Editing Ozone (section)

===Acute ozone exposure===
Acute ozone exposure ranges from hours to a few days. Because ozone is a gas, it directly affects the lungs and the entire respiratory system. Inhaled ozone causes inflammation and acute—but reversible—changes in lung function, as well as airway hyperresponsiveness.<ref>{{cite journal |last1=Jule |first1=Y. |last2=Michaudel |first2=C. |last3=Fauconnier |first3=L. |last4=Togbe |first4=D. |last5=Riffel |first5=B. |year=2018 |title=Ozone-induced acute and chronic alterations in the lung in mice: a combined digital imaging and functional analysis |journal=European Respiratory Journal |volume=52 |page=4313}}</ref> These changes lead to shortness of breath, wheezing, and coughing which may exacerbate lung diseases, like asthma or chronic obstructive pulmonary disease (COPD) resulting in the need to receive medical treatment.<ref>{{cite journal |last1=Burnett |first1=R. T. |last2=Brook |first2=J. R. |last3=Yung |first3=W. T. |last4=Dales |first4=R. E. |last5=Krewski |first5=D. |year=1997 |title=Association between ozone and hospitalization for respiratory diseases in 16 Canadian cities |journal=Environmental Research |volume=72 |issue=1 |pages=24–31 |bibcode=1997ER.....72...24B |pmid=9012369 |doi=10.1006/enrs.1996.3685}}</ref><ref>{{cite journal |last1=Desqueyroux |first1=H. |last2=Pujet |first2=J. C. |last3=Prosper |first3=M. |last4=Squinazi |first4=F. |last5=Momas |first5=I. |year=2002 |title=Short-term effects of low-level air pollution on respiratory health of adults suffering from moderate to severe asthma |journal=Environmental Research |volume=89 |issue=1 |pages=29–37 |bibcode=2002ER.....89...29D |pmid=12051782 |doi=10.1006/enrs.2002.4357}}</ref> Acute and chronic exposure to ozone has been shown to cause an increased risk of respiratory infections, due to the following mechanism.<ref>{{cite journal |last1=Gent |first1=J. F. |last2=Triche |first2=E. W. |last3=Holford |first3=T. R. |last4=Belanger |first4=K. |last5=Bracken |first5=M. B. |last6=Beckett |first6=W. S. |last7=Leaderer |first7=B. P. |year=2003 |title=Association of low-level ozone and fine particles with respiratory symptoms in children with asthma |journal=JAMA |volume=290 |issue=14 |pages=1859–1867 |pmid=14532314 |doi=10.1001/jama.290.14.1859 |doi-access=free}}</ref>

Multiple studies have been conducted to determine the mechanism behind ozone's harmful effects, particularly in the lungs. These studies have shown that exposure to ozone causes changes in the immune response within the lung tissue, resulting in disruption of both the innate and adaptive immune response, as well as altering the protective function of lung epithelial cells.<ref name="ReferenceA">{{cite journal |last1=Al-Hegelan |first1=M. |last2=Tighe |first2=R. M. |last3=Castillo |first3=C. |last4=Hollingsworth |first4=J. W. |title=Ambient ozone and pulmonary innate immunity |journal=Immunol Res |year=2011 |volume=49 |issue=1–3 |pages=173–91 |pmid=21132467 |doi=10.1007/s12026-010-8180-z |pmc=3747041}}</ref> It is thought that these changes in immune response and the related inflammatory response are factors that likely contribute to the increased risk of lung infections, and worsening or triggering of asthma and reactive airways after exposure to ground-level ozone pollution.<ref name="ReferenceA"/><ref name="ncbi.nlm.nih.gov">Informed Health Online [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. The innate and adaptive immune systems. 2010 Dec 7 [Updated 2016 Aug 4]. Available from https://www.ncbi.nlm.nih.gov/books/NBK279396/</ref>

