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Increased cardiopulmonary disease risk in a community-based sample with chemical odor intolerance: implications for women's health and health-care utilization.

Chemical intolerance, or reported illness from odors of common environmental chemicals (e.g., car exhaust, pesticides), is emerging as an important environmental and public health-care issue. Epidemiologic methods provide relevant heuristic devices for studies of complex disorders, such as chemical intolerance. The authors examined personal and reported parental cardiopulmonary disease prevalence rates in a community sample of chemically intolerant and control individuals. A county government (Tucson, Arizona) employee and kin subset (N = 181; 113 households) completed standard health questionnaires. Investigators determined chemical intolerance (n = 41/181) from self-reports of individuals who felt "moderately" to "severely" ill from exposure to at least three of five chemicals (i.e., car exhaust, pesticides, paint, new carpet, and perfume) on a Chemical Odor Intolerance Index. The authors chose the control group (n = 57/181) on the basis of self-reports of "never" feeling ill on the Chemical Odor Intolerance Index. The chemically intolerant group, which primarily comprised women (78% versus 51% of controls, p < .05), was significantly more likely to report-and to have sought--medical attention for heart problems, bronchitis, asthma, and pneumonia. Reports of heart problems in the chemically intolerant index cases and the occurrence of heart disease in both of their parents were significant (Fisher's p < .05). The chemically intolerant individuals were also significantly more likely to report maternal histories of chest problems (e.g., inhalant allergens, tuberculosis) than controls. The findings of the study suggested that the chemically intolerant individuals (a preponderance of whom were women [sex-related risk]) were more likely to have (a) reported cardiopulmonary problems (i.e., greater health risk); (b) actively sought medical care for these problems (i.e., increased medical utilization); and (c) reported more parental illnesses-particularly heart disease, asthma, and diabetes (i.e., genetic risk). Additional community-based studies of chemical intolerance are needed.

Adult↗

Reactive Intestinal Dysfunction Syndrome (RIDS) caused by chemical exposures.

In this study, the authors describe a new "reactive syndrome," Reactive Intestinal Dysfunction Syndrome (RIDS), which has similarities to the previously described clinical syndromes Reactive Airway Dysfunction Syndrome (RADS) and Reactive Upper Airway Dysfunction Syndrome (RUDS). Given that at least 5 neuropeptides are common to both the respiratory tract and digestive tract, the authors propose that the abnormal secretion of these neuropeptides or the abnormal numbers of their receptors play a role in what is perceived clinically as RADS, RUDS, and RIDS. The relatively large surface areas of both the lungs and gut render them especially vulnerable to the environment to which they are exposed constantly.

Adult↗

Medically unexplained symptoms and neuropsychological assessment.

Several illnesses expressed somatically that do not have clearly demonstrated pathophysiological origin and that are associated with neuropsychological complaints are reviewed. Among them are nonepileptic seizures, fibromyalgia, chronic fatigue syndrome, Persian Gulf War unexplained illnesses, toxic mold and sick building syndrome, and silicone breast implant disease. Some of these illnesses may be associated with objective cognitive abnormalities, but it is not likely that these abnormalities are caused by traditionally defined neurological disease. Instead, the cognitive abnormalities may be caused by a complex interaction between biological and psychological factors. Nonepileptic seizures serve as an excellent model of medically unexplained symptoms. Although nonepileptic seizures clearly are associated with objective cognitive abnormalities, they are not of neurological origin. There is evidence that severe stressors and PTSD are associated with immune system problems, neurochemical changes, and various diseases; these data blur the distinctions between psychological and organic etiologies. Diagnostic problems are intensified by the fact that many patients are poor historians. Patients are prone to omit history of severe stressors and psychiatric problems, and the inability to talk about stressors increases the likelihood of suffering from physiological forms of stress.

Behavioral Symptoms↗

Tolerance test in patients with multiple drug allergy syndrome.

