COPD Research Articles

Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice.

Acute lung injury (ALI) represents a life-threatening condition with high morbidity and mortality despite modern mechanical ventilators and multiple pharmacological strategies. Therefore, there is a need to develop efficacious interventions with minimal side effects. The anti-inflammatory activities of sea cucumber (Cucumaria frondosa) and wild blueberry (Vaccinium angustifolium) extracts have been reported recently. However, their anti-inflammatory activities and the mechanism of action against ALI are not fully elucidated. Thus, the present study aims to understand the mechanism of the anti-inflammatory activity of sea cucumber and wild blueberry extracts in the context of ALI. Experimental ALI was induced via intranasal lipopolysaccharide (LPS) instillation in C57BL/6 mice and the anti-inflammatory properties were determined by cytokine analysis, histological examination, western blot, and qRT-PCR. The results showed that oral supplementation of sea cucumber extracts repressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby downregulating the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) in the lung tissue and in the plasma. Wild blueberry extracts also suppressed the expression of IL-4. Furthermore, the combination of sea cucumber and wild blueberry extracts restrained MAPK signaling pathways by prominent attenuation of phosphorylation of NF-κB, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) while the levels of pro-inflammatory cytokines were significantly suppressed. Moreover, there was a significant and synergistic reduction in varying degrees of ALI lesions such as distorted parenchyma, increased alveoli thickness, lymphocyte and neutrophil infiltrations, fibrin deposition, pulmonary emphysema, pneumonia, intra-alveolar hemorrhage, and edema. The anti-inflammatory effect of the combination of sea cucumber and wild blueberry extracts is associated with suppressing MAPK and NF-κB signaling pathways, thereby significantly reducing cytokine storm in LPS-induced experimental ALI.

Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry

BackgroundRecent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group. ObjectivesThe authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema. MethodsWe categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders. ResultsAmong 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis. ConclusionsThis study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541)

Recurrent Hemoptysis Post Re-Embolization in a 49 Year-Old Male with Post Tuberculosis Lung Disease (PTLD) and Bronchiectasis

Introduction: Hemoptysis is a symptom of lung disease, could be caused by lung infections, structural disorders of the lung, malignancy or disorders from outside of the lung. One of the pulmonary intervention for hemoptysis is embolization with a success rate > 70%, but the recurrence rate reaches 10-55%. The prognosis is poor depending on the amount of bleeding (untreated cases can have a mortality risk of over 50%), etiology and presence of recurrences.
 Case Illustration: A 49-year-old Male came to the policlinic with recurrent hemoptysis for a year. Non-smoker. History of Lung Tuberculosis (TB), completed treatment 15 years ago. Imaging result showed widening of the right subcostal artery, right posterior intercostal artery, bronchiectasis, active lung tuberculosis and left pulmonary emphysema. First embolization was done during Anti-Tuberculosis Drug (ATD) treatment for 6 months. Symptom of hemoptysis reappeared, then second embolization and fiber optic bronchoscopy (FOB) was performed. From the evaluation, he was diagnosed with infected bronchiectasis and PTLD, therefore given antibiotic medications for 2 weeks.
 Discussion: Embolization had been done twice in this case, no significant result. Based on literature, recurrent hemoptysis can still occur with a percentage about 10-55% after embolization and in this case, it might be caused by previous lung structural disorder and lung infections (Lung TB and Infected bronchiectasis).
 Conclusion: Although embolization has a success rate of > 70% for hemoptysis treatment, recurrence can still occur and highly dependent on the cause itself and patient's previous lung condition.
 Keywords: Hemoptysis, Embolization, Bronchiectasis, FOB, Lung TB, PTLD, ATD

COPD-FlowNet: Elevating Non-invasive COPD Diagnosis with CFD Simulations (Student Abstract)

Chronic Obstructive Pulmonary Disorder (COPD) is a prevalent respiratory disease that significantly impacts the quality of life of affected individuals. This paper presents COPD-FlowNet, a novel deep-learning framework that leverages a custom Generative Adversarial Network (GAN) to generate synthetic Computational Fluid Dynamics (CFD) velocity flow field images specific to the trachea of COPD patients. These synthetic images serve as a valuable resource for data augmentation and model training. Additionally, COPD-FlowNet incorporates a custom Convolutional Neural Network (CNN) architecture to predict the location of the obstruction site.

