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RATIONALE: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. OBJECTIVE: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. METHODS: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). RESULTS: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohens Kappa = 0.47 ± 0.07; P

BackgroundSkeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD.MethodsForty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype.ResultsAbnormal myofibre proportion was defined in males with COPD (n = 29) as 22% type IIx/IIax fibres and in females with COPD (n = 17) as 12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density.ConclusionsOur findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

BACKGROUND: In tobacco-exposed persons with preserved spirometry (active smoking or secondhand smoke [SHS] exposure), air trapping can identify a subset with worse symptoms and exercise capacity. The physiologic nature of air trapping in the absence of spirometric airflow obstruction remains unclear. The aim of this study was to examine the underlying pathophysiology of air trapping in the context of preserved spirometry and to determine the utility of bronchodilators in SHS tobacco-exposed persons with preserved spirometry and air trapping. METHODS: We performed a double-blinded placebo-controlled crossover randomized clinical trial in nonsmoking individuals at risk for COPD due to exposure to occupational SHS who had preserved spirometry and air trapping defined as either a residual volume-to-total lung capacity ratio (RV/TLC) > 0.35 or presence of expiratory flow limitation (EFL, overlap of tidal breathing on maximum expiratory flow-volume loop) on spirometry at rest or during cardiopulmonary exercise testing (CPET). Those with asthma or obesity were excluded. Participants underwent CPET at baseline and after 4-week trials of twice daily inhalation of 180 mcg of albuterol or placebo separated by a 2-week washout period. The primary outcome was peak oxygen consumption (VO2) on CPET. Data was analyzed by both intention-to-treat and per-protocol based on adherence to treatment prescribed. RESULTS: Overall, 42 participants completed the entire study (66 ± 8 years old, 91% female; forced expiratory volume in 1 s [FEV1] = 103 ± 16% predicted; FEV1 to forced vital capacity [FVC] ratio = 0.75 ± 0.05; RV/TLC = 0.39 ± 0.07; 85.7% with EFL). Adherence was high with 87% and 93% of prescribed doses taken in the treatment and placebo arms of the study, respectively (P = 0.349 for comparison between the two arms). There was no significant improvement in the primary or secondary outcomes by intention-to-treat or per-protocol analysis. In per-protocol subgroup analysis of those with RV/TLC > 0.35 and ≥ 90% adherence (n = 27), albuterol caused an improvement in peak VO2 (parameter estimate [95% confidence interval] = 0.108 [0.014, 0.202]; P = 0.037), tidal volume, minute ventilation, dynamic hyperinflation, and oxygen-pulse (all P

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Overlap Syndrome (OS), the co-occurrence of Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease. Clustering of patients in subgroups with similar pre-clinical manifestations (ie, endothelial dysfunction) may identify relevant therapeutic phenotype categories for patients with OS who are at high risk of CVD. We therefore conducted a cross-sectional pilot study of endothelial function in 7 patients with OS (Forced Expiratory Volume in 1 second/Forced Vital Capacity < 0.7) on continuous positive airway pressure therapy (n = 7) to assess the relationship between FMD and physical activity. We found a strong association between FMD and step counts (rho = 0.77, p = 0.04); and FMD and moderate physical activity (rho = 0.9, p = 0.005). Further, larger studies are needed to confirm that FMD may identify patients with OS at high risk of CVD who benefit from increased physical activity.

Introduction: The homeostasis of the microbiome in lower respiratory tract is crucial in sustaining normal physiological functions of the lung. Different pulmonary diseases display varying degrees of microbiome imbalance; however, the specific variability and clinical significance of their microbiomes remain largely unexplored. Methods: In this study, we delineated the pathogen spectrum and commensal microorganisms in the lower respiratory tract of various pulmonary diseases using metagenomic sequencing. We analyzed the disparities and commonalities of the microbial features and examined their correlation with disease characteristics. Results: We observed distinct pathogen profiles and a diversity in lower airway microbiome in patients diagnosed with cancer, interstitial lung disease, bronchiectasis, common pneumonia, Nontuberculous mycobacteria (NTM) pneumonia, and severe pneumonia. Discussion: This study illustrates the utility of Metagenomic Next-generation Sequencing (mNGS) in identifying pathogens and analyzing the lower respiratory microbiome, which is important for understanding the microbiological aspect of pulmonary diseases and essential for their early and precise diagnosis. [ABSTRACT FROM AUTHOR]

Mitochondria are dynamic organelles that continuously undergo fusion/fission to maintain normal cell physiological activities and energy metabolism. When mitochondrial dynamics is unbalanced, mitochondrial homeostasis is broken, thus damaging mitochondrial function. Accumulating evidence demonstrates that impairment in mitochondrial dynamics leads to lung tissue injury and pulmonary disease progression in a variety of disease models, including inflammatory responses, apoptosis, and barrier breakdown, and that the role of mitochondrial dynamics varies among pulmonary diseases. These findings suggest that modulation of mitochondrial dynamics may be considered as a valid therapeutic strategy in pulmonary diseases. In this review, we discuss the current evidence on the role of mitochondrial dynamics in pulmonary diseases, with a particular focus on its underlying mechanisms in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis (PF), pulmonary arterial hypertension (PAH), lung cancer and bronchopulmonary dysplasia (BPD), and outline effective drugs targeting mitochondrial dynamics‐related proteins, highlighting the great potential of targeting mitochondrial dynamics in the treatment of pulmonary disease. [ABSTRACT FROM AUTHOR]

Since its discovery in 1957, respiratory syncytial virus (RSV) has been widely recognized as a common and deadly pathogen. Although early studies focused on the impact of RSV on the health of children, more recent data show that RSV imposes a significant burden on individuals aged ≥ 70 years. RSV also substantially harms the health of individuals with cardiopulmonary diseases. Early efforts to develop an RSV vaccine were hampered by toxicity due to antibody-enhanced viral pneumonia and a lack of efficacy in vaccines that targeted the postfusion configuration of the F fusion protein, which is crucial to the pathogenesis of RSV-mediated injury. A newer wave of vaccines has targeted a stabilized prefusion F protein, generating effective neutralizing antibodies and reducing the burden of mild and severe RSV lower respiratory tract injury. This review focuses on the burden of RSV in patients with pulmonary diseases, highlights the tumultuous path from the early days of RSV vaccine development to the modern era, and offers insights into key gaps in knowledge that must be addressed to adequately protect the vulnerable population of patients with severe pulmonary diseases. RSV vaccination with bivalent RSVPreF or RSVPreF3OA, which target the stabilized prefusion F protein, can be broadly recommended to adults aged ≥ 60 years with pulmonary diseases. However, more data are needed to understand how these vaccinations affect key clinical outcomes in individuals with pulmonary disease. [ABSTRACT FROM AUTHOR]

