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BackgroundMany respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, a few primary human stem cell-based models of the proximal airway have been reported for drug discovery but scaling them up to a higher throughput platform remains a significant challenge. As a result, most of the drug screening assays for respiratory viruses are performed on commercial cell line-based 2D cultures that provide limited translational ability.MethodsWe optimized a primary human stem cell-based mucociliary airway epithelium model of SARS-CoV-2 infection, in 96-well air-liquid-interface (ALI) format, which is amenable to moderate throughput drug screening. We tested the model against SARS-CoV-2 parental strain (Wuhan) and variants Beta, Delta, and Omicron. We applied this model to screen 2100 compounds from targeted drug libraries using a high throughput-high content image-based quantification method.ResultsThe model recapitulated the heterogeneity of infection among patients with SARS-CoV-2 parental strain and variants. While there were heterogeneous responses across variants for host factor targeting compounds, the two direct-acting antivirals we tested, Remdesivir and Paxlovid, showed consistent efficacy in reducing infection across all variants and donors. Using the model, we characterized a new antiviral drug effective against both the parental strain and the Omicron variant.ConclusionThis study demonstrates that the 96-well ALI model of primary human mucociliary epithelium can recapitulate the heterogeneity of infection among different donors and SARS-CoV-2 variants and can be used for moderate throughput screening. Compounds that target host factors showed variability among patients in response to SARS-CoV-2, while direct-acting antivirals were effective against SARS-CoV-2 despite the heterogeneity of patients tested.

Rationale: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. Objectives: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. Methods: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. Measurements and Main Results: Among 2,255 participants with 6,978 plasma samples, pyrazinamide displayed sevenfold exposure variability (151-1,053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in therapeutic windows of 231-355 mg · h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1,000 mg would have permitted an additional 13.1% (n = 96) of participants allocated to the control and 9.2% (n = 70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared with the current weight-banded dosing. Conclusions: Flat dosing of pyrazinamide at 1,000 mg/d would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registered with www.clinicaltrials.gov (NCT02410772).

Most respiratory microbiome studies use amplicon sequencing due to high host DNA. Metagenomics sequencing offers finer taxonomic resolution, phage assessment, and functional characterization. We evaluated five host DNA depletion methods on frozen nasal swabs from healthy adults, sputum from people with cystic fibrosis (pwCF), and bronchoalveolar lavage (BAL) from critically ill patients. Median sequencing depth was 76.4 million reads per sample. Untreated nasal, sputum, and BAL had 94.1%, 99.2%, and 99.7% host reads, respectively. Host depletion effects varied by sample type, generally increasing microbial reads, species and functional richness; this was mediated by higher effective sequencing depth. Rarefaction curves showed species richness saturation at 0.5-2 million microbial reads. Most methods did not change Morisita-Horn dissimilarity for BAL and nasal samples although the proportion of gram-negative bacteria decreased for sputum from pwCF. Freezing did not affect the viability of Staphylococcus aureus but reduced the viability of Pseudomonas aeruginosa and Enterobacter spp.; this was mitigated by adding a cryoprotectant. QIAamp-based host depletion minimally impacted gram-negative viability even in non-cryoprotected frozen isolates. While some host depletion methods may shift microbial composition, metagenomics sequencing without host depletion severely underestimates microbial diversity of respiratory samples due to shallow effective sequencing depth and is not recommended.

Spatially coordinated ERK signaling events ("SPREADs") transmit radially from a central point to adjacent cells via secreted ligands for EGFR and other receptors. SPREADs maintain homeostasis in non-pulmonary epithelia, but it is unknown whether they play a role in the airway epithelium or are dysregulated in inflammatory disease. To address these questions, we measured SPREAD activity with live-cell ERK biosensors in human bronchial epithelial cell lines (HBE1 and 16HBE) and primary human bronchial epithelial (pHBE) cells, in both submerged and biphasic Air-Liquid Interface (ALI) culture conditions (i.e., differentiated cells). Airway epithelial cells were exposed to pro-inflammatory cytokines relevant to asthma and chronic obstructive pulmonary disease (COPD). Type 1 pro-inflammatory cytokines significantly increased the frequency of SPREADs, which coincided with epithelial barrier breakdown in differentiated pHBE cells. Furthermore, SPREADs correlated with IL-6 peptide secretion and the appearance of localized clusters of phospho-STAT3 immunofluorescence. To probe the mechanism of SPREADs, cells were co-treated with pharmacological treatments (gefitinib, tocilizumab, hydrocortisone) or metabolic modulators (insulin, 2-deoxyglucose). Hydrocortisone, inhibitors of receptor signaling, and suppression of metabolic function decreased SPREAD occurrence, implying that pro-inflammatory cytokines and glucose metabolism modulate SPREADs in human airway epithelial cells via secreted EGFR and IL6R ligands. We conclude that spatiotemporal ERK signaling plays a role in barrier homeostasis and dysfunction during inflammation of the airway epithelium. This novel signaling mechanism could be exploited clinically to supplement corticosteroid treatment for asthma and COPD.

BackgroundPulmonary ischaemia-reperfusion injury (IRI) is a major contributor to poor lung transplant outcomes. We recently demonstrated a central role of airway-centred natural killer (NK) cells in mediating IRI; however, there are no existing effective therapies for directly targeting NK cells in humans.MethodsWe hypothesised that a depleting anti-CD94 monoclonal antibody (mAb) would provide therapeutic benefit in mouse and human models of IRI based on high levels of KLRD1 (CD94) transcripts in bronchoalveolar lavage samples from lung transplant patients.ResultsWe found that CD94 is highly expressed on mouse and human NK cells, with increased expression during IRI. Anti-mouse and anti-human mAbs against CD94 showed effective NK cell depletion in mouse and human models and blunted lung damage and airway epithelial killing, respectively. In two different allogeneic orthotopic lung transplant mouse models, anti-CD94 treatment during induction reduced early lung injury and chronic inflammation relative to control therapies. Anti-CD94 did not increase donor antigen-presenting cells that could alter long-term graft acceptance.ConclusionsLung transplant induction regimens incorporating anti-CD94 treatment may safely improve early clinical outcomes.

ObjectivesDiameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over 3-5 years and subsequent all-cause mortality.MethodsMale veterans with

IntroductionThe co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), or the overlap syndrome, is common and associated with a distinct pattern of nocturnal hypoxemia and worse clinical outcomes than either disease alone. Consequently, identifying who and how to treat these patients is essential.Areas coveredTreatment is recommended in all patients with OSA and symptoms or systemic hypertension, but determining symptoms attributable to OSA can be challenging in patients with COPD. Treatment should be considered in asymptomatic patients with moderate to severe OSA and COPD with pulmonary hypertension and comorbid cardiovascular and cerebrovascular disease, especially if marked hypoxic burden. CPAP is effective, but in patients with the overlap syndrome and daytime hypercapnia, high-intensity noninvasive ventilation aiming to lower PaCO2 may have additional benefits. Additionally, in those with severe resting daytime hypoxemia, supplemental oxygen improves survival and should be added to positive airway pressure. The role of alternative non-positive airway pressure therapies in the overlap syndrome needs further study.Expert opinionBoth COPD and OSA are heterogeneous disorders with a wide range of disease severity and further research is needed to better characterize and prognosticate patients with the overlap syndrome to personalize treatment.

BackgroundPeople with serious mental illnesses (SMIs) have three-fold higher rates of comorbid insomnia than the general population, which has downstream effects on cognitive, mental, and physical health. Cognitive Behavioral Therapy for Insomnia (CBT-i) is a safe and effective first-line treatment for insomnia, though the therapy's effectiveness relies on completing nightly sleep diaries which can be challenging for some people with SMI and comorbid cognitive deficits. Supportive technologies such as mobile applications and sleep sensors may aid with completing sleep diaries. However, commercially available CBT-i apps are not designed for individuals with cognitive deficits. To aid with this challenge, we have developed an integrated mobile application, named "Sleep Catcher," that will automatically incorporate data from a wearable fitness tracker and a bed sensor to track nightly sleep duration, overnight awakenings, bed-times, and wake-times to generate nightly sleep diaries for CBT-i.MethodsThe application development process will be described-writing algorithms to generating useful data, creating a clinician web portal to oversee patients and the mobile application, and integrating sleep data from device platforms and user input.ResultsThe mobile and web applications were developed using Flutter, IBM Code Engine, and IBM Cloudant database. The mobile application was developed with a user-centered approach and incremental changes informed by a series of beta tests. Special user-interface features were considered to address the challenges of developing a simple and effective mobile application targeting people with SMI.ConclusionThere is strong potential for synergy between engineering and mental health expertise to develop technologies for specific clinical populations. Digital health technologies allow for the development of multi-disciplinary solutions to existing health disparities in vulnerable populations, particularly in people with SMI.

BCL-2 family members are known to be implicated in survival in numerous biological settings. Here, we provide evidence that in injury and repair processes in lungs, BCL-2 mainly acts to attenuate endoplasmic reticulum (ER) stress and limit extracellular matrix accumulation. Days after an intratracheal bleomycin challenge, mice lose a fraction of their alveolar type II epithelium from terminal ER stress driven by activation of the critical ER sensor and stress effector IRE1α. This fraction is dramatically increased by BCL-2 inhibition, because IRE1α activation is dependent on its physical association with the BCL-2-proapoptotic family member BAX, and we found BCL-2 to disrupt this association in vitro. In vivo, navitoclax (a BCL-2/BCL-xL inhibitor) given 15-21 days after bleomycin challenge evoked strong activation of IRE-1α in mesenchymal cells and markers of ER stress, but not apoptosis. Remarkably, after BCL-2 inhibition, bleomycin-exposed mice demonstrated persistent collagen accumulation at Day 42, compared with resolution in controls. Enhanced fibrosis proved to be due to the RNAase activity of IRE1α downregulating MRC2 mRNA and protein, a mediator of collagen turnover. The critical role of MRC2 was confirmed in precision-cut lung slice cultures of Day-42 lungs from bleomycin-exposed wild-type and MRC2 null mice. Soluble and tissue collagen accumulated in precision-cut lung slice cultures from navitoclax-treated, bleomycin-challenged mice compared with controls, in a manner nearly identical to that of challenged but untreated MRC2 null mice. Thus, apart from mitochondrial-based antiapoptosis, BCL-2 functions to attenuate ER stress responses, fostering tissue homeostasis and injury repair.

BackgroundInfants with hypoxic-ischemic encephalopathy are often treated with therapeutic hypothermia and high-frequency ventilation. Fluctuations in PaCO2 during therapeutic hypothermia are associated with poor neurodevelopmental outcomes. Transcutaneous CO2 monitors offer a noninvasive estimate of PaCO2 represented by transcutaneously measured partial pressure of carbon dioxide (PtcCO2 ). We aimed to assess the precision between PtcCO2 and PaCO2 values in neonates undergoing therapeutic hypothermia.MethodsThis was a retrospective chart review of 10 neonates who underwent therapeutic hypothermia requiring respiratory support over 2 y. A range of 2-27 simultaneous PtcCO2 and PaCO2 pairs of measurements per neonate were analyzed via linear mixed models and a Bland-Altman plot for multiple observations per neonate.ResultsA linear mixed-effect model demonstrated that PtcCO2 and PaCO2 (controlling for sex) were similar. The 95% CI of the mean difference ranged from -2.3 to 5.7 mm Hg (P = .41). However, precision was poor as the PtcCO2 ranged from > 18 mm Hg to < 13 mm Hg than PaCO2 values for 95% of observations.ConclusionsThe neonates' PtcCO2 was as much as 18 mm Hg higher to 13 mm Hg lower than the PaCO2 95% of the time. Transcutaneous CO2 monitoring may not be a good trending tool, nor is it appropriate for estimating PaCO2 in patients undergoing therapeutic hypothermia.

