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Background: Many patients with chronic obstructive pulmonary disease and fibrotic interstitial lung disease suffer from severe dyspnea and reduced quality of life, despite receiving optimal disease-modifying treatment for their illness. Studies have suggested that these patients may benefit from treatment with low-dose opioids. However, many patients decline opioid treatment. This has led to patients not receiving proper palliative treatment of their lung disease. Aim: To identify potential barriers that prevent patients from receiving adequate palliative care with opioids and enable doctors to address patients' concerns. Design: A qualitative study based on semi-structured interviews. Interviews were transcribed and thematic analysis was done using NVivo. Setting/Participants: Patients were recruited when scheduled for out-patient follow-up at Center for Rare Lung Diseases or at the COPD clinic, Aarhus University Hospital. Eligible patients were 18 years of age, did not currently receive opioids or had ever received opioids for dyspnea. Results: A total of 28 patients participated. One patient was excluded before final analysis of 27 patients. Four themes were identified: Fear of side-effects, Need for more information, Stigma of opioids association with severe illness and dying, and No discernible barriers. Furthermore, three sub-themes to Fear of side-effects were identified: Fear of addiction, concern for sedative effect, and fear for loss of mobility due to inability to drive a car. The most expressed concern was Fear of side-effects, especially addiction. Conclusions: Pre-conceived notions about opioids prevent some patients with chronic obstructive lung disease or interstitial lung disease from receiving palliative care for breathlessness. [ABSTRACT FROM AUTHOR]

Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high‐resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non‐fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non‐IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group‐wise analyses of metabolites altered in ILD phenotypes. We utilized limma one‐way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p‐values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl‐hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non‐ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionParticulate matter (PM) air pollution is associated with an increased incidence of lung diseases, but the underlying mechanisms have not been fully elucidated. In this study, a mouse model of subacute lung inflammation was employed to investigate the cellular responses and gene expression changes induced by exposure to natural ambient air pollution.C57BL/6J mice were exposed to road dust (primarily PM10) at 150 µg/m³ for 21 days (8 h/day) through a nose-only inhalation exposure system. Lung tissues were analyzed for the expression of proinflammatory signaling, oxidative stress, and fibrosis markers. RNA-sequencing analysis was conducted to identify differentially expressed genes (DEGs). A gene ontology over-representation analysis was performed to identify the altered genetic pathways.Elevated levels of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, and an increase in phosphorylated MAPK were determined in the road dust exposure group compared to the control group. Histopathological examinations revealed more severe lung inflammation and damage in the exposed mice, including fibrosis and bronchiolar hyperplasia. Gene expression profiling identified 108 DEGs, with decreases in most except genes such as Krt15 and Reg3g. The protein–protein interaction network analysis together with text-mining identified 18 key hub genes, associated with fatty acid oxidation, lipid metabolism, and peroxisomes.This study identified key genes, signaling pathways, and cellular responses in mouse lung affected by road dust exposure. These findings contribute to a deeper understanding of the transcriptional and cellular responses induced by subacute exposure to the PM in road dust. [ABSTRACT FROM AUTHOR]

Lymphangioleiomyomatosis (LAM) is a rare genetic lung disease. Unfortunately, treatment with the mTORC1 inhibitor Rapamycin only slows disease progression, and incomplete responses are common. Thus, there remains an urgent need to identify new targets for the development of curative LAM treatments. Nitazoxanide (NTZ) is an orally bioavailable antiprotozoal small molecule drug approved for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum in children and adults, with a demonstrated mTORC1 inhibitory effect in several human cell lines. NTZ's excellent safety profile characterized by its more than 20 years of clinical use makes it a promising candidate for repurposing. Our rationale for this study was to further investigate NTZ's effect using in vitro and in vivo LAM models and to elucidate the underlying molecular mechanism beyond mTORC1 inhibition. For this purpose, we investigated cell proliferation, cell viability, and changes in protein phosphorylation and expression in primary human cell cultures derived from LAM lung samples before translating our results into a syngeneic mouse model utilizing Tsc2-null cells. NTZ reduced cell growth for all tested cell lines at a dose of about 30 µM. Lower doses than that had no effect on cell viability, but doses above 45 µM lowered the viability by about 10 to 15% compared to control. Interestingly, our western blot revealed no inhibition of mTORC1 and only a mild effect on active ß-Catenin. Instead, NTZ had a pronounced effect on reducing pAkt. In the mouse model, prophylactic NTZ treatment via the intraperitoneal and oral routes had some effects on reducing lung lesions and improving body weight retention, but the results remain inconclusive. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4–related disease (IgG4-RD) is a multisystem fibroinflammatory condition. A consistent feature of many cases is pulmonary infiltrates, or respiratory failure. This systematic literature review aims to summarise the pulmonary manifestations of IgG4-RD, including clinical outcomes and treatment. This review was registered on PROSPERO (CRD42023416410). Medline, Embase and Cochrane databases were searched for articles discussing IgG4-RD syndrome. Information was extracted on demographics, type and prevalence of pulmonary manifestations, treatment and clinical outcomes. Initially, after deduplication, 3123 articles were retrieved with 18 ultimately included. A pooled total of 724 patients with IgG4-RD were included, 68.6% male, mean age 59.4 years (SD 5.8) at disease onset. The most frequently described pulmonary manifestation was mediastinal lymphadenopathy (n = 186, 48.8%), followed by pulmonary nodules (n = 151, 39.6%) and broncho-vascular thickening (n = 85, 22.3%). Where treatment was reported, the majority of patients received glucocorticoids (n = 211, 93.4%). Other immunosuppressive therapy included cyclophosphamide (n = 31), azathioprine (n = 18), with mycophenolate mofetil (n = 6), rituximab (n = 6), methotrexate (n = 5) and other unspecified immunomodulators (50). Clinical outcomes were reported in 263 patients, where 196 patients had remission of their disease, 20 had relapse, 35 had stable disease, four had progression and eight patients died from complications of IgG4-RD. This systematic review summarises pulmonary manifestations, treatments and outcomes in patients with IgG4-RD. Pulmonary involvement in IgG4-RD is relatively common, leading to high levels of morbidity and mortality. Glucocorticoids remain the mainstay of treatment, but further work is required to explore the management of patients with pulmonary manifestations in association with IgG4-RD. [ABSTRACT FROM AUTHOR]

The intricate relationship between chronic lung diseases and viral infections is a significant concern in respiratory medicine. We explore how pre-existing lung conditions, including chronic obstructive pulmonary disease, asthma, and interstitial lung diseases, influence susceptibility, severity, and outcomes of viral infections. We also examine how viral infections exacerbate and accelerate the progression of lung disease by disrupting immune responses and triggering inflammatory pathways. By summarizing current evidence, this review highlights the bidirectional nature of these interactions, where underlying lung diseasesincrease vulnerability to viral infections, while these infections, in turn, worsen the clinical course. This review underscores the importance of preventive measures, such as vaccination, early detection, and targeted therapies, to mitigate adverse outcomes in patients with chronic lung conditions. The insights provided aim to inform clinical strategies that can improve patient management and reduce the burden of chronic lung diseases exacerbated by viral infections. [ABSTRACT FROM AUTHOR]

