Biomass-related PM2.5 induced inflammatory microenvironment via IL-17F/IL-17RC axis.

Biomass exposure is a significant environmental risk factor for COPD, but the underlying mechanisms have not yet been fully elucidated. Inflammatory microenvironment has been shown to drive the development of many chronic diseases. Pollution exposure can cause increased levels of inflammatory factors in the lungs, leading to an inflammatory microenvironment which is prevalent in COPD. Our findings revealed that IL-17F was elevated in COPD, while exposure to biomass led to increased expression of IL-17F in both alveolar epithelial and macrophage cells in mice. Blocking IL-17F could alleviate the lung inflammation induced by seven days of biomass exposure in mice. We employed a transwell co-culture system to simulate the microenvironment and investigate the interactions between MLE-12 and MH-S cells. We demonstrated that anti-IL-17F antibody attenuated the inflammatory responses induced by BRPM2.5 in MLE-12 and MH-S co-cultured with BRPM2.5-MLE-12, which reduced inflammatory changes in microenvironment. We found that IL-17RC, an important receptor for IL-17F, played a key role in the interactions. Knockout of IL-17RC in MH-S resulted in inhibited IL-17F signaling and attenuated inflammatory response after MH-S co-culture with BRPM2.5-MLE-12. Our investigation suggests that BRPM2.5 induces lung epithelial-macrophage interactions via IL-17F/IL-17RC axis regulating the inflammatory response. These results may provide a novel strategy for effective prevention and treatment of biomass-related COPD.

The gut microbiome as a potential source of non-invasive biomarkers of chronic obstructive pulmonary disease.

Background: The link between gut microbial dysbiosis and the development of chronic obstructive pulmonary disease (COPD) is of considerable interest. However, little is known regarding the potential for the use of the fecal metagenome for the diagnosis of COPD. Methods: A total of 80 healthy controls, 31 patients with COPD severity stages I or II, and 49 patients with COPD severity stages III or IV fecal samples were subjected to metagenomic analysis. We characterized the gut microbiome, identified microbial taxonomic and functional markers, and constructed a COPD disease classifier using samples. Results: The fecal microbial diversity of patients with COPD stages I or II was higher than that of healthy controls, but lower in patients with COPD stages III or IV. Twenty-one, twenty-four, and eleven microbial species, including potential pathogens and pro-inflammatory bacteria, were significantly enriched or depleted in healthy controls, patients with COPD stages I or II, and patients with COPD stages III & IV. The KEGG orthology (KO) gene profiles derived demonstrated notable differences in gut microbial function among the three groups. Moreover, gut microbial taxonomic and functional markers could be used to differentiate patients with COPD from healthy controls, on the basis of areas under receiver operating characteristic curves (AUCs) of 0.8814 and 0.8479, respectively. Notably, the gut microbial taxonomic features differed between healthy individuals and patients in stages I-II COPD, which suggests the utility of fecal metagenomic biomarkers for the diagnosis of COPD (AUC = 0.9207). Conclusion: Gut microbiota-targeted biomarkers represent potential non-invasive tools for the diagnosis of COPD.

Hypoxic Tumor-Derived Exosomes Induce M2 Macrophage Polarization via PKM2/AMPK to Promote Lung Cancer Progression.

Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Exos were isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.

GATA3/long noncoding RNA MHC-R regulates the immune activity of dendritic cells in chronic obstructive pulmonary disease induced by air pollution particulate matter.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness associated with aberrant inflammatory immune reaction in the lung in response to noxious particles and gases. Our previous epidemiological studies discovered that long-term exposure to air pollution PM was associated with an increase in the incidence of COPD and lung function decline, but the impact of air pollution on the onset of COPD and its pathogenesis remains obscure. In recent years, long noncoding RNAs (lncRNAs) have been documented to have a crucial role in COPD. Our preliminary study found that the expression of lncRNA MHC-R in the lung tissues of rats exposed to air pollution PM was dramatically elevated, and the specific expression was mainly focused on the immune-related MHC I, antigen-presenting, and adaptive immune response. After transcription factor prediction, it was found that GATA3 could be combined with the specific sequence of the lncRNA MHC-R promoter region. Dendritic cells (DCs) are necessary antigen-presenting cells (APCs) with the most potent antigen-presenting function. We proved that GATA3/lncRNA MHC-R might regulate the immune activities of DCs to participate in the pathogenic mechanism of COPD induced by air pollution PM, which opens up a new way for early COPD diagnosis and treatment.

Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.

BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood. METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes. RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed. CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.

Changes in the gut microbiome and metabolome in a rat model of pulmonary arterial hypertension.

The gut microbiota is widely considered to be involved in several diseases, including atherosclerosis, obesity, chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH). This study aimed to determine if changes in the gut microbiome and metabolome play a major role in the early pathogenesis of PAH. Male Wistar rats were injected with monocrotaline (MCT) (55 mg/kg) at day 1 and injected with calcium-sensing receptor (CaSR) antagonist NPS2143 (4.5 mg/kg/d) from days 1 to 21. Fecal samples were obtained. The gut microbiota and metabolome were analyzed by 16S rRNA gene sequencing and mass spectrometry-based analysis to investigate the effect of PAH in this rat model. MCT injection had a marked effect on the composition of the gut microbiota. This finding was further confirmed by metabolomic analysis with identification of several metabolites relevant to the gut microflora. However, NPS2143 partially abrogated this intestinal flora disorder and reversed fecal metabolite abnormalities. In conclusion, our study shows correlations between changes in the gut microbiome and the metabolome in PAH, which are affected by NPS2143.

Long noncoding RNA IL6-AS1 is highly expressed in chronic obstructive pulmonary disease and is associated with interleukin 6 by targeting miR-149-5p and early B-cell factor 1.

Chronic obstructive pulmonary disease is a complex condition with multiple etiologies, including inflammation. We identified a novel long noncoding RNA (lncRNA), interleukin 6 antisense RNA 1 (IL6-AS1), which is upregulated in this disease and is associated with airway inflammation. We found that IL6-AS1 promotes the expression of inflammatory factors, especially interleukin (IL) 6. Mechanistically, cytoplasmic IL6-AS1 acts as an endogenous sponge by competitively binding to the microRNA miR-149-5p to stabilize IL-6 mRNA. Nuclear IL6-AS1 promotes IL-6 transcription by recruiting early B-cell factor 1 to the IL-6 promoter, which increases the methylation of the H3K4 histone and acetylation of the H3K27 histone. We propose a model of lncRNA expression in both the nucleus and cytoplasm that exerts similar effects through differing mechanisms, and IL6-AS1 probably increases inflammation via multiple pathways.

Exposure to biomass smoke induces pulmonary Th17 cell differentiation by activating TLR2 on dendritic cells in a COPD rat model.

Almost three billion people in developing countries are exposed to biomass smoke (BS), which predisposes them to developing chronic obstructive pulmonary disease (COPD). COPD is associated with abnormal innate and adaptive immune responses in the lungs and systemic circulation, but the mechanisms underlying BS-COPD development are uncertain. We investigated the role of dendritic cells (DCs) and interleukin (IL)-17A in BS-COPD. We investigated T helper cell responses in the BS-exposed COPD rat model by flow cytometry, quantitative PCR, and enzyme-linked immunosorbent assays. We conducted ex vivo experiments to determine which antigen-presenting cells induce Th17 cell responses. We evaluated the in vitro effects of BS-related particulate matter (BRPM) (2.5 µm) on the function of bone marrow-derived dendritic cells (BMDCs). We found that BS exposure enhanced Th17 responses in the lungs of the COPD-modelled rats, and the stimulated DCs (but not the macrophages) were sufficient to induce naïve CD4 + T cells to produce IL-17A in ex vivo experiments. BRPM significantly enhanced the maturation and activation of DCs through Toll-like receptor 2 (TLR2), but not TLR4, and induced Th17 responses. Therefore, BS activated lung DCs through TLR2, which led to Th17 responses and emphysema in the rats. This process is possibly therapeutically targetable.

Chronic hypoxia promoted pulmonary arterial smooth muscle cells proliferation through upregulated calcium-sensing receptorcanonical transient receptor potential 1/6 pathway.