Feature evaluation of accelerometry signals for cough detection.

Cough is a common symptom of multiple respiratory diseases, such as asthma and chronic obstructive pulmonary disorder. Various research works targeted cough detection as a means for continuous monitoring of these respiratory health conditions. This has been mainly achieved using sophisticated machine learning or deep learning algorithms fed with audio recordings. In this work, we explore the use of an alternative detection method, since audio can generate privacy and security concerns related to the use of always-on microphones. This study proposes the use of a non-contact tri-axial accelerometer for motion detection to differentiate between cough and non-cough events/movements. A total of 43 time-domain features were extracted from the acquired tri-axial accelerometry signals. These features were evaluated and ranked for their importance using six methods with adjustable conditions, resulting in a total of 11 feature rankings. The ranking methods included model-based feature importance algorithms, first principal component, leave-one-out, permutation, and recursive features elimination (RFE). The ranking results were further used in the feature selection of the top 10, 20, and 30 for use in cough detection. A total of 68 classification models using a simple logistic regression classifier are reported, using two approaches for data splitting: subject-record-split and leave-one-subject-out (LOSO). The best-performing model out of the 34 using subject-record-split obtained an accuracy of 92.20%, sensitivity of 90.87%, specificity of 93.52%, and F1 score of 92.09% using only 20 features selected by the RFE method. The best-performing model out of the 34 using LOSO obtained an accuracy of 89.57%, sensitivity of 85.71%, specificity of 93.43%, and F1 score of 88.72% using only 10 features selected by the RFE method. These results demonstrate the ability for future implementation of a motion-based wearable cough detector.

On the curious association of diaphragmatic hernia and Urban-Rifkin-Davis Syndrome (Autosomal Recessive Cutis Laxa-1C): A collective review of 16 cases

Background: Autosomal recessive cutis laxa type-1C is also known as Urban-Rifkin-Davis syndrome (URDS). It is known to affect cardiopulmonary, integumentary, gastrointestinal, musculoskeletal and genitourinary systems. However, its frequent association with congenital diaphragmatic hernia has not previously been highlighted. Case Presentation: A newborn male with cutis laxa presented with respiratory distress at birth. The cause of dyspnoea was perinatal strangulation of the stomach in hiatus hernia. After surgical repair of the hernia, his respiratory distress temporarily improved but kept recurring periodically by various mechanisms in sequence namely pulmonary hypertension, tracheomalacia, pulmonary emphysema and finally he succumbed to pneumothorax. Genetic analysis revealed his skin condition as autosomal recessive cutis laxa type-1C which is also known as URDS. Exome sequencing revealed a novel frameshift mutation c.426delC (p.Cys143Alafs*41) of the LTBP4 gene in the exon 5 of Chromosome 19. Conclusion: Out of the 28 cases of URDS reported in the world literature 57% had congenital diaphragmatic hernia (CDH) and 53% of them died during infancy. Such a high incidence of CDH is not observed in other subtypes of elastic disorders. Thus, congenital diaphragmatic defects appear to be a characteristic diagnostic feature of URDS in patients with cutis laxa.

Efficacy and Safety of Medical Thoracoscopic Bulla Volume Reduction in the Treatment of Chronic Obstructive Pulmonary Disease Combined With Giant Emphysematous Bullae

