The health effects of potentially toxic elements (PTEs) in airborne particulate matter (PM) are strongly dependent on their size distribution and dissolution. This study examined PTEs within nine distinct sizes of PM in a Chinese megacity, with a focus on their deposited and dissolved bioaccessibility in the human pulmonary region. A Multiple Path Particle Dosimetry (MPPD) model was used to estimate the deposited bioaccessibility, and an in-vitro experiment with simulated lung fluid was conducted for dissolved bioaccessibility. During the non-heating season, the dissolved bioaccessible fraction (DBF) of As, Cd, Co, Cr, Mn, Pb and V were greater in fine PM (aerodynamics less than 2.1 μm) than in coarse PM (aerodynamics between 2.1 and 10 μm), and vice versa for Ni. With the increased demand of heating, the DBF of Pb and As decreased in fine particle sizes, probably due to the presence of oxide/silicate compounds from coal combustion. Inhalation health risks based on the bioaccessible concentrations of PTEs displayed the peaks in <0.43 μm and 2.1–3.3 μm particulate sizes. The non-cancer risk was at an acceptable level (95th percentiles of hazard index (HI) was 0.49), but the cancer risk exceeded the threshold value (95th percentiles of total incremental lifetime cancer risk (TCR) was 8.91 × 10⁻⁵). Based on the results of uncertainty analysis, except for the exposure frequency, the total concentrations and DBF of As and Cr in <0.43 μm particle size segment have a greater influence on the uncertainty of probabilistic risk.

Inhalation of respirable silica particles can cause serious lung diseases (e.g., silicosis and lung cancer), and the toxicity of respirable silica is highly dependent on its crystal form. Common combustion processes such as coal and biomass burning can provide high temperature environments that may alter the crystal forms of silica and thus affect its toxic effects. Although crystalline silica (i.e., quartz, tridymite, and cristobalite) were widely found at different temperatures during the burning processes, the sources and crystal transformation pathways of silica in the burning processes are still not well understood. Here, we investigate the crystal transformation of silica in the coal and biomass combustion processes and clarify the detailed transformation pathways of silica for the first time. Specifically, in coal burning process, amorphous silica can transform into quartz and cristobalite starting at 1100 °C, and quartz transforms into cristobalite starting at 1200 °C; in biomass burning process, amorphous silica can transform into cristobalite starting at 800 °C, and cristobalite transforms into tridymite starting at 1000 °C. These transformation temperatures are significantly lower than those predicted by the classic theory due to possibly the catalysis of coexisting metal elements (e.g., aluminum, iron, and potassium). Our results not only enable a deeper understanding on the combustion-induced crystal transformation of silica, but also contribute to the mitigation of population exposure to respirable silica.

Inhalation is the most frequent route and the lung is the primary damaged organ for human exposure to benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). However, there is limited information on the risk and dose-effect of the BTEXS mixture on pulmonary function, particularly the overall effect. We conducted a cross-sectional study in a petrochemical plant in southern China. Spirometry and cumulative exposure dose (CED) of BTEXS were used to measure lung function and exposure levels for 635 workers in 2020, respectively. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁) were tested and interpreted as percentages to predicted values [FVC or FEV₁% predicted], and FEV₁ to FVC ratio [FEV₁/FVC (%)]. We found the reduction in FVC% predicted and the risk of lung ventilation dysfunction (LVD) and its two subtypes (mixed and restrictive ventilation dysfunction, MVD, and MVD) were significantly associated with BTEXS individuals. In addition, pulmonary function damage associated with BTEXS was modified by the smoking status and age. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-effect on lung function damage induced by the BTEXS mixture. Our results show wqs, an index of weighted quartiles for BTEXS, was potentially associated with the reduction in FVC and FEV₁% predicted with the coefficients [95% confidence intervals (CI)] between −1.136 (−2.202, −0.070) and −1.230 (−2.265, −0.195). Odds ratios (ORs) and 95% CIs for the wqs index of LVD, MVD, and RVD were 1.362 (1.129, 1.594), 1.323 (1.084, 1.562), and 1.394 (1.096, 1.692), respectively. Furthermore, xylene, benzene, and toluene in the BTEXS mixture potentially contribute to the development of lung function impairment. Our novel findings demonstrated the dose-response relationships between pulmonary function impairment and the BTEXS mixture and disclosed the potential key pollutants in the BTEXS mixture.

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.

