Progression Of Chronic Disease Research Articles

Unraveling the mediation role of frailty and depression in the relationship between social support and self-management among Chinese elderly COPD patients:a cross-sectional study.

Self-management (SM) is the key factor in controlling the progression of chronic obstructive pulmonary disease (COPD). Previous studies have reported that majority of COPD patients later presented with frailty and mental health diseases, which affect self-management. This study attempted to explore the mediation role of depression and frailty between social support and self-management in elderly COPD population. Six hundred twenty-seven stable elderly COPD patients admitted to 5 public hospitals in Ningxia, China were selected as study subjects by convenience sampling method. Self-management, frailty, depression and social support were assessed using the COPD Self-management Scale (COPD-SMS), Frail Scale (FS), 15-item Geriatric Depression Scale (GDS-15), and Social Support Rating Scale (SSRS) respectively. The Pearson correlation analysis was used to assess the correlation between variables. Additionally, SPSS25.0 PROCESS plugin Model 6 was used to explore the mediating effects of frailty and depression in the relationship between social support and self-management. The mean participant age was 72.87 ± 7.03years, 60.4% of participants were male. The mean total score of the COPD-SMS was 156.99 ± 25.15. Scores for the SSRS, FS, and GDS-15 were significantly correlated with COPD-SMS (p < 0.05). The analysis of the mediation effect demonstrated that social support has a direct predictive effect on self- management (β = 1.687, 95%CI: 1.359 to 2.318). Additionally, social support can also predict self- management indirectly through the mediation of depression (β = 0.290, 95%CI: 0.161 to 0.436) and frailty-depression (β = 0.040, 95%CI: 0.010 to 0.081). However, the mediation effect of frailty alone was not found to be statistically significant (β =-0.010, 95%CI: -0.061 to 0.036). The direct effect accounted for 84.06% of the total effect, while the indirect effect accounted for 15.94% of the total effect. Self-management among elderly COPD patients was relatively moderate to low. Furthermore, frailty and depression were found to have a partially mediation role in the relationship between social support and self-management. Therefore, healthcare professionals need to comprehensively consider the frailty and depression status of patients, and implement targeted intervention measures as part of their care, which can improve the self-management of elderly COPD patients.

Herbal Components for the Treatment of Various Kidney Disorders

Abstract:: Acute kidney injury is described as a loss of renal excretory function that occurs suddenly. AKI is one of several ailments grouped together as acute kidney diseases and disorders (AKD), in which progressive degradation of kidney function or persistent renal dysfunction is associated with irreversible loss of kidney cells and nephrons, potentially leading to chronic kidney disease (CKD). The prevalence and incidence of KDs are assessed in light of population disparities in the prevalence of risk factors such as diabetes, hypertension, and obesity. However, the presence of these associated illnesses does not fully explain the increased rate of progression of chronic renal disease in high-risk patients (CKD). The development of renal disease is accompanied by a decline in renal function, which eventually leads to renal failure. The current status of diagnostic testing does not allow for accurate early disease diagnosis, prognosis, or therapy efficacy monitoring. Despite significant advances in care and understanding of the causes of acute renal failure (ARF), many aspects of ARF remain controversial, confusing, and uncertain. Accurate information on the disease's prevalence, genesis, and clinical manifestations is required to successfully advocate for enough funding and resources to manage the disease. Herbal components for the treatment of a variety of kidney disorders, and the page includes a list of plants that are good for kidney treatment. This review focuses on several herbal products used to treat renal problems. It is clear from this study that medicinal plants play an important role in the fight against many different diseases. Several different plants and plant extracts have been shown to have beneficial effects in treating renal disease. These medications have great promise for use in treating kidney damage because of their nephroprotective, cytoprotective, immunomodulatory, antioxidant, anti-inflammatory, and reducing effects on oxidative stress, renal hypertension, and blood toxins such as urea, creatinine, and others. Therefore, India's traditional medicine offers a wide variety of medications that can be utilized in renal illnesses due to their effectiveness in both treating the ailment and restoring normal kidney function. Therefore, it is suggested that additional research be conducted to learn many aspects and mechanisms of medications.