To explore the efficacy and safety of medical thoracoscopic bulla volume reduction for the treatment of chronic obstructive pulmonary disease (COPD) combined with giant emphysematous bullae (GEB). A total of 66 patients with COPD combined with GEB were enrolled in the study. All the subjects received treatment at Zhengzhou Central Hospital affiliated with Zhengzhou University between March 2021 and December 2022. The subjects were divided into two groups, a medical thoracoscope group consisting of 30 cases treated with medical thoracoscopic bulla volume reduction and a surgical thoracoscope group consisting of 36 cases treated by video-assisted thoracoscopic surgery. All patients were followed up before discharge and 3 months and 6 months after discharge. The preoperative and postoperative levels of the pulmonary function, 6-minute walk distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores and differences in postoperative complications were compared between the two groups. The operative duration, postoperative length-of-stay, and surgical costs and hospitalization bills, and the maximum visual analog scale (VAS) pain scores at 24 h after the procedure were assessed. The baseline data of the two groups were comparable, showing no statistically significant difference. The forced expiratory volume in 1 second (FEV1) 6 months after the procedures improved in both the medical thoracoscopy group ([0.78±0.29] L vs. [1.02±0.31] L, P<0.001) and the surgical thoracoscopy group ([0.80±0.21] L vs. [1.03±0.23] L, P<0.001) compared to that before the procedures. Improvements to a certain degree in 6MWT and SGRQ scores were also observed in the two groups at 3 months and 6 months after the procedures (P<0.05). In addition, no statistically significant difference in these indexes was observed during the follow-up period of the patients in the two groups. There was no significant difference in operating time between the two groups. The medical thoracoscopy group had shorter postoperative length-of-stay ([7.3±2.6] d) and 24-hour postoperative VAS pain scores (3.0 [2.0, 3.3]) than the surgical thoracoscopic group did ([10.4±4.3] d and 4.5 [3.0, 5.0], respectively), with the differences being statistically significant (P<0.05). Surgical cost and total hospitalization bills were lower in the medical thoracoscopy group than those in the surgical thoracoscopy group (P<0.05). The complication rate in the medical thoracoscopy group was lower than that in the surgical thoracoscopy group (46.7% vs. 52.8%), but the difference was not statistically significant. Medical thoracoscopic reduction of bulla volume can significantly improve the pulmonary function, quality of life, and exercise tolerance of patients with COPD combined with GEB, and it can reduce postoperative short-term pain and shorten postoperative length-of-stay. The procedure has the advantages of minimal invasiveness, quick recovery, and low costs. Hence extensive clinical application is warranted.

Pathological characterization of pulmonary lesion and identification of associated bacteria and parasite infection in sheep and goat slaughtered at Dessie municipal abattoir, North-East Ethiopia

BackgroundLung is susceptible and vulnerable to many infectious and non-infectious agents. From this, a large number of specific and nonspecific diseases conditions can be diagnosed. A cross-sectional study design was conducted from December 2022 to May 2023 on major pulmonary lesion of sheep and goat slaughtered at Dessie municipal abattoir with the objective of characterizing the pulmonary pathological lesions, and isolating and identifying potential aerobic bacteria and parasite from pneumonic lung.Materials and MethodsA total of 420 (302 sheep and 118 goats) were examined for gross lung lesions and histopathological investigation using standard techniques. Additionally, detailed pathological investigation was conducted on purposively selected lung lesions. Besides, pneumonic lesions were subjected to routine bacteriological and parasitological analysis.ResultsThe overall abattoir prevalence of pulmonary abnormalities in sheep and goat was 81.2% (341/420). The common gross lesions encountered were Pneumonia (55.5%), emphysema (7.1%), atelectasis (3.3%), Hydatid cyst (4.3%), congestion (2.4%), haemorrhage (3.1%), Anthracosis (0.9%), adhesion (0.7%), and Bronchoectasis (0.7%) respectively. Pneumonia, hydatidosis, and pulmonary emphysema were significantly associated (p < 0.05) with animal age groups. Pneumonia was the most common disorder, accounting for 233 (55.5%). Dictyocaulus filaria (47.7%), Mullerius capillaries (23.2%) and Protostrongylus rufescens (17.16%) were isolated lung worm parasites; whereas E. coli (20.6%), Klebsiella Pneumoniae (12.7%), Mannheimia haemolytica (10.8%), Streptococcus species (4.9%), Staphylococcus aurous (7.8%) and Pasteurella multocida (2.9%), Pseudomonas (6.9%), Proteus (1.9%) and Cornybacterium (1%) were the isolated bacteria. Moreover, 18 (4.3%) Hydatid cysts were identified by cyst viability test. The pulmonary disorder of sheep and goats in the study are relatively high prevalent and posing great health and economic impacts.ConclusionPulmonary infection with different agents is very common in the study areas. Feasible and affordable control measures and using latest diagnostic techniques like molecular detections of bacteria, viruses, and fungi, is necessary.

Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women

BackgroundBreathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.MethodsCross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50–64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.ResultsWe included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0–29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6–66.0%), stress (31.6–76.8%), respiratory disease (20.1–37.1%), depression (17.1–26.6%), cardiac disease (6.3–12.7%), anemia (0.8–3.3%), and peripheral arterial disease (0.3–0.8%). Stress was the main factor in women and current smokers.ConclusionBreathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting—supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Smoking And The Risk Of Developing Diabetes Mellitus Type 2 In Young Adult Patients

“According to the latest data from the Vigitel survey (Surveillance of Risk Factors and Protection for Chronic Diseases by Telephone Survey), from the Ministry of Health, the rate of young consumers between 18 and 24 years old jumped from 7.4% in 2016, to 8.5% in 2017.” This statement demonstrates that even with public policies to combat smoking, the prevalence of this problem is still specific in Brazil and has become a common practice among young people. Smoking is a public health problem and can be defined as a chronic disease characterized by nicotine dependence, which is acquired through the consumption of products containing tobacco. Several health problems related to tobacco use, such as pulmonary emphysema, lung cancer, tongue cancer, chronic bronchitis, cataracts, osteoporosis and several studies demonstrate their relationship with the development of diabetes mellitus, this is because cigarettes increase resistance insulin by decreasing its peripheral action. Therefore, the use of tobacco deregulates glycemic control and increases the manifestation of the disease, or generates decompensation for those patients who already have the pathology. According to Dr. Fernanda Pena (endocrinologist specializing in metabolism), the risk of developing diabetes is 30 to 40% higher in smokers than in non-smokers and studies suggest that 10% of all cases of type 2 diabetes can be directly targeted to smoking.

Pulmonary hypertension in newly diagnosed obstructive sleep apnea-chronic obstructive pulmonary disease overlap syndrome patients attending a tertiary care centre-a cross-sectional analysis.

Overlap syndrome is the association of obstructive sleep apnea (OSA) with chronic obstructive pulmonary disorder and with other chronic respiratory diseases. Patients with overlap syndrome have a worse prognosis compared with chronic obstructive pulmonary disorder or OSA alone. Additionally, patients with combined chronic obstructive pulmonary disorder and OSA are more likely to develop pulmonary hypertension and right heart failure much earlier than those without overlap. To assess the occurrence of pulmonary hypertension (PH) in newly diagnosed OSA-chronic obstructive pulmonary disorder overlap syndrome patients attending a tertiary care centre. This cross-sectional study was conducted at Department of Pulmonary Medicine, Government Medical College, Kozhikode, Kerala, South India, among patients with OSA above 40years of age who were proactively evaluated to pick out those with undiagnosed overlap. A period of 6months after getting ethical clearance from June 2018 was selected as the study period. Among patients with symptoms suggestive of OSA above 40years of age who gave the informed consent were enrolled after screening with Standard Sleep questionnaires (Berlin questionnaire, STOP BANG and Epworth Sleepiness Scale). Enrolled patients underwent routine spirometry and sleep study using the standard Level 1 overnight polysomnography (Level1 OPSG). Patients were classified in to two groups as OSA patients (group I), having an apnea hypopnea index (AHI) > 5/hr alone and the second group as those OSA patients (group II), with an obstructive spirometry pattern who were the overlap group. Arterial blood gas analysis (a sample of radial arterial blood was drawn with the patient awake and supine, and was analyzed for pH, PaCO2 and PaO2) and echocardiography (ECHO) of the two groups were compared as a non-invasive method to assess pulmonary artery hypertension and results were analyzed in a systematic manner. Among the 84 patients enrolled, 16.7% had overlap syndrome and the rest had OSA alone. Statistically significant higher mean weight and BMI for those with overlap syndrome compared to the OSA group were observed. Mean FVC (forced vital capacity), FEV1 (forced expiratory volume 1s), and FEV1/FVC were lower in those with overlap syndrome compared to OSA group. The mean values of ABG parameters revealed higher PaCO2 and lower PaO2 among the group with overlap syndrome which were statistically significant. However, there was no significant difference in resting room air SaO2 value between the two groups. The mean values of sleep duration and efficiency were significantly lower in those with overlap syndrome with a p value < 0.001. The mean value of arousal and REM (rapid eye movement) sleep percentage were significantly higher among those with overlap syndrome (p < 0.001). Mean value of NREM (non-rapid eye movement) sleep percentage was lower among the group with overlap syndrome compared with the OSA group, and this difference was statistically significant. The mean AHI value of the overlap syndrome group was 39.79 ± 7.54 and this was significantly higher than the OSA group (p < 0.004). Among the 14 patients who had ECHO evidence of pulmonary hypertension, 9 (64.3%) belonged to the overlap group which shows that they are a highly vulnerable group for developing pulmonary hypertension (PH) and requires early detection and more rigorous treatment. This study confirms that OSA patients with modest daytime level of hypoxemia and mild-moderate chronic airflow limitation have a high prevalence of PH. Chronic airway obstruction may be asymptomatic in some subjects and this stresses the necessity of pulmonary function test in OSA.

