Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 183
Filtrar
1.
J Cell Mol Med ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34994052

RESUMO

The role of alveolar macrophages (AMs) in chronic obstructive pulmonary disease is unclear. We characterized the function of AMs in rats chronically exposed to biomass fuel smoke (BMF) and studied the signal pathways that regulate AMs polarization. One hundred and eighty male Sprague-Dawley rats were divided into BMF group and clean air control (CON) group. After BMF smoke exposure for 4 days, 1 month and 6 months, the cytokine secretion and function of AMs were determined by flow cytometry, quantitative polymerase chain reaction, Western blotting and immunofluorescence. Bone marrow-derived macrophages were cultured and exposed to particulate matter (PM) from the smoke. Exposure initially promoted pro-inflammatory factors, but pro-inflammatory macrophages shared features of anti-inflammatory macrophages. Consistent with IL-4 upregulated in bronchoalveolar lavage fluid, p-Stat6 and peroxisome proliferator-activated receptor γ (PPARγ) in AMs elevated at 4 days of exposure. After 6 months of exposure, CD206, TGF-ß1 and p-Smad3 were significantly higher than the control groups. PPARγ reversed the M1 phenotype induced by PM in vitro and drove the macrophages into the M2 phenotype. Altogether, the study demonstrates the dynamic phenotype and functional changes in AMs during exposure to BMF smoke.

2.
Environ Pollut ; 292(Pt B): 118464, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34763019

RESUMO

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.


Assuntos
Células Epiteliais , Pulmão , Animais , Biomassa , Humanos , Pulmão/química , Camundongos , Material Particulado/análise , Material Particulado/toxicidade , Espécies Reativas de Oxigênio
3.
Int J Chron Obstruct Pulmon Dis ; 16: 3285-3295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887658

RESUMO

Background: Fine-particulate matter ≤2.5 µm in diameter (PM2.5)-associated airway remodeling has recently been recognized as a central feature of COPD. Activation of the Wnt/ß-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether the Wnt5a/ß-Catenin pathway is involved in PM2.5-induced smooth muscle proliferation in vivo and in vitro, which promotes the development of airway remodeling in subjects with COPD. Methods: The effect of Wnt5a on ß-Catenin-mediated airway remodeling was assessed using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cells (HBSMCs) in vitro. Small animal spirometry was used to measure lung function in mice. H&E staining and immunohistochemistry were performed to inspect emphysema and airway remodeling indices. Real-time PCR was used to detect Wnt5a, ß-Catenin, TGF-ß1, CyclinD1 and c-myc mRNA expression. The CCK8 assay was performed to detect cellular activity. Western blotting was performed to assess PCNA, α-SMA, Wnt5a, ß-Catenin, PDGFRß and TenascinC protein expression. ß-Catenin expression was detected using cellular immunofluorescence. Results: Exposure to PM2.5 led to emphysema, airway wall thickening, an increased smooth muscle layer thickness, decreased lung function and increased expression of the Wnt5a, ß-Catenin, PDGFRß and Tenascin C proteins in the mouse lung tissue. BOX5 (a Wnt5a antagonist) alleviated these PM2.5-induced outcomes in mice. Moreover, PM2.5 induced the expression of the Wnt5a, ß-Catenin, TGF-ß1, CyclinD1 and c-myc mRNAs in HBSMCs. BOX5 also inhibited the PM2.5-induced increases in PCNA, α-SMA, Wnt5a, ß-Catenin, PDGFRß and Tenascin C protein expression in HBSMCs. Conclusion: Our findings suggest that PM2.5 exposure induces HBSMC proliferation, contributing to airway remodeling via the Wnt5a/ß-Catenin signaling pathway in vivo and in vitro, which might be a target for COPD treatment.

