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Our Changed Environment After World War II, people began using a broad range of synthetic organic chemicals in their homes and work. From cleaning fluids and fragrances to construction materials and pesticides, many of these chemicals are novel—having been “invented” within the past 70 years. Over this time, our genes have not changed. This means our bodies’ elaborate detoxification systems are not equipped to effectively deal with these new substances. Chemical exposures can harm mental and physical health in a variety of ways. Cancer‐causing substances are one example. Surprisingly, “indoor air” is the most common source of chemical exposures in many people’s lives. Ninety percent of us spend 90 percent of our day indoors in tightly closed “boxes”—homes, automobiles, daycares, schools, office buildings—exposed to synthetic organic substances that did not exist before the 1940s.

Figure 1. Indoor vs. Outdoor Air Gas chromatography/mass spectrometry helps identify specific chemicals present in air. Each of the peaks in these two graphs represents a single VOC (volatile organic compound) that was present in the air sampled. The two graphs provide a comparison of chemicals (the number of peaks) and their concentrations (height of the peaks) present in two samples. In this recently remodeled building, there were many more chemicals present and at much higher concentrations indoors than outdoors. Source: Trace organic chemical contaminants in office spaces, Building Ventilation and Indoor Air Quality Program, Energy and Environment Division, Lawrence Berkeley Laboratory, University of California Berkeley.

Effects can be significant for adults, but even more so for children during critical windows of development—particularly brain development. Some of us are especially vulnerable to the adverse effects of environmental exposures depending upon our individual genetic susceptibility. Families expecting a baby may be at especially high risk for such exposures. A move to a new house or renovation of a room often brings new furnishings, carpet, paint, fragrances and pesticides. These chemical exposures often occur during times of critical neuronal growth and differentiation in a fetus. Importantly, these exposures are generally preventable. While chemical exposures impact our mental and physical health in myriad ways, we now recognize that there is a wholly new, related disease mechanism called Toxicant‐induced Loss of Tolerance or TILT. TILT is more difficult to understand because it is a two‐step process that is both initiated and, later, triggered, by exposures. 2


TILT (Toxicant‐induced Loss of Tolerance) Toxicant‐induced Loss of Tolerance (TILT) is a two‐step disease mechanism first described in 1996 (Ashford and Miller). It is a new paradigm that has emerged from observations of groups of chemically exposed adults in more than a dozen countries. TILT begins following an acute exposure, e.g., to a pesticide, or a series of low‐level exposures, such as indoor air contaminants in a new home or during remodeling. Susceptible individuals lose tolerance for everyday exposures that never bothered them before and do not bother most people. Thereafter, these everyday exposures trigger symptoms such as such as attention and memory difficulties, mood changes like depression and irritability, gastrointestinal problems, allergies and more. Triggers include various foods, medications, caffeine, alcoholic beverages (in adults) and common chemicals at low levels.

Phenomenology of TILT. TILT develops in two stages: (1) Initiation, i.e., loss of prior, natral tolerance resulting from an acute or chronic exposure (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of multi‐system symptoms by small quantities of previously tolerated substances, e.g., traffic exhaust, cleaning agents, fragrances, foods, drugs, and food/drug combinations (alcohol, caffeine). A physician sees only the tip of the iceberg—the patient’s symptoms—and formulates a diagnosis, a “label,” based on them, e.g., asthma, AD/HD, autism. Background exposures “mask” the relationship between symptoms and triggers. The initial exposure event that caused loss of tolerance may go unrecognized.

“Most diagnoses in medicine are not etiologic—they don’t tell us what caused the illness. They are simply labels for constellations of signs and symptoms. In contrast, TILT is an etiologic diagnosis because it links illnesses with specific exposures.” -Claudia S. Miller, MD, MS 3


When to Consider TILT TILT is not an explanation for every illness. It is an overlooked process that may occur at the same time as other health problems. Some health problems may be totally unrelated and require interventions like surgery or antibiotics. Other health conditions may be improved when TILT is considered as a contributory or causal factor. For patients with high QEESI scores who are suffering with conditions listed in the 7 A’s, understanding the TILT process can identify low‐ risk interventions that can improve quality of life for patients and their families. The following common conditions appear to be on the rise. Are they related to TILT? We suspect that they may be related, because our genes have not changed much and our exposures have increased greatly. Gene-environment interactions play a role in virtually every chronic medical condition. The Human Genome Project drew attention to the fact that genes alone cannot explain most disease. Yet, the contribution of environmental exposures has been comparatively understudied and the research underfunded. Without research, doctors and patients are essentially on their own in seeking possible connections between these conditions and common exposures.

The 7 A’s These are increasingly common diagnoses which may be initiated or exacerbated by food and chemical exposures Autism

2% of children

Attention Deficit / Hyperactivity Disorder (AD/HD)

3 - 7% of children

Autoimmune Disease

3% of adults (Jacobson, 1997)

Asthma

9% of children and 8% of adults

Allergy

20% (AAFA.org)

Food Allergy

4-6% of children (CDC/NIAID)

Eczema

11% of children (Shaw, 2003)

Affective (Mood) Disorders

(Overall): 9.5%

Depression

11% adolescents 5% adults

Bipolar Disorder

3%

Panic Disorder

3%

Addiction

47% of Americans report an addictive disorder (Sussman 2011) including: tobacco, alcohol, illicit drugs and eating

 All prevalence estimates from CDC except where otherwise noted. 4


Potential Initiators and Triggers for TILT Indoor Air Volatile Organic Compounds (VOCs) New carpet Plasticizers Formaldehyde Fragrances Mold VOCs

