COPD Research Articles

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.

The impact of chronic obstructive pulmonary disease on bone strength.

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties.

Abstract WP281: Investigating the Incidence of Stroke in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Background: Chronic obstructive pulmonary disorder (COPD) is a progressive respiratory disorder ranking third in global mortality. It often correlates with new cardiovascular incidents including stroke, affecting both management and prognostic considerations. The precise relationship between the incidence of stroke and COPD remains unclear. We performed a meta-analysis to determine the incidence of stroke in COPD patients. Methods: The PubMed and EMBASE databases were searched using predefined search terms encompassing COPD, emphysema, chronic bronchitis, and stroke related terms. The search timeline included the earliest available date until April 2023, including studies that investigated stroke occurrence in COPD patients. The analysis was conducted using CMA v.3 and R (Version: 4.3.1). The number of patients with COPD and stroke in each study were extracted and analyzed. A random-effects model was employed to calculate the incidence, pooled odds ratio (OR), and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the I^2 statistic. The prediction interval was calculated to explain the distribution of the true effects. Results: A total of 33 studies matched our inclusion criteria, with a total of 865521 COPD patients. The weighted mean age of the population was 60.46 years, and 98739 of them had an incident of stroke in their lifetime. From the pooled analysis of all 33 included studies, using the random effects model, the incidence of stroke was 7.6% (Proportion, 0.076; 95% CI, 0.060 - 0.095, I2=99%). The prediction interval was calculated to be 0.02-0.27. Our analysis also showed a pooled odds ratio of 1.355 (95% CI:1.281-1.432, I2=99.96%) using the random effects model. Conclusion: We report a 7.6% incidence of stroke in COPD patients, and an increase in the odds of stroke in individuals with COPD. The cardiovascular health of such patients should be adequately monitored to mitigate the risk of stroke.

Alpha-1 Antitrypsin Gene Variants in Patients without Severe Deficiency Diagnosed with Pulmonary Emphysema on Chest CT.

Although pulmonary involvement due to alpha-1 antitrypsin (AAT) deficiency has been widely described, most studies focus on the genotypes causing severe deficiency (<60 mg/dL). The aim of this study was to analyze the prevalence of the different AAT gene variants that do not cause severe deficiency in patients with pulmonary emphysema diagnosed by thoracic computed tomography (CT). Furthermore, we assessed the risk associated with a non-severe decrease in AAT values in the pathogenesis of emphysema. Case-control study design that included patients who had a CT scan available of the entire thorax. In total, 176 patients with emphysema (cases) and 100 control subjects without emphysema were analyzed. The prevalence of variants was higher among cases (25.6%; 45/176) than controls (22%; 22/100), although the difference was not statistically significant (P=0.504) when analyzed globally. In the control group, all the variants detected were MS. Excluding this variant, statistically significant differences were observed in the remaining variants (MZ, SS and SZ). Only 18% of the controls (all MS) presented values below our limit of normality, and all had values very close to the reference value (90 mg/dL). In contrast, 76% of patients with the other variants presented pathological levels. In a logistic regression model, both smoking and a non-severe reduction in AAT (60 to 90 mg/dL) increased the probability of emphysema. Our study confirms an association between certain variants in the alpha-1 antitrypsin gene that do not cause severe deficiency and the presence of pulmonary emphysema. This association with variants that are associated with reductions in serum AAT values is statistically significant and independent of smoking habit.

Dementia and Multimorbidity Trends in Al-Baha, Saudi Arabia: An Analytical Retrospective Study Using Records-Based Data.

