Multiple Chemical Sensitivity Etiology
Airway Genetics and Ambient Combustion Aerosol
MCS ak Etiology: Words to the Wise
It seems no one wants to believe combustion byproducts are the biggest culprit - reviews of MCS have often been misleading or incomplete - leaving out decades of clear, consistent evidence.
The Kimata 2004 study showed MCS people were hyperinflammatory upon arrival - coming in off the street - before exposure to paint - MCS substance P and nerve growth factor 105 and 1129 compared to controls at 38 and 148. Exposure to paint raised MCS numbers to 153 and 1696 with controls nearly unchanged at 39 and 156.
The following strongly supports MCS people were inflammatory before exposure to paint by the combustion aerosol - leaving us to recognize that happy motoring, opulent consumption, and unrestrained growth have consequences.
Damaged Airway Epithelium Exposing C-fiber Nerves
Bascom 1992 (MCS 6):
...the airway epithelium and the airway surface fluid it produces and regulates are the first line of defence against the multiple, "non-self" constituents in the 10-20,000 liters of air inhaled each day. The airway epithelium is not an inert barrier, as was once thought, but contains a great capacity for xenobiotic metabolism...the observation that the airway can release cytokines...flu-like symptoms, low grade fever, and fatigue that...usually begin several hours after the exposure and last up to 48 hours...a type of acute phase response. Cytokines are now recognized as responsible..."
"...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..."
"...The mechanism by which inflammatory conditions are provoked by chemicals is via chemoreceptors on sensory nerve C-fibers with the release of substance P and other mediators of neurogenic inflammation..."
Airway Epithelium a Focal point for Xenobiotic Metabolism
"...inhaled bioavailable PAH's...deposited, slowly absorbed, and extensively metabolized in airway epithelium at prolonged elevation of the local tissue concentration (Gerde 1997)..."
Genetically Sensitive Airway Equals More Tissue Damaging Inflammatory Response Per Any Pollutant Exposure
"...taken together, the above in vivo and in vitro studies suggested that the variable inflammatory sensitivity to PM observed in different mouse strains (ie Balb/C, B6) related to quantitative differences in the neuropeptide, VR1 (now TRP) receptors and acid sensitive pathways found on sensory neurons that innervate the nasal and upper pulmonary airway. Such data showed how genetically determined differences in sensory neural pathways could influence expressions of PM-induced airway inflammation...genetic differences are thought to underlie these variations and have been experimentally demonstrated for ozone (Kleeberger 1995, Zhang et al 1995), nitrogen dioxide (Holroyd et al 1997), and diesel exhaust (Ichinose et al 1997, Miyabara et al 1998)...
...In normal physiological settings, the respiratory epithelial population and its sensory innervation act reciprocally to influence the growth, differentiation, and homeostasis of each other...These relationships are especially critical to the organism's inflammatory response...In all instances, sensory neurons release 10-200 fold higher levels of IL-6 (pro-inflammatory cytokine) relative to epithelial cells...conditions associated with chemical pollutants are characterized by damage to the epithelial barrier that lines the airways. Such damage not only results in the loss of critical neuropeptide deactivating enzymes (e.g. NEP) but allows the sensory fiber to physically extend closer to the airway lumen and in closer proximity to the inhaled PM particles...enhanced and prolonged inflammatory events...increased inflammatory response...".
Chronic and Sequential
"...a persistent ongoing airway inflammatory process the result of exposure to air pollutants in a sequential and chronic manner...the imbalance and dysregulation of cytokines and their ample systemic effects...
...their phenotype is altered to one that secretes cytokines, mediators, chemokines, and growth factors..." - confirmed in MCS people (Deluca 2010, Kimata 2004)...
...the epithelium responds with increased proliferation and repair; under chronic, repeated injury, the epithelium becomes a continuous source of inflammatory products...Further, cytokines can reach the systemic circulation and are likely to produce systemic effects...(Blum 1996), (Pulkki 1997) (Orbe 1999), (Schwertschlag 1999),Shanley 1995)..."