Lung disease is one of the leading causes of death worldwide. This emphasizes the need for early diagnosis in order to provide appropriate treatment and save lives. Physicians typically require information about patients' clinical symptoms, various laboratory and pathology tests, along with chest X-rays to confirm the diagnosis of lung disease. In this study, we present a transformer-based multimodal deep learning approach that incorporates imaging and clinical data for effective lung disease diagnosis on a new multimodal medical dataset. The proposed method employs a cross-attention transformer module to merge features from the heterogeneous modalities. Then unified fused features are used for disease classification. The experiments were performed and evaluated on several classification metrics to illustrate the performance of the proposed approach. The study's results revealed that the proposed method achieved an accuracy of 95% in terms of accurate classification of tuberculosis and outperformed other traditional fusion methods on multimodal tuberculosis data used in this study. [ABSTRACT FROM AUTHOR]

Hyperuricemia is a known predictor of World Health Organization (WHO) Group 1 pulmonary hypertension (PH) (pulmonary arterial hypertension), but its role in excluding PH secondary to chronic lung diseases (WHO Group 3) remains unclear. We retrospectively analyzed data from 323 patients with severe chronic pulmonary diseases who underwent evaluation for lung transplantation at a tertiary medical center between June 2017 and February 2023. We examined the association between hyperuricemia (serum uric acid > 6 mg/dL or > 0.357 mmol/L) and PH [mean pulmonary arterial pressure (MPAP) > 20 mmHg]. Compared to the normouricemia group (n = 211), hyperuricemic patients (n = 112) were more likely to be younger (P = 0.02), male (P < 0.001), and present with PH (P = 0.001) and severe PH (MPAP > 35 mmHg; P < 0.001). These patients also had a higher body mass index (P = 0.004), plasma N-terminal pro-B-type natriuretic peptide (P < 0.001), serum creatinine (P < 0.001), and C-reactive protein levels (P = 0.03). Significant associations with PH included higher body mass index (P = 0.005), uric acid levels (P < 0.001), total lung capacity (P = 0.02), and residual volume (P = 0.01); shorter 6-min walk test distance (P = 0.005); and lower forced expiratory volume in one second (P = 0.006) and diffusing capacity for carbon monoxide (P < 0.001). Multivariate analysis showed elevated uric acid levels remained significantly associated with PH (OR 1.29, 95% CI 1.05–1.58, P = 0.01). In conclusion, normal serum uric acid levels serve as a significant predictor for excluding pulmonary hypertension in patients with severe chronic lung diseases. [ABSTRACT FROM AUTHOR]

A major global source of disability as well as mortality is respiratory illness. Though visual evaluation of computed tomography (CT) images and chest radiographs are a primary diagnostic for respiratory illnesses, it is limited in its ability to assess severity and predict patient outcomes due to low specificity and fundamental infectious organisms. In order to address these problems, world cup optimization-based Bi-LSTM classification and lung disease prediction on CT images using REINF-net were employed. To enhance the image quality, the gathered lung CT images are pre-processed using Lucy Richardson and CLAHE algorithms. For the purpose of lung infection segmentation, the pre-processed images are segmented using the REInf-net. The GLRLM method is used to extract features from the segmented images. In order to predict lung disease in CT images, the extracted features are trained using the Bi-LSTM based on world cup optimization. Accuracy, Precision, recall, Error and Specificity for the proposed model are 97.8%, 96.7%, 96.7%, 2.2% and 98.3%. These evaluated values are contrasted with the results of existing methods like WCO-BiLSTM, MLP, CNN and LSTM. Finally, the Lung disease prediction based on CT images using REINF-Net and world cup optimization based BI-LSTM classification performs better than the existing model. [ABSTRACT FROM AUTHOR]

Limited treatments and a lack of appropriate animal models have spurred the study of scaffolds to mimic lung disease in vitro. Decellularized human lung and its application in extracellular matrix (ECM) hydrogels has advanced the development of these lung ECM models. Controlling the biochemical and mechanical properties of decellularized ECM hydrogels continues to be of interest due to inherent discrepancies of hydrogels when compared to their source tissue. To optimize the physiologic relevance of ECM hydrogel lung models without sacrificing the native composition we engineered a binary fabrication system to produce a Hybridgel composed of an ECM hydrogel reinforced with an ECM cryogel. Further, we compared the effect of ECM-altering disease on the properties of the gels using elastin poor Chronic Obstructive Pulmonary Disease (COPD) vs non-diseased (ND) human lung source tissue. Nanoindentation confirmed the significant loss of elasticity in hydrogels compared to that of ND human lung and further demonstrated the recovery of elastic moduli in ECM cryogels and Hybridgels. These findings were supported by similar observations in diseased tissue and gels. Successful cell encapsulation, distribution, cytotoxicity, and infiltration were observed and characterized via confocal microscopy. Cells were uniformly distributed throughout the Hybridgel and capable of survival for 7 days. Cell-laden ECM hybridgels were found to have elasticity similar to that of ND human lung. Compositional investigation into diseased and ND gels indicated the conservation of disease-specific elastin to collagen ratios. In brief, we have engineered a composited ECM hybridgel for the 3D study of cell-matrix interactions of varying lung disease states that optimizes the application of decellularized lung ECM materials to more closely mimic the human lung while conserving the compositional bioactivity of the native ECM. The lack of an appropriate disease model for the study of chronic lung diseases continues to severely inhibit the advancement of treatments and preventions of these otherwise fatal illnesses due to the inability to recapture the biocomplexity of pathologic cell-ECM interactions. Engineering biomaterials that utilize decellularized lungs offers an opportunity to deconstruct, understand, and rebuild models that highlight and investigate how disease specific characteristics of the extracellular environment are involved in driving disease progression. We have advanced this space by designing a binary fabrication system for a ECM Hybridgel that retains properties from its source material required to observe native matrix interactions. This design simulates a 3D lung environment that is both mechanically elastic and compositionally relevant when derived from non-diseased tissue and pathologically diminished both mechanically and compositionally when derived from COPD tissue. Here we describe the ECM hybridgel as a model for the study of cell-ECM interactions involved in COPD. [Display omitted] [ABSTRACT FROM AUTHOR]

To study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases. Umbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth. The umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease. Umbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period. [ABSTRACT FROM AUTHOR]