An Insight on Microfluidic Organ-on-a-Chip Models for PM2.5-Induced Pulmonary Complications.

Pulmonary diseases like asthma, chronic obstructive pulmonary disorder, lung fibrosis, and lung cancer pose a significant burden to global human health. Many of these complications arise as a result of exposure to particulate matter (PM), which has been examined in several preclinical and clinical trials for its effect on several respiratory diseases. Particulate matter of size less than 2.5 μm (PM2.5) has been known to inflict unforeseen repercussions, although data from epidemiological studies to back this are pending. Conventionally utilized two-dimensional (2D) cell culture and preclinical animal models have provided insufficient benefits in emulating the in vivo physiological and pathological pulmonary conditions. Three-dimensional (3D) structural models, including organ-on-a-chip models, have experienced a developmental upsurge in recent times. Lung-on-a-chip models have the potential to simulate the specific features of the lungs. With the advancement of technology, an emerging and advanced technique termed microfluidic organ-on-a-chip has been developed with the aim of identifying the complexity of the respiratory cellular microenvironment of the body. In the present Review, the role of lung-on-a-chip modeling in reproducing pulmonary complications has been explored, with a specific emphasis on PM2.5-induced pulmonary complications.

Exploring the Potential Role of Metabolomics in COPD: A Concise Review.

Chronic Obstructive Pulmonary Disease (COPD) is a pathological condition of the respiratory system characterized by chronic airflow obstruction, associated with changes in the lung parenchyma (pulmonary emphysema), bronchi (chronic bronchitis) and bronchioles (small airways disease). In the last years, the importance of phenotyping and endotyping COPD patients has strongly emerged. Metabolomics refers to the study of metabolites (both intermediate or final products) and their biological processes in biomatrices. The application of metabolomics to respiratory diseases and, particularly, to COPD started more than one decade ago and since then the number of scientific publications on the topic has constantly grown. In respiratory diseases, metabolomic studies have focused on the detection of metabolites derived from biomatrices such as exhaled breath condensate, bronchoalveolar lavage, and also plasma, serum and urine. Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy are powerful tools in the precise identification of potentially prognostic and treatment response biomarkers. The aim of this article was to comprehensively review the relevant literature regarding the applications of metabolomics in COPD, clarifying the potential clinical utility of the metabolomic profile from several biologic matrices in detecting biomarkers of disease and prognosis for COPD. Meanwhile, a complete description of the technological instruments and techniques currently adopted in the metabolomics research will be described.

Prevalence and characteristics of patients prescribed opioids and central nervous system depression agents on discharge to hospice care.

