Airway Genetics and Ambient Combustion Aerosol

MCS 2ab Etiology: Nasal Cytokines in Context

Bascom 1992 observation that the airway can release cytokines - is not necessarily reflected as an increase of cytokines and chemokines in MCS nasal secretions - found the same in controls - at baseline - and after exposure to n-butanol (Dantoft 2015) - despite the altered systemic cytokine profile confirmed previously (Dantoft 2014).

Primary to MCS is usually genetic sensitivity (Veronesi 2001, 2000, Roy 2000, Jung 1921) together with cumulative exposure including ambient combustion aerosol (ACA) particulate matter (PM) resulting in altered structure and function of the neuro-inflammatory system (Bascom 1997) - exposed and multiplied nerves confirmed in the nasal epithelium (Meggs 1997), nerve growth factor (NGF) elevated in MCS nasal secretions (Millqvist 2005), greater cough upon exposure to capsaicin (Nogami 2004) - NGF, vasoactive intestinal peptide (VIP), and substance P (SP) increased systemically both at baseline and after exposure to paint (Kimata 2004) - and the initiating role of TRPA1 and TRPV1 receptors on peptidergic airway nerve terminals has been elucidated by many well qualified and credible contributors as outlined in MCS 2a Etiology: TRPA1 Precision (Deering-Rice 2011, Hazari 2011, Costa 2010, Taylor-Clark 2010, Caceres 2009, Latremoliere 2009, Anand 2008, Bessac 2008, Nassenstein 2008, Bautista 2006, Inoue 2005, Kobayashi 2005, Veronesi 2001). Symptoms of MCS are often of a flu like pattern (Dantoft 2014, Bascom 1992) with increased nasal congestion (Doty 1994), hyperalgesia (Tran 2013, Holst 2011, Latremoliere 2009), neurocognitive impairment - and lightheaded aspects of cerebral hypoperfusion (Belpomme 2015, Orriols 2009).

Systemic elevation of cytokines involves alveolar macrophages, epithelial, sensory nerve, and other cells - and is relative to inflammatory exudation of fluid and cells into both large and small bronchi, bronchioles, and gas exchanging tissue (Hogg 2009, Veronesi 2001).

For example, inflammatory cytokine IL-6, rising in proportion to the amount of ACA PM reaching alveolar macrophages (Hiraiwa 2014, 2013, Hogg 2009, Goto 2004, Mukae 2001) - is nearly double among residents of Japan compared to living on the South Pole - due largely to ACA PM (Sakai 2004) - which also supports MCS disease process because many ACA components activate TRPA1 receptors (Deering-Rice 2011, Hazari 2011, Costa 2010, Taylor-Clark 2010, Caceres 2009, Anand 2008, Bessac 2008, Nassenstein 2008, Bautista 2006, Inoue 2005, Kobayashi 2005, Veronesi 2001). There is no proven safe level of chronic and repeated exposure to ACA PM - consequences include an insidious neuro-degeneration throughout the lifetime (Calderon-Garciduenas 2008, McGeer 2006 , Jellinger 2003 , Nguyen 2002 , Selkoe 2002 , 2001 ).

At baseline - without study provocation - MCS often includes neurocognitive impairment, SPECT hypoactivity (Orriols 2009), electroencephalographic alterations (Bell 1998, 1996), central sensitization - a functional synaptic plasticity resulting in pain hypersensitivity (Tran 2013, Holst 2011, Latremoliere 2009) - Orriols 2009 suggested that permanent neuronal damage and reduced inhibitory neuronal activity in the olfactory pathways to the orbito-frontal cortex and the limbic system may be due to penetration of UFPM, and Belpomme 2015 - in measurement of reduced brain blood flow in the temporal lobes reported cerebral capsulothalamic hypoperfusion - a potentially lightheaded hypoxia in approx 50% of MCS cases - further confirming involvement of the limbic system and thalamus in the inflammatory process - and two markers of blood brain barrier disruption (protein S100B and nitrotyrosin) elevated in 15 and 28%.

The major components of PM 2.5 and UFPM - ultrafine particulate matter less than 0.1 micron median aerodynamic diameter (Hiraiwa 2013) - an ambient exposure of 24/7/365 proportions - include transition metals, sulfate and nitrate ions, organics, minerals, adsorbed gases, and biocontaminants (endotoxins, mold, pollen) attached to a core of carbonaceous material (Gillespie 2013) acting as a vector (Bonvallot 2001, 2000, Boland 2000, 1999, Baeza-Squiban 1999, Bayram 1998, Kumagai 1997, Thomas 1997) with prolonged tissue residence time (Gerde 2001, 1997, 1991 , Burtscher 1986 , Adamson 1982 , Natusch 1978) - most from vehicle exhaust, wood burning, and coal burning (Bernstein 2004) - and to a lesser but significant extent from oil refineries, metal processing facilities, smelters, and wildfires (Block 2009, Muhlfeld 2008, Rothen-Rutishauser 2008, Valavanidis 2008).

The Sakai 2004 study comparing exposure in Japan to the South Pole - average of all on the expedition - measured tissue damaging immature PMN (band cells) 2.37 to 1.18 - monocytes were also nearly halved 3.04 to 1.46, and inflammatory cytokine IL-6 1.45 to 0.67 day 271 in Antarctica, IL-6 back up to 1.25 day 576 on return to Japan.

Multiple regression test showed that ACA PM had more effect on segmented PMN, band PMN, and monocyte counts than cigarette smoking and type of work - demonstrated in results of the separately accomodated smokers and those with toxic occupational exposure on the voyage (Sakai 2004).

Consistent with studies (Hiraiwa 2014, 2013, Sakai 2004, Goto 2004, Mukae 2001) - Hogg 2009 concluded: "...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..."

Baldwin 1998 found increased cardiopulmonary disease risk in a community based sample having odor intolerance.

With respect to the role ACA PM has in supporting disease conditions such as MCS and the physiological consequences of increased systemic inflammation and CNS neurodegenerative process - it is not realistic to dismiss MCS as a psychological syndrome or disease of unknown etiology. In this context - psychological inquiry not requested by the patient is inappropriate because it has no utility in the diagnosis, treatment, or cure of the disease.

Links

Lost from website: google MCS Etiology

MCS 1a 2019 MCS Consensus Criteria

MCS 2 The Etiology of MCS

MCS 2a Etiology: TRPA1 Precision

MCS 2a Etiology: Notes on References

MCS 2ab Etiology: Nasal Cytokines in Context

MCS 2 The Etiology of MCS

MCS 3 Definition and Consensus Criteria

MCS 3a Etiology: Criteria Amendment Research (CAR)

MCS 3a AKA Multiple Chemical Sensitivity: 2019 Consensus Criteria

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