Association of volatile organic compound levels with chronic obstructive pulmonary diseases in NHANES 2013-2016.

Volatile organic compounds (VOCs) represent a significant component of air pollution. However, studies evaluating the impact of VOC exposure on chronic obstructive pulmonary disease (COPD) have predominantly focused on single pollutant models. This study aims to comprehensively assess the relationship between multiple VOC exposures and COPD. A large cross-sectional study was conducted on 4983 participants from the National Health and Nutrition Examination Survey. Four models, including weighted logistic regression, restricted cubic splines (RCS), weighted quantile sum regression (WQS), and the dual-pollution model, were used to explore the association between blood VOC levels and the prevalence of COPD in the U.S. general population. Additionally, six machine learning algorithms were employed to develop a predictive model for COPD risk, with the model's predictive capacity assessed using the area under the curve (AUC) indices. Elevated blood concentrations of benzene, toluene, ortho-xylene, and para-xylene were significantly associated with the incidence of COPD. RCS analysis further revealed a non-linear and non-monotonic relationship between blood levels of toluene and m-p-xylene with COPD prevalence. WQS regression indicated that different VOCs had varying effects on COPD, with benzene and ortho-xylene having the greatest weights. Among the six models, the Extreme Gradient Boosting (XGBoost) model demonstrated the strongest predictive power, with an AUC value of 0.781. Increased blood concentrations of benzene and toluene are significantly correlated with a higher prevalence of COPD in the U.S. population, demonstrating a non-linear relationship. Exposure to environmental VOCs may represent a new risk factor in the etiology of COPD.

The impact of oral diseases on respiratory health and the influence of respiratory infections on the oral microbiome.

OBJECTIVE: The objective of this review is to examine the relationship between oral diseases and respiratory health, investigating how oral microbiome disruptions contribute to respiratory tract infections. Additionally, it aims to explore the impact of respiratory disease symptoms and treatments on the oral microbiome. DATA SOURCES: The literature utilized in this review was sourced from studies focusing on the correlation between oral health and respiratory infections, spanning a period of 40 years. Various databases and scholarly sources were likely consulted to gather relevant research articles, reviews, and clinical studies. STUDY SELECTION: This review summarizes four decades-long research, providing insights into the intricate relationship between oral and respiratory health. It delves into how oral diseases influence respiratory tract conditions and vice versa. The selection process likely involved identifying studies that addressed the interaction between oral microbiome disruptions and respiratory complications. CONCLUSION: Oral diseases or poor oral habits have been known to increase the risk of getting respiratory infections. Modern techniques have demonstrated the relationship between oral disease and respiratory tract infections like influenza, chronic obstructive pulmonary diseases, asthma, and Pneumonia. Apart from that, the medications used to treat respiratory diseases affect oral physiological factors like the pH of saliva, and saliva flow rate, which can cause significant changes in the oral microbiome. This review provides regular oral hygiene and care that can prevent respiratory health and respiratory infections. CLINICAL SIGNIFICANCE: Understanding the intricate relationship between oral health and respiratory infections is crucial for healthcare providers. Implementing preventive measures and promoting good oral hygiene habits can reduce respiratory tract infections and improve overall respiratory health outcomes.

Zataria multiflora affects pulmonary function tests, respiratory symptoms, bronchodilator drugs use and hematological parameters in chronic obstructive pulmonary disease patients: A randomized doubled-blind clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Zataria multiflora is employed as an antitussive, anti-spasmodic, analgesic and etc. Agent in traditional medicine. The modern medical studies are also confirmed effects of this plant for treatment of respiratory problems via anti-inflammatory, anti-oxidant and immunomodulatory properties. AIM OF STUDY: We evaluated efficacy of Z. multiflora on tests of pulmonary function, respiratory symptoms, inhaled bronchodilator drugs use, and hematological factors in COPD patients. METHODS: Patients (n = 45) were randomly grouped in the following three groups: placebo group (P), groups received Z. multiflora extract 3 and 6 mg/kg/day (Z3 and Z6). FEV1 and MEF25-75, respiratory symptoms, inhaled bronchodilator drugs use and hematological factors were evaluated before and 1-2 months after treatment. RESULTS: Z. multiflora led to significant enhancement of FEV1 (p < 0.05 to p < 0.01). Respiratory symptoms were also considerably ameliorated following treatment with extracts for 1 and 2 months compared to baseline values (p < 0.05 to p < 0.001). In groups received extract, inhaled bronchodilator drugs use was remarkably declined at the end of study (both, p < 0.05). Reduction of total WBC was observed 1-2 months after treatment in treated groups with extract compared to baseline values (p < 0.05 to p < 0.001). Neutrophils were remarkably declined in Z3 and Z6 groups after 2-monthes compared to 1-month treatment (p < 0.05 to p < 0.01). CONCLUSION: The evidence show therapeutic effect of this herb on COPD patients which could be result from properties that help to decrease inflammation.

