Genetics and environment are the two major factors in the development of allergic rhinitis. In the last 20 years, the incidence of allergic rhinitis has been on the rise worldwide. This trend is difficult to explain solely by genetic alterations and should take into account that changes in environmental factors also play an important role in the development of allergic rhinitis. These changes in environmental factors include mainly increasing air pollution, changes in dietary habits and nutritional structure, and decreases in bacterial and/or viral infections. This article summarizes the effects of three factors on allergic rhinitis, including air pollution, diet and nutrition, and infection.
[Air pollution] The health problems caused by air pollution have a long history. As early as 1873, Charles Harrison Blackley confirmed that grass pollen was the real cause of chytridiomycosis, but he also found that the disease was more prevalent among urban residents than rural residents. The air was so polluted that a livestock fair in December 1873 had a foggy event followed by the death of a large number of livestock. Ironically, Claude Monet, a famous French Impressionist painter, was living in London in 1901 when he saw the Waterloo Bridge near his home shrouded in thick smog, appearing in the background. He was inspired to create the famous painting “Waterloo Bridge”.
Air pollutants are mainly divided into two categories: gases and particulate matter (PM). Air pollutants are produced in two main ways: firstly, primary pollutants – including gases such as nitrogen oxides (NOx) and sulfur dioxide (SO2), as well as particulate matter such as soot – are emitted directly through the exhaust pipes or chimneys of internal combustion engines; secondly, primary pollutants in the atmosphere under the action of sunlight and humidity undergo chemical action to produce secondary pollutants – including ozone (ozone). secondary pollutants – including ozone (O3) and secondary particulate matter such as sulfate – are produced. Almost all of the original air pollutants came from the combustion of coal fuels. As society has evolved, emissions from vehicles are now a major source of air pollution, including volatile organic compounds (VOCs), inhaled particles matter, and a variety of irritant gases (NO2, SO2, O3). There is growing evidence that air pollution is closely related to the development of respiratory allergic diseases. Air pollution has a higher susceptibility in specific populations such as the elderly or children with asthma or chronic obstructive pulmonary disease (COPD). In addition, specific genetic characteristics may increase the risk of disease after exposure to air pollutants. Air pollutants are usually most strongly associated with the worsening of acute respiratory pathologies. For example, upper respiratory tract infections and worsening of COPD. Chronic exposure to pollutants affects the normal growth and development of the nasal mucosa and lungs and leads to the development of allergic rhinitis and asthma. Pollutants in the environment can cause a Th2-directed response to the initial exposure to allergens and an IgE-mediated allergic reaction after subsequent re-exposure to allergens.
It is now generally accepted that the amount and type of air pollution influences the development of allergic diseases. This is supported by epidemiological studies in two German cities: after studying 7653 children in Munich and 2623 children in Leipzig, Von Mutius et al. found that the incidence of allergic rhinitis, asthma, and positive skin tests to allergens in children in Leipzig was 2.7%, 3.9%, and 18.2%, respectively, which was significantly lower than that in children in Munich ( 8.6%, 5.9%, and 36.7%). In contrast, the air pollution profiles of the two cities differ, with Leipzig being dominated by SO2 from coal combustion as the main air pollutant, while Munich is dominated by pollutant emissions from cars. Most of the opinions suggest that air pollutants can directly cause inflammation of the respiratory mucosa, including the release of inflammatory cytokines and the aggregation of inflammatory cells. In turn, the inflammation results in an enhanced response of the organism to allergens. For example, NOX is an important indoor and outdoor air pollutant and is also a precursor substance (Precursors) for ozone production. Increased levels of NO2 in the air can lead to a range of respiratory symptoms (cough, wheezing, mucous sputum, bronchitis symptoms). The risk of asthma was significantly higher in infants exposed to high NO2 concentrations (>17.4 ppb) than in those exposed to low concentrations (<5.1 ppb). And white et al. also demonstrated that school-age children with asthma had a significant decrease in lung function after 1 h of exposure to 0.11 ppm ozone.
