal peptide, and S-100 (nerve fibers), and fixed in glutaraldehyde for electron microscopy. Biopsies of three nonexposed subjects were performed for comparison. A pathologist blinded to clinical data interpreted the specimens. RESULTS: Inflammation ratings of exposed individuals were higher than for the nonexposed individuals. The number of nerve fibers stained was greater for patients vs controls. Substance P and vasointestinal peptide staining was nonspecific. Electron microscopy showed desquamation of the epithelium and permeability of epithelial cell junctions. CONCLUSION: This study suggests a mechanism by which ongoing low level exposures perpetuate airway inflammation after an inducing toxic inhalation. A possible overlap between reactive airways dysfunction syndrome, reactive upper-airway dysfunction syndrome and the multiple chemical sensitivity syndrome is suggested.

Adult↗
PubMed2000

Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder.

BACKGROUND: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), and temporomandibular disorder (TMD) share many clinical illness features such as myalgia, fatigue, sleep disturbances, and impairment in ability to perform activities of daily living as a consequence of these symptoms. A growing literature suggests that a variety of comorbid illnesses also may commonly coexist in these patients, including irritable bowel syndrome, chronic tension-type headache, and interstitial cystitis. OBJECTIVE: To describe the frequency of 10 clinical conditions among patients with CFS, FM, and TMD compared with healthy controls with respect to past diagnoses, degree to which they manifested symptoms for each condition as determined by expert-based criteria, and published diagnostic criteria. METHODS: Patients diagnosed as having CFS, FM, and TMD by their physicians were recruited from hospital-based clinics. Healthy control subjects from a dermatology clinic were enrolled as a comparison group. All subjects completed a 138-item symptom checklist and underwent a brief physical examination performed by the project physicians. RESULTS: With little exception, patients reported few past diagnoses of the 10 clinical conditions beyond their referring diagnosis of CFS, FM, or TMD. In contrast, patients were more likely than controls to meet lifetime symptom and diagnostic criteria for many of the conditions, including CFS, FM, irritable bowel syndrome, multiple chemical sensitivities, and headache. Lifetime rates of irritable bowel syndrome were particularly striking in the patient groups (CFS, 92%; FM, 77%; TMD, 64%) compared with controls (18%) (P<.001). Individual symptom analysis revealed that patients with CFS, FM, and TMD share common symptoms, including generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. However, several symptoms also distinguished the patient groups. CONCLUSIONS: This study provides preliminary evidence that patients with CFS, FM, and TMD share key symptoms. It also is apparent that other localized and systemic conditions may frequently co-occur with CFS, FM, and TMD. Future research that seeks to identify the temporal relationships and other pathophysiologic mechanism(s) linking CFS, FM, and TMD will likely advance our understanding and treatment of these chronic, recurrent conditions.

Adult↗
PubMed1993

The science of toxicology and its relevance to MCS.

The definitions and current practice of multiple chemical sensitivity (MCS) are considered in relation to the fundamental principles of toxicology. The salient problem with MCS is that there is no consistent and specific effect from exposure to any specific chemical. This does not allow for any objective test for any disease entity which might be caused by the chemicals as indicated by the theory of MCS. The effects of exposure to chemicals as defined today as MCS are subjective and no report is available to convincingly demonstrate that these effects would not have occurred merely by chance. It is concluded that (1) MCS, as defined, does not allow specificity or consistency for biological reactions to the effects of chemicals; (2) MCS does not provide a testable hypothesis; (3) MCS is contradictory to the fundamental principles of toxicology; (4) current testing procedures for MCS are so subjective that they are useless; (5) there is no evidence that the responses attributed to MCS are any other than those that would occur merely by chance; and (6) the MCS literature attaches an emotional bias to chemicals.

Environmental Pollutants↗
PubMed2004

Long-term exposure to low levels of formaldehyde increases the number of tyrosine hydroxylase-immunopositive periglomerular cells in mouse main olfactory bulb.