Surgery for Secondary Spontaneous Pneumothorax with Chronic Lung Diseases.

PURPOSES: Secondary spontaneous pneumothorax (SSP) is occasionally observed in elderly patients suffering from diffuse lung diseases. The purpose of this study was to analyze the outcomes of surgical treatment of SSP patients with chronic lung diseases. METHODS: In total, 242 patients who underwent surgery for spontaneous pneumothorax at Chiba University Hospital from January 2006 to October 2016 were included in this study. The patients' records were reviewed retrospectively for data on their background, surgical treatment, morbidity, mortality, and recurrence. RESULTS: Of the spontaneous pneumothorax cohort, primary spontaneous pneumothorax (PSP) accounted for 144 patients. Among the 98 patients with SSP, 57 cases were caused by chronic obstructive pulmonary disease (COPD) and 21 were caused by interstitial pneumonia (IP). The postoperative complication rate was 19.3% in the COPD group, 42.9% in the IP group, and 11.1% in the PSP group. The recurrence rate was 5.3% in the COPD group, 28.6% in the IP group, and 21.5% in the PSP group. CONCLUSIONS: The morbidity and recurrence were comparable between PSP and SSP cases with COPD, whereas these values were unfavorable in SSP cases with IP compared with PSP ones. Surgical intervention should be carefully considered in SSP patients with IP.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Telehealth nursing interventions for phenotypes of older adults with COPD: an exploratory study.

Introduction: Inconclusive results exist around the effectiveness of telemonitoring for patients with COPD, and studies recommended conducting subgroup analyses to identify patient phenotypes that could benefit from these services. This exploratory study investigated what type of COPD patients were receiving which type of telenursing interventions more frequently using the telemonitoring platform. Methods: A sample of 36 older adults with COPD were receiving telenursing services for 12 months and were asked to answer five COPD-symptom related questions and submit their vital signs daily. Results: Findings revealed two phenotypes of older adults for whom the frequency of telenursing calls and related interventions differed. Although no statistically significant differences were observed in participants' GOLD grades and hospitalizations, cluster one participants used their COPD action plan significantly more frequently, and were in frequent contact with the telenurse. Discussion: It is paramount that further research is needed on the development of patient phenotypes who may benefit from telemonitoring.

Effect of a pulmonary rehabilitation program combined with cognitive training on exercise tolerance and cognitive functions among Tunisian male patients with chronic obstructive pulmonary disease: A randomized controlled trial.

BACKGROUND: Cognitive impairment has been well described in patients with Chronic Obstructive Pulmonary Disease (COPD) in addition to cardiorespiratory disability. To reduce this impairment, researchers have recommended the use of single or combined exercise training. However, the combined effect of cognitive training (CT) and pulmonary rehabilitation (PR) program on selective cognitive abilities in patients with COPD has not been fully evaluated. Therefore, we aimed to assess the impact of PR combined with CT on 6 minutes walking test (6MWT) and cognitive parameters in Tunisian males' patients with COPD. METHODS: Thirty-nine patients with COPD were randomly assigned to an intervention group (n = 21, age = 65.3 ± 2.79) and a control group (n = 18, age = 65.3 ± 3.2). The intervention group underwent PR combined with CT, and the control group underwent only PR, three times per week for 3 months. The primary outcomes were 6MWT (6 minutes walking test -6MWT-parameters) and cognitive performance, as evaluated by Montreal cognitive assessments (MOCA) and P300 test. Secondary outcomes were patient's characteristics and spirometric data. These tests were measured at baseline and after 3 months of training programs. RESULTS: Results showed a significant improvement of the 6MWT distance after the rehabilitation period in both groups (p < .001). Moreover, both groups showed significant improvement (p < .001) in cognitive performance including MOCA score and P300 test latency in three midline electrodes. However, the improvement in cognitive performance was significantly greater in the PR+CT group than the PR group. CONCLUSION: In conclusion, although PR alone improves 6MWT parameters and cognitive function, the addition of CT to PR is more effective in improving cognitive abilities in patients with COPD. This combined approach may provide clinicians with a complementary therapeutic option for improving cognitive abilities in patients with COPD.

