Airway Genetics and Ambient Combustion Aerosol

Multiple Chemical Sensitivity: 2021 Consensus Criteria Part II Diagnosis, Patient Rights, Etiology

Multiple Chemical Sensitivity: 2021 Consensus Criteria

Baseline, Diagnosis, Patient Rights, Etiology

Part II Diagnosis, Patient Rights, Etiology

Expertise from the most Prestigious Academic, Medical, and Government Research Facilities

Consensus Amendment Research, TRPA1 Precision

I. Baseline GSAA, ACA, SRPE 1-8

II. Diagnosis, Patient Rights, Etiology 9-14

III. Baseline: Nutrition and Exercise 15-31

A. SJF, LE 15-20

B. Whole Food Nutrition 21-31

IV. Baseline: Nutrition and Exercise 32-38

C. Suboptimal Actors 32

D. Maintaining Bone Density 33-37

E. Preventing Atherosclerosis 38

II. Diagnosis, Patient Rights, Etiology 9-14

A. Diagnosis 9a-g

B. Patient Rights 10a-e, 11-13

C. Etiology 14a-u

GSAA: Genetically Susceptible Acquired Alteration

ACA: Ambient Combustion Aerosol

SRPE: Subjectively Recognized Personal Exposure

IIA. Diagnosis 9a-g

9. MCS 2021 Consensus Criteria

a. Genetically susceptible acquired alteration (GSAA): ambient combustion aerosol (ACA) and subjectively recognized personal exposure (SRPE) - at levels to which most do not attribute symptoms - result in precipitation of symptomatology involving multiple organ systems.

b. A chronic condition - symptoms may improve when incitants are removed (SRPE relieved) - however, exposure to the ambient combustion aerosol (ACA) supporting the disease process is continuous.

c. Responses occur to multiple chemicals - usually those having greater acidic, electrophilic, oxidizing, or solvent properties [toxicity] - increased further if instilled by particulate vector as in the ACA .

italics above from: mcsrr.org / Bartha P. et al. Multiple Chemical Sensitivity: a 1999 Consensus. Arch Env H 54:147-49 1999

d. Particulate matter including diesel exhaust particles - and numerous acidic, electrophilic, and oxidizing components of the ambient combustion aerosol (ACA) - to which all are continuously exposed - activate airway sensory c fiber nerves that express TRPA1, TRPV1, and substance P (Deering-Rice 2011, Hazari 2011, Costa 2010, Taylor-Clark 2010, Caceres 2009, Anand 2008, Bessac 2008, Nassenstein 2008, Bautista 2006, Inoue 2005, Kobayashi 2005, Veronesi 2001).

Therefore, the ACA and SRPE support the underlying disease process - including central sensitization from excessive nociceptor inputs (Latremoliere 2009).

TRPV1 is activated by chemical irritants, inflammatory mediators, and tissue damaging stimuli - most famously capsaicinoids and has been referred to as the capsaicin receptor (Veronesi 2006). Observing a lower cough threshold among MCS patients compared to controls when exposed to capsaicin - Nogami 2004 suggested such provocation as a diagnostic test for MCS. However, TRPA1 may be the major reactive irritant receptor (Bessac 2008).

TRPA1 is activated by formaldehyde, acetaldehyde, tear gas agents, and industrial isocyanates (Bessac 2009, Brone 2008, Bang 2007, McNamara 2007), smoke constituents - methacrolein, methyl vinyl ketone, and croton aldehyde (Andre 2008, Escalera 2008), and oxidizing agents including hypochlorite (Bessac 2008a).

Almost all oxidizing and electrophilic agents effect TRPA1 function (Bessac 2008).

Endogenous agonists include reactive oxygen species (ROS), hypochlorite, lipid peroxidation products, cyclopentenone prostaglandins, and isoprostanes (Bessac 2008).

