Lung最新文献

Background: Telomere shortening, a hallmark of cellular aging, is associated with poor outcomes in idiopathic pulmonary fibrosis (IPF). This study aimed to explore the relationships between telomere length (TL), pulmonary function tests, and telomere-related gene (TRG) mutations in a real-world IPF population.

Methods: We included IPF patients from two Belgian academic hospitals, collecting demographic and clinical data. TL was measured using Flow-FISH and expressed as a percentile. Short TL was defined as below the 10th percentile (P10), and very short TL as below the 1st percentile (P1).

Results: We analysed 143 patients (106 men, 74%), with a median age of 70 years. Thirty patients (21%) met the European Respiratory Society (ERS) criteria for familial pulmonary fibrosis (FPF). Short TL was found in 74 patients (50%), predominantly in men (p < 0.05). Patients with short TL experienced a greater decline in lung function over 24 months compared to those with normal TL (- 4% vs + 3% FVC, p < 0.05; - 7% vs - 3% DLCO, p < 0.05). Patients with very short TL were younger at diagnosis and tended to have a more pronounced FVC decline (- 5% vs - 1%, p = 0.06). TRG variants were identified in 16 individuals, occurring more frequently in those with short (14/27, 52%) or very short TL (10/20, 50%).

Conclusion: Short TL is common in both sporadic and familial IPF and serves as a predictive biomarker for accelerated lung function decline. Additionally, the presence of short TL is indicative of an underlying TRG mutation.

Background: Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, primarily due to late-stage diagnosis and the absence of effective early detection methods.

Objective: This review aims to explore the principles, technological advancements, current limitations, and future prospects of electronic nose (E-nose) systems in the early detection of lung cancer.

Methods: The review analyzes recent literature on E-nose devices that detect volatile organic compounds (VOCs) in exhaled breath, focusing on their integration with artificial intelligence (AI) and machine learning for pattern recognition and diagnostic classification.

Results: E-noses have demonstrated high sensitivity and specificity in differentiating cancerous from non-cancerous breath samples. However, challenges such as sensor stability, lack of standardization in breath collection, demographic variability, and the need for large training datasets for AI models limit their clinical adoption.

Conclusion: Despite current limitations, E-nose technology shows strong potential as a rapid, non-invasive, and cost-effective tool for early LC screening. Enhancing sensor durability, improving data processing, and conducting large-scale validation studies are critical next steps. Integration with imaging and molecular biomarkers may further improve diagnostic accuracy and clinical utility.

Purpose: Pulmonary fibrosis is defined as progressive based on the combination of radiological, clinical, and functional criteria. Nintedanib can reduce the rate of lung function decline, but no data are available on its effectiveness to hamper disease progression evaluated by these criteria. The primary aim of the study was to assess the number of patients with progressive pulmonary fibrosis (PPF) who no longer meet progression criteria after one year of treatment with nintedanib.

Methods: A retrospective, observational, multicenter study was carried out in Italy.

Results: 172 patients (91 (52.9%) males) with PPF were recruited, and 135 (78.5%) completed one year of treatment. After one year, 87 (64.4%) patients no longer met INBUILD progression criteria, while 107 (79.3%) did not meet 2022 ATS/ERS/JRS/ALAT guidelines criteria. Nintedanib hampered progression regardless of inclusion criteria, radiological pattern, and etiological diagnosis. Forced vital capacity (FVC) decline was significantly higher in the 12 months before than in those of treatment (mean, SD): 2512.3 (863.2) ml vs. 2313.6 (821.9) ml; p < 0.0001; 2313.6 (821.9) vs. 2335.7 (865.1); p = 0.82). FVC decline was significantly higher in the year before than in the year of treatment regardless of radiological pattern, etiological subtypes, and respiratory function. Diarrhea (mostly mild) was the most frequent adverse event (51.7%). A permanent discontinuation of the drug was recorded in 15 (9%) patients.

Conclusion: Nintedanib is effective and safe in patients with PPF. Besides slowing lung function decline, it hampers progression regardless of etiological diagnosis, radiological pattern, respiratory function, and baseline inclusion criteria.

Purpose: Ventilator-associated pneumonia (VAP) is a common ICU complication linked to high morbidity and mortality. Inhaled antibiotics may offer targeted prophylaxis, but their effectiveness has shown mixed results. This study aims to further evaluate whether inhaled antibiotics reduce VAP incidence and ICU mortality through a systematic review and meta-analysis of the most updated available evidence.