As environmental protection measures continue to be strengthened and global industrial pollution is curbed to varying degrees, the major air pollutants have changed at the same time. The pollution caused by diesel exhaust particle (DEP), which consists of a carbon nucleus at the center and adsorbs a variety of chemicals and metals on its surface, has received increasing attention in recent years. Most DEPs are fine particles (0.1-2.5 μm in diameter) and ultrafine particles (<0.1 μm in diameter). However, multiple DEPs can be linked together to form polymers of different sizes and shapes, and have a wider range of biological effects because they carry more chemicals. In vitro and in vivo experiments have shown that DEP may induce or exacerbate allergic inflammation in the nose through the following effects: (1) DEP has adjuvant-like effects, enhancing allergenic immune responses and promoting IgE antibody production; (2) enhancing histamine H1 receptor mRNA expression in nasal mucosa epithelial and endothelial cells, promoting interleukin (IL (2) Enhance the production of proinflammatory cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-8 in nasal mucosal epithelial cells and endothelial cells. (3) Enhanced gene transcription of T-helper cells (T-helper cells, Th) type 2 cytokines such as IL-4, IL-5 and IL-13, and decreased expression of Th1 cytokine interferon (IFN-γ) mRNA, resulting in a shift of the immune response to Th2 type. Eosinophil cationic protein (ECP); ⑤ Enhance airway hyperresponsiveness (AHR) and hypersensitize the nasal mucosa by stimulating sensory nerves. In addition, DEP has a direct immunological effect on a variety of cells (Table 1).
Table 1: Direct effects of DBP on various tissue cells
Cell type
Effect of DBP
Nasal and bronchial epithelial cells and endothelial cells
Increased cytokine expression (IL-8, eotaxin, RANTES, GM-CSF, IL-6)
Increased expression of histamine-type receptors
Upregulate ICAM-1 expression
Eosinophils
Enhance adhesion to nasal epithelial cells
Induced eosinophil degranulation
Mast cells
Increase IgE-mediated histamine release
Increased cytokine production (IL-4, IL-6)
Basophilic granulocytes
Induces histamine release in the absence of IgE
Enhance cytokine production (IL-4)
Peripheral blood mononuclear cells
Induces cytokine production (IL-8, RANTES, and TNFα production)
B cells
Increased IgE production after IL-4 and anti-CD40 stimulation
Monocyte-macrophage
Regulation of cytokine production and inhibition of prostaglandin E2 release
Regarding the biological effects of air pollutants, most studies suggest that air pollutants acting on macrophages, neutrophils, and eosinophils in the airways produce reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and hydroxyl radicals, which interact with proteins, lipids, and DNA to cause oxidative stress. (oxidative stress), leading to cellular damage. It is now recognized that inflammation is by its nature an oxidative process. It has been shown that superoxide production can be found in allergen-induced bronchial tests, and conversely, the amount of oxygen radicals in animal studies correlates with the level of antigen-induced airway hyperreactivity. Hydrogen peroxide, nitric oxide, and carbon monoxide in exhaled air can be used as markers to reflect the degree of airway inflammation. Thus, air pollutants often have a dual damaging effect: directly by inducing ROS production leading to oxidative stress and indirectly by enhancing the inflammatory response, resulting in more ROS and more intense inflammation. Long-term exposure of the respiratory tract to air pollutants is often accompanied by a loss of antioxidant components of the airway mucosa. Some drugs with antioxidant effects such as vitamin C and vitamin E can provide some protective effect against ozone-induced pulmonary responses.
[Diet and Nutrition] Since the 1990s, it has been suggested that in addition to air pollution, the increase in allergic diseases is also associated with changes in the dietary structure of Western societies. Because air pollution has been significantly controlled in recent years in some European countries, even with good air quality, the incidence of allergic diseases is still increasing. This change in diet structure includes three main aspects.
1. Decreased intake of foods with antioxidant activity in the diet
Intake of vitamin C. Water-soluble vitamin C enhances intracellular and extracellular antioxidant capacity by scavenging oxygen free radicals and inhibiting the secretion of superoxide negative ions by macrophages. In general, most studies have shown that adequate dietary vitamin C intake contributes to improved ventilation, but few studies have mentioned the relationship between vitamin C and allergic rhinitis.Rubin et al. found a 19% reduction in the risk of asthma in children aged 4-16 years with high serum vitamin C levels. Another study showed that serum vitamin C levels in adults were negatively associated with the development of wheezing symptoms.
