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Rationale: Early detection of respiratory diseases is critical to facilitate delivery of disease-modifying interventions. Extracellular vesicle-enriched microRNAs (EV-miRNAs) may represent reliable markers of early lung injury. Objectives: Evaluate associations of plasma EV-miRNAs with lung function. Methods: The prospective NAS (Normative Aging Study) collected plasma EV-miRNA measurements from 1996-2015 and spirometry every 3-5 years through 2019. Associations of EV-miRNAs with baseline lung function were modeled using linear regression. To complement the individual miRNA approach, unsupervised machine learning was used to identify clusters of participants with distinct EV-miRNA profiles. Associations of EV-miRNA profiles with multivariate latent longitudinal lung function trajectories were modeled using log binomial regression. Biological functions of significant EV-miRNAs were explored using pathway analyses. Results were replicated in an independent sample of NAS participants and in the HEALS (Health Effects of Arsenic Longitudinal Study). Measurements and Main Results: In the main cohort of 656 participants, 51 plasma EV-miRNAs were associated with baseline lung function (false discovery rate-adjusted P value

BackgroundThe sex differences in use, safety outcomes, and health-care resource use of patients with pulmonary embolism (PE) undergoing percutaneous pulmonary artery thrombectomy are not well characterized.Research questionWhat are the sex differences in outcomes for patients diagnosed with PE who undergo percutaneous pulmonary artery thrombectomy?Study design and methodsThis retrospective cross-sectional study used national inpatient claims data to identify patients in the United States with a discharge diagnosis of PE who underwent percutaneous thrombectomy between January 2016 and December 2018. We evaluated the demographics, comorbidities, safety outcomes (in-hospital mortality), and health-care resource use (discharge to home, length of stay, and hospital charges) of patients with PE undergoing percutaneous thrombectomy.ResultsAmong 1,128,904 patients with a diagnosis of PE between 2016 and 2018, 5,160 patients (0.5%) underwent percutaneous pulmonary artery thrombectomy. When compared with male patients, female patients showed higher procedural bleeding (16.9% vs 11.2%; P < .05), required more blood transfusions (11.9% vs 5.7%; P < .05), and experienced more vascular complications (5.0% vs 1.5%; P < .05). Women experienced higher in-hospital mortality (16.9% vs 9.3%; adjusted OR, 1.9; 95% CI, 1.2-3.0; P = .003) when compared with men. Although length of stay and hospital charges were similar to those of men, women were less likely to be discharged home after surviving hospitalization (47.9% vs 60.3%; adjusted OR, 0.7; 95% CI, 0.50-0.99; P = .04).InterpretationIn this large nationwide cohort, women with PE who underwent percutaneous thrombectomy showed higher morbidity and in-hospital mortality compared with men.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with worsened outcomes in COVID-19 (coronavirus disease 2019). However, data remain fraught with heterogeneity and bias from comorbid conditions. Additionally, data on the impact of COPD-specific factors, such as pre-hospital medications and pulmonologist involvement, remain sparse.ObjectiveWe report a single-center analysis of COPD patients hospitalized with COVID-19 compared to those without COPD. Primary outcomes include ICU admission, mechanical ventilation, and in-hospital mortality.MethodsWe evaluated all patients ≥40 years admitted with PCR-confirmed COVID-19 between February 2020 and February 2021. COPD was defined by documented ICD-10 diagnosis of COPD, confirmed smoking history, and active bronchodilator use. We compared outcomes between COPD patients and the remainder of the COVID-19 cohort. Multivariable analyses were adjusted for age, sex, smoking status, and comorbid conditions.ResultsOf 1537 hospitalized COVID-19 patients, 122 (7.9%) carried a diagnosis of COPD. The COPD cohort was older (74 ± 13 vs 66 ± 15 years, P < 0.001) and more often former smokers (P < 0.001). Comorbid conditions including diabetes, cardiovascular disease, and kidney disease were more prevalent in the COPD group (P < 0.001). After adjusting for comorbid conditions, the COPD cohort had higher severity scores and trended towards fewer hospital-free days. Among patients with COPD, pre-hospital use of aspirin was associated with decreased ICU admissions (aHR 0.56, P = 0.049) and mechanical ventilation (aHR 0.25, P = 0.008), while LAMAs (long-acting muscarinic antagonists) were associated with decreased in-hospital mortality (aHR 0.34, P = 0.047). Involvement of pulmonology in pre-hospital management of COPD was not found to significantly affect outcomes.ConclusionWhen corrected for comorbid illnesses, COPD was associated with more severe disease but not with increased ICU admission, mechanical ventilation, or in-hospital mortality rates. Among COPD patients, prehospital treatment with aspirin and COPD-directed therapies were associated with improved outcomes.

BackgroundPulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis.ResultsWe found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial-mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM.ConclusionsOverall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.

PurposeTissue acquisition in lung cancer is vital for multiple reasons. Primary reasons reported for molecular testing failure in lung cancer biopsy specimens include insufficient amount of tumor cells provided and inadequate tissue quality. Robotic bronchoscopy is a new tool enabling peripheral pulmonary lesion sampling; however, diagnostic yield remains imperfect possibly due to the location of nodules adjacent to or outside of the airway. The 1.1-mm cryoprobe is a novel diagnostic tool and accesses tissue in a 360-degree manner, thus potentially sampling eccentric/adjacent lesions. This study examines the diagnostic yield of the cryoprobe compared to standard needle aspiration and forceps biopsy. It additionally evaluates yield for molecular markers in cases of lung cancer.MethodsThis is a retrospective analysis of 112 patients with 120 peripheral pulmonary lesions biopsied via robotic bronchoscopy using needle aspirate, forceps, and cryobiopsy.ResultsThe overall diagnostic yield was 90%. Nearly 18% of diagnoses were made exclusively from the cryobiopsy sample. Molecular analysis was adequate on all cryobiopsy samples sent. Digital imaging software confirmed an increase in quantity and quality of samples taken via cryobiopsy compared to needle aspirate and traditional forceps biopsy.ConclusionUsing the 1.1-mm cryoprobe to biopsy PPN combined with the Ion robotic bronchoscopy system is safe, feasible, and provides more diagnostic tissue than needle aspirates or traditional forceps biopsies. The combination of cryobiopsy with robotic-assisted bronchoscopy increased diagnostic yield, likely due to its 360-degree tissue acquisition which is beneficial when targeting extraluminal lesions adjacent to the airway.

Case presentationA 77-year-old woman with asthma, hypothyroidism, irritable bowel syndrome, overactive bladder, and multiple rheumatologic conditions was sent from the clinic to the ED for evaluation of hypoxia. In the clinic, she reported dizziness without shortness of breath and was noted to have perioral cyanosis with an oxygen saturation measured by pulse oximetry (Spo2) of 80%. She was given a nonrebreather mask delivering oxygen at 8 L/min, but the Spo2 remained at 77% to 82%. In the ED, the patient reported intermittent shortness of breath, 2 to 3 days of mild left lower extremity swelling, and a brief episode of lightheadedness earlier in the day that had since resolved. She denied fevers/chills, upper respiratory symptoms, and chest pain. She had been referred to the pulmonology clinic 3 years earlier to evaluate mild hypoxia with Spo2 readings in the low 90% range, but pulmonary function testing failed to identify an etiology. There was no history of VTE. Her rheumatologic conditions included osteoarthritis, rheumatoid arthritis, Sjögren's syndrome, and fibromyalgia.

