Multiple Chemical Sensitivity Etiology

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MCS 1a Etiology: 2019 Consensus Criteria

MCS 1a Etiology: 2019 MCS Consensus CriteriaExpertise from the most Prestigious Academic, Medical, and Government Research FacilitiesOutlineI. Please be an MCS Consensus AuthorII. The 1999 and 2019 Consensus III. Bessac 2008: TRPA1 PrecisionIV.…Continue

Started by michael edward badolato jr in MCS Etiology Jan 14.

MCS ad Etiology: Naturally Sensitive

MCS people are naturally sensitive - in a descriptive portrait attitude and functional typology - genetically introverted intuitive; counterweight to the rarified air of intuition - an extraordinary dependence on sense impressions - and…Continue

Tags: multiple, intuitive, introverted, psychological, receptors

Started by michael edward badolato jr in MCS Etiology Aug 2, 2012.

MCS ae Etiology: Airway Reactivity

TRPA1 and TRPV1 may go in hand. NASSENSTEIN C. ET AL. EXPRESSION AND FUNCTION OF THE ION CHANNEL TRPA1 IN VAGAL AFFERENT NERVES INNERVATING MOUSE LUNGS J…Continue

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Started by michael edward badolato jr in MCS Etiology Aug 2, 2012.

MCS 1 Etiology Narrative

MCS…Continue

Started by michael edward badolato jr in MCS Etiology Jun 26, 2012.

MCS 2a Etiology Detailed

CONTENT OF THIS FORUM HAS BEEN ENTIRELY DISTRIBUTED AMONG FORUMS MCS ab,ac,ad,ae & afMCS usually originates from the airway epithelium and its sensory innervation - which has defects due to genetic disposition and environmental…Continue

Tags: TRPA1, Cytochrome, P450, TRPV1, Sensitivity

Started by michael edward badolato jr in Uncategorized Jun 26, 2012.

MCS 4 Top Studies in a Nutshell

MCS is usually very high levels of neurogenic inflammation - including release of inflammatory cytokines, chemokines, and growth factors    Mohankumar…Continue

Tags: definition, etiology, studies, sensitivity, multiple

Started by michael edward badolato jr in MCS Etiology Apr 20, 2012.

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Cost of Air Pollution

Posted by michael edward badolato jr on April 30, 2012 at 4:30pm

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Info

Standard of Kindness

MCS Etiology is about Love and God

In Memory of Cindy Duehring

MCS 1a 2019 MCS Consensus Criteria

MCS 2 The Etiology of MCS

MCS 2a Etiology: TRPA1 Precision

MCS 2a Etiology: Notes on References 

MCS 2ab Etiology: Nasal Cytokines in Context

MCS 2ac Etiology: Belpomme 2015 - Formula or Reality?

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research (CAR)

MCS 3a AKA Multiple Chemical Sensitivity: 2019 Consensus Criteria

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

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Carefully researched - fact and evidence based with no conflict of interest - MCS Etiology is the most advanced and credible statement on this subject. 

Principles apply also to pollution supported disease in general.

CALDERON-GARCIDUENAS 2008: 

"...Breakdown of the nasal respiratory and olfactory epithelium and the BBB facilitates the access of systemic inflammatory mediators and components of air pollution to the central nervous system (CNS) (Calderon-Garciduenas 2004)..."

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Complete list of MCS and Management forums - in large easy to read print - are linked at right and in feature elsewhere. A select list is highlighted below. 

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Careful analysis:

MCS 2ac Etiology: Belpomme 2015 - Formula or Reality?

MCS 14 Genetics in Detox Enzymes: Not Majority Etiology

Advanced Research Consensus:

MCS 3a Criteria Amendment Research (CAR)

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MCS 3a AKA Multiple Chemical Sensitivity:  2015 Consensus Criteria

Clear, Concise Etiology and Definition:

MCS 1 Etiology Narrative

MCS 2 The Etiology of MCS 

MCS 3 Definition and Consensus Criteria

Comprehensive CAR Test:

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MCS 3aa Etiology: Consensus Author CAR Test (SPC)

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Highly qualified government and academic researchers:

MCS 3b CAR References

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And Greetings from the President (smile):

There are books containing website content - including 3a and 3aa the CAR Test - available at cost (non-profit) for your convenience. Details linked: MCS Handbooks Available.