"...In vitro, epithelial cells and macrophages (particles target cells) exposed to PM, developed a pro-inflammatory response characterized by the release of inflammatory cytokines (Baulig 2003a, Hetland 2004, Jalava 2008)...
...particulate matter is a very complex mixture containing various components such as carbonaceous core, polyaromatic hydrocarbons (PAH), quinones, metals, endotoxins, and many other components (Harrison and Yin 2000)...
...studies using specific particles either rich in PAH (diesel exhaust particles [DEP}) or metals (residual oil fly ash) have highlighted the role of these components in the pro-inflammatory response (Bonvallot 2001, Nel 2001, Schaumann 2004). Endotoxins can also be present on particles and induce inflammation (Huang 2002, Schins 2004)...
...Paris PM2.5 (particulate matter less than 2.5 microns) modify the cellular redox state and induce a pro-inflammatory response characterized by GM-CSF (granulocyte macrophage-colony stimulating factor - a pro-inflammatory cytokine) release. The effect is similar to that of DEP (diesel exhaust particles)..."
Airway Breakdown: Gateway to the CNS
"...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..."
More Precision: TRPA1 Irritant Receptors on Exposed C-fiber Nerves in Damaged Airway Epithelium
"...A number of studies have correlated responses to urban PM, including DEP with activation of airway sensory neurons, particularly C and A beta fibers that express Transient Receptor Potential Ankyrin-1 (TRPA1), TRP Vanilloid-1 (TRPV1), and substance P (Hazari 2011, Teles 2009, Anand 2008, Nassenstein 2008, Kobayashi 2005)...
...TRPA1 and V1 are members of the superfamily of ion channels, and numerous TRP receptors including TRPA1, V1-4, and M8 are highly expressed in the respiratory tract where they can function as environmental sensors...
...TRPA1, M8, and V1-4 all respond to specific chemical irritants (Vriens 2009, Venkatachalam 2007, Voets 2005) and activation of either TRPA1 or V1 in pulmonary sensory nerves causes neurogenic inflammation via the release of substance P (SP) and neurokinin A (NKA) (Baraldi 2010)...
...TRPV1, V3, V4, and M8, but seemingly not TRPA1 or V2, are also expressed by airway epithelial cells, and activation of TRPV1 (Teles 2009, Agopyan 2004, 2003, Veronesi 2003, 2001, 2000, Oortgiesen 2000) and TRPM8 (Sabnis 2008) in these cells by prototype agonists and select forms of environmental PM is coupled with proinflammatory cytokine/chemokine production and apoptosis..."
"...TRPA1 (transient receptor potential ankyrin 1) is expressed in a subpopulation of TRPV1-expressing c-fiber neurons...
...TRPA1 is activated by (smoke constituents) methacrolein, methyl vinyl ketone, and croton aldehyde (Andre 2008, Escalera 2008)...oxidizing agents...hypochlorite (chlorine gas)...(Bessac 2008a)...formaldehyde, acetaldehyde, tear gas agents, and industrial isocyanates (Bang 2007, Bessac 2009, Brone 2008, McNamara 2007)...almost all oxidizing and electrophilic chemicals will affect TRPA1 function...endogenous agonists include reactive oxygen species (ROS), hypochlorite, lipid peroxidation products, cyclopentenone prostaglandins, and isoprostanes...
...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)..."
"...present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde, and others that are known to be headache triggers and recently identified as TRPA1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain...
...our observations identify umbellone, via its selective TRPA1-agonism, as a trigeminovascular stimulator...for the headache-inducing properties of California bay laurel...a similar pathway may represent the underlying mechanism responsible for headache crises triggered in sensitive people by a series of compounds present in environmental pollutants and botanical perfumes/odours (Blau and Solomon 1985, Kelman 2007, Friedman 2009)..."
"...TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma...
...Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge..."