Multiple chemical sensitivity (MCS) in response to a long-term low-level chemical exposure is as yet an unclarified disorder. To determine the role of olfactory function in the induction of MCS, immunocytochemical analysis of the main olfactory bulb (MOB) was performed after exposure of mice to low levels of formaldehyde. A long-term exposure resulted in an increase in the number of tyrosine hydroxylase-immunopositive periglomerular cells and may affect the neuronal function of the MOB.

Animals↗
PubMed2004

Effect of prolonged exposure to low concentrations of formaldehyde on the corticotropin releasing hormone neurons in the hypothalamus and adrenocorticotropic hormone cells in the pituitary gland in female mice.

We examine the effect on the hypothalamus-pituitary-adrenal gland (HPA) axis of prolonged exposure to low levels of formaldehyde in female C3H/He mice, using immunocytochemical and RT-PCR methods. Two groups of female mice were exposed to differing concentrations (0, 80, 400, 2000 ppb) of formaldehyde inhalation for 16 h/day, 5 days/week, for 12 weeks. The corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons in the hypothalamus were then examined, together with the adrenocorticotropin hormone (ACTH)-ir cells and ACTH mRNA in the pituitary. One group comprised sham control mice. The other group was made allergic by injection of ovalbumin (OVA) and alum prior to exposure to formaldehyde, since most sick building syndrome (SBS) sufferers are women with allergic disease. These animals were further exposed to aerosolized OVA as a booster four times during the exposure period. Our results showed a dose-dependent increase in the number of CRH-ir neurons in the non-allergy (NAG) group. A similar pattern was found in ACTH-ir cells and ACTH mRNA. The allergy (AG) model group showed an increase in basal levels of all markers of HPA activity. Moreover, the AG mice appeared to respond to the lowest concentration of formaldehyde, and all indices of HPA activity were reduced at the highest concentrations of formaldehyde. These results relate to an important clinical issue and also have implications in the broader area of HPA regulation. We conclude that our experimental system may be a suitable animal model for SBS and/or multiple chemical sensitivity (MCS).

Adrenocorticotropic Hormone↗
PubMed2005

Low level lindane exposure alters extinction of conditioned fear in rats.

Gamma-hexachlorocyclohexane (lindane) is a pesticide with the potential to produce long-term effects on fear or anxiety due to its targeting of the GABA(A) receptor in the brain. Multiple chemical sensitivity (MCS) is a human condition that has been attributed to repeated chemical exposures, with pesticides heavily implicated in the initiation of MCS. The symptoms in MCS patients are wide ranging but prominent among these in a subset of patients is increased evoked panic responses. Drawing a parallel between these responses in MCS patients and a panic model in rats, these studies explored a potential animal model for MCS. The effects of repeated lindane exposure on conditioned fear behavior was examined in adult male Sprague-Dawley rats. Animals were administered vehicle or lindane (intraperitoneally) for either 3 days/week (1, 2 or 5mg) or 5 days/week (2mg) over 2 weeks, and 18 days later were examined for anxiety levels on an elevated plus-maze. One day later, animals were trained for fear conditioning to an odor conditioned stimulus (CS). Freezing behavior was measured 1 day later in the context where pairing occurred, and then for a total of 6 days in a different environment in which either no CS or the CS was presented. After a second 18-day period of no treatment, rats were again tested for their freezing response to the CS for 2 days. Lindane pretreatment did not alter elevated plus-maze performance, nor did it alter contextual freezing behavior. However, pretreatment with lindane decreased the extinction of fear conditioning to the CS such that freezing behavior in controls was significantly lower than in lindane-pretreated rats, and this effect persisted during testing 18 days later. The results indicate that repeated low-level lindane exposure may produce long-lasting changes in anxiety-related neural circuitry. This suggests that odor-triggered symptoms associated with an aversive event may persist in MCS patients because of the ability of some chemicals to alter fear or anxiety circuitry in the brain.

