Environmental Stressors and the PINE Network: Comparison
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Please note this is a comparison between Version 2 by Jason Zhu and Version 1 by Grace Branjerdporn.

Both psychosocial and physical environmental stressors have been linked to chronic mental health and chronic medical conditions. The psycho-immune-neuroendocrine (PINE) network details metabolomic pathways which are responsive to varied stressors and link chronic medical conditions with mental disorders, such as major depressive disorder via a network of pathophysiological pathways. Biological links have been established between particulate matter (PM) exposure, key sub-networks of the PINE model and mental health sequelae, suggesting that in theory, long-term mental health impacts of PM exposure may exist, driven by the disruption of these biological networks. This disruption could trans-generationally influence health; however, long-term studies and information on chronic outcomes following acute exposure event are still lacking, limiting what is currently known beyond the acute exposure and all-cause mortality. More empirical evidence is needed, especially to link long-term mental health sequelae to PM exposure, arising from PINE pathophysiology. 

  • psycho-immune-neuroendocrine network
  • chronic illness risk network
  • biological networks

1. Introduction

In 1977, Engel proposed the biopsychosocial model to describe a holistic framework for the determinants of disease. Engel proposed that “… a medical model must also take into account the patient, the social context in which he lives, and the complementary system devised by society to deal with the disruptive effects of illness…” [1]. The biopsychosocial model considers biological, psychological, as well as social and environmental factors as determinants for disease [2]. This model was embraced as a framework for understanding mental illness in particular; however, it may also act as a useful framework for understanding many chronic non-communicable diseases (NCDs). This framework is possibly also an early attempt at understanding disease within a systems context.
Since the introduction of the psycho-immune-neuroendocrine (PINE) network model [3], it was asserted that stress (an environmental factor) acted as a potent driver for the emergence of pathophysiology which can lead to one or multiple mental health and medical conditions [4,5][4][5]. These multiple (and sometimes multimorbid) conditions were described in terms of a chronic illness risk network (CIRN) [5], with non-communicable diseases (NCDs) including atherosclerosis and coronary heart disease (CHD), type 2 diabetes mellitus (T2DM), cerebrovascular accident (CVA) and vascular cognitive impairment (VCI), together with mental disorders such as major depressive disorder (MDD).

2. The PINE Network and Non-Communicable Diseases: PM as a Chronic Stressor

Since the identification of general adaptation syndrome by Selye in 1936 [12][6], describing the impact of chronic stress on physiological systems, and the later establishment of allostatic theory by McEwen and colleagues [13[7][8][9],14,15], there has been a recognition that chronic stress influences multiple interlinked systems, producing pathophysiological changes that lead to chronic disease. Viewing these interlinked pathways as a network using a systems biology approach, the PINE model provides insights as to how behaviour of the entire network can explain transition from health to MDD and other NCDs [3]. This woentrky was expanded to illustrate dynamic behaviour of the PINE network with chronic stress, including feedback loop transitions and a critical transition to disease [4,5][4][5]. The concept of a CIRN then proposed that the increased reciprocal risk between several major NCDs may reflect shared causative pathways within the PINE network; notably immune, autonomic and endocrine dysregulation [5]. Chronic stress acts on the autonomic nervous system (ANS) and HPA axis [16[10][11],17], resulting in sympathovagal imbalance, parasympathetic withdrawal [18,19][12][13] and sympathetic overdrive [19][13]. The long-term stimulation of the HPA axis results in cortisol resistance [16,19,20,21,22][10][13][14][15][16]. The negative regulatory feedback loops in the ANS and HPA axis that normally maintain homeostasis are therefore disrupted by chronic stress. Both vagal withdrawal and glucocorticoid resistance may ultimately push some negative feedback loops through a transition to positive feedback, driving a system-wide transition to disease [4]. Via neural and endocrine modulation of acute inflammation [23,24[17][18][19],25], immune function is intimately linked to this chronic stress response, increasing circulating inflammatory markers [3,4][3][4]. This systemic pro-inflammatory state promotes neuroinflammation, microglial proliferation and astrocyte loss [26,27[20][21][22],28], kynurenine pathway (KP) activation, tryptophan depletion and reduced CNS serotonin production [29][23]. Overactivity of the KP increases neurotoxic metabolites, inhibiting neurotrophic signalling and neuronal maintenance to further suppress astrocyte numbers [29,30,31][23][24][25]. Metabolite effects on hippocampal neurogenesis [32,33][26][27] in turn may influence learning [34][28] and memory [35][29]. These different CNS changes have all been linked to MDD: inflammation is strongly linked to MDD [36][30] and inflammatory mediators such as IL-1 drive sickness behaviours [37,38,39][31][32][33] that are identical to the neurovegetative symptoms and anhedonia of MDD [3,5,40][3][5][34]; reduced CNS serotonin and brain-derived neurotrophic factor (BDNF) are both linked to MDD [41][35], and shifts in neurogenesis and BDNF signalling may mediate cognitive changes in MDD [5,42][5][36]. Other systems constitute elements of the PINE network, notably the gut and gut microbiome. Dietary factors and inflammation affect gut motility [43][37] and permeability [44][38], facilitating the entry of bacteria and associated lipopolysaccharides (LPSs), inducing systemic pro-inflammatory cytokine release in a positive feedback loop [38,45,46][32][39][40]. Recent evidence indicates PM exposure also induces gut dysbiosis in animals and humans, promoting inflammation and metabolic disease [47,48,49][41][42][43]. The pro-inflammatory state arising with chronic stress increases leptin and reduces ghrelin secretion [50][44], leading to hypothalamic leptin resistance [51,52][45][46]. This central leptin resistance further increases circulating leptin levels, which in a positive feedback manner further enhances inflammatory cytokine release [53,54,55,56,57][47][48][49][50][51]. Through this array of changes, spanning multiple biological processes and pathways, long-term stress may give rise to a variety of chronic disorders [5]. WResearchers assert that PM may serve as an environmental trigger of PINE network disruption and then downstream, stress-related disease processes.

