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Nutrition (Burbank, Los Angeles County,... Aug 2023The energy demands of individuals with cystic fibrosis (CF) vary depending on pancreatic function, body composition, lung function, and clinical status. In clinical...
OBJECTIVE
The energy demands of individuals with cystic fibrosis (CF) vary depending on pancreatic function, body composition, lung function, and clinical status. In clinical practice, predictive equations are used to determine energy requirements yet do not reliably account for these factors. Research regarding energy requirements during CF pulmonary exacerbation (CFPEx) and clinical stability is conflicting. The aim of this study was to investigate potential within-individual changes in measured resting energy expenditure (mREE) using indirect calorimetry (IC) at the commencement and completion of intravenous antibiotic treatment (IVABx) for CFPEx and during clinical stability. Secondary aims were to investigate potential differences between predicted resting energy expenditure (pREE) using Schofield equation and correlations between clinical factors with mREE.
METHODS
Body composition using bioimpedance analysis and mREE were conducted at three time points: commencement of IVABx; completion of IVABx; and clinically stable period thereafter.
RESULTS
Twenty-eight adults with CF completed at least one valid IC measurement. No significant within-person changes in mREE and body composition parameters were observed across time points. The mREE was positively correlated with fat-free mass (kg; r = 0.6; P = 0.008). The mREE was significantly higher than pREE at all time points with the mREE/pREE ratio elevated at time point 1:118% ± 19.5%; time point 2: 112% ± 13.2%; and time point 3: 122 ± 14.3%.
CONCLUSION
The mREE remained stable during CFPEx and clinical stability. The pREE underestimated mREE and application of injury factor adjustment of 110% to 130% could potentially account for this discrepancy. The potential role of IC and body composition in individualizing CF nutritional assessment and prescription requires further exploration.
Topics: Adult; Humans; Basal Metabolism; Cystic Fibrosis; Calorimetry, Indirect; Energy Metabolism; Lung
PubMed: 37263161
DOI: 10.1016/j.nut.2023.112073 -
La Radiologia Medica Mar 2024Lung cancer screening (LCS) by low-dose computed tomography (LDCT) demonstrated a 20-40% reduction in lung cancer mortality. National stakeholders and international...
PURPOSE
Lung cancer screening (LCS) by low-dose computed tomography (LDCT) demonstrated a 20-40% reduction in lung cancer mortality. National stakeholders and international scientific societies are increasingly endorsing LCS programs, but translating their benefits into practice is rather challenging. The "Model for Optimized Implementation of Early Lung Cancer Detection: Prospective Evaluation Of Preventive Lung HEalth" (PEOPLHE) is an Italian multicentric LCS program aiming at testing LCS feasibility and implementation within the national healthcare system. PEOPLHE is intended to assess (i) strategies to optimize LCS workflow, (ii) radiological quality assurance, and (iii) the need for dedicated resources, including smoking cessation facilities.
METHODS
PEOPLHE aims to recruit 1.500 high-risk individuals across three tertiary general hospitals in three different Italian regions that provide comprehensive services to large populations to explore geographic, demographic, and socioeconomic diversities. Screening by LDCT will target current or former (quitting < 10 years) smokers (> 15 cigarettes/day for > 25 years, or > 10 cigarettes/day for > 30 years) aged 50-75 years. Lung nodules will be volumetric measured and classified by a modified PEOPLHE Lung-RADS 1.1 system. Current smokers will be offered smoking cessation support.
CONCLUSION
The PEOPLHE program will provide information on strategies for screening enrollment and smoking cessation interventions; administrative, organizational, and radiological needs for performing a state-of-the-art LCS; collateral and incidental findings (both pulmonary and extrapulmonary), contributing to the LCS implementation within national healthcare systems.