The volatile organic chemical monoterpene ketone umbellone - outgas agent from the California Bay Laurel "headache tree" - stimulates the TRPA1 channel activating the trigeminovascular system. TRPA1 deficient mice failed to have the trigeminal response to umbellone. Nassini 2011 concluded that TRPA1 agonism may be responsible for headache crisis in sensitive people after exposure to environmental pollutants and perfume.

BESSAC 2008:

...TRPA1 can be locked into a constitutively active state, indicating saturation of a reactive site (Hinman 2006)...

...three cysteine residues were crucial for channel activation (Macpherson 2007)...activation of TRPA1 by covalent modification through reactive irritants...dose response relationships and activation kinetics of TRPA1 do not conform to standard pharmacological paradigms and are highly dependent on the chemical status of the cellular and tissue environment...

...TRPA1 agonists show wide divergence, sometimes one or two orders of magnitude...TRPA1 agonist activity will depend on the reversible or irreversible nature of the chemical bonds formed and on agonist membrane permeability...

...since most TRPA1 agonist can react with thiols, cellular and extracellular reduced glutathione levels will affect the reach and potency of inhaled airway irritants. Once glutathione is depleted, either as a consequence of disease or during extended exposures, TRPA1 may respond more strongly (Deluca 2010 found MCS people have severe glutathione depletion). With each breath more reactive agonist is delivered, leading to an increase in covalent modifications and heightened TRPA1 activity...robust TRPA1 induced irritation even at low subacute exposure levels...once irreversibly modified channels may remain active for extended periods of time even when the irritant stimulus is removed...(Bessac 2008a)...

...The multiple chemical sensitivity of TRPA1...tissue injury may sensitize TRPA1 channels through inflammatory signaling pathways, thereby establishing prolonged hypersensitivity to multiple reactive chemicals (Bandell 2004, Bautista 2006, Dai 2007, Jordt 2004)..."

e. Provocation tests are not appropriate - confounded by ambient conditions and 48 hour acute phase response from prior ACA and SRPE (Castranova 2002, Bascom 1992).

f. GSAA (genetically susceptible acquired alteration) - MCS is not a psychological illness.

g. MCS - not an allergy - involves immunoglobulin G (IgG) - the most prominent type of serum antibody which protects against bacteria, viruses, and toxins - distinctly different from the bridging of two IgE molecules by allergens causing a release of chemical mediators from mast cells - including histamine - the allergic response (Merck 1999).

MERCK 1999:
"...Histamine is widely distributed in mammalian tissue. In humans the highest concentrations are in skin, lungs, and GI mucosa...The release of histamine from the mast cell storage granules can be triggered by physical tissue disruption, various chemicals (including tissue irritants, opiates, and surface active agents), and most prominently by antigen-antibody interactions..."

Kimata 2004 found the IgE driven allergy people had plasma H (histamine), NGF (nerve growth factor), SP (substance P), and VIP (vasoactive intestinal peptide) all elevated at baseline: 553, 889, 75, 22 but unchanged by exposure to the toxins of paint: 565, 886, 74, 21.

MCS people had NGF, SP, and VIP higher at baseline due to GSAA (genetically susceptible acquired alteration), ACA (ambient combustion aerosol), and prior SRPE (subjectively recognized personal exposure): 1129, 105, 43 further elevated by the paint to 1696, 154, 74 - markers nearly double that of allergy: 886, 74, 21.

MCS people had histamine similar to controls at baseline but elevated 291 to 563 after exposure to paint because mast cell degranulation and histamine release may occur as noted above - either by allergic bridging or as in MCS - upon sudden increase of chemical exposure.

Controls were nearly unaffected by paint and had far lower levels at baseline except close to MCS on histamine: H, NGF, SP, VIP before and after paint: controls 278,261; 148,156; 38,39; 10,12 compared to MCS 291,563; 1129,1696; 105,154; 43,74.

In summary, much like controls MCS people tend to be unaffected by allergens; and allergic people not acutely reactive to toxins.

