Obstructive Pulmonary Disease
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2021 ◽  
Kristin Tsuo ◽  
Wei Zhou ◽  
Ying Wang ◽  
Masahiro Kanai ◽  
Shinichi Namba ◽  

Asthma is a complex disease that affects millions of people and varies in prevalence by an order of magnitude across geographic regions and populations. However, the extent to which genetic variation contributes to these disparities is unclear, as studies probing the genetics of asthma have been primarily limited to populations of European (EUR) descent. As part of the Global Biobank Meta-analysis Initiative (GBMI), we conducted the largest genome-wide association study of asthma to date (153,763 cases and 1,647,022 controls) via meta-analysis across 18 biobanks spanning multiple countries and ancestries. Altogether, we discovered 180 genome-wide significant loci (p < 5x10-8) associated with asthma, 49 of which are not previously reported. We replicate well-known associations such as IL1RL1 and STAT6, and find that overall the novel associations have smaller effects than previously-discovered loci, highlighting our substantial increase in statistical power. Despite the considerable range in prevalence among biobanks, from 3% to 24%, the genetic effects of associated loci are largely consistent across the biobanks and ancestries. To further investigate the polygenic architecture of asthma, we construct polygenic risk scores (PRS) using a multi-ancestry approach, which yields higher predictive power for asthma in non-EUR populations compared to PRS derived from previous asthma meta-analyses and using other methods. Additionally, we find considerable genetic overlap between asthma and chronic obstructive pulmonary disease (COPD) across ancestries but minimal overlap in enriched biological pathways. Our work underscores the multifactorial nature of asthma development and offers insight into the shared genetic architecture of asthma that may be differentially perturbed by environmental factors and contribute to variation in prevalence.

2021 ◽  
Vol 12 ◽  
Laura V. Reid ◽  
C. Mirella Spalluto ◽  
Alastair Watson ◽  
Karl J. Staples ◽  
Tom M. A. Wilkinson

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Individuals with COPD typically experience a progressive, debilitating decline in lung function as well as systemic manifestations of the disease. Multimorbidity, is common in COPD patients and increases the risk of hospitalisation and mortality. Central to the genesis of multimorbidity in COPD patients is a self-perpetuating, abnormal immune and inflammatory response driven by factors including ageing, pollutant inhalation (including smoking) and infection. As many patients with COPD have multiple concurrent chronic conditions, which require an integrative management approach, there is a need to greater understand the shared disease mechanisms contributing to multimorbidity. The intercellular transfer of extracellular vesicles (EVs) has recently been proposed as an important method of local and distal cell-to-cell communication mediating both homeostatic and pathological conditions. EVs have been identified in many biological fluids and provide a stable capsule for the transfer of cargo including proteins, lipids and nucleic acids. Of these cargo, microRNAs (miRNAs), which are short 17-24 nucleotide non-coding RNA molecules, have been amongst the most extensively studied. There is evidence to support that miRNA are selectively packaged into EVs and can regulate recipient cell gene expression including major pathways involved in inflammation, apoptosis and fibrosis. Furthermore changes in EV cargo including miRNA have been reported in many chronic diseases and in response to risk factors including respiratory infections, noxious stimuli and ageing. In this review, we discuss the potential of EVs and EV-associated miRNA to modulate shared pathological processes in chronic diseases. Further delineating these may lead to the identification of novel biomarkers and therapeutic targets for patients with COPD and multimorbidities.

2021 ◽  
Vol 12 ◽  
Mei Qiu ◽  
Li-Min Zhao ◽  
Ze-Lin Zhan

Recently, Lin and colleagues assessed the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2is) by a meta-analysis [1], in which the authors assessed 16 kinds of adverse events (AE) reported in the published articles based on 10 randomized controlled trials. We conducted a further meta-analysis and targeted the association between use of SGLT2is and occurrences of various kinds of serious AE published in the Clinical Trials website (clinicaltrials.gov). Our meta-analysis revealed that use of SGLT2is was not significantly associated with occurrences of 980 kinds of serious AE but was significantly associated with lower risks of 29 kinds of serious AE, especially including several important respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease, sleep apnoea syndrome, and pneumonia). These findings may cause more studies to evaluate the possibilities of gliflozins being used for prevention of these specific diseases.

2021 ◽  
Vol 12 ◽  
Xiaoming Xue ◽  
Lihong Meng ◽  
Hongyu Cai ◽  
Yaoqin Sun ◽  
Ye Zhang ◽  

Background: This study aimed to investigate the protective effect of Xuanfei Pingchuan Capsules (XFPC) on autophagy and p38 phosphorylation in human bronchial epithelial (HBE) cells induced by cigarette smoke extract (CSE).Methods: HBE cells were divided into five groups: blank, CSE, low XFPC dose (XFPC-L), medium XFPC dose (XFPC-M), and high XFPC dose (XFPC-H). HBE cells were induced by CSE to establish a cell model for chronic obstructive pulmonary disease, and different doses of XFPC medicated serum were used to treat the cells. The Cell Counting Kit-8 was used to detect cell viability. Flow cytometry was used to detect cell apoptosis. Fluorescence microscopy and the expression level of microtubule-associated protein light chain 3 (LC3)-II in immunohistochemical method were used to observe autophagy in cells. Western blot was used to detect the protein expression level of p38, phospho-p38 (p-p38), LC3-I, LC3-II and Beclin 1. Real-time polymerase chain reaction was used to detect the expression of LC3-I, LC3-II and Beclin 1 on mRNA level.Results: Compared with the blank group, the cell viability of the CSE group was significantly decreased, and apoptosis and the level of autophagy in cells were significantly increased. The mRNA and protein expression of LC3-I, LC3-II, Beclin 1 and the protein level of p-p38 were significantly increased in the CSE-HBE cells. Compared to the CSE group, the different doses of XFPC medicated serum increased cell viability, decreased cell apoptosis, and inhibited mRNA and protein expression of LC3-I, LC3-II, Beclin 1 and protein level of p-p38. These results were especially observed in the group XFPC-H. After adding a p38 agonist, the therapeutic effect of XFPC on cell viability and autophagy was suppressed.Conclusion: XFPC significantly increased cell viability in a CSE-induced HBE cell model for chronic obstructive pulmonary disease through inhibiting the level of autophagy mediated by phosphorylation of p38.

Andrés Calvache-Mateo ◽  
Laura López-López ◽  
Alejandro Heredia-Ciuró ◽  
Javier Martín-Núñez ◽  
Janet Rodríguez-Torres ◽  

Background: Adults living with Chronic Obstructive Pulmonary Disease (COPD) often have difficulties when trying to access health care services. Interactive communication technologies are a valuable tool to enable patients to access supportive interventions to cope with their disease. The aim of this revision and meta-analysis is to analyze the content and efficacy of web-based supportive interventions in quality of life in COPD. Methods: Medline (via PubMed), Web of Science, and Scopus were the databases used to select the studies for this systematic review. A screening, analysis, and assessment of the methodological quality was carried out by two independent researchers. A meta-analysis of the extracted data was performed. Results: A total of 9 of the 3089 studies reviewed met the inclusion criteria. Most repeated web content elements were educational and involved communication with healthcare professional content. Finally, seven of the nine studies were included in a quantitative analysis. Web-based supportive interventions significantly improved quality of life when added to usual care (SMD = −1.26, 95% CI = −1.65, −0.86; p < 0.001) but no significant differences were found when compared with an autonomous pedometer walking intervention (p = 0.64) or a face-to-face treatment (p = 0.82). Conclusion: This systematic review and meta-analysis suggests that web-based supportive interventions may complement or accompany treatments in COPD patients due to the advantages of online interventions. The results obtained should be treated with caution due to the limited number of studies in this area and methodological weaknesses.

Vijayamma Ajmera ◽  
Iqbal Mohammed Sheikh ◽  
Sumant Kumar Dadhich

Practice related to demonstration on pulmonary rehabilitation techniques are posing a great threat globally in COPD patient's mortality and morbidity, COPD is an increasing health problem globally and India is not an exemption. The patients have poor practice related to pulmonary rehabilitation techniques. Present study is aimed to assess the effectiveness of demonstration on practice regarding pulmonary rehabilitation techniques among patients with chronic obstructive pulmonary disease in selected hospital at Udaipur city, Rajasthan. 60 samples was selected using Non probability purposive sampling techniques. The findings revealed that In pre test 88.33% respondents were found with poor level of practice whereas with post test 21.67% of the respondents had poor practice level, 11.67% respondents had average practice level in the pre test whereas in post test it was 75.00%, there were no respondents found with good practice level in pre test whereas in post test good respondents level improved to 3.33%. The study concluded that there was significant improvement in the level of practice of patient with COPD regarding pulmonary rehabilitation techniques. Which indicated that the demonstration was effective. The study also revealed that there is a significant association between pre test practice scores with selected socio demographic variables. Hence this kind of practice should be conducted from time to time for patients so that their practice can be improved by pulmonary rehabilitation techniques and reduce the breathing complications in COPD patients.

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