3. Air Pollution Induces a Stress Response and Disrupts the PINE Network

3.1. Pro-Inflammatory Response

Inhaled PM triggers pulmonary protein leakage and inflammation in a size-, dose- and solubility-dependent manner [58,59][52][53]. The persistence of inhaled particulates may prolong these effects. Exposure to PM influences multiple organ systems indirectly via the production of inflammatory factors and triggering of nervous reflexes, and directly via access to the circulation where they disrupt cellular, tissue and organ function to modulate autonomic nervous system (ANS) activity [60,61,62,63][54][55][56][57]. The impact of PM on pro-inflammatory responses are associated with the size of the particles. Due to their size, PM10 are restricted to the pulmonary system, where they locally increase reactive oxygen species (ROS) and inflammatory cytokines [64][58]. PM2.5 are associated with elevated inflammation and oxidative stress, together with changes to ANS activity [10][59]. Exposure to PM2.5 elevates inflammatory markers including CRP, TNF-α, PGE2 and Il-1α together with ET-1 [65,66][60][61]. PM0.1 are also heavily implicated in airway diseases, but have also been shown to be associated with inflammation in the cardiovascular and central nervous system [11][62] (Nelin et al., 2012). Chronic inflammation is linked to proximity to roadways, where there are increased PM levels [67][63]. Inhalation of poorly soluble pollutants such as ozone, NO2 and phosgene also induces pulmonary inflammation [68[64][65],69], with changes focused within the lower respiratory tract [70,71][66][67]. Conversely, water soluble sulphur dioxide, chlorine and ammonia may predominantly influence the nasopharynx [70,72,73,74][66][68][69][70]. Volatile organic chemicals in vehicle and other pollutant sources are also detrimental to cardiovascular health [75][71], and lead to immunosuppression [76][72] and Alzheimer’s disease [77][73]. For example, acute acrolein exposure induces dyslipidaemia [78][74] and vascular dysfunction [79[75][76],80], while chronic exposure promotes atherosclerosis and lesion rupture [80,81][76][77] and impairs protective anti-infarct signalling [82][78]. Microparticulate exposure additionally triggers adipose tissue production/release of cytokines, contributing to systemic inflammation and hepatic insulin-resistance [71][67]. There is also evidence of immune cell mobilisation from bone marrow in response to PM exposure [83,84,85][79][80][81]. Despite these clear pro-inflammatory changes, mixed effects of air pollution on circulating cytokines are still reported, ranging from increases in humans and animals [86,87,88][82][83][84] to no apparent change [89,90,91][85][86][87]. These different peripheral changes and inflammatory processes contribute to a neurogenic inflammation with air pollution exposure [92,93][88][89]. Activation of neuronal and epithelial transient receptor potential proteins (TRPs) by pollutant products triggers a tachykinin (e.g., substance P, neurokinin A) release [94,95[90][91][92],96], whilst capsaicin-sensitive TRPV1 channels evoke a neuronal tachykinin release [97][93], and ion channel receptors trigger a neuronal neurokinin release [98,99][94][95]. This induces neurokinin-receptor-dependent pulmonary inflammation [100[96][97],101], with pulmonary injury and cytokine production spilling over into the systemic circulation, contributing to metabolic changes and propagating vascular and CNS inflammation [102,103][98][99]. Neuroinflammation, in turn, contributes to mental health issues such as MDD and other NCDs via perturbation of the PINE network [3,5][3][5]. Inflammatory mediators produced with pollutant exposure may activate glial cells in the CNS [104][100]. Interestingly, cytokine-mediated NFκB signalling in the hypothalamus appears to enhance particulate-induced systemic inflammation and metabolic changes [71][67], supporting positive feedback augmentation of inflammation via the CNS. Central stress-axis regions such as the paraventricular nucleus (PVN) of the hypothalamus may also be activated via sensory irritant activation of the trigeminal and vagal nerves with pulmonary oxidative stress/irritants, stimulating sympathetic and HPA-axis activities and hormone release. These central effects of air pollutants are influenced by, and in turn modulate, systemic metabolic changes. Experimental studies in rodents identify links between long-term particulate exposure and pollution-triggered inflammation with adipose and hepatic inflammation, hepatic ER stress, glucose intolerance and insulin-resistance [103,105][99][101]. These observations are consistent with links between chronic particulate exposure and insulin-resistance, hyperglycaemia and diabetes in humans [106][102]. Studies of acute exposure to gaseous pollutants reveal that lipid oxidation by-products are elevated, promoting skeletal muscle insulin-resistance [107][103].

3.2. HPA-Axis Activation and Dysregulation

Though fewer studies implicate stress hormones and their receptors in environmental disease susceptibilities [108][104], there is substantial evidence of stress-axis modulation in response to air pollutants [58][52]. Ozone has been extensively studied as a specific airborne toxin; however, any air pollutant that interacts with biological components of the airway and triggers neural responses can stimulate a HPA-mediated stress response [58][52]. Virgolini and colleagues [109,110][105][106] demonstrated permanent alteration in HPA-axis function with lead exposure, and heavy metals can form a significant component of air pollution. Heavy metal concentration can also be found in bush fires, with fires in Lithuania being linked to increases in heavy metals such as copper, lead and zinc contaminating river water [111][107], while ash from Californian wildfires in 2007 was shown to contain substantial levels of arsenic, cadmium, copper and lead [112][108]. It has been argued that the environmental stress of air pollution and psychological stress may act synergistically in disrupting health. Clougherty and Kubzansky [113][109] provide a compelling case for air pollution and stress potentiating respiratory disease onset and severity, with a lucid discussion of the central role of the HPA-axis, while Olvera Alvarez et al. [114][110] propose that early life stress and air pollution act synergistically to increase the risk of chronic diseases, including MDD, CHD, T2DM and lung and brain cancer [115][111]. These authors suggest early life stress results in long-term modification of HPA-axis function (e.g., via NR3C1 glucocorticoid receptor gene methylation), rendering the HPA axis susceptible to dysfunction with environmental stressors such as air pollution [114][110]. Similarly, [3,5][3][5] suggest that early developmental diathesis contributes to later disease risk via the PINE network, a ramification of which is that people experiencing early life stress and subsequently exposed to events such as bushfires or elevated levels of PM may be at greater risk of multiple chronic illnesses, including MDD, CHD or T2DM.

3.3. Autonomic Dysregulation

Air pollution can be linked to these chronic disorders via inflammatory, chemical and ischemic influences on the ANS [116][112]. To measure cardiac autonomic control, heart rate variability (HRV) is a well-recognised non-invasive and quantitative marker reflecting rhythmic activity of the sinus node, which is analysed in time, frequency or non-linear domains [117][113]. While HRV measures generally reflect sympathovagal balance, observed HRV may be primarily driven by vagal activity [118[114][115][116],119,120], with reduced HRV linked to vagal withdrawal [18,19][12][13]). Reduced HRV is associated with poor health outcomes and is linked to conditions such as MDD and CHD [121][117] and pathophysiological changes in the PINE network (discussed above). Air pollution, especially PM2.5, is associated with decreased HRV in different populations, including healthy young adults (particularly when simultaneously exposed to amplified noises) [122][118], healthy adult boilermakers [123][119], healthy senior adults [124[120][121][122],125,126], and those with cardiovascular diseases [127,128,129][123][124][125] also identified a decrease in HRV with PM exposure in elderly people, who were non-smokers and had no serious medical conditions. Additional smaller studies compared personal exposure to PM with HRV in healthy and diseased individuals [130,131,132][126][127][128]. For individuals, particularly the elderly, with certain underlying respiratory conditions, PM exposure can have up to a 4-fold increase in autonomic instability compared healthy young individuals [132][128]. Alongside reducing HRV, there is also limited evidence that PM increases coagulation [131][127]. Although limited by small sample sizes, these studies add to a body of evidence linking PM exposure, autonomic dysregulation and inflammation and indicating that pre-existing diseases can increase vulnerability to autonomic imbalance. There is noted heterogeneity within study findings. [130][126] (2003) report that for (a limited cohort) patients with stable, severe CHD, CO but not PM exposure may briefly modify autonomic control. Furthermore, studies of older people presenting with chronic obstructive pulmonary disease (COPD), found no associations between HRV and PM2.5 [133,134][129][130], potentially reflecting differences in systemic inflammation compared to other subgroups [135][131], including a baseline lower HRV in individuals with COPD [136,137][132][133]. Taken together, these results suggest that the acute cardiovascular toxicity of PM alters the autonomic control of the heart depending on the underlying health status of the individual.

4. Evidence PM Exposure Promotes Chronic Non-Communicable Diseases

The acute or direct health effects of elevated background PM exposure and following significant events, such as bush fires, has been relatively well documented [138][134]. For instance, exposure to smoke is associated with increased hospitalisations [139][135], respiratory morbidity such as asthma and COPD [140][136], stroke [141][137], cardiovascular disease [142][138], poorer birth outcomes [143][139] and premature deaths [144][140]. Analysis of acute smoke exposure and premature deaths in Sydney from 1994 to 2007 reveals a 5% increase in mortality during bushfires [145][141]. In terms of the acute effects of recent fires in eastern and southern Australia, [146][142] estimated ~420 excess deaths from this smoke exposure, together with 3151 additional cardio-respiratory related hospitalisations and 1305 emergency department attendances for asthma. In addition to immediate or early effects, air pollution has been linked to later development of chronic diseases and emerging evidence supports epigenetic promotion of such disease risk across generations. The WHO estimates that >80% of those individuals in urban areas are exposed to air pollution levels exceeding guideline limits [147][143], with pollution disproportionately impacting those in less economically developed populations [148][144], mirroring the demographics for major NCDs. Inhaled pollutants impact organ systems beyond the lungs (Kurt et al., 2016), including the heart and blood vessels [149[145][146][147],150,151], liver [152][148], kidneys [153,154][149][150] and as detailed above, the CNS [155][151]. Air pollution also affects developmental programming [156][152]. Beyond predictable associations with respiratory disorders [157][153], air pollution is linked to NCDs including steatohepatitis [158][154], diabetes [106][102], neurodegenerative diseases [159][155] and cancers [115,160][111][156]. Cardiovascular disorders, such as hypertension [161][157] and CHD [162[158][159],163], are particularly strongly associated with air pollution. Even brief exposure is linked to AMI, stroke, arrhythmias, worsening of heart failure and hypertension [164[160][161][162][163],165,166,167], while chronic exposure accelerates atherosclerosis, impacts blood pressure control, thrombosis, endothelial function, insulin sensitivity [164,166][160][162] and increases the risk of hypertension, Long-term effects of ambient PM2. 5 on hypertension and blood pressure and attributable risk among older Chinese adults [167,168][163][164]. The WHO estimates that air pollution contributes to ~7 million premature deaths globally per annum, with cardiovascular impacts, for example, rivalling the most widely studied and powerful drivers of smoking, hypertension and inactivity [165][161]. More recent analysis ascribes 9 million premature deaths to pollution in 2015 (16% of global deaths), and welfare costs approaching USD 5 trillion annually [169][165]. There appear to be no safe levels of air pollution in terms of increased mortality [170][166]. Exposure to PM2.5, predominantly generated from fossil fuel combustion and bushfires, is linked to premature death due to cancer, respiratory, metabolic and cardiovascular diseases [138][134]. As with air pollution more broadly, those with existing conditions are particularly sensitive to PM exposure [166][162], exacerbating acute cardiovascular events and promoting chronic CVD. While the relatively large size of PM10 particles (predominantly pollen, dust and construction or agriculture by-products) limits penetration to the upper respiratory tract, PM2.5 and smaller reach the alveoli which may underlie greater impacts of PM2.5 on multiple organ systems. One body of evidence linking airborne PM to NCDs comes from studies of air pollution exposure in socioeconomically disadvantaged people. The markedly increased NCD risks in minority and low-socioeconomic-standing (SES) groups may involve disproportionate exposures to pollutants. For example, diabetes is linked to increased pollutant exposure in high-risk groups in the USA [171,172,173][167][168][169]. Proximity to major roadways, strongly linked to low SES, is associated with increased carotid-intima thickness [174][170], abdominal adiposity [175][171], hypertension [77][73], the risk of AMI [176][172] sudden cardiac death [177][173], mortality due to acute heart failure [178][174] and stroke [179][175]. Concentration of chemical plants and waste sites in low SES communities also contributes to increased exposure and thus disease risk [180][176]. The health impacts of pollution are also influenced by SES, dietary and other factors. For example, a lack of association between PM exposure and CVD in a study of male health professionals has been attributed to a higher SES and healthier lifestyle of this sub-population [181][177]. In summary, PM is linked to NCDs in both short-term and longer-term timeframes. WResearchers have detailed how PM impacts PINE subsystems and have shown that PM is linked to not only respiratory disease, but NCDs that have previously been linked to PINE network pathophysiology [5].