Swimming produces many psychophysiological effects, including blood, hormonal, enzymatic, pulmonary, cardiovascular and energetic adaptations. However, asthma and allergies are becoming increasingly prevalent medical issues among elite endurance-trained swimmers, where exercise-induced asthma or bronchospasm is frequently reported. Heavy endurance swimming training, especially under adverse conditions, stresses the airway mucosa, leading to inflammatory changes, as observed in induced sputum in competitive swimmers. In addition, chlorine-based disinfectants (CBDs) are commonly used in indoor pools due to their effectiveness and lower relative cost. Many of these substances have carcinogenic and genotoxic properties, and exposure to DBPs have been linked to adverse respiratory effects. The association between long-term exposure to a chlorinated swimming pool and elevated serum sIgE levels suggests a link between allergens, chlorine exposure and the development of various pulmonary dysfunctions. Thus, the combination of intense and repeated physical endurance training over extended periods, along with suboptimal environmental conditions, may contribute to the development of rhinitis, asthma and bronchial hyperresponsiveness in athletes. While occasional or low-level exposure to chlorine might not be harmful, regular swimmers, especially those at competitive levels, are at a higher risk of developing respiratory disorders. Because these potential risks of exposure to CBDs must be balanced against the benefits of swimming and the risk of microbial infections in pools, we recommend better pool management and regular health checks for swimmers. Fortunately, the reduction of bronchial symptoms in swimmers who reduce training volume and intensity suggests that the negative effects on pulmonary function may be reversible. For these reasons, it is crucial to develop effective respiratory protection strategies, including medical interventions and modifications to the pool environment. Practical steps such as reducing chlorine use, ensuring proper hygiene before swimming and using swim caps can minimise risks. Research should also explore safer alternatives to CBDs, such as ozonation, and improved ventilation to reduce air pollutants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hoxa5 plays numerous roles in development, but its downstream molecular effects are mostly unknown. We applied bulk RNA-seq assays to characterize the transcriptional impact of the loss of Hoxa5 gene function in seven different biological contexts, including developing respiratory and musculoskeletal tissues that present phenotypes in Hoxa5 mouse mutants. This global analysis revealed few common transcriptional changes, suggesting that HOXA5 acts mainly via the regulation of context-specific effectors. However, Hox genes themselves appeared as potentially conserved targets of HOXA5 across tissues. Notably, a trend toward reduced expression of HoxA genes was observed in Hoxa5 null mutants in several tissue contexts. Comparative analysis of epigenetic marks along the HoxA cluster in lung tissue from two different Hoxa5 mutant mouse lines revealed limited effect of either mutation indicating that Hoxa5 gene targeting did not significantly perturb the chromatin landscape of the surrounding HoxA cluster. Combined with the shared impact of the two Hoxa5 mutant alleles on phenotype and Hox expression, these data argue against the contribution of local cis effects to Hoxa5 mutant phenotypes and support the notion that the HOXA5 protein acts in trans in the control of Hox gene expression. [ABSTRACT FROM AUTHOR]

The chemokine CCL20, a small cytokine that belongs to the C–C chemokine family, interacts with its homologous receptor CCR6, which is expressed on wide range of cell types. According to current research, the CCL20-CCR6 has been established as acritical player in a diverse range of inflammatory, oncogenic, and autoimmune diseases. Within the respiratory system, CCL20-CCR6 demonstrates heightened expression in conditions such as allergic asthma, chronic airway inflammation, non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), and other respiratory diseases, which is conducive to the inflammatory mediators recruitment and tumor microenvironment remodeling. Numerous studies have demonstrated that therapeutic interventions targeting CCL20 and CCR6, including antibodies and antagonists, have the potential to mitigate disease progression. Despite the promising research prospects surrounding the CCL20-CCR6 chemokine axis, the precise mechanisms underlying its action in respiratory diseases remain largely elusive. In this review, we delve into the potential roles of the CCL20-CCR6 axis within the respiratory system by synthesizing and analyzing current research findings. Our objective is to provide a comprehensive understanding of the CCL20-CCR6 axis and its implications for respiratory health and disease. And we aspire to propel research endeavors in this domain and furnish valuable insights for the development of future therapeutic strategies. [ABSTRACT FROM AUTHOR]

The search for new non-invasive methods of investigating the functioning of human internal organs is an urgent task. One of these methods for assessing the functioning of the human respiratory system is electromagnetic sensing, which is based on a significant difference in the dielectric permittivity of muscle tissue and air. During breathing, when the lungs are filled with air, the dielectric permittivity of the lungs decreases, which leads to a change in the level of the electromagnetic signal passing through the body. The results of experiments on recording changes in the level of electromagnetic radiation passing through the human body performed on an experimental device consisting of eight transmitting and receiving antennas located on opposite sides of the chest have been presented in the article. The possibility of visualizing the measured "pulmonograms" in the form of dynamic two-dimensional images showing the process of filling various parts of the lungs with air has been demonstrated. [ABSTRACT FROM AUTHOR]

Objective: Numerous illnesses, such as bacterial and viral infections, affect the respiratory system. Since no known therapy for viruses directly influences health, viral infections are typically more deadly than bacterial ones. The study aimed to ascertain the degree of many immunological markers in patients recovering from viral respiratory infections. The amounts of these indicators were ascertained using the ELISA technique. Material and Methods: The study includes 74 sample collections from June to September (2023), including 28 males and 46 females, aged over 18. Blood samples, overall, were taken. The study was conducted in the Research Laboratory of the Department of Biology, College of Science, University of Mosul. Seventy-four individuals were involved in the study; forty-six of them were recovering from being severe acute respiratory syndrome coronavirus-2 positive (after 6 months), and twenty-eight were not. Results: The findings revealed highly variable levels of interleukin-17 (IL-17), immunoglobulin M (IgM), and immunoglobulin G (IgG) between the patient samples and the control samples. While the IgG level was higher in the first age group (20-40 years), the levels of both IgM and IL-17 were higher in older ages (41-60 years). The levels of immune markers were higher in females than in males, with IL-17, IgG, and IgM reaching 133.3 pg/mL, 1707.9 ng/mL, and 56.8 ng/mL, respectively. Conclusion: According to the current study, the parameters measured in coronavirus disease-2019 recovery participants after six months were higher than those in control samples.

Abstract The chemokine CCL20, a small cytokine that belongs to the C–C chemokine family, interacts with its homologous receptor CCR6, which is expressed on wide range of cell types. According to current research, the CCL20-CCR6 has been established as acritical player in a diverse range of inflammatory, oncogenic, and autoimmune diseases. Within the respiratory system, CCL20-CCR6 demonstrates heightened expression in conditions such as allergic asthma, chronic airway inflammation, non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), and other respiratory diseases, which is conducive to the inflammatory mediators recruitment and tumor microenvironment remodeling. Numerous studies have demonstrated that therapeutic interventions targeting CCL20 and CCR6, including antibodies and antagonists, have the potential to mitigate disease progression. Despite the promising research prospects surrounding the CCL20-CCR6 chemokine axis, the precise mechanisms underlying its action in respiratory diseases remain largely elusive. In this review, we delve into the potential roles of the CCL20-CCR6 axis within the respiratory system by synthesizing and analyzing current research findings. Our objective is to provide a comprehensive understanding of the CCL20-CCR6 axis and its implications for respiratory health and disease. And we aspire to propel research endeavors in this domain and furnish valuable insights for the development of future therapeutic strategies.