The prevalence of dementia is escalating significantly, posing a substantial societal burden. Currently, there exists a dearth of comprehensive health data about dementia patients in Saudi Arabia, particularly within Al-Baha City. A retrospective case-series study was undertaken to ascertain the prevalence of dementia within the populace of the Al-Baha region, Kingdom of Saudi Arabia. This investigation utilized hospital-based records encompassing individuals exhibiting symptoms or diagnosed with dementia and its related forms across the Al-Baha region. Furthermore, the study aimed to evaluate the burden of comorbidities among dementia patients and document the pharmacological therapeutic interventions administered to manage dementia and its associated concurrent health conditions. Our investigation explored the prevalence rates of various forms of dementia and the accompanying comorbidities among affected individuals. The study spanned from August 2020 to August 2023. Our study encompassed 407 patients diagnosed with Alzheimer's disease (AD), Parkinson's disease, vascular dementia (VaD), or other forms of dementia who were either admitted to or attended tertiary hospitals in Al-Baha. Assessment of the comorbidity burden was conducted using the Charlson Comorbidity Index (CCI). Our findings revealed that among these patients, 13.3% presented with AD, 23.6% with VaD, 33.4% with Parkinson's disease, 15.75% with amnesia, and 14.0% with other types of dementia. The spectrum of comorbidities observed among dementia patients encompassed various conditions, with diabetes mellitus emerging as the predominant comorbidity (19.1%), followed by hypertension (16.4%). Additionally, manifestations of depression were noted in 14% of patients, while 9.82% suffered from paralysis. Chronic conditions such as cancer, chronic obstructive pulmonary disorder (COPD), and cervical spondylosis were also observed among individuals afflicted with dementia and its varied forms. Statistically significant correlations were established between gender, age, nationality, comorbidities, and the prevalence of dementia. Therapeutic interventions in the form of pharmacological treatments were prescribed for dementia patients with comorbidities. Commonly administered medications included Amlod (6.3%), Amlodipine (6.6%), Amlor (5.8%), Aspirin (10.5%), chemotherapeutic drugs (4.4%), Glipizide (8.5%), Lantus (11.3%), Levodopa (23.5%), Metformin (7.8%), acetylcholinesterase inhibitors (6.8%), and Pulmicort (7.86%). These medications aimed to alleviate symptoms associated with dementia and its accompanying comorbidities. Our investigation underscores the substantial burden of comorbidities experienced by dementia patients. These findings offer crucial insights into the overall health status of individuals grappling with dementia, serving as a catalyst for increased awareness among clinicians and policymakers. Such awareness can drive improvements in medical care and support frameworks tailored to the specific needs of dementia patients.

Risk factors for herpes zoster infections: a systematic review and meta-analysis unveiling common trends and heterogeneity patterns

PurposeThe burden of herpes zoster (HZ) is substantial and numerous chronic underlying conditions are known as predisposing risk factors for HZ onset. Thus, a comprehensive study is needed to synthesize existing evidence. This study aims to comprehensively identify these risk factors.MethodsA systematic literature search was done using MEDLINE via PubMed, EMBASE and Web of Science for studies published from January 1, 2003 to January 1, 2023. A random-effects model was used to estimate pooled Odds Ratios (OR). Heterogeneity was assessed using the I2 statistic. For sensitivity analyses basic outlier removal, leave-one-out validation and Graphic Display of Heterogeneity (GOSH) plots with different algorithms were employed to further analyze heterogeneity patterns. Finally, a multiple meta-regression was conducted.ResultsOf 6392 considered records, 80 were included in the meta-analysis. 21 different conditions were identified as potential risk factors for HZ: asthma, autoimmune disorders, cancer, cardiovascular disorders, chronic heart failure (CHF), chronic obstructive pulmonary disorder (COPD), depression, diabetes, digestive disorders, endocrine and metabolic disorders, hematological disorders, HIV, inflammatory bowel disease (IBD), mental health conditions, musculoskeletal disorders, neurological disorders, psoriasis, renal disorders, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and transplantation. Transplantation was associated with the highest risk of HZ (OR = 4.51 (95% CI [1.9–10.7])). Other risk factors ranged from OR = 1.17–2.87, indicating an increased risk for all underlying conditions. Heterogeneity was substantial in all provided analyses. Sensitivity analyses showed comparable results regarding the pooled effects and heterogeneity.ConclusionsThis study showed an increased risk of HZ infections for all identified factors.

A formula for predicting emphysema extent in combined idiopathic pulmonary fibrosis and emphysema

BackgroundNo single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema.MethodsThe development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema.ResultsThe formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) – (0.65 x percent predicted forced expiratory volume in 1 second) – (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R2 = 0.25, P < 0.0001; R2 = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105).ConclusionThe formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests.Trial registrationNCT00047645; NCT00075998.

An Uncommon Cause of Large Hemoptysis

Bullous emphysema is a recognized complication of chronic obstructive pulmonary disease (COPD), often leading to pneumothorax. However, intrabullous fluid accumulation is an uncommon manifestation. We present a case of a 55-year-old chronic smoker with a history of pulmonary tuberculosis and COPD, admitted with large hemoptysis. Imaging revealed a massive cystic lesion within an emphysematous bulla. Despite negative infectious and embolic workup, the patient's critical condition precluded surgical intervention. Embolization with interventional radiology yielded good results and controlled bleeding. This case emphasizes the significance of meticulous history-taking, comprehensive imaging review, and a multidisciplinary approach to diagnosis and management in challenging clinical scenarios.

Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase.

Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50µl, 0.667IU) to induce emphysema. Treatment with PNU-282987 (2.0mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1β, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.

Pneumothorax and pulmonary hemorrhage after C-arm cone-beam computed tomography-guided percutaneous transthoracic lung biopsy: incidence, clinical significance, and correlation

ObjectiveThis study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters.MethodsA retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH.ResultsPTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH.ConclusionsCBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.

Social Determinants of Health Associated with Inpatient Admissions for Congestive Heart Failure, Diabetes, Chronic Obstructive Pulmonary Disease, and Asthma

Introduction: The CDC and American Lung Association estimate that congestive heart failure (CHF), diabetes, chronic obstructive pulmonary disorder (COPD), and asthma (COPD/asthma) cost Americans $30.7 billion, $327 billion, and $50 billion respectively each year. They account for most inpatient readmissions at St. Mary Medical Center (SMMC), an urban hospital in Northwest Indiana. There is need for further research on the social, behavioral, and demographic determinants associated with these conditions. This study examined the social, behavioral, and demographic determinants associated with inpatient admission for CHF, diabetes, COPD/asthma in SMMC’s service area.&#x0D; Methods: This retrospective study was part of a multi-phased Community-Based Participatory Research partnership between SMMC and Indiana University School of Medicine Northwest. SMMC implemented a pilot screening and referral program to assess social determinants of health in their service area as part of their Hospital Readmission Reduction Program. This study included data from 10,953 inpatient admissions between January 2021 to March 2023, majority of whom were transferred from the emergency department. Data analysis consisted ofunivariate, bivariate (Chi-square), and multivariate (binary logistic regression) analysis in SPSS 29.0.&#x0D; Results: Bivariate analysis revealed a statistically significant association between CHF and smoking, age, insurance type, and income. Diabetes was significantly associated with smoking, smokeless tobacco use, age group, race, income, and sex. COPD/asthma was significantly associated with smoking, age group, transportation needs, stress, insurance, ethnicity, and sex. Multivariate analysis found the following significant associations: age group with both CHF (p&lt;0.001) and diabetes (p&lt;0.001), former smoking with both CHF (p = 0.007) and COPD/asthma (p = 0.049), current smoking with COPD/asthma (p = 0.016), and sex with diabetes (p &lt;0.001).&#x0D; Conclusions: These findings indicate significant associations between multiple sociobehavioral factors and admission for CHF, diabetes, COPD/asthma. Multi-risk-factor interventions may address these interactions and contribute to reducing readmission.

MiR‑186‑5p regulates the inflammatory response of chronic obstructive pulmonary disorder by targeting HIF‑1α.

Chronic obstructive pulmonary disorder (COPD) is a chronic respiratory disease that is a major cause of morbidity and mortality worldwide. Previous studies have shown that miR‑186‑5p expression is significantly increased in COPD and is involved in multiple physiological and pathological processes. However, the role of miRNA‑186‑5p in the inflammatory response of COPD remains unclear. In this study, an invitro model of COPD was established using lipopolysaccharide (LPS)‑induced human bronchial epithelial cells (BEAS‑2B). CCK‑8 assays, flow cytometry, and a Muse cell analyzer were used to determine cell viability, cell cycle distribution, and apoptosis, respectively. The production of TNF‑α and IL‑6 were measured by ELISA. Reverse‑transcription‑quantitative PCR and western blotting were used to analyze mRNA and protein expression levels. The targeting relation between miR‑186‑5p and HIF‑1α was discovered using dual‑luciferase reporter assays. The results showed that transfection of miR‑186‑5p inhibitor inhibited cell proliferation and promoted cell apoptosis in the LPS‑induced BEAS‑2B cells. Inhibition of miR‑186‑5p markedly increased the levels of TNF‑α and IL‑6. miR‑186‑5p directly targeted and negatively regulated HIF‑1α expression. In addition, inhibition of miR‑186‑5p increased the expression of the NF‑κB pathway protein p‑p65. In conclusion, it was found that inhibiting miR‑186‑5p may improve inflammation of COPD through HIF‑1α in LPS‑induced BEAS‑2B cells, possibly by regulating NF‑κB signaling. These findings provide a novel potential avenue for the clinical management of COPD. Future research is required to determine the mechanism of the interaction between miR‑186‑5p and HIF‑1α in COPD.