Methods: A systematic review was conducted following PRISMA 2020 guidelines. Multiple databases were searched for studies published up to November 14, 2024. Ten studies including 2876 patients (1485 intervention; 1391 control) met inclusion criteria. A random-effects meta-analysis was performed to estimate pooled risk ratios (RR) for VAP incidence and ICU mortality. Risk of bias was assessed using ROBINS-I and certainty of evidence via GRADE.

Results: Inhaled antibiotics significantly reduced the incidence of VAP compared to controls (RR = 0.67; 95% CI: 0.58-0.77; p < 0.001), but showed no significant effect on ICU mortality (RR = 0.92; 95% CI: 0.79-1.06; p = 0.25). Moderate heterogeneity was observed in VAP outcomes (I² = 46.8%), while mortality analysis showed no heterogeneity. Funnel plot analysis suggested minimal publication bias, and GRADE rated the evidence as moderate in certainty.

Conclusion: Inhaled antibiotics significantly reduce VAP incidence but show no clear mortality benefit. While promising for prevention, their survival impact remains uncertain. Clinical use should consider patient context and microbial patterns for targeted approach. Future research should identify high-risk subgroups, assess long-term outcomes, and evaluate antibiotic resistance.

Background: The methacholine challenge requires a 20% fall in forced expiratory volume in one second (FEV₁). The fall is measured as litre (L) change from the pre-challenge (baseline) value. A higher baseline FEV₁ requires a greater volume change to reach a 20% fall. The aim of this study was to evaluate change using percent predicted, which may remove dependence on the baseline value.

Methods: Challenge data from a cohort of 114 asthma patients was re-analysed. The dose causing an 20% fall from baseline (PD₂₀) was compared to a 15% fall in predicted value (PD_15%) for the classification of bronchial hyperresponsiveness.

Results: There was significant agreement between PD₂₀ and PD_15% (r = 0.95, p < 0.0001), with an ICC of 0.97. PD₂₀ was significantly higher than PD_15% (0.0055 mg, p < 0.0001). Greater decreases in FEV₁ were observed with PD₂₀ versus PD_15% (21.4% pred vs 19.1% pred respectively, p = 0.0004), with 29% of patients requiring at least one additional dose of methacholine to achieve PD₂₀ compared to PD_15%. A higher baseline FEV₁ resulted in higher PD₂₀ values, whereas no relationship was found for PD_15%. Variability in FEV₁ between repeated visits (n = 15) was associated with the change in PD₂₀, but not the change in PD_15%.

Conclusion: We suggest a PD criteria based on 15% predicted change should be used for bronchial challenge testing. This method is less influenced by baseline airflow obstruction, and is a more efficient and safer way of measuring airway hyperresponsiveness.

Purpose: Acute respiratory distress syndrome (ARDS)/Acute lung injury (ALI), characterized by severe hypoxemia and pulmonary edema, involves mitochondrial dysfunction. Cytidine/uridine monophosphate kinase 2 (Cmpk2), a mitochondrial metabolic enzyme, modulates inflammation and senescence, yet its role in ARDS remains unclear. We investigated Cmpk2's function in Pseudomonas aeruginosa (P. aeruginosa)-induced ALI using Cmpk2 global knockout (KO) mice.

Methods: Cmpk2 was identified through mitochondrial gene expression analysis of ARDS datasets (GEO). Murine ALI was induced by intratracheal P. aeruginosa injection. Lung pathology (hematoxylin and eosin staining), leukocyte recruitment (flow cytometry), and cytokines (ELISA) were assessed. GO/KEGG analyses were conducted to identify Cmpk2-associated biological processes and pathways. The expression of Cmpk2 in leukocyte populations was analyzed using single-cell RNA sequencing (scRNA-seq) data from ARDS patient samples. Mouse neutrophils' phagocytosis of P. aeruginosa was quantified by flow cytometry. Zebrafish embryos were infected with P. aeruginosa and Staphylococcus aureus for bacterial burden and survival assays.

Results: Cmpk2 expression was significantly upregulated in ARDS. Cmpk2 KO exacerbated P. aeruginosa-induced ALI in mice, as evidenced by increased pathological damage and permeability, elevated proinflammatory cytokines and enhanced neutrophil infiltration. GO/KEGG analyses linked Cmpk2 to innate immunity. scRNA-seq analysis revealed an enriched expression of Cmpk2 in neutrophils. Cmpk2 deficiency impaired neutrophil phagocytosis and reduced host survival during bacterial infection, accomplished by decreased STING expression. The differences in phagocytosis between the wild-type and Cmpk2 KO mouse neutrophils/zebrafish embryos were eliminated by STING inhibitor C176.

Conclusion: Cmpk2 protects against pneumonia by attenuating neutrophil recruitment and enhancing bacterial phagocytosis via STNG-dependent mechanisms.