Background and Study Aim. The progressive aging of the global population presents significant challenges, particularly in maintaining the functional reserves of vital systems. The respiratory system is crucial for sustaining physical performance. However, it is especially vulnerable to age-related decline. This study aims to assess the impact of structured physical activity on the respiratory function of sports-active veteran track-and-field athletes aged 50–59 and 60–75 years. Material and methods. A total of 93 men were examined, including 54 in the reference group (30 men with an average age of 53.67±0.25 years and 24 with an average age of 67.08±0.35 years). These men were involved in athletics in the past but did not participate in veteran sports. The study group included 29 athletics veterans. Among them, 18 individuals had an average age of 52.27±0.18 years, and 11 had an average age of 65.64±0.16 years. These athletes engage in specifically organized physical activity 2–4 times a week and have participated in athletics competitions over the last five years. Anthropometric measurements included the assessment of chest circumference at rest, maximal inspiration, maximal exhalation, and diaphragmatic excursion (DE). The functional state of the respiratory system was assessed using the SpiroCom diagnostic complex (HAI). The data were processed using the SPSS Statistics 17.0 software. Results. Sports veterans aged 50–59 years and those over 60 years exhibit statistically significant differences compared to their peers in several indicators. These include diaphragmatic excursion, tidal volume, minute volume, respiratory rate, tidal volume maximal, respiratory rate maximal, and maximal voluntary ventilation. The respiratory reserve indicator showed a lower degree of respiratory function tension during physical exertion. Statistically significantly higher values of external respiration indicators were found in veteran athletes compared to men with no regular activity (NRA). These indicators include expiratory time, forced expiratory volume in 1 second, and forced expiratory volume maximal. Additionally, veteran athletes showed higher values in the modified Tiffeneau-Pinelli index, peak expiratory flow, and forced expiratory flow at 25%, 50%, 75%, and forced mid-expiratory flow. As a result, sports veterans with high regular activity (RA) exhibited the lowest rates of regressive-destructive changes in the respiratory system indicators overall, with the exception of HOD and BH. In contrast, men with low RA are characterized by an accelerated rate of aging in the respiratory system. Conclusions. The results of the study identified indicators that can serve as spirographic criteria for selecting functional types. These types include individuals with low, medium, and high regular activity (RA). It has been proven that systematic exercises involving specially organized cyclic motor activity form a rational, physiologically optimal type of breathing. Additionally, these exercises inhibit age-related degenerative-dystrophic processes in the human respiratory system.

BackgroundContinuation of continuous positive airway pressure (CPAP) therapy after initial prescription has been shown to reduce all-cause mortality versus therapy termination. However, there is a lack of data on the rates and impact of resuming CPAP in patients with obstructive sleep apnoea (OSA). This analysis determined the prevalence of CPAP resumption in the year after termination, characterised determinants of CPAP resumption, and examined the impact of CPAP resumption on all-cause mortality.MethodsFrench national health insurance reimbursement system data for adults aged ≥18 years were used. CPAP prescription was identified by specific treatment codes. Patients who resumed CPAP after first therapy termination and continued to use CPAP for 1 year were matched with those who resumed CPAP then terminated therapy for a second time.ResultsOut of 103 091 individuals with a first CPAP termination, 26% resumed CPAP over the next 12 months, and 65% of these were still using CPAP 1 year later. Significant predictors of CPAP continuation after resumption included male sex, hypertension and CPAP prescription by a pulmonologist. In the matched population, the risk of all-cause death was 38% lower in individuals who continued using CPAP after therapy resumption versus those who had a second therapy discontinuation (hazard ratio 0.62, 95% CI 0.48-0.79; p=0.0001).ConclusionThese data suggest that individuals with OSA who fail initial therapy with CPAP should be offered a second trial with the device to ensure that effective therapy is not withheld from those who might benefit.

ObjectivesPulmonary arterial hypertension (PAH) is characterized by the remodeling of the pulmonary vascular bed leading to elevation of the pulmonary arterial pressure. Oxidized fatty acids, such as hydroxyeicosatetraenoic acids (HETEs), play a critical role in PAH. We have previously established that dietary supplementation of 15-HETE is sufficient to cause PH in mice, suggesting a role for the gut-lung axis. However, the mechanisms are not known.ApproachAnalysis of RNA-seq data obtained from the lungs and intestines of mice on 15-HETE diet together with transcriptomic data from PAH patient lungs identified IFN inducible protein 44 (IFI44) as the only gene significantly upregulated in mice and humans. We demonstrate that IFI44 is also significantly increased in PBMCs from PAH patients. In mice, 15-HETE diet enhances IFI44 and its inducer IFN⍺4 expression sequentially in the intestine first and then in the lungs. IFI44 expression in PAH is highly correlated with expression of Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL), which is upregulated in CD8 cells in PH lungs of both mice and humans. We show that IFNα4 produced by intestinal epithelial cells facilitates IFI44 expression in CD8 cells. Finally, we demonstrate that IFN receptor 1-KO in mice do not develop PH on 15-HETE diet. In addition, silencing IFI44 expression in the lungs of mice on 15-HETE diet prevents the development of PH and is associated with significantly lower expression of IFI44 and TRAIL in CD8 cells in the lungs.ConclusionOur data reveal a novel gut-lung axis driven by 15-HETE in PH.

BackgroundSepsis is a common cause of death in patients with pulmonary arterial hypertension (PAH). Treatment requires careful fluid management and hemodynamic support. This study compares patients with or without PAH presenting with sepsis with a focus on initial fluid resuscitation.MethodsThis retrospective analysis compared adults with and without PAH admitted for sepsis at two academic hospitals between 2013 and 2022. Prior PAH diagnosis was verified by review of right heart catheterization data and sepsis present on admission was verified by chart review. Demographics, vital signs, laboratory values, imaging results, treatment approaches, and all-cause mortality data were obtained. Controls were propensity score weighted by age, sex, and Charlson Comorbidity index. Logistic regression models controlling for age and Charlson comorbidity indices were used to examine factors associated with survival.ResultsThirty patients admitted for sepsis with pre-existing PAH were compared to 96 matched controls. Controls received significantly more fluids at 24 h compared to PAH patients (median 0 mL v. 1216 mL, p

BackgroundPatients with multiple myeloma are immunosuppressed due to both the disease itself and immunosuppressive therapies. Thus, when presenting with respiratory failure and pulmonary opacities, pneumonia must be considered. However, while rare, immunomodulating medications used in the treatment of multiple myeloma can also cause potentially life-threatening respiratory failure, a distinction which has important treatment implications.Case presentationAn 80-year-old male with recently diagnosed multiple myeloma undergoing treatment with lenalidomide and daratumumab presented with acute, rapidly progressive hypoxic respiratory failure ultimately requiring intubation and mechanical ventilatory support. Imaging revealed bilateral pulmonary opacities, however infectious workup was negative, and he was ultimately diagnosed with lenalidomide-induced interstitial pneumonitis, a rare but serious adverse effect of this medication. He was treated with drug discontinuation and methylprednisolone, and quickly recovered.ConclusionLenalidomide is an immunomodulating medication used in the treatment of multiple myeloma, and is associated with rare but serious cases of drug-induced interstitial pneumonitis. Thus, if a patient receiving lenalidomide develops shortness of breath and/or hypoxia, drug-induced pneumonitis must be on the differential. Permanent drug discontinuation with or without corticosteroids is the mainstay of treatment, and patients are often able to fully recover, underscoring the need for early recognition of this condition.