Abstract WP247: Potential Predictors for Progression of Adult Moyamoya Disease: A Study From Multicenter Registry

Background and aims: Moyamoya disease refers to a chronic progressive steno-occlusive disease at the distal portion of the internal carotid arteries (ICAs) and compensatory abnormal collateral vessel formation. However, the incidence of progression and its’ related factors in adult moyamoya disease has not been well known. Our study was to investigate the prevalence of progression of steno-occlusion of intracranial vessels and clinical outcome in the patients with adult moyamoya disease. Methods: From Jan 2001 to Jun 2021, we included the patients who was diagnosed with symptomatic or asymptomatic moyamoya disease from moyamoya registries of 4 hospitals in Korea. We excluded patients who did not have any follow-up angiography more than 1 year after baseline angiography [digital subtraction angiography (DSA) or magnetic resonance angiography (MRA)]. We adopted Suzuki’s angiographic staging and MRA score for the analysis. Results: A total of 293 moyamoya patients were included, and mean follow-up period was 92.7 ±52.8 months. Among them, progression of vessel stenosis in DSA and/or MRA was found in 110 patients (37.5%). Recurrent stroke occurred in 39/183 (21.3%) in non-progression group and 40/110 (36.4%) in progression group. Clinical characteristics were not significantly different between two groups. However, previous ischemic stroke history is independently associated with angiographic progression (odds ratio, 3.384 [95% CI, 1.521-7.531]) in multivariable logistic regression analysis. Conclusions: Occlusive arterial status worsened in one-third of the patients with adult moyamoya disease during approximately 8 years of follow-up. Careful neurological and radiological follow-up would be essential to prevent additional stroke occurrence, especially in patients with a history of cerebral infarction.

Imaging of Pulmonary Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis.

Pulmonary fibrosis is recognized as occurring in association with a wide and increasing array of conditions, and it presents with a spectrum of chest CT appearances. Idiopathic pulmonary fibrosis (IPF), which corresponds histologically with usual interstitial pneumonia and represents the most common idiopathic interstitial pneumonia, is a chronic progressive fibrotic interstitial lung disease (ILD) of unknown cause. Progressive pulmonary fibrosis (PPF) describes the radiologic development of pulmonary fibrosis in patients with ILD of a known or unknown cause other than IPF. The recognition of PPF impacts management of patients with ILD-for example, in guiding initiation of antifibrotic therapy. Interstitial lung abnormalities are an incidental CT finding in patients without suspected ILD and may represent an early intervenable form of pulmonary fibrosis. Traction bronchiectasis and/or bronchiolectasis, when detected in the setting of chronic fibrosis, is generally considered evidence of irreversible disease, and progression predicts worsening mortality risk. Awareness of the association between pulmonary fibrosis and connective tissue diseases, particularly rheumatoid arthritis, is increasing. This review provides an update on the imaging of pulmonary fibrosis, with attention given to recent advances in disease understanding with relevance to radiologic practice. The essential role of a multidisciplinary approach to clinical and radiologic data is highlighted.

Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: enhancing gut probiotics abundance and the tryptophan-melatonin pathway.

Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.

Mallory-Denk bodies and hepatocellular senescence: a causal relationship?

Mallory-Denk bodies (MDBs) are hepatocellular cytoplasmic inclusions, which occur in certain chronic liver diseases, such as alcohol-related (ASH) and metabolic dysfunction-associated (MASH) steatohepatitis, copper toxicosis, some drug-induced liver disorders, chronic cholangiopathies, and liver tumors. Our study focused on the expression of the senescence markers p21WAF1/cip1 and p16INK4a in hepatocytes containing MDBs in steatohepatitis, chronic cholangiopathies with fibrosis or cirrhosis, Wilson’s disease, and hepatocellular carcinomas. Cytoplasm and nuclei of MDB-containing hepatocytes as well as MDB inclusions, except those associated with carcinoma cells, were strongly p16-positive, p21-positive, as well as p21-negative nuclei in MDB-containing hepatocytes which were observed whereas MDBs were p21-negative. Expression of the senescence marker p16 suggests that MDB formation reflects an adaptive response to chronic stress resembling senescence with its consequences, i.e., expression of inflammation- and fibrosis-prone secretome. Thus, senescence can be regarded as “double-edged sword” since, on the one hand, it may be an attempt of cellular defense, but, on the other, also causes further and sustained damage by inducing inflammation and fibrosis related to the senescence-associated secretory phenotype and thus progression of chronic liver disease.

COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors

IntroductionEnvironmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.MethodsWe delineated...

Anti-Inflammatory Properties of Oxygenated Isocoumarins and Xanthone from Thai Mangrove-Associated Endophytic Fungus Setosphaeria rostrata.