Combustion-related Products Engine exhaust Tobacco smoke Oil well fire smoke Natural gas Tar/asphalt

Solvents Glues Paints Gasoline Nail polish/remover

Drugs/Medical Devices Vaccines Anesthetics Implants Antibiotics Chemotherapy

TOXICANT-INDUCED LOSS OF TOLERANCE

Pesticides Organophosphates Carbamates Pyridostigmine bromide Pentachlorophenol Pyrethrins/pyrethroids DEET

Cleaning Agents Phenolic disinfectants Ammonia Bleach

Conditions That May Have Their Origins in TILT Neuropsychological Autism Spectrum Disorders (ASD) Attention Deficit Hyperactivity Disorder (AD/HD) Depression Bipolar disorder Anxiety, panic states Migraines and other headaches Seizures Confusion, memory and concentration difficulties Irritability, sudden rage Skin Eczema Hives Other rashes, skin eruptions

Cardiovascular Arrhythmias Hypertension Hypotension Raynaud’s Phenomenon

Respiratory Asthma Reactive Airways Dysfunction Syndrome (RADS) Toluene Diisocyanate (TDI) Hypersensitivity

TOXICANT-INDUCED LOSS OF TOLERANCE

Miscellaneous Syndromes Chronic Fatigue Syndrome “Gulf War Syndrome” Post-911, oil spills, and other Connective Tissue/Musculoskeletal Fibromyalgia disasters Temporomandibular Joint Dysfunction (TMJ) Arthritis Lupus and other autoimmune diseases 5

Combustion-related Products Engine exhaust Tobacco smoke Oil well fire smoke Natural gas Tar/asphalt Ear, Nose and Throat Sinusitis Polyps Recurrent infections and other problems Dizziness


THE ENVIRONMENTAL MEDICAL UNIT: How Eliminating Exposures Can Reveal Sources of Chronic Illness

H

ow can families determine whether their loved one will benefit from a change in diet and environment? We now know that there is a sound, scientific way to get answers— by using a specially designed and constructed hospital facility called an Environmental Medical Unit (EMU). EMU’s employ what I call “Takeaway Medicine” by eliminating all potential exposures in a chemically “clean” hospital environment while controlling diet. Individuals with chronic illness may be unable to link their symptoms to exposures because they are heavily “masked”. Masking results from overlapping reactions to many different chemicals, foods and drugs and normal habituation associated with chronic exposures. Until “masked” people reduce their overall exposures, it is impossible to know which, if any, of their symptoms or underlying health problems may be related to these exposures. Environmental Medical Units, or EMUs, are needed for research, diagnosis, and treatment of TILT. Without an EMU it will be difficult to determine which chemical and food triggers may underlie chronic conditions such as those described as the 7 A’s. Unfortunately, no EMU is currently available in the United States.

Persons who are “TILTed” can improve if all triggers are simultaneously removed. There is a clear and compelling need for EMU’s in every major medical center for research and diagnosis. We appear to be dealing with a new theory of disease— paralleling the germ theory—but involving synthetic organic chemical exposures, resulting in loss of tolerance for foods and our natural environment. Just as the microscope enabled scientists to see “germs” responsible for infectious diseases in the late 1800s, the EMU is a tool that will allow us to “see” the role of exposures in today’s chronic illnesses. With the availability of EMU’s, we can better identify the link between exposures and chronic illness and in so doing, set our loved ones on a path toward wellness. 6


How Does an EMU Work? The EMU is a pristine, environmentally‐controlled hospital or medical unit in which patients can be housed long enough, about 4 to 7 days, to achieve a clean baseline, free of environmentally‐ triggered symptoms. EMU facilitates double-blind, placebo‐controlled challenges with even very low levels of exposures. It will allow researchers to observe patients’ symptoms prior to entry into the EMU after unmasking, and before and after specific challenges, while at the same time employing objective measures such as proteomics, pulmonary function testing, and brain imaging. An EMU must be constructed, furnished, and operated so as to minimize exposure to airborne chemicals. It must be made from non-outgassing materials. No disinfectants, fragrances, or pesticides would be allowed. Ventilation should maximize fresh air and provide optimal filtration for particles (HEPA filters) and gases (charcoal filters). Pure water and organic foods for a rotary elimination diet would be used and, in some cases, fasting may be necessary for achieving a clean baseline. Enter EMU

1

2

4-7 days

3

4

4-7 days

What happens in the EMU? In the figure above we see sine waves which represent the overlapping, waxing and waning of symptoms that occur in a chemically intolerant individual who is responding to multiple exposures. When all exposures are eliminated concurrently in the EMU, environmentally‐induced symptoms will resolve, generally within 4 to 7 days. During this period, withdrawal symptoms typically occur (e.g., headaches, fatigue, joint pain) but once a clean baseline is reached, patients often report their symptoms improved or completely removed. Once the individual has reached a clean baseline, researchers can perform challenges with single exposures one‐at‐a‐time and observe responses in the absence of background noise. 7


Plans for an EMU It’s impossible to imagine a major hospital without an ICU or a CCU. Likewise, large hospitals need EMUs for diagnosing and treating illnesses, like the 7 A’s, in which environmental exposures are suspected of playing a role, e.g., chemical intolerance, asthma, autoimmune diseases, and autism. Without an EMU, physicians and researchers are unable to eliminate background exposures to definitively determine whether a patient can improve when chemical and food triggers are removed. A hospital, in which emergency services are readily available, is the safest location for an EMU.