Rationale: Acute lung injury (ALI) carries a high risk of mortality but has no established pharmacologic therapy. We previously found that experimental ALI occurs through natural killer (NK) cell NKG2D receptor activation and that the cognate human ligand, MICB, was associated with ALI after transplantation. Objectives: To investigate the association of a common missense variant, MICBG406A, with ALI. Methods: We assessed MICBG406A genotypes within two multicenter observational study cohorts at risk for ALI: primary graft dysfunction (N = 619) and acute respiratory distress syndrome (N = 1,376). Variant protein functional effects were determined in cultured and ex vivo human samples. Measurements and Main Results: Recipients of MICBG406A-homozygous allografts had an 11.1% absolute risk reduction (95% confidence interval [CI], 3.2-19.4%) for severe primary graft dysfunction after lung transplantation and reduced risk for allograft failure (hazard ratio, 0.36; 95% CI, 0.13-0.98). In participants with sepsis, we observed 39% reduced odds of moderately or severely impaired oxygenation among MICBG406A-homozygous individuals (95% CI, 0.43-0.86). BAL NK cells were less frequent and less mature in participants with MICBG406A. Expression of missense variant protein MICBD136N in cultured cells resulted in reduced surface MICB and reduced NKG2D ligation relative to wild-type MICB. Coculture of variant MICBD136N cells with NK cells resulted in less NKG2D activation and less susceptibility to NK cell killing relative to the wild-type cells. Conclusions: These data support a role for MICB signaling through the NKG2D receptor in mediating ALI, suggesting a novel therapeutic approach.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by airflow limitation and persistent respiratory symptoms. People with HIV (PWH) are particularly vulnerable to COPD development; PWH have demonstrated both higher rates of COPD and an earlier and more rapid decline in lung function than their seronegative counterparts, even after accounting for differences in cigarette smoking. Factors contributing to this HIV-associated difference include chronic immune activation and inflammation, accelerated aging, a predilection for pulmonary infections, alterations in the lung microbiome, and the interplay between HIV and inhalational toxins. In this review, we discuss what is known about the epidemiology and pathobiology of COPD among PWH and outline screening, diagnostic, prevention, and treatment strategies.

IntroductionLung disease remains a frequent complication in children with perinatal HIV infection (CHIV) and exposure without infection (CHEU), resulting in diminished lung function. In CHIV, early antiretroviral therapy (ART) initiation improves survival and extrapulmonary outcomes. However, it is unknown if there is benefit to lung function.MethodsCohorts of CHIV (ART initiated at median 4.0 months), CHEU and HIV-unexposed children (CHU) prospectively performed pulmonary function testing (PFT) consisting of spirometry, plethysmography and diffusing capacity from 2013 to 2020. We determined lung function trajectories for PFT outcomes comparing CHIV to CHU and CHEU to CHU, using linear mixed effects models with multiple imputation. Potential confounders included sex, age, height, weight, body mass index z-score, urine cotinine and Tanner stage.Results328 participants (122 CHIV, 126 CHEU, 80 CHU) performed PFT (ages 6.6-15.6 years). Spirometry (forced expiratory volume in 1 s, FEV1, forced vital capacity (FVC), FEV1/FVC) outcomes were similar between groups. In plethysmography, the mean residual volume (RV) z-score was 17% greater in CHIV than CHU (95% CI 1% to 33%, p=0.042). There was no difference in total lung capacity (TLC) or RV/TLC z-scores between groups. Diffusing capacity for carbon monoxide was similar in all groups, while alveolar volume (VA) differed between HIV groups by sex.ConclusionOur study indicates that early ART initiation can mitigate the loss of lung function in CHIV with lasting benefit through childhood; however, there remains concern of small airway disease. CHEU does not appear to disrupt childhood lung function trajectory.

MicroRNAs (miRNAs) are classified as small, non-coding RNAs that play crucial roles in diverse biological processes, including cellular development, differentiation, growth, and metabolism. MiRNAs regulate gene expression by recognizing complementary sequences within messenger RNA (mRNA) molecules. Recent studies have revealed that miR-145-5p functions as a tumor suppressor in several cancers, including lung, liver, and breast cancers. Notably, miR-145-5p plays a vital role in the pathophysiology underlying HIV and chronic obstructive pulmonary diseases associated with cigarette smoke. This miRNA is abundant in biofluids and shows potential as a biomarker for the diagnosis and prognosis of several infectious diseases, such as hepatitis B, tuberculosis, and influenza. Additionally, numerous studies have indicated that other non-coding RNAs, including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate miR-145-5p. Given the significance of miR-145-5p, a comprehensive overview focusing on its roles in health and disease is essential. This review discusses the dual role of miR-145-5p as a protagonist and antagonist in important human diseases, with particular emphasis on disorders of the respiratory, digestive, nervous, reproductive, endocrine, and urinary systems.

Objective(s): Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This study investigates the anti-inflammatory effects of FLV used as an antidepressant in a lipopolysaccharide (LPS)-induced ALI model. Materials and Methods: Thirty-two female Wistar Albino rats aged 14-16 weeks and weighing 300-350 g, with 8 animals in each group, were divided into four groups: control, LPS, LPS+FLV, and FLV. After LPS administration, rats were euthanized, and histopathological analysis, immunohistochemistry for tumor necrosis factor-a (TNF-a) and caspase-3 (Cas-3), ELISA for oxidative stress markers, and PCR for CHOP, Cas-12, and Cas-9 gene expressions were conducted. Results: In the LPS group, lung tissue damage, increased inflammatory cell infiltration, increased Cas-3 and TNF-a expressions, increased oxidative stress markers, and increased CHOP, Cas-9, and Cas-12 mRNA expressions were observed compared to the control group. FLV treatment in the LPS+FLV group significantly reversed these effects in the LPS group. Conclusion: FLV exhibits protective effects against ALI by mitigating inflammation, ERS, and apoptosis via the CHOP/Cas-9/Cas-12 pathway. Further studies are needed to explore additional pathways and potential clinical applications of FLV. [ABSTRACT FROM AUTHOR]