Family caregivers care for individuals in the home environment. Family caregivers of individuals with chronic obstructive pulmonary disease (COPD) observe breathlessness in the care recipient. Breathlessness is a main symptom of COPD, and watching breathlessness creates emotional distress and a toll on family caregivers. The purpose of this integrative review was to explore the literature on family caregivers and witnessed breathlessness in individuals with COPD. An understanding of family caregiver experiences of breathlessness will allow for further development of evidence-based practice and research. An integrative review was performed using the five-step process of the Whittemore and Knafl Integrative Review Model. Literature search results were reported using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. An overarching theme of constant care and burden resulted from the 18 studies on family caregivers and witnessed breathlessness in individuals with COPD. Three themes: psychosocial implications of caregivers, response ambiguity, and knowledge of interventions represented family caregivers and breathlessness in the care recipient among the studies. This integrative review provides insight on family caregivers and witnessed breathlessness in individuals with COPD. An understanding of the family caregiver perception of breathlessness in the care recipient can help home healthcare professionals empathize with and offer support specific to the needs of family caregivers of individuals with breathlessness from COPD, heart failure, and other chronic diseases. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-28 （MMP-28） is widely expressed in vertebrates and plays diverse biological roles, participating in the regulation of various pathophysiological processes in the body. Increased expression of MMP-28 has been observed in chronic obstructive pulmonary disease, pulmonary fibrosis, and other lung diseases. Studies have demonstrated that MMP-28 promotes chronic inflammation and tissue remodeling by regulating macrophage recruitment and M2 polarization, and is involved in the pathogenesis of lung diseases by promoting cell proliferation and epithelial-mesenchymal transition. This article provides a review of the relationship between the basic characteristics of MMP-28 and pulmonary diseases. [ABSTRACT FROM AUTHOR]

Medical imaging is an indispensable and very important step in the diagnosis and treatment of illnesses. However, due to large amounts of resources necessary for training the model, training from scratch may not invariably emerge as the optimal recourse. Transfer learning has emerged as a viable solution, where pretrained weights from ImageNet are initially utilized and fine-tuninned afterwards. This paper presents a novel approach employing transfer learning to classify both respiratory diseases and radiological findings from chest X-rays. The dataset comprises 191 660 X-ray images gathered from public databases and 752 chest X-ray images obtained from a retrospective study at the University Clinical Center of Kragujevac, forming the foundation of Big data analysis. It includes various conditions such as atelectasis, cardiomegaly, infiltration, pleural thickening, non-viral pneumonia, pneumothorax, COVID-19 viral pneumonia, tuberculosis, etc. as well as masses and nodules indicative of tumors and images of healthy subjects. Although there are existing solutions with some diseases, this is the first paper that inlcludes differentiation between healthy and diseased cases, as well as in case of present disease, as much as 18 different classes are inlcuded in the analysis, which has not been done so far. The proposed methodology included transfer learning with DenseNet121 as the backbone and CheXNeXt weights as initialisation scheme, upon which additional layers were added for fine tuning. The results demonstrate the model's capacity to distinguish between healthy and diseased, with an average area under curve (AUC) of 0.99. The AUC ranges from 0.86 for nodules to 0.99 for pneumonia and 0.99 for COVID-19. Our method outperforms the state-of-the-art in accuracy across all 18 classes, with the exception of classes consolidation, mass, and nodule. These findings are promising for a tested clinical site, though further validation in clinical environment accros multiple sites may be necessary before using the model as a standalone decision system, rather than a decision support system for disease diagnosis based on chest X-rays. [ABSTRACT FROM AUTHOR]

Background/Objectives: Pulmonary diseases are common in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Although high prevalences of chronic obstructive pulmonary disease and lung cancer (LC) are known, the prevalence of these and other pulmonary diseases regarding their relation to the outcome of TAA and/or AAA are not determined. Methods: Pulmonary diseases present at aortic aneurysm (AA) diagnosis and follow-up periods and cause of death of 952 patients with TAA, AAA, or TAA + AAA (including thoracoabdominal AA) treated at our institution in Japan were retrospectively analyzed. Cox regression analysis was used to investigate potential risk factors of mortality. Results: The mean patient age was 72.4 years, and the median follow-up was 4.92 years. At diagnosis, 528 (55.5%) patients had pulmonary diseases, including emphysema without interstitial lung disease (ILD) or LC, LC, idiopathic pulmonary fibrosis (IPF) without LC, non-IPF ILD without LC, and interstitial lung abnormalities (ILAs) without LC in 250, 85, 65, 15, and 58 patients, respectively. During follow-up, LC and acute exacerbation (AE) of IPF developed in 50 and 12 patients, respectively. In 213 patients who died, there were 45 (21.1%) aortic disease-related deaths. Other causes of death included LC (27.7%), cardiovascular events (9.4%), pneumonia (5.6%), and interstitial lung disease (4.7%). In a multivariate Cox regression hazard model, age; larger maximum aneurysm diameter; and coexisting LC, IPF, or concomitant cancer were associated with poor prognosis. Conclusions: In patients with AA, not only age and aneurysm diameter but also coexisting LC and IPF were prognostic factors for mortality. [ABSTRACT FROM AUTHOR]

Background The therapeutic challenges posed by nontuberculous mycobacterial pulmonary disease (NTM-PD) contribute to an unmet medical need. In this study, we aimed to investigate NTM-PD–specific metabolic pathways using serum metabolomics to understand disease pathogenesis. Methods Mass spectrometry–based untargeted metabolomic profiling of serum from patients with NTM-PD (n = 50), patients with bronchiectasis (n = 50), and healthy controls (n = 60) was performed. Selected metabolites were validated by an independent cohort and subjected to pathway analysis and classification modeling. Results Leucine, tyrosine, inosine, proline, 5-oxoproline, and hypoxanthine levels increased in the NTM-PD group compared with the healthy control group. Furthermore, levels of antioxidant metabolites (ferulic acid, α-lipoic acid, biotin, and 2,8-phenazinediamine) decreased in patients with NTM-PD. These changes were associated with arginine- and proline-related metabolism, leading to generation of reactive oxygen species. Interestingly, the observed metabolic changes in the NTM-PD group overlapped with those in the bronchiectasis group. Conclusions In NTM-PD, 11 metabolites linked to increased oxidative stress were significantly altered from those in healthy controls. Our findings enhance a comprehensive understanding of NTM-PD pathogenesis and provide insights for novel treatment approaches. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a debilitating condition that significantly impacts patients' quality of life (QoL). Mindfulness-based stress reduction (MBSR) is a complementary therapy for chronic conditions. This study aimed to assess the efficacy of an eight-weekMBSR program in improving QoL, self-compassion, mindfulness, depression, and anxiety among COPD patients. Methods: A randomized controlled trial was conducted with 120 COPD patients allocated to either an MBSR intervention group (n = 60) or a control group (CG) receiving standard care (n = 60). The MBSR program consisted of weekly 2.5-hour sessions for eight weeks. The primary outcome was the change in St. George's Respiratory Questionnaire (SGRQ) total scores from baseline to post-intervention. Secondary outcomes included changes in the Hospital Anxiety and Depression Scale (HADS), Five Facet Mindfulness Questionnaire (FFMQ), and Self-Compassion Scale (SCS) scores. Assessments were conducted at baseline, post-intervention, and three months follow-up. Results: The MBSR group showed a significantly greater reduction in SGRQ total scores (-12.4 ± 8.7) compared to the CG (P < 0.001) at post-intervention. Significant improvements were also observed in the MBSR group relative to the CG for HADS-Anxiety (change: -3.5 ± 2.8, P < 0.001), HADS-Depression (change: -3.1 ± 2.6, P < 0.001), FFMQ total (change: 22.3 ± 12.5, P < 0.001), and SCS total (change: 15.7 ± 10.2, P < 0.001) scores at post-intervention. The improvements were maintained at the three months follow-up (all P< 0.001). Conclusion: An 8-week MBSR program significantly improves QoL, depression, anxiety, mindfulness, and self-compassion in COPD patients compared to standard care alone. These findings support the integration of mindfulness-based interventions into the standard care of COPD patients. Further research is needed to validate these findings and explore the optimal implementation of MBSR in COPD care. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multi organ involvement. One of the most common manifestations is pulmonary disease with a reported prevalence between 5%–90%. Purpose: Given this wide range of prevalence, there is a need to more closely define types of pulmonary disease in SLE and associated risk factors. Research Design: We sought to characterize the presentation of pulmonary manifestations in an established SLE cohort using electronic health record data. Study Sample: All patients were >18 years of age and had confirmed SLE by a rheumatologist using SLICC or 2019 ACR/EULAR classification criteria. 220 patients with imaging were included in this study; average age was 42.5 years, 86.7% identified as female, 60.5% identified as white, 37.3% as Black, and 1.82% as Asian. Analysis: Generalized estimating equations were utilized to analyze the data, accounting for its repeated measured nature. Results: We found an association between smoking (present/prior smoker) and radiologist reported disease on computerized tomography (CT) scan, as well as an association between smoking (present/prior smoker), older age, and male sex with having pulmonary disease identified on chest X-ray. The most common findings on CT and X-ray were increased lung density (24%, 12%) and atelectasis (18%, 10%). The most common disease found on CT was pleural effusion (24%) and mediastinal/axillary lymphadenopathy (16%). Conclusion: While our study is limited by the retrospective nature, our results show that certain factors, namely smoking, older age, or male sex should prompt clinicians to have a higher suspicion for lung disease in SLE patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Continuous monitoring of pulse oximetry (...) is recommended during the 6-min walk test (6MWT) to ensure that the lowest ... is recorded. In this case, severe exercise-induced desaturation (EID; ... < 80%) triggers walking interruption by the examiner. Our main objective was to assess the impact of this approach on 6MWT distance in patients with chronic respiratory diseases and, second, to evaluate the safety of the test without interruption due to severe EID. METHODS: 6MWTs with continuous monitoring of ... were prospectively performed in subjects with chronic respiratory disease. The participants were randomly allocated to walk with or without ... real-time assessment. ... visualization during the test execution was available only in the first group, and walking interruption was requested by the examiner if ... < 80%. RESULTS: One hundred forty-five participants were included in each group (68.6% females, 62 [52-69] y old) without differences in demographic and resting lung function parameters between them. The main respiratory conditions were COPD (n = 101), asthma (n = 73), pulmonary hypertension (n = 47), and interstitial lung disease (n = 39). The walked distance was similar comparing groups (349.5 ± 117.5 m vs 351.2 ± 105.4 m). Twenty-five subjects presented with severe EID in the group with real-time ... assessment, and 20 subjects had severe EID in the group without real-time assessment respectively (overall prevalence of 15.5%). The 23 participants who had their test interrupted by the examiner due to severe EID in the first group (2 subjects stopped by themselves due to excessive symptoms) walked a shorter distance compared to the 11 subjects with severe EID without test interruption in the second group (9 subjects stopped by themselves due to excessive symptoms): 240.6 ± 100.2 m versus 345.9 ± 73.4 m. No exercise-related serious adverse events were observed. CONCLUSIONS: Interruption driven by severe EID reduced the walked distance during the 6MWT. No serious adverse event, in turn, was observed in subjects with severe desaturation without real-time ... assessment. [ABSTRACT FROM AUTHOR]

