Canadian Respiratory Journal

Background. Immune checkpoint inhibitors (ICIs) have become a standard care in non-small-cell lung cancer (NSCLC). However, its application to epidermal growth factor receptor (EGFR)-mutant NSCLC patients is confronted with drug resistance. This study aimed to clarify the potential role of Yes1-associated transcriptional regulator (YAP1) in ICIs treatment for EGFR-mutant NSCLC population. Methods. All the clinical data of NSCLC were downloaded from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) for GSE11969 and GSE72094. Based on YAP1 expression, all the NSCLC patients including the EGFR-mutant and EGFR-wildtype (WT) patients were divided into two groups, YAP1_High and YAP1_Low. Using cBioPortal, genetic alterations were analyzed for identification of immunogenicity in EGFR-mutant NSCLC. MR analysis was used to analyze the hub gene of EGFR. The infiltration of immune cells and the expression of the identified tumor-associated antigens were identified with TIMER. By graph learning-based dimensionality reduction analysis, the immune landscape was visualized. Moreover, survival analysis was performed to verify the predictive value of YAP1 in ICIs treatment for EGFR-mutant NSCLC population using Ren’s research data (NCT03513666). Results. YAP1 was a poor prognostic factor of EGFR-mutant NSCLC population rather than lung adenocarcinoma (LUAD) patients. MR analysis revealed that the EGFR gene regulated YAP1 expression. YAP1 was identified as a hub gene closely associated with immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population in TCGA LUAD. Tumors with YAP1_High showed an immune-“cold” and immunosuppressive phenotype, whereas those with YAP1_Low demonstrated an immune-“hot” and immunoactive phenotype. More importantly, it was verified that YAP1_High subpopulation had a significantly shorter progression-free survival (PFS) and overall survival (OS) after ICIs treatment in EGFR-mutant NSCLC patients in the clinical trial. Conclusions. YAP1 mediates immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population. YAP1 is a novel negative biomarker of ICIs treatment in EGFR-mutant NSCLC population. Clinical Trials. This trial is registered with NCT03513666.

This study aimed to explore the predictive factors of nonmalignant pathological diagnosis and final diagnosis of ultrasound-guided cutting biopsy for peripheral pulmonary diseases. A total of 470 patients with peripheral lung disease diagnosed as nonmalignant by ultrasound-guided cutting biopsy in the First Affiliated Hospital of Guangxi Medical University from January 2017 to May 2020 were included. Ultrasound biopsy was performed to determine the correctness of pathological diagnosis. Independent risk factors of malignant tumor were predicted by multivariate logistic regression analysis. Pathological biopsy results showed that 162 (34.47%) of the 470 biopsy data were specifically benign, and 308 (65.53%; malignant lesions: 25.3%, benign lesions: 74.7%) were nondiagnostic findings. The final diagnoses were benign in 387 cases and malignant in 83 cases. In the nondiagnostic biopsy malignant risk prediction analysis, lesion size (OR = 1.025, ), partial solid lesions (OR = 2.321, ), insufficiency (OR = 6.837, ), and presence of typical cells (OR = 34.421, ) are the final important independent risk factors for malignant tumors. In addition, 30.1% (25/83) of patients with nonmalignant lesions who were finally diagnosed with malignant tumors underwent repeated biopsy, and 92.0% (23/25) were diagnosed during the second repeated biopsy. 59.0% (49/83) received additional invasive examination. Nondiagnostic biopsy predictors of malignant risk include lesion size, partial solid lesions, insufficiency, and presence of atypical cells. When a nonmalignant result is obtained for the first time, the size of the lesion, whether the lesion is subsolid, and the type of pathology obtained should be reviewed.

Introduction. Chronic obstructive pulmonary disease (COPD) is the third leading cause of death, and COPD exacerbation worsens the prognosis. Eosinophilic airway inflammation is a COPD phenotype that causes COPD exacerbation and is correlated with peripheral blood eosinophil count. We analyzed real-world data of COPD patients to assess the risk factors of COPD exacerbation focusing on blood eosinophils. Materials and Methods. Patients with COPD who visited our hospital between January 1, 2018, and December 31, 2018, were recruited, and their background information, spirometry data, laboratory test results, and moderate-to-severe exacerbation events during the one-year follow-up period were collected from the electronic medical records and analyzed. The COPD exacerbation risk factors were assessed using univariate and multivariate logistic regression analyses. Results. Twenty-two of 271 (8.1%) patients experienced moderate-to-severe exacerbation. Patients with exacerbation showed worse pulmonary function, and we found that a high blood eosinophil count (≥350 cells/μL; ), low % FEV1 (<50%; ), increase in white blood cell (≥9000 cells/μL; ), and use of home oxygen therapy () were risk factors for future exacerbations. We also found a strong correlation between eosinophil count cut-offs and exacerbation risk (r = 0.89, ). On the other hand, there was no relation between exacerbation risk and inhalation therapy for COPD. Conclusion. In a real-world setting, peripheral blood eosinophil count could be a predictor of future COPD exacerbation.