The innate (cellular) immune system consists of various chemical signals and cell types that work broadly and against multiple pathogen types, typically bacteria or foreign bodies/substances in the host.<ref name="ncbi.nlm.nih.gov"/><ref name="Travers P 2001">Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The components of the immune system. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27092/</ref> The cells of the innate system include phagocytes, neutrophils,<ref name="Travers P 2001"/> both thought to contribute to the mechanism of ozone pathology in the lungs, as the functioning of these cell types have been shown to change after exposure to ozone.<ref name="ncbi.nlm.nih.gov"/> Macrophages, cells that serve the purpose of eliminating pathogens or foreign material through the process of "phagocytosis",<ref name="Travers P 2001"/> have been shown to change the level of inflammatory signals they release in response to ozone, either up-regulating and resulting in an inflammatory response in the lung, or down-regulating and reducing immune protection.<ref name="ReferenceA"/> Neutrophils, another important cell type of the innate immune system that primarily targets bacterial pathogens,<ref name="Travers P 2001"/> are found to be present in the airways within 6 hours of exposure to high ozone levels. Despite high levels in the lung tissues, however, their ability to clear bacteria appears impaired by exposure to ozone.<ref name="ReferenceA"/>

The adaptive immune system is the branch of immunity that provides long-term protection via the development of antibodies targeting specific pathogens and is also impacted by high ozone exposure.<ref name="ncbi.nlm.nih.gov"/><ref name="Travers P 2001"/> Lymphocytes, a cellular component of the adaptive immune response, produce an increased amount of inflammatory chemicals called "cytokines" after exposure to ozone, which may contribute to airway hyperreactivity and worsening asthma symptoms.<ref name="ReferenceA"/>

The airway epithelial cells also play an important role in protecting individuals from pathogens. In normal tissue, the epithelial layer forms a protective barrier, and also contains specialized ciliary structures that work to clear foreign bodies, mucus and pathogens from the lungs. When exposed to ozone, the cilia become damaged and mucociliary clearance of pathogens is reduced. Furthermore, the epithelial barrier becomes weakened, allowing pathogens to cross the barrier, proliferate and spread into deeper tissues. Together, these changes in the epithelial barrier help make individuals more susceptible to pulmonary infections.<ref name="ReferenceA"/>

Inhaling ozone not only affects the immune system and lungs, but it may also affect the heart as well. Ozone causes short-term autonomic imbalance leading to changes in heart rate and reduction in heart rate variability;<ref>{{cite journal |last1=Gold |first1=D. R. |last2=Litonjua |first2=A. |last3=Schwartz |first3=J. |last4=Lovett |first4=E. |last5=Larson |first5=A. |last6=Nearing |first6=B. |last7=Verrier |first7=R. |year=2000 |title=Ambient pollution and heart rate variability |journal=Circulation |volume=101 |issue=11 |pages=1267–1273 |pmid=10725286 |doi=10.1161/01.cir.101.11.1267 |doi-access=free}}</ref> and high levels exposure for as little as one-hour results in a supraventricular arrhythmia in the elderly,<ref>{{cite journal |last1=Sarnat |first1=S. E. |last2=Suh |first2=H. H. |last3=Coull |first3=B. A. |last4=Schwartz |first4=J. |last5=Stone |first5=P. H. |last6=Gold |first6=D. R. |year=2006 |title=Ambient particulate air pollution and cardiac arrhythmia in a panel of older adults in Steubenville, Ohio |journal=Occupational and Environmental Medicine |volume=63 |issue=10 |pages=700–706 |pmid=16757505 |doi=10.1136/oem.2006.027292 |pmc=2078044}}</ref> both increase the risk of premature death and stroke. Ozone may also lead to vasoconstriction resulting in increased systemic arterial pressure contributing to increased risk of cardiac morbidity and mortality in patients with pre-existing cardiac diseases.<ref>{{cite journal |last1=Brook |first1=R. D. |last2=Brook |first2=J. R. |last3=Urch |first3=B. |last4=Vincent |first4=R. |last5=Rajagopalan |first5=S. |last6=Silverman |first6=F. |year=2002 |title=Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults |journal=Circulation |volume=105 |issue=13 |pages=1534–1536 |pmid=11927516 |doi=10.1161/01.cir.0000013838.94747.64 |doi-access=free}}</ref><ref>{{cite journal |last1=Zanobetti |first1=A. |last2=Canner |first2=M. J. |last3=Stone |first3=P. H. |last4=Schwartz |first4=J. |last5=Sher |first5=D. |last6=Eagan-Bengston |first6=E. |last7=Gold |first7=D. R. |year=2004 |title=Ambient pollution and blood pressure in cardiac rehabilitation patients |journal=Circulation |volume=110 |issue=15 |pages=2184–2189 |pmid=15466639 |doi=10.1161/01.cir.0000143831.33243.d8 |doi-access=free}}</ref>