Summary Because some hypnotics worsen respiratory conditions, it was important to determine the respiratory safety of lemborexant, a competitive dual orexin‐receptor antagonist approved to treat adults with insomnia, in subjects with moderate‐to‐severe chronic obstructive pulmonary disease. E2006‐A001‐113 (Study 113; NCT04647383) was a multicentre, multiple‐dose, randomised, double‐blind, placebo‐controlled, two‐period crossover study in adult subjects with moderate or severe chronic obstructive pulmonary disease (per spirometry‐based Global Initiative for Chronic Obstructive Lung Disease [GOLD] criteria). Subjects (N = 30) were randomised to two treatment sequences comprising 8‐night treatment periods (washout ≥ 14 days) with lemborexant 10 mg or placebo. Peripheral oxygen saturation (SpO2; primary endpoint), apnea–hypopnea index, objective sleep parameters and sleep architecture measures were assessed after single (Day 1) and multiple (Day 8) doses. There was no significant difference in least‐squares mean SpO2 after a single dose of lemborexant (91.1%) versus placebo (91.5%). Although a statistically significant difference in SpO2 was observed after multiple doses (least‐squares mean: lemborexant, 91.3%; placebo, 90.8%) favouring lemborexant, this was not considered clinically meaningful. Apnea–hypopnea index was not significantly different between treatments after single or multiple doses. Total sleep time and total rapid eye movement sleep were significantly greater on Days 1 and 8 with lemborexant versus placebo. Treatment‐emergent adverse events were reported in five (16.7%) subjects when taking lemborexant and four (13.3%) subjects when taking placebo; treatment‐emergent adverse events were mostly mild. Lemborexant was well tolerated and did not adversely impact SpO2 or apnea–hypopnea index after single and multiple doses relative to placebo in subjects with moderate‐to‐severe chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Highlights Doppler ultrasound may be used to assess leg blood flow (Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$), but the reliability of this method remains unexplored in patients with chronic obstructive pulmonary disease (COPD), where between‐subject variability may be larger than healthy due to peripheral vascular changes. This study aimed to investigate the reliability of Doppler ultrasound in quantifying Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ during single‐leg knee‐extensor exercise (KEE) in COPD patients compared with those obtained from healthy matched controls. In this case–control study, 16 participants with COPD were matched based on sex and age with 16 healthy controls. All participants underwent measurement of Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ using Doppler ultrasound in a KEE set‐up at various intensities on two separate visits. Confounding factors on Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ were controlled for, and the ultrasound scans were consistently performed by the same sonographer. During exercise, smallest real difference (SRD) ranged from 367 mL to 583 mL in COPD and 438 mL to 667 mL in the control group. The coefficient of variation (CV) ranged from 7.9% to 14.3% in COPD and 9.4% to 10.4% in the control group. The intraclass correlation coefficient ranged from 0.75 to 0.92 in COPD and 0.67 to 0.84 in the control group. CV was lower in the control group during exercise at 0 W, but apart from that, reliability was not different between groups during exercise. Doppler ultrasound showed nearly equal reliability when evaluating Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$ in COPD patients and healthy individuals with a CV below 15% during exercise for both groups. What is the central question of this study? What is the between‐day reliability of Doppler ultrasound when quantifying leg blood flow during single‐leg knee‐extensor exercise in COPD patients compared to healthy matched controls? What is the main finding and its importance? This study demonstrates a coefficient of variation ranging from 7.9 to 14.3% during single‐leg knee‐extensor exercise for between‐day reliability when applying Doppler ultrasound to assess leg blood flow in patients with COPD. Furthermore, it offers insights into the peripheral circulatory constraints in COPD, as evidenced by diminished leg blood flow. This study is the first of its kind to evaluate the reliability of Doppler ultrasound in the assessment of the peripheral circulation during exercise in COPD. What is the central question of this study?What is the between‐day reliability of Doppler ultrasound when quantifying leg blood flow during single‐leg knee‐extensor exercise in COPD patients compared to healthy matched controls?What is the main finding and its importance?This study demonstrates a coefficient of variation ranging from 7.9 to 14.3% during single‐leg knee‐extensor exercise for between‐day reliability when applying Doppler ultrasound to assess leg blood flow in patients with COPD. Furthermore, it offers insights into the peripheral circulatory constraints in COPD, as evidenced by diminished leg blood flow. This study is the first of its kind to evaluate the reliability of Doppler ultrasound in the assessment of the peripheral circulation during exercise in COPD. [ABSTRACT FROM AUTHOR]

Background: The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. Methods: This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40–80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. Results: Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. Conclusions: Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects. [ABSTRACT FROM AUTHOR]

