Airway Genetics and Ambient Combustion Aerosol

SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop

SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop

If lost: google MCS Etiology

Links: 35 CAR Test SPC Questions
CAR Warm Up
SPC 1 Introduction: South Pole CAR (SPC) - A Character Test
SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop
SPC 3 ACA PM and ME/CFS: Do We Hear An Echo?
SPC 4 ACA UFPM: In the RBC - Through the BBB
SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS
SPC 6 ACA UFPM: Nerve Penetration
SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS
SPC 8 ACA PM: Gastro-Inflammation, Immunity, Vagal Circuitry
SPC 9 Veronesi: Sensory Nerve Insight
SPC 10 Kimata: Histamine Warning - Return to Masking
SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

On CAR
SPC 12 Disease Conditions Begin: Airway Epithelial Injury
SPC 13 Exposed Sensory Nerves - TRPA1
SPC 14 Exposed TRPA1: Central Sensitization
SPC 15 ACA: Loud and Clear
SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation
SPC 17 Calderon-Garciduenas: Airway to Systemic: Putting It Together
SPC 18 Airway Gaps - Exposed Nerves - UFPM to the CNS
SPC 19 ACA PM: Months and Years Residence Time
SPC 20 Airway Gaps: Reduced Detox Enzyme Intervention
SPC 21 Solvents and Pesticides Primary: Shoe Fits Glove?
SPC 22 Veronesi and Roy: Genetic Difference in Airway Sensitivity

SPC 23 Jung Was Right Sort Of

SPC 24 Veronesi and Jung: A Perfect Match
SPC 25 Tailpipe and Chimney Emissions: Horizontal Coning
SPC 26 How Far Symptoms Travel: 25 Years, 500 Locations, 22 States
SPC 27 Not Into That Kind of Entertaining
SPC 28 Does it Cost More Than Money?
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
SPC 30 Airway to systemic: Dysfunction of Detox Enzymes - Khatsenko
SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?
SPC 32 Phase I and II Detox Enzymes Defined

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Consensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

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

MCS 3b CAR References

SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop

Please choose the Incorrect Statement

SPC 2a)

HIRAIWA 2013:
"...Of all the pollutants, inhalable particles (PM-10) showed the strongest association with adverse respiratory health effects (Schwartz 1995)...data from large population cohorts have indicated an association between exposure to PM and cardiovascular morbidity and mortality (Brook 2010, Eftim 2008, Miller 2007, Pope 2004)...due to the systemic inflammatory response induced by exposure to PM air pollution (Hogg 2009)..."

SPC 2b)

GILLESPIE 2013:
"...The major components of PM include transition metals, sulfate and nitrate ions, organics, minerals, adsorbed gases, and biocontaminants (e.g., endotoxins, mold, pollen), attached to a core of carbonaceous material. The size of the particulates found in PM has been inversely related to its inflammatory damage (Pedata 2010, Valavanidis 2008, deHaar 2006, Oberdorster 1996) with smaller, ultra fine size particles being more toxic to the target tissue..."

SPC 2c)

HIRAIWA 2013:
"...PM-2.5 and UFPM (ultra fine particulate matter less than 0.1 micron median aerodynamic diameter) are primarily derived from direct emissions from combustion processes such as vehicle use of fossil fuel products, wood burning, and coal burning (Bernstein 2004)...several studies have shown that PM 2.5 and UFPM have the strongest association with adverse cardiovascular effects (Franck 2011, Stolzel 2007 ), which is a direct consequence of the systemic response induced by these particles (Nemmar 2002, Nemmar 2001)..."

SPC 2d)

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%...
...Neutropenia...A reduction in the blood neutrophil (granulocyte count)...Neutropenia may be classified by the neutrophil count (total WBC X % neutrophils and bands [immature granulocytes])..."

Polymorphonuclear leukocytes (PMN) and neutrophils are terms used synonymously as are also immature granulocytes, immature polymorphonuclear leukocytes, band neutrophils, and band cells.

SPC 2e)

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)...
...Muchmore 1970 during an American expedition to the South Pole...was the first to show that travel to this region of the earth was associated with a neutropenia that recovered quickly on return to their base camp in New Zealand...measurement of PMN band forms indicated that the low leukocyte levels were due to a reduced production and release of these cells from the marrow..."

SPC 2f)

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..."