Combustion Aerosol: Extinction
Today when starting car or truck - contributing to a combustion aerosol - senseless as smoking in a hospital - there seems not thought of the consequences. This same aerosol raises CO2 levels in the atmosphere changing the climate - and soaks into the ocean causing acidification and anoxia - with expectation of the worst mass extinction of ocean species in history.
Even without point sources of notoriety - we're still left with disease and going extinct due to the combustion aerosol from burning fuels.
Moral Responsibility
It's beyond blaming someone else. We have to improve our everyday morality - stop using energy frivolously and take pleasure in doing the right thing - like going places without a 4000 lb machine on our back, keeping warm with the thermostat at 50 instead of 70, staying cool by using a fan or breeze - not an air conditioner, disengaging from wasteful products and activities, design walking distance urban geography, shift back to making basic consumer goods - recyclable or biodegradable materials - the goal not to bury anything out of the loop.
No One To Blame
Concerning disability due to negligence at specific sites - there may be some helpful rules of moral behavior. Respectfully reporting it to an agency such as EPA and obtaining Social Security disability may be appropriate.
Beyond that filing a lawsuit is highly questionable - and if done should be as a humble supplicant asking for a fair and modest compensation recognizing that all regret the circumstances and wish things had been done differently - and using those very words and tone for a noncontentious settlement.
The worst action is an aggressive claim for wealth and presenting a public nuisance resulting in jailtime and other legal problems. Seeking publicity and forum to impugn reputation and allege conspiracy and coverup - is not constructive. Blame game, vendetta, excuse for a fight, litigation for self enrichment - have no place.
A good attitude: I hope that greater knowledge will lead to better recognition of environmental hazards so no one is harmed - and we can all work together for a better World.
When the Ocean Programme - leading authority - reported expectation of the worst mass extinction in history largely due to absorption of the combustion aerosol - the BBC commentator said this is important and horrible but you know in a week old news and forgotten - and will anything change?
Imagine 2000 smiling faces - real people caring about each other - 20 envelopes - twice a year reminding 40,000 doctors with warm, kind letters.
References
Bascom R. MCS: A Respiratory Disorder. Tox Ind H 8;4: 221-28 1992 in Badolato Jr. M.E. MCS 6 Neurogenic Inflammation: Delayed Effects. mcsmultiplechemicalsensitivity.ning.com 2012
Baulig A.et al.Role of Paris PM 2.5 components in the pro-inflammatory response induced in airway epithelial cells. Tox 261: 126-35 2009
Bessac B.F. and Jordt S.E. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiol 23: 360-70 2008
Caceres A. et al. A sensory neuronal ion channel essential for airway inflammation and hypereactivity in asthma. PNAS 106;22:9099-9104 2009
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 accumulation of amyloid beta-42 and alpha-synuclein in children and young adults. Tox Pathol 36: 289-310 2008
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): 373-378 2000
Deering-Rice et al. Electrophilic components of diesel exhaust particles (DEP) activate transient receptor potential ankyrin-1 (TRPA1): a probable mechanism of acute pulmonary toxicity for DEP. Chem Res Toxicol 24;6:950-9 2011
Gerde P. et al. The rapid alveolar absorption of diesel-soot adsorbed benzo[a]pyrene: bioavailability, metabolism, and dosimetry of an inhaled particle-borne carcinogen. Carcinogenesis 22;5:741-49 2001
Gerde P. et al. Benzo{a}pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium. Carcinogenesis 18:1825-32 1997
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.
MEGGS W.J. ARCH ENV HEALTH 54(5) 309-11 1999
Meggs W.J. Hypothesis for induction and propagation of chemical sensitivity based on biopsy studies. EHP 105;2: 473-78 1997
Nassini R. et al. The 'headache tree' via umbellone and TRPA1 activates the trigeminovascular system. Brain doi:10 1093/brain/awr272 2011
VERONESI B. & OORTGIESEN M. NEUROGENIC INFLAMMATION AND PARTICULATE MATTER (PM) AIR POLLUTANTS. NEUROTOXICOLOGY (22):795-810 2001
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