Hospice patients with end-stage liver disease (ESLD) have an increased risk of adverse drug events due to physiological changes and changes in pharmacokinetic and pharmacodynamic properties of medications; however, the use of opioid and central nervous system (CNS) depressant prescribing among patients with ESLD is prevalent. This study quantified the frequency and distribution of opioid and concomitant respiratory and CNS depressant prescribing among hospice patients with ESLD compared to other common hospice diagnoses of cancer, chronic obstructive pulmonary disorder (COPD), heart failure, and end-stage renal disease. This was a cross-sectional study of adult (age 18 years or older) decedents of a large hospice chain. Patients included had a primary diagnosis of liver, cancer, cardiovascular, or respiratory disease. Among 119,424 hospice decedents, mean age of 77.9 years (standard deviation =13.5 years), 54.6% were female, and 58.9% were of a non-Hispanic white race. There was a similar frequency of prescribing a "scheduled" and "as needed [pro re nata (PRN)]" opioid or benzodiazepine in patients with ESLD compared to other common hospice diagnoses. In addition, there was a high prevalence of concurrent opioid and benzodiazepine prescriptions among patients with ESLD compared to cardiovascular and respiratory disease at admission (65.4% vs. 63.9% and 64.9%). Opioid requirements, oral morphine equivalent (OME) median [interquartile range (IQR)] at discharge were similar between cancer, liver, and respiratory disease, 120 OME [60-300], 120 OME [50-240], and 120 OME [50-240], respectively. We observed a high frequency of opioid and CNS depressant prescribing in a hospice patient population with ESLD which was similar to other common admitting hospice diagnoses.

MTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERTCI. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema.

Catastrophic complications following microvascular free tissue transfer: A 10-year review of NSQIP data

IntroductionThere is an absence of literature regarding the risks of catastrophic medical outcomes (CMOs) such as stroke, cardiac arrest, and pulmonary embolism in microvascular free tissue transfer. This study aims to determine the CMO and mortality rates, as well as risk factors, associated with microvascular reconstruction of the head and neck, extremity, and breast. MethodsThis study uses data from the American College of Surgeons National Surgical Quality Improvement Program. Cases of microvascular free tissue transfer from 2012 to 2021 were analyzed to assess the 30-day rates of CMOs, including death, as well as associated risk factors. ResultsOf the 22,839 included patients, 785 (3.44%) experienced 1043 CMOs, including 99 (0.43%) deaths. Pulmonary complications of prolonged respiratory failure and pulmonary embolism were the most common. Independent risk factors included age, male sex, underweight status, longer operation times, American Society of Anesthesiologists (ASA) class of III or above, wound classification other than clean, and underlying conditions such as diabetes, hypertension, chronic obstructive pulmonary disorder, dyspnea, metastatic cancer, and ventilator dependence. CMOs were associated with an average 10-day delay in hospital discharge. Multivariate regression analysis revealed that head and neck reconstructions were associated with increased risk of CMO (OR 4.96; p < 0.0001). ConclusionThis is the largest study to examine CMOs following microvascular free tissue transfer. Compared to previous literature spanning the period between 2006 and 2011, we observed a decreased rate of CMOs but a slight increase in 30-day mortality. Our data provide updated and comprehensive criteria for risk stratification and patient counseling. The modifiable risk factors reported in our study should be considered in elective, non-urgent cases of microvascular reconstruction.

Prevalence and Impact of Thyroid Dysfunction in Patients With Chronic Pulmonary Obstructive Pulmonary Disorder: A Systematic Review and Meta-Analysis.

Thyroid gland dysfunction (TGD) has been increasingly recognized as a potential comorbidity in patients with chronic obstructive pulmonary disease (COPD). This study was designed to determine the prevalence of TGD in COPD patients.This systematic review and meta-analysis was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).To comprehensively identify relevant studies, a systematic search was conducted in major electronic databases, including PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHIL).The search was limited to English-language studies published after 31December 2000. To determine the prevalence of TGDand assess the impacts, we compared forced vital capacity (FVC) (%), forced expiratory volume in one second (FEV1) (%), partial pressure of oxygen (PaO2) (mmHg), and partial pressure of carbon dioxide (PaCO2) (mmHg) between patients with and without TGD. A total of nine articles were included in this meta-analysis.The sample size of included studies ranged from 50 to 309.The pooled prevalence of TGD in patients with COPD was 45% (95% CI: 25% to 65%). The most common form of TGD was hypothyroidism. The study identified a lack of significant associations between TGD and COPD severity or various characteristics, highlighting the need for future prospective multi-center research, particularly with larger sample sizes to determine the clinical factors and biomarkers affecting the development of thyroid dysfunction in this population.

