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Respiratory Research May 2024Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid...
BACKGROUND
Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients' response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro.
METHODS
Primary airway smooth muscle cells (ASMC) were established from endobronchial biopsies obtained from patients with asthma (n = 10), patients with COPD (n = 10) and subjects that underwent diagnostic bronchoscopy without pathological findings and served as controls (n = 6). ASMC were also established from 18 COPD patients, 10 responders and 8 non-responders to ICS, who participated in the HISTORIC study, an investigator-initiated and driven clinical trial that proved the hypothesis that COPD patients with high ASMC in their endobronchial biopsies respond better to ICS than patients with low ASMC. Expression of GR and its isoforms GRα and GRβ and HDACs was investigated in primary ASMC in the absence or in the presence of dexamethasone (10M) by western blotting. The complex formation of GR with transcription factors was assessed by co-immunoprecipitation.
RESULTS
Expression of GR and its isoform GRα but not GRβ was significantly reduced in ASMC from COPD patients as compared to controls. There were no significant differences in the expression of GR, GRα and GRβ between responders and non-responders to ICS. However, treatment with dexamethasone upregulated the expression of total GR (p = 0.004) and GRα (p = 0.005) after 30 min in responders but not in non-responders. Τhe formation of the complex GR-c-Jun was increased 60 min after treatment with dexamethasone only in responders who exhibited significantly lower expression of HDAC3 (p = 0.005) and HDAC5 (p < 0.0001) as compared to non-responders.
CONCLUSIONS
These data suggest that ASMC from COPD patients who do not respond to treatment with ICS, are characterized by reduced GR-c-Jun complex formation and increased expression of HDAC3 and HDAC5.
TRIAL REGISTRATION
ISRCTN11017699 (Registration date: 15/11/2016).
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Receptors, Glucocorticoid; Histone Deacetylases; Myocytes, Smooth Muscle; Male; Middle Aged; Female; Aged; Cells, Cultured; Adrenal Cortex Hormones; Glucocorticoids; Dexamethasone; Treatment Outcome; Administration, Inhalation; Bronchi
PubMed: 38812021
DOI: 10.1186/s12931-024-02769-3 -
Oncology Letters Jul 2024The purpose of the present study was to assess and compare the efficacy of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) in the treatment of lung...
The purpose of the present study was to assess and compare the efficacy of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) in the treatment of lung metastases from patients with colorectal cancer (CRC) and to identify the preferable treatment modality based on patient and tumor characteristics. Records of 118 patients with CRC with a total of 307 lung metastases who underwent SBRT or MWA between January 2015 and December 2022 were retrospectively analyzed, including the essential clinicopathological information on patients (age, sex and underlying diseases), diagnosis and treatment information [primary tumor site, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9], imaging data [diameter of lung metastasis, location of the metastasis (i.e., whether or not the tumor was adjacent to the vessel or bronchus) and internal features] and follow-up data (postoperative therapy, complications or adverse effects and survival outcomes). For statistical analysis of the local tumor progression (LTP), disease-free survival and overall survival (OS) rates, Cox regression analysis, along with the Kaplan-Meier method adjusted using inverse probability of treatment weighting (IPTW), were performed. The median follow-up duration in the present study was 31.5 months. Multivariable Cox regression analysis revealed that the CEA level, metastasis diameter and internal features were independent predictors of OS. In the IPTW-adjusted analysis, no significant difference in the 1-year OS rate was observed between the SBRT and MWA groups (92.9 vs. 93.9%; P=0.483); however, a notable discrepancy in the treatment modalities was noted, leading to significant differences in the 2- and 3-year OS rates (65.9 vs. 57.6%, P=0.001, and 44.7 vs. 36.4%, P<0.001, respectively). A significant interaction effect for the treatment modality was observed for LTP (P=0.021). In conclusion, the present study revealed that SBRT and MWA have similar therapeutic effects in terms of prolonging the survival of patients with CRC with lung metastases; however, regarding the local control of lung metastases, MWA is associated with a number of significant advantages.
PubMed: 38807676
DOI: 10.3892/ol.2024.14455 -
Oncology Letters Jul 2024There has been rapid advancement in the development of neoadjuvant therapy for non-small cell lung cancer (NSCLC), which holds great promise as an effective treatment...