References

  1. Engel, G.L. The need for a new medical model: A challenge for biomedicine. Science 1977, 196, 129–136.
  2. Engel, G.L. The need for a new medical model: A challenge for biomedicine. Holist. Med. 1989, 4, 37–53.
  3. Stapelberg, N.J.C.; Neumann, D.L.; Shum, D.H.K.; McConnell, H.; Hamilton-Craig, I. From Physiome to Pathome: A Systems Biology Model of Major Depressive Disorder and the Psycho-Immune-Neuroendocrine Network. Curr. Psychiatry Rev. 2015, 11, 32–62.
  4. Stapelberg, N.J.C.; Pratt, R.; Neumann, D.; Shum, D.; Brandis, S.; Muthukkumarasamy, V.; Stantic, B.; Blumenstein, M.; Headrick, J. From Feedback Loop Transitions to Biomarkers in the Psycho-Immune-Neuroendocrine Network: Detecting the Critical Transition from Health to Major Depression. Neurosci. Biobehav. Rev. 2018, 90, 1–15.
  5. Stapelberg, N.J.C.; Neumann, D.L.; Shum, D.; Headrick, J.P. Health, pre-disease and critical transition to disease in the psycho-immune-neuroendocrine network: Are there distinct states in the progression from health to major depressive disorder? Physiol. Behav. 2019, 198, 108–119.
  6. Selye, H. A syndrome produced by diverse nocuous agents. Nature 1936, 138, 32.
  7. McEwen, B.S.; Stellar, E. Stress and the individual: Mechanisms leading to disease. Arch. Intern. Med. 1993, 153, 2093.
  8. McEwen, B.S. Interacting mediators of allostasis and allostatic load: Towards an understanding of resilience in aging. Metabolism 2003, 52, 10–16.
  9. McEwen, B.S. Protection and damage from acute and chronic stress: Allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Ann. N. Y. Acad. Sci. 2004, 1032, 1–7.
  10. Cohen, S.; Janicki-Deverts, D.; Miller, G.E. Psychological stress and disease. JAMA 2007, 298, 1685–1687.
  11. McEwen, B.S. Protective and damaging effects of stress mediators. N. Engl. J. Med. 1998, 338, 171–179.
  12. Rottenberg, J. Cardiac vagal control in depression: A critical analysis. Biol. Psychol. 2007, 74, 200–211.
  13. Tsigos, C.; Chrousos, G.P. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J. Psychosom. Res. 2002, 53, 865–871.
  14. Cohen, S.; Janicki-Deverts, D.; Doyle, W.J.; Miller, G.E.; Frank, E.; Rabin, B.S.; Turner, R.B. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc. Natl. Acad. Sci. USA 2012, 109, 5995–5999.
  15. Derijk, R.; Sternberg, E.M. Corticosteroid resistance and disease. Ann. Med. 1997, 29, 79–82.
  16. Chrousos, G.P.; Gold, P.W. The concepts of stress and stress system disorders: Overview of physical and behavioral homeostasis. JAMA 1992, 267, 1244–1252.
  17. Dantzer, R.; Konsman, J.P.; Bluthe, R.M.; Kelley, K.W. Neural and humoral pathways of communication from the immune system to the brain: Parallel or convergent? Auton. Neurosci. 2000, 85, 60–65.
  18. Olofsson, P.S.; Rosas-Ballina, M.; Levine, Y.A.; Tracey, K.J. Rethinking inflammation: Neural circuits in the regulation of immunity. Immunol. Rev. 2012, 248, 188–204.
  19. Tracey, K.J. The inflammatory reflex. Nature 2002, 420, 853–859.
  20. Rajkowska, G.; Miguel-Hidalgo, J. Gliogenesis and glial pathology in depression. CNS Neurol. Disord. Drug Targets 2007, 6, 219.
  21. Cotter, D.R.; Pariante, C.M.; Everall, I.P. Glial cell abnormalities in major psychiatric disorders: The evidence and implications. Brain Res. Bull. 2001, 55, 585–595.
  22. Cotter, D.; Mackay, D.; Landau, S.; Kerwin, R.; Everall, I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch. Gen. Psychiatry 2001, 58, 545.
  23. Müller, N.; Schwarz, M. The immune-mediated alteration of serotonin and glutamate: Towards an integrated view of depression. Mol. Psychiatry 2007, 12, 988–1000.
  24. Zou, J.Y.; Crews, F.T. TNFα potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: Neuroprotection by NFκB inhibition. Brain Res. 2005, 1034, 11–24.
  25. Stone, T.; Perkins, M. Quinolinic acid: A potent endogenous excitant at amino acid receptors in CNS. Eur. J. Pharmacol. 1981, 72, 411.
  26. Gould, E.; Tanapat, P.; McEwen, B.S.; Flügge, G.; Fuchs, E. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc. Natl. Acad. Sci. USA 1998, 95, 3168–3171.
  27. Pittenger, C.; Sanacora, G.; Krystal, J.H. The NMDA receptor as a therapeutic target in major depressive disorder. CNS Neurol. Disord. Drug Targets 2007, 6, 101–115.
  28. Gould, E.; Beylin, A.; Tanapat, P.; Reeves, A.; Shors, T.J. Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci. 1999, 2, 260.
  29. Shors, T.J.; Miesegaes, G.; Beylin, A.; Zhao, M.; Rydel, T.; Gould, E. Neurogenesis in the adult is involved in the formation of trace memories. Nature 2001, 410, 372.
  30. Lee, C.-H.; Giuliani, F. The role of inflammation in depression and fatigue. Front. Immunol. 2019, 10, 1696.
  31. Dantzer, R.; Bluthé, R.; Laye, S.; Bret-Dibat, J.L.; Parnet, P.; Kelley, K.W. Cytokines and sickness behavior. Ann. N. Y. Acad. Sci. 1998, 840, 586–590.
  32. Dantzer, R.; Aubert, A.; Bluthe, R.M.; Gheusi, G.; Cremona, S.; Laye, S.; Konsman, J.P.; Parnet, P.; Kelley, K.W. Mechanisms of the behavioural effects of cytokines. Adv. Exp. Med. Biol. 1999, 461, 83–105.
  33. Dantzer, R. Cytokine, sickness behavior, and depression. Immunol. Allergy Clin. N. Am. 2009, 29, 247.
  34. Headrick, J.P.; Peart, J.N.; Budiono, B.P.; Shum, D.H.; Neumann, D.L.; Stapelberg, N.J.C. The heartbreak of depression: ‘Psycho-cardiac’ coupling in myocardial infarction. J. Mol. Cell. Cardiol. 2017, 106, 14–28.
  35. Sahay, A.; Hen, R. Adult hippocampal neurogenesis in depression. Nat. Neurosci. 2007, 10, 1110.
  36. Kuipers, S.; Trentani, A.; Den Boer, J.; Ter Horst, G. Molecular correlates of impaired prefrontal plasticity in response to chronic stress. J. Neurochem. 2003, 85, 1312–1323.
  37. Kashyap, P.C.; Marcobal, A.; Ursell, L.K.; Larauche, M.; Duboc, H.; Earle, K.A.; Sonnenburg, E.D.; Ferreyra, J.A.; Higginbottom, S.K.; Million, M. Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology 2013, 144, 967–977.
  38. Nicholson, J.K.; Holmes, E.; Kinross, J.; Burcelin, R.; Gibson, G.; Jia, W.; Pettersson, S. Host-gut microbiota metabolic interactions. Science 2012, 336, 1262–1267.
  39. Chavez, A.M.; Menconi, M.J.; Hodin, R.A.; Fink, M.P. Cytokine-induced intestinal epithelial hyperpermeability: Role of nitric oxide. Crit. Care Med. 1999, 27, 2246–2251.
  40. Maes, M.; Mihaylova, I.; Leunis, J.-C. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut–intestinal permeability. J. Affect. Disord. 2007, 99, 237–240.
  41. Wang, W.; Zhou, J.; Chen, M.; Huang, X.; Xie, X.; Li, W.; Cao, Q.; Kan, H.; Xu, Y.; Ying, Z. Exposure to concentrated ambient PM 2.5 alters the composition of gut microbiota in a murine model. Part. Fibre Toxicol. 2018, 15, 17.
  42. Mutlu, E.A.; Comba, I.Y.; Cho, T.; Engen, P.A.; Yazıcı, C.; Soberanes, S.; Hamanaka, R.B.; Niğdelioğlu, R.; Meliton, A.Y.; Ghio, A.J. Inhalational exposure to particulate matter air pollution alters the composition of the gut microbiome. Environ. Pollut. 2018, 240, 817–830.
  43. Liu, T.; Chen, X.; Xu, Y.; Wu, W.; Tang, W.; Chen, Z.; Ji, G.; Peng, J.; Jiang, Q.; Xiao, J. Gut microbiota partially mediates the effects of fine particulate matter on type 2 diabetes: Evidence from a population-based epidemiological study. Environ. Int. 2019, 130, 104882.