IIB. Patient Rights 10a-e, 11-13

10. Malpractice includes:

a. having a patient do anything not of utility in diagnosis, treatment, or cure

b. anything not agreed upon by the patient

c. testing a patient to prove a disability claim

d. involuntary psychological testing, observation, or evaluation

e. accusing of psych - MCS is not a psychological disorder

11. Voluntary research testing of MCS subjects is to understand signs and symptoms - eliminating testing of patients.

12. An MCS claim requires medical doctor support (not naturopathic) and it is claimant responsibility to provide evidence of disability in employment and lifestyle.

13. Career, prestige, financial motives - medication instead of lifestyle change, false cures, protocals without warning, hypnosis, unnecessary testing, expensive books, consultation fees - better to respect MCS - a canary sentinel disorder.

IIC. Etiology 14a-u

14. Summary: Etiology of MCS

a) Most MCS people have genetically sensitive airway tissue (MCS 15, Veronesi 2001, 2000, Roy 2000, Jung 1921).

b) Experiments with mice confirmed genetic variability of the sensory innervation - including quantitative differences in neuropeptides, TRP receptors, and acid sensitive pathways - determine the degree of inflammatory response to environmental exposure (Veronesi 2001, 2000, Roy 2000, Miyabara 1998). Heritability of respiratory symptoms has been shown (Elberling 2009).

c) A sensitive airway is usually a physiological counterpart to an introverted intuitive psychological function type - all genetically determined and apparently occurring more frequently in women (Jung 1921).

d) The airway epithelium and its sensory innervation become altered to a proinflammatory condition (GSAA - genetically susceptible acquired alteration)

(Deering-Rice 2011, Hazari 2011, Li 2011, Taylor-Clark 2010, Baulig 2009, 2003a, Calderon-Garciduenas 2008, 2000, Veronesi 2003, 2002a, 2002b, 2001, 2000, 1999a, 1999b, Agopyan 2003, 2003a, Bonvallot 2001, 2000, Gerde 2001, 1997, Oortgiesen 2000, Roy 2000, Chin 1998, Miyabara 1998,1998a, Steerenberg 1998, Meggs 1997, Bond 1988);

usually by exposure to a continuous ambient combustion aerosol (ACA) - diesel, gasoline, propane and other exhaust, woodsmoke, and tobacco smoke

(Gillespie 2013, Block 2012, 2009, OSHA 2012, Pakkanen 2003, Schauer 2002, 2001, 1999, US DOT FHA 2000, Society of Automotive Engineers SAE 940233 1994);

including UFPM, PM2.5, and PM LPS - particle agglomerates with adsorbed hydrocarbons, singlet nonagglomerated nanoparticles, and acid sulfate resulting from catalytic converter transformation of sulfur dioxide

(Lucchini 2012, Mohankumar 2008, Inoue 2005, Cadle 1999, Kleeman 1999, Kittelson 1998);

fine particles expected to reach the CNS via trigeminal and olfactory nerve pathways

(MCS 11, Calderon-Garciduenas 2010, Genter 2009, Matsui 2009, Elder 2006, Lewis 2005).

e) MCS people have elevated levels of neuropeptides, chemokines, cytokines, growth factors, and nitric oxide (Dantoft 2014, Deluca 2010, Kimata 2004, MCS 7) that mediate serious and multiple dysfunction of chemical defense systems (MCS 13, Deluca 2010, Liptrott 2009, Oslund 2008, Kimata 2004, Chun 2002, Sterner-Kock 1999, Tinel 1999, Tanabe 1996, Tapner 1996, Nadin 1995, Stadler 1994, Khatsenko 1993).

f) Proinflammatory peptidenergic transmitters such as substance P, calcitonin gene related protein, and neurokinin A released by sensory nerves interact with immune cells including lymphocytes, neutrophils, macrophages, and eisinophils exascerbating and perpetuating initial symptoms of inflammation with nitric oxide overproduction and amplification of immune response