OBJECTIVES: Although both calcium-sensing receptor (CaSR) and canonical transient receptor potential (TRPC) proteins contribute to chronic hypoxia (CH)-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation, the relationship between CaSR and TRPC in hypoxic PASMCs proliferation remains poorly understood. The goal of this study was to identify that CH promotes PASMCs proliferation through CaSR-TRPC pathway. METHODS: Rat PASMCs were isolated and treated with CH. Cell proliferation was assessed by cell counting, CCK-8 assay, and EdU incorporation. CaSR and TRPC expressions were determined by qPCR and Western blotting. Store-operated Ca2+ entry (SOCE) was assessed by extracellular Ca2+ restoration. RESULTS: In PASMCs, CH enhanced the cell number, cell viability and DNA synthesis, which is accompanied by upregulated expression of CaSR, TRPC1 and TRPC6. Negative CaSR modulators (NPS2143, NPS2390) inhibited, whereas positive modulators (spermine, R568) enhanced, the CH-induced increases in cell number, cell viability and DNA synthesis in PASMCs. Knockdown of CaSR by siRNA inhibited the CH-induced upregulation of TRPC1 and TRPC6 and enhancement of SOCE and attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. However, neither siTRPC1 nor siTRPC6 had an effect on the CH-induced CaSR upregulation, although both significantly attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. CONCLUSION: These results demonstrate that upregulated CaSR-TRPC1/6 pathway mediating PASMCs proliferation is an important pathogenic mechanism under hypoxic conditions.

Chronic exposure to ambient particulate matter induces gut microbial dysbiosis in a rat COPD model.

BACKGROUND: The role of the microbiota in the pathogenesis of chronic obstructive pulmonary disease (COPD) following exposure to ambient particulate matter (PM) is largely unknown. METHODS: Fifty-four male Sprague-Dawley rats were exposed to clean air, biomass fuel (BMF), or motor vehicle exhaust (MVE) for 4, 12, and 24 weeks. We performed pulmonary inflammation evaluation, morphometric measurements, and lung function analysis in rat lung at three different times points during exposure. Lung and gut microbial composition was assessed by 16S rRNA pyrosequencing. Serum lipopolysaccharide levels were measured and short-chain fatty acids in colon contents were quantified. RESULTS: After a 24-week PM exposure, rats exhibited pulmonary inflammation and pathological changes characteristic of COPD. The control and PM exposure (BMF and MVE) groups showed similar microbial diversity and composition in rat lung. However, the gut microbiota after 24 weeks PM exposure was characterized by decreased microbial richness and diversity, distinct overall microbial composition, lower levels of short-chain fatty acids, and higher serum lipopolysaccharide. CONCLUSION: Chronic exposure to ambient particulate matter induces gut microbial dysbiosis and metabolite shifts in a rat model of chronic obstructive pulmonary disease.

LncRNA RP11-86H7.1 promotes airway inflammation induced by TRAPM2.5 by acting as a ceRNA of miRNA-9-5p to regulate NFKB1 in HBECS.

Traffic-related air pollution particulate matter 2.5 (TRAPM2.5), is involved in chronic obstructive pulmonary disease (COPD), which is characterized by airway inflammation. Specifically, these harmful particles or gases can increase chronic airway inflammation. Some recent studies have shown that lncRNAs are closely related to COPD and participate in the regulation of airway inflammation. However, the precise mechanisms remain unknown. In the present study, we investigated the effect of TRAPM2.5 on airway inflammation in human bronchial epithelial cells (HBECs) and the underlying mechanisms mediated by a lncRNA. After exposure to TRAPM2.5, the novel lncRNA RP11-86H7.1 was markedly upregulated in HBECs. Functional assays indicated that the lncRNA RP11-86H7.1 was required for the TRAPM2.5-induced expression of inflammatory factors in HBECs. A mechanistic study demonstrated that lncRNA RP11-86H7.1 might participate in TRAPM2.5-induced inflammatory responses by activating the NF-κB signaling pathway. Moreover, the lncRNA RP11-86H7.1 can promote the inflammatory response by acting as a competing endogenous RNA of miR-9-5p, reversing the inhibitory effect of its target gene NFKB1, and sustaining NF-κB activation. In summary, our study elucidates the pro-inflammatory roles of the lncRNA RP11-86H7.1-miR-9-5p-NFKB1 regulatory network in airway inflammation induced by TRAPM2.5 and indicates that the components of this network might serve as novel diagnostic biomarkers and potential therapeutic targets.

Identification of abnormally expressed lncRNAs induced by PM2.5 in human bronchial epithelial cells.