  44. Kalra, S.P.; Ueno, N.; Kalra, P.S. Stimulation of appetite by ghrelin is regulated by leptin restraint: Peripheral and central sites of action. J. Nutr. 2005, 135, 1331–1335.
  45. Brennan, A.M.; Mantzoros, C.S. Drug insight: The role of leptin in human physiology and pathophysiology—Emerging clinical applications. Nat. Clin. Pract. Endocrinol. Metab. 2006, 2, 318–327.
  46. Lu, X.-Y. The leptin hypothesis of depression: A potential link between mood disorders and obesity? Curr. Opin. Pharmacol. 2007, 7, 648–652.
  47. Black, P.H. The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav. Immun. 2003, 17, 350–364.
  48. Loffreda, S.; Yang, S.; Lin, H.; Karp, C.; Brengman, M.; Wang, D.; Klein, A.; Bulkley, G.; Bao, C.; Noble, P. Leptin regulates proinflammatory immune responses. FASEB J. 1998, 12, 57–65.
  49. Matarese, G.; Moschos, S.; Mantzoros, C.S. Leptin in immunology. J. Immunol. 2005, 174, 3137–3142.
  50. Santos-Alvarez, J.; Goberna, R.; Sánchez-Margalet, V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell. Immunol. 1999, 194, 6–11.
  51. Abella, V.; Scotece, M.; Conde, J.; Pino, J.; Gonzalez-Gay, M.A.; Gómez-Reino, J.J.; Mera, A.; Lago, F.; Gómez, R.; Gualillo, O. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat. Rev. Rheumatol. 2017, 13, 100.
  52. Kodavanti, U. Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response. Biochim. Biophys. Acta-Gen. Subj. 2016, 1860, 2880–2890.
  53. Gottipolu, R.R.; Wallenborn, J.G.; Karoly, E.D.; Schladweiler, M.C.; Ledbetter, A.D.; Krantz, T.; Linak, W.P.; Nyska, A.; Johnson, J.A.; Thomas, R. One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats. Environ. Health Perspect. 2009, 117, 38–46.
  54. Jankowska-Kieltyka, M.; Roman, A.; Nalepa, I. The Air We Breathe: Air Pollution as a Prevalent Proinflammatory Stimulus Contributing to Neurodegeneration. Front. Cell. Neurosci. 2021, 15, 239.
  55. Kim, H.; Kim, W.-H.; Kim, Y.-Y.; Park, H.-Y. Air Pollution and Central Nervous System Disease: A Review of the Impact of Fine Particulate Matter on Neurological Disorders. Front. Public Health 2020, 8, 575330.
  56. Routledge, H.; Ayres, J.G. Air pollution and the heart. Occup. Med. 2005, 55, 439–447.
  57. Peters, A.; Skorkovsky, J.; Kotesovec, F.; Brynda, J.; Spix, C.; Wichmann, H.E.; Heinrich, J. Associations between mortality and air pollution in central Europe. Environ. Health Perspect. 2000, 108, 283–287.
  58. de Oliveira Alves, N.; Vessoni, A.T.; Quinet, A.; Fortunato, R.S.; Kajitani, G.S.; Peixoto, M.S.; de Souza Hacon, S.; Artaxo, P.; Saldiva, P.; Menck, C.F.M. Biomass burning in the Amazon region causes DNA damage and cell death in human lung cells. Sci. Rep. 2017, 7, 10937.
  59. Chuang, K.-J.; Chan, C.-C.; Su, T.-C.; Lee, C.-T.; Tang, C.-S. The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. Am. J. Respir. Crit. Care Med. 2007, 176, 370–376.
  60. Pope III, C.A.; Burnett, R.T.; Thurston, G.D.; Thun, M.J.; Calle, E.E.; Krewski, D.; Godleski, J.J. Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation 2004, 109, 71–77.
  61. Calderón-Garcidueñas, L.; Solt, A.C.; Henríquez-Roldán, C.; Torres-Jardón, R.; Nuse, B.; Herritt, L.; Villarreal-Calderón, R.; Osnaya, N.; Stone, I.; Garcia, R. 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 β-42 and α-synuclein in children and young adults. Toxicol. Pathol. 2008, 36, 289–310.
  62. Nelin, T.D.; Joseph, A.M.; Gorr, M.W.; Wold, L.E. Direct and indirect effects of particulate matter on the cardiovascular system. Toxicol. Lett. 2012, 208, 293–299.
  63. Hoffmann, B.; Moebus, S.; Dragano, N.; Stang, A.; Möhlenkamp, S.; Schmermund, A.; Memmesheimer, M.; Bröcker-Preuss, M.; Mann, K.; Erbel, R. Chronic residential exposure to particulate matter air pollution and systemic inflammatory markers. Environ. Health Perspect. 2009, 117, 1302–1308.
  64. Kodavanti, U.P.; Ledbetter, A.D.; Thomas, R.F.; Richards, J.E.; Ward, W.O.; Schladweiler, M.C.; Costa, D.L. Variability in ozone-induced pulmonary injury and inflammation in healthy and cardiovascular-compromised rat models. Inhal. Toxicol. 2015, 27 (Suppl. S1), 39–53.
  65. Gift, J.S.; McGaughy, R.; Singh, D.V.; Sonawane, B. Health assessment of phosgene: Approaches for derivation of reference concentration. Regul. Toxicol. Pharmacol. 2008, 51, 98–107.
  66. Luo, P.; Bao, L.-J.; Li, S.-M.; Zeng, E.Y. Size-dependent distribution and inhalation cancer risk of particle-bound polycyclic aromatic hydrocarbons at a typical e-waste recycling and an urban site. Environ. Pollut. 2015, 200, 10–15.
  67. Liu, T.; Zhang, Y.H.; Xu, Y.J.; Lin, H.L.; Xu, X.J.; Luo, Y.; Xiao, J.; Zeng, W.L.; Zhang, W.F.; Chu, C. The effects of dust–haze on mortality are modified by seasons and individual characteristics in Guangzhou, China. Environ. Pollut. 2014, 187, 116–123.
  68. Kilburn, K.H.; McKenzie, W.N.; Thurston, R.J. Cellular effects of cigarette smoke on hamster airways. Chest 1975, 67 (Suppl. S2), 54S.
  69. Li, W.-L.; Pauluhn, J. Comparative assessment of the sensory irritation potency in mice and rats nose-only exposed to ammonia in dry and humidified atmospheres. Toxicology 2010, 276, 135–142.
  70. Tuck, S.A.; Ramos-Barbón, D.; Campbell, H.; McGovern, T.; Karmouty-Quintana, H.; Martin, J.G. Time course of airway remodelling after an acute chlorine gas exposure in mice. Respir. Res. 2008, 9, 61.
  71. Bhatnagar, A. Cardiovascular pathophysiology of environmental pollutants. Am. J. Physiol.-Heart Circ. Physiol. 2004, 286, H479–H485.
  72. Kirkham, P.A.; Spooner, G.; Rahman, I.; Rossi, A.G. Macrophage phagocytosis of apoptotic neutrophils is compromised by matrix proteins modified by cigarette smoke and lipid peroxidation products. Biochem. Biophys. Res. Commun. 2004, 318, 32–37.
  73. Kingsley, S.L.; Eliot, M.N.; Whitsel, E.A.; Wang, Y.; Coull, B.A.; Hou, L.; Margolis, H.G.; Margolis, K.L.; Mu, L.; Wu, W.-C.C. Residential proximity to major roadways and incident hypertension in post-menopausal women. Environ. Res. 2015, 142, 522–528.
  74. Conklin, D.J.; Barski, O.A.; Lesgards, J.-F.; Juvan, P.; Rezen, T.; Rozman, D.; Prough, R.A.; Vladykovskaya, E.; Liu, S.; Srivastava, S. Acrolein consumption induces systemic dyslipidemia and lipoprotein modification. Toxicol. Appl. Pharmacol. 2010, 243, 1–12.
  75. Awe, S.O.; Adeagbo, A.; D’Souza, S.; Bhatnagar, A.; Conklin, D. Acrolein induces vasodilatation of rodent mesenteric bed via an EDHF-dependent mechanism. Toxicol. Appl. Pharmacol. 2006, 217, 266–276.
  76. O’Toole, T.E.; Zheng, Y.-T.; Hellmann, J.; Conklin, D.J.; Barski, O.; Bhatnagar, A. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages. Toxicol. Appl. Pharmacol. 2009, 236, 194–201.
  77. Srivastava, S.; Sithu, S.D.; Vladykovskaya, E.; Haberzettl, P.; Hoetker, D.J.; Siddiqui, M.A.; Conklin, D.J.; D’Souza, S.E.; Bhatnagar, A. Oral exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Atherosclerosis 2011, 215, 301–308.
  78. Wang, G.-W.; Guo, Y.; Vondriska, T.M.; Zhang, J.; Zhang, S.; Tsai, L.L.; Zong, N.C.; Bolli, R.; Bhatnagar, A.; Prabhu, S.D. Acrolein consumption exacerbates myocardial ischemic injury and blocks nitric oxide-induced PKCε signaling and cardioprotection. J. Mol. Cell. Cardiol. 2008, 44, 1016–1022.
  79. Thomson, E.M.; Vladisavljevic, D.; Mohottalage, S.; Kumarathasan, P.; Vincent, R. Mapping acute systemic effects of inhaled particulate matter and ozone: Multiorgan gene expression and glucocorticoid activity. Toxicol. Sci. 2013, 135, 169–181.