Assessing volatile organic compounds exposure and chronic obstructive pulmonary diseases in US adults.

Background: Volatile organic compounds (VOCs) are a large group of chemicals widely used in People's Daily life. There is increasing evidence of the cumulative toxicity of VOCs. However, the association between VOCs and the risk of COPD has not been reported. Objective: We comprehensively evaluated the association between VOCs and COPD. Methods: Our study included a total of 1,477 subjects from the National Health and Nutrition Examination Survey, including VOCs, COPD, and other variables in the average US population. Multiple regression models and smooth-curve fitting (penalty splines) were constructed to examine potential associations, and stratified analyses were used to identify high-risk groups. Results: We found a positive association between blood benzene and blood o-xylene concentrations and COPD risk and identified a concentration relationship between the two. That is, when the blood benzene and O-xylene concentrations reached 0.28 ng/mL and 0.08 ng/mL, respectively, the risk of COPD was the highest. In addition, we found that gender, age, and MET influence the relationship, especially in women, young people, and people with low MET. Significance: This study revealed that blood benzene and blood o-xylene were independently and positively correlated with COPD risk, suggesting that long-term exposure to benzene and O-xylene may cause pulmonary diseases, and providing a new standard of related blood VOCs concentration for the prevention of COPD.

KCa2 and KCa3.1 Channels in the Airways: A New Therapeutic Target.

K+ channels are involved in many critical functions in lung physiology. Recently, the family of Ca2+-activated K+ channels (KCa) has received more attention, and a massive amount of effort has been devoted to developing selective medications targeting these channels. Within the family of KCa channels, three small-conductance Ca2+-activated K+ (KCa2) channel subtypes, together with the intermediate-conductance KCa3.1 channel, are voltage-independent K+ channels, and they mediate Ca2+-induced membrane hyperpolarization. Many KCa2 channel members are involved in crucial roles in physiological and pathological systems throughout the body. In this article, different subtypes of KCa2 and KCa3.1 channels and their functions in respiratory diseases are discussed. Additionally, the pharmacology of the KCa2 and KCa3.1 channels and the link between these channels and respiratory ciliary regulations will be explained in more detail. In the future, specific modulators for small or intermediate Ca2+-activated K+ channels may offer a unique therapeutic opportunity to treat muco-obstructive lung diseases.

Bio-medical imaging (X-ray, CT, ultrasound, ECG), genome sequences applications of deep neural network and machine learning in diagnosis, detection, classification, and segmentation of COVID-19: a Meta-analysis & systematic review.

This review investigates how Deep Machine Learning (DML) has dealt with the Covid-19 epidemic and provides recommendations for future Covid-19 research. Despite the fact that vaccines for this epidemic have been developed, DL methods have proven to be a valuable asset in radiologists' arsenals for the automated assessment of Covid-19. This detailed review debates the techniques and applications developed for Covid-19 findings using DL systems. It also provides insights into notable datasets used to train neural networks, data partitioning, and various performance measurement metrics. The PRISMA taxonomy has been formed based on pretrained(45 systems) and hybrid/custom(17 systems) models with radiography modalities. A total of 62 systems with respect to X-ray(32), CT(19), ultrasound(7), ECG(2), and genome sequence(2) based modalities as taxonomy are selected from the studied articles. We originate by valuing the present phase of DL and conclude with significant limitations. The restrictions contain incomprehensibility, simplification measures, learning from incomplete labeled data, and data secrecy. Moreover, DML can be utilized to detect and classify Covid-19 from other COPD illnesses. The proposed literature review has found many DL-based systems to fight against Covid19. We expect this article will assist in speeding up the procedure of DL for Covid-19 researchers, including medical, radiology technicians, and data engineers.