(Costa 2010, Oslund 2008, Mohankumar 2008, Calderon-Garciduenas 2008, 2000, Agopyan 2003, Veronesi 2001, 1999a, 1999b, Steerenberg 1998, Meggs 1997, Bascom 1992 MCS 6).

g) Airway defects have been confirmed in MCS patients biopsied and rhinoscopied - conditions found were consistent with expectation of cytokine release and proliferation of nerve fibers was observed (Meggs 1997, 1996, 1993).

h) Reactive and measurable (Milqvist 2005, Nogami 2004, Lee and Pisarri 2001, Bonham 2001) - stimulation of c-fiber nerves may cause multiplication of nerve fibers to a 24-48 hour peak - not returning to baseline until 72-96 hours (Castranova 2002) accompanied with a rise in plasma vasoactive intestinal peptide, substance P, and nerve growth factor (Kimata 2004); ongoing flu-like symptoms attributed to cytokine release (Dantoft 2014, Bascom 1992 MCS 6); higher respiratory rate, increased nasal resistance (Doty 1994); secondary punctate hyperalgesia indicating facilitated central sensitization (Tran 2013, Holst 2011, Latremoliere 2009); head pain expected through increased trigeminal afferent activity from TRPA1 receptors on the exposed C fiber innervation of the nasal mucosa producing meningeal vasodilitation (Kunkler 2011, Nassini 2011); and connection to eye involvement through opthalmic branch of the trigeminal nerve in the olfactory bulb (Jordt 2011, Finger 1993).

i) Xenobiotic penetration and mediators of inflammation - activation and release involving TRPV1, TRPA1, substance P, CGRP, glutamate, NMDA, cytokines, and nitric oxide (Deering-Rice 2011, Costa 2010, Taylor-Clark 2010, Bessac 2008, Calderon-Garciduenas 2008, 2000, Mohankumar 2008, Nassenstein 2008, Oslund 2008, Nilius 2007, Agopyan 2003, Veronesi 2001, 1999a, 1999b, Steerenberg 1998, Meggs 1997, Bascom 1992 MCS 6) cause neurocognitive impairment, SPECT hypoactivity, permanent neuronal damage - reduced inhibitory activity in the olfactory pathways to the orbito-frontal cortex and the limbic system (Orriols 2009, Elder 2006); electroencephalographic alterations (Bell 1998, 1996); central sensitization - a functional synaptic plasticity resulting in pain hypersensitivity (Tran 2013, Holst 2011, Latremoliere 2009); and Belpomme 2015 - in measurement of reduced brain blood flow in the temporal lobes reported cerebral capsulothalamic hypoperfusion - a potentially lightheaded hypoxia in approx 50% of MCS cases further confirming involvement of the limbic system and thalamus in the inflammatory process.

j) Endogenous production of electrophiles and oxidants result in an environment of oxidative stress: glutathione depletion and catalase deficiency, high levels of hydrogen peroxide and 4 HNE, lipid peroxidation with atherogenic implications (MCS 13, Deluca 2010, Calderon-Garciduenas 2008, Yang 2008, Terlecky 2006, Kennedy 2005), increased cardiopulmonary disease risk (Baldwin 1998), and disturbance in heme synthesis (porphyrin abnormalities) (Daniell 1997, Hahn 1997). Elevated cytokine TNF alpha may cause gastrointestinal stasis experienced as queasiness or nausea via vagal circuitry (Emch 2000).

k) ACA PM induced release of inflammatory cytokines including IL-1 beta and IL-6 from alveolar macrophages, epithelial cells, and exposed sensory nerves in damaged airway epithelium - found elevated in MCS and ME/CFS (Dantoft 2014, Maes 2012) - stimulate the bone marrow to increase output of platelets and polymorphonuclear leukocytes (PMN), accelerate more immature PMN (band cells) into the circulation prone to sequestration in microvascular beds - and increase the liver output of acute phase proteins including fibrinogen, CRP, and C-reactive protein - all associated with vascular activation and the extent of atherosclerosis (Hiraiwa 2014, 2013, Hogg 2009, Goto 2004, Mukae 2001) - and indicated by elevated PMN-elastase, lysozyme, and neopterin confirmed in ME/CFS (Maes 2012).