Animals↗
PubMed2006

Effect of long-term exposure to low-level toluene on airway inflammatory response in mice.

Volatile organic compounds are the main substances causing multiple chemical sensitivity reactions in human. Our laboratory has previously showed that the exposure of low-level formaldehyde causes immunogenic and neurogenic inflammatory responses in mice. The aim of the present study was to investigate the effect of long-term, low-level toluene exposure on airway inflammatory responses in mice lung. We exposed female C3H mice to filtered air (0ppm) or 50ppm of toluene for 6h/day on 5days/week for 6 or 12 weeks in the whole body exposure chamber. One day following the last toluene exposure, we collected bronchoalveolar lavage fluid from each mouse and examined cellular infiltration and production of cytokines, chemokines, neurotrophins and substance P by using ELISA method. We found that the number of total cells and macrophages increased significantly in both 6 and 12-week-exposed mice. In addition, the production of interferon-gamma and substance P were decreased significantly and nerve growth factor was not affected in both 6 and 12-week-exposed mice. In contrast, neurotrophin-3 production in bronchoalveolar lavage fluid was significantly increased only in 12-week-exposed mice. Our findings suggest that long-term (12-week) exposure of mice to low-level toluene modulates airway inflammatory response via neurological signaling.

Administration, Inhalation↗
PubMed2006

Explanatory and pragmatic perspectives regarding idiopathic physical symptoms and related syndromes.

In recent years, research-methods literature mainly addressing controlled clinical trials has arisen regarding explanatory and pragmatic treatment trials. Explanatory trials tend to examine causal mechanisms and questions of efficacy and value internal validity (creating optimal study conditions) over generalizability (using study results to understand treatment effects in real-life patient populations). In contrast, pragmatic trials value "external relevance" (generalizability) of study results over "internal elegance" so that clinicians and health policymakers can better understand how treatments might impact their patients and policies. This review draws inspiration from these contrasting explanatory and pragmatic perspectives and develops them for clinical and research pertaining to idiopathic physical symptoms and related syndromes (eg, somatization disorder, chronic fatigue syndrome, multiple chemical sensitivities, irritable bowel syndrome). Explanatory and pragmatic perspectives are used to examine these idiopathies with regard to causation, case definition, labels, and treatment. It is concluded that idiopathic symptom syndromes are fundamentally pragmatic clinical and research challenges. For epidemiologic and methodologic reasons, the complex explanations for these syndromes remain largely elusive. Even so, scientific and clinical pragmatism offers the opportunity to reduce disagreement between competing medical disciplines and between clinicians and affected patients with regard to irreconcilable etiologic questions and to remain evidence-based in the care of patients.

Anxiety Disorders↗
PubMed1994

Measuring strategies for the nineties. Future needs from the health point of view.

Technological progress and related social processes will determine the measuring strategies of workplace air monitoring for the nineties even if the objective is dose estimation or compliance. Expectations of the lowest possible exposure, require workplace air monitoring to be closely linked to process control in a life cycle approach. Production regularity and preventive maintenance also become important factors for strategy design. Workroom air may lose some importance as a dose estimate for the estimation of toxicological risk, as multi-factorial causes for work-related diseases become more evident and a number of syndromes of unknown aetiology become increasingly important. Cancer, cardiovascular diseases, the indoor air syndrome and multiple chemical sensitivity are given as examples. Biotechnology and the information revolution have changed the basic principles of health monitoring and surveillance. The individual worker becomes the target and the possibility of individually adjusted monitoring, surveillance and workplace design becomes important.

Air Pollutants, Occupational↗
PubMed2001

[Syndromes in environmental medicine: variants of somatoform disorders].