Images courtesy of HKS Architects

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Design Criteria for an EMU

Filtered air supply and continuous air monitoring to ensure the removal of: • VOCs (charcoal filter) • Fine particles (HEPA filter)

Positive pressure, relative to surrounding hospital areas

Pure spring or filtered water

Organic foods

Non‐outgassing furnishings and construction materials (no chemicals being released to the air)

Safest possible cleaning and operational practices 9


Are You TILTed? The Quick Environmental Exposure and Sensitivity Inventory (QEESI) The Quick Environmental Exposure and Sensitivity Inventory is a validated and published questionnaire that helps patients and doctors identify symptoms and responses to various exposures. The QEESI is used in both clinical practice and research, and has been translated into several languages as researchers in other countries have adopted it for their own studies. The QEESI can be self‐administered. There are 5 sections with a total of 50 questions which take only 12 to 15 minutes to answer. It has high sensitivity and specificity for chemical intolerance. It includes four scales: Symptom Severity, Chemical Intolerances, Other Intolerances, and Life Impact. Each scale contains 10 items, scored from 0 = “not a problem” to 10 = “severe or disabling problem.” A 10‐item Masking Index measures a number of common exposures that often impair individuals’ awareness of their intolerances.

The QEESI is available for download, along with my book and papers—all free of charge at drclaudiamiller.com. You can also take the QEESI online, confidentially, at www.qeesi.org where the Symptom Star is automatically generated for you. The hallmark of TILT is new‐onset intolerances, accompanied by multi‐system symptoms. When evaluating patients, it is important to consider not just a snapshot of current symptoms and intolerances, but how these have changed over time, for example, before and after a pesticide application, home remodeling, or an exposure at work. Roughly half of chemically intolerant patients point to a specific exposure event. Others don’t recall a specific initiating event, or attribute their illness to a series of exposures over time. 10


Symptom Star The Symptom Star, which appears on the front of the QEESI questionnaire, provides a way to graph changes in symptoms over time. Especially in clinical practice, this is a useful, visual way for patients to communicate changes in their symptoms, for example, before and after their “initiating event,” or in response to a therapeutic intervention. The Symptom Star provides a “gestalt” so doctors can know immediately whether they may be dealing with one of these complex individuals.

Before exposure event

After exposure event

HEAD = Head-related symptoms AFF = Affective (mood-related) symptoms NM = Neuromuscular symptoms COR = Heart/chest-related symptoms AIR/NM = Airway or mucous membrane symptoms 11

MS = Musculoskeletal symptoms SKIN = Skin-related symptoms GU = Genitourinary symptoms GI = Gastrointestinal symptoms COG = Cognitive symptoms (difficulty with memory or thinking; confusion)


How Are Chemical Intolerances, Autism and AD/HD Alike? Features

CI

Autism

AD/HD

Multi-system symptoms, especially neurocognitive, mood and GI

X

X

+/–

Can be initiated by pesticides and other xenobiotics

X

X

X

Food intolerances (e.g., wheat, milk)

X

X

X

Food cravings

X

X

X

Chemical intolerances

X

X

X

Drug allergies/adverse drug reactions

X

X

X

“Chemical intolerances, autism and AD/HD are growing concerns in every developed country.” - Claudia S. Miller, MD, MS

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What’s In Your Air?

Potential Sources of Indoor Air Pollution o

Pesticides

o

Fragrances (plug-ins, fragrance-emitting devices (FEDs), carpet freshener, air fresheners, sprays)

o

Cleaning chemicals (phenolic disinfectants, bleach, ammonia, polishes, fragranced cleaners)

o

Scented laundry products (scented dryer sheets, softeners, detergents)

o

Personal care products (perfume/cologne, cosmetics, lotions, fragranced hair/bath products, deodorants; nail polish/remover)

o

Remodeling/construction (paint, caulk, glues, plywood/particle board)

o

Furnishings (formaldehyde/adhesives, foam cushions)

o

Flooring (vinyl, carpet, adhesives)

o

Cooking (combustion gases from gas stove)

o

Molds (including mold VOCs)

Japan’s largest home manufacturer—Sekisui House, Ltd—places a priority on indoor air quality, as well as sustainability and

energy efficiency. The goal is to protect pregnant women, fetal development, and chemically intolerant individuals.

Healthy housing is a fundamental, yet visionary, way of protecting the health of future generations.

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Chemical Exposures in Pregnancy How do chemicals cause TILT? The most direct connection between the air we breathe and our brains is via our noses, the so‐called “nose‐to‐brain” (olfactory‐limbic) pathway. When chemicals or tiny particles such as smoke or traffic exhaust, enter our noses, they are taken up by the olfactory nerves (below olfactory bulb)—tiny exposed nerve endings inside the top of our noses that allow us to smell odors. Here there is no protective blood‐brain barrier. These nerve endings are bathed in the air around us. After entering the olfactory nerves, chemicals are carried (via “retrograde transneuronal transport,” within the nerve cell bodies) up into the olfactory bulb (green) which is, in fact, a part of the brain that extends forward above the nose. The olfactory bulb provides much of the input to the limbic system, or “primitive smell brain” a region present in mammals but not in reptiles. The limbic system is vital for feeding, taking care of our young, temperature regulation and many behaviors that are essential to our survival as a species. This region contains several vital structures: •

The amygdala (light blue), also called “emotion central,” regulates our mood states, including anxiety, depression and irritability.