There has been rapid advancement in the development of neoadjuvant therapy for non-small cell lung cancer (NSCLC), which holds great promise as an effective treatment strategy. Some clinical trials have confirmed that immunotherapy in combination with chemotherapy can be a recommended first-line regimen for neoadjuvant treatment of NSCLC. The present study describes the case of a male patient aged 65 years who was diagnosed with stage IIIA (cT2N2M0) adenosquamous carcinoma of the lung. After the administration of two cycles of neoadjuvant immunotherapy (sintilimab) in combination with chemotherapy, stable disease was observed in the primary tumor, whereas partial remission was detected in the mediastinal lymph nodes based on imaging assessment. The patient underwent an immediate upper lobectomy of the left lung. Pathological analysis revealed a complete response in the primary lesion, with only minimal presence of tumor cells observed in the lymph nodes surrounding the mediastinum and bronchi. This indicated that the present neoadjuvant therapy could be used in the treatment of stage III adenosquamous lung carcinoma; however, to conclusively determine its efficacy, further studies targeting this specific cancer type are essential.
PubMed: 38807664
DOI: 10.3892/ol.2024.14448 -
Frontiers in Medicine 2024Embolization Coil has been reported to effectively treat postoperative bronchopleural fistula (BPF). Little detailed information was available on computer tomography...
BACKGROUND
Embolization Coil has been reported to effectively treat postoperative bronchopleural fistula (BPF). Little detailed information was available on computer tomography (CT) imaging features of postoperative BPF and treating procedures with pushable Embolization Coil.
OBJECTIVE
We aimed to specify the imaging characteristics of postoperative BPFs and present our experience treating them with the pushable Embolization Coil.
METHODS
Six consecutive patients (four males and two females aged 29-56 years) diagnosed with postoperative BPF receiving bronchoscopic treatment with the pushable Nester® Embolization Coil (Cook Medical, Bloomington, Indiana) were included in this single-center, retrospective study. Multiplanar reconstruction of multidetector CT scans was reviewed for the presence, location, size, and radiological complications of each BPF, including air collection, pneumothorax, bronchiectasis, and chest tube. Using standardized data abstraction forms, demographic traits and clinical outcomes were extracted from the medical files of these patients.
RESULTS
The underlying diseases for lung resection surgery were pulmonary tuberculosis ( = 3), lung adenocarcinoma ( = 2), and pulmonary aspergillosis ( = 1). All patients had air or air-fluid collection with chest tubes on radiological findings. Multiplanar reconstruction identified the presence of postoperative BPF in all patients. Five fistulas were central, located proximal to the main or lobar bronchus, while one was peripheral, distant from the lobar bronchus. Fistula sizes ranged from 0.8 to 5.8 mm. Subsequent bronchoscopy and occlusion testing confirmed fistula openings in the bronchial stump: right main bronchus ( = 1), right upper lobe ( = 2), and left upper lobe ( = 3). The angioplasty catheter-based procedure allows precise fistula occlusion "like a sandwich" with the pushable Embolization Coil. Five patients with BPF sizes ranging from 0.8 to 1.5 mm were successfully treated with a pushable Embolization Coil, except for one with a BPF size of 5.8 mm. No adverse events or complications were observed throughout follow-up, ranging from 29 to 1,307 days.
CONCLUSION
The pushable Nester® Embolization Coil seems a minimally invasive, cost-effective, and relatively easy-to-perform bronchoscopic treatment for postoperative BPF with a size less than 2 mm. Further studies are required to ensure the use of pushable Embolization Coil in treating postoperative BPF.
PubMed: 38803344
DOI: 10.3389/fmed.2024.1333157 -
BMC Public Health May 2024This study aimed to analyze the trends and burden of occupational exposure to asbestos in the United States (U.S.) from 1990 to 2019, focusing on mortality rates,...
BACKGROUND
This study aimed to analyze the trends and burden of occupational exposure to asbestos in the United States (U.S.) from 1990 to 2019, focusing on mortality rates, geographic distribution, age and sex patterns, and causes of death.
METHODS
Data on the number of deaths attributable to occupational exposure to asbestos were collected from 1990 to 2019 in the U.S. Joinpoint analysis was conducted to assess trends over time, and regression models were applied to calculate annual percentage changes (APC) and annual average percentage changes (AAPC). Geographic distribution was examined using mapping techniques. Age and sex patterns were analyzed, and causes of death were identified based on available data.
RESULTS
From 1990 to 2019, the overall number of deaths due to occupational exposure to asbestos in the U.S. increased by 20.2%. However, age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALYs) rates (ASDR) exhibited a decline over the same period. Geographic analysis revealed differences in the number of deaths across states in 2019, with California reporting the highest number of fatalities. Age-specific mortality and DALYs showed an increase with age, peaking in older age groups. Tracheal, bronchus, and lung cancer were the leading causes of death attributed to asbestos exposure, with increasing trends observed over the past five years.
