Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.

Background: Particulate matter (PM) is a high risk factor for various respiratory diseases and triggers an inflammatory response in lung tissues. However, the molecular mechanism of the PM-induced inflammatory response is incompletely understood. Methods: Human bronchial epithelial cells (HBECs) were treated with the urban PM 1649b for assessment of the inflammatory response. The intracellular level of reactive oxygen species (ROS) was measured by flow cytometry. PM-activated signaling pathways were addressed with specific inhibitors. In vivo, the C57 mice model of PM-induced acute lung inflammation was established with intratracheal instillation of PM for 2 consecutive days. The oxidant stress in lung tissues was assessed with dihydroethidium (DHE) staining, and malondialdehyde (MDA) activity and hydrogen peroxide (H2O2) assays. The histopathologic changes in lung tissues and number of inflammatory cells in bronchoalveolar lavage fluid (BALF) were examined. Expression of pro-inflammatory cytokines in BALF was measured by ELISA. Results: PM increased the expression of interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP)- 9 and cyclooxygenase (COX)-2 in a dose-dependent manner. ROS generation and activation of MAPK (ERK, JNK, p38 MAPK) and NF-κB pathways were detected in PM-exposed HBECs. Pretreatment with N-acetylcysteine (NAC) led to the inflammatory response, ROS level and activation of the MAPK and NF-κB pathways to be attenuated. Blockade of ERK, JNK or p38 MAPK pathway with specific inhibitor prevented the release of pro-inflammatory cytokines and activation of the NF-κB pathway. Inhibition of the NF-κB pathway reduced the expression of pro-inflammatory cytokines. In vivo, PM exposure increased oxidant stress in lung tissues, infiltration of inflammatory cells around PM in lung tissues, the number of total cells and inflammatory cells in BALF, and the concentrations of IL-1β, IL-6, IL-8 and MMP-9 in BALF, all of which were reversed partially upon NAC treatment. Conclusions: PM exposure enhanced the airway inflammatory response significantly through ROSmediated activation of MAPK (ERK, JNK, p38 MAPK) and downstream NF-κB signaling pathways. Oxidative stress appeared to be the key regulator for PM-induced lung inflammation. These results suggested the molecular mechanism of lung inflammation caused by PM.

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Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway.

Air pollution associated epigenetic modifications: Transgenerational inheritance and underlying molecular mechanisms

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. 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. 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. These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.

/pdf/gut-microbiota-dysbiosis-contributes-to-the-development-of-298n5q28mt.pdf

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

Chronic obstructive pulmonary disease (COPD) and lung cancer comprise the leading causes of lung disease-related mortality worldwide. Exposure to tobacco smoke is a mutual aetiology underlying the two diseases, accounting for almost 90% of cases. There is accumulating evidence supporting the role of immune dysfunction, the lung microbiome, extracellular vesicles and underlying genetic susceptibility in the development of COPD and lung cancer. Further, epigenetic factors, involving DNA methylation and microRNA expression, have been implicated in both diseases. Chronic inflammation is a key feature of COPD and could be a potential driver of lung cancer development. Using next generation technologies, further studies investigating the genomics, epigenetics and gene-environment interaction in key molecular pathways will continue to elucidate the pathogenic mechanisms underlying the development of COPD and lung cancer, and contribute to the development of novel diagnostic and prognostic tools for early intervention and personalised therapeutic strategies.

Chronic obstructive pulmonary disease (COPD) and lung cancer: common pathways for pathogenesis

Objective The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM 10 / 2.5 ) and COPD remains unclear. Our study objective was to examine the association between ambient PM 10 / 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 FEV 1 /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/m 3 and 2.530 (1.280 to 5.001) for >75 µg/m 3 compared with the level of ≤35 µg/m 3 for PM 2.5 ; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m 3 compared with the level of ≤50 µg/m 3 for PM 1 . A 10 µg/m 3 increase in PM 2.5 concentrations was associated with a 26 mL (95% CI −43 to −9) decrease in FEV 1 , a 28 mL (−49 to −8) decrease in FVC and a 0.09% decrease (−0.170 to −0.010) in FEV 1 /FVC ratio. The associations of COPD with PM 10 were consistent with PM 2.5 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.

https://thorax.bmj.com/content/thoraxjnl/72/9/788.full.pdf

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

Clinical impact of the lower limit of normal of FEV1/FVC on detecting chronic obstructive pulmonary disease: A follow-up study based on cross-sectional data

Shiliang Liu

Papers

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

Clinical impact of the lower limit of normal of FEV1/FVC on detecting chronic obstructive pulmonary disease: A follow-up study based on cross-sectional data