The COVID-19 pandemic has affected clinicians in many different ways. Clinicians have their own experiences and lessons that they have learned from their work in the pandemic. This article outlines a few lessons learned from the eyes of CHEST Critical Care Editorial Board members, namely practices which will be abandoned, novel practices to be adopted moving forward, and proposed changes to the health care system in general. In an attempt to start the discussion of how health care can grow from the pandemic, the editorial board members outline their thoughts on these lessons learned.

ObjectiveThe Ross procedure is an excellent option for children or young adults who need aortic valve replacement because it can restore survival to that of the normal aged-matched population. However, autograft remodeling can lead to aneurysmal formation and reoperation, and the biomechanics of this process is unknown. This study investigated postoperative autograft remodeling after the Ross procedure by examining patient-specific autograft wall stresses.MethodsPatients who have undergone the Ross procedure who had intraoperative pulmonary root and aortic specimens collected were recruited. Patient-specific models (n = 16) were developed using patient-specific material property and their corresponding geometry from cine magnetic resonance imaging at 1-year follow-up. Autograft ± Dacron for aneurysm repair and ascending aortic geometries were reconstructed to develop patient-specific finite element models, which incorporated material properties and wall thickness experimentally measured from biaxial stretching. A multiplicative approach was used to account for prestress geometry from in vivo magnetic resonance imaging. Pressure loading to systemic pressure (120/80) was performed using LS-DYNA software (LSTC Inc, Livermore, Calif).ResultsAt systole, first principal stresses were 809 kPa (25%-75% interquartile range, 691-1219 kPa), 567 kPa (485-675 kPa), 637 kPa (555-755 kPa), and 382 kPa (334-413 kPa) at the autograft sinotubular junction, sinuses, annulus, and ascending aorta, respectively. Second principal stresses were 360 kPa (310-426 kPa), 355 kPa (320-394 kPa), 272 kPa (252-319 kPa), and 184 kPa (147-222 kPa) at the autograft sinotubular junction, sinuses, annulus, and ascending aorta, respectively. Mean autograft diameters were 29.9 ± 2.7 mm, 38.3 ± 5.3 mm, and 26.6 ± 4.0 mm at the sinotubular junction, sinuses, and annulus, respectively.ConclusionsPeak first principal stresses were mainly located at the sinotubular junction, particularly when Dacron reinforcement was used. Patient-specific simulations lay the foundation for predicting autograft dilatation in the future after understanding biomechanical behavior during long-term follow-up.

PurposeOptimal cognitive performance might prevent vehicle accidents. Identifying time-related circadian and homeostatic parameters having an impact on cognitive performance of drivers may be crucial to optimize drivers' performance.MethodsIn this prospective study conducted on bus drivers, two drivers alternated driving during a 24-h round trip and were accompanied by an interviewer. Each driver was tested using Karolinska Sleepiness Scale (KSS) and the reversed digit span Wechsler Working Memory test before the start of his shift and then every 6 h during a "work/driving" day. Psychomotor Vigilance Task (PVT) was assessed before and after the journey. Linear mixed model was used to explore the factors affecting cognitive performance and sleepiness in univariate and multivariate analysis.ResultsAmong 35 bus drivers, the effect of time of day on working memories was statistically significant (p = 0.001), with the lowest working memory scores at 04:00 am (± 1). The highest score of subjective sleepiness was also at 04:00 am (± 1). The time on task parameter affected sleepiness significantly (p = 0.024) and sleepiness was significantly associated with decreased working memory. Psychomotor Vigilance Task reaction time mean and the number of minor lapses were significantly increased after the journey, which suggested decreased vigilance. In multivariable analysis, a longer interval between the beginning of working hours and testing time (B (95% CI) = 15.25 (0.49 to 30), p = 0.043) was associated with higher (i.e., slower) PVT reaction time mean.ConclusionsThese results suggest that optimizing bus drivers' working schedules may improve drivers' sleepiness and cognitive performance and thus increase road safety.

BackgroundIncidental and screening-identified lung nodules are common, and a bronchoscopic evaluation is frequently nondiagnostic. The Percepta Genomic Sequencing Classifier (GSC) is a genomic classifier developed in current and former smokers which can be used for further risk stratification in these patients. Percepta GSC has the capability of up-classifying patients with a pre-bronchoscopy risk that is high (> 60%) to "very high risk" with a positive predictive value of 91.5%. This prospective, randomized decision impact survey was designed to test the hypothesis that an up-classification of risk of malignancy from high to very high will increase the rate of referral for surgical or ablative therapy without additional intervening procedures while increasing physician confidence.MethodsData were collected from 37 cases from the Percepta GSC validation cohort in which the pre-bronchoscopy risk of malignancy was high (> 60%), the bronchoscopy was nondiagnostic, and the patient was up-classified to very high risk by Percepta GSC. The cases were randomly presented to U.S pulmonologists in three formats: a pre-post cohort where each case is presented initially without and then with a GSG result, and two independent cohorts where each case is presented either with or without with a GSC result. Physicians were surveyed with respect to subsequent management steps and confidence in that decision.ResultsOne hundred and one survey takers provided a total of 1341 evaluations of the 37 patient cases across the three different cohorts. The rate of recommendation for surgical resection was significantly higher in the independent cohort with a GSC result compared to the independent cohort without a GSC result (45% vs. 17%, p

The management of pulmonary arterial hypertension (PAH) has become more complex in recent years because of increased pharmacotherapy options and longer patient survival with increasing numbers of comorbidities. As such, more opportunities exist for drug-drug interactions between PAH-targeted medications and medications potentially used to treat comorbid conditions. In this review, we provide an overview of pharmaceutical metabolism by cytochrome P450 and discuss important drug-drug interactions for the 14 Food and Drug Administration-approved medications for PAH in the nitric oxide (NO), endothelin, and prostacyclin pathways. Among the targets in the NO pathway (sildenafil, tadalafil, and riociguat), important interactions with nitrates, protease inhibitors, and other phosphodiesterase inhibitors can cause profound hypotension. In the endothelin pathway, bosentan is associated with more drug interactions via CYP3A4 inhibition; macitentan and ambrisentan have fewer interactions of note. Although the parenteral therapies in the prostacyclin pathway bypass significant liver metabolism and avoid drug interactions, selexipag and oral treprostinil may exhibit interactions with CYP2C8 inhibitors such as gemfibrozil and clopidogrel, which can raise drug levels. Finally, we provide a framework for identifying potential drug-drug interactions and avoiding errors.

BackgroundChronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF.MethodsWe performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets.ResultsWe found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts.ConclusionsWe identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.

BackgroundMechanical ventilation is often employed to facilitate breathing in patients suffering from respiratory illnesses and disabilities. Despite the benefits, there are risks associated with ventilator-induced lung injuries and death, driving investigations for alternative ventilation techniques to improve mechanical ventilation, such as multi-oscillatory and high-frequency ventilation; however, few studies have evaluated fundamental lung mechanical local deformations under variable loading.MethodsPorcine whole lung samples were analyzed using a novel application of digital image correlation interfaced with an electromechanical ventilation system to associate the local behavior to the global volume and pressure loading in response to various inflation volumes and breathing rates. Strains, anisotropy, tissue compliance, and the evolutionary response of the inflating lung were analyzed.ResultsExperiments demonstrated a direct and near one-to-one linear relationship between applied lung volumes and resulting local mean strain, and a nonlinear relationship between lung pressures and strains. As the applied air delivery volume was doubled, the tissue surface mean strains approximately increased from 20 to 40%, and average maximum strains measured 70-110%. The tissue strain anisotropic ratio ranged from 0.81 to 0.86 and decreased with greater inflation volumes. Local tissue compliance during the inflation cycle, associating evolutionary strains in response to inflation pressures, was also quantified.ConclusionVentilation frequencies were not found to influence the local stretch response. Strain measures significantly increased and the anisotropic ratio decreased between the smallest and greatest tidal volumes. Tissue compliance did not exhibit a unifying trend. The insights provided by the real-time continuous measures, and the kinetics to kinematics pulmonary linkage established by this study offers valuable characterizations for computational models and establishes a framework for future studies to compare healthy and diseased lung mechanics to further consider alternatives for effective ventilation strategies.