SPC 2g)

HOGG 2009:

"...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)...
...In the majority of persons...inhalational injury causes a low-grade inflammatory exudation of fluid and cells into both large and small bronchi, bronchioles, and gas exchanging tissue...In addition, there is a mild systemic response characterized by an elevation in circulating leukocyte counts. However, in the susceptible minority of persons, this inflammatory response is amplified..."

It is a serious error to consider the majority systemic response mild - a presumptive tendency considering the subclinical nature. 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.

Considering those inflammatory indices are nearly double in Japan compared to the clean air of Antarctica - it is more appropriate to respect the majority response as a significant public health concern - while minority amplification makes the ACA (ambient combustion aerosol) a disaster.

CALDERON-GARCIDUENAS 2001:

"...Chronic exposures to air pollutants pose significant public health concerns for healthy individuals as well as those at higher risk, such as asthmatics and patients with compromised cardiorespiratory function. A compromised nasal epithelium has a diminished ability to protect itself and the lower respiratory tract..."

SPC 2h)
In the clearest language - hard to get words around something this bad - what the researchers have alluded to above - the most credible academic and government studies - paid to investigate and report truth - not industry propaganda. But then its a political issue - if you want to buy they will sell - UFPM free pass the nasal and upper airway to the alveolar macrophages, RBC (red blood cells), BBB (blood-brain barrier) - and directly via neural pathways to the CNS - past upper airway irritation and warning - penetrating to the core. There is nothing benevolent about happy motoring - not moral conscience - but to sell cars and trucks. While you're not paying attention - every breath 24/7/365 - environmental illness going through the roof - from autism to MCS, AD and PD - there is nothing really high tech about a pollution control strategy of blowing UFPM past the public - catalytic converters and filters not sufficient - like 80 mph and air bags - how low does it go to keep using these vehicles. Where is it written that the maker creates such a poor human constitution - that can't live to old age wise, clear headed, and fully functional without widespread illness and medical bills but to breathe diesel and company 24/7/365. It is willingness to not exercise conscience but to drive the very life off the earth we have worked so hard to live on.

SPC 2i)

HOGG 2009:
"...The tennis court-sized epithelial surface lining of the human lung bears the brunt of exposure to inhaled particles...
...local conditions within the lung...determine the diffusion of toxic gases and deposition of particles. The innate inflammatory immune system (Abbas 2007) provides the primary protection...
...The protective features of the innate system include the tight junctions that join epithelial cells and keep foreign material on the surface, an efficient mucociliary clearance apparatus that rapidly clears foreign material out of the lower respiratory tract, macrophages that take up foreign material deposited on the bronchial and alveolar surface, and a very thin alveolar surface liquid layer that carries macrophages and associated foreign debris from the alveolar surface to the mucociliary clearance apparatus in the conducting airways..."

SPC 2j)
CALDERON-GARCIDUENAS 2001:
"...Control biopsy (non-smoking Veracruz children). Unremarkable respiratory nasal epithelium is seen; pseudostratified columnar epithelium is comprised of basal, ciliated, and mucous cells. The integrity of the tissue is maintained..."

Although non-smoking children of less polluted Veracruz and Tlaxcala fared better - four of the five Calderon-Garciduenas 2008 subjects aged 27 and above from those control cities - 27, 36, 40, and 45 - demonstrated dysruption of the BBB (blood-brain barrier) by confocal microscopy for tight junction abnormalities (Zonula Occlulens ZO-1) or Abeta42 (42 amino acid-isoform of beta amyloid) immunoreactivity by immunohistochemistry in olfactory bulb and cortical neurons of one subject - and in diffuse and mature senile plaques in another - a preAlzheimer's-like indicator of brain neuroinflammation.

CALDERON-GARCIDUENAS 2008:

"...Both Abeta42 (42 amino acid-isoform of beta amyloid associated with Alzheimer's) and alpha synuclein ( an abundant brain 140-residue-protein linked to Parkinson's disease) are proteins capable of aggregation and misfolding (shown to occur more rapidly in conditions of PM exposure), leading to progressive neurodegeneration that develops insidiously over the lifetime of the individual (McGeer 2006, Jellinger 2003, Nguyen 2002, Selkoe 2002, 2001)..."

