Does improving indoor air quality lessen symptoms associated with chemical intolerance?

Aim: To determine whether environmental house calls that improved indoor air quality (IAQ) is effective in reducing symptoms of chemical intolerance (CI). Background: Prevalence of CI is increasing worldwide. Those affected typically report symptoms such as headaches, fatigue, ‘brain fog’, and gastrointestinal problems – common primary care complaints. Substantial evidence suggests that improving IAQ may be helpful in reducing symptoms associated with CI. Methods: Primary care clinic patients were invited to participate in a series of structured environmental house calls (EHCs). To qualify, participants were assessed for CI with the Quick Environmental Exposure and Sensitivity Inventory. Those with CI volunteered to allow the EHC team to visit their homes to collect air samples for volatile organic compounds (VOCs). Initial and post-intervention IAQ sampling was analyzed by an independent lab to determine VOC levels (ng/L). The team discussed indoor air exposures, their health effects, and provided guidance for reducing exposures. Findings: Homes where recommendations were followed showed the greatest improvements in IAQ. The improvements were based upon decreased airborne VOCs associated with reduced use of cleaning chemicals, personal care products, and fragrances, and reduction in the index patients’ symptoms. Symptom improvement generally was not reported among those whose homes showed no VOC improvement. Conclusion: Improvements in both IAQ and patients’ symptoms occur when families implement an action plan developed and shared with them by a trained EHC team. Indoor air problems simply are not part of most doctors’ differential diagnoses, despite relatively high prevalence rates of CI in primary care clinics. Our three-question screening questionnaire – the BREESI – can help physicians identify which patients should complete the QEESI. After identifying patients with CI, the practitioner can help by counseling them regarding their home exposures to VOCs. The future of clinical medicine could include environmental house calls as standard of practice for susceptible patients.

Multiple Chemical Sensitivity

Multiple Chemical Sensitivity (MCS), a condition also known as Chemical Sensitivity (CS), Chemical Intolerance (CI), Idiopathic Environmental Illness (IEI) and Toxicant Induced Loss of Tolerance (TILT), is an acquired multifactorial syndrome characterized by a recurrent set of debilitating symptoms. The symptoms of this controversial disorder are reported to be induced by environmental chemicals at doses far below those usually harmful to most persons. They involve a large spectrum of organ systems and typically disappear when the environmental chemicals are removed. However, no clear link has emerged among self-reported MCS symptoms and widely accepted objective measures of physiological dysfunction, and no clear dose-response relationship between exposure and symptom reactions has been observed. In addition, the underlying etiology and pathogenic processes of the disorder remain unknown and disputed, although biologic and psychologic hypotheses abound. It is currently debated whether MCS should be considered a clinical entity at all. Nevertheless, in the last few decades MCS has received considerable scientific and governmental attention in light of the many persons reporting this illness. In this review, we provide a general overview of the history, definition, demographics, prevalence, and etiologic challenges in defining and understanding MCS.

Mast cell activation may explain many cases of chemical intolerance

Background This paper explores the relationship between chemical intolerance (CI) and mast cell activation syndrome (MCAS). Worldwide observations provide evidence for a two-stage disease process called toxicant-induced loss of tolerance (TILT) as a mechanism for CI. TILT is initiated by a major exposure event or a series of lower-level exposures. Subsequently, affected individuals report that common chemical inhalants, foods, and drugs (i.e., various xenobiotics) trigger multi-system symptoms. Purpose To determine whether MCAS provides a plausible biological mechanism for CI/TILT. Methods Using the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI), we compared patients diagnosed with MCAS (n = 147) to individuals who reported chemical intolerances (CI/TILT) following various exposures (n = 345) and to healthy controls (n = 76). Using ANOVA, we compared QEESI scores across groups. Clinical scores for the MCAS patient group were used to predict CI status using logistic regression. Results More than half (59%) of the MCAS group met criteria for CI. A logistic regression model illustrates that as the likelihood of patients having MCAS increased, their likelihood of having CI/TILT similarly increased, to a near-perfect correspondence at the high ends of the QEESI and clinical MCAS scores. Symptom and intolerance patterns were nearly identical for the CI and MCAS groups. Discussion We present data suggesting that xenobiotic activation of mast cells may underlie CI/TILT. The strikingly similar symptom and intolerance patterns for MCAS and TILT suggest that xenobiotics disrupt mast cells, leading to either or both of these challenging conditions. Faced with patients suffering from complex illness affecting multiple organ systems and fluctuating inflammatory, allergic, and dystrophic symptoms, clinicians can now ask themselves two questions: (1) Could MCAS be at the root of these problems? (2) Could environmental exposures be driving MC activation and mediator release? Increasing our understanding of the connection between TILT and MCs has the potential to expose a new link between environmental exposures and illness, offering new opportunities for improving individual and public health. Conclusion The close correspondence between QEESI scores and symptom patterns for MCAS and TILT patients supports xenobiotic-driven mast cell activation and mediator release (i.e., MCAS) as a plausible unifying biological mechanism for CI/TILT, with profound implications for medicine, public health, and regulatory toxicology.