• Cardiometabolic disorders are associated with lung ageing. • The highest percentage of cardiometabolic complications occurs in workers with obesity. • Obesity without cardiometabolic abnormalities is not associated with patterns of pulmonary dysfunction. Four phenotypes relate metabolism and obesity: metabolically healthy (MHO) and unhealthy (MUO) people with obesity and metabolically healthy (MHNO) and unhealthy (MUNO) people without obesity. No studies have addressed the association between these categories and lung function in the working population. The aim was to determine the relationship of phenotypes to lung ageing as measured by lung age and its relationship to lung dysfunction. A descriptive cross-sectional study was conducted in a working population. The outcome variable was lung function assessed by lung age. The four phenotypes of obesity and metabolic health (MHNO, MHO, MUO and MUNO) were determined using NCEP-ATP III criteria. Lung dysfunctions were classified into restrictive, obstructive, and mixed patterns. The mean age of the participants was 43.7 years, ranging from 18 to 67 years. Of the 1860 workers, 51.3 % were women. The prevalences found were 71.4 %, 12 %, 10.6 % and 6 % for MHNO, MUO, MHO, and MUNO, respectively. MHO (β = 0.66; p = 0.591) was not associated with increased lung ageing compared with MHNO, but MUO (β = 7.1; p < 0.001) and MUNO (β = 6.6; p < 0.001) were. Concerning pulmonary dysfunctions, MUNO (OR = 1.93; p < 0.001) and MUO (OR = 2.91; p < 0.001) were found to be related to the presence of a restrictive pattern, and MUNO (OR = 2.40; p = 0.028) to the mixed pattern. The results show that metabolic abnormalities, not obesity, are responsible for premature lung ageing and, therefore, lung function decline. In our study, having obesity without metabolic abnormality was not significantly associated with the presence of dysfunctional respiratory patterns. [ABSTRACT FROM AUTHOR]

Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory condition with onset in childhood. It is sporadic, but elements of its stereotypical innate immune responses are likely genetically encoded by both common variants with small effect sizes and rare variants with larger effects. Genomic investigations have defined the unique genetic architecture of sJIA. Identification of the class II HLA locus as the strongest sJIA risk factor for the first time brought attention to T lymphocytes and adaptive immune mechanisms in sJIA. The importance of the human leukocyte antigen (HLA) locus was reinforced by recognition that HLA-DRB1*15 alleles are strongly associated with development of drug reactions and sJIA-associated lung disease (sJIA-LD). At the IL1RN locus, genetic variation relates to both risk of sJIA and may also predict non-response to anakinra. Finally, rare genetic variants may have critical roles in disease complications, such as homozygous LACC1 mutations in families with an sJIA-like illness, and hemophagocytic lymphohistiocytosis (HLH) gene variants in some children with macrophage activation syndrome (MAS). Genetic and genomic analysis of sJIA holds great promise for both basic discovery of the course and complications of sJIA, and may help guide personalized medicine and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases. Method: Umbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth. Results: The umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease. Conclusion: Umbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period.

Alaska Native and American Indian children experience frequent respiratory illness. Indoor air quality is associated with the severity and frequency of respiratory infections in children. High efficiency particulate air (HEPA) purifiers effectively improve indoor air quality and may protect respiratory health. In 2019, the Yukon-Kuskokwim Health Corporation implemented a pilot programme that provided education and HEPA purifiers to households of children with chronic lung conditions. The team evaluated HEPA purifier acceptability and use by interviewing representatives from 11 households that participated in the pilot programme. All interviewees reported improvement in their child’s health, and some believed that the health of other household members was also improved because of the HEPA purifier. Interviewees reported that the HEPA purifiers were easy to use, quiet, and not expensive to run. Five of 11 households were still using the HEPA purifier at the time of the interview, which was about three years after receipt of the unit. The most common reasons for discontinuing use were equipment failure and lack of replacement filter, suggesting that programme support could increase sustainability. Our evaluation suggests that HEPA purifiers are acceptable and feasible for use in rural Alaska Native households. [ABSTRACT FROM AUTHOR]

Abstract Background The immunologic features of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely unclear. This study investigated the immunologic features of NTM-PD using digital spatial profiling techniques. Methods Lung tissues obtained from six patients with NTM-PD between January 1, 2006, and December 31, 2020, at Seoul National University Hospital were subjected to RNA sequencing. Cores from the peribronchial areas were stained with CD3, CD68, and DNASyto13, and gene expression at the whole-transcriptome level was quantified using PCR amplification and Illumina sequencing. Lung tissues from six patients with bronchiectasis collected during the same period were used as controls. The RNA sequencing results were validated using immunohistochemistry (IHC) in another cohort (30 patients with NTM-PD and 15 patients with bronchiectasis). Results NTM-PD exhibited distinct gene expression patterns in T cells and macrophages. Gene set enrichment analysis revealed that pathways related to antigen presentation and processing were upregulated in NTM-PD, particularly in macrophages. Macrophages were more prevalent and the expression of genes associated with the M1 phenotype (CD40 and CD80) was significantly elevated. Although macrophages were activated in the NTM-PD group T cell activity was unaltered. Notably, expression of the costimulatory molecule CD28 was decreased in NTM-PD. IHC analysis showed that T cells expressing Foxp3 or TIM-3, which facilitate the regulatory functions of T cells, were increased. Conclusions NTM-PD exhibits distinct immunologic signatures characterized by the activation of macrophages without T cell activation.

Background: Occupational lung diseases (OLDs) contribute a significant proportion to the global burden of pulmonary morbidities but are grossly misdiagnosed due to the relative lack of attribution given to occupational exposures. Obstructive lung diseases are known to be associated with long-lasting disability and loss of earning capacity (LOEC) among workers in industrial setups, thus reducing nationwide productivity. Objective: In this context, the study aimed to find out the pattern of OLD and factors associated with the severity of it among patients in a tertiary care hospital. Materials and Methods: The study was a record-based secondary data analysis conducted in the Medical Records Department of a Medical College in Kolkata. A computerized database of patients attending Special Medical Board (SMB) examinations from the Department of Medical Records was utilized for data collection. A data abstraction format was constructed to collect information on pulmonary morbidity, occupational exposure, and sociodemographic and behavioral variables. Extracted data were analyzed in Microsoft Excel and Statistical Package for Social Sciences (SPSS) software Results: After a review of records, it was shown that 62.3% (66 out of 106 people) of the study subjects had an obstructive type of OLD, the most common being Jute Byssinosis. A negative correlation (Spearman’s ρ = -0.136) was found between pulmonary function (FEV1/FVC) and LOEC (%) in the study subjects. In the multivariable logistic regression, exposure to organic dust was found to be significantly associated with worsened lung function {adjusted-Odd’s Ratio (95% Confidence Interval) =3.11 (1.1–8.8), P value = 0.03}. Conclusion: OLD is an understated health issue, especially in an industrial diaspora of developing countries, like India. Healthcare facilities should utilize their resources properly for the advancement of medical surveillance in industries where organic dust is produced. Health education of the stakeholders regarding the consequences of OLDs and the benefits of preventive primary approaches will go a long way in alleviating the burden of disease.

