Lung最新文献

Purpose: Cough hypersensitivity is characterized by exaggerated cough responses to mild stimuli, which is frequently associated with laryngeal abnormal sensation (LAS). However, the clinical characteristics of LAS and its prevalence in a non-clinical working population remain unclear. This study aimed to investigate the clinical characteristics and prevalence of LAS.

Methods: This cross-sectional study included 556 healthcare workers (aged 20-72) from Gamagori City Hospital, Japan. Participants completed the Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ), Hull Airway Reflux Questionnaire, and Leicester Cough Questionnaire (LCQ). LAS was defined as an NLHQ score < 17.1. Binary logistic regression was used to analyze LAS-associated factors.

Results: LAS was present in 9.5% of participants. The LAS-positive group had significantly higher prevalence of asthma (13.2% vs. 3.4%, P = 0.005), chronic rhinosinusitis (7.5% vs. 1.0%, P = 0.006), and gastroesophageal reflux disease (GERD; 11.3% vs. 1.2%, P < 0.001). Cough prevalence was significantly higher in the LAS( +) group (45.2% vs. 9.5%, P < 0.001), and quality of life was impaired, as indicated by lower LCQ scores. Multivariate analysis revealed that asthma (OR = 5.092, P = 0.002), GERD (OR = 12.397, P < 0.001), and mood swings (OR = 2.957, P = 0.003) were independent risk factors for LAS.

Conclusion: LAS markedly affects symptoms like cough and impairs quality of life, and is independently associated with asthma, GERD, and mood swings. It may reflect a sensory phenomenon of vagal hypersensitivity that could contribute to the pathophysiology of such chronic conditions.

Viral pneumonia causes significant morbidity and mortality worldwide. However, there is limited ability to predict outcomes and treatment responses. We analyzed data from a recently published placebo-controlled trial of inhaled high molecular weight hyaluronan (HMWHA) in 146 patients with severe COVID-19 pneumonia, to determine whether admission cytokines and demographic information is associated with disease outcomes and response to HMWHA treatment. We found that serum levels of CXCL10 are strongly associated with both endpoints. Our data thus identify CXCL10 as a possible predictor of viral pneumonia outcome and response to anti-inflammatory treatment.

Background: Antimicrobial-resistant pathogens such as Pseudomonas aeruginosa (P. aeruginosa) represent a significant challenge to patients with respiratory diseases including Cystic Fibrosis (CF) and chronic obstructive pulmonary disease (COPD), where treatment of such infections is exacerbated by a shortage of new and effective antibiotic classes. One novel approach utilises 'antibiotic enhancers' that potentiate the antimicrobial activity of existing antibiotics. HT61, a small quinolone-derived compound, potentiates the activity of the aminoglycosides tobramycin and gentamicin against Staphylococcus aureus and P. aeruginosa. In this study, we have investigated synergism between tobramycin and HT61 using a panel of tobramycin-sensitive and -resistant clinical isolates of P. aeruginosa from CF patients.

Methods: Microdilution methods and chequerboard analysis were used to evaluate antimicrobial synergy of drug combinations against 63 isolates. Bacterial time-kill assays and biofilm eradication assays were then used to further characterise antimicrobial synergy against 13 selected isolates.

Results: 74% of isolates (47/63) demonstrated evidence of either positive interactions (29/63) determined by a Fractional Inhibitory Concentration Index (FICI) ≤ 1.0, or synergy (18/63) determined by an FICI value of ≤ 0.5. Using a sub-selection of these isolates, clear augmentation of tobramycin's antimicrobial activity was observed in both time-kill assays and biofilm eradication assays regardless of FICI classification with significant reductions observed in combination therapies vs monotherapies.

Conclusions: The expansion of previous studies highlighting the potentiating capabilities of HT61 on/with antibiotics in vivo across a further 63 clinical isolates of P. aeruginosa in a laboratory setting further highlights the potential therapeutic benefits of HT61-tobramycin combinations in respiratory diseases associated with drug-resistant P. aeruginosa.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic airway inflammation and remodeling. Fibrinogen gamma chain (FGG) has been implicated in the pathogenesis of multiple inflammatory and fibrotic conditions. However, the role and mechanisms of FGG in COPD remain unclear.

Methods: FGG expression in lung tissues and plasma of COPD patients and CS-exposed mice was assessed. To investigate its functional role in cigarette smoke extract (CSE)-induced inflammation and epithelial-mesenchymal transition (EMT), we employed FGG knockdown (KD) and recombinant human FGG (rFGG) protein treatment in BEAS-2B cells and in a murine COPD model. To elucidate the related mechanisms in CSE-induced airway inflammation and EMT, BEAS-2B cells were treated with PF573228 (10 µM, a FAK inhibitor) or SB431542 (10 µM, a TGF-β type I receptor inhibitor).

Results: FGG was up-regulated in both the lung tissue and plasma of COPD patients. Plasma FGG levels were negatively correlated with lung function in COPD patients. Similarly, elevated FGG expression was verified in CS-exposed mice and CSE-induced BEAS-2B cells. Both in vitro (FGG-KD in BEAS-2B) and in vivo (mouse model) experiments demonstrated that inhibition of FGG expression attenuated CSE-induced inflammatory cytokine release and EMT. Treatment with PF573228 or SB431542 inhibited airway inflammation and EMT, implicating the focal adhesion and TGF-β/Smad2 pathways.

Conclusions: FGG contributes to airway inflammation and remodeling in COPD. Cigarette smoke enhances FGG expression and secretion in bronchial epithelium. Increased FGG promotes the release of inflammatory cytokines and EMT through the focal adhesion and TGF-β/Smad2 pathways.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor survival rate and undefined molecular mechanisms. The identification of reliable biomarkers to help early diagnosis and predict disease progression is crucial for improving patient life. Although many biomarkers have been proposed, there is no consensus on reliable markers for IPF. Alterations in fatty acid (FA) metabolism have drawn increasing attention in the IPF pathogenesis.

Methods: This single-center, prospective, cross-sectional study enrolled 35 IPF patients and 24 control participants. Demographic, clinical, and pulmonary function data were collected. FA profiles were compared between the two groups, with statistical analyses including chi-square tests, ANOVA, Spearman's rank correlation, and ROC curve analysis.

Results: We found significant differences in serum FA levels between IPF patients and controls. Cis-Palmitoleic acid (26.4 mg/L vs 22.1 mg/L; p = 0.04), oleic acid (457.6 mg/L vs 376.4 mg/L, p = 0.04), and elaidic acid (33.7 mg/dL vs 28.2 mg/L, p = 0.02) were increased in IPF patients, while arachidonic acid (79.7 mg/dL vs 97.9 mg/L, p = 0.01) levels were significantly lower compared to the control group. Spearman's correlation analysis revealed positive correlations between these fatty acids. Notably, arachidonic acid levels showed a positive correlation with FEV1% (r = 0.348; p = 0.043) and FVC% (r = 0.431; p = 0.01), although ROC curve analysis indicated that this did not demonstrate strong diagnostic potential for IPF.

Conclusion: In this study, we identified a dysregulation of cis-palmitoleic acid, oleic acid, elaidic acid, and arachidonic acid in IPF patients, indicating alterations in lipid metabolism and inflammatory pathways. Additionally, while arachidonic acid levels correlate with lung function, its diagnostic potential remains uncertain and warrants further evaluation in a larger patient population.

Introduction: While the structural damage to the airway epithelium from ozone (O₃) or diesel exhaust particles (DEP) is known, the common regulatory mechanisms activated during mixed exposures, which mirror real-world scenarios, remain poorly understood. This study aimed to identify shared molecular pathways initiated by exposure to O₃ and DEP using an in vitro air-liquid interface (ALI) model to understand the initial cellular responses.

Methods: Polarized Calu-3 cell monolayers at the ALI were acutely exposed to non-cytotoxic O₃ or DEP. Barrier integrity was assessed via transepithelial electrical resistance (TEER) and FITC-dextran permeability. Gene expression of tight junctions and alarmin cytokines was quantified by qPCR, while the protein level of tight junctions was identified by immunofluorescence. The cellular secretome was comprehensively analyzed using label-free liquid chromatography-tandem mass spectrometry.

Results: Both pollutants impaired barrier integrity, evidenced by decreased TEER and increased permeability, and induced a potent inflammatory response via upregulation of alarmin cytokines IL-25, IL-33, and TSLP. Critically, secretome analysis revealed that although O₃ and DEP initiated distinct upstream damage patterns, their responses converged on common downstream pathways, including the activation of Wnt signaling and antigen processing and presentation.

Conclusion: Exposure to O₃ and DEP compromises airway epithelial barrier function and triggers a robust alarmin-driven inflammatory response. Our identification of convergent downstream pathways, such as Wnt signaling, provides crucial mechanistic insights into the shared pathophysiology of mixed pollutant exposure. These findings highlight potential therapeutic targets for mitigating the adverse health effects of complex air pollution.

Background: Refractory chronic cough (RCC) significantly impairs patient quality of life and poses a major challenge in clinical management. However, little is known about the healthcare resource utilization (HRU) of patients with RCC.

Objective: The goal of our study is to describe the HRU and associated costs of RCC patients and those with non-refractory chronic cough (non-RCC).

Methods: Patients with chronic cough were prospectively recruited from 6 centers in France. At 6 months, the patients were classified as having RCC or no RCC. A retrospective analysis was made using the French National Health Insurance Database (SNDS) in order to determine healthcare utilization for the one-year period preceding inclusion at the site and for the one-year period thereafter.

Results: Sixty-eight patients were included. Among them, 32 (47%) patients had RCC. There was no difference between groups regarding clinical data apart from cough duration (56.8 ± 59.5 months in the no RCC group vs. 139.3 ± 123.8 months in the RCC group, p = 0.002). Within 1 year prior to inclusion, there was no difference in terms of drug dispensations between the 2 groups. During the 1-year post-inclusion period, a significantly higher proportion of patients with RCC received at least one dispensation of opioids and amitriptyline compared to those with no RCC (8 (25%) vs. 2 (6%) for opioids, p = 0.038 and 14 (44%) vs. 3 (8%) for amitriptyline, p = 0.0015, respectively). Within 1 year after inclusion, more patients with RCC had attended speech pathologist visits in comparison to patients with no RCC (14 (44%) patients vs. 10 (28%) patients, p = 0.21, respectively). Total costs within 12 months prior to inclusion were 3,878€ [2,498 - 5,755€] for patients with no RCC and 5,159€ [3,426 - 7,138€] with RCC, but the difference was not significant. No change occurred in the 1-year period following inclusion.

Conclusion: RCC has a high healthcare utilization with substantial costs.