  80. Abplanalp, W.; Haberzettl, P.; Bhatnagar, A.; Conklin, D.J.; O’Toole, T.E. Carnosine Supplementation Mitigates the Deleterious Effects of Particulate Matter Exposure in Mice. J. Am. Heart Assoc. 2019, 8, e013041.
  81. Goto, Y.; Ishii, H.; Hogg, J.C.; Shih, C.-H.; Yatera, K.; Vincent, R.; van Eeden, S.F. Particulate matter air pollution stimulates monocyte release from the bone marrow. Am. J. Respir. Crit. Care Med. 2004, 170, 891–897.
  82. Chiarella, S.E.; Soberanes, S.; Urich, D.; Morales-Nebreda, L.; Nigdelioglu, R.; Green, D.; Young, J.B.; Gonzalez, A.; Rosario, C.; Misharin, A.V. β 2-Adrenergic agonists augment air pollution–induced IL-6 release and thrombosis. J. Clin. Investig. 2014, 124, 2935–2946.
  83. Tsai, D.-H.; Amyai, N.; Marques-Vidal, P.; Wang, J.-L.; Riediker, M.; Mooser, V.; Paccaud, F.; Waeber, G.; Vollenweider, P.; Bochud, M. Effects of particulate matter on inflammatory markers in the general adult population. Part. Fibre Toxicol. 2012, 9, 24.
  84. Marchini, T.; Wolf, D.; Michel, N.A.; Mauler, M.; Dufner, B.; Hoppe, N.; Beckert, J.; Jäckel, M.; Magnani, N.; Duerschmied, D. Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages. Basic Res. Cardiol. 2016, 111, 44.
  85. Miller, D.B.; Karoly, E.D.; Jones, J.C.; Ward, W.O.; Vallanat, B.D.; Andrews, D.L.; Schladweiler, M.C.; Snow, S.J.; Bass, V.L.; Richards, J.E. Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats. Toxicol. Appl. Pharmacol. 2015, 286, 65–79.
  86. Bleck, B.; Grunig, G.; Chiu, A.; Liu, M.; Gordon, T.; Kazeros, A.; Reibman, J. MicroRNA-375 regulation of thymic stromal lymphopoietin by diesel exhaust particles and ambient particulate matter in human bronchial epithelial cells. J. Immunol. 2013, 190, 3757–3763.
  87. Rudež, G.; Janssen, N.A.; Kilinc, E.; Leebeek, F.W.; Gerlofs-Nijland, M.E.; Spronk, H.M.; Cate, H.T.; Cassee, F.R.; de Maat, M.P. Effects of ambient air pollution on hemostasis and inflammation. Environ. Health Perspect. 2009, 117, 995–1001.
  88. Arjomandi, M.; Witten, A.; Abbritti, E.; Reintjes, K.; Schmidlin, I.; Zhai, W.; Solomon, C.; Balmes, J. Repeated exposure to ozone increases alveolar macrophage recruitment into asthmatic airways. Am. J. Respir. Crit. Care Med. 2005, 172, 427–432.
  89. Veronesi, B.; Oortgiesen, M. Neurogenic inflammation and particulate matter (PM) air pollutants. Neurotoxicology 2001, 22, 795–810.
  90. Meng, J.; Wang, J.; Steinhoff, M.; Dolly, J.O. TNFα induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18–1/syntaxin1/SNAP-25 mediated fusion. Sci. Rep. 2016, 6, 21226.
  91. Driessen, A.K.; Farrell, M.J.; Mazzone, S.B.; McGovern, A.E. Multiple neural circuits mediating airway sensations: Recent advances in the neurobiology of the urge-to-cough. Respir. Physiol. Neurobiol. 2016, 226, 115–120.
  92. Kinawy, A.A.; Ezzat, A.R.; Al-Suwaigh, B.R. Inhalation of air polluted with gasoline vapours alters the levels of amino acid neurotransmitters in the cerebral cortex, hippocampus, and hypothalamus of the rat. Exp. Toxicol. Pathol. 2014, 66, 219–224.
  93. Saria, A.; Martling, C.-R.; Yan, Z.; Theodorsson-Norheim, E.; Gamse, R.; Lundberg, J.M. Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. Am. Rev. Respir. Dis. 1988, 137, 1330–1335.
  94. Nassini, R.; Pedretti, P.; Moretto, N.; Fusi, C.; Carnini, C.; Facchinetti, F.; Viscomi, A.R.; Pisano, A.R.; Stokesberry, S.; Brunmark, C. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS ONE 2012, 7, e42454.
  95. Benemei, S.; Fusi, C.; Trevisan, G.; Geppetti, P. The TRPA1 channel in migraine mechanism and treatment. Br. J. Pharmacol. 2014, 171, 2552–2567.
  96. D’Amato, G.; Holgate, S.T.; Pawankar, R.; Ledford, D.K.; Cecchi, L.; Al-Ahmad, M.; Al-Enezi, F.; Al-Muhsen, S.; Ansotegui, I.; Baena-Cagnani, C.E. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization. World Allergy Organ. J. 2015, 8, 1.
  97. Lewis, E.R.G.; David, V.R.; Doyle, A.L.; Rajabi, K.; Kiefer, J.A.; Pirrotte, P.; Barker, B.M. Differences in Host Innate Responses among Coccidioides Isolates in a Murine Model of Pulmonary Coccidioidomycosis. Eukaryot. Cell 2015, 14, 1043–1053.
  98. Kampfrath, T.; Maiseyeu, A.; Ying, Z.; Shah, Z.; Deiuliis, J.A.; Xu, X.; Kherada, N.; Brook, R.D.; Reddy, K.M.; Padture, N.P. Chronic fine particulate matter exposure induces systemic vascular dysfunction via NADPH oxidase and TLR4 pathways. Circ. Res. 2011, 108, 716–726.
  99. Rao, X.; Patel, P.; Puett, R.; Rajagopalan, S. Air pollution as a risk factor for type 2 diabetes. Toxicol. Sci. 2015, 143, 231–241.
  100. Fonken, L.K.; Xu, X.; Weil, Z.M.; Chen, G.; Sun, Q.; Rajagopalan, S.; Nelson, R.J. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Mol. Psychiatry 2011, 16, 987–995.
  101. Rivera, M.; Basagaña, X.; Aguilera, I.; Foraster, M.; Agis, D.; de Groot, E.; Perez, L.; Mendez, M.A.; Bouso, L.; Targa, J. Association between long-term exposure to traffic-related air pollution and subclinical atherosclerosis: The REGICOR study. Environ. Health Perspect. 2013, 121, 223–230.
  102. Thiering, E.; Heinrich, J. Epidemiology of air pollution and diabetes. Trends Endocrinol. Metab. 2015, 26, 384–394.
  103. Vella, R.E.; Pillon, N.J.; Zarrouki, B.; Croze, M.L.; Koppe, L.; Guichardant, M.; Pesenti, S.; Chauvin, M.-A.; Rieusset, J.; Géloën, A. Ozone exposure triggers insulin resistance through muscle c-Jun N-terminal kinase activation. Diabetes Care 2015, 64, 1011–1024.
  104. Clougherty, J.E.; Rossi, C.A.; Lawrence, J.; Long, M.S.; Diaz, E.A.; Lim, R.H.; McEwen, B.; Koutrakis, P.; Godleski, J.J. Chronic social stress and susceptibility to concentrated ambient fine particles in rats. Environ. Health Perspect. 2010, 118, 769–775.
  105. Virgolini, M.B.; Bauter, M.R.; Weston, D.D.; Cory-Slechta, D.A. Permanent alterations in stress responsivity in female offspring subjected to combined maternal lead exposure and/or stress. Neurotoxicology 2006, 27, 11–21.
  106. Virgolini, M.B.; Chen, K.; Weston, D.D.; Bauter, M.R.; Cory-Slechta, D.A. Interactions of chronic lead exposure and intermittent stress: Consequences for brain catecholamine systems and associated behaviors and HPA axis function. Toxicol. Sci. 2005, 87, 469–482.
  107. Ignatavièius, G.; Sakalauskienë, G.; Oškinis, V. Influence of land fires on increase of heavy metal concentrations in river waters of Lithuania. J. Environ. Eng. Landsc. Manag. 2006, 14, 46–51.
  108. Wittig, V.; Williams, S.; DuTeaux, S.B. Public health impacts of residential wildfires: Analysis of ash and debris from the 2007 Southern California fires. Epidemiology 2008, 19, S207.
  109. Clougherty, J.E.; Kubzansky, L.D. A framework for examining social stress and susceptibility to air pollution in respiratory health. Cien. Saude Colet. 2010, 15, 2059–2074.
  110. Olvera Alvarez, H.A.; Kubzansky, L.D.; Campen, M.J.; Slavich, G.M. Early life stress, air pollution, inflammation, and disease: An integrative review and immunologic model of social-environmental adversity and lifespan health. Neurosci. Biobehav. Rev. 2018, 92, 226–242.
  111. Turner, M.C.; Krewski, D.; Diver, W.R.; Pope, C.A., 3rd; Burnett, R.T.; Jerrett, M.; Marshall, J.D.; Gapstur, S.M. Ambient air pollution and cancer mortality in the cancer prevention study II. Environ. Health Perspect. 2017, 125, 087013.