Membership is free - and can read without joining. There are many links to important studies.

Please take the self study CAR Test and be a 3a Consensus Author if you'd like.

Forums may be posted in any category except those of Mike's sequence. If anyone generates a series of forums - a separate category can be set up if desired.

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MCS 3c CAR Documentation

MCS 3d Etiology: CAR Case Example

MCS 3e Etiology: CAR Impossibly Good City Design

MCS 3f Criteria Amendment Q and A

MCS 3g CAR Nutritional Considerations

Precision Etiology: Forums aa-af

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Restatements...

MCS A-1 Etiology: Dantoft 2014

MCS ak Etiology: Words to the Wise

The 2016 MCS Consensus Criteria: A Kindness Trip

AKA The 2016 MCS Consensus Criteria: Reduced Suffering

AKA The 2016 MCS Consensus Criteria: Saving lives

AKA The 2016 MCS Consensus Criteria: Preventing Extinction

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Environmental Dilemma:

MCS aj Impossibly Good

Mgt 101 Consume Less or Extinction  

Mgt 101a Impossibly Good City Design

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Clean Diesel: Public Health Nightmare

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180,000 people are added to the World every day

Consume Less or Extinction

 A Plan for Avoiding Extinction:

Mgt 101a Impossibly Good City Design

Better Morality

Population Stabilization

Low Speed, Injury Proof, Zero Emission Vehicles

Walk to School, Work, and Shopping

Thermostats 50 Degrees or Less

Engage Only Unwasteful Products and Activities

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Consequences:

Love 201 Standard of Kindness

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Love 202 10 Alternatives

Management:

Nutrition: Mgt 110111112

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Exercise: Mgt 109

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GS Filters for Electromagnetic Hypersensitivity

 

The Etiology of MCS

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

2) 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).

3) 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).

4) The airway epithelium and its sensory innervation become altered to a proinflammatory condition

Deering-Rice 2011, Hazari 2011, Li 2011, Taylor-Clark 2010Baulig 2009, 2003aCalderon-Garciduenas 2008, 2000Veronesi 2003, 2002a, 2002b, 2001, 2000, 1999a, 1999b, Agopyan 20032003a, Bonvallot 2001, 2000, Gerde 2001, 1997Oortgiesen 2000, Roy 2000, Chin 1998, Miyabara 1998,1998a, Steerenberg 1998, Meggs 1997, Bond 1988

usually by exposure to a continuous ambient combustion byproduct 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, Kittelson 1998, Cadle 1999, Kleeman 1999  

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

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

5) 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 2008Kimata 2004, Chun 2002, Sterner-Kock 1999, Tinel 1999, Tanabe 1996, Tapner 1996, Nadin 1995, Stadler 1994, Khatsenko 1993).

6) Elevated cytokines are released by expression of the c-fiber sensory innervation of the nasal and upper pulmonary airway -including TRPA1 and TRPV1 irritant receptors

Deering-Rice 2011,Taylor-Clark 2010, Bessac 2008, Nassenstein 2008, Nilius 2007

Proinflammatory peptidenergic transmitters such as substance P, calcitonin gene related protein, and neurokinin A released by the 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 2010Oslund 2008, Mohankumar 2008, Calderon-Garciduenas 20082000, Agopyan 2003, Veronesi 2001, 1999a, 1999bSteerenberg 1998, Meggs 1997, Bascom 1992 MCS 6

7) 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).

8) Reactive and measurable (Millqvist 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).