Introduction/purpose: Right ventricle (RV) dysfunction in the setting of acute pulmonary embolism (PE) is associated with worse outcomes. The ratio of tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) provides an estimate of right ventricular-arterial (RV-PA) coupling and has been associated with adverse outcomes in patients with pulmonary hypertension. In this study, we examined if RV-PA uncoupling can further risk stratify acute PE.

Methods: This is a single-center, retrospective analysis of patients admitted to a tertiary center with the diagnosis of acute PE. The Kruskal-Wallis Rank Sum, Wilcoxon Rank Sum, and Chi-square tests were used to identify clinical features associated with reduced RV-PA uncoupling at three distinct thresholds, severe (< 0.31), moderate (0.31-0.4) and mild (> 0.4-1.75) derived from prior studies.

Results: 146 patients were included in our analysis. Patients with severely impaired RV-PA uncoupling ratios were more likely to have RV dysfunction by CT defined as CT RV/LV ratio > 0.9 (p < 0.01) and were more likely to need veno-arterial extracorporeal membrane oxygenation (VA-ECMO) compared to those that had moderate or mild impairment (p < 0.01). We also found a correlation between BNP (r = - 0.44, p < 0.01), lactate levels (r = - 0.18 p = 0.04), and the TAPSE/PASP ratio. European Society of Cardiology, sPESI, and BOVA risk stratification scores did not distinguish between patients with mild, moderate, or severe RV-PA uncoupling.

Conclusion: Patients with acute PE who have severely impaired RV-PA uncoupling ratios have more severe disease, characterized by elevated biomarkers and need for VA-ECMO. TAPSE/PASP values can be used to risk stratify and guide treatment of acute PE.

Background: Smoking is a major risk factor for lung function decline and chronic obstructive pulmonary disease (COPD), but the individual susceptibility to these traits cannot be explained solely by environmental risk factors.

Aim: To estimate the relative contribution of genetic and environmental factors to lung function, chronic bronchitis and COPD.

Methods: 12,449 twins aged 40-80 years participated in a nationwide survey using the Danish Twin Registry, which included a questionnaire, clinical examination and spirometry. Clinical COPD was defined by respiratory symptoms plus airflow obstruction. Biometric models of genetic and environmental latent factors were used to estimate the heritability after adjusting for sex, age, and height.

Results: Mean (SD) age of the study population was 58.4 (9.6) years and mean BMI (kg/m²) was 26.6 (4.4); 20% were current smokers and 52% were females. The heritability of FEV₁, FVC and FEV₁/FVC was 64% (60-67%), 61% (57-65%), and 50% (46-55%), respectively. Genetic factors explained 48% (24-72%) and 47% (16-78%), respectively, of the individual susceptibility to chronic bronchitis and clinical COPD.

Conclusion: Genetic factors explain at least half of the variation in lung function and around half of the individual susceptibility to chronic bronchitis and clinical COPD, respectively, when adjusted for sex, age, height.

Background: Macrophage polarization is essential for inflammatory regulation in COPD. The precise role of BPI Fold-Containing Family B Member 4 (BPIFB4) in regulating the inflammatory processes underlying COPD pathogenesis remains to be fully elucidated. This investigation seeks to clarify how BPIFB4 modulates macrophage polarization by activating the phosphoinositide 3-kinase (PI3K)-AKT1 signaling pathway, thereby influencing inflammatory progression in COPD.

Methods: In a COPD mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS) and in cigarette smoke extract (CSE)-treated THP-1 cells, BPIFB4 was overexpressed or silenced. Bronchoalveolar lavage fluid, lung tissues, and serum were collected. qPCR and western blots assessed BPIFB4 and PI3K-AKT1 pathway expression in lung tissues and THP-1 cells. Flow cytometry evaluated M1/M2 macrophage polarization, and enzyme-linked immunosorbent assay (ELISA) measured related cytokine levels.

Results: The results demonstrated how BPIFB4 gene silencing resulted in more pronounced lung tissue and functional damage compared to BPIFB4 overexpression, alongside an elevated presence of M1 macrophages and associated pro-inflammatory factors. In contrast, BPIFB4 overexpression in both COPD mice and CSE-treated THP-1 cells significantly enhanced p-AKT1 and p-PI3K levels while reducing the number of M1 macrophages. In addition, inhibition of the PI3K-AKT1 pathway reversed these effects, resulting in a marked increase in M1 macrophages and their associated cytokines.

Conclusion: BPIFB4 overexpression alleviates M1 macrophage polarization by activating the PI3K-AKT1 pathway, thereby reducing lung tissue damage and dysfunction in COPD mice.