L) Induction of upper respiratory, lung epithelial and endothelial injury leading to persistent chronic inflammation in the respiratory tract and systemic inflammation accompanied by the production of IL-6 and IL-1beta elevated in MCS and ME/CFS (Dantoft 2014, Maes 2012) may activate endothelial cells of brain capillaries opening the BBB (blood-brain barrier) involving upregulation of COX-2 (cyclooxygenase-2), activation of NFkB (nuclear factor kB), and increased expression of iNOS (inducible nitric oxide synthase) found in ME/CFS ( Calderon-Garciduenas 2008, Maes 2007a, 2007b).

m) Because MCS people have airway defects there may be a sharing of at least some aspects of the following description (Block 2009, Calderon-Garciduenas 2008):

Airway breakdown occurs universally beginning in childhood among non-smoking residents of ACA PM 2.5, UFPM, and PM LPS - highly polluted Mexico City (MC) (Calderon-Garciduenas 2008, 2001) - and is accompanied by a closely investigated CNS (central nervous system) pathology of neuroinflammation - subclinical early - but associated with eventual neurodegeneration due to ACA PM, adsorbed compounds, byproducts of ozone exposure (photochemical smog resulting mostly from vehicle exhaust), and cytokines reaching the brain.

The CNS condition includes increased inflammatory markers iNOS (inducible nitric oxide synthesis), TNF alpha, Il-1beta, COX-2 (cyclooxygenase-2), and NFkB (nuclear factor kB) especially in frontal cortex, substantia nigrae, and vagus nerves (found systemically elevated in ME/CFS [Maes 2012]);

neuron damage or loss, microglial activation (innate immune system macrophages of the brain - their job to engulf and digest but with cumulative collateral damage) indicated by increase of HLA-DR surface antigen positive cells and CD-14 lipopolysaccharide (LPS) receptors - LPS a potent inflammatory cell wall component of gram negative bacteria (endotoxin) commonly adsorbed on DEP (diesel exhaust particles) ((Block 2004) - with resulting ROS (reactive oxygen species) and cytokine production, blood-brain barrier (BBB) dysfunction - changes in inflammatory, tight junction, and transport proteins of the cerebral vascular microvessels (3 to 8 micron diameter) that comprise the BBB - endothelial cell damage with increase in leukocyte adhesion molecules - and confirmed using Positive Emission Tomography - activated microglia and astrocytes evidencing brain neuroinflammation in ME/CFS patients - found to correlate with degree of cognitive impairment (Nakatomi 2014) - and two markers of BBB opening - nitrotyrosin and protein S100B - elevated in a subset of MCS and EHS (electrohypersensitivity) subjects (Belpomme 2015);

accumulation of Abeta-42 as neuronal, vascular and diffuse plaques - CALDERON-GARCIDUENAS 2008: "...Both Abeta42 (42 amino acid-isoform of beta amyloid associated with Alzheimer's) and alpha synuclein ( an abundant brain 140-residue-protein linked to Parkinson's disease) are proteins capable of aggregation and misfolding (shown to occur more rapidly in conditions of PM exposure), leading to progressive neurodegeneration that develops insidiously over the lifetime of the individual (McGeer 2006, Jellinger 2003, Nguyen 2002, Selkoe 2002, 2001)...";

lipid peroxidation (systemically confirmed in MCS people [Deluca 2010]); astrogliosis evidenced by enhanced glial fibrilliary acid protein (GFAP) expression; and DNA damage (Block 2009, Calderon-Garciduenas 2008).