High oxygen(hyperoxia) concentration may damage multiple organs and systems in newborns, such as the lung, brain and intestines. Metabolic abnormalities are important early events in the pathogenesis of neonatal hyperoxia related pulmonary diseases. This article reviews the increased glucose and lipid metabolism as well as dys-regulation of amino acid metabolism after hyperoxia related bronchopulmonary dysplasia in newborns. The potential mechanism may be that the high oxygen concentration increases formation of mitochondrial reactive oxygen species (mtROS), and also change the mitochondrial dynamics of neonatal bronchopulmonary dysplasia, leading to reduction of mitochondrial fusion, enhances fission and autophagy. This study also finds that many metabolism-related enzymes and metabolites are changed during hyperoxia related diseases. However, clinical research has not yet been conducted. Future research should focus on combining metabolic profiles with multi omics data, including transcriptome sequencing, genomics and proteomics to identify potential biomarkers and therapeutic targets for hyperoxia related neonatal lung injury in order to develop new strategies for the treatment of metabolic abnormalities resulted from neonatal hyperoxia related pulmonary diseases.

May Hagiwara,1 Victoria Divino,2 Swapna Munnangi,2 Mark Delegge,2 Suna Park,1 Ed G Marins,3 Kaili Ren,4 Charlie Strange5 1Global Evidence and Outcomes, Takeda Development Center Americas, Inc., Cambridge, MA, USA; 2Medical and Scientific Services, IQVIA Inc., Falls Church, VA, USA; 3Global Medical Affairs, Takeda Development Center Americas, Inc., Cambridge, MA, USA; 4Statistics and Quantitative Sciences, Takeda Development Center Americas, Inc., Cambridge, MA, USA; 5Department of Medicine, Medical University of South Carolina, Charleston, SC, USACorrespondence: May Hagiwara, Takeda Development Center Americas, Inc., 500 Kendall Street, Cambridge, MA, 02142, USA, Tel +1 781-482-0426, Email may.hagiwara@takeda.comBackground and Aims: Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA.Methods: This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics® Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022. Patients had a diagnosis of liver and/or lung disease with ≥ 180 days of continuous enrollment in the IQVIA PharMetrics Plus database before and ≥ 90 days after their first diagnosis. Follow-up time was assigned to the AATD with liver disease health state or AATD with both liver and lung disease health state (for patients aged ≥ 18 years only). Baseline demographic characteristics and liver-related clinical events of interest were reported.Results: Of 5136 eligible patients, 771 adult and 123 pediatric patients contributed time to the AATD with liver disease health state; 541 adults contributed time to the AATD with both liver and lung disease health state. Among adults, patients with both liver and lung disease had higher rates of liver-related clinical events than patients with liver disease alone. Ascites was the most frequently observed clinical event among adults in both health states, and the median time to the composite of any liver-related clinical event was 26.5 days among all adults combined. Across all pediatric age groups, ascites, gastrointestinal bleed and hepatic encephalopathy were more common than spontaneous bacterial peritonitis and hepatocellular carcinoma, but median time to liver-related clinical event varied by age group at index date and type of event. No liver transplantations occurred in patients aged 6– 17 years.Conclusion: Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events.Keywords: alpha-1 antitrypsin deficiency, genetic disease, liver disease, lung disease, pediatric, adult

Abstract Background Recent advances in Vision Transformer (ViT)-based deep learning have significantly improved the accuracy of lung disease prediction from chest X-ray images. However, limited research exists on comparing the effectiveness of different optimizers for lung disease prediction within ViT models. This study aims to systematically evaluate and compare the performance of various optimization methods for ViT-based models in predicting lung diseases from chest X-ray images. Methods This study utilized a chest X-ray image dataset comprising 19,003 images containing both normal cases and six lung diseases: COVID-19, Viral Pneumonia, Bacterial Pneumonia, Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and Tuberculosis. Each ViT model (ViT, FastViT, and CrossViT) was individually trained with each optimization method (Adam, AdamW, NAdam, RAdam, SGDW, and Momentum) to assess their performance in lung disease prediction. Results When tested with ViT on the dataset with balanced-sample sized classes, RAdam demonstrated superior accuracy compared to other optimizers, achieving 95.87%. In the dataset with imbalanced sample size, FastViT with NAdam achieved the best performance with an accuracy of 97.63%. Conclusions We provide comprehensive optimization strategies for developing ViT-based model architectures, which can enhance the performance of these models for lung disease prediction from chest X-ray images.

Background: Computed tomography (CT) has a larger role in the noninvasive examination of congenital lung abnormalities, thanks to the introduction of multidetector CT (MDCT). If a surgical lesion is suspected, it is often necessary to use cross-sectional imaging, such as CT, for diagnosis confirmation, further lesion definition, and preoperative evaluation. Aims and Objectives: The aim of this study was to enhance comprehension of the occurrence and varieties of congenital lung abnormalities in children, as well as to assess and compare the diagnostic precision of MDCT with that of surgical intervention. Methodology: MDCT with contrast CT was performed in children with respiratory complaints and prenatal history of suspicion in targeted imaging for fetal anomalies (TIFFA) or congenital lung malformations (CLMs) using TOSHIBA 8 slice CT; the study population consisted of 40 pediatric patients with a history of chest anomalies during pregnancy in TIFFA or children with abnormal chest X-ray suspicion of lung anomalies for 18 months. Results: In a study of 40 pediatric patients who underwent MDCT with contrast to evaluate CLMs, 6 were excluded from further evaluation with contrast due to the absence of pulmonary anomalies on plain CT, leaving a possible diagnosis of s CLM in the remaining 34 cases. Of these, cystic pulmonary airway malformations (CPAM) (41.1%) were the most common, followed by congenital lobar emphysema (17.6%), bronchogenic cyst (14.7%), lung agenesis (11.6%), and phylogenetic lung. Conclusion: To notice the characteristics and related anomalies of CLMs and aid in the presurgical evaluation of CLMs, the study concludes that MDCT with contrast is the imaging of choice.

Abstract Background The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. Method Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. Results The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p

Background: The immunologic features of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely unclear. This study investigated the immunologic features of NTM-PD using digital spatial profiling techniques. Methods: Lung tissues obtained from six patients with NTM-PD between January 1, 2006, and December 31, 2020, at Seoul National University Hospital were subjected to RNA sequencing. Cores from the peribronchial areas were stained with CD3, CD68, and DNASyto13, and gene expression at the whole-transcriptome level was quantified using PCR amplification and Illumina sequencing. Lung tissues from six patients with bronchiectasis collected during the same period were used as controls. The RNA sequencing results were validated using immunohistochemistry (IHC) in another cohort (30 patients with NTM-PD and 15 patients with bronchiectasis). Results: NTM-PD exhibited distinct gene expression patterns in T cells and macrophages. Gene set enrichment analysis revealed that pathways related to antigen presentation and processing were upregulated in NTM-PD, particularly in macrophages. Macrophages were more prevalent and the expression of genes associated with the M1 phenotype (CD40 and CD80) was significantly elevated. Although macrophages were activated in the NTM-PD group T cell activity was unaltered. Notably, expression of the costimulatory molecule CD28 was decreased in NTM-PD. IHC analysis showed that T cells expressing Foxp3 or TIM-3, which facilitate the regulatory functions of T cells, were increased. Conclusions: NTM-PD exhibits distinct immunologic signatures characterized by the activation of macrophages without T cell activation. [ABSTRACT FROM AUTHOR]