Olfactory Limbic System

The hippocampus (dark blue) is essential for memory, attention and concentration. Any injury can temporarily or permanently alter our ability to concentrate and retain short‐term memories, such as recalling directions we’ve been told or something we just read. The hypothalamus (red) regulates eating, drinking, and other appetitive behaviors. Exposures may affect food cravings/ addictions/obesity and other addictions. 14


Chemicals entering the limbic system can neurochemically “sensitize” these structures so that subsequent exposure to very tiny amounts of the same or even other substances that enter the body (e.g., odors, pesticides, solvents, alcohol, caffeine, foods) may trigger symptoms involving the respiratory, nervous, gastrointestinal or other systems. The onset of these symptoms in a person who has been “TILTed” can be remarkably rapid, occurring within a breath or two. Our Inside the Womb genes and our personal history of exposures determine who will develop TILT. Effects in a susceptible adult may be reversible within hours to days. However, a genetically susceptible infant whose mother was exposed during pregnancy may sustain permanent and irreversible brain injury. Embryonic brain development begins around 3 weeks post‐conception, before the mother knows she is pregnant! That is when the neural tube, precursor of the brain and central nervous system, begins to form. Disruption of brain development at any stage can have lifelong consequences. A developing child shares one half of its mother’s susceptibility genes, which determine its ability to detoxify chemical and drug exposures. Glutathione and Cytochrome P450 enzymes, among others, determine our individual detoxification abilities. Further, during pregnancy, the mother shares most of her exposures, except those removed by her own detoxification system and the placenta. After birth, infants encounter an enormous array of drugs and chemicals, via inhalation, injection or skin contact ingestion (diet; hand‐to‐mouth activity). 15


16


Environmental Factors Can Disrupt Normal Brain Development Researchers have identified both structural and biochemical abnormalities in the brains of individuals with autism. No single abnormality explains autism. However, infection and the mother’s use of certain drugs during pregnancy have been linked with some cases. Researchers are working to identify genetic and environmental factors that may underlie Autism Spectrum Disorders.

Neuron – Processes and transmits information in the nervous system. The tree‐like dendrites of these cells receive information from other neurons. A long filament (axon) conveys information away from the nerve cell body to terminal knobs or buttons that release chemical signals to other cells. Impaired axon growth, dendrite branching and formation of connections between neurons occur in ASDs. ❶ Corpus Callosum – Connects the left and right hemi‐ spheres of the brain so that information can pass between them. In ASDs these connections are reduced.

❷ Limbic System – Influences memory, emotional memory, and social behavior. In autism, the neurons are smaller and densely packed, suggesting arrested development. Two major components of the Limbic System are: Amygdala – “Emotion central”

Hippocampus – Essential for recording new memories

❸ Cerebellum – Controls balance, posture and coordination, but also facilitates shifting attention, verbal processing and other functions. The most characteristic finding in ASDs is the decreased numbers of this region’s large, densely branched, specialized neu‐ rons (Purkinje cells).

❹ Brain Stem – Controls facial expression and the relaying of audi‐ tory information. Development of the brain stem can be affected by drugs or infections as early as the first month of pregnancy—before a woman even knows she’s pregnant. Autism globally affects the brain’s ability to process a wide variety of information, especially when the information becomes complex. Abnormal cellular organization may affect the Frontal and Temporal Lobes. ❺ Frontal Lobe – Responsible for planning, reasoning, movement and some speech.

❻ Temporal Lobe – Controls speech perception, hearing and some memory. ❼ Parietal Lobe – Responsible for sensation and touch. ❽ Occipital Lobe – Processes visual information.

“At a year of age, if a child’s “joint attention” is lacking, which means that when his parent points to an object, the child does not follow with his gaze, the parent should seek professional advice. Early identification is key because joint attention can be taught, and may lead to improved language development.” ‐ Claudia Miller, M.D., M.S. 17


The Personal Precautionary Principle Expectant mothers can take precautions Within the last 60 years, thousands of new chemicals have been introduced into our lives and homes. Yet little is known about the long‐term health effects of low‐level chemical exposures on the developing brain. Increasingly, researchers today suspect exposures to various medications, pesticides, traffic exhaust, plasticizers, and flame retardants, to name a few, could play a role in the rising numbers of children diagnosed with Autism Spectrum Disorders. In the absence of definitive scientific information, expectant mothers can take precautions by reducing unnecessary exposures during pregnancy. What’s their best weapon? Their nose!

The best odor in your house is no odor. If you smell something, you are inhaling molecules. The odors of certain solvents, pesticides or harsh cleaning products serve as early warning signs that a potentially harmful chemical is nearby. Smells, such as strong fragrances or the smell of new plastics, may simply be irritating to sensitive individuals, but are being studied for their health effects.

Below is a list of some of the things moms‐to‐be can do to reduce unnecessary exposures to chemicals. When to start? Consider the fact that the neural tube, precursor of the brain and nervous system, begins to develop during the first few weeks of pregnancy, before a woman even knows she is pregnant. “We must identify and eliminate potentially harmful exposures in our personal environments. The government is not going to do it for us. There is no profit in regulations to reduce exposures. It is up to us to make better choices and to influence the government and the marketplace. There are many things we cannot control but we can educate ourselves and our patients and make safer choices in every aspect of our daily lives.”

