International Journal of Chronic Obstructive Pulmonary Disease最新文献

Purpose: The miR-125a-5p has been reported influence the development of lung cancer, however, the link between it and chronic obstructive pulmonary disease (COPD) is still not well understood. Hence, this study was designed to investigate the molecular pathway by which miR-125a-5p related biomarkers were involved in COPD.

Patients and methods: The differentially expressed genes (DEGs) and module genes related to COPD in GSE100153 were screened out by differential analysis and weighted gene co-expression network analysis, respectively. Then, the target genes of miR-125a-5p obtained from miRWalk database were intersected with DEGs and module genes, followed by identification of biomarkers through SVM-RFE algorithms. Moreover, the gene set enrichment analysis, immune infiltration analysis, construction of regulatory network, single-cell analysis and Mendelian randomization (MR) analysis were performed. At last, the expression levels of the biomarkers were further validated in GSE100153 and GSE146560 as well as in qRT-PCR.

Results: A total of 10 genes were acquired by intersecting the 126 DEGs, the 3989 module genes, and 2329 target genes, of which PITHD1, CNTNAP2 and GUCD1 were identified as biomarkers. Enrichment analysis showed their roles in various cellular functions. In addition, significant associations were identified between 9 distinct cells and biomarkers. Subsequently, 5 TFs and 63 therapeutic agents were predicted as biomarkers. Moreover, GUCD1 and PITHD1 were significantly different between case and control in T cells and Alveolar cells. In COPD, GUCD1 and PITHD1 were significantly down-regulated in GSE100153 and GSE146560 datasets and confirmed by qRT-PCR.

Conclusion: In our study, PITHD1, CNTNAP2, and GUCD1 were recognized as biomarkers related to miR-125a-5p-related genes in COPD, providing new references for treatment of COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease with high morbidity and mortality worldwide. Observational studies have shown correlations between common extrapulmonary comorbidities and COPD, but the existence of correlations does not necessarily prove a causal association. Therefore, causal relationships between diseases need to be explored by means of causal inference methods.

Materials and methods: Genetic correlation and two-sample Mendelian randomization (MR) analysis were explored to assess the causal relationship between exposures and outcomes with the genome-wide association studies (GWAS) dataset. Different sensitivity analyses were conducted to verify the robustness and consistency of results.

Results: The linkage disequilibrium score regression showed that cardiovascular disease (CVD), hypertension (HTN) and type 2 diabetes mellitus (T2DM) were significantly genetically associated with COPD. T2DM and HTN were found to have a positive causal effect on COPD. The odds ratio (OR) of T2DM on COPD was 1.111 (95% CI, 1.063-1.160; P<0.0001) and that of HTN on COPD was 1.125 (95% CI, 1.084-1.167; P < 0.0001). Similar results were verified by different MR methods. Furthermore, COPD had a positive causal effect on T2DM (OR 1.152 (95% CI, 1.064-1.246; P=0.0005)).

Conclusion: Our findings provided evidence for the causal association between HTN, T2DM and COPD, which would render new insights into the pathogenesis, prevention and intervention for COPD.

Purpose: Following the relatively recent introduction of single-inhaler triple therapies in Japan, this study compared the effectiveness of switching from multiple-inhaler triple therapy (MITT) to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) by investigating COPD exacerbations and adherence among patients with chronic obstructive pulmonary disease (COPD) in Japan.

Methods: This retrospective, pre-post cohort study using the Medical Data Vision Co. Ltd database identified patients with ≥1 inpatient diagnosis and/or ≥2 outpatient diagnoses of COPD at age ≥40 years prior to the index date (first/earliest date of single-inhaler FF/UMEC/VI initiation from May 1, 2019-February 28, 2022, following a switch from MITT). The proportion of patients with ≥1 overall (moderate-to-severe), moderate, or severe COPD exacerbation and rate of exacerbations were assessed at 6 months pre- and post-index. Medication adherence (proportion of days covered [PDC]) was also assessed.

Results: In total, 2365 patients were included, with a mean (standard deviation) age of 75.3 (9.7) years, and 77.1% were male. In the 6 months post-switch from MITT to FF/UMEC/VI, there was a statistically significant decrease in the proportion of patients who experienced ≥1 overall (11.2% to 8.8%; p=0.0014) and severe exacerbation (4.6% to 3.2%; p=0.0069). There was a similar proportion of patients who experienced ≥1 moderate exacerbation pre- and post-switch (6.9% to 6.2%; p=0.2394). Rates of overall (rate ratio [RR]: 0.86, 95% confidence interval [CI]: 0.74-1.00; p=0.0528) and moderate exacerbations (RR: 0.95, 95% CI: 0.79-1.13; p=0.5796) were numerically lower post-switch. There was a significant reduction in severe exacerbations post-switch (RR: 0.68, 95% CI: 0.51-0.90; p=0.0084). Mean PDC was significantly higher in the 6 months post- versus pre-switch (0.83 versus 0.80; p<0.0001).

Conclusion: Patients who switched from MITT to FF/UMEC/VI had reduced exacerbations and improved adherence. These results may help inform healthcare providers on the optimum management strategy for patients with COPD in Japan.