An increasing body of evidence has linked greenspace and various health outcomes in children and adolescents, but the conclusions were inconsistent. For this review, we comprehensively summarized the measurement methods of greenspace, resultant health outcomes, and potential mechanisms from epidemiological studies in children and adolescents (aged ≤19 years). We searched for studies published and indexed in MEDLINE and EMBASE (via Ovid) up to April 11, 2022. There were a total of 9,291 studies identified with 140 articles from 28 countries finally assessed and included in this systematic review. Over 70% of the studies were conducted in highly urbanised countries/regions, but very limited research has been done in low-and middle-income countries and none in Africa. Measures of greenspace varied. Various health outcomes were reported, including protective effects of greenspace exposure on aspects of obesity/overweight, myopia, lung health, circulatory health, cognitive function, and general health in children and adolescents. The associations between greenspace exposure and other health outcomes were inconsistent, especially for respiratory health studies. We pooled odds ratios (OR) using random-effects meta-analysis for health outcomes of asthma (OR = 0.94, 95%CI: 0.84 to 1.06), allergic rhinitis (OR = 0.95; 95% CI: 0.73 to 1.25), and obesity/overweight (OR = 0.91, 95%CI: 0.84 to 0.98) with per 0.1 unit increase in normalized difference in vegetation index (NDVI). These associations have important implications for the assessment and management of urban environment and health in children and adolescents.

Inhalation exposure to fine particulate matter (PM₂.₅) represents a global concern due to the adverse effects in human health. In the last years, scientific community has been adopted the assessment of the PM₂.₅-bound pollutant fraction that could be released (bioaccessible fraction) in simulated lung fluids (SLFs) to achieve a better understanding of PM risk assessment and toxicological studies. Thus, bioaccessibility of 49 organic pollutants, including 18 polycyclic aromatic hydrocarbons (PAHs), 12 phthalate esters (PAEs), 11 organophosphorus flame retardants (OPFRs), 6 synthetic musk compounds (SMCs) and 2 bisphenols in PM₂.₅ samples was evaluated. The proposed method consists of a physiologically based extraction test (PBET) by using artificial lysosomal fluid (ALF) to obtain bioaccessible fractions, followed by a vortex-assisted liquid-liquid microextraction (VALLME) and a final analysis by programmed temperature vaporization-gas chromatography-tandem mass spectrometry (PTV-GC-MS/MS). The highest inhalation bioaccessibility ratio was found for bisphenol A (BPA) with an average of 83%, followed by OPFRs, PAEs and PAHs (with average bioaccessibilities of 68%, 41% and 34%, respectively). Correlations between PM₂.₅ composition (major ions, trace metals, equivalent black carbon (eBC) and UV-absorbing particulate matter (UVPM)) and bioaccessibility ratios were also assessed. Principal Component Analysis (PCA) suggested that PAHs, PAES and OPFRs bioaccessibility ratios could be positively correlated with PM₂.₅ carbonaceous content. Furthermore, both inverse and positive correlations on PAHs, PAEs and OPFRs bioaccessibilites could be accounted for some major ions and metal (oid)s associated to PM₂.₅, whereas no correlations comprising considered PM₂.₅ major ions and metal (oid)s contents and BPA bioaccessibility was observed. In addition, health risk assessment of target PM₂.₅-associated PAHs via inhalation was assessed in the study area considering both total and bioaccessible concentrations, being averaged human health risks within the safe carcinogenic and non-carcinogenic levels.

Fine particulate matter 2.5 (PM2.5) exposure leads to the progress of pulmonary disease. It has been reported that N6-methyladenosine (m6A) modification was involved in various biological processes and diseases. However, the critical role of m6A modification in pulmonary disease during PM2.5 exposure remains elusive. Here, we revealed that lung inflammation and mucus production caused by PM2.5 were associated with m6A modification. Both in vivo and in vitro assays demonstrated that PM2.5 exposure elevated the total level of m6A modification as well as the methyltransferase like 3 (METTL3) expression. Integration analysis of m6A RNA immunoprecipitation-seq (meRIP-seq) and RNA-seq discovered that METTL3 up-regulated the expression level and the m6A modification of Interleukin 24 (IL24). Importantly, we explored that the stability of IL24 mRNA was enhanced due to the increased m6A modification. Moreover, the data from qRT-PCR showed that PM2.5 also increased YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) expression, and the up-regulated YTHDF1 augmented IL24 mRNA translation efficiency. Down-regulation of Mettl3 reduced Il24 expression and ameliorated the pulmonary inflammation and mucus secretion in mice exposed to PM2.5. Taken together, our finding provided a comprehensive insight for revealing the significant role of m6A regulators in the lung injury via METTL3/YTHDF1-coupled epitranscriptomal regulation of IL24.