SPC 2k)

Little more than 30 years ago many people - including those of the medical profession - were taken in by smoking - which was permitted in hospitals - at least in designated areas. As awareness increased - persons in a business office might put an air filter machine on the desk as if to protect from the smoking of those among them. The next step was the belief that allowing a smoking section or room would be an adequate solution. It took a long time to respect there is no safe level of second hand smoke.
The same principle applies to tailpipe and chimney emissions. There is something in the collective attitude that attaches benevolence to these emissions. Mexico City is heavily polluted - control city Veracruz not so much - but accepting Veracruz as okay is unawareness like having a designated smoking section in a hospital, business, or restaurant.

The obvious truth is as follows: if the only person on earth, but situated in all 4 directions is an idling car - continuous exposure of horizontal coning 24/7/365 - there is going to be a health cost - just a question of how soon and to what extent depending on the genetic constitution of the individual - and yet even in the smallest cities and towns we are condemned to an exposure level multiple times greater with use of these high speed combustion fueled vehicles.

Plus and minus of the 110 year combustion vehicle history could be counted - but at this point their usage is a disaster happening - local and global - the know-how and where-with-all they may have facilitated needs to be directed now at discontinuing their usage. In other words, high speed combustion vehicles have outlived their usefulness. There is plenty of knowledge and technology - but a shortage of moral intelligence.

The growth and profit model won't correct the situation - making no more sense than American consumer goods hauled from manufacture in China, proposed increase of coal and oil from the US and Canadian interior to seaport and delivery for burning in China, and the continued use of combustion fueled vehicles - not great exhibitions of moral intelligence or good judgement. If there is any hope - it appears only possible from the efforts of a grass roots movement.

SPC 2L

CALDERON-GARCIDUENAS 2001:
"...Every child in the Southwest Metropolitan Mexico City (SWMMC) group displayed an abnormal nasal biopsy. Major findings included lack of cohesion between cells, epithelial shedding, necrotic cells, PMN (polymorphonuclear leukocyte) epithelial infiltration, and short or absent cilia...
...A multinucleated PMN is seen infiltrating the nasal epithelium. Notice the wide intercellular spaces occupied by electron-dense granular material reflecting potential deficiencies in epithelial junction integrity...PMN epithelial infiltration was seen in every SWMMC biopsy...
...An unexpected finding was the presence of PM (particulate matter) in 5 of 15 SWMMC children...PM was localized in the widely abnormal intercellular spaces, in the cytoplasm of adjacent epithelial cells, and surrounding the abnormal cilia...deposition of dark osmiophilic granular material could be seen at the epithelial borders and inside large lysosomal bodies in neighboring epithelial cells...
...the electron microscopic findings observed in the nasal epithelium of children growing up in a polluted environment are likely a reflection of sustained airway epithelial injury...Because the children had no exposure to tobacco and had negative histories of upper and/or lower respiratory diseases (either acute or chronic), the findings described here may be attributed in large part to the chronic and sequential exposure to air pollutants...
...PM clearance from the nose depends largely on intact mucociliary mechanisms, and whereas deposition of particles larger than 3 microns (um) takes place in the anterior part of the nose (devoid of ciliated epithelium), particles beween 0.5 and 3 um are filtered by an intact respiratory nasal mucosa and transported by ciliary propulsion to the nasopharynx (Fry 1973)...
...Diesel exhaust particles undergo endocytosis in primary cultures of human nasal epithelial cells, resulting in time- and dose-dependent membrane damage. This is followed by an inflammatory response whose extent seems to depend on the content of organic compounds adsorbed to the particles (Boland 2000)...
...The observation of intercellular deposition of PM and its presence in heterolysosomes in adjacent cells suggest that clearance of particulates may also be compromised in these children...
...Chronic exposures to air pollutants pose significant public health concerns for healthy individuals as well as those at higher risk, such as asthmatics and patients with compromised cardiorespiratory function. A compromised nasal epithelium has a diminished ability to protect itself and the lower respiratory tract..."

MEGGS 1997:

Biopsy of MCS subjects

"...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..."

CALDERON-GARCIDUENAS 2001:

"...presence of an intraepithelial inflammatory infiltrate supports the view that the nasal epithelium is likely responding to the injury with the production of inflammatory cytokines such as interleukin(IL)-6 and IL-8, which are enhancing the migration of both PMN and mononuclear cells (Adler 1994, Kenney 1994)..."

SPC 2m)
HOGG 2009:
"... IL-8 is a critically important chemoattractant and activator, and facilitates the recruitment of both PMN and monocytes into the airspaces (Lukacs 2004)..."