The Brief Environmental Exposure and Sensitivity Inventory (BREESI) An International Validation Study

Background Chemical intolerance is a condition that may result in multisystem symptoms triggered by low levels of exposure to xenobiotics such as chemicals, foods, and drugs. The prevalence of chemical intolerance is estimated to be between 8% and 33% across several countries. Clinicians and researchers require a brief, practical tool for identifying chemical intolerance. Objectives This 5-country, population-based study investigates the validity of a three-item screening questionnaire, the Brief Environmental Exposure and Sensitivity Inventory (BREESI), against the 50-item Quick Environmental Exposure and Sensitivity Inventory (QEESI). Methods One thousand individuals (n = 1,000) in each of 5 countries, the U.S., Japan, Italy, Mexico, and India responded to both the QEESI and the BREESI on a Qualtrics platform by Dyanata, a survey company that provides recruitment services for researchers. We determined performance metrics for BREESI responses comparing the number of items chosen on the BREESI with QEESI scores for chemical intolerance. We used logistic regression to determine the likelihood of chemical intolerance based on scoring 0, 1, 2 or 3 items on the BREESI. We report BREESI sensitivity and specificity, positive and negative predictive values, and positive and negative likelihood ratios. Results Compared to the QEESI reference standard, the BREESI had excellent sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values for chemical intolerance in all countries except Japan. In Japan, the BREESI had poor sensitivity and a poor negative predictive value. Logistic regression shows that in all countries, with each increase in BREESI items endorsed, there is 4- to 5-fold increase in the odds of CI. Although the samples are relatively small for estimating population prevalence, our results suggest interesting differences and overall high prevalence of chemical intolerance. Applying QEESI criteria, India appears to have very high rates of chemical intolerance—over 50% of those sampled (54.7%, 95% CI = 52–58) followed by Japan (40.3%, 95% CI = 40–77), Italy (34.3%, 95% CI = 32–37), U.S. (31.2%, 95% CI = 28–34) and Mexico (26.0%, 95% CI = 23–29). Discussion This study confirms the results of a two recently published validation papers in the U.S. The BREESI performs well as a screening tool for chemical intolerance. The BREESI is a practical tool for researchers, clinicians, and epidemiologists seeking to understand and address this important and prevalent condition.

Validation of a Brief Screening Instrument for Chemical Intolerance in a Large U.S. National Sample

Background: Chemical intolerance (CI) is characterized by multisystem symptoms triggered by low levels of exposure to xenobiotics including chemicals, foods/food additives, and drugs/medications. Prior prevalence estimates vary from 8–33% worldwide. Clinicians and researchers need a brief, practical screening tool for identifying possible chemical intolerance. This large, population-based study describes the validation of a three-item screening questionnaire, the Brief Environmental Exposure and Sensitivity Inventory (BREESI), against the international reference standard used for assessing chemical intolerance, the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Methods: More than 10,000 people in the U.S. responded to the BREESI and the QEESI in a population-based survey. We calculated the overall prevalence of CI in this sample, as well as by gender, age, and income. Common statistical metrics were used to evaluate the BREESI as a screener for CI against the QEESI. Results: The prevalence estimate for QEESI-defined chemical intolerance in the U.S. was 20.39% (95% CI 19.63–21.15%). The BREESI had 91.26% sensitivity (95% CI: 89.20–93.04%) and 92.89% specificity (95% CI: 91.77–93.90%). The positive likelihood ratio was 12.83 (95% CI: 11.07–14.88), and the negative likelihood ratio was 0.09 (95% CI: 0.08–0.12). Logistic regression demonstrates that the predicted probability of CI increased sharply with each increase in the number of BREESI items endorsed (Odds Ratio: 5.3, 95% CI: 4.90–5.75). Conclusions: Chemical intolerance may affect one in five people in the U.S. The BREESI is a new, practical instrument for researchers, clinicians, and epidemiologists. As a screening tool, the BREESI offers a high degree of confidence in case ascertainment. We recommend: screen with the BREESI, confirm with the QEESI.