In a patient with interstitial lung disease (ILD) of known or unknown etiology other than idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF) is defined by worsening lung fibrosis on high-resolution computed tomography (HRCT), decline in lung function, and/or deterioration in symptoms. The INBUILD trial involved 663 patients with PPF who were randomized to receive nintedanib or placebo. The median exposure to trial medication was approximately 19 months. The INBUILD trial provided valuable learnings about the course of PPF and the efficacy and safety of nintedanib. The relative effect of nintedanib on reducing the rate of forced vital capacity decline was consistent across subgroups based on ILD diagnosis, HRCT pattern, and disease severity at baseline, and between patients who were and were not taking glucocorticoids or disease-modifying anti-rheumatic drugs and/or glucocorticoids at baseline. The adverse events most frequently associated with nintedanib were gastrointestinal, particularly diarrhea, but nintedanib was discontinued in only a minority of cases. The results of the INBUILD trial highlight the importance of prompt detection and treatment of PPF and the utility of nintedanib as a treatment option. Plain language summary: What did we find out from the INBUILD trial about progressive lung fibrosis? Lung fibrosis is a rare disease in which the lung tissue becomes scarred and hardened. This makes it more difficult for the lungs to inflate and for the lungs to exchange oxygen with the blood. In some patients, lung fibrosis gets worse over time. This is known as progressive lung fibrosis. In the INBUILD trial, researchers looked at the effects of a drug called nintedanib in patients with progressive lung fibrosis. In this trial, 663 patients were randomly allocated to receive either nintedanib or a placebo and then followed for approximately 19 months. The patients and the researchers did not know which patients were taking the active drug (nintedanib) and which patients were taking placebo. The results showed that the criteria used to find patients with progressive lung fibrosis to take part in the trial successfully identified patients whose disease would continue to worsen. These criteria were based on a decline in the volume (size) of the lungs, worsening symptoms such as shortness of breath, and worsening of changes seen on a scan of the chest. The trial results also showed that nintedanib slowed down loss of lung function and had a similar benefit in patients with different severities of disease at the start of the trial. The most common side-effects of nintedanib were gastrointestinal problems, particularly diarrhea, but most patients given nintedanib were able to cope with these side-effects without needing to stop treatment. Large trials like the INBUILD trial are important for helping us understand how diseases progress and in which patients particular drugs should be used. [ABSTRACT FROM AUTHOR]

Fish oil, renowned for its high content of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has gained considerable attention for its potential health benefits. EPA and DHA exhibit anti-inflammatory effects by promoting the production of specialized pro-resolving mediators (SPMs), such as resolvins and protectins. Fish oil has been studied for its potential to reduce bronchial inflammation, a key feature of respiratory conditions like asthma and COPD. This study investigates the cellular mechanisms of fish oil in an in vitro model of lung inflammation using lipopolysaccharide (LPS) on a healthy human bronchial epithelium cell line. LPS exposure for 24 h reduced cell viability, elevated reactive oxygen species (ROS), depleted glutathione (GSH), and induced mitochondrial depolarization, indicating oxidative stress and inflammation. Fish oil administration significantly mitigated ROS production, prevented GSH depletion, and reduced mitochondrial depolarization. This was associated with the upregulation of the endogenous antioxidant system, evidenced by restored GSH levels and the increased gene expression of glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2). Fish oil also suppressed IL-6 and IL-1β expression and increased anti-inflammatory cytokine IL-10 expression. Furthermore, fish oil upregulated the expression of pro-resolving mediator receptors, suggesting a role in inflammation resolution. These findings highlight the potential of fish oil supplementation as a preventive measure against pulmonary diseases characterized by unresolved inflammation such as lung inflammation. [ABSTRACT FROM AUTHOR]

Autophagy is a complex physiological pathway mediating homeostasis and survival of cells degrading damaged organelles and regulating their recycling. Physiologic autophagy can maintain normal lung function, decrease lung cellular senescence, and inhibit myofibroblast differentiation. It is well known that autophagy is activated in several chronic inflammatory diseases; however, its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and the expression of autophagy-related genes (ATGs) in lower airways of COPD patients is still controversial. The expression and localization of all ATG proteins that represented key components of the autophagic machinery modulating elongation, closure, and maturation of autophagosome membranes were retrospectively measured in peripheral lungs of patients with stable COPD (n = 10), control smokers with normal lung function (n = 10), and control nonsmoking subjects (n = 8) using immunohistochemical analysis. These results show an increased expression of ATG4 protein in alveolar septa and bronchiolar epithelium of stable COPD patients compared to smokers with normal lung function and non-smoker subjects. In particular, the genes in the ATG4 protein family (including ATG4A, ATG4B, ATG4C, and ATG4D) that have a key role in the modulation of the physiological autophagic machinery are the most important ATGs increased in the compartment of lower airways of stable COPD patients, suggesting that the alteration shown in COPD patients can be also correlated to impaired modulation of autophagic machinery modulating elongation, closure, and maturation of autophagosomes membranes. Statistical analysis was performed by the Kruskal–Wallis test and the Mann–Whitney U test for comparison between groups. A statistically significant increased expression of ATG4A (p = 0.0047), ATG4D (p = 0.018), and ATG5 (p = 0.019) was documented in the bronchiolar epithelium as well in alveolar lining for ATG4A (p = 0.0036), ATG4B (p = 0.0054), ATG4C (p = 0.0064), ATG4D (p = 0.0084), ATG5 (p = 0.0088), and ATG7 (p = 0.018) in patients with stable COPD compared to control groups. The ATG4 isoforms may be considered as additional potential targets for the development of new drugs in COPD. [ABSTRACT FROM AUTHOR]

There is a pressing need for novel pharmacological interventions and drug delivery innovations to attenuate the cigarette smoke-associated oxidative stress and lung disease. We report here on the attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR) and metabolomics of Wistar rats exposed to cigarette smoke for 28 days. The animals were treated for 15 days with plain cysteamine given orally or cysteamine as nanoemulsion given orally or via inhalation. The study design also included two control groups as follows: rats exposed to cigarette smoke but did not receive a treatment (diseased control group) and rats neither exposed to cigarette smoke nor a treatment (normal control group). The targeted metabolomics using Parallel Reaction Monitoring showed that in the diseased control group, ornithine, nicotinamide, xanthine, hypoxanthine, and caprolactam were increased compared with the normal control group. In addition, (±)8(9)-DiHET, which was initially downregulated in the diseased control group, exhibited a reversal of this trend with cysteamine nanoemulsion given via inhalation. The cysteamine nanoemulsion delivered by inhalation highlighted the importance of the route of drug administration for targeting the lungs. To the best of our knowledge, this is the first work to use ATR-FTIR and metabolomics in Wistar rat lung tissues, suggesting how cysteamine nanoemulsion can potentially reduce cigarette smoke-induced oxidative damage. The metabolites reported herein have potential implications for discovery of novel theranostics and, thus, to cultivate diagnostic and therapeutic innovation for early prevention and treatment of cigarette smoke-associated lung diseases. [ABSTRACT FROM AUTHOR]