Topics: Humans; Early Detection of Cancer; Lung; Lung Neoplasms; Mass Screening; Smoking Cessation; Tomography, X-Ray Computed; Middle Aged; Aged
PubMed: 38319494
DOI: 10.1007/s11547-024-01764-4 -
Journal of Ethnopharmacology Jan 2024Pulmonary fibrosis (PF) is an irreversible lung disease that severely affects human respiratory function. Traditionally, the natural plant Quzhou Fructus Arantii (QFA)...
ETHNOPHARMACOLOGICAL RELEVANCE
Pulmonary fibrosis (PF) is an irreversible lung disease that severely affects human respiratory function. Traditionally, the natural plant Quzhou Fructus Arantii (QFA) has therapeutic effects on respiratory diseases. However, the effects and the mechanism of anti-fibrotic have not been elucidated.
AIM OF THE STUDY
In this study, QFAE-nB was extracted from QFA, the aims of this study include understanding the correlation between Bleomycin (BLM)-induced PF and STING pathway in mice, as well as exploring the role and mechanisms of QFAE-nB in the treatment of PF.
MATERIALS AND METHODS
QFAE-nB was extracted from QFA, six main chemical components in QFAE-nB were identified by HPLC-QTOF-MS/MS, and quantitative analysis was conducted by HPLC. qPCR and Western blot were used to verify the molecular mechanism of QFAE-nB, and the anti-fibrotic effect of QFAE-nB was determined by hematoxylin-eosin (HE) staining and Masson staining as well as immunohistochemistry. TREX1-KO and STING-KO mice were used to verify the relationship between STING and PF and the important target action of QFAE-nB.
RESULTS
Six main flavonoids in QFAE-nB were identified as eriocitrin (0.76%), neoeriocitrin (2.79%), narirutin (4.31%), naringin (35.41%), hesperidin (1.74%), and neohesperidin (27.18%). The results showed that BLM-induced PF was associated with its exacerbated release of proinflammatory factors and chemokines in lung tissues. In addition, QFAE-nB alleviated BLM-induced lung fibrosis in mice by inhibiting the activation of the STING signaling pathway and reducing the signal transduction of TBK1-IRF3 and TBK1-NF-κB pathways. Notably, knockout of the TREX1 gene caused massive inflammation and even induced PF in the lung tissues, whereas QFAE-nB effectively alleviated inflammation and reduced PF. The deletion of the STING gene suppressed BLM-induced PF and inflammation, but STING-KO mice treated with QFAE-nB showed even lower expression levels of proinflammatory factors and chemokine.
CONCLUSIONS
The STING pathway plays an important role in PF, and QFAE-nB alleviates PF by mainly targeting the inhibition of the STING pathway to reduce inflammation. Together, the study paves the way for targeting the STING pathway in PF treatment.
Topics: Animals; Mice; Humans; Pulmonary Fibrosis; Tandem Mass Spectrometry; Lung; Bleomycin; Inflammation
PubMed: 37806536
DOI: 10.1016/j.jep.2023.117295 -
Chemosphere Nov 2023Growing research has demonstrated that exposure to fine particulate matter (PM) was associated with decreased pulmonary function and obvious inflammatory response....