Background: Chronic obstructive pulmonary disease (COPD) has emerged as a very consequential issue threatening human life and health; therefore, research on its pathogenesis is urgently needed. A prior investigation discovered a significant elevation in the phosphoglycerate mutase 5 (PGAM5) expression in the lung tissue of COPD smoking patients. This rise in expression is closely associated with COPD severity. Nevertheless, the precise molecular processes by which PGAM5 influences the COPD initiation and advancement remain unknown.

Materials and methods: A COPD model was created using murine alveolar macrophages (MH-S). Flow cytometry, enzyme-linked immunosorbent assay, Western blotting, and other methods were used to detect macrophage polarization, inflammatory factor secretion levels, and changes in PGAM5 and the nuclear factor-κB (NF-κB) pathway.

Results: PGAM5 stimulated macrophage M1 polarization and secretion of the proinflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). PGAM5 bound and activated apoptotic signaling-regulated kinase 1 (ASK1), further activating the NF-κB pathway. These implications were reversed when PGAM5 expression was silenced.

Conclusion: PGAM5 can cause an increase in p-ASK1^T838, trigger the NF-κB pathway activation, and stimulate the M1 macrophage polarization and production of proinflammatory factors. This finding has significant implications for preventing and treating COPD.

Background: Recent evidence suggests that remote pulmonary rehabilitation (PR) meeting international criteria may be as effective as traditional in-person PR. During social distancing associated with COVID-19, in-person PR services were suspended in England. We assessed the use of remote PR services during COVID-19 social distancing.

Methods: An online questionnaire survey to assess the use of remote PR during the COVID-19 pandemic and the subsequent availability and delivery of remote PR in England was conducted. The characteristics of PR services in England that provided remote PR, and the barriers and facilitators of delivery of remote online PR by videoconferencing were assessed.

Results: Sixty-three services took part. Provision of remote PR rose from 17% to 95% for participating PR services during the pandemic. Remote PR was provided by telephone (65% of services), group videoconferencing (56%) and by individual patient videoconferencing (51%). Remote PR continued to be provided by 49 (76%) services following the relaxation of COVID-19-related restrictions on social contact. Barriers to the delivery of remote online PR using videoconferencing included patients' lack of internet access through inability to use smart phones or computers and perceived preference of patients for in-person provision. Perceived facilitators of remote online PR using videoconferencing were ease of staff delivery and the belief that it would be beneficial to patients.

Conclusion: Remote PR was widely used during the social distancing phase of the COVID-19 pandemic in England. Service users' lack of access to the internet was an important barrier to videoconferencing, the form of remote online PR for which evidence of effectiveness is most compelling. The provision of digital equipment and internet training should be considered to enable more equitable access to remote online PR. Despite no guideline recommendations for its utility at present, remote pulmonary rehabilitation via telephone or online videoconferencing appears to be a safe and feasible alternative when in-person pulmonary rehabilitation is unavailable.

Background: Severe alpha-1-antitrypsin deficiency (AATD) is a known risk factor for early development of emphysema and COPD. By the Swedish national screening program within the years 1972-74 a cohort of individuals with severe AATD (PiZZ) was identified and regularly followed up. The aim of this study was to investigate alveolar volume (V_A) and the ratio V_A/Total lung capacity (V_A/TLC) for the detection of signs of hyperinflation and ventilation heterogeneity in PiZZ individuals compared with an age-matched control group (phenotype PiMM), randomly selected from the population registry.

Methods: All study participants underwent pulmonary function tests (PFT) including dynamic spirometry and total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC) and alveolar volume (V_A). They answered a questionnaire on smoking habits and symptoms. Quality of life was assessed by answering the Saint George´s Respiratory Questionnaire (SGRQ).

Results: Fifty-six PiZZ and 66 PiMM individuals participated in the study. The PiZZ individuals had a significantly lower V_A/TLC ratio (p=0.004) and significantly higher RV (p<0.001) and RV/TLC ratio (p=0.001) than the PiMM individuals. The 13 PiZZ ever-smokers had a significantly higher TLC (p=0.025), RV (p=0.003) and FRC (p=0.003) and a significantly lower V_A/TLC ratio (p=0.006) than the 24 PiMM ever-smokers. No significant differences in RV, TLC, V_A, and V_A/TLC ratio were found between the never-smoking PiZZ and PiMM individuals. The ratio RV/TLC was significantly higher in the PiZZ never-smokers than in the PiMM never-smokers (p=0.026).

Conclusion: At the age of 42 the PiZZ ever-smokers have signs of hyperinflation and ventilation heterogeneity.