Background and objectiveCOVID-19 remains a major cause of respiratory failure, and means to identify future deterioration is needed. We recently developed a prediction score based on breath-holding manoeuvres (desaturation and maximal duration) to predict incident adverse COVID-19 outcomes. Here we prospectively validated our breath-holding prediction score in COVID-19 patients, and assessed associations with radiological scores of pulmonary involvement.MethodsHospitalized COVID-19 patients (N = 110, three recruitment centres) performed breath-holds at admission to provide a prediction score (Messineo et al.) based on mean desaturation (20-s breath-holds) and maximal breath-hold duration, plus baseline saturation, body mass index and cardiovascular disease. Odds ratios for incident adverse outcomes (composite of bi-level ventilatory support, ICU admission and death) were described for patients with versus without elevated scores (>0). Regression examined associations with chest x-ray (Brixia score) and computed tomography (CT; 3D-software quantification). Additional comparisons were made with the previously-validated '4C-score'.ResultsElevated prediction score was associated with adverse COVID-19 outcomes (N = 12/110), OR[95%CI] = 4.54[1.17-17.83], p = 0.030 (positive predictive value = 9/48, negative predictive value = 59/62). Results were diminished with removal of mean desaturation from the prediction score (OR = 3.30[0.93-11.72]). The prediction score rose linearly with Brixia score (β[95%CI] = 0.13[0.02-0.23], p = 0.026, N = 103) and CT-based quantification (β = 1.02[0.39-1.65], p = 0.002, N = 45). Mean desaturation was also associated with both radiological assessment. Elevated 4C-scores (≥high-risk category) had a weaker association with adverse outcomes (OR = 2.44[0.62-9.56]).ConclusionAn elevated breath-holding prediction score is associated with almost five-fold increased adverse COVID-19 outcome risk, and with pulmonary deficits observed in chest imaging. Breath-holding may identify COVID-19 patients at risk of future respiratory failure.

BackgroundHigh loop gain (unstable ventilatory control) is an important-but difficult to measure-contributor to obstructive sleep apnea (OSA) pathogenesis, predicting OSA sequelae and/or treatment response. Our objective was to develop and validate a clinical prediction tool of loop gain.MethodsA retrospective cohort of consecutive adults with OSA (apnea-hypopnea index, AHI > 5/hour) based on in-laboratory polysomnography 01/2017-12/2018 was randomly split into a training and test-set (3:1-ratio). Using a customized algorithm ("reference standard") loop gain was quantified from raw polysomnography signals on a continuous scale and additionally dichotomized (high > 0.7). Candidate predictors included general patient characteristics and routine polysomnography data. The model was developed (training-set) using linear regression with backward selection (tenfold cross-validated mean square errors); the predicted loop gain of the final linear regression model was used to predict loop gain class. More complex, alternative models including lasso regression or random forests were considered but did not meet pre-specified superiority-criteria. Final model performance was validated on the test-set.ResultsThe total cohort included 1055 patients (33% high loop gain). Based on the final model, higher AHI (beta = 0.0016; P

BackgroundRelationships between gut microbiomes and airway immunity have been established in murine and human studies of allergy and asthma. Early life Lactobacillus supplementation alters the composition and metabolic productivity of the gut microbiome. However, little is known of how Lactobacillus supplementation impacts the gut microbiota in children with cystic fibrosis (CF) and whether specific microbiota states that arise following gut microbiome manipulation relate to pulmonary outcomes.MethodsStool samples were collected from CF patients enrolled in a multi-center, double-blind, randomized placebo-controlled trial of daily Lactobacillus rhamnosus strain GG (LGG) probiotic supplementation over a 12-month period. Fecal 16S rRNA biomarker sequencing was used to profile fecal bacterial microbiota and analyses were performed in QiiME.ResultsBifidobacteria-dominated fecal microbiota were more likely to arise in LGG-treated children with CF (P = 0.04). Children with Bifidobacteria-dominated gut microbiota had a reduced rate of pulmonary exacerbations (IRR = 0.55; 95% CI 0.25 to 0.82; P = 0.01), improved pulmonary function (+ 20.00% of predicted value FEV1; 95% CI 8.05 to 31.92; P = 0.001), lower intestinal inflammation (Calprotectin; Coef =  - 16.53 μg g-1 feces; 95% CI - 26.80 to - 6.26; P = 0.002) and required fewer antibiotics (IRR = 0.43; 95% CI 0.22 to 0.69; P = 0.04) compared to children with Bacteroides-dominated microbiota who were less likely to have received LGG.ConclusionsThe majority of pediatric CF patients in this study possessed a Bacteroides- or Bifidobacteria-dominated gut microbiota. Bifidobacteria-dominated gut microbiota were more likely to be associated with LGG-supplementation and with better clinical outcomes.

Abstract An accurate understanding of the ecology and complexity of the poultry respiratory microbiota is of utmost importance for elucidating the roles of commensal or pathogenic microorganisms in the respiratory tract, as well as their associations with health or disease outcomes in poultry. This comprehensive review delves into the intricate aspects of the poultry respiratory microbiota, focusing on its colonization patterns, composition, and impact on poultry health. Firstly, an updated overview of the current knowledge concerning the composition of the microbiota in the respiratory tract of poultry is provided, as well as the factors that influence the dynamics of community structure and diversity. Additionally, the significant role that the poultry respiratory microbiota plays in economically relevant respiratory pathobiologies that affect poultry is explored. In addition, the challenges encountered when studying the poultry respiratory microbiota are addressed, including the dynamic nature of microbial communities, site-specific variations, the need for standardized protocols, the appropriate sequencing technologies, and the limitations associated with sampling methodology. Furthermore, emerging evidence that suggests bidirectional communication between the gut and respiratory microbiota in poultry is described, where disturbances in one microbiota can impact the other. Understanding this intricate cross talk holds the potential to provide valuable insights for enhancing poultry health and disease control. It becomes evident that gaining a comprehensive understanding of the multifaceted roles of the poultry respiratory microbiota, as presented in this review, is crucial for optimizing poultry health management and improving overall outcomes in poultry production.

Lujian Zhu,1,&ast; Jing Zhou,1,&ast; Chen Yu,2 Lei Gu,3 Qin Wang,1 Hanglu Xu,1 Yin Zhu,4 Maodong Guo,5 Minli Hu,5 Wei Peng,6 Hao Fang,7 Haizhen Wang8 1Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 4Department of Infectious Diseases, Taizhou Enze Medical Center (Group), Enze Hospital, Taizhou, People’s Republic of China; 5Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 6Department of Intensive Care Unit, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 7Department of Trauma Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 8Department of Health Management Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haizhen Wang, Department of Health Management Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China, Email whz002012@sina.comAbstract: Ferroptosis, a type of programmed cell death that relies on iron, is distinct in terms of its morphological, biochemical and genetic features. Unlike other forms of cell death, such as autophagy, apoptosis, necrosis, and pyroptosis, ferroptosis is primarily caused by lipid peroxidation. Cells that die due to iron can potentially trigger an immune response which intensifies inflammation and causes severe inflammatory reactions that eventually lead to multiple organ failure. In recent years, ferroptosis has been identified in an increasing number of medical fields, including neurological pathologies, chronic liver diseases and sepsis. Ferroptosis has the potential to cause an inflammatory tempest, with many of the catalysts and pathological indications of respiratory ailments being linked to inflammatory reactions. The growing investigation into ferroptosis in respiratory disorders has also garnered significant interest to better understand the mechanism of ferroptosis in these diseases. In this review, the recent progress in understanding the molecular control of ferroptosis and its mechanism in different respiratory disorders is examined. In addition, this review discusses current challenges and prospects for understanding the link between respiratory diseases and ferroptosis.Keywords: respiratory system, ferroptosis, iron metabolism, oxidative stress, treatment