Herpes zoster vaccine effectiveness against herpes zoster and postherpetic neuralgia in New Zealand: a retrospective cohort study.

Background: Herpes zoster (HZ) and associated complications cause significant burden to older people. A HZ vaccination programme was introduced in Aotearoa New Zealand in April 2018 with a single dose vaccine for those aged 65 years and a four-year catch up for 66-80 year-olds. This study aimed to assess the 'real-world' effectiveness of the zoster vaccine live (ZVL) against HZ and postherpetic neuralgia (PHN). Methods: We conducted a nationwide retrospective matched cohort study from 1 April 2018 to 1 April 2021 using a linked de-identified patient level Ministry of Health data platform. A Cox proportional hazards model was used to estimate ZVL vaccine effectiveness (VE) against HZ and PHN adjusting for covariates. Multiple outcomes were assessed in the primary (hospitalised HZ and PHN - primary diagnosis) and secondary (hospitalised HZ and PHN: primary and secondary diagnosis, community HZ) analyses. A sub-group analysis was carried out in, adults ≥ 65 years old, immunocompromised adults, Maori, and Pacific populations. Findings: A total of 824,142 (274,272 vaccinated with ZVL matched with 549,870 unvaccinated) New Zealand residents were included in the study. The matched population was 93.4% immunocompetent, 52.2% female, 80.2% European (level 1 ethnic codes), and 64.5% were 65-74 years old (mean age = 71.1±5.0). Vaccinated versus unvaccinated incidence of hospitalised HZ was 0.16 vs. 0.31/1,000 person-years and 0.03 vs. 0.08/1000 person-years for PHN. In the primary analysis, the adjusted overall VE against hospitalised HZ and hospitalised PHN was 57.8% (95% CI: 41.1-69.8) and 73.7% (95% CI:14.0-92.0) respectively. In adults ≥ 65 years old, the VE against hospitalised HZ was 54.4% (95% CI: 36.0-67.5) and VE against hospitalised PHN was 75·5% (95% CI: 19.9-92.5). In the secondary analysis, the VE against community HZ was 30.0% (95% CI: 25.6-34.5). The ZVL VE against hospitalised HZ for immunocompromised adults was 51.1% (95% CI: 23.1-69.5), and PHN hospitalisation was 67.6% (95% CI: 9.3-88.4). The VE against HZ hospitalisation for Maori was 45.2% (95% CI: -23.2-75.6) and for Pacific Peoples was 52.2% (95% CI: -40.6 -83·7). Interpretation: ZVL was associated with a reduction in risk of hospitalisation from HZ and PHN in the New Zealand population. Funding: Wellington Doctoral Scholarship awarded to JFM.

Modified MRC assessment and FEV1.0 can predict frequent acute exacerbation of COPD: An observational prospective cohort study at a single-center in Japan.

INTRODUCTION: Acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) is a fatal event, leading to poor outcomes among COPD patients. However, exact frequency and poor prognostic factors are not well known in Japan. METHODS: and patients, To assess the frequency and risk factors of AE, we performed this prospective cohort study at the Kameda Medical Center in Japan between during 2011 and 2013. AE was defined as an acute worsening of respiratory symptoms according to the GOLD guideline. Furthermore, we compared the exacerbation-free time between the groups. RESULTS: A total of 330 patients (230 COPD patients and 100 smoking controls) were enrolled in the study. The mean age in the study was 73 years, and 94% of the patients were male. As for the frequency of AE, 0.17 times/patients/year was found in all patients. The frequency of AE increased as the COPD disease severity (p = 0.042 by Jonch-Heere terpla test). GOLD I patients had longer exacerbation-free time than GOLD II, and GOLD II grade COPD patients had longer exacerbation-free time than GOLD III grade COPD patients. In terms of risk factors for AE, logistic regression analysis showed that Modified Medical Research Council (mMRC) scale ≥3 and FEV1.0% <50% were independent poor prognostic factors for moderate grade of AE events, and mMRC scale ≥3 was independent poor prognostic factor for severe AE events. CONCLUSION: The frequency of AE increases as the disease severity becomes more severe. We found mMRC scale >3 and FEV1 <50% were risk factors for AE-COPD.