Background. To explore the prognostic risk factors of 30-day death in patients with traumatic lower limb fracture (TLLF) complicated with acute pulmonary embolism (APE). Methods. 295 consecutive TLLF patients diagnosed as APE according to pulmonary artery CT angiography, hospitalized in our hospital from January 2017 to December 2021, were included in this study. Patients were divided into nonsurvival group and survival group according to 30-day follow-up results. After adjusting age, sex, and all the clinical variables with values of <0.2 with backward stepwise method (likelihood ratio), multivariate Cox regression analysis was used to analyze risk factors of 30 days all-cause death in TLLF patients with APE. The area under curve (AUC) calculated by receiver operating characteristic curve (ROC) and the incremental model were used to determine the prognostic potential of identified risk factors. Results. 29 patients died during 30-day follow-up. Simplified pulmonary embolism severity index (sPESI) score ≥1 (), Wells score ≥7 (), and pulmonary hypertension () were associated with higher risk, while anticoagulant therapy () was associated with lower risk of all-cause death during 30 days follow-up in APE patients. Compared with sPESI score, Wells score plus pulmonary hypertension produced better predictive efficacy. Prognostic value of sPESI score could be enhanced by adding Wells score, pulmonary hypertension, and anticoagulant therapy to the predicting models. Conclusions. Wells score ≥7 and pulmonary hypertension are independent predictive risk factors of 30-day all-cause death in TLLF patients with APE.

The aim of our study was to examine the production of monocyte chemoattractant protein (MCP-4) and eotaxin-3 during the onset and progression of COPD. The expression levels of MCP-4 and eotaxin-3 were evaluated in COPD samples and healthy controls using immunostaining and ELISA. The relationship between the clinic pathological features in the participants and the expression of MCP-4 and eotaxin-3 were evaluated. The association of MCP-4/eotaxin-3 production in COPD patients was also determined. The results revealed enhanced production of MCP-4 and eotaxin-3 in COPD patients especially the cases with AECOPD in both bronchial biopsies and bronchial washing fluid samples. Furthermore, the expression signatures of MCP-4/eotaxin-3 show high AUC values in distinguishing COPD patients and healthy volunteers and AECOPD and stable COPD cases, respectively. Additionally, the number of MCP-4/eotaxin-3 positive cases was notably increased in AECOPD patients compared to those with stable COPD. Moreover, the expression of MCP-4 and eotaxin-3 was positively correlated in COPD and AECOPD cases. In addition, the levels of MCP-4 and eotaxin-3 could be increased in HBEs stimulated with LPS, which is a risk factor of COPD. Moreover, MCP-4 and eotaxin-3 may exert their regulatory functions in COPD by regulating CCR2, 3, and 5. These data indicated that MCP-4 and eotaxin-3 were potential markers for the clinical course of COPD, which could provide guidance for accurate diagnosis and treatment for this disease in future clinical practice.

Background. There are very few professional recommendations or guidelines on the needle thoracentesis decompression (NTD) for the tension pneumothorax in the elderly. This study aimed to investigate the safety and risk factors of tension pneumothorax NTD in patients over 75 years old based on CT evaluation of the chest wall thickness (CWT). Methods. The retrospective study was conducted among 136 in-patients over 75 years old. The CWT and closest depth to vital structure of the second intercostal space at the midclavicular line (second ICS-MCL) and the fifth intercostal space at the midaxillary line (fifth ICS-MAL) were compared as well as the expected failure rates and the incidence of severe complications of different needles. We also analyzed the influence of age, sex, presence or absence of chronic obstructive pulmonary disease (COPD), and body mass index (BMI) on CWT. Results. The CWT of the second ICS-MCL was smaller than the fifth ICS-MAL both on the left and the right side (). The success rate associated with a 7 cm needle was significantly higher than a 5 cm needle (), and the incidence of severe complications with a 7 cm needle was significantly less than an 8 cm needle (). The CWT of the second ICS-MCL was significantly correlated with age, sex, presence or absence of COPD, and BMI (), whereas the CWT of the fifth ICS-MAL was significantly correlated with sex and BMI (). Conclusion. The second ICS-MCL was recommended as the primary thoracentesis site and a 7 cm needle was advised as preferred needle length for the older patients. Factors such as age, sex, presence or absence of COPD, and BMI should be considered when choosing the appropriate needle length.