Validation of a Brief Screening Instrument for Chemical Intolerance in a large U.S. National Sample

Keywords: Chemical Intolerance, Drug Intolerance, Food Intolerance, QEESI, BREESI, Multiple Chemical Sensitivity, Toxicant-induced Loss of Tolerance, Prevalence

Mast Cell Sensitization as a Plausible and Researchable Mechanism for Chemical Intolerance

Background Worldwide observations provide evidence for a two-stage disease process called Toxicant-Induced Loss of Tolerance (TILT), described in this journal in the first of two related papers. The disease process is initiated by a major exposure event, or a series of lower level exposures (Stage I, Initiation). Subsequently, affected individuals report that common chemical inhalants, foods, and drugs trigger multisystem symptoms (Stage II, Triggering). Given that foods and drugs also are comprised of chemicals, we refer to these intolerances simply as “chemical intolerance” (CI). In this second, companion paper we propose mast cell sensitization and mediator release as a plausible and researchable biological explanation for TILT. Methods Using the Quick Environmental Exposure and Sensitivity Inventory (QEESI), we compared patients diagnosed with mast cell activation syndrome (MCAS) (n = 147) to individuals who reported chemical intolerances following various exposures (n = 345), and to controls (n = 76). We compared QEESI scores using ANOVA across groups. Clinical scores for the MCAS patient group were used to predict CI status using logistic regression. Results As the likelihood of patients’ having CI increased, their likelihood of having MCAS similarly increased, to a near-perfect correspondence at the high ends of the QEESI and clinical MCAS scores. Symptom patterns were near-identical for CI and MCAS groups. Conclusion The close correspondence between QEESI scores for MCAS and TILT patients supports mast cell sensitization and mediator release as a plausible biological mechanism underlying both conditions, with implications for medicine, environmental health, and regulatory toxicology.

Toxicant-induced loss of tolerance for chemicals, foods, and drugs: assessing patterns of exposure behind a global phenomenon

Background Despite 15–36% of the U.S. population reporting Chemical Intolerances (CI) or sensitivity, the condition has been overlooked in medicine and public health. CI is characterized by multisystem symptoms and new-onset intolerances that develop in a subset of individuals following a major chemical exposure event or repeated low-level exposures. While Toxicant-Induced Loss of Tolerance (TILT) is a two-stage disease mechanism proposed to explain CI, less is known about the exposures that initiate the disease, than about the intolerances that have been documented. Methods We reviewed eight major exposure events that preceded onset of chemical intolerance in groups of individuals sharing the same exposure. Our goal was to identify the chemicals and/or groups of chemicals that were most pervasive during each exposure event as well as identify the concentrations of key chemicals involved in each exposure event and the proportions of exposed individuals who ultimately developed TILT following exposure. Case studies we selected for review included (1) workers at U.S. Environmental Protection Agency (EPA) headquarters during renovations; (2) Gulf War veterans; (3) pesticide exposure among casino workers; (4) exposure to aircraft oil fumes; (5) the World Trade Center tragedy; (6) surgical implants; (7) moldy environments; and (8) tunnel workers exposed to solvents. Results Mixed volatile and semi-volatile organic compounds (VOCs and SVOCs), followed by pesticides and combustion products were most prevalent across TILT initiation events. As a broader category, synthetic organic chemicals and their combustion products were the primary exposures associated with chemical intolerance. Such chemicals included pesticides, peroxides, nerve agents, anti-nerve agent drugs, lubricants and additives, xylene, benzene, and acetone. Conclusion A select group of exposures were predominant in several major initiating events, suggesting their potential role in TILT initiation. Such insights are useful to public health scientists, physicians, and policymakers seeking to minimize harmful exposures and prevent future disease.