Multiple Chemical Sensitivity Etiology
Airway Genetics and Ambient Combustion Aerosol
MCS 2 The Etiology of MCS
1) MCS people usually do not have genetic differences in chemical defense as major part of the disease (Badolato MCS 14, Berg 2010, Deluca 2010).
2) Most MCS people have genetically sensitive airway tissue (MCS 15, Veronesi 2001, 2000, Roy 2000, Jung 1921).
3) 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 (Eberling 2009).
4) 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).
5) The airway epithelium and its sensory innervation become altered to a proinflammatory condition usually by exposure to a continuous combustion byproduct aerosol - diesel and other exhaust, woodsmoke, and tobacco smoke including particle agglomerates with adsorbed hydrocarbons and singlet nonagglomerated nanoparticles
(OSHA 2012, Deering-Rice 2011, Hazari 2011, Li 2011, Lucchini 2011, Taylor-Clark 2010, Baulig 2009, 2003a, Block 2009, 2004, Mohankumar 2008, Calderon-Garciduenas 2008, 2000, Inoue 2005, Veronesi 2005, 2003, 2002a, 2002b, 2001, 2000, 1999a, 1999b, Agopyan 2003, Oortgiesen 2000, Roy 2000, Pakkanen 2003, Schauer 2002, 2001, 1999, Kittelson 1998, Cadle 1999, Kleeman 1999 , Bonvallot 2001, 2000, Gerde 2001, 1997, US DOT FHA 2000, Miyabara 1998,1998a, Steerenberg 1998, Society of Automotive Engineers SAE 940233 1994)
Fine particles expected to reach the CNS via trigeminal and olfactory nerve pathways
(Badolato MCS 11, Calderon-Garciduenas 2010, Genter 2009, Matsui 2009, Elder 2006, Lewis 2005)
6) MCS people have elevated levels of neuropeptides, chemokines, cytokines, growth factors, and nitric oxide that mediate serious and multiple dysfunction of xenobiotic enzyme chemical defense systems (Badolato MCS 13, 7, Deluca 2010, Kimata 2004).
7) 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 2010, Oslund 2008, Mohankumar 2008, Calderon-Garciduenas 2008, 2000, Agopyan 2003, Veronesi 2001, 1999a, 1999b, Steerenberg 1998, Meggs 1997, Bascom 1992 MCS 6).
8) 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).
9) Reactive and measurable (Millquist 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 (Bascom 1992 MCS 6), higher respiratory rate, increased nasal resistance (Doty 1994), secondary punctate hyperalgesia indicating facilitated central sensitization (Tran 2012), 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).
10) Xenobiotic penetration and mediators of inflammation - activation and release involving TRPV1, TRPA1, substance P, CGRP, glutamate, NMDA, cytokines, and nitric oxide cause neurocognitive impairment, SPECT hypoactivity (Orriols 2009), electroencephalographic alterations (Bell 1999, 1998) sensitization - permanent neuronal damage and reduced inhibitory neuronal activity in the olfactory pathways to the orbito-frontal cortex and the limbic system.
11) 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 (Badolato MCS 13, Deluca 2010, Calderon-Garciduenas 2008, Yang 2008, Terlecky 2006, Kennedy 2005) and disturbance in heme synthesis (porphyrin abnormalities) Hahn 1997, Daniell 1997. Elevated cytokine TNF alpha may cause gastrointestinal stasis experienced as queasiness or nausea via vagal circuitry (Emch 2000).
12) It may be surmised that in apparent sudden onset of MCS from a large toxic exposure, usually the disease pre-existed as a genetic disposition in a continuous environment of combustion byproduct fine particle aerosol - with airway epithelial cells and the sensory innervation already altered proinflammatory - releasing cytokines mediating dysfunction of xenobiotic enzyme chemical defense systems - whereas those without genetic predisposition and subsequent alteration usually suffer such large toxic exposures and cumulative exposure without developing MCS.
13) The MCS etiology presented here applies to most cases of MCS - but there are exceptions and variations - including circumstances that may involve genetic differences in detox in some individuals (Schnakenberg 2007, McKeown-Eyssen 2004). However, there is no evidence that such variants account for the severity of inflammatory response to all pollutants involved with MCS - and they have been found to occur no more often among MCS people than in the general population (Badolato MCS 14, Berg 2010, Deluca 2010).
Other secondary genetic factors may also determine multi-organ effects with ongoing oxidative stress.
14) The genetic predisposition and subsequently defective airway - combined with exposure to a continuous atmosphere of combustion derived particulate - results in a condition of systemic oxidative stress peculiar to MCS people. Other genetic factors lead to the oxidative susceptibility of Parkinsons disease where .22 micron diesel exhaust particles have been shown to enter the brain effecting dopaminergic nerves in such way as to provoke symptoms (Veronesi 2005, Block 2004).
!5) 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 for nearly everyone - all the time - every breath is exhaust. 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 (Bessac 2008).
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 (US DOT FHA 2000) and need for a non-combustion way of life.
Links
Etiology
Precision: easy as a b c...
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 aj Etiology: Impossibly Good
Defining Moments
MCS 3 Definition: What is MCS?
MCS 4 Top Studies in a Nutshell
Focus
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 Overlooks Airway Genetics
MCS 14 Genetics in Detox Enzymes: Same as Controls
Implications
Mgt 101 Consume Less or Extinction
Mgt 101a Impossibly Good City Design
Management
Mgt 104 Respirators: Particles and Adsorbed Hydrocarbons
Mgt 110 Remedies: Black or White?
Mgt 112 Nutrition: A Package Deal
Golden Rule
Love 201 20 Commandments: Who's Overdoing It?
Love 203 Send Yours In Right Away
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