9) 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 2008Nassenstein 2008Oslund 2008, Nilius 2007, Agopyan 2003, Veronesi 2001, 1999a, 1999b, Steerenberg 1998, Meggs 1997, Bascom 1992 MCS 6) cause neurocognitive impairment, SPECT hypoactivity (Orriols 2009), electroencephalographic alterations (Bell 1998, 1996) sensitization - permanent neuronal damage and reduced inhibitory neuronal activity in the olfactory pathways to the orbito-frontal cortex and the limbic system.

10)  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 2008Terlecky 2006, Kennedy 2005) -  increased cardiopulmonary disease risk  (Baldwin 1998), and disturbance in heme synthesis (porphyrin abnormalities) Daniell 1997Hahn 1997. Elevated cytokine TNF alpha may cause gastrointestinal stasis experienced as queasiness or nausea via vagal circuitry (Emch 2000).

11) 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).

12) 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).

13) 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 pathology of neuroinflammation - subclinical early - but associated with eventual neurodegeneration due to ACA PM, adsorbed compounds, byproducts of ozone exposure (photochemical smog resulting principally 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,

accumulation of Abeta-42 (42 amino acid form of amyloid beta) as neuronal, vascular and diffuse plaques, Abeta and alpha synuclein aggregation (associated with Alzheimers and Parkinsons Disease respectively) - 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 Abeta42 (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 chronic and repeated exposure to combustion byproducts including vehicle exhaust.

14) 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 certain intolerances 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.

15) 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.


16) 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 2011Manfredi 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).

 

17) 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 2004Canals 2003, Griffith 1999, Sterner-Kock 1999Tanabe 1996).

 

18) In apparent sudden onset of MCS from a large toxic exposure, usually the disease pre-existed as a genetic disposition (Eberling 2009, Veronesi 2001, 2000, Roy 2000, Jung 1921)

in a continuous environment of combustion byproduct fine particle aerosol - with airway epithelial cells and the sensory innervation already altered proinflammatory (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).

19) 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 - 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 2011Deluca 2010, Orriols 2009, Millqvist 2005Kimata 2004, Bell 1999, 1998) laboratory tests may have no utility for the patient - therefore mandatory testing is unethical and immoral.

20) If cause and effect were isolated - one breath of exhaust would exceed in reactivity all personal exposures of a careful person over several days - and yet the exhaust is continuous. Failure to recognize the effect of combustion byproduct particulate with adsorbed incompletely combusted gasoline and diesel fuel hydrocarbon - 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, US DOT FHA 2000) and need for a non-combustion way of life.

21) 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: 1960/2015 - 3 to 7.4 billion in just 55 years (Worldometers 2015), 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.

There is perhaps more than enough study - there is a need to apply morality - and learn to be impossibly good.

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

MCS 3b Etiology: 1, 2, & 3 References

 
 
 

MCS Forums

Introduction 

MCS Etiology 2018 Update: Activated Microglia

Honestly, What is MCS and Environmental Illness?

MCS Etiology: Take the CAR Test: Here's Why!

Etiology

Precision: easy as a b c...