DANTOFT 2014:

"...IL-12p70 and IL-8/CXCL8 are often increased together with IL-1 beta, IL-6, and TNF alpha as mediators of the acute phase response to an infection. However, in contrast to IL-1 beta, IL-6, and TNF alpha which mediate both local and systemic effects, the effector functions of IL-8/CXCL8 and IL-12p70 are more isolated to specific tissue areas affected by inflammation (Parham 2009). Increased levels of IL-8/CXCL8 are therefore less likely to be measured in blood..."

SPC 2n)
SAKAI 2004:

"...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)..."

SPC 2o)

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..."

HOGG 2009:

"...IL-6 stimulates the liver cells to produce acute phase proteins such as CRP, fibrinogen, and anti-proteases (Gabay 2007, Le 1987)..."

HIRAIWA 2014:
"...fibrinogen increases blood coagulability, which is a major risk factor for acute cardiovascular events in susceptible individuals (Heinrichy 1995)...CRP is strongly associated with inflammation in general but, in epidemiological studies, has also been correlated with the extent of atherosclerosis and heart disease (Torres 2003, Haverkate 1997). C-reactive protein has become hallmark biomarker indicative of the extent and severity of cardiovascular disease (Ridker 1998, 1997, Tracy 1997)..."

HOGG 2009:

"...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)..."

DANTOFT 2014:

"...plasma levels of IL-1 beta, IL-2, IL-4, and IL-6 were found to be statistically significantly increased in MCS..."

HOGG 2009:

"...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..."

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..."

HOGG 2009:

"...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..."

SPC 2p)
The observation that inflammatory intrigue turns off on a voyage to the South Pole as indicated by reduced leukocytes from the bone marrow and neutropenia (Sakai 2004, Muchmore 1970) should tell you something right there - but experience shows its hard to get through the rum dumb - so CAR Test continues. Hogg 2009 found ACA PM induces cytokine release from alveolar macrophages and epithelial cells producing a systemic inflammatory response designed to increase the output of acute-phase proteins and circulating inflammatory cells from the liver and bone marrow.

SPC 2q)
Amplification of the inflammatory response usually is initiated by changes induced in the innate inflammatory immune system - including the tight junctions that join epithelial cells and keep foreign materials on the surface. Recall that MCS people have tight junction defects - gaps and focal desquamation, proliferation of sensory nerve fibers, and lymphocytic infiltrates (Meggs 1997).

SPC 2r)

IL-1beta, IL-6, and IL-8 are credited as principle mediators of the systemic inflammatory response including atherogenic implications (Hiraiwa 2014, 2013, Hogg 2009, Goto 2004, Mukae 2001) - IL-1beta and IL-6 reported elevated in MCS and ME/CFS, IL-8 expected elevated but increase not usually detectable in blood (Dantoft 2014, Maes 2012).

SPC 2s)
Hogg 2009 did not reveal the Veronesi 2001 critical insight - significance of exposed sensory nerves in releasing 10-200 times more inflammatory cytokine IL-6 than intact epithelial cells - such as in the damaged airway epithelium described by Meggs 1997. Exposed sensory nerves and their TRPA1 expressing peptidergic terminals are key ingredient in amplified, enhanced, and prolonged inflammatory response (Bessac 2008).

VERONESI 2001:

"...In all instances, sensory neurons release 10-200 fold higher levels of IL-6 (pro-inflammatory cytokine) relative to epithelial cells... Found elevated in MCS patients (Dantoft 2014)...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...

...BALB/c mice were deenervated of polymodal sensory c fibers by neonatal capsaicin treatment. Sensory neurons , dissected from the DGR (dorsal root ganglia) of these deenervated animals and exposed to various PM (50mg/ml) or prototype irritants failed to release IL-6 in response - implicating the sensory c fibers as critical to cytokine release in response to PM..."

SPC 2t)
Thousands of studies and billions research money later we have done little but further our careers because we prefer the benefits of ACA PM - sedentary to a 30% prediabetic condition (Kavanagh 2013, Guerrerio 2012) - burning fuels fast as possible - destroying health and ending life on earth. We support billions of people suffering continuous exposure - horizontal coning of largely invisible emissions - one vehicle enough for several miles downwind intoxication.
We propose the value of our work is insight for pharmaceutical intervention and ineffective pollution control devices - unable to eliminate UFPM and gas phase emissions. We are content not among the susceptible minority - never mind that anyone can develop airway defects, resulting increased systemic inflammation, and disabling illness - reaching a critical mass of exposure and genetics.