Multiple Chemical Sensitivity Etiology

Airway Genetics and Ambient Combustion Aerosol

MCS A-1 Etiology: Dantoft 2014

MCS A-1 Etiology: References

MCS 1 Etiology Narrative

MCS 2 The Etiology of MCS 

MCS 3 Definition and Concensus Criteria

MCS 3a Etiology: Criteria Amendment Research Points (CAR)

MCS 3a AKA Multiple Chemical Sensitivity:  2015 Concensus Criteria

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

MCS 3b Etiology: CAR References A-H including MCS 1, 2, &3

MCS 3b Etiology: CAR References I-Q including MCS 1, 2, &3

MCS 3b Etiology: CAR References R-Z including MCS 1, 2, &3

MCS 3b Etiology: References of MCS 3a only

MCS 3c Etiology: CAR Documentation

MCS 3d Etiology: CAR Case Example

MCS 3e Etiology: CAR Impossibly Good City Design

MCS 3f Etiology: Criteria Amendment Q and A

MCS 3g CAR Nutritional Considerations

MCS Etiology includes work at the National Health and Environmental Effects Research Laboratory (NHEERL US EPA) reported by Veronesi 1999-2003 and Roy 2000 - most insightful - summarized in Veronesi 2001 - yet seemingly no one concerned with MCS has referred to it.

They found that a mouse strain inflammatory in response to pollution had genetically determined quantitative differences in vanilloid receptors (now referred to as TRPV1), acid sensitive pathways, and neuropeptides on c-fiber sensory nerves in the airway - compared to a mouse strain that had little reaction. It was determined inflammation set forth by the nerves (neurogenic inflammation) concerns immune system involvement and cytokine release - and occurs especially where there is damage to the epithelial barrier that lines the airways.

Meggs 1997, 19961993 confirmed tight junction defects and focal desquamation in MCS people - exposed nerves, lymphocytic infiltrates, and multiplication of nerve endings.

Kimata 2004 measured plasma nerve growth factor 7-10 times higher in MCS people than controls. Dantoft 2014 of the Danish Research Center of Chemical Sensitivities found an altered cytokine profile and Deluca 2010 - funded by the Italian Ministry of Health and the Swedish Medical Society - found elevated cytokines, chemokines, growth factors, and nitric oxide - glutathione depletion, catalase deficiency, and a fatty acid profile indicating lipid peroxidation - increased SFA with losses in PUFA, N-6, N-3, arachidonic acid and omega 3.

Although findings with mice were never confirmed in a comparative study of MCS nerve receptors and pathways - pieces of the puzzle fit - including experiments with human epithelial cell line and Jung's observed hypersensitivity of the sense organs among the introverted intuitives - that genetically determined differences of sensory nerve receptors and pathways would be found in MCS people.

Deluca 2010 found that chemical defense xenobiotic and antioxidant enzymes were dysfunctional, there was no difference in the genetics of these detox systems between MCS and controls, and concluded that dysfunction was cytokine mediated (Deluca 2010, Liptrott 2009, Oslund 2008, Chun 2002, Sterner-Kock 1999, Tinel 1999, Tanabe 1996, Tapner 1996, Nadin 1995, Stadler 1994, Khatsenko 1993).

Assembling the puzzle - cytokines were released by the neuroinflammatory immune response occurring in the airway. Earlier studies such as Schnakenberg 2007 suggested variants in genetics involving Phase I and II xenobiotic antioxidant enzymes could be involved and were incorrectly promoted as etiology. The studies of Deluca 2010 and Berg 2010 - along with recognition that one or more of the GSTM1 and GSTT1 deletions occur in over 50% of the population (Piacentini 2011, Block 2011, Ginsberg 2009, Hayes 1995) - a percentage not corresponding with the incidence of MCS - have proved such an explanation incorrect. For details please see MCS 14. 

Supporting the neuro-inflammatory etiology is the work of Millqvist 2005 and Nogami 2004 showing MCS nerve reactivity and cough when provoked by capsaicin - with much greater nerve growth factor release.

The Merck Manual of Medicine for physicians presents the immune system in terms of antigen, antibody, T-cells, B-cells and so forth with considerable detail - but does not include the structure and function of the sensory nervous system and its critical role concerning inflammatory immune response. In not doing so - the etiology of MCS is unacknowledged.

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).