Chronic inflammation plays a crucial role in the development and progression of numerous chronic diseases. To search for anti-inflammatory metabolites from endophytic fungi isolated from plants growing in Thai mangrove areas, a chemical investigation of those fungi was performed. Five new oxygenated isocoumarins, setosphamarins A-E (1-5) were isolated from the EtOAc extract of an endophytic fungus Setosphaeria rostrata, along with four known isocoumarins and one xanthone. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of the undescribed compounds were established by comparative analysis between experimental and calculated circular dichroism (ECD) spectroscopy. All the compounds were evaluated for their anti-inflammatory activity by monitoring nitric oxide inhibition in lipopolysaccharide-induced macrophage J774A.1 cells. Only a xanthone, ravenelin (9), showed potent activity, with an IC50 value of 6.27 μM, and detailed mechanistic study showed that it suppressed iNOS and COX-2 expression.

DECREASED HEALTHCARE UTILIZATION IN UNINSURED PATIENTS WITH PERIANAL CROHN’S DISEASE UNDERGOING PROCTECTOMY

Abstract INTRODUCTION Perianal Crohn's disease (CD) is a debilitating subtype affecting nearly 20% of CD patients, primarily characterized by the presence of perianal fistulas. It is associated with poor health outcomes, significantly decreased quality of life, and is an independent predictor of work disability. Proctectomy is generally reserved for patients with severe, refractory disease. Social determinants of health, including health insurance status, can impact the progression and outcomes of chronic diseases. Here we examine healthcare utilization and clinical characteristics of patients with perianal CD who undergo proctectomy for those with and without health insurance. METHODS This retrospective study follows perianal CD patients who underwent a proctectomy from 2008 to 2021 at Mount Sinai Hospital. We collected demographic, insurance status, and clinical data, such as diagnosis-to-surgery time, hospitalization rates, number of MRIs utilized, and number of medications utilized (Tables 1 and 2). Univariate analysis comparing patients with and without insurance was performed using Chi-Square or Fisher's Exact Tests. RESULTS Our study included 130 patients (50.8% female) with a mean age of 52.0 ± 14.9 years. The majority were insured (n = 106, 81.5%). Results were significant for a shorter diagnosis-to-surgery time in the uninsured group (6.9 vs. 11.1 years, p = 0.050), fewer hospitalizations (p = 0.002), MRIs (p = 0.008), clinic visits (p = 0.007), as well as reduced use of antibiotics (p = 0.016), and biologics (p =0.001) in the uninsured group (Tables 1 and 2). Data trended towards a later mean age at the time of diagnosis in the uninsured group (37.8 vs. 33.1 years, p=0.241). There was no statistical difference between the groups regarding race, comorbidities, extraintestinal manifestations, presence of skin tags, strictures, and fissures, presence of proctitis or abscess at proctectomy, age at proctectomy, surgical approach, number of lifetime GI surgeries, endoscopies, or corticosteroid treatments. DISCUSSION Our findings suggest that the uninsured patients with perianal CD have decreased utilization of healthcare resources compared to the insured group. This disparity, combined with the observed trend of older age at, and therefore likely delay of, CD diagnosis and treatment may contribute to a more rapid and severe CD course, ultimately leading to a shorter diagnosis-to-surgery interval. This study was limited by a small, single-center population sample, as well as other confounding factors associated with lack of insurance. Future research will include multivariate analysis to identify specific discrepancies in annual healthcare utilization between these populations, evaluate the contribution of race and language to this issue, and investigate the role that a decreased delay in diagnosis could play in preventing last resort proctectomy. Table 1 Patient Characteristics Table 2 Comparison of Healthcare Utilization by Insurance Status

Personalized Prediction of Parkinson's Disease Progression Based on Deep Gaussian Processes.

Parkinson's disease is a chronic progressive neurodegenerative disease with highly heterogeneous symptoms and progression. It is helpful for patient management to establish a personalized model that integrates heterogeneous interpretation methods to predict disease progression. In the study, we propose a novel approach based on a multi-task learning framework to divide Parkinson's disease progression modeling into an unsupervised clustering task and a disease progression prediction task. On the one hand, the method can cluster patients with different progression trajectories and discover new progression patterns of Parkinson's disease. On the other hand, the discovery of new progression patterns helps to predict the future progression of Parkinson's disease markers more accurately through parameter sharing among multiple tasks. We discovered three different Parkinson's disease progression patterns and achieved better prediction performance (MAE=5.015, RMSE=7.284, r2=0.727) than previously proposed methods on Parkinson's Progression Markers Initiative datasets, which is a longitudinal cohort study with newly diagnosed Parkinson's disease.

