Longitudinal changes in the volume of residual lung lobes after lobectomy for lung cancer: a retrospective cohort study.

It is unclear how the residual lobe volume changes over time after lobectomy. This study aims to clarify the temporal patterns of volume changes in each remaining lung lobe post-lobectomy. A retrospective review was conducted on patients who underwent lobectomy for lung cancer at Yueyang Central Hospital from January to December 2021. Lung CT images were reconstructed in three dimensions to calculate the volumes of each lung lobe preoperatively and at 1, 6, and 12 months postoperatively. A total of 182 patients were included. Postoperatively, the median total lung volume change rates relative to preoperative values were -20.1%, -9.3%, and -5.9% at 1, 6, and 12 months, respectively. Except for the right middle lobe in patients who underwent right upper lobectomy, the volumes of individual lung lobes exceeded preoperative values. The volume growth of the lung on the side of the resection was significantly more than that of the lung on the opposite side. For left lobectomy patients, the right lower lobe's volume change rate exceeded that of the right upper and middle lobes. Among right lobectomy patients, the left lower lobe and the relatively inferior lobe of right lung had higher volume change rates than the superior one. Right middle lobe change rate was more in patients with right lower lobectomy than right upper lobectomy. Six months postoperatively, FEV1% and right middle lobectomy were positively correlated with the overall volume change rate. One year postoperatively, only age was negatively correlated with the overall volume change rate. 75 patients had pulmonary function tests. Postoperative FEV1 change linearly correlated with 1-year lung volume change rate, but not with theoretical total lung volume change rate or segmental method calculated FEV1 change. Time-dependent compensatory volume changes occur in remaining lung lobe post-lobectomy, with stronger compensation observed in the relatively inferior lobe compared to the superior one(s). Preoperative lung function and age may affect compensation level.

Efficacy and safety of tralokinumab in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To assess the efficacy and safety of Tralokinumab in the treatment of moderate-to-severe atopic dermatitis (AD). METHODS: PubMed, Embase, Clinical Trials Website, and Cochrane Library were systematically searched for eligible randomized controlled trials which assessed the effects of Tralokinumab on AD. Primary outcomes included Scoring Atopic Dermatitis score, EASI-75%, and Investigator's Global Assessment score of 0 or 1 in 12 to 16 weeks. Secondary outcomes included the Eczema area and severity index score, the Numeric Rating Scales score, the dermatology life quality index score, and the overall incidence of adverse events. The quality of included studies was evaluated using the Cochrane System and the modified Jadad scale. Analysis was performed using Stata 16 software. RESULTS: Eight randomized controlled trials involving 2878 patients were included in this meta-analysis. Compared to placebo, Tralokinumab treatment exhibited a significantly higher Scoring Atopic Dermatitis score [SMD = -0.53, 95% confidence intervals [CI]: -0.62 to -0.44, P < .00001], an increased number of patients with EASI-75% [odds ratio (OR) = 2.44, 95% CI: 2.00-2.97, P < .00001] and Investigator's Global Assessment score of 0 or 1 in 12 to 16 weeks [OR = 2.12, 95% CI: 1.71-2.63, P < .00001]. No significant difference was observed in the incidence of overall adverse events [OR = 1.00, 95% CI: 0.85-1.18, P = 1.00] between the 2 groups. CONCLUSION: Tralokinumab is effective and safe in treatment of moderate-to-severe AD.

Metagenomic next-generation sequencing for the diagnosis of Chlamydia psittaci pneumonia.

The aim of this study was to investigate the clinical characteristics of Chlamydia psittaci pneumonia and evaluate the diagnostic value of Metagenomic Next-Generation Sequencing (mNGS). A total of 44 patients diagnosed with Chlamydia psittaci pneumonia using mNGS were retrospectively analysed. The demographic and clinical features, laboratory data, imaging findings and clinical outcomes were collected. Results showed that 65.91% of the patients had a history of exposure to poultry or birds. All patients presented with fever. Apart from systemic and respiratory symptoms, some patients also presented with digestive and neurological symptoms. Respiratory failure was common among patients. The key laboratory tests were normal white blood cell counts, slightly elevated PCT, changes in levels of cardiac enzymes, liver enzymes and hyponatremia. Chest imaging revealed that most of the lesions contained patchy exudation or lobar consolidation of one lobe, especially in the lower lobe. Consolidation of both lungs was seen in critically ill patients. Although quinolones were effective in most patients, tetracyclines should be the first choice of treatment. The overall prognosis was good; however, patients who developed severe pneumonia had poor prognosis. The incidence of chlamydia psittaci pneumonia may be underestimated due to the nonspecific clinical manifestations and lack of confirmatory testing methods. The use of mNGS has increased the number of patients diagnosed with chlamydia psittaci pneumonia. mNGS is an effective diagnostic method for chlamydia psittaci pneumonia.

Incubation period, clinical and lung CT features for early prediction of COVID-19 deterioration: development and internal verification of a risk model.

BACKGROUND: Most severe, critical, or mortal COVID-19 cases often had a relatively stable period before their status worsened. We developed a deterioration risk model of COVID-19 (DRM-COVID-19) to predict exacerbation risk and optimize disease management on admission. METHOD: We conducted a multicenter retrospective cohort study with 239 confirmed symptomatic COVID-19 patients. A combination of the least absolute shrinkage and selection operator (LASSO), change-in-estimate (CIE) screened out independent risk factors for the multivariate logistic regression model (DRM-COVID-19) from 44 variables, including epidemiological, demographic, clinical, and lung CT features. The compound study endpoint was progression to severe, critical, or mortal status. Additionally, the model's performance was evaluated for discrimination, accuracy, calibration, and clinical utility, through internal validation using bootstrap resampling (1000 times). We used a nomogram and a network platform for model visualization. RESULTS: In the cohort study, 62 cases reached the compound endpoint, including 42 severe, 18 critical, and two mortal cases. DRM-COVID-19 included six factors: dyspnea [odds ratio (OR) 4.89;confidence interval (95% CI) 1.53-15.80], incubation period (OR 0.83; 95% CI 0.68-0.99), number of comorbidities (OR 1.76; 95% CI 1.03-3.05), D-dimer (OR 7.05; 95% CI, 1.35-45.7), C-reactive protein (OR 1.06; 95% CI 1.02-1.1), and semi-quantitative CT score (OR 1.50; 95% CI 1.27-1.82). The model showed good fitting (Hosmer-Lemeshow goodness, X2(8) = 7.0194, P = 0.53), high discrimination (the area under the receiver operating characteristic curve, AUROC, 0.971; 95% CI, 0.949-0.992), precision (Brier score = 0.051) as well as excellent calibration and clinical benefits. The precision-recall (PR) curve showed excellent classification performance of the model (AUCPR = 0.934). We prepared a nomogram and a freely available online prediction platform ( https://deterioration-risk-model-of-covid-19.shinyapps.io/DRMapp/ ). CONCLUSION: We developed a predictive model, which includes the including incubation period along with clinical and lung CT features. The model presented satisfactory prediction and discrimination performance for COVID-19 patients who might progress from mild or moderate to severe or critical on admission, improving the clinical prognosis and optimizing the medical resources.

A Clinically Applicable Nomogram for Predicting the Risk of Invasive Mechanical Ventilation in Pneumocystis jirovecii Pneumonia.

Objective: Pneumocystis jirovecii pneumonia (PCP) is a life-threatening disease associated with a high mortality rate among immunocompromised patient populations. Invasive mechanical ventilation (IMV) is a crucial component of treatment for PCP patients with progressive hypoxemia. This study explored the risk factors for IMV and established a model for early predicting the risk of IMV among patients with PCP. Methods: A multicenter, observational cohort study was conducted in 10 hospitals in China. Patients diagnosed with PCP were included, and their baseline clinical characteristics were collected. A Boruta analysis was performed to identify potentially important clinical features associated with the use of IMV during hospitalization. Selected variables were further analyzed using univariate and multivariable logistic regression. A logistic regression model was established based on independent risk factors for IMV and visualized using a nomogram. Results: In total, 103 patients comprised the training cohort for model development, and 45 comprised the validation cohort to confirm the model's performance. No significant differences were observed in baseline clinical characteristics between the training and validation cohorts. Boruta analysis identified eight clinical features associated with IMV, three of which were further confirmed to be independent risk factors for IMV, including age (odds ratio [OR] 2.615 [95% confidence interval (CI) 1.110-6.159]; p = 0.028), oxygenation index (OR 0.217 [95% CI 0.078-0.604]; p = 0.003), and serum lactate dehydrogenase level (OR 1.864 [95% CI 1.040-3.341]; p = 0.037). Incorporating these three variables, the nomogram achieved good concordance indices of 0.829 (95% CI 0.752-0.906) and 0.818 (95% CI 0.686-0.950) in predicting IMV in the training and validation cohorts, respectively, and had well-fitted calibration curves. Conclusions: The nomogram demonstrated accurate prediction of IMV in patients with PCP. Clinical application of this model enables early identification of patients with PCP who require IMV, which, in turn, may lead to rational therapeutic choices and improved clinical outcomes.

Chronic hypoxia promoted pulmonary arterial smooth muscle cells proliferation through upregulated calcium-sensing receptorcanonical transient receptor potential 1/6 pathway.

OBJECTIVES: Although both calcium-sensing receptor (CaSR) and canonical transient receptor potential (TRPC) proteins contribute to chronic hypoxia (CH)-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation, the relationship between CaSR and TRPC in hypoxic PASMCs proliferation remains poorly understood. The goal of this study was to identify that CH promotes PASMCs proliferation through CaSR-TRPC pathway. METHODS: Rat PASMCs were isolated and treated with CH. Cell proliferation was assessed by cell counting, CCK-8 assay, and EdU incorporation. CaSR and TRPC expressions were determined by qPCR and Western blotting. Store-operated Ca2+ entry (SOCE) was assessed by extracellular Ca2+ restoration. RESULTS: In PASMCs, CH enhanced the cell number, cell viability and DNA synthesis, which is accompanied by upregulated expression of CaSR, TRPC1 and TRPC6. Negative CaSR modulators (NPS2143, NPS2390) inhibited, whereas positive modulators (spermine, R568) enhanced, the CH-induced increases in cell number, cell viability and DNA synthesis in PASMCs. Knockdown of CaSR by siRNA inhibited the CH-induced upregulation of TRPC1 and TRPC6 and enhancement of SOCE and attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. However, neither siTRPC1 nor siTRPC6 had an effect on the CH-induced CaSR upregulation, although both significantly attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. CONCLUSION: These results demonstrate that upregulated CaSR-TRPC1/6 pathway mediating PASMCs proliferation is an important pathogenic mechanism under hypoxic conditions.

Clinical characteristics of COVID-19 infection in chronic obstructive pulmonary disease: a multicenter, retrospective, observational study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been a global pandemic disease, with more than 4 million cases and nearly 300,000 deaths. Little is known about COVID-19 in patients with chronic obstructive pulmonary disease (COPD). We aimed to evaluate the influence of preexisting COPD on the progress and outcomes of COVID-19. METHODS: This was a multicenter, retrospective, observational study. We enrolled 1,048 patients aged 40 years and above, including 50 patients with COPD and 998 patients without COPD, and with COVID-19 confirmed via high-throughput sequencing or real-time reverse transcription-polymerase chain reaction, between December 11, 2019 and February 20, 2020. We collected data of demographics, pathologic test results, radiologic imaging, and treatments. The primary outcomes were composite endpoints determined by admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: Compared with patients who had COVID-19 but not COPD, those with COPD had higher rates of fatigue (56.0% vs. 40.2%), dyspnea (66.0% vs. 26.3%), diarrhea (16.0% vs. 3.6%), and unconsciousness (8.0% vs. 1.7%) and a significantly higher proportion of increased activated partial thromboplastin time (23.5% vs. 5.2%) and D-dimer (65.9% vs. 29.3%), as well as ground-glass opacities (77.6% vs. 60.3%), local patchy shadowing (61.2% vs. 41.4%), and interstitial abnormalities (51.0% vs. 19.8%) on chest computed tomography. Patients with COPD were more likely to develop bacterial or fungal coinfection (20.0% vs. 5.9%), acute respiratory distress syndrome (ARDS) (20.0% vs. 7.3%), septic shock (14.0% vs. 2.3%), or acute renal failure (12.0% vs. 1.3%). Patients with COPD and COVID-19 had a higher risk of reaching the composite endpoints [hazard ratio (HR): 2.17, 95% confidence interval (CI): 1.40-3.38; P=0.001] or death (HR: 2.28, 95% CI: 1.15-4.51; P=0.019), after adjustment. CONCLUSIONS: In this study, patients with COPD who developed COVID-19 showed a higher risk of admission to the intensive care unit, mechanical ventilation, or death.

LncRNA RP11-86H7.1 promotes airway inflammation induced by TRAPM2.5 by acting as a ceRNA of miRNA-9-5p to regulate NFKB1 in HBECS.

Traffic-related air pollution particulate matter 2.5 (TRAPM2.5), is involved in chronic obstructive pulmonary disease (COPD), which is characterized by airway inflammation. Specifically, these harmful particles or gases can increase chronic airway inflammation. Some recent studies have shown that lncRNAs are closely related to COPD and participate in the regulation of airway inflammation. However, the precise mechanisms remain unknown. In the present study, we investigated the effect of TRAPM2.5 on airway inflammation in human bronchial epithelial cells (HBECs) and the underlying mechanisms mediated by a lncRNA. After exposure to TRAPM2.5, the novel lncRNA RP11-86H7.1 was markedly upregulated in HBECs. Functional assays indicated that the lncRNA RP11-86H7.1 was required for the TRAPM2.5-induced expression of inflammatory factors in HBECs. A mechanistic study demonstrated that lncRNA RP11-86H7.1 might participate in TRAPM2.5-induced inflammatory responses by activating the NF-κB signaling pathway. Moreover, the lncRNA RP11-86H7.1 can promote the inflammatory response by acting as a competing endogenous RNA of miR-9-5p, reversing the inhibitory effect of its target gene NFKB1, and sustaining NF-κB activation. In summary, our study elucidates the pro-inflammatory roles of the lncRNA RP11-86H7.1-miR-9-5p-NFKB1 regulatory network in airway inflammation induced by TRAPM2.5 and indicates that the components of this network might serve as novel diagnostic biomarkers and potential therapeutic targets.

PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.

BACKGROUND: The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. METHODS: HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively. The role of the hedgehog pathway in cell migration was assessed by western blotting to measure the expression of Sonic hedgehog (Shh), Gli1 and Snail. Furthermore, siRNA was used to knock down Gli1 or Snail expression. RESULTS: PM2.5 induced HBSMC apoptosis in a dose-dependent manner, although certain concentrations of PM2.5 did not induce HBSMC proliferation or apoptosis. Interestingly, cell migration was stimulated by PM2.5 doses far below those that induced apoptosis. Additional experiments revealed that these PM2.5 doses enhanced the expression of Shh, Gli1 and Snail in HBSMCs. Furthermore, PM2.5-induced cell migration and protein expression were enhanced by recombinant Shh and attenuated by cyclopamine. Similar results were obtained by knocking down Gli1 or Snail. CONCLUSIONS: These findings suggest that PM2.5, which may exert its effects through the Shh signaling pathway, is necessary for the migration of HBSMCs. These data define a novel role for PM2.5 in airway remodeling in COPD.

Positive feedback of the amphiregulin-EGFR-ERK pathway mediates PM2.5 from wood smoke-induced MUC5AC expression in epithelial cells.

Biomass fuel smoke is thought to contribute to chronic obstructive pulmonary disease, which is characterized by mucous cell metaplasia and enhanced mucus secretion. We investigated the effect of particulate matter (PM) with a diameter <2.5 µm (PM2.5) from wood smoke (WSPM2.5) on the expression of the most prominent secreted mucin, MUC5AC. Wood smoke was able to induce MUC5AC expression in the rat respiratory tract after 3 months of exposure. WSPM2.5 could induce MUC5AC production in both primary human airway epithelial cells and the NCI-H292 cell line. This induction process was mediated by activation of epithelial growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signaling through an EGFR ligand-dependent mechanism. Amphiregulin (AR) was identified as the major ligand responsible for EGFR-ERK signaling activation and MUC5AC expression. In turn, EGFR-ERK pathway activation was found to contribute to the de novo synthesis of AR. This positive feedback loop might play an important role in a sustained mucus hypersecretion response.

Nicotine-Induced Airway Smooth Muscle Cell Proliferation Involves TRPC6-Dependent Calcium Influx Via α7 nAChR.

BACKGROUND/AIMS: The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation. METHODS: Cell viability was assessed with a CCK-8 assay. Proliferation was measured by cell counting and EdU immunostaining. Fluorescence calcium imaging was performed to measure intracellular Ca2+ concentration ([Ca2+]i). RESULTS: The results showed that nicotine promotes HBSMC proliferation, which is accompanied by elevated store-operated calcium entry (SOCE), receptor-operated calcium entry (ROCE) and basal [Ca2+]i in HBSMCs. Moreover, we also confirmed that canonical transient receptor potential protein 6 (TRPC6) and α7 nicotinic acetylcholine receptor (α7 nAChR) are involved in nicotine-induced upregulation of cell proliferation. Furthermore, we verified that activation of the PI3K/Akt signaling pathway plays a pivotal role in nicotine-enhanced proliferation and calcium influx in HBSMCs. Inhibition of α7 nAChR significantly decreased Akt phosphorylation levels, and LY294002 inhibited the protein expression levels of TRPC6. CONCLUSION: Herein, these data provide compelling evidence that calcium entry via the α7 nAChR-PI3K/Akt-TRPC6 signaling pathway plays an important role in the physiological regulation of airway smooth muscle cell proliferation, representing an important target for augmenting airway remodeling.

Exposure to Ambient Particulate Matter Induced COPD in a Rat Model and a Description of the Underlying Mechanism.

While the health effects of air pollution have been an international public health concern since at least the 1950s, recent research has focused on two broad sources of air pollution, namely, biomass fuel (BMF) and motor vehicle exhaust (MVE). Many studies have shown associations between air pollution PM and exacerbations of pre-existing COPD, but the role of air pollution PM in the development and progression of COPD is still uncertain. The current study indicates that rats can develop pronounced COPD following chronic exposure to air pollution PM (BMF and MVE), as characterized by lung function reduction, mucus metaplasia, lung and systemic inflammation, emphysema, and small airway remodeling. Comparative analyses demonstrate that both BMF and MVE activate similar pathogenesis that are linked to the development of COPD. These findings also show that some differences are found in the lungs of rats exposed to BMF or MVE, which might result in different phenotypes of COPD.

Association between exposure to ambient particulate matter and chronic obstructive pulmonary disease: results from a cross-sectional study in China.

OBJECTIVE: The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear. Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults. METHODS: A cross-sectional study was conducted in southern China. Seven clusters were randomly selected from four cities across Guangdong province. Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry. COPD was defined as a post-bronchodilator FEV1/FVC less than 70%. Atmosphere PM sampling was conducted across the clusters along with our survey. RESULTS: Of the subjects initially recruited, 84.4% (n=5993) were included for analysis. COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters. COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1. A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI -43 to -9) decrease in FEV1, a 28 mL (-49 to -8) decrease in FVC and a 0.09% decrease (-0.170 to -0.010) in FEV1/FVC ratio. The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker. CONCLUSIONS: Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function. TRIAL REGISTRATION NUMBER: ChiCTR-OO-14004264; Post-results.