MCS A-1 Etiology: Dantoft 2014

MCS A-1 Etiology: References

MCS aa Etiology: Not Always Visible

MCS ab Etiology: Particulate Vector

MCS ac Etiology: Redox and CYPs

MCS acc Etiology: Lipid Peroxidation

MCS ad Etiology: Naturally Sensitive

MCS ae Etiology: Airway Reactivity

MCS af Etiology: Central Sensitization

MCS ag Etiology: A Straight Line

MCS ah Etiology: Jung's Introverted Intuitive

MCS ai Etiology: Highlights

MCS aj Etiology: Impossibly Good

MCS ak Etiology: Words to the Wise

Defining Moments

MCS 1 Etiology Narrative

MCS 1a MCS 2019 Consensus Criteria

MCS 2 The Etiology of MCS

MCS 2a Etiology: TRPA1 Precision

MCS 2a Etiology: Notes on References

MCS 2ab Etiology: Nasal Cytokines in Context

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

MCS 3c CAR Documentation

MCS 3d Etiology: CAR Case Example

MCS 3e Impossibly Good City Design

MCS 3f Criteria Amendment Q and A

MCS 3g CAR Nutritional Considerations

MCS 4 Top Studies in a Nutshell

Focus

MCS 5 Research Letter

MCS 6 Neurogenic Inflammation: Delayed Effects

MCS 7 Kimata 2004: Neurogenic Inflammation Measured

MCS 8 Airway Origin: Reactive, Measurable, and Releasing Systemically

MCS 9 Airway Origin: PM and a Defective Scrubber

MCS 10 Credible Proof: The Study of all Studies

MCS 11 PM: Trigeminal and Olfactory Pathways

MCS 12 Skin Contact Hypersensitivity and Fibromyalgia

Genetics

MCS 13 Deluca 2010: Severe Oxidative Stress

MCS 14 Genetics in Detox Enzymes: Not Majority Etiology

MCS 15 Airway Genetics

Implications

Mgt 101 Consume Less or Extinction

Mgt 101a Impossibly Good City Design

Mgt 102 Ambient Environment

Management

Mgt 103 Filtration

Mgt 104 Respirators: Particles and Adsorbed Hydrocarbons

Mgt 104a Carbon in Respirators

Mgt 105 Home and Clean

Mgt 106 Clothing

Mgt 107 Sport Wash

Mgt 108 Vehicle

Mgt 109 Walking

Mgt 110 Nutrients Helpful: But Not Cure

Mgt 111 Vitamin D: How Much?

Mgt 112 Nutrition: A Package Deal

Golden Rule

Love 201 Standard of Kindness

Love 202 10 Alternatives

Love 203 Send Yours In Right Away

The following includes:

2015 Physiological Definition of MCS

2015 Consensus Criteria for MCS

2015 Physiological Definition of MCS

MCS is usually genetic vulnerability in the nasal and tracheal bronchial upper pulmonary airway epithelial cell population and its sensory innervation - including quantitative differences in neuropeptides, TRP receptors, and acid sensitive pathways critical to the homeostatic regulation of inflammatory neuroimmune response

MCS 15, Veronesi 2001, 2000, Roy 2000, Jung 1921

which becomes altered to a proinflammatory condition

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

in a continuous ambient combustion byproduct 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, Kittelson 1998, Cadle 1999, Kleeman 1999

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

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

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).

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).

Airway damage and exposed C-fiber nerves - including TRPA1 expressing peptidergic neurons (Materazzi 2013, Battacharya 2008, Bessac 2008, Veronesi 2001, Meggs 1997, 1996, 1993)

reactive and measurable (Millqvist 2005, Nogami 2004)

result in the MCS chain reaction: elevated plasma levels of neuropeptides, chemokines, cytokines, growth factors, and NO that mediate serious and multiple dysfunction of metabolizing and antioxidant enzymes (Deluca 2010, Liptrott 2009, Oslund 2008, Chun 2002, Sterner-Kock 1999, Tinel 1999, Tanabe 1996, Tapner 1996, Nadin 1995, Stadler 1994, Khatsenko 1993) - endogenous production of electrophiles and oxidants in an environment of oxidative stress - glutathione depletion and catalase deficiency - suppression of cytochrome P450 and aryl hydrocarbon receptor activity - high levels of hydrogen peroxide and 4 HNE - an atherogenic fatty acid profile of lipid peroxidation (Dantoft 2014, Deluca 2010, Kimata 2004) and increased cardiopulmonary disease risk  (Baldwin 1998).

ongoing flu-like symptoms (Dantoft 2014, Bascom 1992)

porphyrin abnormalities (Hahn 1997, Daniell 1997)

and central nervous system effects - xenobiotic penetration including UFPM (ultrafine particulate matter) and mediators of inflammation - intense, repeated, and sustained inputs from exposed airway sensory nerves - including TRPA1 expressing peptidergic terminals - involving TRPA1, TRPV1, substance P, CGRP, NKA, cytokines, NO, BDNF, bradykinin, glutamate, NMDAR, AMPAR, and mGluR (Materazzi 2013, Nassini 2011, Latremoliere 2009, Battacharya 2008) 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), and central sensitization - a functional synaptic plasticity resulting in pain hypersensitivity (Tran 2013, Holst 2011, Latremoliere 2009).