P621 Safety and effectiveness of vedolizumab and ustekinumab in inflammatory bowel disease patients after liver transplantation for primary sclerosing cholangitis: results from an ECCO-confer case series

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease often necessitating liver transplantation (LTX). Approximately 70% of PSC patients have a concomitant diagnosis of inflammatory bowel disease (IBD) and could need treatment with biological therapy on top of the immunosuppression to prevent transplant rejection. Vedolizumab (VDZ) and ustekinumab (UST), both agents with a favorable safety profile, are often used in this population despite lack of data concerning safety and effectiveness in the post-LTX setting. Methods A retrospective multicenter case series was performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Primary endpoints were clinical and endoscopic remission at week 52, occurrence of infectious complications, occurrence of malignancy, hospitalizations, and death after liver transplantation. Results In this retrospective study, 58 patients (male n= 34 (59%), median age 42 (interquartile range (IQR) 32-52) were included across 16 participating centers of which 24 (38%) were treated with UST and 40 (63%) with VDZ. Twelve patients (20%) were diagnosed with Crohn’s disease (CD), 44 (76%) with ulcerative colitis (UC), 2 (3%)- with unclassified IBD (IBD-U) and in 12 (20%) patients had an ileal pouch anal anastomosis (IPAA). Median disease duration was 16 years (IQR 13-26) and 33 (56%) had received biological therapy prior to LTX (33% anti-TNF, 11% VDZ, 5% UST). Median disease duration for PSC was 15.5 years (IQR 11-25) and median time since LTX was 6 years (IQR 4-10). Clinical remission, assessed according to physician global assessment, at week 52 was achieved in 44% of VDZ compared to 38% of UST treated patients (p=0.17), while endoscopic remission was seen in 17% of patients in the VDZ group versus 33% in the UST treated patients (p=0.87). Clinical effectiveness was similar across CD (respectively 33% and 20%), UC (33% and 37%) and IPAA patients (36% vs 60%). Infectious complications occurred in 21 patients (29%; 27% VDZ vs 33% UST) post LTX on biological therapy (p=0.66), malignancy occurred in 10 patients (14.1%, 12.8% VDZ vs 16.7% UST, p=0.66), hospitalizations in 32 (45%; 51% VDZ vs 34% UST, p=0.15), and death in 2 patients (3.4%; 2.1% VDZ vs 4.2% UST, p=0.66) (see table). Conclusion In IBD-PSC patients who underwent LTX both UST and VDZ show similar effectiveness with clinical remission rates of respectively 44% and 38% after 1 year. Safety profiles are similar although infectious complications and occurrence of malignancy remains an important concern in this patient group.

Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes

ObjectivePhase II trials suggest glucagon-like peptide-1 receptor (GLP1) agonists resolve metabolic dysfunction-associated steatohepatitis but do not affect fibrosis regression. We aimed to determine the long-term causal effect of GLP1 agonists...

The Impact of Chronic Comorbidities on Outcomes in Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause with a high associated mortality. We aimed to compare the impact of chronic medical conditions on hospital outcomes of patients with acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This was a retrospective cohort study using the NIS database from 2016 to 2018. We included patients aged 60 and older hospitalized in academic medical centers with the diagnoses of IPF and acute respiratory failure. We examined factors associated with hospital mortality and length of stay (LOS) using survey-weighted multivariate logistic and negative binomial regression. Out of 4975 patients with AE-IPF, 665 (13.4%) did not survive hospitalization. There was no difference in the mean age between survivors and non-survivors. Patients were more likely to be male, predominantly white, and have Medicare coverage. Most non-survivors were from households with higher median income. Hospital LOS was longer among non-survivors than survivors (9.4 days vs. 9.8 days; p < 0.001). After multivariate-logistic regression, diabetes was found to be protective (aOR 0.62, 95% CI 0.50-0.77; p < 0.0001) while chronic kidney disease (CKD) conferred a significantly higher risk of death after AE-IPF (aOR 6.85, 95% CI 1.90-24.7; p = 0.00). Our multivariate adjusted negative binomial regression model for LOS identified obesity (IRR 0.85, 95% CI 0.76-0.94; p ≤ 0.00) and hypothyroidism (IRR 0.90, 95% CI 0.83-0.98; p = 0.02) to be associated with shorter hospital LOS. Our results suggest that CKD is a significant contributor to hospital mortality in AE-IPF, and diabetes mellitus may be protective. Obesity and hypothyroidism are linked with shorter hospital LOS among patients hospitalized with AE-IPF in US academic medical centers.