Multiple Drug Allergy Syndrome (MDAS) is a frequent clinical condition characterized by reactions to more than one different class of antibiotics. Even if some studies have previously reported an increased rate of allergic reactions to drugs in patients with a history of antimicrobials and NSAIDs allergy, risk factors and pathogenesis of MDAS are still object of investigation. Moreover, in these subjects it is often difficult to prescribe a safe alternative antibiotic without a tolerance test. In this study we carried out 504 tests in 460 patients with a history of immediate adverse reactions to antibiotics. From the analysis of our results it emerges that risk factors for MDAS are female sex and intolerance to NSAIDs. Risk factors for positive tolerance test are male sex, intolerance to NSAIDs and a history of MDAS, respectively. In conclusion, it seems that tolerance test may represent a valid approach to detect a safe antibiotic in these patients.

Adolescent↗

Occupational and environmental medicine: moving the factory fence or hedging our bets?

Occupational and environmental medicine evolved out of concern for the effect of work hazards on health. The experienced gained in considering such hazards has been extended to understanding general risks in the environment. As we look toward the future, classical occupational and environmental hazards such as over exposure to lead, asbestos and mercury are waning and being replaced by concerns around sustainable development, toxicology testing and exposure information for high production volume chemicals, development of better approaches for setting workplace and community exposure limits, environmental justice and many others. The opportunities for the future exist in overcoming these new challenges.

Endocrine System Diseases↗

Comparison of pharmacokinetic interactions and physiologically based pharmacokinetic modeling of PCB 153 and PCB 126 in nonpregnant mice, lactating mice, and suckling pups.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that can induce neurological defects in infants and children via placental and lactational transfer. To investigate the lactational transfer of PCBs and compare pharmacokinetic interactions among nonpregnant, lactating mice and suckling pups, quantitative time-course measurements of PCB accumulation in tissues were performed. On postnatal day 1, nonpregnant and lactating C57BL/6 mice were exposed to PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl, 20 mg/kg) alone or a mixture of PCB 153 (20 mg/kg) and PCB 126 (3,3',4,4',5-pentachlorobiphenyl, 0.2 mg/kg) by oral gavage. At 1, 3, 6, and 13 days after treatment, PCB 153 and PCB 126 were determined in nonpregnant and maternal tissues as well as in neonatal tissues by gas chromatography (GC). Coadministration of PCB 153 and PCB 126 increased PCB 153 retention in the liver and decreased PCB 153 accumulation in the fat of nonpregnant mice. Lactational transfer was confirmed to be an efficient elimination mechanism for the lactating mice but a major source of exposure in the pups. However, little or no significant pharmacokinetic interactions were observed in lactating mice and suckling pups. To describe pharmacokinetic interactions between PCB 153 and PCB 126, a physiologically based pharmacokinetic model for PCB 153 disposition was developed. The effects of PCB 126 on the fat content in liver and a diffusion permeation constant in fat were incorporated into the physiologically based pharmacokinetic (PBPK) model. This model successfully describes PCB 153 disposition altered by PCB 126 in nonpregnant mice.

Adipose Tissue↗

Deployment stressors and a chronic multisymptom illness among Gulf War veterans.

Unusual health problems have been reported by Gulf War (GW) veterans, but no single etiology has been linked to these illnesses. This study was conducted to determine the association between self-reported GW deployment stressors and an illness defined by a combination of fatigue, mood-cognition, and musculoskeletal symptoms. A total of 1002 GW veterans from this cross-sectional survey of four Air Force units completed a self-administered questionnaire that asked about symptoms, demographic and military characteristics, and stressors during deployment. Severe and mild-moderate illness was positively associated with self-reports of pyridostigmine bromide use, insect repellent use and belief in a threat from biological or chemical weapons. Injuries requiring medical attention were only associated with severe illness. These results suggest a link between self-reported chemical, emotional, and physical exposures, and GW veterans' illness. Further research is needed to determine physiological and psychological mechanisms through which such stressors could have contributed to this symptom complex.

Adult↗

Occupational disease surveillance using disability insurance at an automotive stamping and assembly complex.