In contrast, non-smoking residents of less polluted cities Veracruz and Tlaxcala - upon the same examination appeared in good shape during childhood - but four of the five oldest subjects age 27 and above - 27, 36, 40, and 45 demonstrated either dysruption of the BBB (blood-brain barrier) by confocal microscopy for tight junction abnormalities (Zonula Occlulens ZO-1) or Abeta-42 (42 amino acid-isoform of beta amyloid) immunoreactivity by immunohistochemistry in olfactory bulb and cortical neurons of one subject - and in diffuse and mature senile plaques in another, a preAlzheimer's-like indicator of brain neuroinflammation (Calderon-Garciduenas 2008).

Although more is worse - there is no safe level of repeated exposure to combustion byproducts including vehicle exhaust. Every breath cumulative damage - breakdown of the respiratory epithelium and BBB facilitates access of inflammatory mediators and components of air pollution to the CNS (Calderon-Garciduenas 2008, 2004).

n) Studies involving large diagnosed MCS groups found no significant differences in allele and genotype frequencies of CYP's, UGT, GSTM, GSTT, and GSTP (Deluca 2010) - and CYP2D6, NAT2, PON1, MTHFR, and CCK2R (Berg 2010) comparing the MCS and control groups - with the conclusion that multiple dysfunction of chemical defense systems in MCS patients mainly does not depend on genetic defects in chemical defense but instead modifications by redox active agents such as NO and inflammatory cytokines found higher among MCS patients in the Dantoft and Deluca studies.

Caccamo 2013 - research group of the Deluca 2010 study - reversed earlier findings concerning gene variants in cytochrome P450 detox enzymes - instead now reporting agreement with Mckeown-Eyssen 2004 - finding certain CYP variants have different frequency of occurrence - though most occur in both MCS and control groups.

If these results hold true - they are an association - not an established causative factor - it is not known whether these variants confer protection or increase harmful effects - if the latter they may be of significance regarding intolerance among a subset of MCS patients - keeping in mind gene variants in detox enzymes are not major etiology of MCS (Berg 2010 , Deluca 2010).

The reported CYP variants of Caccamo 2013 are few relative to the many forms of cytochrome P450 expressed - making a major causative role in most cases less plausible and competing with the observation that sensitivity of the sense organs occurs along with an introverted intuitive cast of mind - both genetically determined (Jung 1921) - further supported by the relationship between genetic quantitative differences in neuropeptides, TRP receptors, and acid sensitive pathways on airway sensory nerves and contrasting inflammatory sensitivity of mouse strains (MCS 15, Veronesi 2001, 2000, Roy 2000). Also Elberling 2009 showed heritability concerning respiratory symptoms from perfume.

0) Earlier studies - Schnakenberg 2007, Mckeown-Eyssen 2004, and Haley 1999 - are inconclusive when applied to a diagnosed MCS group (Berg 2010, Deluca 2010). Schnakenberg did not use diagnosed MCS patients - instead defined 52% of a general population sample as the chemically sensitive group based upon filling out a questionnaire. Mckeown-Eyssen cautioned against drawing conclusions from their results - stating that in view of the small numbers such an association must be viewed cautiously - and the Haley study involved Gulf war veterans rather than MCS patients.

p) GSTM1 and GSTT1 - objects of the Deluca and Schnakenberg studies - concern the activation of Phase II enzymes known as GSH S-transferases (GST) which catalyze the reaction of glutathione (GSH) with electrophiles - a broad class of xenobiotic and endogenous compounds - including environmental toxins and reactive oxygen species (Block 2011, Manfredi 2009, Hayes 2005, Wu 2004, Griffith 1999).