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 pathology of neuroinflammation - subclinical early - but associated with eventual neurodegeneration due to ACA PM, adsorbed compounds, byproducts of ozone exposure (photochemical smog resulting principally from vehicle exhaust), and cytokines reaching the brain.

The CNS condition includes increased inflammatory markers iNOS (inducible nitric oxide synthase), 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,

accumulation of Abeta-42 (42 amino acid form of amyloid beta) as neuronal, vascular and diffuse plaques, Abeta and alpha synuclein aggregation (associated with Alzheimers and Parkinsons Disease respectively) - 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 Abeta42 (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 chronic and repeated exposure to combustion byproducts including vehicle exhaust.

2015 Consensus Criteria for MCS

While leaving five of the six 1999 Consensus Criteria essentially intact - the 2015 Consensus corrects impression MCS is a syndrome in response to unrelated chemicals in a low level, commonly tolerated, non inciting background atmosphere.

Amendment includes language more consistent with intent (2,3,4) and information - especially concerning the ACA (3,4).

Pt 1 of the 1999 Consensus is not included because reproducibility of symptoms upon repeated exposure is effected by masking and overlap of continuous exposure to the ACA and other chemicals - saturating trigeminal and olfactory receptor sites and eliciting both immediate and delayed precipitation of symptomatology.

2015 Consensus Criteria for MCS

1) The condition is chronic

2) Levels of exposure to which most do not attribute symptoms result in precipitation of symptomatology

3) Symptoms may improve when incitants are removed - however exposure to the Ambient Combustion Aerosol (ACA) supporting the disease process is continuous

4) 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

5) Symptoms involve multiple organ systems

KIMATA 2004:

"...plasma levels of SP (substance P), VIP (vasoactive intestinal peptide), and NGF (nerve growth factor), but not histamine are significantly (p<0.01 by ANOVA) elevated in sMCS patients...

exposure to VOC further increased levels of SP, VIP, and NGF...exposure to VOC also increased plasma histamine levels...

these results indicate that sMCS patients may suffer from ongoing neurogenic inflammation which is aggravated by VOC..." 

ORRIOLS 2009:

"Neurologic dysfunction observed prior to chemical exposure could point to persistent subclinical neurologic changes. In fact, basal SPECT brain cortical hypoactivity was found in our patients. In animal models, inflammation and permanent damage of the olfactory neuronal pathways could result from translocation of inhaled ultrafine particles to the brain (Elder 2006)..."

It may seem incomprehensible - present in every breath since birth - exhaust saturated in the olfactory region - and along the entire nasal and upper respiratory tract of sensory receptors - fine particles with adsorbed chemicals - particulate vector and a prolonged residence time (Li 2011, Bonvallot 2001) stored in lung tissue and lymph nodes for months and years - desorption in 2 phases - initial rapid burst and extended gradual release (Gerde 2001, 1997) a physiological hijacking in a continual particulate shower - the ambient combustion aerosol - nearly all are rum dumb on this issue.

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

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 4of 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, US DOT FHA 2000and need for a non-combustion way of life.

GERDE 2001:

During combustion particles are generated and PAHs (polycyclic aromatic hydrocarbons) form in the gas phase. When the exhaust cools - PAHs adsorb or condense on the particles (Burtscher 1998).

rapidly desorbed PAHs "...are deposited, slowly absorbed, and extensively metabolized in airway epithelium at prolonged elevation of the local tissue concentration (Gerde 1997)..."

LI 2011:

"...DEP injures respiratory epithelia via a luminal-apical unloading mechanism of DEP organics delivered by carbonaceous nanoparticles..."

