This study systematically evaluated the relationship between short-term exposure to PM2.5, NO2, and CO and the risk of infection with suspected respiratory pathogens using a time-stratified case-crossover design. In the single-pollutant model, we observed a significant increase in the risk of hospitalization associated with higher concentrations of these pollutants, particularly on lag day 0. A distinct effect pattern emerged, with PM2.5 and NO2 being more closely linked to bacterial infections than viral ones. Using a generalized additive model, after adjusting for confounders such as daily temperature, precipitation, wind speed, seasonality, and weekends, we identified a nonlinear relationship between PM2.5 exposure and infection risk: the risk was higher at lower concentrations, decreased as concentrations rose, and increased again at higher levels. In contrast, NO2 and CO showed a different relationship with infection risk, with an 11.66% increase in odds per unit rise in NO2 and a 0.64% increase per unit rise in CO. Subgroup analysis confirmed the robustness of these associations, especially for PM2.5, NO2, and CO exposure (per standard deviation increments), and the risk of respiratory infections. Notably, the association between PM2.5 and CO exposure and infection risk was stronger in adolescents (< 18 years) compared to adults, with no significant gender differences. Additionally, the risk associated with NO2 exposure was more pronounced in patients exposed to higher PM2.5 levels, suggesting a possible interaction between pollutants. A similar pattern was observed in patients visiting the hospital on weekends and in those enrolled after 2019. These findings provide further evidence supporting the link between acute air pollution exposure and respiratory pathogen infection, helping to fill gaps in current epidemiological knowledge.
The relationship between outdoor air pollutants and respiratory pathogens remains a key area of interest in academic research, and our study aligns with numerous findings from both domestic and international studies, while also highlighting notable distinctions. For instance, Wang et al. [7] conducted a study in Shanghai, demonstrating that a 10 µg/m3 increase in PM2.5 concentration was linked to a 0.37% rise in respiratory infection hospitalizations, which closely mirrors the 0.3% increase observed in our study on lag day 0. Similarly, research from yang et al. [8] found that on lag day 0, an interquartile increase in PM2.5 was associated with a 3.08% rise in influenza-like illness at national level.
Internationally, similar patterns have been identified. A study from South Korea [12] also showed that short-term exposure to elevated PM2.5 levels significantly increased hospitalization rates for respiratory infections, particularly among children, who appeared especially vulnerable. These findings emphasize the global public health burden posed by PM2.5 as a fine particulate matter. However, the nonlinear relationship between PM2.5 and infection risk observed in our study contrasts with the linear trends seen in other countries. For example, a nationwide study by Dominici et al. [13] in the United States found that that PM2.5 exposure consistently increased infection risk, particularly at higher concentrations, suggesting regional variations in pollutant sources and effects.
In southern Chinese cities like Guangzhou, PM2.5 primarily originates from traffic emissions, secondary organic aerosols, and industrial sources, whereas northern cities such as Beijing see higher contributions from coal burning and industrial emissions during the winter. Northern PM2.5 is more likely to contain toxic elements like heavy metals and sulfur dioxide, which, under cold and still atmospheric conditions, which are easy to accumulate under low temperature and calm wind conditions, causing acute damage to respiratory mucosa [22,23,24]. In contrast, due to the warm and humid climate in Guangzhou, pollutants are easy to diffuse in the atmosphere, and the proportion of organic carbon and sulfate in PM2.5 is high, but its acute toxicity is relatively low, which is more manifested by chronic effects on respiratory tract [25,26,27]. PM2.5 particles may form more complex chemical reactions after contact with respiratory tract, leading to different infection risk modes. These regional differences suggest that when studying the effects of air pollution on respiratory health, it is necessary to consider local pollutant composition and climatic conditions and take targeted public health interventions.
Compared to particulate matter, gaseous pollutants may directly impact respiratory susceptibility by damaging the respiratory mucosa and impairing immune function. Studies have shown that NO2, as one of the main markers of traffic pollution, can cause damage to respiratory epithelial cells through oxidative stress response, thereby increasing the chances of bacterial and viral invasion. This finding is consistent with prior literature. For example, Chen et al. [28] demonstrated that NO2 exposure can significantly increase the risk of respiratory infection in patients with chronic obstructive pulmonary disease (COPD) by triggering an inflammatory response. Similarly, our study is the first in southern China to document a significant effect of CO and NO2 on hospitalization rates for respiratory pathogen infections using a time-stratified cross-analysis method. This mirrors findings from a study [29] in America, which reported that NO2 exposure significantly elevated respiratory infection rates in children. The pronounced effect of CO exposure can be explained by its ability to inhibit hemoglobin’s oxygen-binding capacity, leading to hypoxia in the respiratory mucosa and weakening the immune defense [30, 31]. Liu et al. [30] further confirmed that short-term CO exposure was significantly associated with the incidence of acute respiratory infections.
