Lin Liu

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is known to impose a significant burden on patients, but its demographic and clinical features in patients with AECOPD at high altitude (HA) still need to be addressed. A total of 142 patients with AECOPD at HA [>2,500 meters (m)] and 142 patients with AECOPD at low altitude (LA) (<500 m) as controls, matched 1:1 by age and sex, encountered at West China Hospital of Sichuan University (Chengdu, China) between January 2023 and December 2023, were retrospectively analyzed. Demographics, cardiopulmonary comorbidities, laboratory data and length of hospital stay (LOHS) of patients with AECOPD at HA and LA were comparatively analyzed. Univariate and multivariate binary logistic regression analyses were used to identify factors associated with prolonged LOHS in patients with AECOPD at HA. Compared to the LA group, patients with AECOPD at HA, regardless of sex and age, demonstrate certain different demographic and clinical features, including more Tibetans and non‑smokers, different prevalences of cardiopulmonary comorbidities and indicators in blood routine and biochemical tests, particularly higher hemoglobin levels and eosinophils count, which were negatively associated with LOHS. The present findings highlight that these differences could play an important role in the evaluation and prognosis of AECOPD at HA, and future studies should investigate the mechanisms underlying these differences and explore novel interventions to improve clinical outcomes for patients with AECOPD at HA.

Objectives: Diagnosis and assessment of chronic obstructive pulmonary disease (COPD) rely extensively on spirometry, which necessitates patient cooperation. The clinical value of impulse oscillometry (IOS) as a non-volitional method in patients with COPD remains uncertain.Design: This retrospective observational study was conducted using patient data from between January 2014 and December 2015.Setting: Five public hospitals in China: West China Hospital, Nuclear Industry 416 Hospital, Suining Central Hospital, Affiliated Hospital, Medical College of Chengdu University and 363 Hospital.Participants: The study included 6307 participants aged>40 years, comprising 2109 COPD patients and 4198 general non-COPD individuals, according to the Global Initiative for Obstructive Lung Disease (GOLD) spirometry standard. Participants with lung cancer, pulmonary tuberculosis, pneumonia or those who underwent lung resection were excluded from the study.Outcome measures and analysis: Demographic data, spirometry results and IOS results were collected. Spearman’s correlation analysis was used to examine the correlation between the IOS and spirometry parameters. Receiver operating characteristic curve analysis was used to evaluate the IOS performance in COPD diagnosis and severity staging.Results: Patients with COPD exhibited significant increases in Z5, R5, R20, R5−R20, Fres and Rp, but a decrease in X5 compared with non-COPD subjects (p25%–75%, forced expiratory volume in one second (FEV₁)/forced vital capacity and FEV_1%, respectively. However, the combination of these five IOS parameters did not exhibit ideal performance in diagnosing COPD (area under the curve (AUC) 0.78; sensitivity 63.68%; specificity 80.09%), differentiating GOLD stage 1 patients from the general non-COPD population (AUC 0.71; sensitivity 54.71%; specificity 77.49%) or identifying GOLD stages 3 and 4 patients among those with COPD (AUC 0.75; sensitivity 69.51%; specificity 70.32%).Conclusion: IOS parameters, while showing good correlation with spirometry in patients with COPD, did not perfectly substitute for spirometry in diagnosing COPD, especially in the early and advanced stages of the disease.

Introduction: NOD-like receptor protein 3 (NLRP3) is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Here, we explored the role of NLRP3 in cigarette smoke (CS)-induced airway inflammation in COPD.Material and methods: NLRP3 expression level was assessed with the microarray data in GEO datasets and validated in serum by ELISA from a case-control cohort. Male C57BL/6J mice were randomly divided into: saline, CS, MCC950 (a specific NLRP3 inhibitor, 10 mg/kg) and CS + MCC950 (5 mg/kg and 10 mg/kg) groups (n = 5 per group). All mice were exposed to CS or air for 4 weeks. Then, broncho-alveolar lavage (BAL) fluid and lung tissues were collected for cell counting, ELISA, HE staining and RNA sequencing with validation by real-time qPCR.Results: Compared to non-smokers, NLRP3 expression was significantly elevated in the lung tissues and sera of COPD smokers. CS remarkably induced airway inflammation in mice, characterized by an increase of inflammatory cells and proinflammatory cytokines in BAL fluid and HE inflammatory score, which were ameliorated by MCC950 treatment dose-dependently. Subsequently, 84 candidate genes were selected following RNA sequencing, and five hub genes (Mmp9, IL-1α, Cxcr2, Cxcl10, Ccr1) were then identified by PPI and MCODE analyses, which were confirmed by real-time qPCR. GO and KEGG analysis suggested that the five genes were enriched in a complicated network of inflammatory processes and signaling pathways.Conclusions: NLRP3 expression is elevated in lungs and sera of COPD smokers. Inhibition of NLRP3 significantly attenuates CS-induced airway inflammation in mice via inactivation of multiple hub genes and their related inflammatory processes and signaling pathways.