Geometrical models of the airways offer a comprehensive perspective on the complex interplay between lung structure and function. Originating from mathematical frameworks, these models have evolved to include detailed lung imagery, a crucial enhancement that aids in the early detection of morphological changes in the airways, which are often the first indicators of diseases. The accurate representation of airway geometry is crucial in research areas such as biomechanical modeling, acoustics, and particle deposition prediction. This review chronicles the evolution of these models, from their inception in the 1960s based on ideal mathematical constructs, to the introduction of advanced imaging techniques like computerized tomography (CT) and, to a lesser degree, magnetic resonance imaging (MRI). The advent of these techniques, coupled with the surge in data processing capabilities, has revolutionized the anatomical modeling of the bronchial tree. The limitations and challenges in both mathematical and image-based modeling are discussed, along with their applications. The foundation of image-based modeling is discussed, and recent segmentation strategies from CT and MRI scans and their clinical implications are also examined. By providing a chronological review of these models, this work offers insights into the evolution and potential future of airway geometry modeling, setting the stage for advancements in diagnosing and treating lung diseases. This review offers a novel perspective by highlighting how advancements in imaging techniques and data processing capabilities have significantly enhanced the accuracy and applicability of airway geometry models in both clinical and research settings. These advancements provide unique opportunities for developing patient-specific models. [ABSTRACT FROM AUTHOR]

Purpose:This study examined the effectiveness and safety of a home-based pulmonary rehabilitation (HBPR) program in Veterans. Methods:Patients were evaluated from five Veteran Affairs facilities that enrolled in the 12-week program. Pre- to postchanges were completed on clinical outcomes using paired t-tests and the Wilcoxon signed rank sum test. Descriptive statistics were used for patient demographics, emergency room visits, and hospitalizations. Results:Two hundred eighty-five patients with a mean age of 69.6 ± 8.3 years enrolled in the HBPR program from October 2018 to March 2020. There was a 62% (n = 176) completion rate of both pre- and post assessments. Significant improvements were detected after completion of the HBPR program in dyspnea (modified Medical Research Council: 3.1 ± 1.1 vs. 1.9 ± 1.1; p < 0.0001); exercise capacity (six-minute walk distance: 263.1 m ± 96.6 m vs. 311.0 m ± 103.6 m; p < 0.0001; Duke Activity Status Index: 13.8 ± 9.6 vs. 20.0 ± 12.7; p < 0.0001; self-reported steps per day: 1514.5 ± 1360.4 vs. 3033.8 ± 2716.2; p < 0.0001); depression (patient health questionnaire-9: 8.3 ± 5.7 vs. 6.4 ± 5.1); nutrition habits (rate your plate, heart: 45.3 ± 9.0 vs. 48.9 ± 9.2; p < 0.0001); multicomponent assessment tools (BODE Index: 5.1 ± 2.5 vs. 3.4 ± 2.4; p < 0.0001), GOLD ABCD Assessment: p < 0.0009); and quality of life (chronic obstructive pulmonary disease assessment test: 25.4 ± 7.7 vs. 18.7 ± 8.5; p < 0.0001). No adverse events were reported due to participation in HBPR. Conclusions:The HBPR program is a safe and effective model and provides an additional option to address the gap in pulmonary rehabilitation access and utilization in the Veterans Affairs. [ABSTRACT FROM AUTHOR]

In accordance to the World Health Organization (WHO), various pulmonary diseases cause thousands of deaths annually. The early diagnosis is required to lessen the mortality rate. For this reason, A Convolutional Neural Network (CNN)-based Lung Disease (LD) detection system is developed to classify segregated lung sections into various pulmonary diseases types. However, epistemic uncertainty in the scanned images affecting the performance of detection classifiers. Hence, in this paper, a multi-modal approach is proposed to solve the epistemic uncertainty issue and provides a reliable solution for rapid detection of various LD types from CXR images. In this method, CT images are additionally used to improve model's performance as it contains detailed information that might be exploited to provide efficient results. Initially, the collected images are segmented using U-Net model to get enhanced lung Region of Interest (ROIs). Then ResNet50, DenseNet121, InceptionResNetV2 and XceptionV3 are used to hierarchically extract informative and discriminative features from collected CXR and CT images. The retrieved deep features are fed into the Ensemble-Convolutional Long Short Term Memory with Extreme Machine Learning (EconLSTM-ELM) to minimize the computational time and increase the accuracy. Moreover, Transfer Learning (TL) model is employed to learn the weight of the E-conLSTM-ELM to exchange the knowledge between features and classes relation among CXR and CT images. Also, the domain adaptation approach is a variant of TL model that relies on employing similar datasets for a shared learning problem. This adaption strategy reduces the domain shift (data dispersion) using Maximum Mean Discrepancy (MMD). The shared semantic features from CT images through TL improve the in-depth learning of softmax layer to classify different LD types. The proposed work is simply named as Convolutional LD Scan (CovLscan) framework The test outcomes reveal that the CovLscan model accomplishes an overall accuracy of 95.46% and 96.15% on the collected ChestX-ray8 and NIH-CXR datasets, which is higher than the existing models like Automated Hierarchical Deep Learning based LD Diagnosis(AHDL-LDD), EfficientNet version2-Medium (EfficientNet v2-M), Lung diseases prediction Network22(LungNet22), Chest tract disorder prediction using Dilated Convolutional Network(CDCNet) and Auction-Based Optimization Algorithm-CNN (ABOA-CNN). [ABSTRACT FROM AUTHOR]

BACKGROUND: Race-specific spirometry reference equations are used globally to interpret lung function for clinical, research, and occupational purposes, but inclusion of race is under scrutiny. RESEARCH QUESTION: Does including self-identified race in spirometry reference equation formation improve the ability of predicted FEV1 values to explain quantitative chest CT abnormalities, dyspnea, or Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification? STUDY DESIGN AND METHODS: Using data from healthy adults who have never smoked in both the National Health and Nutrition Survey (2007-2012) and COPDGene study cohorts, race-neutral, race-free, and race-specific prediction equations were generated for FEV1. Using sensitivity/specificity, multivariable logistic regression, and random forest models, these equations were applied in a cross-sectional analysis to populations of individuals who currently smoke and individuals who formerly smoked to determine how they affected GOLD classification and the fit of models predicting quantitative chest CT phenotypes or dyspnea. RESULTS: Race-specific equations showed no advantage relative to race-neutral or race-free equations in models of quantitative chest CT phenotypes or dyspnea. Race-neutral reference equations reclassified up to 19% of Black participants into more severe GOLD classes, while race-neutral/race-free equations may improve model fit for dyspnea symptoms relative to race-specific equations. INTERPRETATION: Race-specific equations offered no advantage over race-neutral/race-free equations in three distinct explanatory models of dyspnea and chest CT scan abnormalities. Race-neutral/race-free reference equations may improve pulmonary disease diagnoses and treatment in populations highly vulnerable to lung disease.

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.