Growing research has demonstrated that exposure to fine particulate matter (PM) was associated with decreased pulmonary function and obvious inflammatory response. However, few pieces of research focus on the effects of PM-bound metals on people with asthma. Here, we assessed whether PM and PM-bound metals exposure could worsen pulmonary function in asthmatic patients and further elucidate the possible mechanisms. Thirty-four asthmatic patients were recruited to follow up for one year with eight visits in 2019-2020 in Taiyuan City, China. The index of pulmonary function was detected and blood and nasal epithelial lining fluid (ELF) samples were acquired for biomarkers measurement at each follow-up. Linear mixed-effect (LME) models were used to evaluate the relations between PM, PM-bound metals, and blood metals with lung function and biomarkers of Th17/Treg balance. The individual PM exposure concentration varied from 37 μg/m to 194 μg/m (mean: 59.63 μg/m) in the present study. An interquartile range (IQR) increment of PM total mass was associated with a faster decline in maximal mid-expiratory flow (MMEF) and higher interleukin-23 (IL-23). PM-bound metals [e.g. copper (Cu), nickel (Ni), manganese (Mn), titanium (Ti), and zinc (Zn)] were significantly associated with IL-23 (Cu: 5.1126%, 95% CI: 9.3708, 0.8544; Mn: 14.7212%, 95% CI: 27.926, 1.5164; Ni: 1.0269%, 95% CI: 2.0273, 0.0264; Ti: 16.7536%, 95% CI: 31.6203, 1.8869; Zn: 24.5806%, 95% CI: 46.609, 2.5522). Meanwhile, blood lead (Pb) and Cu were associated with significant declines of 0.382-3.895% in MMEF and maximum ventilatory volume (MVV). Blood Pb was associated with descending transforming growth factor β (TGF-β). In conclusion, exposure to PM-bound metals and blood metals is a risk factor for decreased pulmonary function, especially in small airways. These alterations might be partially attributed to the imbalance of Th17/Treg.
Topics: Humans; Adult; Lead; T-Lymphocytes, Regulatory; Asthma; Zinc; Manganese; Nickel; Titanium; Interleukin-23; Lung
PubMed: 37597628
DOI: 10.1016/j.chemosphere.2023.139869 -
Biosensors & Bioelectronics Mar 2024Methylation is one of the most prevalent epigenetic modifications in natural organisms, and the processes of methylation and demethylation are closely associated with...
Methylation is one of the most prevalent epigenetic modifications in natural organisms, and the processes of methylation and demethylation are closely associated with cell growth, differentiation, gene transcription and expression. Abnormal methylation may lead to various human diseases including cancers. Simultaneous analysis of multiple DNA demethylases remains a huge challenge due to the requirement of diverse substrate probes and scarcity of proper signal transduction strategies. Herein, we propose a sensitive and label-free method for simultaneous monitoring of multiple DNA demethylases on the basis of demethylation-activated light-up dual-color RNA aptamers. The presence of targets AlkB homologue-3 (ALKBH3) and fat mass and obesity-associated enzyme (FTO) erases the methyl group in DNA substrate probes, activating the ligation-mediate bidirectional transcription amplification reaction to produce enormous Spinach and Mango aptamers. The resulting RNA aptamers (i.e., Spinach and Mango aptamers) can bind with their cognate nonfluorescent fluorogens (DFHBI and TO1-biotin) to significantly improve the fluorescence signals. This aptamersensor shows high specificity and sensitivity with a limit of detection (LOD) of 8.50 × 10 M for ALKBH3 and 6.80 × 10 M for FTO, and it can apply to screen DNA demethylase inhibitors, evaluate DNA demethylase kinetic parameters, and simultaneously measure multiple endogenous DNA demethylases in a single cell. Importantly, this aptamersensor can accurately discriminate the expressions of ALKBH3 and FTO between healthy tissues and non-small cell lung cancer (NSCLC) patient tissues, offering a powerful platform for clinical diagnosis and drug discovery.
Topics: Humans; RNA; Aptamers, Nucleotide; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Biosensing Techniques; DNA; Demethylation; Lung; AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 38147719
DOI: 10.1016/j.bios.2023.115966 -
Frontiers in Immunology 2023is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and...
INTRODUCTION
is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with are incompletely resolved.
METHODS
We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with
RESULTS
AM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration.
DISCUSSION
In conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with and reveals profound alterations critical for effective antimicrobial immunity.
Topics: Animals; Mice; Integrins; Lung; Macrophages, Alveolar; Pneumonia, Pneumococcal; Proteomics; Streptococcus pneumoniae; Transcriptome; CD11b Antigen
PubMed: 37790937
DOI: 10.3389/fimmu.2023.1227191 -
Microbiology Spectrum Aug 2023Influenza A virus (IAV)-methicillin-resistant Staphylococcus aureus (MRSA) coinfection causes severe respiratory infections. The host microbiome plays an important role...