Sickness and accident-insurance (sick leave) claims at an automotive stamping and assembly complex were analyzed using Poisson regression over a 4-year period to identify occupational health problems. The incidence of lower-respiratory disability (excluding asthma) was higher in painting operations (rate ratio [RR] = 2.9, 95% confidence interval [CI] = 1.2 to 6.8), and final assembly and processing areas (RR = 2.7, 95% CI = 1.0 to 7.4) at the assembly plant, and in metal assembly (welding) areas (RR = 2.8, 95% CI = 1.4 to 5.7) at the stamping plant. Disability rates for upper-extremity musculoskeletal disorders were statistically significantly higher (RR = 3.1 to 3.8) in major assembly plant production areas, as were back disability rates (RR = 1.5). During the first 6 months of new work assignments in painting or final assembly, respiratory problem rates were four times higher than in other areas. Upper-extremity musculoskeletal rate ratios ranged from 4.4 to 5.7 for new assignments in body, hard trim, and chassis areas. Higher rates in new assignments appeared to result from assignment changes precipitated by developing health problems, or from routine assignments to new tasks, some of which conferred high risk and were tolerated for less than 6 months. Musculoskeletal disability was consistent with known ergonomic hazards and paralleled that reported on the Occupational Safety and Health Administration log. Work-related musculoskeletal and other problems can be readily identified from disability insurance claims without dependence on plant medical visits or workers' compensation records. Disability insurance appears to absorb considerable work-related medical and absence costs.

Accidents, Occupational↗

Media warnings about environmental pollution facilitate the acquisition of symptoms in response to chemical substances.

OBJECTIVE: Previous studies showed that somatic symptoms can be acquired in response to chemical substances using an associative learning paradigm, but only when the substance was foul smelling and not when it smelled pleasant. In this study, we investigated whether warnings about environmental pollution would facilitate acquiring symptoms, regardless of the pleasantness of the smell. METHOD: One group received prior information framing the study in the context of the rapidly increasing chemical pollution of our environment. Another group received no prior information. Conditional odor stimuli (CS) were diluted ammonia (foul-smelling) and niaouli (neutral-positive smelling); the unconditional stimulus (UCS) was 10% CO2-enriched air. Each subject breathed one odor mixed with CO2 and a control odor mixed with air in 80-sec breathing trials. The type of odor mixed with CO2 was counterbalanced across participants. Next, the same breathing trials were administered without CO2. Breathing behavior was measured during each trial; subjective symptoms were assessed after each trial. RESULTS: Only participants who had been given warnings about environmental pollution reported more symptoms to the odor that had previously been associated with CO2, compared with the control odor. This was so for both the foul- and the pleasant-smelling odor. Symptom learning did not occur in the group that did not receive warnings. The elevated symptom level could not be accounted for by altered respiratory behavior, nor by experimental demand effects. CONCLUSIONS: Raising environmental awareness through warnings about chemical pollution facilitates learning of subjective health symptoms in response to chemical substances.

Administration, Inhalation↗

The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate to the site of the symptoms in the airways and was not associated with increased capsaicin cough responsiveness. In conclusion, respiratory symptoms elicited by perfume may reflect local hyperreactivity related to defensive reflexes in the airways, and measurements of the capsaicin cough reflex are relevant when patients with lower respiratory symptoms related to environmental perfume exposures are investigated.

Adult↗

Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity.

BACKGROUND: Exposure to perfume and fragrance products may, in some individuals, cause symptoms from the eyes and airways. The localization, character and risk factors of such symptoms in the general population are unknown. OBJECTIVE: To investigate both the localization and character of symptoms from the eyes and airways elicited by fragrance products, and the associations between such symptoms and skin prick test reactivity (atopy), methacholine bronchial hyper-reactivity (BHR), allergic rhinitis and asthma. METHODS: A questionnaire on mucosal symptoms elicited by fragrance products was posted to 1189 persons who had participated in a Danish population-based study of allergic diseases in 1997/1998. The study included measurement of BHR, atopy, forced expiratory volume in 1 s (FEV1), and serum eosinophilic cationic protein (serum ECP). RESULTS: The response rate was 79.6%. Symptoms from the eyes or airways elicited by fragrance products were reported by 42%. BHR (adjusted odds ratio 2.3, 95% confidence interval 1.5-3.5) was independently associated with symptoms from the eyes and airways elicited by fragrance products. There were no significant associations between these symptoms and atopy, FEV1 or serum ECP. CONCLUSIONS: Mucosal symptoms from the eyes and airways were common in this population. BHR was a significant and independent predictor of these symptoms. The lack of association with atopy suggested that IgE-mediated allergic mechanisms do not play a major role in the development of these symptoms.