Abstract Medical imaging is an indispensable and very important step in the diagnosis and treatment of illnesses. However, due to large amounts of resources necessary for training the model, training from scratch may not invariably emerge as the optimal recourse. Transfer learning has emerged as a viable solution, where pretrained weights from ImageNet are initially utilized and fine-tuninned afterwards. This paper presents a novel approach employing transfer learning to classify both respiratory diseases and radiological findings from chest X-rays. The dataset comprises 191 660 X-ray images gathered from public databases and 752 chest X-ray images obtained from a retrospective study at the University Clinical Center of Kragujevac, forming the foundation of Big data analysis. It includes various conditions such as atelectasis, cardiomegaly, infiltration, pleural thickening, non-viral pneumonia, pneumothorax, COVID-19 viral pneumonia, tuberculosis, etc. as well as masses and nodules indicative of tumors and images of healthy subjects. Although there are existing solutions with some diseases, this is the first paper that inlcludes differentiation between healthy and diseased cases, as well as in case of present disease, as much as 18 different classes are inlcuded in the analysis, which has not been done so far. The proposed methodology included transfer learning with DenseNet121 as the backbone and CheXNeXt weights as initialisation scheme, upon which additional layers were added for fine tuning. The results demonstrate the model’s capacity to distinguish between healthy and diseased, with an average area under curve (AUC) of 0.99. The AUC ranges from 0.86 for nodules to 0.99 for pneumonia and 0.99 for COVID-19. Our method outperforms the state-of-the-art in accuracy across all 18 classes, with the exception of classes consolidation, mass, and nodule. These findings are promising for a tested clinical site, though further validation in clinical environment accros multiple sites may be necessary before using the model as a standalone decision system, rather than a decision support system for disease diagnosis based on chest X-rays.

Abstract Background Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that cause chronic lung disease. Rates of NTM pulmonary disease (NTM PD) have increased over the last several decades, yet national estimates in the United States (US) have not been assessed since 2015. Methods We used a nationally representative population of Medicare beneficiaries aged ≥ 65 years to assess rates of NTM PD in a high-risk population from 2010 to 2019. Poisson generalized linear models were used to assess the annual percent change in incidence in the overall population and among key demographic groups such as sex, geography, and race/ethnicity. We evaluated the relative prevalence of various comorbid conditions previously found to be associated with NTM PD. Results We identified 59,724 cases of incident NTM PD from 2010 to 2019 from an annual mean population of 29,687,097 beneficiaries, with an average annual incidence of 20.1 per 100,000 population. NTM PD incidence was overall highest in the South and among women, Asian individuals, and persons aged ≥ 80 years relative to other studied demographic groups. The annual percent change in NTM PD incidence was highest in the Northeast, at 6.5%, and Midwest, at 5.9%, and among women, at 6.5%. Several comorbid conditions were highly associated with concurrent NTM diagnosis, including allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic fibrosis. Conclusions Here we provide current estimates of NTM PD incidence and prevalence and describe increasing trends in the US from 2010 to 2019. Our study suggests a need for improved healthcare planning to handle an increased future caseload, as well as improved diagnostics and therapeutics to better detect and treat NTM PD in populations aged ≥ 65 years.

Abstract Background The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. Methods This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40–80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. Results Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. Conclusions Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence is a rising public health concern. We assessed the long-term healthcare systems perspective of costs incurred by 147 NTM-PD patients at a tertiary hospital in South Korea. Median cumulative total medical cost in managing NTM-PD patients was US $5,044 (interquartile range US $3,586–$9,680) over 49.7 months (interquartile range 33.0–68.2 months) of follow-up. The major cost drivers were diagnostic testing and medication, accounting for 59.6% of total costs. Higher costs were associated with hospitalization for Mycobacterium abscessus infection and pulmonary comorbidities. Of the total medical care costs, 50.2% were patient co-payments resulting from limited national health insurance coverage. As South Korea faces significant problems of poverty during old age and increasing NTM-PD prevalence, the financial and socio-economic burden of NTM-PD may become a major public health concern that should be considered with regard to adequate strategies for NTM-PD patients.

BACKGROUND: COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV1/FVC

Occupation is an important contributor to disparities in respiratory disease, affecting financial status, health-care access, and exposure to hazardous substances. Although occupation and associated exposures are included in the socioecological models, work exposures remain persistently absent from research on health inequities and their contribution to health. This article focuses on the occupational contribution to disparities in asthma, chronic obstructive pulmonary disease, silicosis, coronavirus disease 2019, and lung cancer. Because occupational exposures are largely preventable through proper workplace controls, the recognition of occupational causes of disease can provide an opportunity for interventions to bring about health equity.

In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes of these populations vary depending on their spatial distribution within the tissue and the immunopathologic cues contributing to disease progression. In addition to their roles in structurally supporting organs and remodeling tissue, fibroblasts mediate critical interactions with diverse immune cells. These interactions have important implications for defining mechanisms of disease and identifying potential therapeutic targets. Fibroblasts in the respiratory tract, in particular, determine the severity and outcome of numerous acute and chronic lung diseases, including asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and idiopathic pulmonary fibrosis. Here, we review recent studies defining the spatiotemporal identity of the lung-derived fibroblasts and the mechanisms by which these subsets regulate immune responses to insult exposures and highlight past, current, and future therapeutic targets with relevance to fibroblast biology in the context of acute and chronic human respiratory diseases. This perspective highlights the importance of tissue context in defining fibroblast-immune crosstalk and paves the way for identifying therapeutic approaches to benefit patients with acute and chronic pulmonary disorders.

The segmentation of airway from computed tomography (CT) images plays a vital role in pulmonary disease diagnosis, evaluation, surgical planning, and treatment. Nevertheless, it is still challenging for current methods to handle distal thin and low-contrast airways, leading to mis-segmentation issues. This paper proposes a detail-sensitive 3D-UNet (DS-3D-UNet) that incorporates two new modules into 3D-UNet to segment airways accurately from CT images. The feature recalibration module is designed to give more attention to the foreground airway features through a new attention mechanism. The detail extractor module aims to restore multi-scale detailed features by fusion of features at different levels. Extensive experiments were conducted on the ATM'22 challenge dataset composed of 300 CT scans with airway annotations to evaluate its performance. Quantitative comparisons prove that the proposed model achieves the best performance in terms of Dice similarity coefficient (92.6%) and Intersection over Union (86.3%), outperforming other state-of-the-art methods. Qualitative comparisons further exhibit the superior performance of our method in segmenting thin and confused distal bronchi. The proposed model could provide important references for the diagnosis and treatment of pulmonary diseases, holding promising prospects in the field of digital medicine. Codes are available at https://github.com/nighlevil/DS-3D-UNet/tree/master. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate clinical outcomes after SABR in a cohort of early-stage non-small cell lung cancer (NSCLC) or pulmonary metastases in chronic obstructive pulmonary disease (COPD) patients with forced expiratory volume in the first second predicted (FEV1) ≤ 50%. Methods: Retrospective single-center study was performed to analyze clinical outcomes and toxicities in COPD patients with severe lung dysfunction treated with SABR from 1st June 2015 to 31st October 2022. Results: Thirty four patients (forty locations) were enrolled for analysis. Median follow-up was 2.9 years. Median age was 73.5 years (range, 65.6–80.1). FEV1 was 38% (range, 28.2–50.0) prior to radiotherapy. Median overall survival (OS) was 41.1 months (95% CI 38.9—not reached). OS rates at 2-, 3-, and 5- years were 79%, 71%, and 36%, respectively. Cancer-specific survival rates at 2-, 3-, and 5- years were 96%, 96%, and 68%, respectively. Local control rates at 2-, 3-, and 5- years were 88%, 83%, and 83%, respectively. No grade 4 or 5 toxicity was observed. The most common acute toxicity was pneumonitis (38.2%), of which only 1 patient (2.9%) reported grade 3 acute toxicity. Conclusions: Lung SABR in patients with poor pulmonary function may be effective with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Summary: Purpose: The prevalence of psychological distress is frequently observed among old adults with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, current researches are insufficient to clarify the correlation among these relevant factors. This study examined the effects of symptom burden, psychological resilience, coping styles, and social support on psychological distress. Methods: Two hundred fifty five elderly patients with AECOPD were conveniently selected in Taian, Shandong Province. The General Information Questionnaire, Distress Thermometer, The Revised Memorial Symptom Assessment Scale, Connor-Davidson Resilience Scale, Simplified Coping Style Questionnaire, Perceived Social Support Scale were used to investigate. The relationship among factors was estimated by using a structural equation model. Results: Psychological distress score of elderly patients with AECOPD was (5.25 ± 1.01); coping styles, psychological resilience, symptom burden, and social support directly affected psychological distress (the direct effects were −.93, .17, .17, and −.09); coping styles had the largest total effect on psychological distress (the total effect was −.93); psychological resilience indirectly affected psychological distress through coping styles (the indirect effect was −.74); symptom burden indirectly affected psychological distress through psychological resilience (the indirect effect was .25); social support indirectly affected psychological distress through symptom burden, psychological resilience, and coping styles (the indirect effect was −.80). Conclusion: The psychological distress of elderly patients with AECOPD is at a moderate level; coping styles, psychological resilience, and social support have positive effects on alleviating the psychological distress of elderly patients with AECOPD; symptom burden is negatively correlated with psychological distress. Healthcare professionals should pay more attention to elderly patients with AECOPD who are particularly prone to experience higher levels of psychological distress, especially in the presence of low coping style, limited psychological resilience, inadequate levels of social support, and high symptom burden.