Introduction: The shaping of the human intestinal microbiota starts during the intrauterine period and continues through the subsequent stages of extrauterine life. The microbiota plays a significant role in the predisposition and development of immune diseases, as well as various inflammatory processes. Importantly, the proper colonization of the fetal digestive system is influenced by maternal microbiota, the method of pregnancy completion and the further formation of the microbiota. In the subsequent stages of a child’s life, breastfeeding, diet and the use of antibiotics influence the state of eubiosis, which determines proper growth and development from the neonatal period to adulthood. The literature data suggest that there is evidence to confirm that the intestinal microbiota of the infant plays an important role in regulating the immune response associated with the development of allergic diseases. However, the identification of specific bacterial species in relation to specific types of reactions in allergic diseases is the basic problem. Background: The main aim of the review was to demonstrate the influence of the microbiota of the mother, fetus and newborn on the functioning of the immune system in the context of allergies and asthma. Methods: We reviewed and thoroughly analyzed the content of over 1000 articles and abstracts between the beginning of June and the end of August 2024. Over 150 articles were selected for the detailed study. Results: The selection was based on the PubMed National Library of Medicine search engine, using selected keywords: “the impact of intestinal microbiota on the development of immune diseases and asthma”, “intestinal microbiota and allergic diseases”, “the impact of intrauterine microbiota on the development of asthma”, “intrauterine microbiota and immune diseases”, “intrauterine microbiota and atopic dermatitis”, “intrauterine microbiota and food allergies”, “maternal microbiota”, “fetal microbiota” and “neonatal microbiota”. The above relationships constituted the main criteria for including articles in the analysis. Conclusions: In the present review, we showed a relationship between the proper maternal microbiota and the normal functioning of the fetal and neonatal immune system. The state of eubiosis with an adequate amount and diversity of microbiota is essential in preventing the development of immune and allergic diseases. The way the microbiota is shaped, resulting from the health-promoting behavior of pregnant women, the rational conduct of the medical staff and the proper performance of the diagnostic and therapeutic process, is necessary to maintain the health of the mother and the child. Therefore, an appropriate lifestyle, rational antibiotic therapy as well as the way of completing the pregnancy are indispensable in the prevention of the above conditions. At the same time, considering the intestinal microbiota of the newborn in relation to the genera and phyla of bacteria that have a potentially protective effect, it is worth noting that the use of suitable probiotics and prebiotics seems to contribute to the protective effect.

Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes. Objectives: To search for rare variants contributing to OSA severity. Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry. Measurements and Main Results: Linkage analysis in the CFS identified a suggestive linkage peak on chromosome 7q31 (LOD = 2.31). Gene-based analysis identified 21 noncoding rare variants in CAV1 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons (P = 7.4 × 10-8). These noncoding variants together significantly contributed to the linkage evidence (P

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P

Rationale: The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain. Objectives: Using data in the Severe Asthma Research Program 3 (SARP-3), we evaluated relationships between homeostatic measure of IR (HOMA-IR), lung function (cross-sectional and longitudinal analyses), and treatment responses to bronchodilators and corticosteroids. Methods: HOMA-IR values were categorized as without (5.0). Lung function included FEV1 and FVC measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide and yearly for 5 years. Measurements and Main Results: Among 307 participants in SARP-3, 170 (55%) were obese and 140 (46%) had IR. Compared with patients without IR, those with IR had significantly lower values for FEV1 and FVC, and these lower values were not attributable to obesity effects. Compared with patients without IR, those with IR had lower FEV1 responses to β-adrenergic agonists and systemic corticosteroids. The annualized decline in FEV1 was significantly greater in patients with moderate IR (-41 ml/year) and severe IR (-32 ml/year,) than in patients without IR (-13 ml/year, P

ObjectiveAscending thoracic aortic aneurysms carry a risk of acute type A dissection. Elective repair guidelines are designed around size thresholds, but the 1-dimensional parameter of maximum diameter cannot predict acute events in small aneurysms. Biomechanically, dissection can occur when wall stress exceeds strength. Patient-specific ascending thoracic aortic aneurysm wall stresses may be a better predictor of dissection. Our aim was to compare wall stresses in tricuspid aortic valve-associated ascending thoracic aortic aneurysms based on diameter.MethodsPatients with tricuspid aortic valve-associated ascending thoracic aortic aneurysm and diameter 4.0 cm or greater (n = 221) were divided into groups by 0.5-cm diameter increments. Three-dimensional geometries were reconstructed from computed tomography images, and finite element models were developed taking into account prestress geometries. A fiber-embedded hyperelastic material model was applied to obtain longitudinal and circumferential wall stress distributions under systolic pressure. Median stresses with interquartile ranges were determined. The Kruskal-Wallis test was used for comparisons between size groups.ResultsPeak longitudinal wall stresses for tricuspid aortic valve-associated ascending thoracic aortic aneurysm were 290 (265-323) kPa for size 4.0 to 4.4 cm versus 330 (296-359) kPa for 4.5 to 4.9 cm versus 339 (320-373) kPa for 5.0 to 5.4 cm versus 318 (293-351) kPa for 5.5 to 5.9 cm versus 373 (363-449) kPa for 6.0 cm or greater (P = 8.7e-8). Peak circumferential wall stresses were 460 (421-543) kPa for size 4.0 to 4.4 cm versus 503 (453-569) kPa for 4.5 to 4.9 cm versus 549 (430-588) kPa for 5.0 to 5.4 cm versus 540 (471-608) kPa for 5.5 to 5.9 cm versus 596 (506-649) kPa for 6.0 cm or greater (P = .0007).ConclusionsCircumferential and longitudinal wall stresses are higher as diameter increases, but size groups had large overlap of stress ranges. Wall stress thresholds based on aneurysm wall strength may be a better predictor of patient-specific risk of dissection than diameter in small ascending thoracic aortic aneurysms.

BackgroundExposure to ozone (O3) is associated with increased risk of exacerbations of asthma, but the underlying mechanisms are not well studied.ObjectiveWe sought to determine whether O3 exposure would enhance airway inflammatory responses to allergen and the GSTM1-null genotype would modulate this enhancement.MethodsIn a crossover design, 10 asthmatic participants (5 with GSTM1-null genotype) who had specific sensitization to Dermatophagoides pteronyssinus (DP) were exposed to 160 ppb O3 or filtered air (FA) control for 4 hours on 2 separate days at least 3 weeks apart. At 20 hours after exposure, endobronchial challenge with DP allergen, and sham normal saline (NS) instillation, were performed in separate bronchi. Six hours later, a second bronchoscopy was performed to collect bronchoalveolar lavage (BAL) from the DP- and NS-challenged segments for analyses of inflammatory biomarkers. Linear regression compared cell and cytokine responses across the 4 exposure groups (FA-NS, O3-NS, FA-DP, O3-DP). Effect modification by GSTM1 genotype was assessed in stratified regressions.ResultsBAL eosinophil counts were increased in segments challenged with DP compared to sham-challenged segments (P < .01). DP challenge compared to sham also caused a significant increase in BAL concentrations of the TH2 cytokines IL-4, IL-5, IL-10, and IL-13 (P < .03 for all comparisons). O3 exposure did not significantly affect BAL cells or cytokine after DP challenge. Compared to GSTM1-present participants, GSTM1-null participants had significantly lower eosinophil (P < .041) and IL-4 (P < .014) responses to DP challenge after O3 exposure.ConclusionsWhile O3 did not cause a clear differential effect on airway inflammatory responses to allergen challenge, those responses did appear to be modulated by the antioxidant enzyme, GSTM1.