5.
Int J Chron Obstruct Pulmon Dis ; 16: 3387-3396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34949919

RESUMO

Purpose: Anxiety and depression are often underdiagnosed and affect the prognosis of patients with chronic obstructive pulmonary disease (COPD). We analyzed data from the China Pulmonary Health (CPH) study to assess the prevalence of anxiety and depression in COPD patients and their relationship with disease severity. Patients and Methods: A total of 57,779 subjects aged 20 years or older were recruited in the CPH study. All participants were assessed using a standard questionnaire and underwent pulmonary function tests before and after the use of a bronchodilator in local health centers. The Hospital Anxiety and Depression Scale (HADS) questionnaire with a cutoff score of 8 was used to define anxiety and depression. The prevalence of anxiety and depression in patients of COPD were investigated. Multivariate logistic regression was used to investigate the effects of COPD and lung function on anxiety and depression. Results: A total of 49,053 participants (20,661 men and 28,392 women) completed the questionnaire with reliable post-bronchodilator pulmonary function test results and were included in the final analysis, of which 4686 (9.55%) were diagnosed with COPD. Of the patients with COPD, 10.79% had anxiety, 13.65% had depression, and 7.08% had anxiety and depression concomitantly. In the multivariate logistic regression analysis, COPD was not significantly associated with anxiety, depression, or both. After adjusting for confounders in model 1, patients in the GOLD III-IV group had a significantly higher risk of anxiety, depression, and their coincidence. After further adjusting for respiratory symptoms in model 2, lung function impairment in the GOLD III-IV group was only significantly associated with a higher risk of depression or at least one of anxiety and depression. Conclusion: Anxiety and depression are prevalent in patients with COPD in China. More severe lung function impairment is significantly associated with a higher risk of depression.

6.
Respir Med ; 190: 106681, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34784563

RESUMO

BACKGROUND: Small airway dysfunction (SAD) is an early lesion of chronic respiratory disease that is best detected using impulse oscillometry (IOS). Few studies have investigated risk factors for IOS-defined SAD (IOS-SAD) in a large population. We aimed to explore the clinical features of and risk factors for IOS-SAD in a community-based population. METHODS: We divided subjects into IOS-SAD and non-SAD groups based on a cutoff of >0.07 kPa/L/s in the difference between the resistance at 5 Hz versus the resistance at 20 Hz (R5-R20). All participants underwent spirometry, IOS, and completed a questionnaire; some participants underwent computed tomography (CT). We analyzed the risk factors for SAD based on binary logistic regression. RESULTS: The total cohort comprised 1327 subjects. The prevalence of IOS-SAD was 32.9% (437/1327). Compared with the non-SAD group, the IOS-SAD group was older (64.0 ± 7.8 vs. 59.6 ± 7.8 years, p < 0.001), included less never-smokers (30.2% vs. 35.8%, p < 0.001), had greater airway resistance and worse lung function, indicated by a larger R5-R20 (0.15 ± 0.08 vs. 0.03 ± 0.02 kPa/L/s, p < 0.001) and smaller forced expiratory volume in 1 s to forced vital capacity after bronchodilation (60.2 ± 14.4% vs. 72.6 ± 10.0%, p < 0.001); on CT, the IOS-SAD group had higher prevalences of emphysema and gas trapping. Risk factors for SAD were older age, high BMI, smoking, childhood cough, and asthma. CONCLUSION: Subjects with IOS-SAD had increased airway resistance and visible CT changes. Individuals with smoking exposure, advanced age, high BMI, childhood cough, and asthma were more prone to SAD. CLINICAL TRIAL REGISTRATION: ChiCTR1900024643.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34813411

RESUMO

RATIONALE: It remains unknown whether long-term ozone exposure can impair lung function. OBJECTIVES: To investigate the associations between long-term ozone exposure and adult lung function in China. METHODS: Lung function results and diagnosis of small airways dysfunction (SAD) were collected from a cross-sectional study, China Pulmonary Health Study (N=50,991). We used multivariate linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trend. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). MEASUREMENTS AND MAIN RESULTS: We observed each 1-standard deviation (SD, 4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 mL/s [95% confidence interval (CI): 8.8, 19.6] decrease in forced expiratory flow at 75th percentile of vital capacity and a 29.5 mL/s (95% CI: 19.6, 39.5) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI: 1.06, 1.11) for a 1-SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with a decreased ratio of expiratory volume in 1 second to forced vital capacity (FEV1/FVC) but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. CONCLUSION: We found independent associations of long-term ozone exposure with impaired small airways function and higher SAD risks, while the associations with airflow obstruction were weak. COPD patients appear to be more vulnerable.

9.
Int J Chron Obstruct Pulmon Dis ; 16: 2845-2856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703220

RESUMO

Background and Purpose: PM2.5-associated airway inflammation has recently been recognized as pivotal to the development of COPD. Aberrant glycogen synthase kinase (GSK)-3ß signaling is linked to the inflammatory response. Therefore, we investigated the effects of GSK-3ß inhibitors on the PM2.5-induced inflammatory response in bronchial epithelial cells. Methods: The production of phosphorylated GSK-3ß (p-GSK-3ß) was analyzed by immunohistochemistry with PM2.5-induced mice. HBECs were treated with various inhibitors targeting GSK-3ß or JNK before PM2.5 stimulation. The production of GSK-3ß signaling was analyzed by Western blotting. Inflammatory cytokine production was detected by qRT-PCR and ELISA. Results: PM2.5 exposure caused lung inflammation, upregulated serum concentrations of HMGB1 and IL-6, decreased IL-10 expression, and significantly attenuated p-GSK-3ß production in mice. HBECs exposed to PM2.5 showed significantly reduced p-GSK-3ß production, an increased ratio of p-JNK/JNK, increased NF-κB activation and IκB degradation, and upregulated the inflammatory cytokines HMGB1 and IL-6. Intervention with GSK-3ß inhibitors TDZD-8 and SB216763 significantly suppressed PM2.5-induced outcomes. Moreover, the JNK inhibitor SP600125 also reduced the level of NF-κB phosphorylation induced by PM2.5. The differences in the levels of inflammation-related cytokines in the TDZD-8 groups were greater than those in the SB216763 groups. Conclusion: Inhibition of GSK-3ß weakens the PM2.5-induced inflammatory response by regulating the JNK/NF-κB signaling pathway in bronchial epithelial cells.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Animais , Células Epiteliais , Glicogênio Sintase Quinase 3 beta , Camundongos , NF-kappa B , Material Particulado/toxicidade
10.
Respir Res ; 22(1): 274, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696775

RESUMO

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.

11.
Int J Chron Obstruct Pulmon Dis ; 16: 2575-2584, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531653

RESUMO

Background and Objective: To determine the effects of BSE (biomass smoke exposure) on pulmonary and non-pulmonary changes in patients with COPD compared with normal individuals. Methods: Using a cohort, we recruited 16 healthy individuals with BSE (BSE normal), 19 patients with BSE+COPD, 13 healthy individuals with cigarette smoke exposure (CSE normal), 25 patients with CSE+COPD, and 25 healthy controls. Patients with GOLD stage I and II COPD were included. Baseline data (demographic data, BSE or CSE, lung function, and CT findings) and follow-up lung function data were collected. CT parameters of emphysema, pulmonary small vessels, airway remodeling, pectoralis muscles, and erector spinae muscle were measured. Results: Individuals with BSE were mainly women (32/35, 91.43%). Compared with the CSE+COPD group, the BSE+COPD group demonstrated slower lung function decline, increased lower lung emphysema, narrower airway lumen dimensions and increased airway wall thickening in the moderate and small airways (all P<0.05). Compared with healthy controls, the CSE normal and BSE normal groups exhibited significant reductions in pulmonary small vessel area and obvious airway remodeling in small airways (P<0.05). Compared with the BSE normal group, the BSE+COPD group showed significantly more severe emphysema and airway remodeling, as well as reduced left pectoralis major muscle area (all P<0.05). Conclusion: Healthy individuals with BSE had reduced pulmonary small vessel area and evidence of airway remodeling; patients with BSE and COPD showed more severe emphysema, airway remodeling, and reductions in pectoralis major muscle area. Clinical Trial Registration: ChiCTR-OO-14004264.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Biomassa , Feminino , Humanos , Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/etiologia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/etiologia , Fumaça , Tomografia Computadorizada por Raios X
12.
Bioengineered ; 12(1): 5173-5183, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34405758

RESUMO

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.

13.
J Thorac Dis ; 13(7): 4043-4053, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34422334

RESUMO

Background: To reappraise the prevalence and characteristics of chronic obstructive pulmonary disease (COPD) in China with a criterion of FEV1/FVC < the lower limit of normal (LLN). Methods: We assessed the incidence and characteristics of airflow limitation using data from the Chinese Epidemiological Survey of COPD study-a multicenter, randomized trial, with an age-dependent LLN reference equation [established by the Guangzhou Institute of Respiratory Health (GIRH)]. Questionnaire and spirometry data were collected for all eligible subjects. COPD prevalence, risk factors, severity distribution, as well as comparisons of characteristics between the LLN and 0.7 were analyzed. Results: COPD prevalence was 9.0% among participants aged 40-80 years in China with the criterion of LLN. Greater prevalence was observed in female sex, rural areas and never smokers than with the GOLD 0.7 fixed ratio. Age distribution showed a higher incidence of COPD in people under 60 years but lower in participants over 60 years of age. With the LLN FEV1 reference equation, patients in stage I were decreased (15.8% vs. 24.6%, P<0.001), while the proportion of patients in stage III and IV were increased when compared with the China 2002 revised equation (27.7% vs. 21.1%, for stage III, P<0.001; 8.7% vs. 5.6% for stage IV, P=0.001). Only 30.8% of patients with COPD had ever been "diagnosed" with COPD and 60.6% of the patients had respiratory symptoms, both lower than that under the GOLD 0.7 fixed-ratio criterion (35.5%, P=0.004; 64.8% for symptoms, P=0.014). Conclusions: With the GIRH-LLN criterion, COPD prevalence was slightly higher, and a large number of women, rural patients and nonsmokers with young age and little symptoms were diagnosed when compared with GOLD 0.7 fixed ratio. These subjects may, therefore, deserve further attention and may warrant regular follow-up. Trial Registration: Registration number: ChiCTR-ECS-13004110.

14.
Clin Transl Med ; 11(7): e479, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34323408

RESUMO

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.

15.
Int J Chron Obstruct Pulmon Dis ; 16: 2039-2047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267511

RESUMO

Purpose: The use of simple and affordable screening tools for chronic obstructive pulmonary disease (COPD) is limited. We aimed to assess the validity of a handheld expiratory flowmeter (Vitalograph Ltd., COPD-6®, Ireland) for COPD screening in Chinese primary care settings. Methods: In our cross-sectional study, subjects were randomly selected in eight primary care settings. Tests with the handheld expiratory flowmeter and the conventional spirometry were sequentially performed on all participants. The correlation between the handheld expiratory flowmeter and the conventional spirometry was determined. Validity was determined by the area under the receiver operator characteristic curve (AUC) of the forced expiratory volume in one second (FEV1)/forced expiratory volume in six seconds (FEV6) that used to detect airway obstruction. The sensitivity, specificity, predictive values, and likelihood ratio were calculated according to different FEV1/FEV6 cut-off points. Results: A total of 229 subjects (15.4%) were diagnosed with airflow limitation by conventional spirometry. FEV1, FEV6, and FEV1/FEV6 measured by the handheld expiratory flowmeter were correlated with FEV1, FVC, and FEV1/FVC measured by the conventional spirometry (r=0.889, 0.835 and 0.647, p<0.001), respectively. AUC of the FEV1/FEV6 to determine airflow obstruction was 0.857 (95% CI: 0.826 to 0.888). No significant difference of AUC was observed between the symptomatic group and the asymptomatic group (AUC=0.869 vs 0.843, P=0.425). A similar phenomenon was found in the AUC of smokers and never-smokers (AUC=0.862 vs 0.840; P=0.515). The cut-off point for FEV1/FEV6 was 0.77 and the corresponding sensitivity and specificity were 71.2% and 89.8%, respectively. Conclusion: The handheld expiratory flowmeter might be used as a screening device for COPD in Chinese primary care settings.


Assuntos
Fluxômetros , Doença Pulmonar Obstrutiva Crônica , China , Estudos Transversais , Volume Expiratório Forçado , Humanos , Atenção Primária à Saúde , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Espirometria , Capacidade Vital
16.
Environ Int ; 156: 106707, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34182192

RESUMO

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 µm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25-75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 µg/m3 to 92 µg/m3 (average: 53 µg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30-28.33), FVC (17.45 mL, 95% CI: 7.16-27.74), PEF (86.64 mL/s, 95% CI: 59.77-113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64-47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Volume Expiratório Forçado , Humanos , Pulmão , Material Particulado/análise
17.
Environ Res ; 201: 111544, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34157271