  112. Utell, M.J.; Frampton, M.W.; Zareba, W.; Devlin, R.B.; Cascio, W.E. Cardiovascular effects associated with air pollution: Potential mechanisms and methods of testing. Inhal. Toxicol. 2002, 14, 1231–1247.
  113. Task Force, Heart Rate Variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur. Heart J. 1996, 17, 354–381.
  114. Brown, A.D.; Barton, D.A.; Lambert, G.W. Cardiovascular abnormalities in patients with major depressive disorder: Autonomic mechanisms and implications for treatment. CNS Drugs 2009, 23, 583–602.
  115. Levy, M.N. Autonomic interactions in cardiac control. Ann. N. Y. Acad. Sci. 1990, 601, 209–221.
  116. Thayer, J.F.; Lane, R.D. A model of neurovisceral integration in emotion regulation and dysregulation. J. Affect. Disord. 2000, 61, 201–216.
  117. Stapelberg, N.J.C.; Hamilton-Craig, I.; Neumann, D.L.; Shum, D.H.; McConnell, H. Mind and heart: Heart rate variability in major depressive disorder and coronary heart disease—A review and recommendations. Aust. N. Z. J. Psychiatry 2012, 46, 946–957.
  118. Huang, J.; Deng, F.; Wu, S.; Lu, H.; Hao, Y.; Guo, X. The impacts of short-term exposure to noise and traffic-related air pollution on heart rate variability in young healthy adults. J. Expo. Sci. Environ. Epidemiol. 2013, 23, 559–564.
  119. Magari, S.R.; Hauser, R.; Schwartz, J.; Williams, P.L.; Smith, T.J.; Christiani, D.C. Association of heart rate variability with occupational and environmental exposure to particulate air pollution. Circulation 2001, 104, 986–991.
  120. Creason, J.; Neas, L.; Walsh, D.; Williams, R.; Sheldon, L.; Liao, D.; Shy, C. Particulate matter and heart rate variability among elderly retirees: The Baltimore 1998 PM study. J. Expo. Anal. Environ. Epidemiol. 2001, 11, 116–122.
  121. Holguín, F.; Téllez-Rojo, M.M.; Hernández, M.; Cortez, M.; Chow, J.C.; Watson, J.G.; Mannino, D.; Romieu, I. Air pollution and heart rate variability among the elderly in Mexico City. Epidemiology 2003, 14, 521–527.
  122. Gold, D.R.; Litonjua, A.; Schwartz, J.; Lovett, E.; Larson, A.; Nearing, B.; Allen, G.; Verrier, M.; Cherry, R.; Verrier, R. Ambient Pollution and Heart Rate Variability. Circulation 2000, 101, 1267–1273.
  123. Park, S.K.; O’Neill, M.S.; Vokonas, P.S.; Sparrow, D.; Schwartz, J. Effects of air pollution on heart rate variability: The VA normative aging study. Environ. Health Perspect. 2005, 113, 304–309.
  124. Liao, D.; Creason, J.; Shy, C.; Williams, R.; Watts, R.; Zweidinger, R. Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly. Environ. Health Perspect. 1999, 107, 521–525.
  125. Pope, C.A., 3rd; Verrier, R.L.; Lovett, E.G.; Larson, A.C.; Raizenne, M.E.; Kanner, R.E.; Schwartz, J.; Villegas, G.M.; Gold, D.R.; Dockery, D.W. Heart rate variability associated with particulate air pollution. Am. Heart J. 1999, 138 Pt 1, 890–899.
  126. Tarkiainen, T.H.; Timonen, K.L.; Vanninen, E.J.; Alm, S.; Hartikainen, J.E.K.; Pekkanen, J. Effect of acute carbon monoxide exposure on heart rate variability in patients with coronary artery disease. Clin. Physiol. Funct. Imaging 2003, 23, 98–102.
  127. Riediker, M.; Cascio, W.E.; Griggs, T.R.; Herbst, M.C.; Bromberg, P.A.; Neas, L.; Williams, R.W.; Devlin, R.B. Particulate Matter Exposure in Cars Is Associated with Cardiovascular Effects in Healthy Young Men. Am. J. Respir. Crit. Care Med. 2004, 169, 934–940.
  128. Chan, C.C.; Chuang, K.J.; Shiao, G.M.; Lin, L.Y. Personal exposure to submicrometer particles and heart rate variability in human subjects. Environ. Health Perspect. 2004, 112, 1063–1067.
  129. Suh, H.H.; Zanobetti, A. Exposure error masks the relationship between traffic-related air pollution and heart rate variability. J. Occup. Environ. Med. 2010, 52, 685–692.
  130. Brauer, M.; Ebelt, S.T.; Fisher, T.V.; Brumm, J.; Petkau, A.J.; Vedal, S. Exposure of chronic obstructive pulmonary disease patients to particles: Respiratory and cardiovascular health effects. J. Expo. Anal. Environ. Epidemiol. 2001, 11, 490–500.
  131. Luttmann-Gibson, H.; Suh, H.H.; Coull, B.A.; Dockery, D.W.; Sarnat, S.E.; Schwartz, J.; Stone, P.H.; Gold, D.R. Systemic inflammation, heart rate variability and air pollution in a cohort of senior adults. Occup. Environ. Med. 2010, 67, 625–630.
  132. Volterrani, M.; Scalvini, S.; Mazzuero, G.; Lanfranchi, P.; Colombo, R.; Clark, A.L.; Levi, G. Decreased heart rate variability in patients with chronic obstructive pulmonary disease. Chest 1994, 106, 1432–1437.
  133. Pagani, M.; Lucini, D.; Pizzinelli, P.; Sergi, M.; Bosisio, E.; Mela, G.S.; Malliani, A. Effects of aging and of chronic obstructive pulmonary disease on RR interval variability. J. Auton. Nerv. Syst. 1996, 59, 125–132.
  134. Reisen, F.; Brown, S.K. Implications for community health from exposure to bushfire air toxics. J. Environ. Chem. 2006, 3, 235–243.
  135. Horsley, J.A.; Broome, R.A.; Johnston, F.H.; Cope, M.; Morgan, G.G. Health burden associated with fire smoke in Sydney, 2001–2013. Med. J. Aust. 2018, 208, 309–310.
  136. Liu, J.C.; Pereira, G.; Uhl, S.A.; Bravo, M.A.; Bell, M.L. A systematic review of the physical health impacts from non-occupational exposure to wildfire smoke. J. Environ. Res. 2015, 136, 120–132.
  137. Huang, K.; Liang, F.; Yang, X.; Liu, F.; Li, J.; Xiao, Q.; Chen, J.; Liu, X.; Cao, J.; Shen, C.; et al. Long term exposure to ambient fine particulate matter and incidence of stroke: Prospective cohort study from the China-PAR project. BMJ 2019, 367, l6720.
  138. Adetona, O.; Reinhardt, T.E.; Domitrovich, J.; Broyles, G.; Adetona, A.M.; Kleinman, M.T.; Ottmar, R.D.; Naeher, L.P. Review of the health effects of wildland fire smoke on wildland firefighters and the public. Inhal. Toxicol. 2016, 28, 95–139.
  139. Holstius, D.M.; Reid, C.E.; Jesdale, B.M.; Morello-Frosch, R. Birth weight following pregnancy during the 2003 Southern California wildfires. Environ. Health Perspect. 2012, 120, 1340–1345.
  140. Fann, N.; Alman, B.; Broome, R.A.; Morgan, G.G.; Johnston, F.H.; Pouliot, G.; Rappold, A.G. The health impacts and economic value of wildland fire episodes in the US: 2008–2012. J. Sci. Total Environ. 2018, 610, 802–809.
  141. Johnston, F.; Hanigan, I.; Henderson, S.; Morgan, G.; Bowman, D. Extreme air pollution events from bushfires and dust storms and their association with mortality in Sydney, Australia 1994–2007. Environ. Res. 2011, 111, 811–816.
  142. Borchers Arriagada, N.; Palmer, A.J.; Bowman, D.M.; Morgan, G.G.; Jalaludin, B.B.; Johnston, F.H. Unprecedented smoke-related health burden associated with the 2019–20 bushfires in eastern Australia. Med. J. Aust. 2020, 213, 282–283.
  143. World Health Organization. Ambient (Outdoor) Air Quality and Health: Fact Sheet Number 313. Available online: http://www.who.int/mediacentre/factsheets/fs313/en (accessed on 22 January 2015).
  144. Osseiran, N.; Chriscaden, K. Air Pollution Levels Rising in Many of the World’s Poorest Cities; WHO: Geneva, Switzerland, 2016.
  145. Shah, A.S.V.; Langrish, J.P.; Nair, H.; McAllister, D.A.; Hunter, A.L.; Donaldson, K.; Newby, D.E.; Mills, N.L. Global association of air pollution and heart failure: A systematic review and meta-analysis. Lancet 2013, 382, 1039–1048.