Influenza A virus (IAV)-methicillin-resistant Staphylococcus aureus (MRSA) coinfection causes severe respiratory infections. The host microbiome plays an important role in respiratory tract infections. However, the relationships among the immune responses, metabolic characteristics, and respiratory microbial characteristics of IAV-MRSA coinfection have not been fully studied. We used specific-pathogen-free (SPF) C57BL/6N mice infected with IAV and MRSA to build a nonlethal model of IAV-MRSA coinfection and characterized the upper respiratory tract (URT) and lower respiratory tract (LRT) microbiomes at 4 and 13 days postinfection by full-length 16S rRNA gene sequencing. Immune response and plasma metabolism profile analyses were performed at 4 days postinfection by flow cytometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships among the LRT microbiota, the immune response, and the plasma metabolism profile were analyzed by Spearman's correlation analysis. IAV-MRSA coinfection showed significant weight loss and lung injury and significantly increased loads of IAV and MRSA in bronchoalveolar lavage fluid (BALF). Microbiome data showed that coinfection significantly increased the relative abundances of Enterococcus faecalis, Enterobacter hormaechei, Citrobacter freundii, and Klebsiella pneumoniae and decreased the relative abundances of Lactobacillus reuteri and Lactobacillus murinus. The percentages of CD4/CD8 T cells and B cells in the spleen; the levels of interleukin-9 (IL-9), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8 in the lung; and the level of mevalonolactone in plasma were increased in IAV-MRSA-coinfected mice. L. murinus was positively correlated with lung macrophages and natural killer (NK) cells, negatively correlated with spleen B cells and CD4/CD8 T cells, and correlated with multiple plasma metabolites. Future research is needed to clarify whether mediates or alters the severity of IAV-MRSA coinfection. The respiratory microbiome plays an important role in respiratory tract infections. In this study, we characterized the URT and LRT microbiota, the host immune response, and plasma metabolic profiles during IAV-MRSA coinfection and evaluated their correlations. We observed that IAV-MRSA coinfection induced severe lung injury and dysregulated host immunity and plasma metabolic profiles, as evidenced by the aggravation of lung pathological damage, the reduction of innate immune cells, the strong adaptation of the immune response, and the upregulation of mevalonolactone in plasma. was strongly correlated with immune cells and plasma metabolites. Our findings contribute to a better understanding of the role of the host microbiome in respiratory tract infections and identified a key bacterial species, , that may provide important references for the development of probiotic therapies.
Topics: Mice; Animals; Methicillin-Resistant Staphylococcus aureus; Influenza A virus; Coinfection; Lung Injury; CD8-Positive T-Lymphocytes; Chromatography, Liquid; RNA, Ribosomal, 16S; Mice, Inbred C57BL; Tandem Mass Spectrometry; Lung; Respiratory Tract Infections; Microbiota; Immunity
PubMed: 37318361
DOI: 10.1128/spectrum.05247-22 -
Critical Reviews in Toxicology Sep 2023The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of... (Review)
Review
A review of pulmonary neutrophilia and insights into the key role of neutrophils in particle-induced pathogenesis in the lung from animal studies of lunar dusts and other poorly soluble dust particles.
The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), which differed 14-fold in levels of psROS, and two toxicity reference dusts (TiO and quartz) indicated that psROS had no significant contribution to the dusts' toxicity in the lung. Reported here are results of further investigations by the LD toxicity study team on the toxicological role of oxidants in alveolar neutrophils that were harvested from rats in the 5-dust ITI study and from rats that were exposed to airborne LD for 4 weeks. The oxidants per neutrophils and all neutrophils increased with dose, exposure time and dust's cytotoxicity. The results suggest that alveolar neutrophils play a critical role in particle-induced injury and toxicity in the lung of dust-exposed animals. Based on these results, we propose an adverse outcome pathway (AOP) for particle-associated lung disease that centers on the crucial role of alveolar neutrophil-derived oxidant species. A critical review of the toxicology literature on particle exposure and lung disease further supports a neutrophil-centric mechanism in the pathogenesis of lung disease and may explain previously reported animal species differences in responses to poorly soluble particles. Key findings from the toxicology literature indicate that (1) after exposures to the same dust at the same amount, rats have more alveolar neutrophils than hamsters; hamsters clear more particles from their lungs, consequently contributing to fewer neutrophils and less severe lung lesions; (2) rats exposed to nano-sized TiO have more neutrophils and more severe lesions in their lungs than rats exposed to the same mass-concentration of micron-sized TiO; nano-sized dust has a greater number of particles and a larger total particle-cell contact surface area than the same mass of micron-sized dust, which triggers more alveolar epithelial cells (AECs) to synthesize and release more cytokines that recruit a greater number of neutrophils leading to more severe lesions. Thus, we postulate that, during chronic dust exposure, particle-inflicted AECs persistently release cytokines, which recruit neutrophils and activate them to produce oxidants resulting in a prolonged continuous source of endogenous oxidative stress that leads to lung toxicity. This neutrophil-driven lung pathogenesis explains why dust exposure induces more severe lesions in rats than hamsters; why, on a mass-dose basis, nano-sized dusts are more toxic than the micron-sized dusts; why lung lesions progress with time; and why dose-response curves of particle toxicity exhibit a hockey stick like shape with a threshold. The neutrophil centric AOP for particle-induced lung disease has implications for risk assessment of human exposures to dust particles and environmental particulate matter.
Topics: Cricetinae; Rats; Humans; Animals; Dust; Neutrophils; Lung; Lung Diseases; Cytokines; Oxidants; Particle Size
PubMed: 37850621
DOI: 10.1080/10408444.2023.2258925 -
Critical Care (London, England) Aug 2023Positive end-expiratory pressure (PEEP) individualized to a maximal respiratory system compliance directly implies minimal driving pressures with potential outcome...
Dynamic lung aeration and strain with positive end-expiratory pressure individualized to maximal compliance versus ARDSNet low-stretch strategy: a study in a surfactant depletion model of lung injury.
BACKGROUND
Positive end-expiratory pressure (PEEP) individualized to a maximal respiratory system compliance directly implies minimal driving pressures with potential outcome benefits, yet, raises concerns on static and dynamic overinflation, strain and cyclic recruitment. Detailed accurate assessment and understanding of these has been hampered by methodological limitations. We aimed to investigate the effects of a maximal compliance-guided PEEP strategy on dynamic lung aeration, strain and tidal recruitment using current four-dimensional computed tomography (CT) techniques and analytical methods of tissue deformation in a surfactant depletion experimental model of acute respiratory distress syndrome (ARDS).
METHODS
ARDS was induced by saline lung lavage in anesthetized and mechanically ventilated healthy sheep (n = 6). Animals were ventilated in a random sequence with: (1) ARDSNet low-stretch protocol; (2) maximal compliance PEEP strategy. Lung aeration, strain and tidal recruitment were acquired with whole-lung respiratory-gated high-resolution CT and quantified using registration-based techniques.