Abstract Background Chronic obstructive pulmonary disease (COPD) is commonly associated with anxiety/depression which can affect self-management and quality of life. The TANDEM trial evaluated a cognitive behavioural approach intervention targeting COPD-related symptoms of anxiety and/or depression, comprising up to eight one-to-one sessions delivered by respiratory healthcare professionals prior to pulmonary rehabilitation (PR). The intervention showed no improvement in anxiety/depression or uptake/completion of PR. We present patient perspectives of the intervention to help understand these results. Method Semi-structured individual interviews, using a semi-structured topic guide informed by Sekhon’s Theoretical Framework of Acceptability, were conducted with 19 patients between September 2019 and April 2020. The interviews were audio-recorded, transcribed verbatim and analysed thematically. Results The following could have limited the impact of the intervention: (1) The lives of patients were complex and commonly affected by competing comorbidities or other external stressors which they managed through previously adopted long-standing coping strategies. (2) Some patients were reluctant to talk about their mood despite the Facilitators' training and person centred-skills which aimed to enable patients to talk freely about mood. (3) The intervention handouts and ‘home-practice’ were perceived as helpful for some, but not suitable for all. (4) Many patients perceived improvements in their physical and mental health, but this was not sustained due to a mix of personal and external factors, and some did not perceive any benefits. (5) PR non-attendance/non-completion was a result of personal and PR service-related reasons. (6) Discussing COPD and mental health with the Facilitator was a novel experience. Many patients felt that TANDEM could be of benefit if it was offered earlier on/at different time points in the COPD illness journey. Conclusion We found the delivery of TANDEM prior to PR was not helpful for patients with advanced COPD often experiencing other comorbidities, and/or difficult personal/external events. These patients already utilised long-standing coping strategies to manage their COPD. Holistic interventions, that address the impact of COPD in relation to wider aspects of a patients’ life, may be more beneficial. Trial registration ISRCTN Registry 59,537,391. Registration date 20 March 2017.

Abstract Cigarette smoke (CS) is one of the leading causes of pulmonary diseases and can induce lung secretome alteration. CS exposure-induced damages to human pulmonary epithelial cells and microvascular endothelial cells have been extensively demonstrated; however, the effects of the secretome of lung epithelial cells exposed to CS extracts (CSE) on lung microvascular endothelial cells are not fully understood. In this study, we aimed to determine the effects of the secretome of lung epithelial cells exposed to CSE on lung microvascular endothelial cells. Human lung epithelial cells, A549, were exposed to CSE, and the secretome was collected. Human lung microvascular endothelial cells, HULEC-5a, were used to evaluate the effect of the secretome of A549 exposed to CSE. Secretome profile, endothelial cell death, inflammation, and permeability markers were determined. CSE altered the secretome expression of A549 cells, and secretome derived from CSE-exposed A549 cells caused respiratory endothelial cell death, inflammation, and moderately enhanced endothelial permeability. This study demonstrates the potential role of cellular interaction between endothelial and epithelial cells during exposure to CSE and provides novel therapeutic targets or beneficial biomarkers using secretome analysis for CSE-related respiratory diseases.

Hye-Rin Kang,1,&ast; So Jeong Kim,2,&ast; Ju Gang Nam,3 Young Sik Park,4 Chang-Hoon Lee4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Veteran Health Service Medical Center, Seoul, 05368, Republic of Korea; 2Division of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Gyeonggi-do, 18450, Republic of Korea; 3Department of Radiology, Seoul National University Hospital, Seoul, 03080, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chang-Hoon Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 03080, Republic of Korea, Tel +82-2-2072-4743, Fax +82-2-762-9662, Email kauri670@empal.comIntroduction: Mortality differences in chronic obstructive pulmonary disease (COPD) between nonsmokers and smokers remain unclear. We compared the risk of death associated with smoking and COPD on mortality.Methods: The study included participants aged ≥ 40 years who visited pulmonary clinics and were categorised into COPD or non-COPD and smoker or nonsmoker on the basis of spirometry results and cigarette consumption. Mortality rates were compared between groups using statistical analysis for all-cause mortality, respiratory disease-related mortality, and cardiocerebrovascular disease-related mortality.Results: Among 5811 participants, smokers with COPD had a higher risk of all-cause (adjusted hazard ratio (aHR), 1.69; 95% confidence interval (CI), 1.23– 2.33) and respiratory disease-related mortality (aHR, 2.14; 95% CI, 1.20– 3.79) than nonsmokers with COPD. Non-smokers with and without COPD had comparable risks of all-cause mortality (aHR, 1.39; 95% CI, 0.98– 1.97) and respiratory disease-related mortality (aHR, 1.77; 95% CI, 0.85– 3.68). However, nonsmokers with COPD had a higher risk of cardiocerebrovascular disease-related mortality than nonsmokers without COPD (aHR, 2.25; 95% CI, 1.15– 4.40).Conclusion: The study found that smokers with COPD had higher risks of all-cause mortality and respiratory disease-related mortality compared to nonsmokers with and without COPD. Meanwhile, nonsmokers with COPD showed comparable risks of all-cause and respiratory mortality but had a higher risk of cardiocerebrovascular disease-related mortality compared to nonsmokers without COPD.Keywords: pulmonary disease, chronic obstructive, smokers, nonsmokers, cigarette smoking, comorbidity

Background: Chronic obstructive pulmonary disease (COPD) is commonly associated with anxiety/depression which can affect self-management and quality of life. The TANDEM trial evaluated a cognitive behavioural approach intervention targeting COPD-related symptoms of anxiety and/or depression, comprising up to eight one-to-one sessions delivered by respiratory healthcare professionals prior to pulmonary rehabilitation (PR). The intervention showed no improvement in anxiety/depression or uptake/completion of PR. We present patient perspectives of the intervention to help understand these results. Method: Semi-structured individual interviews, using a semi-structured topic guide informed by Sekhon's Theoretical Framework of Acceptability, were conducted with 19 patients between September 2019 and April 2020. The interviews were audio-recorded, transcribed verbatim and analysed thematically. Results: The following could have limited the impact of the intervention: (1) The lives of patients were complex and commonly affected by competing comorbidities or other external stressors which they managed through previously adopted long-standing coping strategies. (2) Some patients were reluctant to talk about their mood despite the Facilitators' training and person centred-skills which aimed to enable patients to talk freely about mood. (3) The intervention handouts and 'home-practice' were perceived as helpful for some, but not suitable for all. (4) Many patients perceived improvements in their physical and mental health, but this was not sustained due to a mix of personal and external factors, and some did not perceive any benefits. (5) PR non-attendance/non-completion was a result of personal and PR service-related reasons. (6) Discussing COPD and mental health with the Facilitator was a novel experience. Many patients felt that TANDEM could be of benefit if it was offered earlier on/at different time points in the COPD illness journey. Conclusion: We found the delivery of TANDEM prior to PR was not helpful for patients with advanced COPD often experiencing other comorbidities, and/or difficult personal/external events. These patients already utilised long-standing coping strategies to manage their COPD. Holistic interventions, that address the impact of COPD in relation to wider aspects of a patients' life, may be more beneficial. Trial registration: ISRCTN Registry 59,537,391. Registration date 20 March 2017. [ABSTRACT FROM AUTHOR]