‐ Claudia S. Miller, MD, MS 18


Instead of using:

Try using:

Pesticides indoors or on lawns, or mothballs

Baits or traps to control bugs indoors (Avoid attracting bugs by tightly sealing foods, including pet foods)

Paints, varnishes, glues and polishes with high solvent content

Low-solvent-content paints, water-based finishes and glues (Have these applied when you are away from home)

Bleach, ammonia, disinfectants and strong cleaning products

“Elbow grease,� soap and water, baking soda and vinegar

Scented products, Unscented cleansers, laundry perfumes, air detergent, fabric softeners and fresheners and incense cosmetics Hair coloring, New haircut and hair gel or permanents, hair styling products that do not spray or any aerosol require spraying product Dry cleaning, odorous soft plastic toys or mattress covers

Washable toys, bedding and clothes

Odorous flooring, such as vinyl, pressed wood or particle board, or carpeting, which can also trap allergens

Ceramic, stone tile, or hardwood floors

Commercial foods that may contain pesticides or other questionable ingredients

Organic foods and foods without additives or artificial colors

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Theories of Disease: A Historical Perspective Germ Theory

Immune Theory

TILT Theory

150 years ago

75 years ago

20 years ago

Anaphylaxis

New-onset intolerances to structurally unrelated substances

Naturally occurring proteins

Acute or chronic chemical exposures, e.g., sick building, pesticides

Co-evolved with humans

Co-evolved with humans

Evolutionarily novel—since WWII and the introduction of petrochemicals

Antibiotics, vaccines

Antihistamines, steroids, immunotherapy

Unknown

Susceptibility Factors

General health genetics, developmental stage

General health genetics, developmental stage

General health genetics, developmental stage

Prevention

AVOIDANCE of sources

AVOIDANCE of sources

AVOIDANCE of sources

Awareness Began

Hallmark Symptom

Causative Agents

How long have we been living with this? Principal Treatment

Fever

Bacteria, viruses, rickettsia, etc.

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To My Fellow Physicians: Treating patients who present with a confusing array of symptoms, that don’t respond to usual therapies and who have no unifying diagnosis is challenging, particularly since chemically induced illnesses were not emphasized in medical school. Currently, we are at the “Germ Theory” stage in our understanding of TILT. TILT emerged from the collective observations of researchers, physicians and patients in more than a dozen countries and introduces a new paradigm for understanding and treating illness. In contrast to current practice, one approach to the treatment of TILTed patients is removing or “taking away” exposures to substances that may be causing harm, including drugs. I call this “Take‐away Medicine.” The QEESI can be useful for predicting Checklist whether a patient might benefit from o Have patient take QEESI reducing triggering exposures. A vast majority of patients with TILT also o Reduce exposures at experience adverse reactions to foods, home and work including non‐IgE mediated reactions. Because patients suffering from TILT o Eliminate unnecessary respond to multiple food, drug, and medications chemical triggers, all contributory exposures must be removed entirely o Implement a supervised before symptoms will improve. rotary elimination diet Patients are best treated in a specially o Wish we had an EMU.... designed and constructed hospital facility called an “Environmental Medical Unit (EMU),” a chemically “clean” hospital environment. When no EMU is available, identifying the triggering exposures is an arduous process. Lacking this resource, physicians can do their best to help TILTed patients by scaling back on non‐essential medications, suggesting a supervised rotary elimination diet, and guiding them to reduce unnecessary chemical exposures. Once the medical community understands how difficult the diagnosis and treatment of TILT is, it becomes clear that the most important message is prevention. Physicians have the power to recommend a “Personal Precautionary Principle” approach to all of their patients. 21

‐ Claudia S. Miller, MD, MS


Key References Katerndahl, DA, Miller CS: Chemical intolerance in primary care settings: prevalence, comorbidity, and outcomes. Ann Fam Med. 2012;10(4):357‐65. PMID 22778124 Using the QEESI, chemical intolerance was diagnosed in 1 of 5 primary care patients. Only ¼ of the patients studied had previously received a related diagnosis.

Miller CS: The compelling anomaly of chemical intolerance. Ann NY Acad Sci. 2001;933:1‐23. PMID 12000012 TILT is a unique pattern of illness observed among chemically exposed groups in more than a dozen countries who subsequently report multi‐system symptoms and new‐onset chemical, food, and drug intolerances. Parallel to drug addiction, cravings and withdrawal symptoms suggest involvement of multiple neural pathways.

Miller CS: Toxicant‐induced loss of tolerance. Addiction. 2000;96(1):115‐137. PMID 11177524 Published in the millennial edition of the journal Addiction, a review of theories of addiction. Paper on the relationship between addiction, chemical intolerance and TILT. Addictive drugs and environmental contaminants cause similar brain responses including withdrawal symptoms and cravings. TILT opens a new window between the fields of addiction and environmental medicine, with profound implications for medicine, psychology and psychiatry.

Nawab SS, Miller CS, Dale JK, Greenberg BD, Friedman TC, Straus SE, Chrousos GP, Rosenthal NE: Self‐reported sensitivity to chemical exposures in five clinical populations and healthy controls. Psychiatry Res. 2000; 95(1):67‐74. PMID 10904124 Patients with chronic fatigue syndrome, Addison’s Disease, and Seasonal Affective Disorder reported greater sensitivity to chemical exposures than did normal controls.

Miller CS:. Are we on the threshold of a new theory of disease? Toxicant‐induced loss of tolerance and its relationship to addiction and abdiction. Toxicol Ind Health. 1999;15(3‐4):284‐94. PMID 10416280

Evidence for TILT as a new theory of disease involving 1) initiation by a toxic exposure, 2) followed by triggering by previously tolerated foods, drugs and common chemicals at low levels. Masking hides the relationship between exposures and symptoms. TILT may underlie certain cases of asthma, migraine headaches, depression, chronic fatigue, fibromyalgia, and the unexplained illnesses of Gulf War Veterans.