BONVALLOT 2001:

"...the carbonaceous core could be considered mostly as a vector allowing the entry of organic compounds into the cells and their slow diffusion leading to sustained stimulation of the cells as native diesel exhaust particles-induced NFkB DNA binding started later but was more persistent than that induced by organic extracts of diesel exhaust particles...(Boland 2000, 1999Bonvallot 2000, Baeza-Squiban 1999, Bayram 1998, Kumagai 1997, Thomas 1997)..."

MATSUI 2009 

"...The results obtained support that nano-sized DEPs do in fact translocate to the central nervous system through the olfactory nerve..." 

LEWIS 2005:

"...Although the neuronal architecture of the olfactory and trigeminal systems differ , the fact that both have sensory receptors within the nasal epithelium and project directly to the CNS suggest that similar pathways for toxicant entry may exist ..."

...These data support the conclusion that a similar pattern of uptake may occur within the trigeminal system as has been observed  in the olfactory system...

...into the CNS in concentrations greater than those found with systemic distribution and without penetrating the blood-brain barrier... 

...These data underscore the importance of considering routes of toxicant entry that allow for bypassing of the protection afforded by the blood brain barrier, and the importance of understanding the conditions under which these pathways are operative..." 

GENTER 2009 

"...Tight junctions are critical barrier features in tissues throughout the body. In the olfactory epithelium, tight junctions are found at the apical surface of cells, adjacent to the nasal airways..."

MEGGS 1997 

Biopsy of MCS subjects

"...There are defects in the tight junctions between respiratory epithelial cells , focal desquamation of the epithelial cells in places, hypertrophy of glandular structures, lymphocytic infiltrates, and proliferation of sensory nerve fibers ..."

CALDERON-GARCIDUENAS 2008 

"...Induction of upper respiratory , lung epithelial, and endothelial injury leading to persistent chronic inflammation in the respiratory tract and systemic inflammation. The systemic inflammation is accompanied by the production of pro-inflammatory cytokines such as TNF alpha, IL-6, and IL-1 beta...can...disrupt the BBB..." 

...Breakdown of the nasal barrier in pollution exposed subjects may also contribute to brain inflammation by increasing the access of PM to the brain through the olfactory and trigeminal pathways..."

ADDENDUM TO THE 1997 FEDERAL HIGHWAY COST ALLOCATION STUDY FINAL REPORT. U.S. DEPARTMENT OF TRANSPORTATION. FEDERAL HIGHWAY ADMINISTRATION MAY 2000:
"...Total social costs of air pollution associated with motor vehicle use are
estimated to range from $30 billion to $349 billion per year (Delucchi 1998). Most of those costs are associated with premature death and illness caused by particulate matter, including both direct particulate emissions and the secondary formation of particulates from other emissions. The wide range of air pollution cost estimates is indicative of the many uncertainties surrounding costs of motor-vehicle-related air pollution..."

PERVIN 2008:

"...Moreover, ambient PM, including sulfates, nitrates, and organic aerosols, accounts for about 95% of the total damage cost, and mortality related to ambient PM accounts for about 70% of the total damage cost..."

Therefore, as mentioned above the 2015 Consensus corrects impression MCS is a syndrome in response to unrelated chemicals in a low level, commonly tolerated, non inciting background atmosphere (Block 2009, Calderon-Garciduenas 2008,  Veronesi 2001).

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 - 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 2011Deluca 2010, Orriols 2009, Millqvist 2005Kimata 2004, Bell 1999, 1998) laboratory tests may have no utility for the patient - therefore mandatory testing is unethical and immoral.

However, it is important to acknowledge the physiological definition - not necessarily for the purpose of medical diagnosis - but to recognize this is an environmental crisis - not only to a subset of the population effected most acutely - but threatening life on earth (Rogers 2011) - a continuous combustion aerosol - and move the lifestyle to a higher level of morality making possible change to a non combustion basis.

We should be together in addressing the crisis of unrestrained growth and consumption. Consequences are catastrophic - geopolitical turmoil, overpopulation: 4.4 billion 1960/2015 - 3 to 7.4 billion in just 55 years (Worldometers 2015), 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.

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