Nocardia species are gram-positive, acid-fast, saprophytic, aerobic bacilli, predominantly resulting in opportunistic infections in immunocompromised individuals. Here, we reported a case of Nocardia infection in a 27-year-old woman with normal immunocompetence, who presented as a solitary neoplasm in the left principal bronchus with a chief complaint of postural dyspnea. By electrotomy via bronchoscopy, the neoplasm was successfully removed, and it was further identified as Nocardia farcinica by metagenomic next-generation sequencing.

Objectives Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the risk of COPD and COPD-related clinical events. Design A systematic review and meta-analysis. Data sources PubMed, Ovid EMBASE and Ovid CENTRAL were searched from inception to 22 February 2023. Eligibility criteria for studies We included trials and observational studies evaluating association of PD with the risk of COPD or COPD-related events (exacerbation and mortality), with statistical adjustment for smoking. Data extraction and synthesis Two investigators independently extracted data from selected studies using a standardised Excel file. Quality of studies was evaluated using the Newcastle-Ottawa Scale. OR with 95% CI was pooled in a random-effect model with inverse variance method. Results 22 observational studies with 51 704 participants were included. Pooled analysis of 18 studies suggested that PD was weakly associated with the risk of COPD (OR: 1.20, 95% CI 1.09 to 1.32). However, in stratified and subgroup analyses, with strict adjustment for smoking, PD no longer related to the risk of COPD (adjusting for smoking intensity: OR: 1.14, 95% CI 0.86 to 1.51; smokers only: OR: 1.46, 95% CI 0.92 to 2.31; never smokers only: OR: 0.93, 95% CI 0.72 to 1.21). Moreover, PD did not increase the risk of COPD-related exacerbation or mortality (OR: 1.18, 95% CI 0.71 to 1.97) in the pooled result of four studies. Conclusions This study demonstrates PD confers no risk for COPD and COPD-related events when strictly adjusted by smoking. Large-scale prospective cohort studies with control of potential confounding factors are warranted to validate the present findings.

Purpose: DNA methylation, a major epigenetic modification, has been documented to play an important role in chronic obstructive pulmonary disease (COPD). In this study, we aimed to profile the DNA methylation patterns in a mouse model of airway inflammation induced by cigarette smoke (CS), a foremost risk factor of COPD. Material and Methods: To establish a model of airway inflammation, wild-type mice were exposed to mainstream CS or room air for 2 hours twice daily, 6 days per week for consecutive 4 weeks. Lung tissues of the mice were collected for genome-wide DNA methylation analysis by liquid hybridization capture-based bisulfite sequencing, which were used for intersection analysis with gene expression by cDNA microarray to identify candidate methylated genes. Then, functional enrichment analyses with protein–protein interaction (PPI) network regarding these genes were conducted to explore the potential mechanisms. Results: After 4-week CS exposure, the level of DNA methylation accompanied by a subacute airway inflammation was markedly enhanced, and 2002 differentially methylated genes (DMGs) were annotated, including 565 DMGs contained methylations in gene promoters, which were used for intersection with the differentially expressed genes. Then, 135 candidate methylated genes were further selected by the intersection, among which 58 genes with functional methylated modification were finally identified. Further analyses revealed candidate methylated genes were significantly enriched in a complicated network of signals and processes, including interleukins, toll-like receptors, T-cells differentiation, oxidative stress, mast cells activation, stem cells proliferation, etc., as well as the 58 functional methylated genes were partially located at key positions in PPI network, especially CXCL1, DDX58 and JAK3. Conclusion: This study suggests CS exposure significantly enhances DNA methylated level, and the potential functional methylated genes are closely related to complicated inflammatory-immune responses, which may provide some new experimental evidence in understanding the epigenetic mechanisms of CS-induced airway inflammation in COPD.