Concerning the syndromes in environmental medicine, like Multiple Chemical Sensitivities (MCS), Idiopathic Environmental Intolerances (IEI), Sick Building Syndrome (SBS), Chronic Fatigue Syndrome (CFS), Candida Syndrome (CS), and Burnout Syndrome (BS), scientific knowledge in etiology, pathology, pathophysiology, diagnosis, therapy, prevention and prognosis is still lacking until now. A critical comparison shows that it is still impossible to find a scientifically satisfying delimitation. Syndromes in environmental medicine show clinical similarities to somatoform disorders. Furthermore, there are the following possible explanations for the existence of these syndromes: Firstly, they may be a complex interaction of environmental impacts, individual predispositions, psychological influences, as well as processes of mental perception and interpretation. Secondly, they may be an effect of distress influenced by culture and social structures and/or thirdly, they may be an latrogenic determination. A more comprehensive characterisation which better considers the complex clinical manifestations is overdue. Although there are neither scientifically validated procedures for diagnosis or therapy nor prophylactic measures, a hardly comprehensible number of partly unvalidated methods is in practical use. Until the syndromes are not finally defined the terms for the syndromes should not be applied to a certain disease. Despite all uncertainities in the evaluation of syndromes in environmental medicine, physicians have the duty to take the affected persons' problems seriously.

Environmental Medicine↗
PubMed1998

Porphyria and porphyrinology--the past fifteen years.

The porphyrias are diseases caused by defective biosynthesis of heme. Leavened by digressions on porphyria trivia, this article presents selected highlights from the last 15 years of research on the chemistry, diagnosis, and treatment of the porphyrias. Thanks largely to genetic analysis and new light shed on the magical chemistry of heme biosynthesis, this period has seen great advances in the understanding of porphyria. Sequence analyses of the genes for all of the enzymes required for heme biosynthesis have revealed the porphyrias as highly heterogeneous, with multiple mutations underlying each type. As a result of technical advances, clinical porphyrin analyses are easier and more detailed, but their misapplication to "multiple chemical sensitivity syndrome" or "intoxication porphyria" is unfortunate. The prospect of gene therapy shines ever brighter but is neither safe nor effective enough to be considered for porphyria. As practical spin-offs, porphyrins are in use increasingly for diagnosis and treatment of cancer and as herbicides and pesticides. Accounts of alleged porphyria in "Prominent People" in the popular press continue to appear, generating fanciful misconceptions, often at the expense of patients with these fascinating diseases.

Heme↗
PubMed2002

An interdisciplinary therapeutic approach for dealing with patients attributing chronic fatigue and functional memory disorders to environmental poisoning--a pilot study.

Nonspecific symptoms and a general feeling of ill health that is difficult to objectify are the commonest health problems with which patients present to an Environmental Medicine Outpatient Department (OPD). Of this group, a great proportion meets the classification criteria for Chronic Fatigue Syndrome (CFS) or Functional Memory Disorders in association with Idiopathic Chronic Fatigue (FMD-ICF). This is a longitudinal study of the OPD of Environmental Medicine, Freiburg University Hospital, Germany, to determine the feasibility and impact of an interdisciplinary therapeutic approach (self-help program, acupuncture, psychosomatic support by group interventions) in 8 patients with CFS, FMD-ICF, or CFS in association with self-reported Multiple Chemical Sensitivities (sr-MCS). The intervention took into consideration the patients' need for treatment of physical aspects of their disease. This is an important step to motivate patients into required psychosomatic support. Although none of the patients was willing to accept psychosomatic support or psychotherapy at study outset, acceptance of psychosomatic group interventions was high during the study course. Additionally five patients started with personal counseling at the Psychosomatic Clinic, and, without feeling stigmatized, 4 patients started with specific psychotherapy. The patients' quality of life showed no increase after four months, but, as shown by the Sum-Score of SF-36, it had improved significantly at the end of the study, which covered eight months' treatment (p = 0.015). Two follow-up investigations showed that this improvement probably persisted in part (mainly in the dimensions mental health, social function, physical role function, and vitality). In conclusion our interdisciplinary therapeutic approach indicates successful treatment of patients attributing CFS, CFS/sr-MCS, and FMD-ICF to environmental poisoning. We now plan to conduct a randomized controlled trial in the future.