COPD is a multifactorial illness characterized by a long-term restriction of airflow and an inflammatory reaction in the lungs. The associated emphysema leads to the breakdown of alveolar proteins and abnormal expansion of the lung air spaces. Chronic bronchitis caused by the same disease can result in increased deposition of structural proteins, narrowing of the airways, and excessive mucus secretion leading to acute exacerbation of COPD (AECOPD). The most commonly prescribed medications for it, such as glucocorticoids and bronchodilators, provide important therapeutic benefits, but they also have negative side effects, including immunosuppression and infection. Therefore, it is necessary to develop medications for the treatment of COPD that specifically target the immune system and molecular components. This review focuses on non-eosinophilic aspects of immunological modulation in COPD management. Since, existing literature extensively covers eosinophilic inflammation, this review aims to fill the gap by examining alternative immunological pathways and their therapeutic implications. The findings suggest that targeting specific immune responses may enhance treatment efficacy while minimizing adverse effects associated with traditional therapies. In summary, this review emphasizes the importance of advancing research into non-eosinophilic immunological mechanisms in COPD, prescribing for the development of novel therapies that can more effectively manage this disease.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disorder characterized by irreversible airflow limitation and systemic immune impacts. COPD patients demonstrate an increased susceptibility to sepsis and septic shock, underscoring the importance of understanding its effects on splenic function.

Methods: A rat COPD model was established using lipopolysaccharide (LPS) and cigarette smoke exposure. Splenic function was assessed through carbon clearance assays, histological analysis, and high-throughput mRNA sequencing. In vitro assays were conducted to evaluate the role of secretoglobin family 1a member 1 (SCGB1A1) in macrophage activation and lymphocyte proliferation.

Results: Carbon clearance assays revealed a significant reduction in splenic phagocytic activity in the smoke-exposed group. Histological analysis showed lymphoid follicle atrophy and connective tissue hyperplasia. High-throughput mRNA sequencing identified 102 upregulated and 32 downregulated genes in the smoke-exposed group, with SCGB1A1 notably upregulated. In vitro assays confirmed that SCGB1A1 inhibits LPS-induced macrophage activation and Phytohemagglutinin (PHA)-induced lymphocyte proliferation.

Conclusion: These findings suggest that SCGB1A1 contributes to splenic immune dysfunction in COPD. Targeted inhibition of SCGB1A1 expression in the spleen may represent a potential therapeutic strategy to reduce the risk of sepsis in COPD patients.

Introduction: The Italian COPD Patient Association (Associazione Pazienti BPCO) conducted an online survey among its 2814 members with COPD to investigate the reasons for the widespread use of mucolytic therapies by patients, often including self-prescription using over the counter (OTC) alternatives.

Methods: After consulting with several respiratory specialists, the Association's steering committee developed a list of nine questions with possible answers that was posted on the website of the Association. The survey was open to all members of the Association, with responses to be e-mailed to the Association.

Results: Approximately 78% the 502 participants surveyed reported having used mucolytics in the previous six months, with 54.5% using prescribed medications and 23.5% opting for OTC medications. Usage patterns revealed that 43.4% utilized mucolytics during episodes of excessive mucus, while 35.5% used them regardless of the presence of mucus. In terms of formulation preferences, water-soluble granulated sachets (34.9%) and effervescent/dispersible tablets (22.8%) were the most preferred, followed by capsules (14.1%) and aerosol ampoules (11.2%). The factors influencing these preferences were the hydration benefits of sachets and tablets, the portability and taste advantages of capsules, and the swallowing difficulties of aerosol formulations. The data showed that 26.5% of survey participants consumed the entire contents of the prescribed or OTC package, while 19.9% utilised it for a minimum of 10 days, 31.5% for a period between 5 and 10 days, and 10.2% for less than 5 days. Cost was cited as a reason for discontinuation by 8.3% of participants. Notably, 29.5% of respondents believed that mucolytic efficacy was dependent on the amount of mucus. Most patients (66.3%) used mucolytics at home, and 57.4% took the medication once daily and 24.3% twice daily. Additionally, 41.8% were aware of the dual antioxidant and mucolytic properties of the medication.

Conclusion: These findings emphisise the need for a patient-centred approach, encouraging healthcare providers to consider individual preferences and offer personalised advice that has the potential to improve adherence and overall outcomes for COPD patients.

Aim: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by airflow limitation, which often leads to malnutrition and reduced quality of life. This study aims to evaluate the effect of individualized nutritional management on the nutritional status, pulmonary function, and overall quality of life of patients with COPD.

Methods: This research is a retrospective analysis, and the patients were grouped according to the treatment methods. This study involved 100 patients with chronic obstructive pulmonary disease and were hospitalized at our hospital from March 2022 to March 2024. Among them, 43 patients with individualized nutritional management were classified as the observation group, 57 patients with regular dietary therapy management were classified as the control group. We collect clinical data on lung function, nutritional status, scores of quality of life, psychological state evaluation index, clinical efficacy, and diet satisfaction.

Results: The total effective rate of the observation group was 88.37%, which was higher than that of the control group (85.96%), and the differences were statistically significant (P < 0.05). The FEV1, FVC and FVE1% of the observation group were significantly higher than those of the control group after intervention (all P < 0.05). Moreover, after the intervention, the 6-Minute Walk Test (6MWT) distance increased, and COPD Assessment Test (CAT) scores decreased significantly in both groups, with the observation group showing greater improvements (P < 0.05).

Conclusion: Nutrition management has a remarkable clinical curative effect in treating COPD patients, which can improve their nutritional status and quality of life.