Clinical Respiratory Journal最新文献

Introduction

This expanded access program (EAP) provided ruxolitinib (oral, selective Janus kinase [JAK]1/JAK2 inhibitor) for emergency treatment of COVID-19–associated cytokine storm in patients eligible for hospitalization (NCT04355793).

Methods

Patients received ruxolitinib 5 mg twice daily (preferred regimen when tolerated) or once daily for ≤ 14 days, or until determination of no clinical benefit was made. Outcomes were clinical status, physician-assessed clinical benefit, and serious adverse event (SAE) incidence.

Results

Of 312 patients, 45.5% achieved ≥ 1-point clinical status improvement. Physician-assessed clinical benefit was reported in 42.6% of evaluable patients. SAEs occurred in 42.9%, with 2.6% experiencing an SAE suspected to be ruxolitinib related.

Conclusions

Overall, some hospitalized patients with COVID-19–associated cytokine storm who received ruxolitinib experienced clinical status improvement; ruxolitinib was well tolerated.

Trial Registration

ClinicalTrials.gov identifier: NCT04355793

Background

This study aims to summarize the similarities and differences in immune cell characteristics, and potential therapeutic targets between systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF).

Methods

This study included SSc-ILD and SSc-nonILD patients who were admitted to Beijing Chaoyang Hospital between April 4th, 2013, to June 30th, 2023. Publicly available datasets, including peripheral blood monocular cell (pbmc) single-cell data, SSc, SSc-ILD pbmc transcriptome data, and SSc-ILD, IPF lung tissue transcriptome data were analyzed. Statistical analyses were conducted using the SPSS and R software, employing standard statistical methods and bioinformatics packages such as Seurat, DESeq2, enrichR, and CellChat.

Results

The results revealed that the CD4+/CD8+ T cell ratio of pbmc in SSc-ILD patients was significantly higher than in SSc-nonILD patients. In IPF patients, an elevated CD4+/CD8+ T cell ratio was also observed in progressive group, and Treg and mature CD4+ T cells might cause this change. JAK–STAT pathway and the cytokine–cytokine receptor interaction pathway were activated in peripheral blood T cells of IPF patients. The CD30, CD40, and FLT3 signaling pathways were found to play crucial roles in T cell interactions with other immune cells among IPF patients. SPA17 as a commonly upregulated gene among SSc, SSc-ILD, and IPF pbmc and lung, with its expression correlating positively with disease severity and lung function progression.

Conclusion

CD4+/CD8+ T cell ratio might associate with ILD initiation and progression; Treg cells and mature CD4+ T cells play key roles of it. SPA17 might serve as a pan-ILD marker and associated with lung function progression.

Objectives

This study aims to investigate the association between elderly patients with COPD with different blood eosinophil on admission and those without COPD and the prognosis of COVID-19.

Method

A territory-wide retrospective study was conducted to investigate the association between elderly COPD patients with different blood eosinophil on admission and the prognosis of COVID-19. Elderly patients admitted to public hospitals and community treatment facility in Hong Kong for COVID-19 from January 23, 2020, to September 31, 2021, were included in the study. Severe diseases were defined as those who develop respiratory complications, systemic complications and death.

Results

Among the 1925 patients included, 133 had COPD. Forty had admission blood eosinophil count ≥ 150 cells/μL, and 93 had blood eosinophil count < 150 cells/μL. Patients with COPD and admission blood eosinophil count ≥ 150 cells/μL, but not those with admission blood eosinophil count < 150 cells/μL, had severe COVID-19 with the development of respiratory and systemic complications. They were more likely to develop respiratory failure (OR = 5.235, 95% CI = 2.088–13.122, p < 0.001) and require invasive mechanical ventilation (OR = 2.433, 95% CI = 1.022–5.791, p = 0.045) and intensive care unit admission (OR = 2.214, 95% CI = 1.004–4.881, p = 0.049).

Discussion

Our study suggested that the blood eosinophil count on admission could have significant prognostic implications among elderly patients with COPD. Patients with COPD and admission blood eosinophil count ≥ 150 cells/μL, but not those with admission blood eosinophil count < 150 cells/μL, have significantly increased risks of developing respiratory and systemic complications from COVID-19, when compared with non-COPD patients.

Introduction

Anti-neutrophil cytoplasmic antibody (ANCA) seropositivity strongly correlates to ANCA-associated vasculitis. Patients with idiopathic interstitial pneumonias (IIPs) without systemic vasculitis are sometimes ANCA-positive. Radiological and pathological differences between patients with myeloperoxidase (MPO)-ANCA-positive and those with proteinase 3 (PR3)-ANCA-positive IIPs remain unclear. To determine whether high-resolution computed tomography (HRCT) features and pathology findings differ by ANCA subtype in ANCA-positive IIP patients in a national database. Clinical, radiological, and pathological data were examined along with a web-based multidisciplinary discussion.

