Source: Journal of Clinical Pulmonology

In recent decades, air pollution has increased with the progress of industrialization, especially in recent years due to the large amount of automobile exhaust emissions, air pollutants have shown an upward trend in large and medium-sized cities, and have become a serious environmental health problem faced by mankind. . Among atmospheric pollutants, particulate matter (PM) pollution is the most harmful to human health. PM can be divided into coarse particles (2.5-5 μm, PM10) and fine particles (0.1-2. 5 μm, PM2.5) and ultra-fine particles (<0.1 μm). The diameter of atmospheric particulate matter determines the location where it finally enters the respiratory tract: 2. 5μm particulate matter deposits in the lungs can reach 83%, while 8.2μm and 11.5μm particles only 49% and 31% deposited, particulate matter The size is inversely proportional to the total amount of deposits in the lungs. Particles with a diameter greater than 10 μm are easily removed by respiratory mucus and ciliary systems, while particles with a diameter less than 10 μm can enter the lower respiratory tract, especially PM2.5 is easily deposited in the bronchiole and alveoli, and can enter the blood circulation. Therefore, in addition to the impact on the lungs, PM2.5 will have a certain impact on various systems throughout the body. This article reviews the impact of PM2.5 on systemic diseases and related mechanisms.

 

1. PM2.5 and respiratory diseases

 

1. PM2.5 and chronic obstructive pulmonary disease

 

Chronic obstructive pulmonary disease (referred to as COPD) is characterized by incompletely reversible airflow limitation, which is usually progressive and is related to the lung's excessive inflammatory response to toxic particles and gases. COPD has become an important public health problem in recent years. Prevention of acute exacerbation of COPD (AECOPD) is even more important in the prevention of COPD. In recent years, epidemiological studies have suggested that approximately 30% of the causes of AECOPD may be related to air pollution. Joel et al. comprehensively analyzed atmospheric PM2.5 monitoring data and daily death number data in six cities in the United States, and found that when the average daily PM2.5 concentration increased by 10 μg/m3, the daily deaths due to AECOPD increased by 1.5%. Toxicological experiments have shown that PM2.5 can impair the phagocytic function of rat alveolar macrophages (AM) and induce AM cells to secrete the inflammatory factors nitric oxide (NO), interleukin-8 (IL-8), tumor necrosis Factor-α (TNF-α), etc.; PM2.5 can also inhibit mitochondrial succinate dehydrogenase activity of human lung fibroblasts, and cause cytoplasmic lactate dehydrogenase (LDH) and acid phosphatase (ACP) to the cell membrane External leakage. Studies have confirmed that PM2.5 can cause damage to the red blood cells of patients with COPD, which reduces the activity of phosphotyrosinase and glucose 6 phosphate dehydrogenase, and reduces the anion exchange function and antioxidant capacity. The main mechanism of PM causing AECO-PD may be oxidative stress and anti-oxidation imbalance. This study also confirmed that short-term exposure to PM2.5 can aggravate chronic airway inflammation and oxidative stress in passive smoking rats. The generation of large amounts of oxygen free radicals (ROS), which aggravates the chronic inflammation of the respiratory tract, is an important cause of AECOPD. The oxidative stress caused by PM increases the expression of Atg5 and Beclin1, which plays an important role in the autophagy process of A549 cells, which is also an important reason for PM2.5 to reduce lung function.

 

2. PM2.5 and bronchial asthma

 

Bronchial asthma is a chronic airway inflammation involving multiple cells and cellular components. Such inflammation is often accompanied by increased airway responsiveness, leading to repeated symptoms of wheezing, shortness of breath, chest tightness, and/or cough. The acute attack of bronchial asthma has brought great health hazards and economic burden to the social population. Therefore, it is particularly important to avoid the causes of asthma and study related mechanisms. The study found that after adjusting for weather, temperature, day and night changes, seasons, age and other influencing factors, there is still a certain correlation between the PM2.5 concentration of the patient's long-term residence and the acute attack of asthma. In winter, the concentration of smoke (mainly PM2.5) in the atmosphere increases, especially the next day after the increase, the number of people who can see a doctor for an asthma attack can increase significantly; and PM2.5 has a good effect on acute asthma attacks Warning function. The exact mechanism of the acute attack of PM2.5 into asthma is currently unclear. It is currently believed that PM2.5 penetrates the alveolar epithelial cells and enters the blood circulation, and releases biologically active substances in the blood to promote the occurrence of allergic inflammation. The mechanism of acute exacerbation of COPD caused by oxidative stress is the same. After inhaling PM2.5, oxygen free radicals (ROS) are formed in the body, which can make NF-κβ and activator protein-1 (AP-1) in the airway epithelium. ) Activation, the activation of NF-κβ can make the genes of inflammatory factors [IL-1β, IL-8, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), etc.] Expression is up-regulated. These inflammatory mediators can chemoattract and activate the relevant inflammatory cells so that the chronic inflammatory state of asthma persists.