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2; inactivated viral particles; or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.

Rationale: Although the contribution of air pollution to lung cancer risk is well characterized, few studies have been conducted in racially, ethnically, and socioeconomically diverse populations. Objectives: To examine the association between traffic-related air pollution and risk of lung cancer in a racially, ethnically, and socioeconomically diverse cohort. Methods: Among 97,288 California participants of the Multiethnic Cohort Study, we used Cox proportional hazards regression to examine associations between time-varying traffic-related air pollutants (gaseous and particulate matter pollutants and regional benzene) and lung cancer risk (n = 2,796 cases; average follow-up = 17 yr), adjusting for demographics, lifetime smoking, occupation, neighborhood socioeconomic status (nSES), and lifestyle factors. Subgroup analyses were conducted for race, ethnicity, nSES, and other factors. Measurements and Main Results: Among all participants, lung cancer risk was positively associated with nitrogen oxide (hazard ratio [HR], 1.15 per 50 ppb; 95% confidence interval [CI], 0.99-1.33), nitrogen dioxide (HR, 1.12 per 20 ppb; 95% CI, 0.95-1.32), fine particulate matter with aerodynamic diameter  0.21), although participants residing in low-SES neighborhoods had increased lung cancer risk associated with nitrogen oxides, and no association was observed among those in high-SES neighborhoods. Conclusions: These findings in a large multiethnic population reflect an association between lung cancer and the mixture of traffic-related air pollution and not a particular individual pollutant. They are consistent with the adverse effects of air pollution that have been described in less racially, ethnically, and socioeconomically diverse populations. Our results also suggest an increased risk of lung cancer among those residing in low-SES neighborhoods.

Drug susceptibility testing of M. tuberculosis is rooted in a binary susceptible/resistant paradigm. While there are considerable advantages in measuring the minimum inhibitory concentrations (MICs) of a panel of drugs for an isolate, it is necessary to measure the epidemiological cut-off values (ECOFF/ECVs) to permit comparison with qualitative data. Here we present ECOFF/ECVs for 13 anti-tuberculosis compounds, including bedaquiline and delamanid, derived from 20 637 clinical isolates collected by 14 laboratories based in 11 countries on five continents. Each isolate was incubated for 14 days on a dry 96-well broth microdilution plate and then read. Resistance to most of the drugs due to prior exposure is expected and the MIC distributions for many of the compounds are complex, and therefore a phenotypically wild-type population could not be defined. Since a majority of samples also underwent genetic sequencing, we defined a genotypically wild-type population and measured the MIC of the 99th percentile by direct measurement and via fitting a Gaussian using interval regression. The proposed ECOFF/ECVs were then validated by comparing with the MIC distributions of high-confidence genetic variants that confer resistance and with qualitative drug susceptibility tests obtained via the Mycobacterial Growth Indicator Tube (MGIT) system or Microscopic-Observation Drug Susceptibility (MODS) assay. These ECOFF/ECVs will inform and encourage the more widespread adoption of broth microdilution: this is a cheap culture-based method that tests the susceptibility of 12-14 antibiotics on a single 96-well plate and so could help personalise the treatment of tuberculosis.

BackgroundGuidelines for sinus of Valsalva (SOV)-thoracic aortic aneurysms in Marfan syndrome recommend size-based criteria for elective surgical repair. Biomechanics may provide a better prediction of dissection risk than diameter. Our aim was to determine magnitudes of wall stress in the aortic root of Marfan patients using finite element analyses.MethodsForty-six Marfan patients underwent patient-specific 3-dimensional SOV-thoracic aortic aneurysm geometry reconstruction using imaging data. Finite element analyses were performed to determine wall stress distributions at SOV, sinotubular junction (STJ), and ascending aorta (AscAo) at systole.ResultsPeak circumferential stresses were 432.8 ± 111 kPa, 408.1 ± 88.3 kPa, and 321.9 ± 83.8 kPa at the SOV, STJ, and AscAo, respectively, with significant differences between SOV and AscAo (P < 3.08E-07), and STJ and AscAo (P < 2.26E-06). Peak longitudinal wall stresses were 352 ± 73.9 kPa, 277.5 ± 89.5 kPa, and 200.6 ± 81 kPa at SOV, STJ, and AscAo, respectively, with significant differences between SOV and STJ (P < 6.01E-06), SOV and AscAo (P < 9.79E-13), and STJ and AscAo (P < 3.34E-07). Diameter was not correlated to wall stresses. Comparison of wall stresses in aneurysm

Rationale: There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate whether exposure to Agent Orange is associated with an increased risk of IPF among veterans. Methods: We used Veterans Health Administration data to identify patients diagnosed with IPF between 2010 and 2019. We restricted the cohort to male Vietnam veterans and performed multivariate logistic regression to examine the association between presumptive Agent Orange exposure and IPF. We conducted sensitivity analyses restricting the cohort to army veterans (highest theoretical burden of exposure, surrogate for dose response) and a more specific case definition of IPF. Fine-Gray competing risk models were used to evaluate age to IPF diagnosis. Measurements and Main Results: Among 3.6 million male Vietnam veterans, 948,103 (26%) had presumptive Agent Orange exposure. IPF occurred in 2.2% of veterans with Agent Orange exposure versus 1.9% without exposure (odds ratio, 1.14; 95% confidence interval [CI], 1.12-1.16; P

Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P

ObjectiveTranscatheter aortic valve replacement (TAVR), previously reserved for patients of intermediate to prohibitive surgical risk, has now been expanded to patients of any surgical risk with severe aortic stenosis. Bioprostheses are prone to structural valve degeneration (SVD), a progressive and multifactorial process that limits valve durability. As the population undergoing TAVR shifts toward a lower-risk and younger profile, long-term durability is a crucial determinant for patient outcomes. Our objective was to determine the incidence and risk factors of SVD at midterm follow-up in a veteran TAVR population.MethodsPatients undergoing TAVR at our federal facility were retrospectively evaluated for SVD and other endpoints with standardized consensus criteria. Multivariable Cox proportional hazards analysis was performed to evaluate risk factors for mortality and SVD.ResultsFrom 2013 to 2020, 344 patients (median age, 78 years) underwent TAVR. Survival from all-cause mortality was 91.3% at 1 year, 75.1% at 3 years, and 61.7% at 5 years. Cumulative freedom from SVD was 98.2% at 1 year, 96.5% at 3 years, and 93.7% at 5 years. All 13 patients with SVD met hemodynamic criteria, and 1 required intervention. Median time to hemodynamic SVD was 1.04 years. Independent risk factors for SVD included age (hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.86 to 0.99) and valve size (HR = 0.19, 95% CI: 0.04 to 0.89).ConclusionsSVD was evident at a low but detectable rate at 5-year follow-up. Further understanding of TAVR biomechanics as well as continued longer-term follow-up will be essential for informing patient-specific risk of SVD.