Over 50% of the population have one or both of the GSTM1 and GSTT1 deletions (Piacentini 2011, Block 2011, Ginsberg 2009, Hayes 1995).

q) In a condition such as MCS, GSH depletion may be inevitable regardless of deletions - either by excess utilization in spontaneous or GST catalyzed reactions resulting in loss of cysteine - one of the amino acid precursors for the resynthesis of glutathione - or by suppression of synthesis such as with high levels of NO production (Lu 2009, Oslund 2008, Darmaun 2005, Wu 2004, Canals 2003, Griffith 1999, Sterner-Kock 1999, Tanabe 1996).

r) In apparent sudden onset of MCS from a large toxic exposure (SRPE - subjectively recognized personal exposure), usually the disease pre-existed as a genetic disposition (Elberling 2009, Veronesi 2001, 2000, Roy 2000, Jung 1921);

in a continuous environment of combustion byproduct fine particle aerosol (ACA) - with airway epithelial cells and the sensory innervation already altered proinflammatory (GSAA) (Veronesi 2001, Meggs 1997, 1996);

mediating dysfunction of chemical defense systems (Deluca 2010, Liptrott 2009, Oslund 2008, Chun 2002, Sterner-Kock 1999, Tinel 1999, Tanabe 1996, Tapner 1996, Nadin 1995, Stadler 1994, Khatsenko 1993);

and facilitating access of systemic inflammatory mediators and components of air pollution to the central nervous system (Calderon-Garciduenas 2008, 2004).

s) Because MCS - and environmentally caused disease in general - usually involves permanent proinflammatory alteration in the structure and function of the airway epithelium and its sensory innervation (GSAA) - there is no cure (Calderon-Garciduenas 2008, Veronesi 2001, Meggs 1997).

Though chemokines, growth factors, cytokines, and NO are elevated; glutathione depleted; catalase deficient; fatty acid profile altered indicating lipid peroxidation; and CNS changes measurable (Dantoft 2014, Tran 2013, Holst 2011, Deluca 2010, Orriols 2009, Milqvist 2005, Kimata 2004, Bell 1999, 1998) - laboratory tests may have no utility for the patient - therefore mandatory testing is unethical and immoral.

t) If cause and effect were isolated - one breath of exhaust would exceed in reactivity all exposures of a careful person over several days - and yet the exhaust is continuous. Failure to recognize the effect of ambient combustion aerosol particulate with adsorbed gasoline and diesel fuel hydrocarbon (ACA PM) - inhaled at every breath - has been a grand illusion.

Perhaps impossible to express delicately - but the point needs to be made - worrying about a smell in the refrigerator or other perception is missing it - those exposures are relatively minor. They are riding on a continuous horizontal coning (Chapter 4) of tailpipe, chimney, and smokestack combustion particulate with its adsorbed hydrocarbon component - obviously the most significant cumulative and ongoing exposure (Block 2009). For that there is billions in health care costs (Pervin 2008, USDOTFHA 2000) and need for a non-combustion way of life.

u) We should be together in addressing the crisis of unrestrained growth and consumption that is threatening life on earth (Rogers 2011). Consequences are catastrophic - geopolitical turmoil, overpopulation: 1960/2021, 3 to 7.8 billion in 61 years (Worldometers 2021), resource loss, climate change, ocean acidification, mass extinction, speed, violence, pollution, injury, illness, and premature death.

It is to evaluate one's own attitude, character, behavior, and motives - and admit that all are of a grand scheme to destruction so long as the lifestyle of unrestrained growth, consumption, fast pace, preoccupation with competition and violence, and engagement of wasteful products, activities, and traditions persist - including billions of people taking a 4000 lb machine everywhere they go - rather than the healthful effort of walking - drawing upon thousands of years physical development and thoughtful reflection - a moral exertion - strength and integrity - choosing honesty, goodness, kindness, and love - to slow down and live environmentally consistent with those values.

With 1 billion people added to population in 15 years taught that unrestrained growth, consumption, and combustion fueled activity is okay - this world will not support all movement at 25-300 MPH - recognized is a need for Impossibly Good City Design - to slow down, walk more, change to non combustion vehicles, turn down thermostats, reduce population and consumption - using good moral judgement to protect a supporting environment.

A slower paced, reduced consumption, non combustion lifestyle is needed or human beings will go extinct due to loss of environment and resources.

MCS Etiology: CAR References A-H

MCS Etiology: CAR References I-Q

MCS Etiology: CAR References R-Z