The use of biomass for cooking and heating is considered an important factor associated with chronic obstructive pulmonary disease (COPD), but few studies have previously addressed its underlying mechanisms. Therefore, this research aimed to evaluate the effects of biomass-related PM₂.₅ (BRPM₂.₅) exposure on 16HBE human airway epithelial cells and in mice with regard to mitochondrial dysfunction. Our study indicated that BRPM₂.₅ exposure of 16HBE cells resulted in mitochondrial dysfunction, including decreased mitochondrial membrane potential, increased expression of fission proteins-phospho-DRP1, increased mitochondrial ROS (mtROS), and decreased levels of ATP. BRPM₂.₅ altered the mitochondrial metabolism of 16HBE cells by decreasing mitochondrial oxygen consumption and glycolysis. However, Mitochondria targeted peptide SS-31 eliminated mitochondrial ROS and alleviated the ATP deficiency and proinflammatory cytokines release. BRPM2.5 exposure resulted in abnormal mitochondrial morphological alterations both in 16HBE and in lung tissue. Taken together, these results suggest that BRPM₂.₅ has detrimental effects on human airway epithelial cells, leading to mitochondrial dysfunction, abnormal mitochondrial metabolism and altered mitochondrial dynamics. The present study provides the first evidence that disruption of mitochondrial structure and mitochondrial metabolism may be one of the mechanisms of BRPM₂.₅-induced respiratory dysfunction.

Essential trace element zinc is associated with decreased lung cancer risk, but underlying mechanisms remain unclear. This study aimed to investigate role of DNA methylation in zinc-lung cancer association. We conducted a case-cohort study within prospective Dongfeng-Tongji cohort, including 359 incident lung cancer cases and a randomly selected sub–cohort of 1399 participants. Epigenome-wide association study (EWAS) was used to examine association of plasma zinc with DNA methylation in peripheral blood. For the zinc-related CpGs, their mediation effects on zinc-lung cancer association were assessed; their diagnostic performance for lung cancer was testified in the case-cohort study and further validated in another 126 pairs of lung cancer case-control study. We identified 28 CpGs associated with plasma zinc at P < 1.0 × 10⁻⁵ and seven of them (cg07077080, cg01077808, cg17749033, cg15554270, cg26125625, cg10669424, and cg15409013 annotated to GSR, CALR3, SLC16A3, PHLPP2, SLC12A8, VGLL4, and ADAMTS16, respectively) were associated with incident risk of lung cancer. Moreover, the above seven CpGs were differently methylated between 126 pairs of lung cancer and adjacent normal lung tissues and had the same directions with EWAS of zinc. They could mediate a separate 7.05%∼22.65% and a joint 29.42% of zinc-lung cancer association. Compared to using traditional factors, addition of methylation risk score exerted improved discriminations for lung cancer both in case-cohort study [area under the curve (AUC) = 0.818 vs. 0.738] and in case-control study (AUC = 0.816 vs. 0.646). Our results provide new insights for the biological role of DNA methylation in the inverse association of zinc with incident lung cancer.

When the total ambient PM₂.₅ levels are several-fold higher than the recommended limit, it may be important to study the distributions of different sizes of particulate matter (PM). Here, we assess the distributions of various sizes of total PM₂.₅ for 12 months (on a monthly basis) in New Delhi, India. Importantly, we found that ultrafine particles (i.e., particles <0.5 μm) contribute significantly to total PM₂.₅. PM<₀.₂₅ were the most cytotoxic particles to human lung epithelial cells in all the 12 months. In addition, PM<₀.₂₅ were associated with significantly higher cytotoxicity per unit mass compared to other size fractions constituting PM₂.₅. For any given size of PM, the amount of reactive oxygen species (ROS) generated per unit mass is higher for the month of March as compared to that for the rest of the months in the year. The higher ROS generations for all sizes of PM collected in the month of March was not explained by differences in their metal content values. Our data suggests the lack of correlation between total PM₂.₅ levels and the highly cytotoxic PM<₀.₂₅. In summary, this work establishes the need for policy changes to routinely monitor PM<₀.₂₅ and the necessity to establish exposure limits for PM<₀.₂₅, especially when the total PM₂.₅ levels are breached.