An accurate understanding of the ecology and complexity of the poultry respiratory microbiota is of utmost importance for elucidating the roles of commensal or pathogenic microorganisms in the respiratory tract, as well as their associations with health or disease outcomes in poultry. This comprehensive review delves into the intricate aspects of the poultry respiratory microbiota, focusing on its colonization patterns, composition, and impact on poultry health. Firstly, an updated overview of the current knowledge concerning the composition of the microbiota in the respiratory tract of poultry is provided, as well as the factors that influence the dynamics of community structure and diversity. Additionally, the significant role that the poultry respiratory microbiota plays in economically relevant respiratory pathobiologies that affect poultry is explored. In addition, the challenges encountered when studying the poultry respiratory microbiota are addressed, including the dynamic nature of microbial communities, site-specific variations, the need for standardized protocols, the appropriate sequencing technologies, and the limitations associated with sampling methodology. Furthermore, emerging evidence that suggests bidirectional communication between the gut and respiratory microbiota in poultry is described, where disturbances in one microbiota can impact the other. Understanding this intricate cross talk holds the potential to provide valuable insights for enhancing poultry health and disease control. It becomes evident that gaining a comprehensive understanding of the multifaceted roles of the poultry respiratory microbiota, as presented in this review, is crucial for optimizing poultry health management and improving overall outcomes in poultry production. [ABSTRACT FROM AUTHOR]

Background/aim: This study was planned because the radiological distinction of COVID-19 and respiratory viral panel (RVP)-positive cases is necessary to prioritize intensive care needs and ensure non-COVID-19 cases are not overlooked. With that purpose, the objective of this study was to compare radiologic findings between SARS-CoV-2 and other respiratory airway viruses in critically ill children with suspected COVID-19 disease. Materials and methods: This study was conducted as a multicenter, retrospective, observational, and cohort study in 24 pediatric intensive care units between March 1 and May 31, 2020. SARS-CoV-2- or RVP polymerase chain reaction (PCR)-positive patients’ chest X-ray and thoracic computed tomography (CT) findings were evaluated blindly by pediatric radiologists. Results: We enrolled 225 patients in the study, 81 of whom tested positive for Coronovirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The median age of all patients was 24 (7–96) months, while it was 96 (17–156) months for COVID-19-positive patients and 17 (6–48) months for positive for other RVP factor (p < 0.001). Chest X-rays were more frequently evaluated as normal in patients with SARS-CoV-2 positive results (p = 0.020). Unilateral segmental or lobar consolidation was observed more frequently on chest X-rays in rhinovirus cases than in other groups (p = 0.038). CT imaging findings of bilateral peribronchial thickening and/or peribronchial opacity were more frequently observed in RVP-positive patients (p = 0.046). Conclusion: Chest X-ray and CT findings in COVID-19 patients are not specific and can be seen in other respiratory virus infections. [ABSTRACT FROM AUTHOR]

Lung branching morphogenesis relies on intricate epithelial–mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic acid (RA) signaling influences lung proximal–distal patterning and branching morphogenesis, but its role as a metabolic modulator is unknown. Hence, this study investigates how RA signaling affects the metabolic profile of lung branching. We performed ex vivo lung explant culture of embryonic chicken lungs treated with DMSO, 1 µM RA, or 10 µM BMS493. Extracellular metabolite consumption/production was evaluated by using 1H-NMR spectroscopy. Mitochondrial respiration and biogenesis were also analyzed. Proliferation was assessed using an EdU-based assay. The expression of crucial metabolic/signaling components was examined through Western blot, qPCR, and in situ hybridization. RA signaling stimulation redirects glucose towards pyruvate and succinate production rather than to alanine or lactate. Inhibition of RA signaling reduces lung branching, resulting in a cystic-like phenotype while promoting mitochondrial function. Here, RA signaling emerges as a regulator of tissue proliferation and lactate dehydrogenase expression. Furthermore, RA governs fatty acid metabolism through an AMPK-dependent mechanism. These findings underscore RA's pivotal role in shaping lung metabolism during branching morphogenesis, contributing to our understanding of lung development and cystic-related lung disorders. [ABSTRACT FROM AUTHOR]

Background: The mediastinal shift angle is a new fetal magnetic resonance imaging (MRI) index that is reportedly correlated with postnatal survival in fetuses with congenital diaphragmatic hernia. However, its correlation in patients with congenital pulmonary airway malformation (CPAM) has not been assessed. Objective: This study aimed to establish a normal range for the right/left mediastinal shift angles, to evaluate the mediastinal shift angle in fetuses with CPAM, to compare the mediastinal shift angle with the CPAM volume ratio, and to evaluate the predictive value of the mediastinal shift angle measurements. Materials and methods: To establish the normal range, we measured the mediastinal shift angle bilaterally in 124 fetuses without any lung abnormality (the control group). Subsequently, the mediastinal shift angle was measured in 32 fetuses pathologically diagnosed with CPAM. Moreover, the mediastinal shift angle and CPAM volume ratio were compared using fetal MRI. Results: The mean values for the right/left mediastinal shift angles were 18.6°/26.3° and 39.2°/35.9° for control fetuses and fetuses with CPAM, respectively. The mediastinal shift angle and the CPAM volume ratio showed a positive statistical correlation. The area under the curve demonstrated high discriminatory accuracy for the mediastinal shift angle (0.76). Conclusion: The mediastinal shift angle has potential to replace the CPAM volume ratio for evaluating the severity of CPAM in fetal MRI. [ABSTRACT FROM AUTHOR]

Biology is an abstract, elusive science, one of which is respiratory material. It requires a media that can visualize objects on a two-dimensional book of biology to a three-dimensional one with a learning video. Research aims to develop, describe kal, and describe the teacher's assessment and student response to the results of the product developed. This research and development using model 4D consists of define, design, foresight, and develop ate. The result of this realization is the production of a medium of pocket books and apps downloaded on android smartphone platforms, able to present in real, tangible, three-dimensional objects to respiratory matter. The media was declared worthy by the validator of materials and media experts with an average rating score on final validation at 84.68% and 93.17%. Trials in the field as practical tests were obtained an assessment result from teachers by 85.36%, student responses of small groups and large groups are 86% and 83.65%. Also, it is also noted that a media pocket book and applications using this augmented reality technology are worthy to be used by students in studying the human respiratory system for grade 11th MIPA SMAN 1 Kota Jambi. [ABSTRACT FROM AUTHOR]

In this paper, an attempt has been made to analyze the effect of different physiological conditions i.e., rest, moderate and extremely active on the branch Reynolds number, pressure drop, lost work, alveolar partial O2 pressure, airway resistance and surface tension. From the analysis, it has been observed that local Reynolds number and tracheal pressure drop along with the generations of branch. The alveolar O2 pressure and surface tension decrease with the increased activity level. Work lost due to different major and minor losses in the respiratory tract increases with the increase in activity level. A similar trend was also found for the airway resistance i.e., increases with the increase in activity level. A new parameter, Breathing Work Number (BWN) in respiratory mechanics is introduced. BWN is the ratio of the work of breathing to the sum of work of breathing and work loss, which might find a significant application to denote the respiratory health. From the analysis, it is found that BWN decreases with the increase in activity level. [ABSTRACT FROM AUTHOR]