Calderon-Garciduenas 2008, 2001, 2000 - with intensive tissue examination of canines and humans - found permanent airway epithelial damage - release of cytokines, chemokines, and growth factors - as fundamental to the disease process caused by air pollution.

Influenced by genetic predisposition - the systemic oxidative stress involved with the increase of inflammatory mediators, a greater penetration of particles, and dysfunction of xenobiotic and metabolizing enzymes - may express not only as MCS - but other diseases which lack subjective recognition of immediate reactivity to pollutants - such as Alzheimers and Parkinsons (Lucchini 2011, Calderon-Garciduenas 2010Veronesi 2005, Block 2009, 2004).

Environmental degradation, climate change (EPA 2012, CNN-IPSO, Rogers and Laffoley 2011) - and health cost (Pervin 2008, US DOT FHA 2000) show the need to stop population growth, reduce consumption, and move away from a combustion energy basis.

link:

MCS 3b CAR References

References 

MCS 14 Genetics in Detox Enzymes Not Majority Etiology mcsmultiplechemicalsensitivity.ning.com 2012

Berg N.D. et al. Genetic susceptibility factors for multiple chemical sensitivity revisited. Int J Hyg Env H 213: 131-39 2010

Block M.L.and Calderon-Garciduenas L. Air pollution: mechanisms of neuroinflammation & CNS disease. Trends Neuro 32(9): 506-16 2009

Block M.L. et al. Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons; the role of microglia, phagocytosis, and NADPH oxidase. FASEB 10.1096/fj.041945fje 2004

Calderon-Garciduenas L. et al. Urban air pollution: influence on olfactory function and pathology in exposed children and young adults. Exp Tox Pathol 62:91-102 2010

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

CNN-IPSO. Shaikh T. Marine life facing mass extinction, report says. 2011

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

EPA.gov Climate Change 2012

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

Lucchini R.G. et al. Neurological impacts from inhalation of pollutants and the nose-brain connection. Neurotox (2011) doi:10.1016/j.neuro.2011.12.001 in press

Meggs W.J. Hypothesis for induction and propagation of chemical sensitivity based on biopsy studies. EHP 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

Millquist E. et al. Changes in level of nerve growth factor in nasal secretions after capsaicin inhalation in patients with airway symptoms from scents and chemicals. EHP 113;7: 844-52 2005

Nogami H. et al. Capsaicin provocation test as a diagnostic method for determining multiple chemical sensitivity. Allergology Int 2: 153-57 2004

Rogers A.D. and LaffoleyD.d'A. International earth system expert workshop on ocean stresses and impacts. Oxford 18pp 2011. International Programme on the State of the Ocean.org

Roy et al. Susceptibility to pollutant-induced airway inflammation is neurogenically mediated. EPA EIMS Metadata report 59754 2000

Schnakenberg E. et al. A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes. Env H 6:6 2007

US DOT FHA Addendum to the 1997 Federal Highway Cost Allocation Study. Final report. May 2000

Veronesi B. et al. Effects of subchronic exposure to concentrated ambient particles VII Degeneration of dopaminergic neurons in APO E-1 mice. Inhal Tox 17; 4-5: 235-41 2005

Veronesi B. et al. Electrostatic charge activates inflammatory vanilloid (VR1) receptors. Neurotox 24: 463-73 2003

Veronesi B. et al. The surface charge of visible particulate matter predicts biological activation in human bronchial epithelial cells. Tox and Appl Pharm 178: 144-54 2002a

Veronesi B. et al. Particulate matter inflammation and receptor sensitivity are target cell specific. Inhal Tox 14(2): 159-83 2002b

Veronesi B. and Oortgiesen M. Neurogenic inflammation and particulate matter (PM) air pollutants. Neurotox 22: 795-810 2001

Veronesi B. et al. Vanilloid capsaicin receptors influence inflammatory sensitivity in response to particulate matter. Tox Appl Pharm 15;169(1): 66-76 2000

Veronesi B. et al. Particulate matter initiates inflammatory cytoki... by activation of capsaicin and acid receptors in a human bronchial epithelial cell line. Tox and Appl Pharm 154: 106-15 1999a

Veronesi B.et al. Neuropeptides and capsaicin stimulate the release of inflammatory cytokines in a human bronchial epithelial cell line. Neuropep 33;6: 447-56 1999b

 

 

Views: 170

Reply to This

© 2024   Created by michael edward badolato jr.   Powered by

Badges  |  Report an Issue  |  Terms of Service