Background: Current guideline conditionally recommends regular use of anti-reflux medication in idiopathic pulmonary fibrosis (IPF). However, the effect of anti-reflux therapy in this group remains controversial. We systematically reviewed literatures to evaluate whether anti-reflux therapy could ameliorate pulmonary function in IPF. Methods: We performed electronic search in PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) to identify original articles published in English language. We included randomized controlled trials (RCTs) and observational studies regarding anti-reflux therapy on pulmonary function in IPF. Qualitative and quantitative analyses were conducted. In quantitative analysis, the inversevariance method with fixed-effect model was used to analyze pooled data. Results: Fifteen studies (2 RCTs and 13 observational studies) including 3,891 patients with IPF were included. Pooled analysis suggested that anti-reflux therapy did not improve forced vital capacity (FVC)% predicted [mean difference (MD) =0.88, 95% confidence interval (CI): -0.22 to 1.98, P=0.12, I-2 =0%, 8 studies, n=3,076], diffusing capacity of the lung for carbon monoxide (DLCO) % predicted (MD =0.75, 95% CI: -0.13 to 1.62, P=0.10, I-2 =0%, 8 studies, n=3,073), and FVC decline (MD =0.02, 95% CI: -0.01 to 0.04, P=0.29, I-2 =17%, 5 studies, n=1,586) in IPF. Discussion: Anti-reflux therapy may not ameliorate pulmonary function in IPF. However, adequately powered studies are warranted to validate the present findings.

Purpose: Chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD) are common disorders and usually co-exists. However, genetic mechanisms between COPD and LUAD are rarely reported. This study aims to identify susceptible genes of COPD with LUAD. Methods: Using the published data of GSE106899, co-expression modules were constructed by weighted gene co-expression network analysis (WGCNA). Subsequently, top 50 genes in the most tumor-related module were identified, among which hub genes were selected and validated. Results: Twenty co-expression modules were constructed on 13,865 genes from 62 lung tissues of COPD patients with or without LUAD, in which one module (blue) was most related to tumorigenesis. Functional enrichment analyses showed that the genes in the blue module were mainly enriched in cell cycle, DNA transcription/replication and cancer pathways, etc. Combined with protein–protein interaction network, MTA1, PKMYT1 and FZR1 genes had the most intramodular connectivity, which were regarded as the hub genes. However, only FZR1 was validated to be overexpressed in lung tissues of COPD with LUAD and cigarette smoke extract-stimulated A549 cells, a human LUAD cell line. Conclusion: This study suggests overexpression of FZR1 may play a key role in the tumorigenesis of LUAD in patients with COPD.

Background: Pulmonary hypertension (PH) is a multi-causal disease and no satisfactory therapeutic strategies for it. Statins have been suggested as potential drugs in PH, whose effects in different clinic types of PH have not been conclusive. In this study, we included randomized controlled clinical trials (RCTs) evaluating the efficacy and safety of statins therapy in PH. Methods: We searched databases including Medline, Embase, Cochrane, PubMed and Web of science, with time up to January 1, 2019. With 95% confidence interval (CI), weighted mean difference (WMD) or standardized mean difference (SMD) was pooled and calculated in a random or fixed effect model according to I2 statistic. Results: A total of nine RCTs with 657 patients were included. Four types of statins (atorvastatin, pravastatin, rosuvastatin and simvastatin) were used at different doses (10–80 mg daily) for up to 6 months. In the pooled-data analysis, compared with placebo, there were significant improvements in pulmonary arterial pressure (PAP), in addition to low-density lipoprotein (LDL) in patients treated with statins, but not in 6-minute walking distance (6MWD), cardiac index (CDI). No more adverse events and all-cause mortality were revealed. Subgroup analysis indicated that statins could decrease PAP in the subtype of PH due to chronic obstructive pulmonary disease (COPD), but not pulmonary arterial hypertension (PAH). Conclusions: This study indicates that statins can efficiently and safely reduce PAP in PH, especially in the subtype due to COPD. Further RCTs are needed to focus on the efficacy and safety of statin therapy in different subtypes of PH.

OBJECTIVE: Vitamin D deficiency plays an important role in chronic obstructive pulmonary disease (COPD). However, the effects of vitamin D supplementation on lung function decline in COPD were inconsistently reported and a meta-analysis is thus needed. MATERIALS AND MTHODS: Eligible cohort and randomized controlled trials (RCTs) were searched from databases including PubMed. Embase, and Web of Science. Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated in a random or fixed effects model. RESULTS: Eight studies reaching the inclusion criteria and involving 687 COPD patients were included. Pooled effect size showed vitamin D treatment resulted in no significant improvements in FEV1 (SMD: 0.38, 95% CI: -0.13 to 0.88, p= 0.144), FVC (SMD: 0.55, 95% CI: -0.49 to 1.58, p=0.299), and FEV1/FVC (SMD: 0.00, 95% CI: -0.27-0.27, p=0.995) in COPD patents. Subgroup analysis revealed neither short-term (= 6 months) (SMD: 0.52, 95% CI: -0.23 to 1.27, p=0.172) vitamin D exposure could significantly benefit lung function decline in COPD. CONCLUSIONS: This meta-analysis shows neither short-term nor long-term addition; supplementation of vitamin D can benefit the lung function decline in COPD. Moreover, large scale RCTs focusing on COPD smokers with low level of vitamin D should be considered.