Vitamin E intake. Fat-soluble vitamin E is a major barrier to cell membrane damage caused by antioxidants. Unlike vitamin C, in addition to its antioxidant effects, vitamin E has immunomodulatory effects. It has been suggested that vitamin E intake is negatively associated with serum IgE levels and the risk of developing allergic diseases in adults.
Fruit intake. Fruits contain large amounts of important antioxidant components. The amount of fruit consumed in the diet is strongly associated with asthma attacks, ventilatory function, and respiratory symptoms in both adults and children. A study on health and lifestyle showed a positive correlation between FEV1 values in adults and the amount of fresh fruit consumed in winter. Another example is that adequate daily intake of apples reduces the risk of asthma by 30%.
The above epidemiological studies have shown a negative association between dietary antioxidant intake and the development of allergic diseases, while many dietary intervention studies have been conducted. For example, dietary vitamin C supplementation has been used to control or prevent allergic diseases. However, the results of most of these studies have been disappointing – the results have either shown too little effect or a lack of clinical significance.
2. Imbalance in polyunsaturated fatty acid (PUFA) intake.
Black and Sharpe write that current changes in dietary fatty acid intake are paralleled by an increase in the incidence of allergic diseases. In industrialized countries, as a public health measure to reduce cardiovascular disease, dietary intake of saturated fatty acids (butter and lard) has decreased, while intake of n-6 polyunsaturated fatty acids (mostly found in margarine and vegetable oils) has increased. The reduced intake of n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are rich in PUFAs, has also been associated with the development of allergic diseases. The tantalizing aspect of this hypothesis is the suggestion that increased intake of n-6 PUFAs in margarine and vegetable oils and decreased intake of n-3 PUFAs in fish promote increased susceptibility to allergic reactions in the organism. The most common dietary polyvalent unsaturated fatty acids are linoleic acid (n-6) and linolenic acid (n-3), which are metabolized by cyclooxygenase and lipoxygenase to arachidonic acid, ultimately producing inflammatory mediators such as prostaglandin E2 (PGE2), thromboxane, and leukotrienes that promote allergic inflammation. Conversely, increasing dietary intake of n-3 linolenic acid helps to reduce the production of arachidonic acid and PGE2. This is because linolenic acid competitively inhibits linoleic acid metabolism through a single enzymatic cascade reaction. And its metabolite EPA-DHA reduces gene expression of cyclooxygenase-2 and inhibits its activity.
Margarine has 20 times more n-6 linoleic acid than butter, and margarine intake is strongly associated with the development of allergic diseases. dunder reported case-control studies showing the relationship between dietary structure and the development of allergic diseases in children aged 3 to 18 years investigated in 1980 and reviewed in 1986 and 1989. Children with allergic diseases consumed more margarine and less butter than non-atopic individuals. In the longitudinal study, atopic individuals were found to consume less butter and fish than those children without the disease. In addition, investigations in 1986 and 1989 found that children with atopic dermatitis had reduced serum levels of EPA and DHA. Total dietary fat intake was positively correlated with airway hyperresponsiveness.
Increasingly, there is a desire to prevent the development of allergic diseases by supplementing the diet with PUFA. This is despite the fact that most studies have yielded disappointing results. Still, a few studies have shown a protective effect of dietary therapy. Postnatal use of fish oil supplementation and reduced intake of n-6 PUFA in the diet resulted in a significant reduction in wheezing symptoms in atopic infants at 18 months of age. In a group of 40 atopic pregnant women treated with n-3 PUFA fish oil supplementation, no significant reduction in cord blood mononuclear cell proliferation or cytokine production was observed. However, when stimulated with feline allergens a significant reduction in IL-10 production was found in this group. There is not a large body of research and sufficient evidence to support or refute the role of dietary PUFA supplementation in preventing allergic disease.
3.Breastfeeding
Breastfeeding has now been recognized as the most ideal source of nutrition for infants. Breast milk is not only nutritious, but also promotes the establishment of a bond between mother and child. However, the relationship between breastfeeding and allergic diseases is still divided opinion. This is mainly due to the complexity of the interaction between breast milk and the infant’s intestinal microenvironment as well as the immune system. Despite this, the American Academy of Pediatrics and the European Societies of Pediatric Allergy and Clinical Immunology, Pediatric Gastroenterology, Hepatology and Nutrition recommend breastfeeding as an important part of the prevention of allergic reactions in infancy. There is evidence that breastfeeding for at least 4 months after birth significantly reduces the incidence of atopic dermatitis and wheezing in infancy.
The relationship between dietary changes and allergic diseases can be seen: 1 Decreased intake of foods rich in antioxidants (fruits, vegetables), increased intake of n-6 PUFA foods (margarine, vegetable oils), and decreased intake of n-3 PUFA (fish) foods are associated with increased incidence of asthma and atopic dermatitis. 3 Deficiency of antioxidant components in food may influence the development of allergic diseases. The mechanisms include diminished immunomodulatory and antioxidant mechanisms.4 Dietary intake of antioxidants and lipids may be important in preventing the onset of allergic reactions in women during pregnancy and early infancy.5 Breastfeeding may be helpful in reducing the incidence of allergic diseases during infancy.
The [infectious health hypothesis] has seen an increase in the incidence of allergic diseases over the past decade or so, while the incidence of infectious diseases has decreased significantly. This has been attributed to improved health care systems and better hygiene, especially in developed countries. strachan noted that the risk of developing allergic reactions and asthma was negatively correlated with the number of family members. This appears to be because improved family hygiene has reduced the chance of cross-infection between siblings, leading to an increase in allergic diseases. This led to the “hygiene hypothesis” in 1989. Explaining the hygiene hypothesis requires an understanding of the development of the immune system. Early in life, when the immune system is immature, the fetus is characterized by a Th2-dominant response. This increases the risk of developing a metabolic reaction after exposure to allergens. According to the hygiene hypothesis, infection by viruses or bacteria produces Th1-type cytokines such as IFN-γ and IL-12, which downregulate Th2-type immune responses. It is suggested that repeated exposure to microbial stimulation early in life can stimulate the immature immune system toward the Th1 phenotype, thereby reducing the risk of developing allergic disease. However, microbial infections may also lead to the exacerbation of allergic diseases. Lower airway infections such as those caused by respiratory syncytial virus, rubella virus, and pertussis bacteria are known to increase the risk of developing asthma in early childhood instead. A study with a larger sample also showed that rubella virus infection did not provide protection against allergic diseases but was strongly associated with the development of allergic diseases. Therefore, more longitudinal epidemiological studies are needed to clarify the impact of microbial infections in childhood on the development of the immune system and the pathological process of allergic diseases.
The “hygiene hypothesis” is the most convincing explanation to date for the increasing incidence of allergic diseases in the context of the increasing “westernization” of lifestyle. This phenomenon has been suggested to be the result of chronic stimulation of Toll like receptors (TLRs) on the surface of natural immune cells. The accelerated global industrialization and lifestyle changes have led to a decrease in exposure to microorganisms during infancy, and consequently to a decrease in the stimulation of TLRs on the surface of dendritic cells and NK cells, resulting in a decrease in the production of a series of cytokines, such as IL-12, IFN-α, and IFN-γ. These cytokines not only promote the development of TH1 cells, but also inhibit the action of Th2 cells. In turn, the reduction of these cytokines can cause a skewed Th1 to Th2 immune response, leading to an increased incidence of allergic diseases.
In recent years, the discovery of regulatory T cells (Treg) has given a richer meaning to the “hygiene hypothesis”: Treg cells are a specific subset of T cells with immunosuppressive functions that were discovered at the end of the last century and play an important role in mediating peripheral immune tolerance. Treg cells selectively express TLR-4, TLR-5, TLR-7, and TLR-8, and stimulation with high doses of LPS induces their proliferation and increases their suppressive activity. Therefore, long-term, chronic microbial stimulation may induce the immunosuppressive activity of Treg cells, which in turn reduces the organism’s responsiveness to allergens, and the reduction of external pathogen stimulation after “westernization” of lifestyle may contribute to the hypofunction of Treg cells in allergic diseases.