Background: Harmaline exhibits a diverse array of pharmacological properties, including antimicrobial, antidiabetic, osteogenic, immunomodulatory, emmenagogue, and antitumor activities. The current study aimed to investigating the effect of harmaline on oxidative stress factors in lung epithelial cells exposed to elastase. Material and method: oxidative stress markers of lung epithelial cells were investigated in all cell groups including, control, H2O2, elastase and elastase plus harmaline (50, 100, 200 µm). lung epithelial cells (A549) were exposed to elastase with concentrations of 60 U/ml for 24 hours. In other groups, cells exposed to elastase were co-treated with three different doses of harmaline (50, 100 and 200 µm) for 24 hours at 37°C. Results: the results show a significant effect of harmaline's protective effect on cell viability, free radical production (ROS), malondialdehyde (MDA) and total antioxidant capacity (TAC). harmaline significantly increased the viability and TAC level in the cells exposed to elastase. Also, harmaline significantly decreased the percentage of free radicals and the MDA level in the cells exposed to elastase. Conclusion: The results obtained from this study showed a significant protective effect of harmaline on cell viability through increases in antioxidant defense system. Therefore, harmaline, can probably considered as a therapeutic strategy to prevent or treatment of lung diseases. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) are used in a variety of fields, including industry, medicine, and food production. Predicting the potential toxicity and biological effects of NPs is challenging due to the influence of their physicochemical properties, such as particle shape and coating constituents. This study investigated the pulmonary effects of differently coated titanium dioxide (TiO2) NPs in wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2) null mice. C57BL6/J wild-type and Nrf2 null mice were exposed to uncoated TiO2 NPs, or NPs coated with either hydroxide aluminum, or with aluminum hydroxide/ stearic acid. After a two-week exposure period, no significant changes were observed in lung weight, cell counts of bronchoalveolar lavage fluid, mRNA levels of proinflammatory cytokines, and antioxidant gene expression in either mouse strain. In addition, human lung carcinoma A549 cells exposed to three types of TiO2 NPs showed no significant changes in cell viability, cytotoxicity, or intracellular reactive oxygen species production. These findings suggest that the toxicity of the TiO2 NPs, regardless of surface modification, is minimal to the respiratory system of mice and human alveolar epithelial cells. [ABSTRACT FROM AUTHOR]

High-flow nasal cannula (HFNC) is becoming the gold standard to treat respiratory distress at any age since it potentially provides several significant clinical advantages. An obstacle to the diffusion of this simple and effective system of oxygen therapy is the impossibility to know the optimal flow rate leading to such advantages that allows the reduction in the respiratory effort without causing hyperinflation. To assist clinicians during HFNC treatment in setting the optimal flow rate and in determining the most relevant parameters related to respiratory mechanics and the effort of the patient, we developed a new programmable data monitoring, acquisition, and elaborating system (Pro_HFNC). The application of Pro_HFNC is fully compatible with HFNC as it is interfaced with patient through a facial mask and two specific catheters. The unavoidable and unpredictable loss of air flow occurring around the contour of the mask is evaluated and compensated by a specific algorithm implemented by Pro_HFNC. Our preliminary clinical trials on pediatric patients treated with HFNC show that Pro_HFNC is actually capable to detect for any specific patient both the lower threshold of the delivered flow beyond which the benefits of HFNC application are reached and all the parameters useful for a complete evaluation of the respiratory profile. Pro_HFNC can really help physicians in setting the optimal flow rate during HFNC treatment, thus allowing for the most effective HFNC performance. [ABSTRACT FROM AUTHOR]

A previously unknown reference to the Russian ethnologist, biologist, and traveler Nikolai N. Miklucho‐Maclay (1846–1888) was discovered in correspondence between Charles Darwin (1809–1882) and Ernst Haeckel (1834–1919). This reference has remained unknown to science, even to Miklucho‐Maclay's biographers, probably because Darwin used the Russian nickname "Mikluska" when alluding to this young scientist. Here, we briefly outline the story behind the short discussion between Darwin and his German counterpart Haeckel, and highlight its importance for the history of science. Miklucho‐Maclay's discovery of a putative swim bladder anlage in sharks, published in 1867, was discussed in four letters between the great biologists. Whereas, Haeckel showed enthusiasm for the finding because it supported (his view on) evolutionary theory, Darwin was less interested, which highlights the conceptual differences between the two authorities. We discuss the scientific treatment of Miklucho‐Maclay's observation in the literature and discuss the homology, origin, and destiny of gas organs—swim bladders and lungs—in vertebrate evolution, from an ontogenetic point of view. We show that the conclusions reached by Miklucho‐Maclay and Haeckel were rather exaggerated, although they gave rise to fundamental insights, and we illustrate how tree‐thinking may lead to differences in the conceptualization of evolutionary change. Key Findings: We discovered a unique quotation from Charles Darwin related to a delicate homology issue in vertebrate morphology, namely the origin and evolution of swim bladders and lungs. This quote is related to a series of four letters that he exchanged with Ernst Haeckel in 1869. This prominent discussion was never cited by any researcher before and brings completely new insights into different modes of evolutionary thinking at its historical beginning short after the "Origin of Species" and how it still influences current debates on homology questions in evolutionary research. Here, we provide a comprehensive discussion on the historical treatment of the character complex of the swim bladder in embryology and highlight how different scientific conceptions of the evolutionary theory (Darwin vs. Haeckel) have influenced the interpretation of structures in the second half of the 19th century, and we show how modern scientific approaches and improvements in phylogenetic research can help out of this dilemma. We demonstrate that comparative embryonic morphology even helps solve the longstanding question of lung/swim bladder homology. [ABSTRACT FROM AUTHOR]

Pain in early life may seriously impact neonatal outcomes. This study aimed to evaluate whether the perceptions of physicians working in neonatal intensive care units (NICUs) of the short-term adverse outcomes associated with neonatal pain have changed over a 20-year period. Self-administered questionnaires were distributed to 117 and 145 neonatologists, pediatricians, and fellows working in level III NICUs in 2000 (T1) and 2019 (T2), respectively. The questionnaire consisted of four domains, including the central nervous, cardiovascular, and respiratory systems, as well as "other systems" (metabolic/endocrine system, growth, and general condition), with 21 total items overall. Although the proportion of positive (correct) responses to the total and system-specific domain scores was significantly higher at T2 than T1, the knowledge of certain short-term adverse outcomes was suboptimal even at T2. Adjustment for cofactors confirmed the independent association of the survey time-point with the total and system-specific domain scores. Moreover, NICU type was an independent significant factor associated with the adjusted total and central nervous system scores, while young doctors had a better knowledge of adverse cardiovascular effects. Conclusions: The perceptions of NICU physicians concerning the short-term outcomes associated with neonatal pain have significantly improved over the past 20 years, although remaining knowledge gaps mandate ongoing efforts to achieve an improvement in neonatal care. [ABSTRACT FROM AUTHOR]

Radioactivity is a process in which the nuclei of unstable atoms spontaneously decay, producing other nuclei and releasing energy in the form of ionizing radiation in the form of alpha (α) and beta (β) particles as well as the emission of gamma (γ) electromagnetic waves. People may be exposed to radiation in various forms, as casualties of nuclear accidents, workers in power plants, or while working and using different radiation sources in medicine and health care. Acute radiation syndrome (ARS) occurs in subjects exposed to a very high dose of radiation in a very short period of time. Each form of radiation has a unique pathophysiological effect. Unfortunately, higher organisms—human beings—in the course of evolution have not acquired receptors for the direct "capture" of radiation energy, which is transferred at the level of DNA, cells, tissues, and organs. Radiation in biological systems depends on the amount of absorbed energy and its spatial distribution, particularly depending on the linear energy transfer (LET). Photon radiation with low LET leads to homogeneous energy deposition in the entire tissue volume. On the other hand, radiation with a high LET produces a fast Bragg peak, which generates a low input dose, whereby the penetration depth into the tissue increases with the radiation energy. The consequences are mutations, apoptosis, the development of cancer, and cell death. The most sensitive cells are those that divide intensively—bone marrow cells, digestive tract cells, reproductive cells, and skin cells. The health care system and the public should raise awareness of the consequences of ionizing radiation. Therefore, our aim is to identify the consequences of ARS taking into account radiation damage to the respiratory system, nervous system, hematopoietic system, gastrointestinal tract, and skin. [ABSTRACT FROM AUTHOR]