Asthma↗

Working towards healthy air in dwellings in Europe.

Poor indoor air quality has been implicated in the increase in allergic and respiratory diseases seen in industrialized countries in recent decades. Although air pollution in the workplace is well studied, much less is known about the consequences of poor air quality in homes. In an attempt to halt or slow down the increase in allergic and respiratory diseases, the European Federation of Allergy and Airways Diseases Patients Associations (EFA) carried out the EU-funded project entitled 'Towards Healthy Air in Dwellings in Europe' (THADE). The aims were to: compile an overview of evidence-based data about exposure to indoor air pollution and its health effects, particularly in relation to allergies, asthma and other respiratory diseases such as chronic obstructive pulmonary disease; review cost-effective measures and technology to improve indoor air quality; review legislation and guidelines on indoor air pollution; produce maps of pollutants in dwellings; and recommend an integrated strategy that defines appropriate indoor air quality policies for implementation in Europe. This paper summarizes the information about air quality in dwellings and indoor environment-related diseases collected by expert consultants within the framework of THADE and terminates with recommendations for actions aimed at improving air quality in homes. The results of this project confirmed that air pollution in dwellings is a relevant health problem. It is a complex problem that must be addressed at European and international levels, and it involves the medical profession, scientific societies, patients' organizations, lawmakers, architects and the building industry. The complete THADE report is available at http://www.efanet.org/activities/documents/THADEReport.pdf.

Air Pollutants↗

The psychosomatic symptom and the self: a sirens' song.

This paper examines the symbolic nature of the psychosomatic symptom. It is suggested that the psychosomatic symptom is an informationally rich symbolic derivative of the Self that serves to focus attention on developmental disturbances in the archetypal processes of constructing body image and interpreting dysphoric somatic sensations. Clinical examples are offered to illustrate the changing nature of the psychomatic symptom in society. The therapeutic importance of monitoring affectual transactions in the transference-countertransference field is stressed.

Ego↗

The compelling anomaly of chemical intolerance.

In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses spread from sick, feverish individuals to those contacting them, paving the way for the germ theory of disease. The germ theory served as a crude, but elegant formulation that explained dozens of seemingly unrelated illnesses affecting literally every organ system. Today, we are witnessing another medical anomaly-a unique pattern of illness involving chemically exposed groups in more than a dozen countries, who subsequently report multisystem symptoms and new-onset chemical, food, and drug intolerances. These intolerances may be the hallmark for a new disease process or paradigm, just as fever is a hallmark for infection. The fact that diverse demographic groups, sharing little in common except some initial chemical exposure event, develop these intolerances is a compelling anomaly pointing to a possible new theory of disease, one that has been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the potential to explain certain cases of asthma, migraine headaches, and depression, as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to evolve in two stages: (1) initiation, characterized by a profound breakdown in prior, natural tolerance resulting from either acute or chronic exposure to chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of symptoms by small quantities of previously tolerated chemicals (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations (alcohol, caffeine). While the underlying dynamic remains an enigma, observations indicating that affected individuals respond to structurally unrelated drugs and experience cravings and withdrawal-like symptoms, paralleling drug addiction, suggest that multiple neurotransmitter pathways may be involved.

Attitude↗

Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions.

In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.

Animals↗

Pavlovian conditioning of emotional responses to olfactory and contextual stimuli: a potential model for the development and expression of chemical intolerance.

Chemical intolerance (CI) in humans is a poorly understood phenomenon of uncertain etiology, seemingly influenced by multiple factors both within and between affected individuals. Several authors have suggested that the development of CI in some individuals may be due, at least in part, to Pavlovian conditioning processes in which the expression of overt symptoms to certain substances reflects classically conditioned responses to previously neutral olfactory and contextual stimuli. In this paper, we describe the potential relationship between olfactory and contextual conditioning in experimental animals and the development and expression of CI in humans. Furthermore, as significant advances have been made in delineating the brain areas that underlie these learned responses, we also review recent research on the contributions of the amygdala and perirhinal cortical region to olfactory and contextual fear conditioning.

Amygdala↗