Introduction: Convolutional Neural Network (CNN) systems in healthcare are influenced by unbalanced datasets and varying sizes. This article delves into the impact of dataset size, class imbalance, and their interplay on CNN systems, focusing on the size of the training set versus imbalance—a unique perspective compared to the prevailing literature. Furthermore, it addresses scenarios with more than two classification groups, often overlooked but prevalent in practical settings. Methods: Initially, a CNN was developed to classify lung diseases using X-ray images, distinguishing between healthy individuals and COVID-19 patients. Later, the model was expanded to include pneumonia patients. To evaluate performance, numerous experiments were conducted with varied data sizes and imbalance ratios for both binary and ternary classifications, measuring various indices to validate the model's efficacy. Results: The study revealed that increasing dataset size positively impacts CNN performance, but this improvement saturates beyond a certain size. A novel finding is that the data balance ratio influences performance more significantly than dataset size. The behavior of three-class classification mirrored that of binary classification, underscoring the importance of balanced datasets for accurate classification. Conclusions: This study emphasizes the fact that achieving balanced representation in datasets is crucial for optimal CNN performance in healthcare, challenging the conventional focus on dataset size. Balanced datasets improve classification accuracy, both in two-class and three-class scenarios, highlighting the need for data-balancing techniques to improve model reliability and effectiveness. Motivation: Our study is motivated by a scenario with 100 patient samples, offering two options: a balanced dataset with 200 samples and an unbalanced dataset with 500 samples (400 healthy individuals). We aim to provide insights into the optimal choice based on the interplay between dataset size and imbalance, enriching the discourse for stakeholders interested in achieving optimal model performance. Limitations: Recognizing a single model's generalizability limitations, we assert that further studies on diverse datasets are needed. [ABSTRACT FROM AUTHOR]

Background Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6–amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy. Methods LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection. Results Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship. Conclusions These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage. Summary Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage. [ABSTRACT FROM AUTHOR]

Introduction: Airway infections represent one of the most common causes of mortality worldwide. The authors sought to describe patients hospitalized for lung and mediastinum abscesses in Poland from 2009 to 2016. To the authors' knowledge, this is the first evaluation of the disease in Poland. Material and methods: The authors conducted a retrospective, populationbased study, using data from 14,932 hospital discharge records. Lung and mediastinum abscesses incidence rates were estimated on the basis of data from a Polish hospital morbidity study, carried out by the National Institute of Public Health. Results: The study group consisted of 12,049 patients (74.3% male and 25.7% female patients) hospitalized for the first time with the diagnosis of lung or mediastinum abscesses. The mean and median age was 57.2 and 59 years, respectively. The mean age was significantly higher in females than males (57.9 years vs. 57 years, p < 0.05). Patients were hospitalized with the following diagnosis: abscess of lung with pneumonia (60.9%), abscess of lung without pneumonia (24.9%), abscess of lung and mediastinum (2.6%), gangrene and necrosis of lung (2.8%), abscess of mediastinum (9.7%). The average annual incidence of lung abscesses, including gangrene or necrosis of lung, was 35.7 per million (95% CI: 34.1-37.4) and the average annual incidence of mediastinum abscess was 4.8 per million (95% CI: 4.3-5.3). The incidence rates for all cases of lung or mediastinum abscesses did not vary significantly between urban and rural regions. Conclusions: Presented recent data on lung and mediastinum abscesses in Poland may be helpful in comparative analyses among European countries. [ABSTRACT FROM AUTHOR]

Gene delivery therapy has emerged as a popular approach for the treatment of various diseases. However, it still poses the challenges of accumulation in target sites and reducing off-target effects. Aerosol gene delivery for the treatment of pulmonary diseases has the advantages of high lung accumulation, specific targeting and fewer systemic side effects. However, the key challenge is selecting the appropriate formulation for aerosol gene delivery that can overcome physiological barriers. There are numerous existing gene carriers under study, including viral vectors and non-viral vectors. With the development of biomaterials, more biocompatible substances have applied gene delivery via inhalation. Furthermore, many types of genes can be delivered through aerosol inhalation, such as DNA, mRNA, siRNA and CRISPR/Cas9. Aerosol delivery of different types of genes has proven to be efficient in the treatment of many diseases such as SARS-CoV-2, cystic fibrosis and lung cancer. In this paper, we provide a comprehensive review of the ongoing research on aerosol gene delivery therapy, including the basic respiratory system, different types of gene carriers, different types of carried genes and clinical applications. [ABSTRACT FROM AUTHOR]

Objective To study the effect of Qingke Pingchuan Granule on the clinical efficacy in patients with phlegm-heat obstructing lung syndrome (AECOPD). Methods A total of 80 patients with acute exacerbation of chronic obstructive pulmonary disease (syndrome of phlegm-heat stagnation in the lung) hospitalized in the respiratory department of our hospital were selected and divided into the conventional group and the combinational group, with 40 cases in each group. The CAT score, TCM syndrome score, serum IL-6, CRP, lung function FEV1%pred, and FEV1/FVC were retrospectively observed before treatment, at the end of the second week of treatment, and at the follow-up after 1 month of treatment in the two groups. Results The total effective rate was significantly better in the combinational group than that of the conventional group (92.5% vs. 75.0%，P＜0.05). At the end of the second week of treatment, the CAT score, each single syndrome score, serum IL-6 and CRP levels were all improved than those before treatment in the two groups (P＜0.05), and the improvement degree was better in the combined group than that of the conventional group (P＜0.05). The severity of airflow limitation and respiratory failure were significantly improved compared with those before treatment in both groups. At the follow-up after 1 month of treatment, the recovery rate of scores of each single syndrome score and CAT score were significantly lower in the combined group than those in the routine group (P＜0.05). There were no significant differences in adverse drug reactions between the two groups (12.5% and 2.5%, P＞0.05). Conclusion Qingke Pingchuan Granule can effectively relieve the symptoms and improve lung function and the quality of life of AECOPD patients. [ABSTRACT FROM AUTHOR]