Miller CS, Prihoda TJ: The Environmental Exposure and Sensitivity Inventory (EESI): a standardized approach for measuring chemical intolerances for research and clinical applications. Toxicol Ind Health. 1999;15(3‐4):370‐85. PMID 10416289 Validation of the QEESI.

Miller CS, Prihoda TJ: A controlled comparison of symptoms and chemical intolerances reported by Gulf War veterans, implant recipients and persons with multiple chemical sensitivity. Toxicol Ind Health. 1999;15(3‐4):386‐97. PMID 10416290 Miller CS, Gammage RB, Jankovic JT: Exacerbation of chemical sensitivity: a case study. Toxicol Ind Health. 1999;15(3‐4):398‐402. PMID 10416291 Symptoms and intolerances following move to a new office building.

Miller CS: Toxicant‐induced loss of tolerance: an emerging theory of disease? Environ Health Perspect 1997;105 Suppl. 2:445‐53. PMID 9167978 Miller CS, Ashford NA, Doty R, Lamielle M, Otto D, Rahill A, Wallace L: Empirical approaches for the investigation of toxicant‐induced loss of tolerance. Environ Health Perspect. 1997;105 Suppl 2:515‐19. PMID 9167989 Describes the need for environmental medical units (EMU).

Miller CS: Chemical sensitivity: symptom, syndrome or mechanism for disease? Toxicology. 1996;111:69‐86. PMID 8711750 Miller CS, Mitzel HC: Chemical sensitivity attributed to pesticide exposure versus remodeling. Arch Environ Health. 1995;50(2):119‐29. PMID 7786048 Similar symptoms and intolerances among persons exposed to pesticides or remodeling. 22


“Someday, we will look back at how we constructed and operated our buildings, and realize that we should have paid far more attention to Indoor Air Quality (IAQ). It will be clear that we should have designed for the most vulnerable individuals—at least 1/3 of the population! Physicians will recognize that poor IAQ can have lasting effects on health. Unfortunately, for many patients this recognition may come too late. If you protect the most vulnerable people, you will protect everyone.” ‐ Claudia S. Miller, MD, MS Who is most vulnerable?

Children, pregnant women, and more susceptible adults—people with asthma, allergies, or chemical intolerance. At any given time, out of 100 people:

• 3 are pregnant or will become pregnant within a year

• 7 are children under the age of 5 undergoing rapid brain development and who are breathing much more air relative to their size and detoxification ability than adults • 17 are between 5 and 18 years of age—whose brains will continue developing into their early 20’s • 8 have asthma

• 20 have allergies

• 15 have chemical intolerances

Claudia S. Miller, MD, MS University of Texas Health Science Center San Antonio Department of Family & Community Medicine 7703 Floyd Curl Drive, San Antonio, TX 78229‐3900 Phone: (210) 562‐6550 Webpage: www.drclaudiamiller.org QEESI: www.qeesi.org Facebook: www.faceboook.com/qeesi.org Newsletter: http://drclaudiamiller.com/newsletter/

©2013 University of Texas Health Science Center at San Antonio Printed with soy‐based ink on recycled paper 23


QEESI

Quick Environmental Exposure and Sensitivity Inventory V-1 The purpose of this questionnaire is to help identify health problems you may be having and to understand your responses to various exposures. Complete the next 5 pages, describing how you are now. Then fill in the “target” diagram below. If your health problems began suddenly or became much worse after a particular exposure event, such as a pesticide exposure or moving to a new home or office building, then go back through the first 3 pages and indicate how you were before the exposure event. Use different colors or symbols (circles, squares) for “before” and “after.” Symptom Star

Symptom Star

Instructions: Place a dot on the corresponding spoke for each symptom item. Connect these points. Indicate “before” and “after” scores by using different colors or dotted versus solid lines.

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— Chemical Exposures — The following items ask about your responses to various odors or chemical exposures. Please indicate whether or not these odors or exposures would make you feel sick, for example, you would get a headache, have difficulty thinking, feel weak, have trouble breathing, get an upset stomach, feel dizzy, or something like that. For any exposure that makes you feel sick, on a 0-10 scale rate the severity of your symptoms with that exposure. For exposures that do not bother you, answer “0.” Do not leave any items blank. For each item, circle one number only: [0 = not at all a problem] [5 = moderate symptoms] [10 = disabling symptoms]

1. Diesel or gas engine

0 1 2 3 4 5 6 7 8 9 10

2. Tobacco Smoke

0 1 2 3 4 5 6 7 8 9 10

3. Insecticide

0 1 2 3 4 5 6 7 8 9 10

4. Gasoline, for example at a service station while filling the gas tank

0 1 2 3 4 5 6 7 8 9 10

5. Paint or paint thinner

0 1 2 3 4 5 6 7 8 9 10

6. Cleaning products such as disinfectants, bleach, bathroom cleansers or floor cleaners

0 1 2 3 4 5 6 7 8 9 10

7. Certain perfumes, air fresheners or other fragrances

0 1 2 3 4 5 6 7 8 9 10

8. Fresh tar or asphalt

0 1 2 3 4 5 6 7 8 9 10

9. Nailpolish, nailpolish remover, or hairspray

0 1 2 3 4 5 6 7 8 9 10

10. New furnishings such as new carpeting, a new soft plastic shower curtain or the interior of a new car

0 1 2 3 4 5 6 7 8 9 10

Total Chemical Intolerance Score (0-100): Name any additional chemical exposures that make you feel ill and score them

from 1 to 10: ________________________________________________________

____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ 25


— Other Exposures — The following items ask about your responses to a variety of other exposures. As before, please indicate whether these exposures would make you feel sick. Rate the severity of your symptoms on a 0-10 scale. Do not leave any items blank. For each item, circle one number only: [0 = not at all a problem] [5 = moderate symptoms] [10 = disabling symptoms] 1. Chlorinated tap water