To investigate the effect of stimulation of human bronchial epithelial cells (HBECs) by arterial traffic ambient PM2.5 (TAPM2.5) and wood smoke PM2.5 (WSPM2.5) on the expression of long non-coding RNAs (lncRNAs) in order to find new therapeutic targets for treatment of chronic obstructive pulmonary disease (COPD). HBECs were exposed to TAPM2.5 and WSPM2.5 at a series of concentrations. The microarray analysis was used to detect the lncRNA and mRNA expression profiles. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene ontology (GO) enrichment were conducted to analyze the differentially expressed lncRNAs and mRNAs. Quantitative real-time PCR (qRT-PCR) was performed to confirm the differential expression of lncRNAs. Western blot was performed to study the expression of autophagy and apoptosis-associated proteins. Flow cytometry was used to detect the apoptotic cells. The results indicated that fine particulate matter (PM2.5)-induced cell damage of HBECs occurred in a dose-dependent manner. The microarray analysis indicated that treatment with TAPM2.5 and WSPM2.5 led to the alteration of lncRNA and mRNA expression profiles. LncRNA maternally expressed gene 3 (MEG3) was significantly up-regulated in HBECs after PM2.5 treatment. The results of Western blot showed that PM2.5 induced cell apoptosis and autophagy by up-regulating apoptosis-associated gene, caspase-3, and down-regulating autophagy-associated markers, Bcl-2 and LC3 expression. In addition, we demonstrated that TAPM2.5 and WSPM2.5 accelerated apoptosis of human bronchial (HBE) cells, silencing of MEG3 suppressed apoptosis and autophagy of HBE cells. These findings suggested that the lncRNA MEG3 mediates PM2.5-induced cell apoptosis and autophagy, and probably through regulating the expression of p53.

PM2.5 Induced the Expression of Fibrogenic Mediators via HMGB1-RAGE Signaling in Human Airway Epithelial Cells.

Background: The aim of the present study was to test whether fine particulate matter (PM2.5) induces the expression of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, and transforming growth factor-ß1 (TGF-ß1) in human bronchial epithelial cells (HBECs) in vitro via high-mobility group box 1 (HMGB1) receptor for advanced glycation end products (RAGE) signaling. Methods: Sprague-Dawley rats were exposed to motor vehicle exhaust (MVE) or clean air. HBECs were either transfected with a small interfering RNA (siRNA) targeting HMGB1 or incubated with anti-RAGE antibodies and subsequently stimulated with PM2.5. Results: The expression of HMGB1 and RAGE was elevated in MVE-treated rats compared with untreated rats, and PM2.5 increased the secretion of HMGB1 and upregulated RAGE expression and the translocation of nuclear factor κB (NF-κB) into the nucleus of HBECs. This activation was accompanied by an increase in the expression of PDGF-AB, PDGF-BB, and TGF-ß1. The HMGB1 siRNA prevented these effects. Anti-RAGE antibodies attenuated the activation of NF-κB and decreased the secretion of TGF-ß1, PDGF-AB, and PDGF-BB from HBECs. Conclusion: PM2.5 induces the expression of TGF-ß1, PDGF-AB, and PDGF-BB in vitro via HMGB1-RAGE signaling, suggesting that this pathway may contribute to the airway remodeling observed in patients with COPD.

PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.

BACKGROUND: The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. METHODS: HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively. The role of the hedgehog pathway in cell migration was assessed by western blotting to measure the expression of Sonic hedgehog (Shh), Gli1 and Snail. Furthermore, siRNA was used to knock down Gli1 or Snail expression. RESULTS: PM2.5 induced HBSMC apoptosis in a dose-dependent manner, although certain concentrations of PM2.5 did not induce HBSMC proliferation or apoptosis. Interestingly, cell migration was stimulated by PM2.5 doses far below those that induced apoptosis. Additional experiments revealed that these PM2.5 doses enhanced the expression of Shh, Gli1 and Snail in HBSMCs. Furthermore, PM2.5-induced cell migration and protein expression were enhanced by recombinant Shh and attenuated by cyclopamine. Similar results were obtained by knocking down Gli1 or Snail. CONCLUSIONS: These findings suggest that PM2.5, which may exert its effects through the Shh signaling pathway, is necessary for the migration of HBSMCs. These data define a novel role for PM2.5 in airway remodeling in COPD.