Mycobacterium avium is associated with pulmonary disease in otherwise healthy adults. Several clarithromycin-refractory cases have been reported, including some cases caused by clarithromycin-susceptible strains. To characterize the reason for the discrepancy between clinical response and antibiotic susceptibility results. We conducted population analysis of clarithromycin-tolerant and heteroresistant subpopulations of M. avium cultured in vitro and in homogenates of infected lungs of mice. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for 28 M. avium and two M. kansasii strains. Mice were intranasally infected with M. avium and treated with or without clarithromycin (100 mg/kg) thrice weekly. They were sacrificed on day 35 and the bacteria in lung homogenates were tested for clarithromycin resistance. Population analysis assays were performed based on colony growth on plates containing two-fold dilutions of clarithromycin. The MBC/MIC ratios were ≥8 in all 28 strains of M. avium tested. In the population analysis assay, several colonies were observed on the plates containing clarithromycin concentrations above the MIC (2–64 mg/L). No growth of M. kansasii colonies was observed on the plates containing clarithromycin concentrations ≥2 mg/L. M. avium in the homogenates of infected lungs showed clearer clarithromycin-resistant subpopulations than in vitro , regardless of clarithromycin exposure. M. avium shows intrinsic heterogeneous resistance (heteroresistance) to clarithromycin. This may explain the observed discrepancies between clarithromycin susceptibility testing results and clinical response to clarithromycin treatment. Further studies are needed to confirm a link between heteroresistance and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to estimate the proportion of patients who experience a high impact from chronic obstructive pulmonary disease (COPD) on their health status and those who also experience symptoms of depression and anxiety. It also sought to determine whether the health impact of the disease is associated with anxiety and depression. Methods: An analytical cross-sectional study was conducted among 177 randomly selected patients with COPD seeking treatment in various primary health centers in Al Ahsa, Saudi Arabia. The COPD Assessment Test (CAT) was used to determine the impact of COPD on health generally, and the Hospital Anxiety and Depression Scale was used to determine the presence of anxiety and depression symptoms. Multiple logistic regression was performed to determine the association between the health impact of COPD on the respondents and the presence of symptoms of anxiety and depression. Results: Patients who had a CAT Score of >21 were 17.37 times more likely to experience anxiety. Patients with COPD who had a CAT Score of >21 were 5.62 times more likely to experience depression. Conclusion: COPD had a severe impact on the health of nearly 30% of the patients affected. The high impact of COPD on health increases the likelihood of having anxiety and depression symptoms. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial pulmonary disease (NTM-PD) results from opportunistic lung infections by mycobacteria other than Mycobacterium tuberculosis or Mycobacterium leprae species. Similar to many other countries, the incidence of NTM-PD in the United Kingdom (UK) is on the rise for reasons that are yet to be determined. Despite guidelines established by the American Thoracic Society (ATS), the Infectious Diseases Society of America, and the British Thoracic Society, NTM-PD diagnosis and management remain a significant clinical challenge. In this review article, we comprehensively discuss key challenges in NTM-PD diagnosis and management, focusing on the UK healthcare setting. We also propose countermeasures to overcome these challenges and improve the detection and treatment of patients with NTM-PD. [ABSTRACT FROM AUTHOR]

Background: Liquid nutrition delivered through a tube is often used amid difficulty swallowing. Tube feeding has been shown to have a relationship to pneumonia and mortality. Aim: Researchers investigated the relationship of feeding route (oral or tube) to patient outcomes. Design: Data were collected on outcomes (pneumonia, depression, mortality), feeding route, presence/absence of dysphagia, and covariates (chronic obstructive pulmonary disease [COPD], stroke, mortality risk, illness severity, sex, age). Researchers collected data over a 45-month period to ensure an adequate sample size for matching. The method of sampling was retrospective, archival data analysis. Propensity score analysis resulted in 94 matched, balanced pairs. Covariates were isolated from the treatment effect. Participants: The records of 2,180 inpatients treated by Palliative Medicine were considered, and 292 met the inclusion criteria. Results: Results revealed 10.14 times greater odds of pneumonia (OR = 10.14; p <.001) with tube feeding compared to oral feeding in patients with dysphagia and end-stage COPD or end-stage stroke. Results also revealed increased odds of depression (OR = 2.79; p =.01) and mortality (OR = 3.02; p <.01) with tube feeding compared to oral feeding. Conclusion: Study findings should encourage consideration of oral nutrition at the end of life. [ABSTRACT FROM AUTHOR]

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Pulmonary diseases are among the most common illnesses in newborns and children, and they remain a leading cause of mortality in children under five years of age. Therefore, accurate diagnosis and monitoring of these conditions are crucial. While conventional chest X-rays and CT scans have long been the primary diagnostic modalities for pulmonary diseases, they have limitations, such as inadequate identification of specific pulmonary lesions and potential radiation risks to children. In recent years, with increasing understanding of ultrasound technology, it has been found that ultrasound can complement these modalities. As a non-invasive, radiation - free diagnostic tool, pulmonary ultrasound pro- vides real-time, intuitive imaging of the lungs, allowing for rapid detection and evaluation of various pulmonary lesions and facilitating timely adjustment of treatment strategies. Ultrasound, as a real-time imaging technique, has become one of the most popular clinical diagnostic methods, especially with the advent of wearable ultrasound devices that enable rap- id, dynamic, repetitive, and even continuous clinical monitoring. Ultrasound is suitable for the diagnosis and post treatment evaluation of pediatric pulmonary diseases and has broad clinical applicability. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is difficult to differentiate between chronic obstructive pulmonary disease (COPD)-peripheral bronchogenic carcinoma (COPD-PBC) and inflammatory masses. OBJECTIVE: This study aims to predict COPD-PBC based on clinical data and preoperative Habitat-based enhanced CT radiomics (HECT radiomics) modeling. METHODS: A retrospective analysis was conducted on clinical imaging data of 232 cases of postoperative pathological confirmed PBC or inflammatory masses. The PBC group consisted of 82 cases, while the non-PBC group consisted of 150 cases. A training set and a testing set were established using a 7:3 ratio and a time cutoff point. In the training set, multiple models were established using clinical data and radiomics texture changes within different enhanced areas of the CT mass (HECT radiomics). The AUC values of each model were compared using Delong's test, and the clinical net benefit of the models was tested using decision curve analysis (DCA). The models were then externally validated in the testing set, and a nomogram of predicting COPD-PBC was created. RESULTS: Univariate analysis confirmed that female gender, tumor morphology, CEA, Cyfra21-1, CT enhancement pattern, and Habitat-Radscore B/C were predictive factors for COPD-PBC (P < 0.05). The combination model based on these factors had significantly higher predictive performance [AUC: 0.894, 95% CI (0.836–0.936)] than the clinical data model [AUC: 0.758, 95% CI (0.685–0.822)] and radiomics model [AUC: 0.828, 95% CI (0.761–0.882)]. DCA also confirmed the higher clinical net benefit of the combination model, which was validated in the testing set. The nomogram developed based on the combination model helped predict COPD-PBC. CONCLUSION: The combination model based on clinical data and Habitat-based enhanced CT radiomics can help differentiate COPD-PBC, providing a new non-invasive and efficient method for its diagnosis, treatment, and clinical decision-making. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and in silico studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the de novo nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The de novo mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to in silico structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of de novo mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population. Plain language summary: Identifying the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: a case report with insights from microsatellite markers A child can develop Cystic Fibrosis (CF) if both parents pass on mutated genes. In some rare cases, new genetic mutations occur spontaneously, causing CF. This report discusses a unique case where a child has one gene with a spontaneous mutation and inherits another gene mutation from the mother. We used a method called Sanger sequencing to find the two different gene changes in the affected person. We also used computer analysis to predict how these changes might affect the protein responsible for this genetic disease. To confirm that the child's new change is not inherited, we used a type of genetic marker called microsatellite markers. The mutation inherited from the mother and the new spontaneous mutation resulted in a unique change in the responsible protein. This mutation is located in a specific part of the protein called the lasso motif. Our computer simulations show that this mutation disrupts the interaction between the lasso motif and another part of the protein called the R-domain, which ultimately affects the protein's function. This case is significant because it is the first reported instance of a de novo mutation causing CF in Asia. It has important implications for genetic testing, counseling, and understanding how recessive genetic disorders like CF occur within the Iranian population. [ABSTRACT FROM AUTHOR]