Multiple Chemical Sensitivity Etiology

Airway Genetics and Ambient Combustion Aerosol

Forum MCS 9 Airway Origins: PM and a Defective Scrubber - reported the work of Calderon-Garciduenas 2000- since proven true.

The world continues to deteriorate with ever greater input of combustion byproducts. There has not been enough concern..


CALDERON-GARCIDUENAS ET AL. LONG TERM AIR POLLUTION IS ASSOCIATED WITH NEUROINFLAMMATION,  AN ALTERED INNATE IMMUNE RESPONSE, DISRUPTION OF THE BLOOD BRAIN BARRIER, ULTRAFINE PARTICULATE DEPOSITION, AND ACCUMULATION OF AMYLOID BETA-42 AND ALPHA-SYNUCLEIN IN CHILDREN AND YOUNG ADULTS. TOX PATHOL 36: 289-310 2008:

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

"...A coherent pathway linking exposure to air pollution and brain damage includes a chronic inflammatory process involving the respiratory tract, which results in a systemic inflammatory response with the production of inflammatory mediators capable of reaching the brain; continuous expression of crucial inflammatory mediators in the CNS at low levels; and the formation of reactive oxygen species (ROS) (Calderon-Garciduenas et al 2002, 2004; Calderon-Garciduenas, Maronpot et al 2003; Calderon-Garciduenas, Mora-Tiscareno et al 2003)..."

"...sustained exposures to significant levels of air pollutants including UFPM (ultrafine particulate matter) , PM2.5 (less than 2.5 microns), and PM-LPS  produce brain neuroinflammation and neurodegeneration through at least four pathways..."

"...1  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-1beta...these cytokines can activate endothelial cells in the BBB, disrupt the BBB...and trigger cascades...results in increased expression of nitric oxide synthase...and nitric oxide production that opens the BBB..."

"...2  We strongly support the importance of the olfactory pathway...since olfactory neurons are loaded with PM...will potentially translate into an abnormality in the limbic system...(Bedard et al 2004)..."

"...3  The vagus/trigeminal (Lewis et al 2005) pathways are also crucial, given that PM enters the respiratory and digestive systems..."

"...4  Direct access of UFPM to the brain, further accentuating an inflammatory response in the brain parenchyma..."

"...In summary, exposure to significant concentrations of air pollutants including UFPM and PM2.5 produces neuroinflammation and altered innate immune responses in crucial brain target anatomical areas...We strongly propose that neuroinflammation as a result of exposure to air pollution could have a causative role in both Alzheimer's and Parkinson's diseases...  Long term exposure to air pollution should be considered a risk factor for both..."

Neuroinflammation as a result of exposure to air pollution is causative in Multiple Chemical Sensitivity - especially the continuous aerosol of diesel and other exhaust, woodsmoke, and tobacco smoke - including fine particle agglomerates with adsorbed hydrocarbons and singlet nonagglomerated nanoparticles.  Multiple Chemical Sensitivity is accompanied with:

1 (from above) Induction of upper respiratory injury (Meggs 1997, 1996, 1993) leading to persistent chronic inflammation in the respiratory tract and systemic inflammation (Deluca 2010, Kimata 2004) and nitric oxide production (Deluca 2010).

2 the importance of the olfactory pathway since olfactory neurons are loaded with PM...(Matsui 2009)

3 the vagus/trigeminal pathways also allow PM to the CNS - involved in MCS

4 Direct access of UFPM to the brain further accentuating an inflammatory response in the brain parenchyma may also apply to MCS..

Though neuroinflammatory pathways are similar, genetics largely determine which disease a person may develop from exposure to air pollution.

 


References 

Bedard A. and Parent A. Evidence of newly generated neurons in the human olfactory bulb. Dev Brain Res 151: 159-68 2004

Calderon-Garciduenas L. et al. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulationof amyloid beta-42 and alpha-synuclein in children and young adults. Tox Pathol 36: 289-310 2008

Calderon-Garciduenas L. et al. Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Tox Pathol 32: 650-58 2004

Calderon-Garciduenas L. et al. Air pollution and brain damage. Tox Pathol 30: 373-89 2002

Calderon-Garciduenas L. et al. Respiratory tract pathology and cytokine imbalance in clinically healthy children chronically and sequentially exposed to air pollutants. Med hyp 55(5): 373-78 2000

Calderon-Garciduenas L., Maronpot R.R. et al. DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration. Tox Pathol 31: 524-38 2003

Calderon-Garciduenas L., Mora-Tiscareno A. et al. Respiratory damage in children exposed to urban pollution. Pediatr Pulmonal 36: 148-61 2003

Deluca C. et al. Biological definition of multiple chemical sensiti... from redox state and cytokine profiling and not from polymorphisms of xenobiotic metabolizing enzymes. Tox and Appl Pharm 248: 285-92 2010

Kimata H. Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor, and histamine in patients with self-reported multiple chemical sensitivity. Int J Hyg Env H 207(2): 159-63 2004

Lewis J. et al. Trigeminal uptake and clearance of inhaled manganese chloride in rats and mice. Neurotox 26: 113-23 2005

Matsui Y. et al. Tracking the pathway of diesel exhaust particles from the nose to the brain by x-ray florescense analysis. Spectrochimica Acta Part B 64: 796-801 2009

Meggs W.J. Hypothesis for induction and propagation of chemical sensitivity based on biopsy studies. Env H Perspect 105(2): 473-78 1997

Meggs W.J. et al. Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure. J Tox Clin Tox 34;4: 383 1996

Meggs W.J. and Cleveland Jr. C.H. Rhinolaryngoscopic examination of patients with multiple chemical sensitivity syndrome. Arch Env H 48: 1-14 1993

 

 

 

 

 

 

 

 

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