**5.3. Genetic contributions to pneumonia risk and severity**

We mentioned earlier studies reporting gender, racial, and population variability in both pneumonia incidence and outcome. Therefore, it is highly likely that these differences are the result of a complex interplay between both host and pathogen genetic backgrounds together with nongenetic factors, such as those discussed above [182]. With the recent development of fast and affordable high-throughput sequencing techniques, more studies have begun to explore the contributions of host genetics in the context of pneumonia [183–186]. The majority of these have focused on innate immune molecules, such as toll-like receptors and proinflammatory cytokines. Several associations of pneumonia susceptibility and severity with single nucleotide polymorphisms in the interleukin-6, interleukin-10, toll-like receptors TLR2, TLR4, and TLR9, C-reactive protein (CRP), and nitric oxide synthase 3 (NOS3) genes were reported [187–191]. We have summarized these in **Table 5**. Interestingly, most polymorphisms found in the cytokine genes are located in regulatory and promoter regions, where they may be affecting binding of transcription factors, such as GATA1-3, SOX, and heat shock proteins [183].

#### **5.4. Pollution models of infection and pneumonia**

Air pollution has been shown to exacerbate respiratory diseases, such as pneumonia. Air pollutants that reach the respiratory tract are currently responsible for its genesis, especially particulate matter having an aerodynamic diameter equal to or less than 10 μm, sulfur dioxide (SO<sup>2</sup> ), ground level ozone (O<sup>3</sup> ), nitrogen dioxide (NO<sup>2</sup> ), and carbon monoxide (CO) [192, 193]. However, these pollutants may also increase the risk for pneumonia by altering the function of alveolar macrophages, epithelial cells, mucociliary clearance mechanisms, particle transport, and local immunity in the lungs [194]. Because of methodological difficulties and ethical issues, there are a limited number of studies on the effects of controlled pollutant exposure and infection in humans. It has now been almost 50 years since the "infectivity model" has been created. This model is based on the study of the effects of pollutants on pulmonary activity after pollutant exposure with disease and mortality as end-points in animals, particularly rodents [147].

There are several pollution models of pneumonia infection combined with particulate matter

a higher concentration of pollutants than would be normally found in the atmosphere. This is often necessary because a higher dose of most pollutants is required for rodents versus humans to reach comparable concentrations in the distal lung and generating comparable

Ozone exposure can impair breathing, induce coughing, reduce lung function, and trigger lung diseases, such as pneumonia. The effect of ozone exposure has been associated with damage of the entire respiratory epithelia and lung immunity [202]. A study showed that

mice to clear bacteria from the lungs, and that ozone-exposed females were more affected and showed higher mortality rates than males [17, 18]. Contrarily, in the absence of ozoneinduced oxidative stress, males were more prompted to have a higher level of propagation of infection compared to females. These mechanisms appear to be mediated by surfactant biol-

Regulation of the lung inflammatory response is critical to the successful outcome of pneumonia. Exposure to air pollutants has been linked to negative lung health outcomes, and sex hormones have been shown to mediate the lung immune response, especially during lung infection. The negative impact of air pollution on lung health, both in the short and long term, is now well accepted, and air quality indexes or scales are available to alert individuals when the air quality is at harmful levels. In this chapter, we have discussed experimental and epidemiological evidence on pneumonia infection incidence in different populations, influences of air pollution and environmental exposures, and sex-specific mechanisms involving male and female hormones in the context of lung immunity. This information could help researchers better explain the differences observed in pneumonia susceptibility and lung health outcomes in men versus women. Understanding the biological basis of these differences is critical for the development of more effective prevention and management strategies for pneumonia in men and women, and could help in the development of better treatment options for these

mice infected with *K. pneumoniae* following exposure to 2 ppm of O3

[200], CO [201], and other common air pollutants. These models generally involve

Understanding the Intersection of Environmental Pollution, Pneumonia, and Inflammation: Does...

decreased the ability of

http://dx.doi.org/10.5772/intechopen.69627

19

[199], SO<sup>2</sup>

**6. Conclusion**

patients.

**Author details**

Patricia Silveyra\*, Nathalie Fuentes and Lidys Rivera

\*Address all correspondence to: psilveyra@pennstatehealth.psu.edu

The Pennsylvania State University College of Medicine, Hershey, USA

effects on lung function and immunity.

ogy and surfactant protein expression [19].

The infectivity model is used by researchers to determine the amount and concentration of pollutants at which the immune system is compromised and disease is developed. This is accomplished by challenging animals with virulent agents either before or after exposure to different concentrations of the pollutant. Exposure to NO<sup>2</sup> before and after infectious challenge in mice show significantly higher death rates [195]. Moreover, mice infected with *S. aureus* and then challenged with NO<sup>2</sup> displayed a reduction in lung bactericidal capacity [196]. Exposure to varying concentrations of NO<sup>2</sup> affects respiratory tract susceptibility, macrophage viability, systemic cell-mediated and humoral responses to viral infection in CD-1 mice inoculated intratracheally with murine cytomegalovirus [197]. Moreover, the number of viral particles capable of generating infection is lower in animals challenged with NO<sup>2</sup> than in animals exposed to filtered air. In addition, the risk of reinfection is higher in mice after NO<sup>2</sup> exposure indicating damage in the development of virus-specific immunity following a primary infection [198].


**Table 5.** Single nucleotide polymorphisms associated with pneumonia.

There are several pollution models of pneumonia infection combined with particulate matter [199], SO<sup>2</sup> [200], CO [201], and other common air pollutants. These models generally involve a higher concentration of pollutants than would be normally found in the atmosphere. This is often necessary because a higher dose of most pollutants is required for rodents versus humans to reach comparable concentrations in the distal lung and generating comparable effects on lung function and immunity.

Ozone exposure can impair breathing, induce coughing, reduce lung function, and trigger lung diseases, such as pneumonia. The effect of ozone exposure has been associated with damage of the entire respiratory epithelia and lung immunity [202]. A study showed that mice infected with *K. pneumoniae* following exposure to 2 ppm of O3 decreased the ability of mice to clear bacteria from the lungs, and that ozone-exposed females were more affected and showed higher mortality rates than males [17, 18]. Contrarily, in the absence of ozoneinduced oxidative stress, males were more prompted to have a higher level of propagation of infection compared to females. These mechanisms appear to be mediated by surfactant biology and surfactant protein expression [19].