Chronic lung disease, also known as bronchopulmonary dysplasia, affects thousands of infants worldwide each year. The impact on resources is second only to bronchial asthma, with lung function affected well into adolescence. Diagnostic and therapeutic constructs have almost exclusively focused on pulmonary architecture (alveoli/airways) and pulmonary hypertension. Information on systemic hemodynamics indicates major artery thickness/stiffness, elevated systemic afterload, and/or primary left ventricular dysfunction may play a part in a subset of infants with severe neonatal-pediatric lung disease. Understanding the underlying principles with attendant effectors would aid in identifying the pathophysiological course where systemic afterload reduction with angiotensin-converting enzyme inhibitors could become the preferred treatment strategy over conventional pulmonary artery vasodilatation. [ABSTRACT FROM AUTHOR]

Purpose of Review: The human commensal microbiota is now widely accepted as a key regulator of human health and disease. The composition of the mucosal associated microbiota has been shown to play a critical role in the lung health. The role of the mucosal microbiota in the development and severity of allergy, asthma, and occupational lung disease is only beginning to take shape. However, advances in our understanding of these links have tremendous potential to led to new clinical interventions to reduce allergy, asthma, and occupational lung disease morbidity. Recent Findings: We review recent work describing the relationship and role of the commensal microbiota in the development of allergy, asthma, and occupational lung disease. Our review primarily focuses on occupational exposures and the effects of the microbiome, both in composition and function. Data generated from these studies may lead to the development of interventions targeted at establishing and maintaining a healthy microbiota. We also highlight the role of environmental exposures and the effects on the commensal microbial community and their potential association with occupational lung disease. Summary: This review explores the current research describing the role of the human microbiome in the regulation of pulmonary health and disease, with a specific focus on the role of the mucosal microbiota in the development of allergy, asthma, and occupational lung disease. [ABSTRACT FROM AUTHOR]

Objective. To describe the clinical features of patients with congenital heart disease (CHD) who subsequently developed systemic juvenile idiopathic arthritis (sJIA). Methods. We conducted a retrospective review of patients diagnosed with CHD and sJIA at our institution. Detailed clinical, laboratory, and radiographic data were collected from the medical record and reviewed with each patient's primary medical team. Results. Five patients with sJIA and CHD were identified. Each child had a unique cardiac anatomy, but all the patients required surgical repair during the first year of life. Four children had thymectomies at the time of cardiac surgery. Classic signs of sJIA such as fever (n = 5), rash (n = 5), and arthritis (n = 4) developed after surgical intervention in all the patients. The individuals in this cohort displayed risk factors associated with severe sJIA, including disease onset before 2 years of age (n = 5), elevated interleukin 18 levels (n = 5), baseline eosinophilia prior to initiation of biologic disease-modifying antirheumatic drugs (n = 4), and positivity for HLA-DRB1*15:01 alleles (n = 4). Macrophage activation syndrome (MAS) occurred in 3 patients and sJIA-associated lung disease (sJIA-LD) was identified in 4 patients. Two children died from complications of their cardiac and/or pulmonary disease. Conclusion. We identified an association between CHD and severe forms of sJIA. Although these findings will need to be confirmed in larger, multicenter cohorts, the results highlight the importance of considering a diagnosis of sJIA in children with CHD and remaining vigilant for complications such as MAS and sJIA-LD. [ABSTRACT FROM AUTHOR]

Per- and poly-fluoroalkyl substances (PFAS) are a broad class of synthetic compounds widely used in commercial applications. The persistent nature of PFAS in the environment has earned them the epithet "forever chemicals." Concerns arise from widespread exposure to PFAS from occupational, household, and environmental sources. This widespread use of PFAS is particularly concerning, as emerging epidemiological evidence highlights their adverse effects on lung health. Such adverse impacts include impaired fetal lung development, reduced immune function in children, and potential links to lung cancer. Both in vivo and in vitro studies illuminate potential mechanisms underlying such adverse health outcomes subsequent to PFAS inhalation exposure, which may include immunomodulation, oxidative stress, and disruptions to epithelial barriers. However, evidence-based information focusing on the mechanisms of PFAS-mediated lung injury is lacking. Additionally, the discrepancies between data collected from animal and epidemiological studies highlight the need for improved approaches to better understand the toxicity results of PFAS exposure. To address these gaps, we recommend leveraging route-to-route extrapolation for risk assessment, prioritizing research on understudied PFAS, and adopting physiologically relevant, high-throughput approaches. These strategies are aimed at enhancing our understanding of PFAS inhalation effects, aiding in more informed risk management decisions. In this review, we summarize the current literature on PFAS exposure, emphasizing its adverse effects on lung health, particularly through inhalation. We then discuss the current knowledge on mechanisms underlying tissue- and cellular-level adverse outcomes caused by PFAS. [ABSTRACT FROM AUTHOR]

Copyright of Die Radiologie is the property of Springer Nature 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.)

microRNA (miR)-146a emerges as a promising post-transcriptional regulator in various inflammatory diseases with different roles for the two isoforms miR-146a-5p and miR-146a-3p. The present study aimed to examine the dual role of miR-146a-5p and miR-146a 3p in the modulation of inflammation in human pulmonary epithelial and immune cells in vitro as well as their expression in patients with inflammatory lung diseases. Experimental inflammation in human A549, HL60, and THP1 via the NF-kB pathway resulted in the major upregulation of miR-146a-5p and miR-146a-3p expression, which was partly cell-specific. Modulation by transfection with miRNA mimics and inhibitors demonstrated an anti-inflammatory effect of miR-146a-5p and a pro-inflammatory effect of miR-146a-3p, respectively. A mutual interference between miR-146a-5p and miR-146a-3p was observed, with miR-146a-5p exerting a predominant influence. In vivo NGS analyses revealed an upregulation of miR-146a-3p in the blood of patients with cystic fibrosis and bronchiolitis obliterans, while miR-146a-5p levels were downregulated or unchanged compared to controls. The reverse pattern was observed in patients with SARS-CoV-2 infection. In conclusion, miR-146a-5p and miR-146a-3p are two distinct but interconnected miRNA isoforms with opposing functions in inflammation regulation. Understanding their interaction provides important insights into the progression and persistence of inflammatory lung diseases and might provide potential therapeutic options. [ABSTRACT FROM AUTHOR]