RESUMO

BACKGROUND: While temperature changes have been confirmed as one of the contributory factors affecting human health, the association between high-frequency temperature variability (HFTV, i.e., temperature variation at short time scales such as 1, 2, and 5 days) and the hospitalization of chronic obstructive pulmonary disease (COPD) was rarely reported. OBJECTIVES: To evaluate the associations between high-frequency temperature variabilities (i.e., at 1, 2, and 5-day scales) and daily COPD hospitalization. METHODS: We collected daily records of COPD hospitalization and meteorological variables from 2013 to 2017 in 21 cities of Guangdong Province, South China. A quasi-Poisson regression with a distributed lag nonlinear model was first employed to quantify the effects of two HFTV measures, i.e., the day-to-day (DTD) temperature change and the intraday-interday temperature variability (IITV), on COPD morbidity for each city. Second, we used multivariate meta-analysis to pool the city-specific estimates, and stratified analyses were performed by age and sex to identify vulnerable groups. Then, the meta-regression with city-level characteristics was employed to detect the potential sources of the differences among 21 cities. RESULTS: A monotonic increasing curve of the overall exposure-response association was observed, suggesting that positive HFTV (i.e., increased DTD and IITV) will significantly increase the risk of COPD admission. Negative DTD was associated with reduced COPD morbidity while positive DTD elevated the COPD risk. An interquartile range (IQR) increase in DTD was associated with a 24% (95% CI: 12-38%) increase in COPD admissions. An IQR increase in IITV0-1 was associated with 18% (95% CI: 7-27%) increase in COPD admissions. Males and people aged 0-64 years appeared to be more vulnerable to the DTD effect than others. Potential sources of the disparity among different cities include urbanization level, sex structure, industry structure, gross domestic product (GDP), health care services, and air quality. CONCLUSIONS: The increases of DTD and IITV have significant adverse impacts on COPD hospitalization. As climate change intensifies, precautions need to be taken to mitigate the impacts of high-frequency temperature changes.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença Pulmonar Obstrutiva Crônica , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Cidades , Hospitalização , Humanos , Masculino , Morbidade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Temperatura
18.
Microcirculation ; 28(6): e12715, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34008915

RESUMO

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.

19.
Toxicol Lett ; 348: 28-39, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34058311

RESUMO

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.


Assuntos
Células Dendríticas/imunologia , Pulmão/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumaça/efeitos adversos , Células Th17/citologia , Receptor 2 Toll-Like/fisiologia , Animais , Diferenciação Celular , Modelos Animais de Doenças , Interleucina-17/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado/toxicidade , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/imunologia , Ratos , Ratos Sprague-Dawley
20.
Ann Transl Med ; 9(5): 390, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33842611

RESUMO

Background: Prior pulmonary tuberculosis (TB) can cause permanent changes in lung anatomy and is associated with lung function loss. However, it remains unclear whether pulmonary function impairment owing to TB is associated with airflow obstruction, the hallmark of chronic obstructive pulmonary disease (COPD). The aim of this systematic review and meta-analysis was to assess the association and quantify the magnitudes of association between pulmonary TB and COPD, and to evaluate the prevalence of COPD in patients with prior pulmonary TB. Methods: We searched the PubMed, Embase, and Web of Science databases for studies published from inception to January 1, 2020. Pooled effect sizes were calculated according to a random effects model or fixed effect model depending on heterogeneity. Specific subgroups (different diagnostic criteria, smoking status, income level) were examined. Results: A total of 23 articles were included in this study. Compared with controls, patients with pulmonary TB had an odds ratios (ORs) of 2.59 [95% confidence interval (CI): 2.12-3.15; P<0.001] for developing COPD. In jackknife sensitivity analyses, the increased risk of prior pulmonary TB remained consistent for COPD; when the meta-analysis was repeated and one study was omitted each time, the ORs and corresponding 95% CIs were greater than 2. Funnel plots of ORs with Egger's linear regression (t=2.00, P=0.058) and Begg's rank correlation (Z=0.75, P=0.455) showing no significant publication bias. Subgroup analysis showed that the same conclusion was still present in never smokers (ORs 2.41; 95% CI: 1.74-3.32; P<0.001), patients with pulmonary TB diagnosed using chest X-ray (ORs 2.47; 95% CI: 1.23-4.97; P<0.001), and low- and middle-income country (LMIC) settings (ORs 2.70; 95% CI: 2.08-3.51; P<0.001). The pooled prevalence of COPD in patients with prior pulmonary TB was 21% (95% CI: 16-25%; P<0.001). Conclusions: Individuals with prior pulmonary TB have an increased risk and high prevalence of COPD. Future studies identifying the underlying mechanisms for TB-associated COPD and therapeutic strategies are required.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...