Acupuncture Therapy↗
PubMedDate not supplied

Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures.

The present survey of young adult college students investigated the prevalence of self-reported illness from the smell of the five following common environmental chemicals (cacosmia): (1) pesticide, (2) automobile exhaust, (3) paint, (4) new carpet, and (5) perfume. Sixty-six percent of 643 students reported feeling ill from one or more of the five chemicals; 15% identified the smell of at least four chemicals as making them ill. Ratings of illness from pesticide correlated weakly but significantly with ratings for the largest number of individual symptoms (9 of 11); daytime tiredness and daytime grogginess both correlated at high levels of significance with illness ratings (on a 5-point scale) for four of the five chemicals. The most cacosmic group (CS) included significantly more women (79%) than the noncacosmic group (NS) (49%); women overall were more cacosmic than men (p < .001), even with the significant covariate of depression. Ratings of cacosmia correlated only weakly with scores for depression (r = 0.16), anxiety (r = 0.08), and trait shyness (r = 0.18) in the total sample. On stepwise multiple regression with cacosmia score as the dependent measure, shyness accounted for 5.8% of the variance, while depression, anxiety, sense of mastery, and repression did not enter the equation. Histories of physician-diagnosed hay fever, but not asthma, were more frequent in the CS (16%) than in the NS group (5%). Without the confounds of chronic illness or specific treatment programs, these data are similar to patterns described clinically for a subset of patients with multiple chemical sensitivities (MCS), including previous data on increased nasal resistance in MCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Analysis of chlorpyrifos exposure and human health: expert panel report.

This report summarizes the deliberations of an eight-member panel of scientists convened by Dow AgroSciences in cooperation with the U.S. Environmental Protection Agency (EPA). The panel was charged with evaluating the scientific literature on the health effects potentially associated with exposure to the insecticide chlorpyrifos. Specifically, the panel was asked to (1) evaluate human experience data available and address the adequacy of the available current literature; (2) develop a list of recommendations for epidemiology studies, including appropriate endpoints and study populations, and strengths and weaknesses of each approach; and (3) draft a report to summarize its recommendations. The panel assessed the quality of the existing epidemiologic literature on chlorpyrifos and specific outcomes such as neuropathy (including organophosphate induced delayed neurotoxicity), behavior (cognition and affect), immunologic, and multiple complaints (also referred to as multiple chemical sensitivities). The majority of panel members (five members) agreed that the literature reviewed provided little or no scientific evidence that chlorpyrifos exposure causes harm to human health other than its known cholinergic effects associated with acute poisoning. Those panel members voting in the minority (three members) agreed that the studies reviewed provided inadequate evidence to preclude the possibility of adverse effects to human health from chlorpyrifos exposure at levels associated with its manufacture or professional application. Those voting in the minority suggested further investigation of cohort(s) of workers engaged in either the manufacture or the professional application of chlorpyrifos, or both. Compared to the general population, these groups have relatively high levels of exposure to chlorpyrifos. The primary health outcomes recommended for study were cognitive and affective disorders, with consideration of the assessment of peripheral neuropathy also suggested for at least a subset of the cohort.

Agricultural Workers' Diseases↗
PubMed2002

Self-reported symptoms and medical conditions among 11,868 Gulf War-era veterans: the Seabee Health Study.

US Navy Seabees have been among the most symptomatic Gulf War veterans. Beginning in May 1997, the authors mailed Gulf War-era Seabees a health survey in serial mailings. As of July 1, 1999, 68.6% of 17,559 Seabees contacted had returned the questionnaire. Compared with other Seabees, Gulf War Seabees reported poorer general health, a higher prevalence of all 33 medical problems assessed, more cognition difficulties, and a higher prevalence of four physician-diagnosed multisymptom conditions: chronic fatigue syndrome, posttraumatic stress disorder, multiple chemical sensitivity, and irritable bowel syndrome. Because the four multisymptom conditions were highly associated with one another, the authors aggregated them into a working case definition of Gulf War illness. Among the 3,831 (22% cases) Gulf War Seabee participants, multivariable modeling revealed that female, Reserve, and enlisted personnel and participants belonging to either of two particular Seabee units were most likely to meet the case definition. Twelve of 34 self-reported Gulf War exposures were mildly associated with meeting the definition of Gulf War illness, with exposure to fumes from munitions having the highest odds ratio (odds ratio = 1.9, 95% confidence interval: 1.5, 2.4). While these data do not implicate a specific etiologic exposure, they demonstrate a strong association and a high prevalence of self-reported multisymptom conditions in a large group of symptomatic Gulf War veterans.