Lactylation is a process where lactate, a cellular metabolism byproduct, is added to proteins, altering their functions. In the realm of macrophage activation, lactylation impacts inflammatory response and immune regulation. Understanding the effects of lactylation on macrophage activation is vital in lung diseases, as abnormal activation and function are pivotal in conditions like pneumonia, pulmonary fibrosis, COPD, and lung cancer. This review explores the concept of lactylation, its regulation of macrophage activation, and recent research progress in lung diseases. It offers new insights into lung disease pathogenesis and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Recent advances in Vision Transformer (ViT)-based deep learning have significantly improved the accuracy of lung disease prediction from chest X-ray images. However, limited research exists on comparing the effectiveness of different optimizers for lung disease prediction within ViT models. This study aims to systematically evaluate and compare the performance of various optimization methods for ViT-based models in predicting lung diseases from chest X-ray images. Methods: This study utilized a chest X-ray image dataset comprising 19,003 images containing both normal cases and six lung diseases: COVID-19, Viral Pneumonia, Bacterial Pneumonia, Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and Tuberculosis. Each ViT model (ViT, FastViT, and CrossViT) was individually trained with each optimization method (Adam, AdamW, NAdam, RAdam, SGDW, and Momentum) to assess their performance in lung disease prediction. Results: When tested with ViT on the dataset with balanced-sample sized classes, RAdam demonstrated superior accuracy compared to other optimizers, achieving 95.87%. In the dataset with imbalanced sample size, FastViT with NAdam achieved the best performance with an accuracy of 97.63%. Conclusions: We provide comprehensive optimization strategies for developing ViT-based model architectures, which can enhance the performance of these models for lung disease prediction from chest X-ray images. [ABSTRACT FROM AUTHOR]

Aims: Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2–3), but this group is not well‐characterized. Methods and results: Patients with PH enrolled in the prospective, NHLBI‐sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2–3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2–3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2–3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2–3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N‐terminal pro‐B‐type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2–3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6‐min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30–0.86), and patients with G2–3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38–0.86). Conclusions: Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2–3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease. Clinical Trial Registration: ClinicalTrials.gov NCT02980887. [ABSTRACT FROM AUTHOR]

High oxygen (hyperoxia) concentration may damage multiple organs and systems in newborns, such as the lung, brain and intestines. Metabolic abnormalities are important early events in the pathogenesis of neonatal hyperoxia related pulmonary diseases. This article reviews the increased glucose and lipid metabolism as well as dys-regulation of amino acid metabolism after hyperoxia related bronchopulmonary dysplasia in newborns. The potential mechanism may be that the high oxygen concentration increases formation of mitochondrial reactive oxygen species (mtROS), and also change the mitochondrial dynamics of neonatal bronchopulmonary dysplasia, leading to reduction of mitochondrial fusion, enhances fission and autophagy. This study also finds that many metabolism-related enzymes and metabolites are changed during hyperoxia related diseases. However, clinical research has not yet been conducted. Future research should focus on combining metabolic profiles with multi omies data, including transcriptome sequencing, genomics and proteomics to identify potential biomarkers and therapeutic targets for hyperoxia related neonatal lung injury in order to develop new strategies for the treatment of metabolic abnormalities resulted from neonatal hyperoxia related pulmonary diseases. [ABSTRACT FROM AUTHOR]

Copyright of Informatics Control Measurement in Economy & Environment Protection / Informatyka, Automatyka, Pomiary w Gospodarce i Ochronie Środowiska is the property of Lublin University of Technology 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.)

Background: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. Method: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. Results: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. Conclusions: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. Trial registration: www.clinicaltrials.gov (ID: NCT04180319). [ABSTRACT FROM AUTHOR]

Pleural mesothelioma (PM) is a highly aggressive tumor that is caused by asbestos exposure and lacks effective therapeutic regimens. Current procedures for PM diagnosis are invasive and can take a long time to reach a definitive result. Small extracellular vesicles (sEVs) have been identified as important communicators between tumor cells and their microenvironment via their cargo including circular RNAs (circRNAs). CircRNAs are thermodynamically stable, highly conserved, and have been found to be dysregulated in cancer. This study aimed to identify potential biomarkers for PM diagnosis by investigating the expression of specific circRNA gene pattern (hsa_circ_0007386) in cells and sEVs using digital polymerase chain reaction (dPCR). For this reason, 5 PM, 14 non-PM, and one normal mesothelial cell line were cultured. The sEV was isolated from the cells using the gold standard ultracentrifuge method. The RNA was extracted from both cells and sEVs, cDNA was synthesized, and dPCR was run. Results showed that hsa_circ_0007386 was significantly overexpressed in PM cell lines and sEVs compared to non-PM and normal mesothelial cell lines (p < 0.0001). The upregulation of hsa_circ_0007386 in PM highlights its potential as a diagnostic biomarker. This study underscores the importance and potential of circRNAs and sEVs as cancer diagnostic tools. [ABSTRACT FROM AUTHOR]

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15–20 min) and intratracheal administration (6–50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP. [ABSTRACT FROM AUTHOR]

The aim of this multi-part article is straightforward -- to provide a comprehensive understanding of the acupuncture point Chĭ Zé (LU-5). In order to achieve this, we will break down the information into five main categories of knowledge: overview of the point, diseases and indications, successional literature, modern masters and case studies. In Part 1 of the article, we will cover up to the first half of the successional literature. [ABSTRACT FROM AUTHOR]

Objective: To estimate the lung ultrasound (LUS0) scores within 6 hours of birth in neonates with respiratory distress (RD) and assess its ability to predict the severity of RD. Methods: This single-center cross-sectional study included all neonates admitted with RD during the study period for whom a LUS was performed within 6h of birth. LUS0 scoring was done by dividing the lung fields into 3 fields on either side and a score from 0 to 3 per field (maximum score 18). We excluded neonates with congenital heart disease, congenital anomalies of chest/lung, chromosomal anomalies and if the operator for LUS0 was not available. ROC curves were constructed for estimating the cut-off LUS0 score for the severity of RD in terms of the following six outcomes: fraction of inspired oxygen (FiO2) requirement >50% during first 3 days of life, need for invasive ventilation on day 3 of life, Silverman-Anderson score >7, surfactant requirement, radiological grades of RDS, and death. Results: The median (IQR) LUS0 scores were significantly higher in neonates with greater severity of RD in terms of FiO2 requirement >50% during first 3 days of life [12.0, (5.0, 14.0)], need for invasive ventilation on day 3 of life [12.0 (7.5, 12.5)], Silverman-Anderson score ≥ 7 in preterm [9.5, (6.0, 12.0)], surfactant requirement [11.5, (4.0, 12.5)], radiological grades of RDS [10.0, (4.0, 12.0)], and death [12.0, (7.0, 15.0)]. In logistic regression analysis, with continuous LUS0 scores as covariates, the odds ratio significantly increased for every unit increase in LUS0 score. Conclusion: Early LUS0 scores can predict the prognosis and severity of neonatal RD. [ABSTRACT FROM AUTHOR]