Positive feedback of the amphiregulin-EGFR-ERK pathway mediates PM2.5 from wood smoke-induced MUC5AC expression in epithelial cells.

Biomass fuel smoke is thought to contribute to chronic obstructive pulmonary disease, which is characterized by mucous cell metaplasia and enhanced mucus secretion. We investigated the effect of particulate matter (PM) with a diameter <2.5 µm (PM2.5) from wood smoke (WSPM2.5) on the expression of the most prominent secreted mucin, MUC5AC. Wood smoke was able to induce MUC5AC expression in the rat respiratory tract after 3 months of exposure. WSPM2.5 could induce MUC5AC production in both primary human airway epithelial cells and the NCI-H292 cell line. This induction process was mediated by activation of epithelial growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signaling through an EGFR ligand-dependent mechanism. Amphiregulin (AR) was identified as the major ligand responsible for EGFR-ERK signaling activation and MUC5AC expression. In turn, EGFR-ERK pathway activation was found to contribute to the de novo synthesis of AR. This positive feedback loop might play an important role in a sustained mucus hypersecretion response.

Nicotine-Induced Airway Smooth Muscle Cell Proliferation Involves TRPC6-Dependent Calcium Influx Via α7 nAChR.

BACKGROUND/AIMS: The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation. METHODS: Cell viability was assessed with a CCK-8 assay. Proliferation was measured by cell counting and EdU immunostaining. Fluorescence calcium imaging was performed to measure intracellular Ca2+ concentration ([Ca2+]i). RESULTS: The results showed that nicotine promotes HBSMC proliferation, which is accompanied by elevated store-operated calcium entry (SOCE), receptor-operated calcium entry (ROCE) and basal [Ca2+]i in HBSMCs. Moreover, we also confirmed that canonical transient receptor potential protein 6 (TRPC6) and α7 nicotinic acetylcholine receptor (α7 nAChR) are involved in nicotine-induced upregulation of cell proliferation. Furthermore, we verified that activation of the PI3K/Akt signaling pathway plays a pivotal role in nicotine-enhanced proliferation and calcium influx in HBSMCs. Inhibition of α7 nAChR significantly decreased Akt phosphorylation levels, and LY294002 inhibited the protein expression levels of TRPC6. CONCLUSION: Herein, these data provide compelling evidence that calcium entry via the α7 nAChR-PI3K/Akt-TRPC6 signaling pathway plays an important role in the physiological regulation of airway smooth muscle cell proliferation, representing an important target for augmenting airway remodeling.

Exposure to Ambient Particulate Matter Induced COPD in a Rat Model and a Description of the Underlying Mechanism.

While the health effects of air pollution have been an international public health concern since at least the 1950s, recent research has focused on two broad sources of air pollution, namely, biomass fuel (BMF) and motor vehicle exhaust (MVE). Many studies have shown associations between air pollution PM and exacerbations of pre-existing COPD, but the role of air pollution PM in the development and progression of COPD is still uncertain. The current study indicates that rats can develop pronounced COPD following chronic exposure to air pollution PM (BMF and MVE), as characterized by lung function reduction, mucus metaplasia, lung and systemic inflammation, emphysema, and small airway remodeling. Comparative analyses demonstrate that both BMF and MVE activate similar pathogenesis that are linked to the development of COPD. These findings also show that some differences are found in the lungs of rats exposed to BMF or MVE, which might result in different phenotypes of COPD.

Association between exposure to ambient particulate matter and chronic obstructive pulmonary disease: results from a cross-sectional study in China.

OBJECTIVE: The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear. Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults. METHODS: A cross-sectional study was conducted in southern China. Seven clusters were randomly selected from four cities across Guangdong province. Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry. COPD was defined as a post-bronchodilator FEV1/FVC less than 70%. Atmosphere PM sampling was conducted across the clusters along with our survey. RESULTS: Of the subjects initially recruited, 84.4% (n=5993) were included for analysis. COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters. COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1. A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI -43 to -9) decrease in FEV1, a 28 mL (-49 to -8) decrease in FVC and a 0.09% decrease (-0.170 to -0.010) in FEV1/FVC ratio. The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker. CONCLUSIONS: Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function. TRIAL REGISTRATION NUMBER: ChiCTR-OO-14004264; Post-results.