PulDi-COVID: Chronic obstructive pulmonary (lung) diseases with COVID-19 classification using ensemble deep convolutional neural network from chest X-ray images to minimize severity and mortality rates.

Background and Objective: In the current COVID-19 outbreak, efficient testing of COVID-19 individuals has proven vital to limiting and arresting the disease's accelerated spread globally. It has been observed that the severity and mortality ratio of COVID-19 affected patients is at greater risk because of chronic pulmonary diseases. This study looks at radiographic examinations exploiting chest X-ray images (CXI), which have become one of the utmost feasible assessment approaches for pulmonary disorders, including COVID-19. Deep Learning(DL) remains an excellent image classification method and framework; research has been conducted to predict pulmonary diseases with COVID-19 instances by developing DL classifiers with nine class CXI. However, a few claim to have strong prediction results; because of noisy and small data, their recommended DL strategies may suffer from significant deviation and generality failures. Methods: Therefore, a unique CNN model(PulDi-COVID) for detecting nine diseases (atelectasis, bacterial-pneumonia, cardiomegaly, covid19, effusion, infiltration, no-finding, pneumothorax, viral-Pneumonia) using CXI has been proposed using the SSE algorithm. Several transfer-learning models: VGG16, ResNet50, VGG19, DenseNet201, MobileNetV2, NASNetMobile, ResNet152V2, DenseNet169 are trained on CXI of chronic lung diseases and COVID-19 instances. Given that the proposed thirteen SSE ensemble models solved DL's constraints by making predictions with different classifiers rather than a single, we present PulDi-COVID, an ensemble DL model that combines DL with ensemble learning. The PulDi-COVID framework is created by incorporating various snapshots of DL models, which have spearheaded chronic lung diseases with COVID-19 cases identification process with a deep neural network produced CXI by applying a suggested SSE method. That is familiar with the idea of various DL perceptions on different classes. Results: PulDi-COVID findings were compared to thirteen existing studies for nine-class classification using COVID-19. Test results reveal that PulDi-COVID offers impressive outcomes for chronic diseases with COVID-19 identification with a 99.70% accuracy, 98.68% precision, 98.67% recall, 98.67% F1 score, lowest 12 CXIs zero-one loss, 99.24% AUC-ROC score, and lowest 1.33% error rate. Overall test results are superior to the existing Convolutional Neural Network(CNN). To the best of our knowledge, the observed results for nine-class classification are significantly superior to the state-of-the-art approaches employed for COVID-19 detection. Furthermore, the CXI that we used to assess our algorithm is one of the larger datasets for COVID detection with pulmonary diseases. Conclusion: The empirical findings of our suggested approach PulDi-COVID show that it outperforms previously developed methods. The suggested SSE method with PulDi-COVID can effectively fulfill the COVID-19 speedy detection needs with different lung diseases for physicians to minimize patient severity and mortality.

Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease.

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Fibroblast growth factor 10 attenuates chronic obstructive pulmonary disease by protecting against glycocalyx impairment and endothelial apoptosis.

BACKGROUND: The defects and imbalance in lung repair and structural maintenance contribute to the pathogenesis of chronic obstructive pulmonary diseases (COPD), yet the molecular mechanisms that regulate lung repair process are so far incompletely understood. We hypothesized that cigarette smoking causes glycocalyx impairment and endothelial apoptosis in COPD, which could be repaired by the stimulation of fibroblast growth factor 10 (FGF10)/FGF receptor 1 (FGFR1) signaling. METHODS: We used immunostaining (immunohistochemical [IHC] and immunofluorescence [IF]) and enzyme-linked immunosorbent assay (ELISA) to detect the levels of glycocalyx components and endothelial apoptosis in animal models and in patients with COPD. We used the murine emphysema model and in vitro studies to determine the protective and reparative role of FGF10/FGFR1. RESULTS: Exposure to cigarette smoke caused endothelial glycocalyx impairment and emphysematous changes in murine models and human specimens. Pretreatment of FGF10 attenuated the development of emphysema and the shedding of glycocalyx components induced by CSE in vivo. However, FGF10 did not attenuate the emphysema induced by endothelial-specific killing peptide CGSPGWVRC-GG-D(KLAKLAK)2. Mechanistically, FGF10 alleviated smoke-induced endothelial apoptosis and glycocalyx repair through FGFR1/ERK/SOX9/HS6ST1 signaling in vitro. FGF10 was shown to repair pulmonary glycocalyx injury and endothelial apoptosis, and attenuate smoke-induced COPD through FGFR1 signaling. CONCLUSIONS: Our results suggest that FGF10 may serve as a potential therapeutic strategy against COPD via endothelial repair and glycocalyx reconstitution.

