Multiple Chemical Sensitivity Etiology
Airway Genetics and Ambient Combustion Aerosol
MCS Consensus II Postscript Splash: MCS, ME/CFS - Inflammatory Response to Air Pollution
A slower paced, reduced consumption, non combustion lifestyle is needed or human beings will go extinct due to loss of environment and resources.
I. Baseline GSAA, ACA, SRPE 1-8
II. Diagnosis, Patient Rights, Etiology 9-14
III. Baseline: Nutrition and Exercise 15-31
A. SJF, LE 15-20
B. Whole Food Nutrition 21-31
IV. Baseline: Nutrition and Exercise 32-38
C. Suboptimal Actors 32
D. Maintaining Bone Density 33-37
E. Preventing Atherosclerosis 38
Appendix: Added Splash I-VI
Index: MCS, Nutrition, Top Article
MCS 2021: CAR Nutrition References
MCS Consensus Postscript Splash:
I. Ambient Combustion Aerosol (ACA) Composition
II. MCS, ME/CFS - Inflammatory Response to Air Pollution
III. Macronutrients - Starch Preferred Energy
III. Micronutrients - Vegetables Essential
IV. ACA PM Gastro-Inflammation, Vagal Circuitry
MCS Consensus II Postscript Splash: MCS, ME/CFS - Inflammatory Response to Air Pollution
HOGG 2009:
"...fine particulate contamination of the atmosphere in the vicinity of the South Pole is reduced to less than 1% of that observed in Japan, primarily as a result of the extremely low fossil fuel consumption in that region...there was a clear association between a reduction in airborne particulates and the circulating levels of segmented and band polymorphonuclear leukocytes (PMN) and monocytes in the circulation...The circulating PMN fell in association with the reduction in atmospheric particles that began during the voyage to the South Pole, persisted at low levels for the entire 12 months the expedition was in the vicinity of the South Pole and returned to normal on the return voyage to Japan (Sakai 2004)..."
"...The results in this study show that a low level of atmospheric PM is associated with a decrease in bone marrow stimulation, which results in decreased circulating segmented PMN, band formed PMN, and monocyte counts...IL-6 levels were parallel with band formed counts...
...It is considered that the atmospheric PM level is one of the important factors affecting circulating leukocyte counts and basal inflammatory status...
...Multiple regression test showed that PM levels had more significant effects on segmented PMN, band formed PMN, and monocyte counts than cigarette smoking and type of work...
...IL-6 stimulates multipotential cells, releases less mature PMNs (Suwa 2001, 2000, Patchen 1991), and accelerates monocyte differentiation (Jansen 1992, Bot 1989). The association between band-formed PMN, monocyte counts, and IL-6 levels is consistent with previous reports (Suwa 2001, 2000, Jansen 1992, Patchen 1991, Bot 1989)..."
A close look at Sakai 2004 shows that although elevation of total circulating leukocytes is relatively modest comparing exposure in Japan to Antarctica - a value of 6.31 in Japan day 1 and 5.23 day 271 in Antarctica - subset changes were more drastic - tissue damaging immature PMN (band cells) 2.37 to 1.18 - a very large proportional difference - monocytes were also nearly halved 3.04 to 1.46, and inflammatory cytokine IL-6 was half - 1.45 day 1 in Japan - 0.67 day 271 in Antarctica - and 1.25 day 576 on arrival in Japan.
MERCK 1999:
"...the phagocytic system, whose function is to ingest and digest...Phagocytes include neutrophils and monocytes (in the blood) and macrophages (in the tissues). Widely distributed, macrophages are strategically situated at the interfaces of tissues with blood or cavitary spaces; eg, alveolar macrophages (lungs), Kupffer cells (liver sinusoids), synovial cells (joint cavities), perivascular microglial cells (lining of CNS), mesangial phagocytes (kidneys)...
...Cytokines affect the magnitude of inflammatory or immune responses...
...Normal values for the total white blood cell (leukocyte) count range between 4,300 and 10,800/uL;
normal values for the differential WBC count are as follows: segmented neutrophils 34 to 75%; band neutrophils <8%; lymphocytes 12 to 50%; monocytes 3-15%; eosinophils <5%; and basophils <3%...
...Polymorphonuclear leukocytes (PMN) and neutrophils are terms used synonymously as are also immature granulocytes, immature polymorphonuclear leukocytes, band neutrophils, and band cells..."
