MCS 9 Airway Origin: PM and a Defective Scrubber

[michael edward badolato jr]

MCS - in most cases - originates from the airway epithelium and its sensory innervation - which has become defective due to genetic disposition and environmental exposure.

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 Studying children in Southwest Metropolitan Mexico City (SWMMC) they found:

"...a persistent ongoing airway inflammatory process the result of exposure to air pollutants in a sequential and chronic manner..." The authors point out that "...the imbalance and dysregulation of cytokines and their ample systemic effects..." found in SWMMC children could also apply to populations in less polluted areas - especially those with previous respiratory disease.

In consideration of the airway tight junction defects and focal desquamation found in MCS patients (Meggs 1997) - one might appreciate the following from CALDERON-GARCIDUENAS 2000 as applying to MCS:

"...have an altered nasal mucociliary apparatus (including ciliary dysfunction) (Calderon-Garciduenas 1997) suggesting that less ozone and other gaseous pollutants may be removed from their noses, leaving the more distal pulmonary airways vulnerable to increased concentrations of these pollutants...(Calderon-Garciduenas L. 1996) Less uptake of reactive gases, such as formaldehyde and ozone, occurs in an epithelium devoid of intact mucociliary defense mechanisms or in squamous epithelium; hence,these gases can penetrate deeper into the respiratory tracts of individuals with the types of nasal lesions that have been observed (Loden M. 1986, CIIT document 1999)..."

"...Under normal healthy conditions, a nose with an intact mucociliary apparatus acts as an extremely effective filter of inhaled gases and particles (Eccles 1995). For example, 30-40% of inhaled ozone gets scrubbed at this level (Gerrity 1988)..."

"...Another crucial factor is the thickness of the layer that lines the respiratory tract (Miller 1993). Pryor 1992 predicted that ozone can penetrate only an extremely thin liquid lining layer to attack underlying cells...Thus, Miller 1985 predicted sharp increases in the dose of ozone to the first respiratory bronchioles (generation 16) in humans as a result of a large reduction in the thickness of the liquid lining..."

"...particle laden AMs (alveolar macrophages) produce reactive oxygen species and inflammatory mediators...PM10 (particulate matter less than 10 microns) has free radical activity and causes lung inflammation and epithelial injury (Li 1996)...Cytokines are involved in generating the inflammatory response that contributes to injury at the lung epithelial and endothelial barriers (Shanley 1995, Kotecha 1996, Vaillant 1996, Finkelstein 1997, Martin 1997, Mills 1999)..."

"...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)..."

A defective airway releases excessive inflammatory substances, and allows more pollutants to the general circulation - having to be dealt with by the detox enzyme chemical defense systems which are concerned with both xenobiotics and endogenous products. It can easily be imagined they would be more inducted, overwhelmed, suppressed, or inhibited (a conclusion reached by Deluca 2010).

The search for a genetic explanation in detox enzyme chemical defense found no association that could be applied to the majority of MCS cases (Deluca 2011, 2010, Berg 2010). One would not expect such a finding necessary - considering the factor specific to MCS is genetic propensity of the c-fiber nerves - their peptidenergic transmission - greater inflammatory release - furthering local tissue damage and setting forth the systemic reaction of oxidative stress.

The "...sequential and chronic manner..." - every breath but varying in concentration - hugely cumulative - the ambient aerosol - usually the driving force in the development and exascerbation of MCS.

Concerning particulate matter with adsorbed hydrocarbons - from BAULIG A. ET AL. ROLE OF PARIS PM2.5 COMPONENTS IN THE PRO-INFLAMMATORY RESPONSE INDUCED IN AIRWAY EPITHELIAL CELLS. TOX 261: 126-35 2009:

"...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)..."

The study by Gerde 2001 is objectionable concerning subjects and methods - as are combustion fuels.

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:

During combustion particles are generated and PAHs (polycyclic aromatic hydrocarbons) form in the gas phase. When the exhaust cools - PAHs adsorb or condense on the particles (Burtscher 1998).

There are two principal fractions of adsorbed PAHs: one is quickly desorbed - and the other retained on particles for a long time (Gerde 1991, Burtscher 1986, Adamson 1982, Natusch 1978).

Approx 80% of rapidly desorbed PAHS are deposited on the thin alveolar type 1 epithelium deep in the lung (Yeh 1996) and become systemic quickly with blood concentration peaking in several minutes.

3/4 of blood activity from the rapidly absorbed B[a]P (benzo[a]pyrene) used in Gerde 2001 ceased in 10 minutes - nearly all within 30 - and by one hour completely leveled - mostly into conjugated phase ll metabolites (Fung 1999, Thompson 1989, Molliere 1987).

In contrast, the remaining 20%of rapidly desorbed PAHs "...are deposited, slowly absorbed, and extensively metabolized in airway epithelium at prolonged elevation of the local tissue concentration (Gerde 1997)..."

Over 5 months later particles in the lung and lymph nodes had only 37 and 59% of B[a]P desorbed - mostly during the initial rapid release - with the exception of more desorption from particles translocated to the lymph nodes - possibly due to environment within macrophages (Nyberg 1989, Harmsen 1985, Lundborg 1984).

In combination with a genetic predisposition of the airway epithelium and its sensory innervation (Eberling 2009, Veronesi 2001, 2000, Roy 2000, Miyabara 1998, Jung 1921) - MCS is usually caused by exposure to a continuous combustion byproduct aerosol - diesel and other exhaust, woodsmoke, and tobacco smoke - including particle agglomerates with adsorbed hydrocarbons and singlet nonagglomerated nanoparticles.

 

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