Exercise intolerance and dyspnoea are clinical symptoms in both heart failure (HF) reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD), which are suggested to be associated with musculoskeletal dysfunction. We tested the hypothesis that HFrEF + COPD patients would present lower muscle strength and greater fatigue compared to compared to the COPD group. We included 25 patients with HFrEF + COPD (100% male, age 67.8 ± 6.9) and 25 patients with COPD alone (100% male, age 66.1 ± 9.1). In both groups, COPD severity was determined as moderate-to-severe according to the GOLD classification (FEV1/FVC < 0.7 and predicted post-bronchodilator FEV1 between 30%-80%). Knee flexor–extensor muscle performance (torque, work, power and fatigue) were measured by isokinetic dynamometry in age and sex-matched patients with HFrEF + COPD and COPD alone; Functional capacity was assessed by the cardiopulmonary exercise test, the 6-min walk test (6MWT) and the four-minute step test. The COPD group exhibited reduced lung function compared to the HFrEF + COPD group, as evidenced by lower FEV1/FVC (58.0 ± 4.0 vs. 65.5 ± 13.9; p < 0.0001, respectively) and FEV1 (51.3 ± 17.0 vs. 62.5 ± 17.4; p = 0.026, respectively) values. Regarding musculoskeletal function, the HFrEF + COPD group showed a knee flexor muscles impairment, however this fact was not observed in the knee extensors muscles. Power peak of the knee flexor corrected by muscle mass was significantly correlated with the 6MWT (r = 0.40; p < 0.05), number of steps (r = 0.30; p < 0.05) and work ratepeak (r = 0.40; p < 0.05) in the HFrEF + COPD and COPD groups. The presence of HFrEF in patients with COPD worsens muscular weakness when compared to isolated COPD. [ABSTRACT FROM AUTHOR]

Purpose of Review: Chronic obstructive pulmonary disease (COPD) is common in heart failure (HF), and it has a significant impact on the prognosis and quality of life of patients. Additionally, COPD is independently associated with lower adherence to first-line HF therapies. In this review, we outline the challenges of identifying and managing HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction with coexisting COPD. Recent Findings: Spirometry is necessary for COPD diagnosis and prognosis but is underused in HF. Therefore, misdiagnosis is a concern. Also, disease-modifying drugs for HF and COPD are usually safe but underprescribed when HF and COPD coexist. Summary: Patients with HF-COPD are poorly enrolled in clinical trials. Guidelines recommend that HF treatment should be offered regardless of COPD presence, but modern registries show that undertreatment persists. Treatment gaps could be attenuated by ensuring an accurate and earlier COPD diagnosis in patients with HF, clarifying the concerns related to pharmacotherapy safety, and increasing the use of non-pharmacologic treatments. Acknowledging the uncertainties, this review aims to provide key clinical resources to support better physician-patient co-decision-making and improve collaboration between health professionals. [ABSTRACT FROM AUTHOR]

Early detection of lung disease is important for timely intervention and treatment, enhancing patient outcomes and decreasing healthcare cost. Chest X-rays are a widely employed imaging modality to examine the structures within the chest, including the lungs and surrounding tissues. Lung disease detection using chest X-rays is a critical application of medical imaging and artificial intelligence (AI) in healthcare. Recently, lung disease detection using deep learning (DL) becomes a significant research area, which has the potential to improve early detection rate and decrease mortality rate. Therefore, this article introduces a Multi-Feature Fusion Based Deep Transfer Learning with Enhanced Dung Beetle Optimization Algorithm (MFFTL-EDBOA) for lung disease detection and classification. The MFFTL-EDBOA technique aims to recognize the existence of lung diseases on CXR images. At the primary stage, the MFFTL-EDBOA technique uses adaptive filtering (AF) approach to remove the noise level. Besides, a multi-feature fusion-based feature extraction approach is developed based on three DL models namely DenseNet, EfficientNet, and MobileNet. For accurate lung disease detection and classification purposes, the convolutional fuzzy neural network (CFNN) approach is utilized. The hyperparameter tuning of the CFNN model occurs using the EDBOA. To illustrate the enhanced lung disease detection results of the MFFTL-EDBOA technique, a sequence of experiments is carried out on benchmark medical dataset from Kaggle repository. The experimental values highlighted the greater result of the MFFTL-EDBOA system over other recent approaches with maximum accuracy of 98.99%. [ABSTRACT FROM AUTHOR]

IntroductionSeveral studies report that pulmonary oxygen uptake (V̇O 2 ) at the respiratory compensation point (RCP) is equivalent to the V̇O 2 at critical power (CP), suggesting that the variables can be used interchangeably to demarcate the threshold between heavy and severe intensity domains. However, if RCP is a valid surrogate for CP, their values should correspond even when assessed in patients with chronic obstructive pulmonary disease (COPD) in whom the "normal" mechanisms linking CP and RCP are impeded. The aim of this study was to compare V̇O 2 at CP with V̇O 2 at RCP in patients with COPD.MethodsTwenty-two COPD patients (14 male/8 female; forced expiratory volume in 1 s, 46% ± 17% pred) performed ramp-incremental cycle ergometry to intolerance (5-10 W·min -1 ) for the determination of gas exchange threshold (GET) and RCP. CP was calculated from the asymptote of the hyperbolic power-duration relationship from 3-5 constant-power exercise tests to intolerance. CP was validated with a 20-min constant-power ride.ResultsGET was identified in 20 of 22 patients at a V̇O 2 of 0.93 ± 0.18 L·min -1 (75% ± 13% V̇O 2peak ), whereas RCP was identified in just 3 of 22 patients at a V̇O 2 of 1.40 ± 0.39 L·min -1 (85% ± 2% V̇O 2peak ). All patients completed constant-power trials with no difference in peak physiological responses relative to ramp-incremental exercise ( P > 0.05). CP was 46 ± 22 W, which elicited a V̇O 2 of 1.04 ± 0.29 L·min -1 (90% ± 9% V̇O 2peak ) during the validation ride. The difference in V̇O 2 at 15 and 20 min of the validation ride was 0.00 ± 0.04 L, which was not different from a hypothesized mean of 0 ( P = 0.856), thereby indicating a V̇O 2 steady state.ConclusionsIn COPD patients, who present with cardiopulmonary and/or respiratory-mechanical dysfunction, CP can be determined in the absence of RCP. Accordingly, CP and RCP are not equivalent in this group.

A patient with GATA2 deficiency developed corticosteroid-responsive sterile granulomatous lung disease despite monocytopenia. The presence of B-lymphopenia, autoimmunity, an elevated level of serum B-cell–activating factor, and pulmonary plasma cell infiltration, which together suggested an underlying mechanism similar to that of combined variable immunodeficiency lung disease.

DNA plays an indispensable role in ensuring the perpetuation of life and safeguarding the genetic stability of living organisms. The emergence of diseases linked to a wide spectrum of responses to DNA damage has garnered increasing attention within the scientific community. There is growing evidence that patterns of DNA damage response in the lungs are associated with the onset, progression, and treatment of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and bronchopulmonary dysplasia (BPD). Currently, some studies have analyzed the mechanisms by which environmental factors induce lung DNA damage. In this article, we summarize inducible factors of lung DNA damage, current indicators, and methods for diagnosing DNA damage in chronic lung diseases and explore repair mechanisms after DNA damage including nonhomologous end-joining and homology-directed repair end joining pathways. Additionally, drug treatments that may reduce DNA damage or promote repair after it occurs in the lungs are briefly described. In general, more accurate assessment of the degree of lung DNA damage caused by various factors is needed to further elucidate the mechanism of lung DNA damage and repair after damage, so as to search for potential therapeutic targets.

Abstract Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high‐resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non‐fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non‐IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group‐wise analyses of metabolites altered in ILD phenotypes. We utilized limma one‐way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p‐values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl‐hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non‐ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis.