Lung最新文献

Purpose: Staphylococcus aureus (SA) secretes pro-allergic molecules, including staphylococcal enterotoxins (SEs) and serine protease-like proteins (Spls). While IgE sensitization to SE has been relatively well documented in relation to severe eosinophilic late-onset asthma, the clinical implications of IgE sensitization to Spls remain unclear. We explored the clinical relevance of Spl-IgE in late-onset asthmatics.

Methods: Adults with late-onset asthma (onset age ≥ 40 years) were prospectively enrolled. Demographic and clinical characteristics were assessed, and serum levels of total IgE, SE-IgE, and SplA-IgE were measured. Nasal swabs were obtained to assess SA colonization.

Results: Among 109 participants, SplA-IgE levels were significantly associated with blood eosinophilia, total IgE, SE-IgE sensitization, and male sex, but not with SA colonization, asthma severity, or lung function.

Conclusion: Sensitization to SplA-IgE may indicate a type 2 inflammatory phenotype, but its role in asthma warrants further investigation.

Purpose: Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, leading to multisystemic complications, particularly in the lungs. CFTR dysfunction results in altered ion transport, chronic inflammation, and progressive lung damage. The triple therapy elexacaftor/tezacaftor/ivacaftor (ETI) has demonstrated significant improvements in pulmonary function and quality of life. This study aimed to evaluate the anti-inflammatory effects of ETI by analysing systemic cytokine profiles over 12 months.

Methods: A prospective study included 32 CF patients ≥ 18 years with at least one delF508 mutation, undergoing ETI therapy. Clinical stability was ensured prior to therapy initiation. Demographic data, BMI (Body Mass Index), FEV1% (Forced expiratory Volume in the first second), VR/TLC (residual volume/total lung capacity) and sweat chloride concentrations were recorded at baseline, 6 months and 12 months. Inflammatory markers, including fibrinogen, C-reactive protein (CRP), and a panel of 8 cytokines, were measured using multiplex bead-based immunoassays and electrochemiluminescence. Longitudinal changes were analysed using mixed-effects models and statistical tests, with significance set at p < 0.05.

Results: During a 12-month follow-up, the neutrophils number and proinflammatory biomarkers analyzed, fibrinogen, CRP, GM-CSF, IFN- γ, IL-1 α, IL-1 β, IL-8 (CXCL8), IL-12p70, IL-17A (CTLA-8), and TNF-α, significantly decreased, while eosinophils remained stable. Mixed-effects models confirmed the significant association of inflammatory biomarkers with FEV1, BMI, sweat chloride levels, and VR/TLC highlighting the role of inflammation in the progression of CF.

Conclusions: ETI demonstrated marked anti-inflammatory effects in CF patients, reducing systemic inflammation and improving clinical parameters.

Purpose: Cholesterol regulation is essential to maintain pulmonary homeostasis. Studies suggest that increased high-density lipoprotein cholesterol (HDL-C) levels correlate with better lung function. However, the longitudinal association of HDL-C with lung function remains unknown. We aimed to analyze the long-term correlation of HDL-C with lung function decline in a population-based cohort study.

Methods: We included 7,652 participants from a prospective community-based cohort study in South Korea. Participants were categorized into five trajectory groups based on repeated HDL-C measurements. Generalized linear mixed models with random intercepts and slopes were used to examine the longitudinal relationship between HDL-C levels and lung function decline within these groups.

Results: In the five HDL-C trajectory group analyses, the very low HDL-C trajectory group (Group 1) showed faster declines in forced vital capacity (FVC) (-3.1 mL/year) and forced expiratory volume in one second (FEV₁) (-3.1 mL/year) than the middle HDL-C group (Group 3, the reference group) did. The low HDL-C trajectory group (Group 2) also exhibited faster FVC (-1.5 mL/year) and FEV₁ (-1.7 mL/year) declines than the middle HDL-C group; however, the estimated difference was smaller than that in Group 1. Faster lung function decline in the low HDL-C trajectory group was consistently observed even when the population was analyzed using three- or four-HDL-C trajectory groups instead of five.

Conclusion: Participants in the low HDL-C trajectory groups experienced a more rapid lung function decline over time than the reference groups, suggesting a negative longitudinal association between HDL-C and lung function decline.

Lung cancer remains the leading cause of cancer-related mortality worldwide. Since 2024, the non-small-cell lung cancer (NSCLC) landscape has undergone a transformative shift, driven by 11 FDA approvals. Recent advances in molecular profiling, targeted therapies, and immunotherapies have revolutionized NSCLC management, ushering in an era of personalized treatment with improved patient outcomes. The increased adoption of low-dose computed tomography (LDCT) for screening has enhanced early detection, enabling intervention at more curable stages. Molecular diagnostics now play a pivotal role in guiding treatment strategies, with actionable genomic alterations (AGAs) informing the use of EGFR, ALK, ROS1, KRAS, NRG1, and other targeted inhibitors in both early and advanced settings. For instance, targeted therapies are increasingly being integrated into early-stage management, with adjuvant osimertinib for EGFR-mutated NSCLC and alectinib for ALK-positive NSCLC demonstrating substantial survival benefits. Immunotherapy, particularly immune checkpoint inhibitors, has become a cornerstone of treatment for AGA-negative NSCLC, either as monotherapy or in combination with chemotherapy, and is increasingly being utilized in the perioperative setting. Furthermore, emerging therapies such as bispecific antibodies, antibody-drug conjugates (ADCs), and novel immunotherapeutic agents show promise in addressing resistance mechanisms and improving outcomes in advanced-stage disease. Although new challenges arise, the evolving NSCLC treatment paradigm continues to prioritize precision medicine, offering hope for prolonged survival and enhanced quality of life for patients.

Introduction: Low lung function and Preserved Ratio Impaired Spirometry (PRISm) have been associated with increased co-morbid cardiovascular disease. However, the association of abnormal lung function and PRISm with imaging markers of cardiovascular dysfunction has not been well elucidated.

Methods: Participants from the Jackson Heart Study who had spirometry measurements at baseline and underwent cardiac magnetic resonance (CMR) were included. Multivariable adjusted associations between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) and markers of aortic (pulse wave velocity, aPWV, wall thickness) and cardiac function (left ventricular (LV) stroke volume, and indexed LV mass) as measured on CMR were examined using linear regression models. Study participants were then divided into three groups (normal spirometry: FEV1/FVC ≥ 0.70, FEV1 ≥ 80%, airflow obstruction: FEV1/FVC < 0.70, and PRISm: FEV1/FVC ≥ 0.70, FEV1 < 80%). We then examined the associations of spirometry pattern and markers of structure and function as dichotomous outcomes using multivariable adjusted logistic regression models.

Results: A total of 1278 participants (788 women [63%]; 375 (29%) ever smokers, 612 (48%) with hypertension, 1033 [81%] with normal spirometry, 80 [6%] with airflow obstruction, and 165 (13%) with PRISm met criteria for inclusion. In a multivariable model adjusting for age, sex, BMI, smoking status, and systolic blood pressure, aPWV was significantly associated with FEV1% (-0.20 ± 0.03, p = 0.04) and those with airflow obstruction had significantly higher odds of an increased aPWV (OR 2.25, 95% CI 1.29-3.93) compared to controls with a normal spirometry pattern. In the multivariable adjusted model, those with PRISm had a higher likelihood of a reduced LV stroke volume compared to controls (OR 1.69, 95% CI 1.14-2.56).

Discussion: The PRISm pattern is associated with decreased LV stroke volume. This may be a potential mechanism between PRISm pattern and incident heart failure.

Background: Hepatopulmonary syndrome (HPS) is a severe complication in cirrhotic patients and characterized by abnormal intrapulmonary vasodilation (IPVD), resulting in impaired oxygenation. Recent studies highlight the pivotal role and clinical merit of Reticulocalbin 3 (RCN3) in interstitial pulmonary remodeling.

Objectives: This study aimed to investigate the clinical value of plasma RCN3 for early diagnosis of HPS in cirrhotic patients.

Methods: This prospective observational study on a cohort including 41 healthy control subjects and 247 cirrhotic patients with/without HPS, in which most HPS occurs in the mild stage. Plasma levels of RCN3 and key HPS-associated vasoactive factors are compared between patients with and without HPS/IPVD. The predictive value of RCN3 for the diagnosis of HPS is further analyzed.

Results: Patients with HPS had a severe condition. Plasma RCN3 was decreased in cirrhotic patients versus health control, but it is significantly higher in patients with HPS/IPVD than without non-HPS/IPVD. Notably, RCN3 level is positively correlated with P(A-a)O₂ and MELD scores as well as plasma levels of angiogenetic factors VEGF and AngII. Although the plasma levels of vasoactive factors were significantly different between HPS and non-HPS patients, only plasma RCN3 and albumin are independently associated with HPS in cirrhotic patients. Plasma RCN3 exhibits better predictive value in HPS diagnosis (RCN3, AUC = 0.657, 95% CI 0.571-0.744, p < 0.001). Interestingly, the combination of RCN3 and albumin achieves more efficiency in HPS prediction (AUC = 0.711, 95% CI 0.630-0.792, p < 0.0001).