The respiratory system is very important for human life. Its performance determines the quality of life. Physical exercise helps patients suffering from various diseases to build physical fitness, improve respiratory mechanisms, and reduce secretions. It is important to choose the right technique for such patients, using fitness and strength training, breathing exercises, bronchial cleansing. Bronchial clearing aims to remove respiratory tract secretions that contribute to recurrent inflammation and respiratory distress. This is based on the position which facilitates the removal of dense secretions due to the influence of gravity. Pharmacological measures to reduce the secretions in the respiratory tract and facilitate coughing, should be administered prior to drainage. Tracheo-bronchial toilet is a method used to clear mucus and secretions from the airways. The benefits of a tracheo-bronchial toilet include preventing infections such as pneumonia and improving drainage of secretions. Methods used in tracheo-bronchial toilets include temporary naso-tracheal intubation with small tubes, percussion, positioning, and coughing. A tracheotomy can also be performed for lung clearance. Toilet bronchoscopy is a potentially therapeutic intervention to aspirate retained secretions in the endotracheal tube and airway and restore atelectasis.

Abstract Positive expiratory pressure (PEP) is a technique used in respiratory physiotherapy to treat diseases related to the respiratory system through spontaneous breathing. This equipment consists of an oronasal mask coupled to a T connector with a unidirectional valve. Studies that evaluate whether the pressure level in the one-way valve corresponds to the actual pressure level provided are scarce in the scientific literature. In order to investigate the failures, bench tests were carried out on the spring-loaded valves, using a U-tube manometer. This pressure was exerted on the valve using a syringe that generated air flow inside the U-tube, allowing analysis numerical value of the measured pressure and the specified values of the valve, thus verifying the disparity of these measured values in relation to the PEP values operated by valves (0 to 20 cmH2O) from the three manufacturers under study. PEPs generated by spring-loaded valves from all three manufacturers were higher than pressures in the range of 2.5 to 20 cmH2O, with significant differences between manufacturers. This bench study showed inaccurate operation of all spring-loaded PEP valves of the three manufactures. The results obtained and the performance of the valves require a reevaluation of manufacturing procedures to preserve product quality and efficacy in clinical application.

Abstract Background Air quality health index (AQHI), as a developed air quality risk communication tool, has been proved to be more accurate in predicting air quality related health risks than air quality index (AQI) by previous studies. However, the standard method to construct AQHI is summing the excess risks of single-pollutant models directly, which may ignore the joint effect of air pollutant mixtures. Methods In this study, a new method which could solve the aforementioned problem, Analytic hierarchy process (AHP), was introduced. Based on this method, we constructed the respiratory health related AQHI using years of life lost (YLL) as indicator of health outcome and compared its validity with AQI. Results There was a correlation between daily AQI and AQHI in 2019 (R 2 = 0.830, P

This research addresses the need for more engaging and interactive methods to improve elementary students' understanding of complex scientific concepts, particularly the respiratory system. To overcome the limitations of traditional teaching methods, an educational Role-Playing Game (RPG) incorporating the A* (A-Star) algorithm was developed for optimal game navigation. The study followed the ADDIE development model, which involves Analysis, Design, Development, Implementation, and Evaluation. During the analysis phase, learning needs were determined through interviews and classroom observations. The design phase involved creating game scenarios and integrating educational content with interactive elements. The A* algorithm was applied during development to ensure efficient navigation. The game was implemented in a 5th-grade classroom in Kuningan, and its effectiveness was evaluated using pre-tests, post-tests, and student questionnaires. Results demonstrated a significant increase in students' understanding, with average post-test scores rising from 58 to 85. Feedback from both students and teachers was very positive, with the game receiving a 94.2% acceptance rate. The study suggests that RPG-based educational games with intelligent algorithms like A* can greatly enhance science education by offering a more engaging and effective learning experience, contributing to advancements in technology-based learning and setting a standard for future educational game development.

Background: Cancer is still regarded as a major worldwide health issue due to its high health and socioeconomic burden. Currently, lung cancer is the most common cause of cancer‐related fatalities globally. Additionally, mesotheliomas and other cancers of the respiratory system, including those of the trachea, larynx, and bronchi, are also posing a significant health threat. Natural killer (NK) cells are lymphocytes of the innate immune system involved in response against cancer. Objective: This review discussed recent findings in the context of NK cell activity in the immune surveillance of respiratory system cancers and NK cell‐based treatments to combat those malignancies. Results: The presence of natural killer cells in the tumor microenvironment is shown to be associated with a higher survival rate in patients with various malignancies. However, cancerous cells benefit from several mechanisms to evade natural killer cell‐mediated cytotoxicity, including reduced major histocompatibility complex I expression, shedding of ligands, upregulation of inhibitory receptors, and release of soluble factors. Using NK cells to design therapeutic approaches may enhance antitumor immunity and improve clinical outcomes. Clinical trials investigating the use of natural killer cells in combination with cytokine stimulation or immune checkpoint inhibitors have exhibited promising results in various respiratory system malignancies. Conclusion: Respiratory system cancers present significant health challenges worldwide, and while NK cells play a crucial role in tumor surveillance, tumors often evade NK cell responses through various mechanisms. Advances in NK cell‐based therapies, including CAR‐NK cells, immune checkpoint inhibitors, and cytokine stimulation, have shown promising outcomes in tackling these tactics. However, challenges such as the immunosuppressive tumor microenvironment persist. Ongoing research is crucial to improve NK cell therapies by targeting autophagy, modulating miRNAs, and developing combinatorial approaches to enhance treatment efficacy for respiratory cancers. [ABSTRACT FROM AUTHOR]

Objective: Numerous illnesses, such as bacterial and viral infections, affect the respiratory system. Since no known therapy for viruses directly influences health, viral infections are typically more deadly than bacterial ones. The study aimed to ascertain the degree of many immunological markers in patients recovering from viral respiratory infections. The amounts of these indicators were ascertained using the ELISA technique. Material and Methods: The study includes 74 sample collections from June to September (2023), including 28 males and 46 females, aged over 18. Blood samples, overall, were taken. The study was conducted in the Research Laboratory of the Department of Biology, College of Science, University of Mosul. Seventyfour individuals were involved in the study; forty-six of them were recovering from being severe acute respiratory syndrome coronavirus-2 positive (after 6 months), and twenty-eight were not. Results: The findings revealed highly variable levels of interleukin-17 (IL-17), immunoglobulin M (IgM), and immunoglobulin G (IgG) between the patient samples and the control samples. While the IgG level was higher in the first age group (20-40 years), the levels of both IgM and IL-17 were higher in older ages (41-60 years). The levels of immune markers were higher in females than in males, with IL-17, IgG, and IgM reaching 133.3 pg/mL, 1707.9 ng/mL, and 56.8 ng/mL, respectively. Conclusion: According to the current study, the parameters measured in coronavirus disease-2019 recovery participants after six months were higher than those in control samples. [ABSTRACT FROM AUTHOR]