HOGG 2009:
"...We have reported that IL-6 accelerates the transit time of granulocytes through the bone marrow, releases them into the circulation, and promotes their sequestration in microvascular beds (Suwa 2001, 2000)..."
GOTO 2004:
"...these premature granulocytes are less deformable and less chemotactic, preferentially sequestrate in the lung microvessels, and migrate less efficiently into inflammatory sites compared with more mature cells, indicating their greater potential to damage tissue..."
"...IL-6 stimulates the liver cells to produce acute phase proteins such as CRP, fibrinogen, and anti-proteases (Gabay 2007, Le 1987)...
...IL-1beta is one of the 'acute phase' cytokines that induces cytokine production by many cells, stimulates haematopoiesis, activates endothelial cells, induces the acute phase response and is pyrogenic (Le 1987)...
...Collectively, these mediators generated by the deposition of fine particles in the lung contribute to the systemic inflammatory response by increasing circulating leukocytes, platelets and pro-inflammatory and pro-thrombotic proteins...
...elevation in the levels of circulating leukocytes is an important predictor of both an excessive decline in lung function (Chan-Yeung 1988) and increased all cause mortality (Weiss 1995)..."
"...plasma levels of IL-1 beta, IL-2, IL-4, and IL-6 were found to be statistically significantly increased in MCS..."
MAES 2012:
"...Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease characterized by fatigue (CF) and 'somatic symptoms', including a flu-like malaise, fatigue, pain and muscle aches, cognitive impairment, autonomic symptoms, gastrointestinal symptoms, post-exertional malaise, etc...
...Inflammatory and oxidative and nitrosative stress (IO & NS) pathways play a key role in the pathophysiology of ME/CFS (Maes 2010). The findings encompass a low grade inflammation, as indicated by an increased production of nuclear factor kB (NFkB), and cyclooxygenase (COX-2), and inducible nitric oxide synthase (iNOS) (Maes 2007a, 2007b); immune activation with increased expression of activation markers, e.g. CD8+ and CD38+ and HLA-DR+ markers (Lorusso 2009); increased levels of cytokines including interleukin(IL) 1 alpha, IL-1beta, IL-4, IL-5, IL-6 and lowered IL-8, IL-13, and IL-15 levels (Fletcher 2009, Lorusso 2009)...
...all 5 immune variables were significantly increased in patients with ME/CFS, suggesting that ME/CFS is accompanied by a low grade, chronic inflammatory response (increased levels of IL-1 beta. TNF alpha, PMN-elastase, and lysozyme) and by persistent cell mediated immune (CMI) activation (increased serum neopterin)...
...PMN-elastase is a neutrophil [polymorphonuclear leukocyte]-derived protease...lysozyme (muramidase) is a gylcoside hydrolase with antibacterial properties that is found in monocytes, macrophages, neutrophils and glandular cells. It is a putative marker of monocyte/macrophage activity...neopterin, an indicant of cell mediated (CMI) activation...
...the correlations between increased IL-1, TNF alpha, neopterin, and PMN elastase, on the one hand, and specific FF symptoms, such as fatigue, autonomic and neurocognition symptoms, a flu-like malaise and sadness, on the other, suggest that inflammatory mediators may play a role in the characteristic symptoms of ME/CFS (Maes 2010, 2009)..."
Polymorphonuclear leukocytes (PMN) and neutrophils are terms used synonymously. Elevated markers in ME/CFS reported by Maes 2012: IL-1 beta, TNF alpha, PMN elastase, lysozyme, and neopterin - indicate PM Induced bone marrow stimulation and release of immune cells.
"...alveolar macrophages, epithelial and other cells interact with the particles to produce a wide variety of cytokines and chemokines that generate a local inflammatory immune response. These mediators spill over into the blood to stimulate the bone marrow to increase the release of leukocytes from the marrow, and the liver to increase the production of a variety of acute phase proteins. This systemic response is associated with vascular activation and the progression of the atherosclerotic process..."
MUKAE 2001:
"...We conclude that repeated exposure to PM-10 (particulate matter less than 10 microns in diameter) stimulates the bone marrow to increase the production of polymorphonuclear leukocytes (PMN) in the marrow and accelerate the release of more immature PMN into the circulation. The magnitude of these changes was related to the amount of particles phagocytosed by alveolar macrophages..."
CALDERON-GARCIDUENAS 2008:
"...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...