Changes in vaginal secretion lipidom as a result of therapy in patients with vulvovaginal atrophy

Introduction. Vulvovaginal atrophy is a chronic progressive disease that includes physiological and anatomical changes as a result of a decrease in the level of sex hormones. VVA affects approximately 50% of middle-aged and older women and has a detrimental effect on interpersonal relationships, sexual health, and overall quality of life. Dynamic quadripolar radiofrequency (DRF) is a non-invasive procedure that may be a potential treatment for vulvar diseases.Aim. To study the metabolites of vaginal swabs in postmenopausal women treated with DRF.Materials and methods. The study included 180 women divided into 3 groups: treatment with DRF; treatment with a combination of DRF and estradiol, and estradiol treatment. In all patients, vaginal swabs were taken before the start of treatment and a month after treatment, and clinical parameters were assessed at 6 time points. Lipids were extracted from the cervico-vaginal fluid by the Folch method followed by liquid chromatography-mass spectrometric analysis. A comparative analysis of the clinical data of each of the groups and lipid profiles after treatment with a zero time point and their changes and a correlation analysis of changes in lipid levels and changes in clinical parameters before treatment and after 1 month was carried out.Results. There was a statistically significant reduction in the severity of VVA symptoms one month after treatment in all groups. The most pronounced effect of the therapy was observed in groups with the use of DRF with the preservation of the effect up to 12 months. In the first and second groups, a statistically significant difference was found in the levels of 2 lipids, in the third – in 4. In the first group, a correlation was found with lipids related with pain and lubrication, in the second – with vaginal pH, in the third – with the index of vaginal health, orgasm, satisfaction and pain.Conclusions. VVA therapy by DRF and local hormonal treatment triggers an inflammatory cascade in tissues. The use of the strategy of treatment with physical methods of influence has a mechanism of influence similar to the local application of estrogen in VVA. DRF therapy leads to the normalization of the vaginal microbiota and can compete with the use of estrogen in this therapeutic effect.

Whey Protein Peptide Pro-Glu-Trp Ameliorates Hyperuricemia by Enhancing Intestinal Uric Acid Excretion, Modulating the Gut Microbiota, and Protecting the Intestinal Barrier in Rats.

Hyperuricemia (HUA) is a metabolic disorder characterized by an increase in the concentrations of uric acid (UA) in the bloodstream, intricately linked to the onset and progression of numerous chronic diseases. The tripeptide Pro-Glu-Trp (PEW) was identified as a xanthine oxidase (XOD) inhibitory peptide derived from whey protein, which was previously shown to mitigate HUA by suppressing UA synthesis and enhancing renal UA excretion. However, the effects of PEW on the intestinal UA excretion pathway remain unclear. This study investigated the impact of PEW on alleviating HUA in rats from the perspective of intestinal UA transport, gut microbiota, and intestinal barrier. The results indicated that PEW inhibited the XOD activity in the serum, jejunum, and ileum, ameliorated intestinal morphology changes and oxidative stress, and upregulated the expression of ABCG2 and GLUT9 in the small intestine. PEW reversed gut microbiota dysbiosis by decreasing the abundance of harmful bacteria (e.g., Bacteroides, Alloprevotella, and Desulfovibrio) and increasing the abundance of beneficial microbes (e.g., Muribaculaceae, Lactobacillus, and Ruminococcus) and elevated the concentration of short-chain fatty acids. PEW upregulated the expression of occludin and ZO-1 and decreased serum IL-1β, IL-6, and TNF-α levels. Our findings suggested that PEW supplementation ameliorated HUA by enhancing intestinal UA excretion, modulating the gut microbiota, and restoring the intestinal barrier function.

Lactate accumulation induced by Akt2-PDK1 signaling promotes pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with an abnormal accumulation of fibrotic tissue in the lung parenchyma and elevated glycolysis level in associated cells without effective therapy options. Lactate accumulation in pulmonary fibrotic tissue is a significant factor aggravating IPF development, but the main mechanism regulating glycolysis needs further investigation. In this study, lung fibrosis model was induced by bleomycin (BLM) intratracheally in female C57BL/6 mice. The changes of lactate level and fibrotic markers were detected. For invitro studies, cell lines of alveolar epithelial cell and lung fibroblast cell were stimulated with TGF-β1 and BLM respectively, to detect changes in their fibrotic properties. The function of lactate accumulation on facilitating fibrosis was verified. We demonstrated that BLM-induced pulmonary fibrosis is accompanied by lactate accumulation owing to glycolysis upregulation. Significantly high PDK1 expression in lung fibrotic tissue promotes glycolysis. Moreover, PDK1 stimulated trans-differentiation of lung fibroblasts and epithelial-mesenchymal transition (EMT) of alveolar epithelial cells. Furthermore, phosphorylated Akt2 activated PDK1 to cause pulmonary fibrosis and inhibitors of Akt2 and PDK1 could suppress fibrotic process. This study is the first to consider PDK1 facilitated lactate accumulation through glycolysis as a vital factor in pulmonary fibrosis and could be initiated by Akt2. We concluded that the pro-fibrotic properties of PDK1 are associated with Akt2 phosphorylation and thus provide new potential therapeutic targets for pulmonary fibrosis.