Conclusions: Circulating RCN3 is likely a relatively specific earlier biomarker for the prediction of early or latent HPS in cirrhotic patients, and the combination of RCN3-ALB can achieve more efficiency in HPS prediction.

Purpose: The objective was to study comparative efficacies of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, vanzacaftor-tezacaftor-deutivacaftor (VTD), elexacaftor-tezacaftor-ivacaftor (ETI), tezacaftor-ivacaftor (Tez-Iva), and lumacaftor-ivacaftor (Lum-Iva) in people with cystic fibrosis (pwCF), aged ≥ 12 years, carrying at least one F508del-CFTR-allele.

Methods: Data from randomized controlled or randomized active comparator trials were included in this network meta-analysis which used frequentist approach for comparing the efficacy of drugs and ranking based on P-scores. Outcomes of interest were mean differences in percentage-predicted forced expiratory volume in one second (ppFEV₁), CF questionnaire-revised respiratory domain (CFQ-R) scores, sweat chloride (SwCl) levels, and odds ratios (OR) for serious adverse events (SAE).

Results: Data from 13 studies were analyzed. Compared to placebo, the effects of VTD and ETI on ppFEV1 were almost quadruple of Tez-Iva and Lum-Iva (VTD: 12.78 [95% confidence intervals: 6.41; 19.15] and ETI: 11.95 [7.40; 16.50]) and almost seven times of Tez-Iva and Lum-Iva for CFQ-R (VTD: 21.23 [- 28.72; 71.18] and ETI: 19.27 [10.56; 27.98]). A statistically significant difference was noted between VTD and ETI in SwCl reduction (mean difference: - 8.59 [- 15.53; - 1.65]). There were no statistically significant ORs for SAEs for any CFTR modulators but VTD, ETI, and Tez-Iva were least associated with SAEs (ORs were 0.15 [0.01; 1.79], 0.49 [0.31; 0.78], and 0.74 [0.50; 1.09], respectively, as compared to placebo). Overall, P-score ranking ranked VTD as first and ETI as second, followed by others.

Conclusion: VTD and ETI were more efficacious than Tez-Iva and Lum-Iva in pwCF with at least one F508del-CFTR-allele.

Purpose: The popularity of electronic cigarettes (e-cigarettes) has grown exponentially over the past few years, and teenagers now prefer them to tobacco cigarettes. We determined whether exposure to e-cigarette vapour (e-vapour) adversely affects ion transport using human airway epithelial cell lines 16HBE14o- and Calu-3 and well-differentiated primary human bronchial epithelial cells (HBEs).

Methods: We concurrently measured fluorescent signals and short-circuit current (I_SC), an indicator of electrogenic ion transport, in polarised epithelia. The P2Y receptor-mediated signalling pathway was used to induce an increase in intracellular calcium concentration ([Ca²⁺]_i) and I_SC. We used a single-polypeptide fluorescence resonance energy transfer reporter based on exchange proteins directly activated by cAMP (Epac) to measure forskolin-induced changes in cAMP and I_SC.

Results: We compared the effects of e-vapour to those of traditional cigarette smoke (CS) on the human airway cell models. In all three cell types, e-vapour, similar to CS, significantly reduced agonist-induced increases in Ca²⁺ or cAMP signalling and I_SC. However, reductions in the epithelial electrolyte transport activities did not correlate with any changes in the protein levels of various ion channels and transporters.

Conclusion: Our data suggest that e-vapour is not harmless and causes ion transport dysfunction similar to CS, thereby predisposing e-cigarette users to vaping-induced lung injury.

Histone deacetylases (HDACs), a class of enzymes involved in epigenetic modifications, play a pivotal role in modulating chromatin structure and gene expression. Among these, histone deacetylase 3 (HDAC3) has emerged as a key regulator in diverse cellular pathophysiological processes. The remarkable therapeutic potential of HDAC inhibitors in lung cancer has intensified research into the role of HDAC3 in pulmonary diseases. Through deacetylating histones and non-histone proteins, HDAC3 has been increasingly recognized for its critical involvement in regulating inflammatory responses, fibrotic processes, and oncogenic signaling pathways, positioning it as a compelling therapeutic target. This review systematically examines the structural and functional features of HDAC3 and discusses its multifaceted contributions to pulmonary pathologies, including lung injury, pulmonary fibrosis, and lung cancer. Additionally, we critically evaluate advances in HDAC inhibitor-based therapies for lung cancer, with emphasis on the development of HDAC3-targeted therapies. As a promising therapeutic target for pulmonary diseases, HDAC3 needs to be further investigated to elucidate its regulatory mechanisms and facilitate the development of selective inhibitors for clinical translation.