...ultrafine PM (UFPM), particulate-matter-associated lipopolysaccharides (PM-LPS) and metal uptake..through olfactory neurons, cranial nerves such as the trigeminal and vagus, the systemic circulation and macrophage-like cells loaded with PM from the lungs (Calderon-Garciduenas 2004, 2003a, 2003b, 2002, 2001)...
...The systemic inflammation is accompanied by the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1beta...for which brain blood vessels exhibit constitutive and induced expression of receptors...
...These cytokines can activate endothelial cells in the BBB, disrupt the BBB...upregulate COX-2...and trigger cascades leading to activation of mapkinases/NFkB (nuclear transduction of NFkB in endothelial brain cells of exposed subjects). A high level of activation of NFkB in astrocytes results in increased expression of nitric oxide production that opens the BBB...once the BBB is disrupted, significant leaking of RBC and protein such as prothrombin may follow...Concomitantly with the increment in CD 163, immunoreactivity for CD68 and HLA-DR in microglia, perivascular macrophages, and endothelial cells were observed, in keeping with the inflammatory response...
...brain oxidative stress starts in childhood and the teen years...in the scenario of air pollution exposure...progressive neurodegeneration that develops insidiously over the lifetime of the individual (McGeer 2006, Jellinger 2003, Nguyen 2002, Selkoe 2002, 2001)..."
Increased production of nuclear factor kB (NFkB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) reported in ME/CFS (Maes 2010, 2009, 2007a, 2007b) is consistent with UFPM, PM 2.5, and PM-LPS respiratory, lung epithelial and endothelial injury leading to persistent chronic inflammation in the respiratory tract and systemic inflammation producing the same markers - NFkB, COX-2, and iNOS. Calderon-Garciduenas 2008 also aligns with HOGG 2009 on the PM induced release of inflammatory mediators leading to systemic inflammation and immune activation.
Hiraiwa 2014, 2013, Hogg 2009, Goto 2004, and Mukae 2001 include S.F vanEeden - recipient of a career investigator award from the American Lung Association - Dept of Medicine, Univ of British Columbia Research Center, St Paul's Hospital, Vancouver, B.C. Calderon-Garciduenas is highly qualified - previously at the National Health and Environmental Effects Research Laboratory (NHEERL US EPA) - now Univ of Montana - who conducted biopsy and research work on this subject.
MCS Consensus I Postscript Splash: Ambient Combustion Aerosol (ACA) Composition
MCS Consensus II Postscript Splash: ME/CFS - MCS Cousin, ACA PM Lineage
MCS Consensus III Postscript Splash: Macronutrients - Starch Preferred Energy
MCS Consensus II Postscript Splash: ME/CFS - MCS Cousin, ACA PM Lineage
MERCK 1999:
"...Normal values for the total white blood cell (leukocyte) count range between 4,300 and 10,800/uL;
normal values for the differential WBC count are as follows: segmented neutrophils 34 to 75%; band neutrophils <8%; lymphocytes 12 to 50%; monocytes 3-15%; eosinophils <5%; and basophils <3%...
...Polymorphonuclear leukocytes (PMN) and neutrophils are terms used synonymously as are also immature granulocytes, immature polymorphonuclear leukocytes, band neutrophils, and band cells..."
CALDERON-GARCIDUENAS 2008:
"...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...
...ultrafine PM (UFPM), particulate-matter-associated lipopolysaccharides (PM-LPS) and metal uptake..through olfactory neurons, cranial nerves such as the trigeminal and vagus, the systemic circulation and macrophage-like cells loaded with PM from the lungs (Calderon-Garciduenas 2004, 2003a, 2003b, 2002, 2001)...
...The systemic inflammation is accompanied by the production of proinflammatory cytokines such as TNFalpha, IL-6, and IL-1beta...for which brain blood vessels exhibit constitutive and induced expression of receptors...
...These cytokines can activate endothelial cells in the BBB, disrupt the BBB...upregulate COX-2...and trigger cascades leading to activation of mapkinases/NFkB (nuclear transduction of NFkB in endothelial brain cells of exposed subjects). A high level of activation of NFkB in astrocytes results in increased expression of nitric oxide production that opens the BBB...once the BBB is disrupted, significant leaking of RBC and protein such as prothrombin may follow...Concomitantly with the increment in CD 163, immunoreactivity for CD68 and HLA-DR in microglia, perivascular macrophages, and endothelial cells were observed, in keeping with the inflammatory response..."