People's care seeking journey for a chronic illness in rural India: Implications for policy and practice.

Drawing on interviews conducted in 2019-2020, across twenty villages in India, this paper unpacks how people with chronic illness navigate complex care-seeking terrain. We show how the act of seeking care involves navigating through personal, family, social, economic, cultural, and most importantly, difficult health systems spaces-and entails making difficult social, moral, and financial choices. We show how the absence of reliable and accessible points of first contact for primary care results in people running from pillar to post, taking wrong turns, and becoming disappointed, frustrated, and, sometimes, impoverished. We reveal the complex individual and social dynamics of hope and misplaced and misguided expectations, as well as social obligations and their performance that animate the act of navigating care in rural India. We shine light on how a health system with weak primary care and poor regulation amplifies the medical, social, and financial consequences of an otherwise manageable chronic illness, and how these consequences are the worst for those with the least social, network and economic capital. Crucially we highlight the problematic normalisation of the absence of reliable primary care services for chronic illness in India, in rural India specifically. We signpost implications for research, and for policy and practice in India and similar health system contexts, i.e. those with weak primary care and poor regulation of the private sector. We argue that in India, having in place accessible, good quality, and trustworthy sources of advice and care for chronic illness at the first point of call, for all, is critical. We contend that this first point of call should be quality, public primary care services. We conclude that if such arrangements are in place in public services, people will use them.

Camellia sinensis L. Alleviates Pulmonary Inflammation Induced by Porcine Pancreas Elastase and Cigarette Smoke Extract.

Cigarette smoke (CS) is the major factor in the development of chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. Furthermore, although Camellia sinensis (CN) has been known as an anti-inflammatory material, the effect of CN has not yet been known on pulmonary inflammation in COPD. Thus, we investigated the protective effects of Camellia sinensis L. extract (CLE) against pulmonary inflammation in porcine pancreas elastase (PPE) and a cigarette smoke extract (CSE)-induced COPD mouse model. Oral administration of CLE suppressed the symptoms such as infiltration of immune cells, cytokines/chemokines secretion, mucus hypersecretion, and injuries of the lung parenchyma. Increased inflammatory responses in COPD are mediated by various immune cells such as airway epithelial cells, neutrophils, and alveolar macrophages. Thus, we investigated the effect and mechanisms of CLE in H292, HL-60, and MH-S cells. The CLE inhibited the expression of IL-6, IL-8, MUC5AC and MUC5B on CSE/LPS-stimulated H292 cells and also suppressed the formation of neutrophil extracellular traps and secretion of neutrophil elastase by inhibiting reactive oxygen species in PMA-induced HL-60 cells. In particular, the CLE suppressed the release of cytokines and chemokines caused by activating the nuclear factor kappa-light-chain-enhancer of activated B via the activation of nuclear factor erythroid-2-related factor 2 and the heme oxygenase-1 pathway in CSE/LPS-stimulated MH-S cells. Therefore, we suggest that the CLE administration be the effective approach for treating or preventing chronic pulmonary diseases such as COPD induced by CS.

Deciphering Resistome in Patients With Chronic Obstructive Pulmonary Diseases and Clostridioides difficile Infections.