Our findings revealed that PM2.5 and NO2 exposure showed stronger associations with bacterial infections compared to viral infections. This difference may be explained by several mechanisms. First, bacterial pathogens (0.2–2 μm) are typically larger than respiratory viruses (0.02–0.3 μm), potentially leading to different deposition patterns when interacting with air pollutants [32]. The larger bacterial cells may more readily form aggregates with PM2.5 particles in airways. Additionally, gaseous pollutants like NO2 can cause direct damage to respiratory epithelial cells and impair mucociliary clearance, which may preferentially benefit bacterial adherence and invasion. Studies have also shown that air pollutants can alter the expression of pattern recognition receptors and antimicrobial peptides, which are crucial in bacterial defense, potentially explaining the stronger association observed with bacterial infections [33].
Our findings suggest that the presence of elevated PM2.5 levels appeared to be associated with heightened health risks from gaseous pollutants. As shown in our subgroup analysis, the risk of infection associated with NO2 and CO exposure was notably higher in the presence of high PM2.5 concentrations, suggesting these pollutants may have combined effects on respiratory health.
A study from Zhu et al. [34] demonstrated that emergency department visits for respiratory diseases were 1.19% (95%Cl, 0.53%-1.85%) with combined exposure to multiple air pollutants in Chengdu, China. Similarly, research from Colombia [35] supported the existence of a synergistic effect between NO2 and PM2.5, while SO2 showed a similar effect (although not found in our study). These interactions occur because different pollutants can chemically react in the atmosphere to form new harmful substances, while individual pollutant exposure can exacerbate oxidative stress and inflammation. For instance, nitrogen dioxide-induced airway inflammation may increase the permeability of PM2.5, allowing it to penetrate deeper into the lungs, thereby worsening respiratory health outcomes [36, 37]. This evidence highlights that the combined effect of gaseous pollutants and particulate matter may be a critical factor in elevating infection risks. Future research should aim to dissect the mechanisms behind these interactions across different concentrations and population groups, ultimately providing more targeted public health policies.
Identifying more vulnerable subgroups exposed to air pollution can help reduce the burden of respiratory disease with minimal public health resources. Our study also underscores the importance of identifying vulnerable subgroups to minimize the public health burden, particularly among minors. Adolescents, as shown in our findings, appear more susceptible to respiratory pathogen infections following short-term exposure to CO and PM2.5. This aligns with existing literature indicating that adolescents are more vulnerable to air pollutants due to their developing respiratory systems and higher metabolic demands [38]. In addition, due to the immature immune system, the airway is more susceptible to inflammation and infection when exposed to air pollutants [38, 39].
This study has several notable strengths as follows. First, this is the first large-scale investigation (n = 96,927) in southern China to examine the association between short-term exposure to air pollutants and daily risk of hospitalization for respiratory pathogen infections. The large sample size enhances the study’s statistical power and allows for more reliable and robust conclusions. Secondly, this study adopts a time-stratified and cross-sectional study design, which effectively controls potential confounding factors within individuals, making the research results more reliable. Additionally, stratified analyses revealed important subgroup differences, particularly highlighting the increased susceptibility of minors to respiratory infections under air pollution exposure, as well as the interactions between PM2.5 and NO2/CO. These findings provide valuable insights for the development of targeted public health policies aimed at protecting different demographic groups.
Despite its strengths, this study has some important limitations that warrant discussion. First and foremost, all patients were from a single hospital, the first affiliated hospital of Guangzhou Medical University, and the study was confined to one region. This geographical limitation may affect the generalizability of the findings to other regions, where differences in pollutant concentration and composition may result in varying health outcomes. Furthermore, the chemical composition and toxicity of air pollutants can vary substantially across different geographical locations due to diverse emission sources, meteorological conditions, and atmospheric chemistry. Thus, the conclusions drawn may not fully apply to areas with different pollution levels or climatic conditions. Future multi-center studies across different geographical regions would be valuable to validate and expand upon our findings.
In summary, this study identifies a significant association between short-term exposure to NO2 and CO and an increased risk of hospitalization for respiratory pathogen infections, with each unit increase associated with 11.66% and 0.64% elevated odds respectively, particularly at lag day 0. These findings support implementing stricter emission controls and establishing low-emission zones around vulnerable populations in urban areas. Given the observed synergistic effects between pollutants, we recommend developing comprehensive air quality management approaches that include early warning systems and enhanced indoor air quality standards, especially in facilities serving minors. Public health policies should prioritize protecting susceptible groups through targeted interventions and strengthened public education during high-pollution periods. Future research should further explore pollutant interactions and their long-term health effects on different population groups to develop more precise preventive measures.
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