"...It is considered that the atmospheric PM level is one of the important factors affecting circulating leukocyte counts and basal inflammatory status...
Multiple regression test showed that PM levels had more significant effects on segmented PMN, band formed PMN, and monocyte counts than cigarette smoking and type of work..."
MAES 2012:
"...Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease characterized by fatigue (CF) and 'somatic symptoms', including a flu-like malaise, fatigue, pain and muscle aches, cognitive impairment, autonomic symptoms, gastrointestinal symptoms, post-exertional malaise, etc...
...Inflammatory and oxidative and nitrosative stress (IO & NS) pathways play a key role in the pathophysiology of ME/CFS (Maes 2010). The findings encompass a low grade inflammation, as indicated by an increased production of nuclear factor kB (NFkB), and cyclooxygenase (COX-2), and inducible nitric oxide synthase (iNOS) (Maes 2007a, 2007b); immune activation with increased expression of activation markers, e.g. CD8+ and CD38+ and HLA-DR+ markers (Lorusso 2009); increased levels of cytokines including interleukin(IL) 1 alpha, IL-1beta, IL-4, IL-5, IL-6 and lowered IL-8, IL-13, and IL-15 levels (Fletcher 2009, Lorusso 2009)...
...all 5 immune variables were significantly increased in patients with ME/CFS, suggesting that ME/CFS is accompanied by a low grade, chronic inflammatory response (increased levels of IL-1 beta. TNF alpha, PMN-elastase, and lysozyme) and by persistent cell mediated immune (CMI) activation (increased serum neopterin)..."
"...IL-1beta is one of the 'acute phase' cytokines that induces cytokine production by many cells, stimulates haematopoiesis, activates endothelial cells, induces the acute phase response and is pyrogenic (Le 1987)..."
"...PMN-elastase is a neutrophil [polymorphonuclear leukocyte]-derived protease...lysozyme (muramidase) is a gylcoside hydrolase with antibacterial properties that is found in monocytes, macrophages, neutrophils and glandular cells. It is a putative marker of monocyte/macrophage activity...neopterin, an indicant of cell mediated (CMI) activation...
...the correlations between increased IL-1, TNF alpha, neopterin, and PMN elastase, on the one hand, and specific FF symptoms, such as fatigue, autonomic and neurocognition symptoms, a flu-like malaise and sadness, on the other, suggest that inflammatory mediators may play a role in the characteristic symptoms of ME/CFS (Maes 2010, 2009)..."
Polymorphonuclear leukocytes (PMN) and neutrophils are terms used synonymously. Elevated markers in ME/CFS reported by Maes 2012: IL-1 beta, TNF alpha, PMN elastase, lysozyme, and neopterin - indicate PM Induced bone marrow stimulation and release of immune cells.
"...alveolar macrophages, epithelial and other cells interact with the particles to produce a wide variety of cytokines and chemokines that generate a local inflammatory immune response. These mediators spill over into the blood to stimulate the bone marrow to increase the release of leukocytes from the marrow, and the liver to increase the production of a variety of acute phase proteins. This systemic response is associated with vascular activation and the progression of the atherosclerotic process..."
MUKAE 2001:
"...We conclude that repeated exposure to PM-10 (particulate matter less than 10 microns in diameter) stimulates the bone marrow to increase the production of polymorphonuclear leukocytes (PMN) in the marrow and accelerate the release of more immature PMN into the circulation. The magnitude of these changes was related to the amount of particles phagocytosed by alveolar macrophages..."
Increased production of nuclear factor kB (NFkB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) reported in ME/CFS (Maes 2010, 2009, 2007a, 2007b) is consistent with UFPM, PM 2.5, and PM-LPS respiratory, lung epithelial and endothelial injury leading to persistent chronic inflammation in the respiratory tract and systemic inflammation producing the same markers - NFkB, COX-2, and iNOS.
Calderon-Garciduenas 2008 is in agreement with HOGG 2009 on the PM induced release of inflammatory mediators leading to systemic inflammation and immune activation.
Hiraiwa 2014, 2013, Hogg 2009, Goto 2004, and Mukae 2001 include S.F vanEeden - recipient of a career investigator award from the American Lung Association - Dept of Medicine, Univ of British Columbia Research Center, St Paul's Hospital, Vancouver, B.C. Calderon-Garciduenas is highly qualified - previously at the National Health and Environmental Effects Research Laboratory (NHEERL US EPA) - now Univ of Montana - who conducted biopsy and research work on this subject.
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