0 1 2 3 4 5 6 7 8 9 10

2. Particular foods, such as candy, pizza, milk, fatty foods, meats, barbeque, onions, garlic, spicy foods, or food additives such as MSG

0 1 2 3 4 5 6 7 8 9 10

3. Unusual cravings, or eating any foods as through you were addicted to them; or feeling ill if you miss a meal

0 1 2 3 4 5 6 7 8 9 10

4. Feeling ill after meals

0 1 2 3 4 5 6 7 8 9 10

5. Caffeine, such as coffee, tea, Snapple, cola drinks, Big Red, Dr. Pepper or Mountain Dew, or chocolate

0 1 2 3 4 5 6 7 8 9 10

6. Feeling ill if you drink or eat less than your usual amount of coffee, tea, caffeinated soda or chocolate, or miss it altogether

0 1 2 3 4 5 6 7 8 9 10

7. Alcoholic beverages in small amounts such as one beer or a glass of wine

0 1 2 3 4 5 6 7 8 9 10

8. Fabrics, metal jewelry, creams, cosmetics, or other items that touch your skin

0 1 2 3 4 5 6 7 8 9 10

9. Being unable to tolerate or having adverse or allergic reactions to any drugs or medications (such as antibiotics, anesthetics, pain relievers, x-ray contrast dye, vaccines or birth control pills), or to an implant, prosthesis, contraceptive chemical or device, or other medical, surgical or dental material or procedure

0 1 2 3 4 5 6 7 8 9 10

10. Problems with any classical allergic reactions (asthma, nasal symptoms, hives, anaphylaxis or eczema) when exposed to allergens such as: tree, grass, or weed pollen, dust, mold, animal dander, insect stings or particular foods

0 1 2 3 4 5 6 7 8 9 10

Total Other Intolerance Score (0-100): 26


— Symptoms — The following questions ask about symptoms you may have experienced commonly. Rate the severity of your symptoms on a 0-10 scale. Do not leave any items blank. For each item, circle one number only: [0 = not at all a problem] [5 = moderate symptoms] [10 = disabling symptoms] 1. Problems with your muscles or joints, such as pain, aching, cramping, stiffness or weakness?

MS 0 1 2 3 4 5 6 7 8 9 10

2. Problems with burning or irritation of your eyes, or problems with your airway or breathing, such as feeling short of breath, coughing, or having a lot of mucus, post-nasal drainage, or respiratory infections?

AIR/MM 0 1 2 3 4 5 6 7 8 9 10

3. Problems with your heart or chest, such as a fast or irregular heart rate, skipped beats, your heart pounding, or chest discomfort?

COR 0 1 2 3 4 5 6 7 8 9 10

4. Problems with your stomach or digestive tract, such as abdominal pain or cramping, abdominal swelling or bloating, nausea, diarrhea, or constipation?

GI 0 1 2 3 4 5 6 7 8 9 10

5. Problems with your ability to think, such as difficulty concentrating or remembering things, feeling spacey, or having trouble making decisions?

COG 0 1 2 3 4 5 6 7 8 9 10

6. Problems with your mood, such as feeling tense or nervous, irritable, depressed, having spells of crying or rage, or loss of motivation to do things that used to interest you?

AFF 0 1 2 3 4 5 6 7 8 9 10

7. Problems with your balance or coordination, with numbness or tingling in your extremities, or with focusing your eyes?

NM 0 1 2 3 4 5 6 7 8 9 10

8. Problems with your head, such as headaches or a feeling of pressure or fullness in your face or head?

HEAD 0 1 2 3 4 5 6 7 8 9 10

9. Problems with your skin, such as a rash, hives, or dry skin?

SKIN 0 1 2 3 4 5 6 7 8 9 10

10. Problems with your urinary tract or genitals, such as pelvic pain or frequent or urgent urination? (For women: or discomfort or other problems with your menstrual period?)

GU 0 1 2 3 4 5 6 7 8 9 10

Total Symptom Score (0-100): 27


— Masking Index — The following items refer to ongoing exposures you may be having. Circle “0” if the answer is “NO,” or if you don’t know whether you have the exposure. Circle “1” is the answer is “YES,” you do have the exposure. Do not leave any items blank. Circle “0” or “1” only:

1. Do you smoke or dip tobacco once a week or more often?

NO = 0

YES = 1

2. Do you drink any alcoholic beverages, or wine once a week or more often?

NO = 0

YES = 1

3. Do you consume any caffeinated beverages once a week or more often?

NO = 0

YES = 1

4. Do you routinely (once a week or more) use perfume, hairspray, or other scented personal care products?

NO = 0

YES = 1

5. Has either your home or your workplace been sprayed for insects or fumigated in the past year?

NO = 0

YES = 1

6. In your current job or hobby, are you routinely (once a week or more) exposed to any chemicals, smoke or fumes?

NO = 0

YES = 1

7. Other than yourself, does anyone routinely smoke inside your home?

NO = 0

YES = 1

8. Is either a gas or propane stove used for cooking in your home?

NO = 0

YES = 1

9. Is a scented fabric softener (liquid or dryer sheet) routinely used in laundering your clothes or bedding?

NO = 0

YES = 1

10. Do you routinely (once a week or more) take any of the following steroid pills, such as prednisone; pain medications requiring a prescription; medications for depression, anxiety or mood disorders; medications for sleep, or recreational or street drugs?