Background and Study Aim: The progressive aging of the global population presents significant challenges, particularly in maintaining the functional reserves of vital systems. The respiratory system is crucial for sustaining physical performance. However, it is especially vulnerable to age-related decline. This study aims to assess the impact of structured physical activity on the respiratory function of sports-active veteran track-and-field athletes aged 50-59 and 60-75 years. Material and Methods: A total of 93 men were examined, including 54 in the reference group (30 men with an average age of 53.67±0.25 years and 24 with an average age of 67.08±0.35 years). These men were involved in athletics in the past but did not participate in veteran sports. The study group included 29 athletics veterans. Among them, 18 individuals had an average age of 52.27±0.18 years, and 11 had an average age of 65.64±0.16 years. These athletes engage in specifically organized physical activity 2-4 times a week and have participated in athletics competitions over the last five years. Anthropometric measurements included the assessment of chest circumference at rest, maximal inspiration, maximal exhalation, and diaphragmatic excursion (DE). The functional state of the respiratory system was assessed using the SpiroCom diagnostic complex (HAI). The data were processed using the SPSS Statistics 17.0 software. Results: Sports veterans aged 50-59 years and those over 60 years exhibit statistically significant differences compared to their peers in several indicators. These include diaphragmatic excursion, tidal volume, minute volume, respiratory rate, tidal volume maximal, respiratory rate maximal, and maximal voluntary ventilation. The respiratory reserve indicator showed a lower degree of respiratory function tension during physical exertion. Statistically significantly higher values of external respiration indicators were found in veteran athletes compared to men with no regular activity (NRA). These indicators include expiratory time, forced expiratory volume in 1 second, and forced expiratory volume maximal. Additionally, veteran athletes showed higher values in the modified Tiffeneau-Pinelli index, peak expiratory flow, and forced expiratory flow at 25%, 50%, 75%, and forced mid-expiratory flow. As a result, sports veterans with high regular activity (RA) exhibited the lowest rates of regressive-destructive changes in the respiratory system indicators overall, with the exception of HOD and BH. In contrast, men with low RA are characterized by an accelerated rate of aging in the respiratory system. Conclusions: The results of the study identified indicators that can serve as spirographic criteria for selecting functional types. These types include individuals with low, medium, and high regular activity (RA). It has been proven that systematic exercises involving specially organized cyclic motor activity form a rational, physiologically optimal type of breathing. Additionally, these exercises inhibit agerelated degenerative-dystrophic processes in the human respiratory system. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to investigate the influence of a respiratory mucosa-on-a-chip on the respiratory epithelial differentiation potential of human nasal inferior turbinate-derived stem cells (hNTSCs). Materials and Methods: After isolating hNTSCs from five patients, we divided the samples from the patients into the study group with a mucosa-on-a-chip and the control group with conventional differentiation (using conventional differentiation methods). The respiratory epithelial differentiation potential of hNTSCs was analyzed by histology and gene expression. Results: In the quantitative analysis, PCR showed that the hNTSCs expressed the cytokeratin genes (KRT13, 14), transformation-related protein P63 (TP63), and vimentin of basal cells in the airway epithelium at higher levels, but cytokeratin genes (KRT6) at lower levels, in the mucosa-on-a-chip than in conventional differentiation. In the cytokine analysis (GM-CSF, IFNr, IL-1a, IL-1b, IL-4, IL-5, IL-10, IL-12(p70), IL-13, IL-17A, IL-17E/IL-25, RANTES, TNFa, IL-6, and IL-8), the expressions of IFNr, IL-13, RANTES, TNFa, IL-6, and IL-8 were significantly upregulated in the mucosa-on-a-chip than in conventional differentiation. Conclusions: We conclude that the human respiratory mucosa-on-a-chip using human turbinate-derived mesenchymal stem cells allows the respiratory differentiation of hNTSCs and shows the difference in gene and cytokine expression, which could serve as an alternative to conventional differentiation for the production of functionally competent hNTSCs for future clinical applications. [ABSTRACT FROM AUTHOR]

Background: Air quality health index (AQHI), as a developed air quality risk communication tool, has been proved to be more accurate in predicting air quality related health risks than air quality index (AQI) by previous studies. However, the standard method to construct AQHI is summing the excess risks of single-pollutant models directly, which may ignore the joint effect of air pollutant mixtures. Methods: In this study, a new method which could solve the aforementioned problem, Analytic hierarchy process (AHP), was introduced. Based on this method, we constructed the respiratory health related AQHI using years of life lost (YLL) as indicator of health outcome and compared its validity with AQI. Results: There was a correlation between daily AQI and AQHI in 2019 (R2 = 0.830, P < 0.01), and the chi-square test between the two excellent rates showed a statistically significant difference (χ2 = 4.156, P < 0.05). Both AQI and AQHI were correlated with the daily respiratory YLL (P < 0.01), however, the coefficient of AQHI was larger than those of AQI. Conclusions: This study indicated that compared with AQI, the constructed AQHI based on AHP may predict the health risk of air pollution more effectively. AHP may become a new method to construct AQHI which needs to be proved by taking into consideration by more studies. [ABSTRACT FROM AUTHOR]