CONCLUSION
The study highlights significant trends and burden in occupational exposure to asbestos in the U.S., including overall increases in mortality rates, declining ASMR and ASDR, geographic disparities, age and sex patterns, and shifts in causes of death. These findings underscore the importance of continued monitoring and preventive measures to mitigate the burden of asbestos-related diseases.
Topics: Humans; United States; Asbestos; Male; Occupational Exposure; Female; Cause of Death; Middle Aged; Aged; Adult; Disability-Adjusted Life Years
PubMed: 38802850
DOI: 10.1186/s12889-024-18919-7 -
Cureus Apr 2024We report the case of a 53-year-old female who developed tracheobronchomalacia immediately following an uncomplicated robotic hysterectomy with bilateral...
We report the case of a 53-year-old female who developed tracheobronchomalacia immediately following an uncomplicated robotic hysterectomy with bilateral salpingo-oophorectomy to treat postmenopausal bleeding. Induction of anesthesia was notable for moderately difficult intubation, managed with applied cricothyroid pressure and a small 6.5 endotracheal tube placement via GlideScope. The surgical course was uneventful. The patient remained intubated in the post-anesthesia care unit but was not providing end-tidal volumes. Attempts to replace the endotracheal tube with a larger tube were unsuccessful and the patient was temporarily unable to ventilate. Rapid troubleshooting discovered that a laryngeal mask airway (LMA) could sufficiently ventilate the patient. An otolaryngologist was able to perform direct bronchoscopy, which revealed more than 50% dynamic anterior-posterior collapse of the trachea and bronchi. The patient was subsequently awakened from anesthesia and monitored in the intensive care unit, ventilating with an LMA. After a couple of hours, it was determined that the patient's airway was protected, and the LMA was removed.
PubMed: 38800293
DOI: 10.7759/cureus.59078 -
Medicina (Kaunas, Lithuania) May 2024Bronchiectasis is a chronic progressive respiratory disease characterized by permanent dilatation of the bronchi. It is a complex condition with numerous different...
Bronchiectasis is a chronic progressive respiratory disease characterized by permanent dilatation of the bronchi. It is a complex condition with numerous different etiologies, co-morbidities, and a heterogeneous presentation. As we know, there is a lack of studies that describe the differences and compare the characteristics between focal and multifocal bronchiectasis. The aim of this study is to identify differences in clinical characteristics presentation, severity or distribution in focal and multifocal bronchiectasis, and prognostic implications. 126 patients with computed tomography (CT)-verified bronchiectasis were enrolled. Baseline characteristics that included age, sex, smoking history, and respiratory symptoms were recorded, with special attention paid to hemoptysis appearance, body mass index, and comorbidities. The type of bronchiectasis determined by CT scan and the modified Reiff scores indicating radiological severity were recorded. Patients were divided in two groups (I is focal and II is multifocal). There were no statistically significant differences in age, smoking status, comorbidity, and BMI between the two groups. Multifocality was associated with a significantly higher proportion of females ( = 0.014), the rate of hemoptysis ( = 0.023), and the number of hospitalizations, but not of exacerbations and prevalence of immunodeficiency ( = 0.049). Significantly, a high number of subjects with multifocality had bronchiectasis of moderate severity, and post-infective and asthma-associated phenotypes were the dominant in this group. Unexpectedly, the cystic and varicose radiological phenotype (which need more time to develop) were more dominant in the focal group. The cylindrical phenotype was equally observed in the multifocal and focal groups. Our study suggests that multifocality is not related to age, number of exacerbations, or radiological phenotype, but it seems to be associated with the clinical post-infective phenotype, immunodeficiency, frequent hospitalizations, and severity. Thus, the presence of multifocal bronchiectasis may act as a biomarker of severity and poor outcomes in these patients.
Topics: Humans; Bronchiectasis; Female; Male; Middle Aged; Phenotype; Aged; Tomography, X-Ray Computed; Adult; Severity of Illness Index
PubMed: 38792978
DOI: 10.3390/medicina60050795 -
International Journal of Molecular... May 2024Lefamulin is a first-in-class systemic pleuromutilin antimicrobial and potent inhibitor of bacterial translation, and the most recent novel antimicrobial approved for...