Methods

We reviewed records of 10 MPO-ANCA-positive and 9 PR3-ANCA-positive IIP patients who underwent HRCT and surgical lung biopsy between April 2009 and March 2014. Pulmonologists, chest radiologists, and pathologists evaluated HRCT scans and pathological findings independently. Patterns were classified using ATS/ERS/JRS/ALAT 2011 guidelines for idiopathic pulmonary fibrosis.

Results

HRCT patterns were definite usual interstitial pneumonia (UIP) (n = 8; 42.1%), possible UIP (n = 6; 31.6%), and inconsistent with UIP (n = 5; 26.3%). Pathological patterns were definite UIP (n = 5; 26.3%), probable UIP (n = 8; 42.1%), possible UIP (n = 4; 21.1%), and not UIP (n = 2; 10.5%). HRCT and pathological patterns did not differ between MPO-ANCA-positive and PR3-ANCA-positive IIPs. Radiological features were reticulation (n = 13; 68.4%), nodules (n = 12; 63.1%), honeycombing (n = 10; 52.6%), and increased attenuation around honeycombing (n = 7; 36.8%). Pathological findings were cysts (n = 12; 63.1%), lymphoid follicles with germinal centers (n = 11; 57.9%), and peribronchiolar wall lymphocytic infiltration (n = 11; 57.9%).

Conclusion

HRCT and pathological patterns did not differ between MPO-ANCA-positive and PR3-ANCA-positive IIPs. This absence of significant differences suggests a similar mechanism underlying both types of interstitial pneumonia.

Introduction

Mechanical ventilation is a significant risk factor for developing ventilator-associated pneumonia. Although silver-coated endotracheal tubes have been shown to reduce the bacterial burden, the efficacy of silver-based ion additive ventilator circuits in reducing bacterial colonization remains unclear.

Methods

This single-site, randomized controlled trial compared the incidence of bacterial contamination between a silver-additive ventilator circuit and a ventilator circuit that did not have a silver additive. Bacterial samples were collected from the inspiratory limb and Y-adaptor of the circuit and analyzed using culture and identification methods.

Results

Bacterial growth was observed in all samples from the control group and in 93.7% and 81.2% of inspiratory limb and Y-adaptor samples, respectively, from the study group. The colony counts in the inspiratory limb samples were significantly different between the groups, with a higher proportion of undesirable colony counts in the control group compared with the study group. No significant difference between the groups was observed in the colony counts in the Y-adaptor samples.

Conclusion

The use of a silver-additive ventilator circuit may reduce bacterial circuit colonization. However, further research with larger sample sizes and more diverse patient populations is necessary to confirm these findings.

Trial Registration: ClinicalTrial.gov: NCT04927806

Background

The correlation between chronic obstructive pulmonary disease (COPD) and Type 2 diabetes mellitus (T2DM) has long been recognized, but their shared molecular underpinnings remain elusive. This study aims to uncover common genetic markers and pathways in COPD and T2DM, providing insights into their molecular crosstalk.

Methods

Utilizing the Gene Expression Omnibus (GEO) database, we analyzed gene expression datasets from six COPD and five T2DM studies. A multifaceted bioinformatics approach, encompassing the limma R package, unified matrix analysis, and weighted gene co-expression network analysis (WGCNA), was deployed to identify differentially expressed genes (DEGs) and hub genes. Functional enrichment and protein–protein interaction (PPI) analyses were conducted, followed by cross-species validation in Mus musculus models. Machine learning techniques, including random forest and LASSO regression, were applied for further validation, culminating in the development of a prognostic model using XGBoost.

Results

Our analysis revealed shared DEGs such as KIF1C, CSTA, GMNN, and PHGDH in both COPD and T2DM. Cross-species comparison identified common genes including PON1 and CD14, exhibiting varying expression patterns. The random forest and LASSO regression identified six critical genes, with our XGBoost model demonstrating significant predictive accuracy (AUC = 0.996 for COPD).

Conclusions

This study identifies key genetic markers shared between COPD and T2DM, providing new insights into their molecular pathways. Our XGBoost model exhibited high predictive accuracy for COPD, highlighting the potential utility of these markers. These findings offer promising biomarkers for early detection and enhance our understanding of the diseases' interplay. Further validation in larger cohorts is recommended.