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The use of wet spirometers, although once common, has greatly declined because these devices measure only static lung volumes and students often face technical issues in their use. In this study, the wet spirometer has been modified to investigate the fundamental laws of flow and different types of lung disease. This modification was achieved by changing the dimensions of the device, printing a scale on the bell, and attaching an airflow control system (ACS) between the corrugated tube and hollow tube of the inner cylinder. The ACS allowed for flow control during the exercises. Two exercises were performed: exercise I compared the parameters measured by the wet spirometer, modified spirometer, and computerized spirometer to determine the suitability of the modification, while exercise II tested the variables affecting flow. These exercises introduce students to data collection, analysis, and the use of statistical tests as they compare various spirometers. Additionally, students gain valuable experience in experimental design by conducting diverse experiments that investigate factors influencing flow dynamics. By plotting the results and participating in small group discussions, students can apply flow principles in respiratory and circulatory systems, offering a hands-on experience that integrates physics and physiology. The modified spirometer facilitated multifaceted topic exploration, surpassing the traditional wet spirometer's capabilities. [ABSTRACT FROM AUTHOR]

One of the current challenges of biomedicine is to elucidate the multicomponent and multilevel mechanism of integrated neuroimmunoendocrine regulation of physiological functions. Respiratory diseases are leading in the structure of general morbidity among the population and remain one of the most relevant problems of modern healthcare. Numerous risk factors can contribute to the development of such pulmonary pathologies as pneumonia, lung cancer, asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary fibrosis and others, whose incidence tends to increase annually. In this regard, signaling molecules, which are involved in neuroimmunoendocrine respiratory regulation and can be considered as both prognostic biomarkers and potential therapeutic targets, are coming into focus of modern translational biomedicine. This review addresses the role of one of the key actors in the neuroimmunoendocrine regulation of homeostasis, a ubiquitous transcription factor NF-κB, in the regulation of respiratory function in health and during the pathogenesis of lung diseases. There is ample evidence that many pulmonary pathologies, resulting from ongoing inflammatory processes, are associated with NF-κB activation. A comprehensive investigation of the mechanisms underlying NF-κB activation and its relationship with other signaling pathways will contribute to solving the main task of translational biomedicine, the development of innovative approaches to prevention and personalized targeted therapies for human socially significant pathologies, including respiratory diseases. [ABSTRACT FROM AUTHOR]

There is a debate among researchers regarding the impact of environmental factors, such as varying temperatures, on bodily functions, particularly the respiratory system of athletes. Hence, investigating the influence of moderate to cold weather on athletes during exercise is essential for comprehending this relationship and determining optimal strategies for public health maintenance, fitness enhancement, and performance improvement under diverse environmental conditions. Consequently, this study aims to ascertain the impact of the surrounding environment on individuals, the extent to which their physiological systems are affected, and the resultant manifestations, especially during physical exertion. The primary aim of the present study was to assess the differences in respiratory system variables (respiratory rate (RR), tidal volume (TV), pulmonary ventilation (V̇ E)), as well as other parameters (heart rate (HR), completion time (Ct)), at rest and post-cardiorespiratory exercise test (CPET) between moderate heat (24°C ± 1) and cold conditions (15°C ± 1). The researcher hypothesized that there would be no significant disparities in respiratory system variables (RR, TV, V̇ E), HR, and Ct between the moderate and cold conditions, both at rest and after CPET. A descriptive approach was chosen for its suitability to the nature of the study. The research sample comprised eight randomly selected individuals aged between 22 and 24 years who engaged in physical activity. The experimental sessions were conducted in two different thermal conditions: moderate temperature (24°C ± 1) with 30-40% humidity, and cold temperature (15°C ± 1) with 30-40% humidity. Data processing involved the use of statistical and computational methods such as arithmetic mean, standard deviation, coefficient of variation, body mass index, body surface area, and t-tests for two related samples. The findings of the study revealed the following: - Cold environmental conditions led to a significant increase in comfort in the variables TV, V̇ E, and HR at the conclusion of physical exertion, as well as an increase in RR, compared to temperate conditions. - Cold environmental conditions did not result in a significant increase in comfort in RR, TV, V̇ E, and HR at the end of physical exertion in comparison to temperate conditions. - The cold environmental condition during physical exertion did not exhibit a clear negative or positive impact on Ct in terms of the duration of the end of exertion compared to the moderate. [ABSTRACT FROM AUTHOR]

• Medicinal properties (antibacterial- and anti-HIV-1 activities) of South African mushroom species. • Rhodofomitopsis lilacinogilva and Pisolithus tinctorius caused cell membrane damage. • Gymnopilus junonius and R. lilacinogilva showed promising antimycobacterial activity. • P. tinctorius inhibited HIV-1 reverse transcriptase activity. • Chloropyllum molybdites, P. tinctorius and Pycnoporus sanguineus inhibited HIV-1 protease activity. The medicinal properties of South African mushroom species and their associated biological activities have been poorly documented. Increased resistance to antimicrobial drugs is a global problem and growing concern. Ethanol (80 %) and/or aqueous extracts of twenty-one mushroom species were screened against bacterial species infecting the respiratory system (i.e., Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pyogenes, S. pneumoniae, Staphylococcus aureus and Mycobacterium tuberculosis H37), and the minimum inhibitory concentrations (MIC) determined using the p-iodonitrotetrazolium chloride (INT) and microplate Alamar Blue assays. Transmission electron microscopy (TEM) was used to detect morphological changes. Ethanol extracts were screened for HIV-1 reverse transcriptase (RT) and protease inhibition using colourimetric and fluorometric assay kits, respectively. The ethanol extracts showed better antibacterial activity against gram-positive bacteria. Extracts of Rhodofomitopsis lilacinogilva and Pisolithus tinctorius caused cell membrane damage. Gymnopilus junonius (MIC: 62.5 µg/mL) and R. lilacinogilva (MIC: 31.25 µg/mL) showed promising antimycobacterial activity. P. tinctorius (IC 50 : 1.35 µg/mL) inhibited HIV-1 reverse transcriptase activity. Chloropyllum molybdites, P. tinctorius and Pycnoporus sanguineus inhibited HIV-1 protease activity. South African mushroom species contain biologically active compounds with antibacterial- and anti-HIV-1 activities, which may play an important role in the development of novel therapies and antiretrovirals (ARVs) against respiratory associated pathogens. [ABSTRACT FROM AUTHOR]

Copyright of Summa, Animali da Reddito is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Airborne particulate matter (PM) is a global environmental risk factor threatening human health and is a major cause of cardiovascular and respiratory disease-associated death. Current studies on PM exposure have been limited to large-scale cohort and epidemiological investigations, emphasizing the need for detailed individual-level studies to uncover specific differentially expressed genes and their associated signaling mechanisms. Herein, we revealed that PM exposure significantly upregulated inflammatory and immune responses, such as cytokine-mediated signaling pathways, complement system, and the activation and migration of immune cells in gene set enrichment analysis of our RNA sequencing (RNAseq) data. Remarkably, we discovered that the broad gene expression and signaling pathways mediated by macrophages were predominantly expressed in the respiratory system following PM exposure. Consistent with these observations, individual PMs, classified by aerodynamic size and origin, significantly promoted macrophage recruitment to the lungs in the mouse lung inflammation model. Additionally, we confirmed that RNAseq observations from the respiratory system were reproduced in murine bone marrow-derived macrophages and the alveolar macrophage cell line MH-S after individual PM exposure. Our findings demonstrated that PM exposure augmented broad inflammatory and immune responses in the respiratory system and suggested the reinforcement of global strategies for reducing particulate air pollution to prevent respiratory diseases and their exacerbation.