Lefamulin is a first-in-class systemic pleuromutilin antimicrobial and potent inhibitor of bacterial translation, and the most recent novel antimicrobial approved for the treatment of community-acquired pneumonia (CAP). It exhibits potent antibacterial activity against the most prevalent bacterial pathogens that cause typical and atypical pneumonia and other infectious diseases. Early studies indicate additional anti-inflammatory activity. In this study, we further investigated the immune-modulatory activity of lefamulin in the influenza A/H1N1 acute respiratory distress syndrome (ARDS) model in BALB/c mice. Comparators included azithromycin, an anti-inflammatory antimicrobial, and the antiviral oseltamivir. Lefamulin significantly decreased the total immune cell infiltration, specifically the neutrophils, inflammatory monocytes, CD4 and CD8 T-cells, NK cells, and B-cells into the lung by Day 6 at both doses tested compared to the untreated vehicle control group (placebo), whereas azithromycin and oseltamivir did not significantly affect the total immune cell counts at the tested dosing regimens. Bronchioalveolar lavage fluid concentrations of pro-inflammatory cytokines and chemokines including TNF-α, IL-6, IL-12p70, IL-17A, IFN-γ, and GM-CSF were significantly reduced, and MCP-1 concentrations were lowered (not significantly) by lefamulin at the clinically relevant 'low' dose on Day 3 when the viral load peaked. Similar effects were also observed for oseltamivir and azithromycin. Lefamulin also decreased the viral load (TCID) by half a log10 by Day 6 and showed positive effects on the gross lung pathology and survival. Oseltamivir and lefamulin were efficacious in the suppression of the development of influenza-induced bronchi-interstitial pneumonia, whereas azithromycin did not show reduced pathology at the tested treatment regimen. The observed anti-inflammatory and immune-modulatory activity of lefamulin at the tested treatment regimens highlights a promising secondary pharmacological property of lefamulin. While these results require confirmation in a clinical trial, they indicate that lefamulin may provide an immune-modulatory activity beyond its proven potent antibacterial activity. This additional activity may benefit CAP patients and potentially prevent acute lung injury (ALI) and ARDS.
Topics: Animals; Influenza A Virus, H1N1 Subtype; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Disease Models, Animal; Diterpenes; Cytokines; Azithromycin; Oseltamivir; Female; Lung; Antiviral Agents; Tetrahydronaphthalenes; Respiratory Distress Syndrome; Immunomodulating Agents; Bronchoalveolar Lavage Fluid; Polycyclic Compounds; Thioglycolates
PubMed: 38791439
DOI: 10.3390/ijms25105401 -
Frontiers in Veterinary Science 2024Yaks inhabit high-altitude, low-oxygen regions, where ion transport functions play a crucial role in maintaining intracellular and extracellular ionic balance and...
Yaks inhabit high-altitude, low-oxygen regions, where ion transport functions play a crucial role in maintaining intracellular and extracellular ionic balance and regulating pulmonary vascular tension. These functions affect pulmonary ventilation and blood flow rate, aiding tissue development and enhancing oxygen transfer efficiency, thus facilitating better adaptation to hypoxic environments. To investigate the regulatory mechanisms of ion transport-related factors on the growth and development of yak lungs, we employed RNA sequencing (RNA-seq)for sequencing the transcriptome in the lung tissues of neonatal (1-day-old), juvenile (1-year-old), and adult (4-year-old) yaks. We also performed differential gene expression and functional analyses. The results yielded 26 genes associated with ion transport, mainly enriched in the salivary and pancreatic secretion pathways. Finally, we used several methods including quantitative polymerase chain reaction (qRT-PCR), and Western blotting (WB), immunohistochemical (IHC) and immunofluorescence (IF) staining to determine the distribution of the expression of the ion transport genes , , and in yak lung tissues. qRT-PCR and WB results indicated that mRNA and protein relative expression levels of and were significantly higher in neonatal yaks than in juvenile and adult yaks (all < 0.05), whereas those of were significantly higher in adult yaks than in neonatal and juvenile yaks (all < 0.05). IHC and IF results demonstrated that FOXI1, KCNMA1, and SLC12A2 were distributed among the epithelial mucosal layers (including ciliated, goblet, and Clara cells) of the yaks' bronchi and their branches in the lungs across different age groups of yak. Therefore, our results suggested that FOXI1, KCNMA1, and SLC12A2 may be strongly associated with the development and aging processes in yak lungs. These results provide insights into the molecular mechanisms underlying the yak's adaptation to high-altitude environments and valuable references for further research.
PubMed: 38779034
DOI: 10.3389/fvets.2024.1374794 -
The Clinical Respiratory Journal May 2024This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment... (Review)
Review
This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.
Topics: Humans; Pulmonary Surfactants; Contusions; Lung Injury; Respiratory Distress Syndrome; Animals; Respiration, Artificial; Treatment Outcome; Bronchoscopy
PubMed: 38778673
DOI: 10.1111/crj.13776