RESULTS
Relative to the ARDSNet low-stretch protocol, the maximal compliance PEEP strategy resulted in: (1) improved dynamic whole-lung aeration at end-expiration (0.456 ± 0.064 vs. 0.377 ± 0.101, P = 0.019) and end-inspiration (0.514 ± 0.079 vs. 0.446 ± 0.083, P = 0.012) with reduced non-aerated and increased normally-aerated lung mass without associated hyperinflation; (2) decreased aeration heterogeneity at end-expiration (coefficient of variation: 0.498 ± 0.078 vs. 0.711 ± 0.207, P = 0.025) and end-inspiration (0.419 ± 0.135 vs. 0.580 ± 0.108, P = 0.014) with higher aeration in dorsal regions; (3) tidal aeration with larger inspiratory increases in normally-aerated and decreases in poorly-aerated areas, and negligible in hyperinflated lung (Aeration × Strategy: P = 0.026); (4) reduced tidal strains in lung regions with normal-aeration (Aeration × Strategy: P = 0.047) and improved regional distributions with lower tidal strains in middle and ventral lung (Region-of-interest [ROI] × Strategy: P < 0.001); and (5) less tidal recruitment in middle and dorsal lung (ROI × Strategy: P = 0.044) directly related to whole-lung tidal strain (r = 0.751, P = 0.007).
CONCLUSIONS
In well-recruitable ARDS models, a maximal compliance PEEP strategy improved end-expiratory/inspiratory whole-lung aeration and its homogeneity without overinflation. It further reduced dynamic strain in middle-ventral regions and tidal recruitment in middle-dorsal areas. These findings suggest the maximal compliance strategy minimizing whole-lung dynamically quantified mechanisms of ventilator-induced lung injury with less cyclic recruitment and no additional overinflation in large heterogeneously expanded and recruitable lungs.
Topics: Animals; Four-Dimensional Computed Tomography; Lipoproteins; Lung; Positive-Pressure Respiration; Pulmonary Surfactants; Respiratory Distress Syndrome; Sheep; Surface-Active Agents; Tidal Volume; Ventilator-Induced Lung Injury
PubMed: 37537654
DOI: 10.1186/s13054-023-04591-7 -
Academic Radiology Dec 2023Suboptimal chest radiographs (CXR) can limit interpretation of critical findings. Radiologist-trained AI models were evaluated for differentiating suboptimal(sCXR) and...
RATIONALE AND OBJECTIVES
Suboptimal chest radiographs (CXR) can limit interpretation of critical findings. Radiologist-trained AI models were evaluated for differentiating suboptimal(sCXR) and optimal(oCXR) chest radiographs.
MATERIALS AND METHODS
Our IRB-approved study included 3278 CXRs from adult patients (mean age 55 ± 20 years) identified from a retrospective search of CXR in radiology reports from 5 sites. A chest radiologist reviewed all CXRs for the cause of suboptimality. The de-identified CXRs were uploaded into an AI server application for training and testing 5 AI models. The training set consisted of 2202 CXRs (n = 807 oCXR; n = 1395 sCXR) while 1076 CXRs (n = 729 sCXR; n = 347 oCXR) were used for testing. Data were analyzed with the Area under the curve (AUC) for the model's ability to classify oCXR and sCXR correctly.
RESULTS
For the two-class classification into sCXR or oCXR from all sites, for CXR with missing anatomy, AI had sensitivity, specificity, accuracy, and AUC of 78%, 95%, 91%, 0.87(95% CI 0.82-0.92), respectively. AI identified obscured thoracic anatomy with 91% sensitivity, 97% specificity, 95% accuracy, and 0.94 AUC (95% CI 0.90-0.97). Inadequate exposure with 90% sensitivity, 93% specificity, 92% accuracy, and AUC of 0.91 (95% CI 0.88-0.95). The presence of low lung volume was identified with 96% sensitivity, 92% specificity, 93% accuracy, and 0.94 AUC (95% CI 0.92-0.96). The sensitivity, specificity, accuracy, and AUC of AI in identifying patient rotation were 92%, 96%, 95%, and 0.94 (95% CI 0.91-0.98), respectively.
CONCLUSION
The radiologist-trained AI models can accurately classify optimal and suboptimal CXRs. Such AI models at the front end of radiographic equipment can enable radiographers to repeat sCXRs when necessary.
Topics: Adult; Humans; Middle Aged; Aged; Lung; Retrospective Studies; Radiography, Thoracic; Radiography; Radiologists
PubMed: 37019698
DOI: 10.1016/j.acra.2023.03.006