Lysophospholipid Acyltransferase 9 Promotes Emphysema Formation via Platelet-activating Factor.

Cigarette smoking is known to be the leading cause of chronic obstructive pulmonary disease (COPD). However, the detailed mechanisms have not been elucidated. PAF (platelet-activating factor), a potent inflammatory mediator, is involved in the pathogenesis of various respiratory diseases such as bronchial asthma and COPD. We focused on LPLAT9 (lysophospholipid acyltransferase 9), a biosynthetic enzyme of PAF, in the pathogenesis of COPD. LPLAT9 gene expression was observed in excised COPD lungs and single-cell RNA sequencing data of alveolar macrophages (AMs). LPLAT9 was predominant and upregulated in AMs, particularly monocyte-derived AMs, in patients with COPD. To identify the function of LPLAT9/PAF in AMs in the pathogenesis of COPD, we exposed systemic LPLAT9-knockout (LPALT9-/-) mice to cigarette smoke (CS). CS increased the number of AMs, especially the monocyte-derived fraction, which secreted MMP12 (matrix metalloprotease 12). Also, CS augmented LPLAT9 phosphorylation/activation on macrophages and, subsequently, PAF synthesis in the lung. The LPLAT9-/- mouse lung showed reduced PAF production after CS exposure. Intratracheal PAF administration accumulated AMs by increasing MCP1 (monocyte chemoattractant protein-1). After CS exposure, AM accumulation and subsequent pulmonary emphysema, a primary pathologic change of COPD, were reduced in LPALT9-/- mice compared with LPLAT9+/+ mice. Notably, these phenotypes were again worsened by LPLAT9+/+ bone marrow transplantation in LPALT9-/- mice. Thus, CS-induced LPLAT9 activation in monocyte-derived AMs aggravated pulmonary emphysema via PAF-induced further accumulation of AMs. These results suggest that PAF synthesized by LPLAT9 has an important role in the pathogenesis of COPD.

Analysis of body composition with bioelectrical impedance analysis in patients with severe COPD and pulmonary emphysema

BackgroundPatients with chronic obstructive pulmonary disease (COPD) often suffer from cachexia and malnutrition. Less is known about body composition and nutritional behaviour in patients with advanced COPD and pulmonary emphysema. MethodsWe performed a single-center prospective analysis of patients with COPD GOLD III/IV. Metabolic parameters, dietary and exercise behavior, lung function, exercise capacity and body composition by bioelectrical impedance analysis (BIA) were analyzed. Patients with severe emphysema (emphysema index [EI] >20%) were compared to patients with mild emphysema (EI ≤ 20%). ResultsA total of 121 patients (45.5% female, mean age 64.8 ± 8.1 years, mean FEV1 31.0 ± 8.6%, mean RV 234.7 ± 50.6%) were analyzed, of whom 14.1% were underweight. Only 5% of the patients substituted protein and only about 1/3 performed regular exercise training. BIA showed an unfavourable body composition: body fat ↑, ECM/BCM-index ↑, phase angle ↓ (5.0 ± 0.9°), cell percentage ↓, FFMI (fat-free mass index) ↓. The 94 patients with severe emphysema (mean EI 36.6 ± 8.5%) had lower body-mass-index (22.8 ± 4.3 vs. 31.1 ± 5.8 kg/m2, p < 0.001), FFMI, body weight and body fat, but did not differ significantly in the quality of body composition (e.g. phase angle). Their lipid and glucose metabolism were even better than in mild emphysema patients. ConclusionThe finding of significantly lower BMI but similar body composition and better metabolic status in severe emphysema patients needs further investigation. However, it should not distract from the necessity to implement dietary and exercise recommendations for advanced COPD patients.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.