Positive expiratory pressure (PEP) is a technique used in respiratory physiotherapy to treat diseases related to the respiratory system through spontaneous breathing. This equipment consists of an oronasal mask coupled to a T connector with a unidirectional valve. Studies that evaluate whether the pressure level in the one-way valve corresponds to the actual pressure level provided are scarce in the scientific literature. In order to investigate the failures, bench tests were carried out on the spring-loaded valves, using a U-tube manometer. This pressure was exerted on the valve using a syringe that generated air flow inside the U-tube, allowing analysis numerical value of the measured pressure and the specified values of the valve, thus verifying the disparity of these measured values in relation to the PEP values operated by valves (0 to 20 cmH2O) from the three manufacturers under study. PEPs generated by spring-loaded valves from all three manufacturers were higher than pressures in the range of 2.5 to 20 cmH2O, with significant differences between manufacturers. This bench study showed inaccurate operation of all spring-loaded PEP valves of the three manufactures. The results obtained and the performance of the valves require a reevaluation of manufacturing procedures to preserve product quality and efficacy in clinical application. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate viral etiology using molecular methods in cattle with respiratory system problems. The animal material of the study consisted of 200 cattle of different breeds, age and sex, which were not vaccinated against bovine parainfluenza virus 3 (BPIV-3), bovine viral diarrhoea virus (BVDV), bovine respiratory syncytial virus (BRSV) and Bovine adenovirus-3 (BAV-3), brought to the clinics of Kafkas University Faculty of Veterinary Medicine, Department of Internal Medicine, with respiratory system complaints and found to have abnormal respiratory system findings after clinical examination. Blood and swab (if animals had nasal discharge) samples were collected. PCR was performed, positive samples were sent for sequence analysis and the data were subjected to phylogenetic analysis. BVD was detected in 3 of the blood samples collected. From the swab samples; BVD was detected in 8 animals, BPIV-3 in 3 animals, and BRSV in 4 animals. BAV-3 was not detected in any of the collected samples. As a result of the phylogenetic analysis, it was determined that BVD viruses were classified as BVDV-1a, BPIV-3 viruses as genotype C and BRSV viruses as subgroup III (subgroup A). It is thought that these data will be help in guiding in the struggle against viral agents that frequently cause respiratory system diseases. [ABSTRACT FROM AUTHOR]

BackgroundStudies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD).MethodsA retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure.ResultsThe discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL

Aerobic, or endurance, exercise is an energy requiring process supported primarily by energy from oxidative adenosine triphosphate synthesis. The consumption of oxygen and production of carbon dioxide in muscle cells are dynamically linked to oxygen uptake (V̇O2) and carbon dioxide output (V̇CO2) at the lung by integrated functions of cardiovascular, pulmonary, hematologic, and neurohumoral systems. Maximum oxygen uptake (V̇O2max) is the standard expression of aerobic capacity and a predictor of outcomes in diverse populations. While commonly limited in young fit individuals by the capacity to deliver oxygen to exercising muscle, (V̇O2max) may become limited by impairment within any of the multiple systems supporting cellular or atmospheric gas exchange. In the range of available power outputs, endurance exercise can be partitioned into different intensity domains representing distinct metabolic profiles and tolerances for sustained activity. Estimates of both V̇O2max and the lactate threshold, which marks the upper limit of moderate-intensity exercise, can be determined from measures of gas exchange from respired breath during whole-body exercise. Cardiopulmonary exercise testing (CPET) includes measurement of V̇O2 and V̇CO2 along with heart rate and other variables reflecting cardiac and pulmonary responses to exercise. Clinical CPET is conducted for persons with known medical conditions to quantify impairment, contribute to prognostic assessments, and help discriminate among proximal causes of symptoms or limitations for an individual. CPET is also conducted in persons without known disease as part of the diagnostic evaluation of unexplained symptoms. Although CPET quantifies a limited sample of the complex functions and interactions underlying exercise performance, both its specific and global findings are uniquely valuable. Some specific findings can aid in individualized diagnosis and treatment decisions. At the same time, CPET provides a holistic summary of an individual's exercise function, including effects not only of the primary diagnosis, but also of secondary and coexisting conditions.

Introduction Electronic cigarettes have gained widespread popularity by being marketed as a safer alternative to traditional smoking. Possibility of inhaling vapor created by heating nicotine liquid instead of combusting tobacco leaves revolutionized tobacco market, bringing a lot of questions about harmfulness or advantages of e-cigarettes. Their popularity is increasing and many aspects about their influence on health are still unclear. At the same time, better social acceptance than tobacco cigarettes brings out questions if they are a step to smoking cessation or if they encourage more people to start using nicotine. Aim of the review This systematic review provide an analysis of the existing literature on the influence of e-cigarettes on the human body with their economic and behavioral aspects. By examining a wide range of studies, we aim to elucidate the potential risks and benefits associated with e-cigarette use and provide a comparison of both electronic and conventional forms of nicotine consumption. Methods A systematic search was conducted using electronic databases such as PubMed, Scopus, and Web of Science. Keywords included "e-cigarettes", "vaping", "health effects", "conventional cigarettes", "tobacco", "respiratory system", "cardiovascular system", "immune system", "oral health", and "cellular effects". The search was limited to studies published up to December 2023. Both observational and experimental studies were included. Conclusion While e-cigarettes are often promoted as a safer alternative to conventional cigarettes, the evidence suggests that they are not without significant health risks. It is important to remember that they are a new form of substance use, and many aspects related to them are still unknown. E-cigarettes and conventional cigarettes present distinct usage patterns and cost profiles. Years of research on larger sample sizes are needed to determine their impact on humans.

Swimming produces many psychophysiological effects, including blood, hormonal, enzymatic, pulmonary, cardiovascular and energetic adaptations. However, asthma and allergies are becoming increasingly prevalent medical issues among elite endurance-trained swimmers, where exercise-induced asthma or bronchospasm is frequently reported. Heavy endurance swimming training, especially under adverse conditions, stresses the airway mucosa, leading to inflammatory changes, as observed in induced sputum in competitive swimmers. In addition, chlorine-based disinfectants (CBDs) are commonly used in indoor pools due to their effectiveness and lower relative cost. Many of these substances have carcinogenic and genotoxic properties, and exposure to DBPs have been linked to adverse respiratory effects. The association between long-term exposure to a chlorinated swimming pool and elevated serum sIgE levels suggests a link between allergens, chlorine exposure and the development of various pulmonary dysfunctions. Thus, the combination of intense and repeated physical endurance training over extended periods, along with suboptimal environmental conditions, may contribute to the development of rhinitis, asthma and bronchial hyperresponsiveness in athletes. While occasional or low-level exposure to chlorine might not be harmful, regular swimmers, especially those at competitive levels, are at a higher risk of developing respiratory disorders. Because these potential risks of exposure to CBDs must be balanced against the benefits of swimming and the risk of microbial infections in pools, we recommend better pool management and regular health checks for swimmers. Fortunately, the reduction of bronchial symptoms in swimmers who reduce training volume and intensity suggests that the negative effects on pulmonary function may be reversible. For these reasons, it is crucial to develop effective respiratory protection strategies, including medical interventions and modifications to the pool environment. Practical steps such as reducing chlorine use, ensuring proper hygiene before swimming and using swim caps can minimise risks. Research should also explore safer alternatives to CBDs, such as ozonation, and improved ventilation to reduce air pollutants.