  146. Koulova, A.; Frishman, W.H. Air Pollution Exposure as a Risk Factor for Cardiovascular Disease Morbidity and Mortality. Cardiol. Rev. 2014, 22, 30–36.
  147. Franklin, B.A.; Brook, R.; Pope III, C.A. Air pollution and cardiovascular disease. Curr. Probl. Cardiol. 2015, 40, 207–238.
  148. Kim, J.W.; Park, S.; Lim, C.W.; Lee, K.; Kim, B. The role of air pollutants in initiating liver disease. Toxicol. Res. 2014, 30, 65–70.
  149. Boor, P.; Casper, S.; Celec, P.; Hurbánková, M.; Beňo, M.; Heidland, A.; Amann, K.; Šebeková, K. Renal, vascular and cardiac fibrosis in rats exposed to passive smoking and industrial dust fibre amosite. J. Cell. Mol. Med. 2009, 13, 4484–4491.
  150. Omoloja, A.; Jerry-Fluker, J.; Ng, D.K.; Abraham, A.G.; Furth, S.; Warady, B.A.; Mitsnefes, M. Secondhand smoke exposure is associated with proteinuria in children with chronic kidney disease. Pediatr. Nephrol. 2013, 28, 1243–1251.
  151. Cliff, R.; Curran, J.; Hirota, J.A.; Brauer, M.; Feldman, H.; Carlsten, C. Effect of diesel exhaust inhalation on blood markers of inflammation and neurotoxicity: A controlled, blinded crossover study. Inhal. Toxicol. 2016, 28, 145–153.
  152. Wright, R.J.; Brunst, K.J. Programming of respiratory health in childhood: Influence of outdoor air pollution. Curr. Opin. Pediatr. 2013, 25, 232–239.
  153. Dehghan, A.; Khanjani, N.; Bahrampour, A.; Goudarzi, G.; Yunesian, M. The relation between air pollution and respiratory deaths in Tehran, Iran- using generalized additive models. BMC Pulm. Med. 2018, 18, 49.
  154. Tarantino, G.; Capone, D.; Finelli, C. Exposure to ambient air particulate matter and non-alcoholic fatty liver disease. World J. Gastroenterol. 2013, 19, 3951.
  155. Costa, L.G.; Cole, T.B.; Coburn, J.; Chang, Y.-C.; Dao, K.; Roque, P. Neurotoxicants are in the air: Convergence of human, animal, and in vitro studies on the effects of air pollution on the brain. BioMed Res. Int. 2014, 2014, 736385.
  156. Andersen, Z.J.; Stafoggia, M.; Weinmayr, G.; Pedersen, M.; Galassi, C.; Jørgensen, J.T.; Oudin, A.; Forsberg, B.; Olsson, D.; Oftedal, B.; et al. Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 european cohorts within the ESCAPE project. Environ. Health Perspect. 2017, 125, 107005.
  157. Giorgini, P.; Rubenfire, M.; Das, R.; Gracik, T.; Wang, L.; Morishita, M.; Bard, R.L.; Jackson, E.A.; Fitzner, C.A.; Ferri, C. Particulate matter air pollution and ambient temperature: Opposing effects on blood pressure in high-risk cardiac patients. J. Hypertens. 2015, 33, 2032–2038.
  158. Langrish, J.P.; Watts, S.J.; Hunter, A.J.; Shah, A.S.; Bosson, J.A.; Unosson, J.; Barath, S.; Lundbäck, M.; Cassee, F.R.; Donaldson, K. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ. Health Perspect. 2014, 122, 747–753.
  159. Mocevic, E.; Kristiansen, P.; Bonde, J.P. Risk of ischemic heart disease following occupational exposure to welding fumes: A systematic review with meta-analysis. Int. Arch. Occup. Environ. Health Perspect. 2015, 88, 259–272.
  160. Cai, Y.; Zhang, B.; Ke, W.; Feng, B.; Lin, H.; Xiao, J.; Zeng, W.; Li, X.; Tao, J.; Yang, Z. Associations of short-term and long-term exposure to ambient air pollutants with hypertension: A systematic review and meta-analysis. Hypertension 2016, 68, 62–70.
  161. Hajat, A.; Roux, A.D.; Castro-Diehl, C.; Cosselman, K.; Golden, S.H.; Szpiro, A.; Vedal, S.; Kaufman, J.D. The Association between Air Pollution and Stress Hormones: Evidence from the Multi-Ethnic Study of Atherosclerosis. In Proceedings of the ISEE Conference Abstracts, Sao Paulo, Brazil, 30 August–3 September 2015.
  162. Bhatnagar, A. Environmental cardiology: Studying mechanistic links between pollution and heart disease. Circ. Res. 2006, 99, 692–705.
  163. Brook, R.D.; Rajagopalan, S.; Pope III, C.A.; Brook, J.R.; Bhatnagar, A.; Diez-Roux, A.V.; Holguin, F.; Hong, Y.; Luepker, R.V.; Mittleman, M.A. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 2010, 121, 2331–2378.
  164. Zanobetti, A.; Gold, D.R.; Stone, P.H.; Suh, H.H.; Schwartz, J.; Coull, B.A.; Speizer, F.E. Reduction in heart rate variability with traffic and air pollution in patients with coronary artery disease. Environ. Health Perspect. 2010, 118, 324–330.
  165. Landrigan, P.J.; Fuller, R.; Acosta, N.J.; Adeyi, O.; Arnold, R.; Baldé, A.B.; Bertollini, R.; Bose-O’Reilly, S.; Boufford, J.I.; Breysse, P.N. The Lancet Commission on pollution and health. Lancet 2018, 391, 462–512.
  166. Beelen, R.; Raaschou-Nielsen, O.; Stafoggia, M.; Andersen, Z.J.; Weinmayr, G.; Hoffmann, B.; Wolf, K.; Samoli, E.; Fischer, P.; Nieuwenhuijsen, M. Effects of long-term exposure to air pollution on natural-cause mortality: An analysis of 22 European cohorts within the multicentre ESCAPE project. Lancet 2014, 383, 785–795.
  167. Cox, S.; Niskar, A.S.; Narayan, K.V.; Marcus, M. Prevalence of self-reported diabetes and exposure to organochlorine pesticides among Mexican Americans: Hispanic health and nutrition examination survey, 1982–1984. Environ. Health Perspect. 2007, 115, 1747–1752.
  168. Lee, D.-H.; Lee, I.-K.; Song, K.; Steffes, M.; Toscano, W.; Baker, B.A.; Jacobs, D.R. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: Results from the National Health and Examination Survey 1999–2002. Diabetes Care 2006, 29, 1638–1644.
  169. Codru, N.; Schymura, M.J.; Negoita, S.; Rej, R.; Carpenter, D.O.; Akwesasne Task Force on the Environment. Diabetes in relation to serum levels of polychlorinated biphenyls and chlorinated pesticides in adult Native Americans. Environ. Health Perspect. 2007, 115, 1442–1447.
  170. Bauer, M.; Moebus, S.; Möhlenkamp, S.; Dragano, N.; Nonnemacher, M.; Fuchsluger, M.; Kessler, C.; Jakobs, H.; Memmesheimer, M.; Erbel, R. Urban particulate matter air pollution is associated with subclinical atherosclerosis: Results from the HNR (Heinz Nixdorf Recall) study. J. Am. Coll. Cardiol. 2010, 56, 1803–1808.
  171. Williams, C.; Taylor, E.P.; Schwannauer, M. A web-based survey of mother–infant bond, attachment experiences, and metacognition in posttraumatic stress following childbirth. Infant Ment. Health J. 2016, 37, 259–273.
  172. Tonne, C.; Melly, S.; Mittleman, M.; Coull, B.; Goldberg, R.; Schwartz, J. A case–control analysis of exposure to traffic and acute myocardial infarction. Environ. Health Perspect. 2007, 115, 53–57.
  173. Hart, J.E.; Chiuve, S.E.; Laden, F.; Albert, C.M. Roadway proximity and risk of sudden cardiac death in women. Circulation 2014, 130, 1474–1482.
  174. Medina-Ramón, M.; Goldberg, R.; Melly, S.; Mittleman, M.A.; Schwartz, J. Residential exposure to traffic-related air pollution and survival after heart failure. Environ. Health Perspect. 2008, 116, 481–485.
  175. Wilker, E.H.; Mostofsky, E.; Lue, S.-H.; Gold, D.; Schwartz, J.; Wellenius, G.A.; Mittleman, M.A. Residential proximity to high-traffic roadways and poststroke mortality. J. Stroke Cerebrovasc. Dis. 2013, 22, e366–e372.
  176. Brulle, R.J.; Pellow, D.N. Environmental justice: Human health and environmental inequalities. Annu. Rev. Public Health 2006, 27, 103–124.
  177. Puett, R.C.; Hart, J.E.; Suh, H.; Mittleman, M.; Laden, F. Particulate matter exposures, mortality, and cardiovascular disease in the health professionals follow-up study. Environ. Health Perspect. 2011, 119, 1130–1135.
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