NO = 0

YES = 1

Masking Index (0-10): (Total number of YES answers) 28


— Impact of Sensitivities — If you are sensitive to certain chemicals or foods, on a scale of 0-10 rate the degree to which your sensitivities have affected various aspects of your life. If you are not sensitive or if your sensitivities do not affect these aspects of your life, answer “0.” Do not leave items blank. How much have your sensitivities affected: [0 = not at all ] [5 = moderately] [10 = severely]

1. Your diet?

0 1 2 3 4 5 6 7 8 9 10

2. Your ability to work or go to school?

0 1 2 3 4 5 6 7 8 9 10

3. How you furnish your home?

0 1 2 3 4 5 6 7 8 9 10

4. Your choice of clothing?

0 1 2 3 4 5 6 7 8 9 10

5. Your ability to travel to other cities or drive a car?

0 1 2 3 4 5 6 7 8 9 10

6. Your choice of personal care products, such as deodorants or makeup?

0 1 2 3 4 5 6 7 8 9 10

7. Your ability to be around others and enjoy social activities, for example, going to meetings, church, restaurants, etc.?

0 1 2 3 4 5 6 7 8 9 10

8. Your choice of hobbies or recreation?

0 1 2 3 4 5 6 7 8 9 10

9. Your relationship with your spouse or family?

0 1 2 3 4 5 6 7 8 9 10

10. Your ability to clean your home, iron, mow the lawn, or perform other routine chores?

0 1 2 3 4 5 6 7 8 9 10

Total Symptom Score (0-100):

Copyright © 1998 Claudia S. Miller. All rights reserved. This work may not be translated or copied in whole or in part, transmitted in any form or by any means (electronic or mechanical), including photocopying, recording, storage in an information retrieval system or otherwise, without the written permission of the author. 29


— Interpreting the QEESI© — In a study of 421 individuals, including four exposure groups and a control group, the QEESI© provided sensitivity of 92% and specificity of 95% in differentiating between persons with multiple chemical intolerances (MCI) and the general population (Miller and Prihoda 1999a,b). Cronbach’s alpha reliability coefficients for the QEESI©’s four scales—Symptom Severity, Chemical Intolerances, Other Intolerances and Life Impact—were high (0.76-0.97) for each of the groups, as well as over all subjects, indicating that the questions on the QEESI© form scales showing good internal consistency. Pearson correlations for each of the four scales with validity items of interest, i.e., life quality, health status, energy level, body pain, ability to work and employment status, were all significant and in the expected direction, thus supporting good construct validity.

Information on the development of this instrument, its interpretation, and results for several populations have been published (Miller and Prihoda 1999a,b). Proposed ranges for the QEESI©’s scales and guidelines for their interpretation appear in Tables 1 and 2: Scale/Index

Low

Medium

High

Symptom Severity

0-19

20-39

40-100

Chemical Intolerance

0-19

20-39

40-100

Other Intolerance

0-11

12-24

25-100

Life Impact

0-11

12-24

24-100

Masking Index

0-3

4-5

6-10

30


Table 2. Distribution of subjects by group using “high” cutoff points for symptom severity (≥ 40) and chemical intolerances (≥ 40), with masking low or not low (< 4 or ≥ 4). Risk Criteria1

Degree to Which MCI is Suggested2

Symptom Severity Scale

Chemical Intolerance Scale

Masking Score

Very suggestive

≥ 40

≥ 40

≥4

Very suggestive

≥ 40

≥ 40

<4

Somewhat suggestive

≥ 40

< 40

≥4

Not suggestive

≥ 40

< 40

<4

Problematic

< 40

≥ 40

≥4

Problematic

< 40

≥ 40

<4

Not suggestive

< 40

< 40

≥4

Not suggestive

< 40

< 40

<4

Percentage of Each Group Meeting Risk Criteria Controls n=76

MCI— No Event n=90

MCI— Event n=96

Implant n=87

Gulf War Veterans n=72

Very suggestive

7

16

23

39

45

Very suggestive

0

65

66

36

4

Somewhat suggestive

3

1

2

16

26

Not suggestive

0

0

2

3

6

Problematic

7

3

1

1

0

Problematic

3

13

4

2

0

Not suggestive

68

1

0

2

18

Not suggestive

12

1

2

1

1

Total

100

100

100

100

100

Degree to Which MCI is Suggested2

1 Subjects must meet all three criteria, i.e., Symptom Severity, Chemical Intolerance, and Masking scores, as indicated in each row of this table. 2 “Very suggestive” = high symptom and chemical intolerance scores. “Somewhat suggestive” = high symptom score but possibly masked chemical intolerance. “Not suggestive” = either (1) high symptom score but low chemical intolerance score with low masking, or (2) low symptom and chemical intolerance scores. “Problematic” = low symptom score but high chemical intolerance score. Persons in this category with low masking (<4) may be sensitive individuals who have been avoiding chemical exposures for an extended period (months or years). 31



TILT*: A New Class of Diseases