Chi-Square Distribution↗
PubMed2006

Lateral parabrachial lesions disrupt paraoxon-induced conditioned flavor avoidance.

Preliminary clinical evidence obtained in Gulf War veterans and patients suffering multiple chemical sensitivity points to the existence of a potential link between environmental exposure to organosphosphates (OPs) and the emergence of unspecific sickness syndromes in which associative Pavlovian conditioning might be partly involved. A laboratory animal model might be a useful tool for analyzing the involvement of conditioning in sickness syndromes potentially linked to OP poisoning. The first objective in the present study was to determine if paraoxon (PX), the neuroactive metabolite of the OP parathion, elicits a conditioned avoidance response to a novel stimulus (a taste-odor compound) in a conditioned flavor aversion procedure. Data obtained in Experiment 1 show conditioned flavor avoidance, demonstrative of the associative nature of the sickness properties of PX. The second objective was to characterize the nature of the specific physiological cue serving as the unconditioned stimulus in PX-induced conditioned avoidance. Despite PX administration did induce cholinergic hyperactivity, as measured by body hypothermia and increased jaw movements, lesions of the lateral parabrachial area (lPB) disrupted PX-elicited flavor avoidance responses, indicating that cholinergic signs were not sufficient as unconditioned stimuli supporting avoidance responses. Given that lPB neural integrity is necessary to process aversive interoceptive information, disruption of conditioned flavor avoidance as a result of lPB lesions is consistent with a central interruption of interoceptive processing in PX-poisoned animals. Data are discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness syndromes potentially induced by OP exposure.

Animals↗
PubMedDate not supplied

Learning to have psychosomatic complaints: conditioning of respiratory behavior and somatic complaints in psychosomatic patients.

OBJECTIVE: Assuming a subjective similarity between the experience of a hyperventilation episode and inhaling CO2-enriched air, we tested whether a respiratory challenge in association with a particular stimulus could result in altered respiratory behavior and associated somatic complaints upon presenting the stimulus only. METHOD: Psychosomatic patients (N = 28) reporting hyperventilation complaints participated in a differential conditioning paradigm using odors with a positive or negative valence as conditioned stimuli (CS+ or CS-) and 7.4% CO2-enriched air as the unconditioned stimulus (US). Three CS+ and three CS-acquisition trials were run. During the test phase, two CS(+)- and two CS(-)-only trials were run, followed by two new test odors (with a positive or negative valence). Respiratory frequency, tidal volume, end-tidal fractional concentration of CO2, and heart rate were measured throughout the experiment. Somatic complaints were registered after each trial. RESULTS: We observed a) increased respiratory frequency and an elevated level of somatic complaints upon presenting the CS+ only; b) a selective association effect: conditioning was only apparent with the negatively valenced CS+ odor; (c) no generalization of respiratory responses and complaints to the new odors; (d) no conditioning effect on dummy complaints that are usually not reported when inhaling CO2; (e) in exploratory comparisons with normal subjects, stronger conditioning effects on typical hyperventilation complaints in patients, and, in female subjects, on respiratory frequency. CONCLUSION: Respiratory responses and psychosomatic complaints can be elicited by conditioned stimuli in a highly specific way. The findings are relevant for disorders in which respiratory abnormalities and/or psychosomatic complaints may play a role and for multiple chemical sensitivity.

Adult↗