Periodontitis aggravates COPD through the activation of γδ T cell and M2 macrophage.

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease with high morbidity and mortality. Periodontitis exacerbates COPD progression; however, the immune mechanisms by which periodontitis affects COPD remain unclear. Here, by constructing periodontitis and COPD mouse models, we demonstrated that periodontitis and COPD could mutually aggravate disease progression. For the first time, we found that the progression was associated with the activation of γδ T cells and M2 macrophages, and M2 polarization of macrophages was affected by γδ T cells activation. In the lung tissues of COPD with periodontitis, the activation of γδ T cells finally led to the increase of IL 17 and IFN γ expression and M2 macrophage polarization. Furthermore, we found that the periodontitis-associated bacteria Porphyromonas gingivalis (P. gingivalis) promoted the activation of γδ T cells and M2 macrophages ex vivo. The data from clinical bronchoalveolar lavage fluid (BALF) samples were consistent with the in vivo and ex vivo experiments. For the first time, our results identified the crucial role of γδ T-M2 immune mechanism in mediating periodontitis-promoted COPD progression. Therefore, targeting at periodontitis treatment and the γδ T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control.IMPORTANCEPeriodontitis exacerbates chronic obstructive pulmonary disease (COPD) progression. For the first time, the current study identified that the impact of periodontitis on COPD progression was associated with the activation of γδ T cells and M2 macrophages and that M2 polarization of macrophages was affected by γδ T cells activation. The results indicated that targeting at periodontitis treatment and the γδ T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control.

Comprehensive analysis of an endoplasmic reticulum stress-related gene prediction model and immune infiltration in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. This study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in IPF and explore its correlation with immune infiltration. ERS-related differentially expressed genes (ERSRDEGs) were identified by intersecting differentially expressed genes (DEGs) from three Gene Expression Omnibus datasets with ERS-related gene sets. Gene Set Variation Analysis and Gene Ontology were used to explore the potential biological mechanisms underlying ERS. A nomogram was developed using the risk signature derived from the ERSRDEGs to perform risk assessment. The diagnostic value of the risk signature was evaluated using receiver operating characteristics, calibration, and decision curve analyses. The ERS score of patients with IPF was measured using a single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. Subsequently, a prognostic model based on the ERS scores was established. The proportion of immune cell infiltration was assessed using the ssGSEA and CIBERSORT algorithms. Finally, the expression of ERSRDEGs was validated in vivo and in vitro via RT-qPCR. This study developed an 8-ERSRDEGs signature. Based on the expression of these genes, we constructed a diagnostic nomogram model in which agouti-related neuropeptide had a significantly greater impact on the model. The area under the curve values for the predictive value of the ERSRDEGs signature were 0.975 and 1.000 for GSE70866 and GSE110147, respectively. We developed a prognostic model based on the ERS scores of patients with IPF. Furthermore, we classified patients with IPF into two subtypes based on their signatures. The RT-qPCR validation results supported the reliability of most of our conclusions. We developed and verified a risk model using eight ERSRDEGs. These eight genes can potentially affect the progression of IPF by regulating ERS and immune responses.

Magnetic Resonance Imaging of Pulmonary and Paranasal Sinus Abnormalities in Children with Primary Ciliary Dyskinesia Compared to Children with Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z-score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF (r = -0.523 and -0.687; P < 0.01) and with lung clearance index in children with CF (r = 0.650; P < 0.001) but not in PCD (r = 0.353; P = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD (r = 0.075-0.157; P = 0.557-0.788) but correlated moderately with MRI morphology score in CF (r = 0.437; P < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study

BackgroundClinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. MethodsThis was a post hoc analysis of the 24-month Tie-COPD study comparing 18 μg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. ResultsOf the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49–0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. ConclusionsTiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. Trial registrationThis study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).