Air pollution exposure is a public health emergency, which attributes globally to an estimated seven million deaths on a yearly basis We are all exposed to air pollutants, varying from ambient air pollution hanging over cities to dust inside the home. It is a mixture of airborne particulate matter and gases that can be subdivided into three categories based on particle diameter. The smallest category called PM₀.₁ is the most abundant. A fraction of the particles included in this category might enter the blood stream spreading to other parts of the body. As air pollutants can enter the body via the lungs and gut, growing evidence links its exposure to gastrointestinal and respiratory impairments and diseases, like asthma, rhinitis, respiratory tract infections, Crohn's disease, ulcerative colitis, and abdominal pain. It has become evident that there exists a crosstalk between the respiratory and gastrointestinal tracts, commonly referred to as the gut-lung axis. Via microbial secretions, metabolites, immune mediators and lipid profiles, these two separate organ systems can influence each other. Well-known immunomodulators and gut health stimulators are probiotics, prebiotics, together called synbiotics. They might combat air pollution-induced systemic inflammation and oxidative stress by optimizing the microbiota composition and microbial metabolites, thereby stimulating anti-inflammatory pathways and strengthening mucosal and epithelial barriers. Although clinical studies investigating the role of probiotics, prebiotics, and synbiotics in an air pollution setting are lacking, these interventions show promising health promoting effects by affecting the gastrointestinal- and respiratory tract. This review summarizes the current data on how air pollution can affect the gut-lung axis and might impact gut and lung health. It will further elaborate on the potential role of probiotics, prebiotics and synbiotics on the gut-lung axis, and gut and lung health.

Asthma is a respiratory disease that can be exacerbated by certain environmental factors. Both formaldehyde (FA) and PM₂.₅, the most common indoor and outdoor air pollutants in mainland China, are closely associated with the onset and development of asthma. To date, however, there is very little report available on whether there is an exacerbating effect of combined exposure to FA and PM₂.₅ at ambient concentrations. In this study, asthmatic mice were exposed to 1 mg/m³ FA, 1 mg/kg PM₂.₅, or a combination of 0.5 mg/m³ FA and 0.5 mg/kg PM₂.₅, respectively. Results demonstrated that both levels of oxidative stress and inflammation were significantly increased, accompanied by an obvious decline in lung function. Further, the initial activation of p38 MAPK and NF-κB that intensified the immune imbalance of asthmatic mice were found to be visibly mitigated following the administration of SB203580, a p38 MAPK inhibitor. Noteworthily, it was found that combined exposure to the two at ambient concentrations could significantly worsen asthma than exposure to each of the two alone at twice the ambient concentration. This suggests that combined exposure to formaldehyde and PM₂.₅ at ambient concentrations may have a synergistic effect, thus causing more severe damage in asthmatic mice. In general, this work has revealed that the combined exposure to FA and PM₂.₅ at ambient concentrations can synergistically aggravate asthma via the p38 MAPK pathway in mice.

Limited data were on the acute respiratory responses in the elderly in response to personal exposure of particulate matter (PM). In order to evaluate the changes of airway inflammation and pulmonary functions in the elderly in response to individual exposure of particles (PM₁.₀, PM₂.₅ and PM₁₀), we analyzed 43 elderly subjects with either asthma, chronic obstructive pulmonary disease (COPD) or Asthma COPD Overlap (ACO) and 40 age-matched subjects without asthma nor COPD in an urban community in Shanghai, China. Data were collected at the baseline and in 6 follow-ups from August 2016 to December 2018, once every 3 months except for the last twice with a 6-month interval. In each follow-up, pulmonary functions, fractional exhaled nitric oxide (FeNO), 7-day continuous personal exposure to airborne particles were measured. Multivariate linear mixed effect regression models were applied to investigate the quantitative changes of pulmonary functions and FeNO in two respective groups. The results showed that on average 4.7 follow-up visits were completed in each participant. In subjects with CRDs, an inter-quartile range (IQR) increase of personal exposure to PM₁.₀, PM₂.₅ and PM₁₀ was significantly associated with an average increase of FeNO(Lag1) of 6.7 ppb (95%CI 1.2, 9.9 ppb), 6.2 ppb (95%CI 1.5, 12.0 ppb) and 5.6 ppb (95%CI 1.5, 11.0 ppb), respectively, and an average decrease of FEV1(Lag2) of −3.6 L (95%CI -6.0, −1.1 L), −3.6 L (95%CI -6.4, −0.8 L) and −3.2 L (95%CI -5.8, −0.6 L), respectively, in the single-pollutant model. These associations remained consistent in the two-pollutant models adjusting for gaseous air pollutants. Stratified analysis showed that subjects with lower BMI, females and non-allergies were more sensitive to particle exposure. No robust significant effects were observed in the subjects without CRDs. Our study provided data on the susceptibility of the elderly with CRDs to particle exposure of PM₁.₀ and PM₂.₅, and the modification effects by BMI, gender and history of allergies.

Allergic diseases have been one of the leading causes of chronic disorders in the United States. Animal studies have suggested that exposures to perchlorate, nitrate, and thiocyanate could induce allergic inflammation. However, the associations have not been examined among general populations. Here, we investigated data of 7030 participants aged ≥6 years from the National Health and Nutritional Examination Survey (NHANES) 2005–2006. Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography combined with electrospray tandem mass spectrometry. Information on allergic symptoms (hay fever, allergy, rash, sneeze, wheeze, eczema, and current asthma) was collected by questionnaire. Allergic sensitization was defined by a concentration ≥150 kU/L for total immunoglobulin E (IgE) levels. The associations were estimated using multivariate-adjusted logistic regression models. A positive association was observed for urinary nitrate and eczema (p < 0.001 for the trend). Compared with quartile 1 (lowest quartile), the odds ratios of eczema with 95% confidence intervals [ORs (95% CIs)] from quartiles 2 to 4 were 1.72 (95% CI, 1.41, 2.09), 1.94 (1.53, 2.47) and 2.10 (1.49, 2.97) for urinary nitrate. In addition, urinary thiocyanate was positively related to sneeze (ORQ₄ ᵥₛ. Q₁: 1.25, 95% CI: 1.01, 1.55; p = 0.015 for the trend). However, urinary perchlorate was not correlated with any allergic-related outcome. Additionally, the associations were different among subgroups in a four-level polytomous model. Thus, our results suggested that exposures to nitrate and thiocyanate may be associated with allergic symptoms. Further investigations are warranted to concentrate on the practical strategies to monitor exposure levels and the latent mechanisms of the relationship between exposure and allergy.

Some studies have indicated that formaldehyde, a ubiquitous environmental pollutant, can induce or aggravate allergic asthma. Epidemiological studies have also shown that the relative humidity indoors may be an independent and a key factor associated with the aggravation of allergic asthma. However, the synergy of humidity and formaldehyde on allergic asthma and the mechanism underlying this effect remain largely unknown. In this study, we aim to determine the effect of high relative humidity and/or formaldehyde exposure on allergic asthma and explore the underlying mechanisms. Male Balb/c mice were modeled with ovalbumin (OVA) and exposure to 0.5 mg/m3 formaldehyde and/or different relative humidity (60%/75%/90%). Histopathological changes, pulmonary function, Th1/Th2 balance, the status of mucus hypersecretion and the levels of inflammatory factors were detected to assess the exacerbation of allergic asthma. The levels of the transient receptor potential vanilloid 4 (TRPV4), calcium ion and the activation of p38 mitogen-activated protein kinases (p38 MAPK) were detected to explore the underlying mechanisms. The results showed that exposure to high relative humidity or to 0.5 mg/m3 formaldehyde alone had a slight, but not significant, affect on allergic asthma. However, the pathological response and airway hyperresponsiveness (AHR) were greatly aggravated by simultaneous exposure to 0.5 mg/m3 formaldehyde and 90% relative humidity. Blocking TRPV4or p38 MAPK using HC-067047 and SB203580 respectively, effectively alleviated the exacerbation of allergic asthma induced by this simultaneous exposure to formaldehyde and high relative humidity. The results show that when formaldehyde and high relative humidity are present this can enhance the activation of the TRPV4 ion channel in the lung leading to the aggravation of the p38 MAPK activation, resulting in the exacerbation of inflammation and hypersecretion of mucus in the airways.

Epidemiology suggests ambient temperature is the triggers and potential activator of asthma. The role of high and low temperatures on airway inflammation of asthma, and the underlying molecular mechanism are not yet understood. A mouse model of asthma was adopted in our experiment. The BALB/c mice were exposed at different temperature for 4 h (2 h in the morning and 2 h in the afternoon) on weekday. The exposure temperatures were 10 °C, 24 °C and 40 °C. Ovalbumin (OVA) was used to sensitize the mice on days 14, 18, 22, 26, and 30, followed by an aerosol challenge for 30 min from day 32–38. After the final OVA challenge, lung function, serum protein and pulmonary inflammation were assessed. Comparing the OVA with the saline group at 24 °C, we saw a significant increase in: serum Total-IgE (p < 0.05); OVA-sIgE (p < 0.01); IL-4 (p < 0.05); IL-1β (p < 0.01); IL-6 (p < 0.01); TNF-α (p < 0.01); and the ratio of IL-4/IFN-γ (p < 0.01). At the same time, there was a significant decrease in IFN-γ (p < 0.01). As the temperature increase, there is a U shape for immune proteins and pro-inflammatory factors with a peak value at 24 °C, exception for IFN-γ (inverted U-shape). After the high and low temperature exposure, the Ri and Re increased significantly, while Cldyn decreased significantly compared with the 24 °C group. Histopathological analysis of the OVA groups showed airway remodeling, airway wall thickening and deforming, and subepithelial fibrosis. More obvious changes were found in the high and low temperature exposure groups. The immunohistochemistry suggested that TRPs changed with temperatures. High and low temperatures can aggravate airway inflammation in a mouse model of asthma. TRPs play an important role in temperature aggravation of allergic asthma. The results suggest that asthmatics should avoid exposure to high and low temperatures for too long time.

Little information exists on interaction effects between air pollution and influenza vaccination on allergic respiratory diseases. We conducted a large population-based study to evaluate the interaction effects between influenza vaccination and long-term exposure to ambient air pollution on allergic respiratory diseases in children and adolescents.A cross-sectional study was investigated during 2012–2013 in 94 schools from Seven Northeastern Cities (SNEC) in China. Questionnaires surveys were obtained from 56 137 children and adolescents aged 2–17 years. Influenza vaccination was defined as receipt of the influenza vaccine. We estimated air pollutants exposure [nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters ≤1 μm (PM1), ≤2.5 μm (PM2.5) and ≤10 μm (PM10)] using machine learning methods. We employed two-level generalized linear mix effects model to examine interactive effects between influenza vaccination and air pollution exposure on allergic respiratory diseases (asthma, asthma-related symptoms and allergic rhinitis), after controlling for important covariates.We found statistically significant interactions between influenza vaccination and air pollutants on allergic respiratory diseases and related symptoms (doctor-diagnosed asthma, current wheeze, wheeze, persistent phlegm and allergic rhinitis). The adjusted ORs for doctor-diagnosed asthma, current wheeze and allergic rhinitis among the unvaccinated group per interquartile range (IQR) increase in PM1 and PM2.5 were significantly higher than the corresponding ORs among the vaccinated group [For PM1, doctor-diagnosed asthma: OR: 1.89 (95%CI: 1.57–2.27) vs 1.65 (95%CI: 1.36–2.00); current wheeze: OR: 1.50 (95%CI: 1.22–1.85) vs 1.10 (95%CI: 0.89–1.37); allergic rhinitis: OR: 1.38 (95%CI: 1.15–1.66) vs 1.21 (95%CI: 1.00–1.46). For PM2.5, doctor-diagnosed asthma: OR: 1.81 (95%CI: 1.52–2.14) vs 1.57 (95%CI: 1.32–1.88); current wheeze: OR: 1.46 (95%CI: 1.21–1.76) vs 1.11 (95%CI: 0.91–1.35); allergic rhinitis: OR: 1.35 (95%CI: 1.14–1.60) vs 1.19 (95%CI: 1.00–1.42)]. The similar patterns were observed for wheeze and persistent phlegm. The corresponding p values for interactions were less than 0.05, respectively. We assessed the risks of PM1-related and PM2.5-related current wheeze were decreased by 26.67% (95%CI: 1.04%–45.66%) and 23.97% (95%CI: 0.21%–42.08%) respectively, which was attributable to influenza vaccination (both p for efficiency <0.05).Influenza vaccination may play an important role in mitigating the detrimental effects of long-term exposure to ambient air pollution on childhood allergic respiratory diseases. Policy targeted at increasing influenza vaccination may yield co-benefits in terms of reduced allergic respiratory diseases.

Around the globe, worsening air pollution is spawning major public health and environmental concerns, especially in the poorest and most populous cities. As a major secondary air pollutant, ozone is a potential risk factor for exacerbated asthma, although the underlying mechanisms remain uncertain. In this study, we aim to investigate the role of ozone on asthma exacerbation using a classic asthmatic model with allergic airway inflammation by treating Balb/c mice with ovalbumin (OVA). Our study shows ozone exposure significantly exacerbated OVA-induced asthmatic phenotypes, including serum immunoglobulin, Th cytokines, inflammatory cell counts, mucus production, airway remodeling, and airway hyper-responsiveness (AHR). Interestingly, expression of transient receptor potential cation channel subfamily V member1 (TRPV1) was also significantly elevated in ozone-exacerbated asthmatic mice and that treatment with TRPV1 antagonist effectively suppressed AHR, airway inflammation and remodeling. The underlying mechanisms of these effects may be associated with suppression of neuropeptide calcitonin gene-related peptide (CGRP) and thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine. Base on the role of TRPV1 in allergic asthma, this study further revealed that inhibition of TRPV1 by TRPV1 antagonist has significant anti-inflammatory effects on ozone-induced asthma exacerbation in this study. Induction of TRPV1 expression may be an important mechanism underlying the increased risks for asthma after exposure to environmental pollutants.

Particulate matter with diameters <2.5 μm (i.e., PM₂.₅) has multiple natural and anthropological sources. The association between PM₂.₅ and the exacerbation of respiratory allergy and asthma has been well studied, but the components of PM₂.₅ that are responsible for allergies have not yet been determined. Here, we elucidated the effects of aqueous and organic extract of PM₂.₅ collected during four seasons in November 2014–December 2015 in two cities (Kawasaki, an industrial area and Fukuoka, an urban area affected by transboundary pollution matter) of Japan on respiratory health. Ambient PM₂.₅ was collected by high-volume air samplers and extracted into water soluble and lipid soluble components. Human airway epithelial cells, murine bone marrow-derived antigen-presenting cells (APC) and splenocytes were exposed to PM₂.₅ extracts. We measured the cell viability and release of interleukin (IL)-6 and IL-8 from airway epithelial cells, the DEC205 and CD86 expressions on APCs and cell proliferation, and TCR and CD19 expression on splenocytes. The water-soluble or aqueous extracts, especially those from Kawasaki in fall, had a greater cytotoxic effect than the lipid-soluble or organic extracts in airway epithelial cells, but they caused almost no pro-inflammatory response. Extract of fall, especially the aqueous extract from Fukuoka, increased the DEC205 and CD86 expressions on APC. Moreover, aqueous extracts of fall, summer, and spring from Fukuoka significantly increased proliferation of splenocytes. Organic extract of spring and summer from Kawasaki significantly elevated the TCR expression, and organic extract of summer from Kawasaki decreased the CD19 expression. These results suggest that PM₂.₅ extract samples are responsible for cytotoxicity in airway epithelial cells and for activating APCs and T-cells, which can contribute to the exacerbation of respiratory diseases such as asthma. These effects can differ by PM₂.₅ components, collection areas and seasons.

Ambient particulate matter (PM) epidemiologically exacerbates respiratory and immune health, including allergic rhinitis (AR) and bronchial asthma (BA). Although fine and coarse particles can affect respiratory tract, the differences in their effects on the upper and lower respiratory tract and immune system, their underlying mechanism, and the components responsible for the adverse health effects have not been yet completely elucidated. In this study, ambient fine and coarse particles were collected at three different locations in Japan by cyclone technique. Both particles collected at all locations decreased the viability of nasal epithelial cells and antigen presenting cells (APCs), increased the production of IL-6, IL-8, and IL-1β from bronchial epithelial cells and APCs, and induced expression of dendritic and epithelial cell (DEC) 205 on APCs. Differences in inflammatory responses, but not in cytotoxicity, were shown between both particles, and among three locations. Some components such as Ti, Co, Zn, Pb, As, OC (organic carbon) and EC (elemental carbon) showed significant correlations to inflammatory responses or cytotoxicity. These results suggest that ambient fine and coarse particles differently affect nasal and bronchial epithelial cells and immune response, which may depend on particles size diameter, chemical composition and source related particles types.