Antibiotics alter the gut microbiome and cause dysbiosis leading to antibiotic-resistant organisms. Different patterns of antibiotic administration cause a difference in bacterial composition and resistome in the human gut. We comprehensively investigated the association between the distribution of antibiotic resistance genes (ARGs), bacterial composition, and antibiotic treatments in patients with chronic obstructive pulmonary diseases (COPD) and Clostridioides difficile infections (CDI) who had chronic or acute intermittent use of antibiotics and compared them with healthy individuals. We analyzed the gut microbiomes of 61 healthy individuals, 16 patients with COPD, and 26 patients with CDI. The COPD patients were antibiotic-free before stool collection for a median of 40 days (Q1: 9.5; Q3: 60 days), while the CDI patients were antibiotic-free for 0 days (Q1: 0; Q3: 0.3). The intra-group beta diversity measured by the median Bray-Curtis index was the lowest for the healthy individuals (0.55), followed by the COPD (0.69) and CDI groups (0.72). The inter-group beta diversity was the highest among the healthy and CDI groups (median index = 0.89). The abundance of ARGs measured by the number of reads per kilobase per million reads (RPKM) was 684.2; 1,215.2; and 2,025.1 for the healthy, COPD, and CDI groups. It was negatively correlated with the alpha diversity of bacterial composition. For the prevalent ARG classes, healthy individuals had the lowest diversity and abundance of aminoglycoside, ß-lactam, and macrolide-lincosamide-streptogramin (MLS) resistance genes, followed by the COPD and CDI groups. The abundances of Enterococcus and Escherichia species were positively correlated with ARG abundance and the days of antibiotic treatment, while Bifidobacterium and Ruminococcus showed negative correlations for the same. In addition, we analyzed the mobilome patterns of aminoglycoside and ß-lactam resistance gene carriers using metagenomic sequencing data. In conclusion, the ARGs were significantly enhanced in the CDI and COPD groups than in healthy individuals. In particular, aminoglycoside and ß-lactam resistance genes were more abundant in the CDI and COPD groups, but the dominant mobile genetic elements that enable the transfer of such genes showed similar prevalence patterns among the groups.

The Dynamic Contribution of Neutrophils in the Chronic Respiratory Diseases.

Asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis are representative chronic respiratory diseases (CRDs). Although they differ in terms of disease presentation, they are all thought to arise from unresolved inflammation. Neutrophils are not only the first responders to acute inflammation, but they also help resolve the inflammation. Notably, emerging clinical studies show that CRDs are associated with systemic and local elevation of neutrophils. Moreover, murine studies suggest that airway-infiltrating neutrophils not only help initiate airway inflammation but also prolong the inflammation. Given this background, this review describes neutrophil-mediated immune responses in CRDs and summarizes the completed, ongoing, and potential clinical trials that test the therapeutic value of targeting neutrophils in CRDs. The review also clarifies the importance of understanding how neutrophils interact with other immune cells and how these interactions contribute to chronic inflammation in specific CRDs. This information may help identify future therapeutic strategies for CRDs.

Quantitative Determination of Related Substances in Formoterol Fumarate and Tiotropium in Tiomate Transcaps® Dry Powder Inhaler

Objectives: Tiotropium (TIO) and formoterol fumarate (FF) combination in dry powder inhaler (DPI) dosage form used for treating asthma, bronchospasm, chronic bronchitis, emphysema and chronic obstructive pulmonary diseases. Aim to develop an analytical method for estimating emerging and advancing dry powder inhaler combination toward enhanced therapeutics for the estimation of related substances but for this it is foremost to have a sensitive, simple, robust and validated method therefore, a new reverse phase-high performance liquid chromatography (HPLC) method has been developed for the determination of related substances in FF and TIO DPI. Materials and Methods: The analytical method was performed on schimadzu HPLC with a quaternary pump, the separation achieved using BDS Hypersil C18 (250×4.6 mm, 5 µm) column with mobile phase consisting of sodium phosphate buffer pH 3.2 and acetonitrile 1.0 mL min-1 flow rate in the gradient elution. Diluent consists of a mixture of buffer pH 3.2 and acetonitrile in the ratio of (70:30) %v/v. 30°C column temperature and photodiode-array detection detector at a wavelength 240 nm. The run time was 50 min. The Retention time of FF and TIO was found to be at 7.8 and 10.3 min respectively. Results: Both the analyte peaks were found to be free from interference. The method was validated as per the International Council on Harmonisation guidelines, the linearity was performed on 0.015 to 1.089 ppm for TIO and 0.01 to 0.728 ppm for FF concentration with correlation coefficient of 1,000. The precision and accuracy were also performed at the limit of quantification level were within the limits. Forced degradation study was also conducted. Conclusion: The recommended method for the related substance determination of FF and TIO is simple, selective, specific and precise. It also demonstrates the study of the degradation pattern. Moreover, the above developed related substance analytical method was applied to the bulk analysis and pharmaceutical dosage form for routine analysis and stability study.