 

3. PM 2.5 and lung cancer

 

A series of epidemiological investigations have explored the relationship between PM2.5 exposure and lung cancer. Although the results of PM2.5 and lung cancer risk differ among these articles, most articles have confirmed this relationship. exist. The latest research found that PM2.5 is significantly associated with the increased risk of lung cancer. For every 10 μg/m3 increase in PM2.5 concentration, the OR value of lung cancer is 1.29, 95%, and the CI is 0.95 to 1.76. This is similar to the results of a recent meta-study OR = 1.09 (95% CI: 1.04 to 1.14). Lung cancer occupies the first place in the incidence of tumors, which significantly increases the social burden and the personal financial burden of patients. Therefore, reducing the risk of PM exposure may benefit a large proportion of the population. The specific mechanism by which PM2.5 exposure leads to lung cancer is still unclear. It may be caused by the long-term stimulation of lung epithelial cells by the ROS produced by it.

 

2. PM2.5 and cardiovascular diseases

 

Epidemiological studies have found that increasing the concentration of PM2.5 in the atmosphere in a short time can induce arrhythmias, aggravate heart failure, aggravate ischemic cardiomyopathy and ischemic stroke. Recent meta-analysis results have shown a positive correlation between PM2.5 exposure and heart variability (HRV), and may suggest a poor prognosis for cardiovascular events. Animal studies have shown that after mice are exposed to environmental PM2.5, mitochondrial function is impaired in the heart tissue, and it is significantly related to the decrease in myocardial contractility. The apolipoprotein E gene knockout mouse model can cause vascular inflammation after exposure to PM2.5, and atherosclerosis is further exacerbated. PM can also promote vascular calcification by activating the NF-κB inflammation signaling pathway. The mechanism by which PM causes cardiovascular diseases is more complicated. There are several pathogenic pathways: ① Stimulate lung epithelial cells or cells in the lung to release pre-inflammatory factors and vasoactive mediators; ② Activate lung receptors, thereby affecting autonomic nerve function ; ③ PM2.5 from the alveolar epithelium into the lung tissue space can enter the microcirculation through vascular endothelial cells, which as an exogenous tissue factor can activate the vascular endothelial and coagulation / fibrinolysis system, which in turn causes damage to the cardiovascular system. In addition, PM particles are considered to be an important factor in stimulating the autonomic nervous system (ANS), which can affect autonomic balance, which may lead to cardiovascular risk and susceptible arrhythmia through vasoconstriction.

 

3. PM2. 5 and digestive diseases

 

Non-alcoholic fatty liver disease (NAFLD) refers to the clinical pathological syndrome caused by the exclusion of alcohol and other clear liver damage factors, with diffuse hepatocellular bullous fat becoming the main feature. Studies have shown that the prevalence of NAFLD in Western developed countries is 20% to 33%, so NAFLD needs to attract enough attention. A nutritional survey involving 4582 adults showed that serum alanine aminotransferase (ALT) increased significantly after exposure to environmental pollutants (mainly PM2.5). In the age, race, gender, body mass index, poverty income ratio After correction for factors such as insulin resistance, ALT is still significantly increased and with PM2.5 dose, Kupffer cells proliferate significantly. The activation of Kupffer cells can release a large number of cytokines, which in turn triggers inflammation and the synthesis of collagen by hepatic stellate cells The protein eventually causes liver fibrosis. PM can also produce a large amount of ROS through enzymatic reactions, and oxidative stress and insulin resistance may be the central link of NAFLD.

 

In summary, the increase in PM2.5 concentration can cause and aggravate systemic damage to the whole body. This damage includes the body's immune allergy and oxidative stress caused by PM2.5, which in turn leads to systemic inflammatory reactions of the respiratory system, circulatory system, and digestive system, and mediates organ damage. Therefore, it is particularly important to do personal protection and reduce pollutants. With the development of industry and transportation, PM2.5 pollution will become more and more serious, so strengthening population protection and reducing atmospheric particulate pollution will become the focus of future work. Therefore, future goals should be based on mitigating air pollution and making air pollution predictions so that individuals can protect themselves in advance, thereby reducing the occurrence of systemic diseases throughout the body. In addition, more in-depth research should be conducted on the relevant mechanisms to lay a theoretical foundation, clinical basis and corresponding preventive strategies for the prevention and treatment of existing system damage by sudden climate events.