Brief Report: Alternative Pulmonary Function Measures of Emphysema in People With HIV.

INTRODUCTION: People with HIV (PWH) have nearly twice the risk of emphysema than people without HIV. This risk, which has been associated with HIV-mediated changes in the lung immune environment and more extensive radiographic emphysema, may result in different patterns of airflow limitation on pulmonary function testing (PFT) than those traditionally used in people without HIV. METHODS: In this prospective cohort of PWH in Atlanta, Georgia, we analyzed PFT and chest computed tomography data from July 2013 through June 2018. After comparing the prevalence of PFT measures of airflow limitation for those with and without radiographic emphysema, we used binary recursive partitioning to identify PFT measures that differentiated between PWH with and without radiographic emphysema. RESULTS: Among 167 PWH who had both PFT and computed tomography data during the study period, 89 (53%) had radiographic emphysema. Those with radiographic emphysema were more likely to have airflow limitations on PFTs. Recursive partitioning identified partitions at a forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) of 0.78 and a residual volume of 116% predicted. These partitions enabled the identification of 84 (94%) PWH with radiographic emphysema, in contrast to the traditional diagnostic criteria of an FEV1/FVC ratio of 0.7, which only identified 49 (55%) of those with radiographic emphysema. CONCLUSIONS: Emphysema in PWH may have different patterns of airflow limitation on PFTs that are not adequately captured by traditional diagnostic criteria. Future studies can seek to validate these findings and determine optimal thresholds for diagnosing HIV-associated emphysema.

The Role of the Extracellular Matrix in the Pathogenesis and Treatment of Pulmonary Emphysema.

Pulmonary emphysema involves progressive destruction of alveolar walls, leading to enlarged air spaces and impaired gas exchange. While the precise mechanisms responsible for these changes remain unclear, there is growing evidence that the extracellular matrix plays a critical role in the process. An essential feature of pulmonary emphysema is damage to the elastic fiber network surrounding the airspaces, which stores the energy needed to expel air from the lungs. The degradation of these fibers disrupts the mechanical forces involved in respiration, resulting in distension and rupture of alveolar walls. While the initial repair process mainly consists of elastin degradation and resynthesis, continued alveolar wall injury may be associated with increased collagen deposition, resulting in a mixed pattern of emphysema and interstitial fibrosis. Due to the critical role of elastic fiber injury in pulmonary emphysema, preventing damage to this matrix component has emerged as a potential therapeutic strategy. One treatment approach involves the intratracheal administration of hyaluronan, a polysaccharide that prevents elastin breakdown by binding to lung elastic fibers. In clinical trials, inhalation of aerosolized HA decreased elastic fiber injury, as measured by the release of the elastin-specific cross-linking amino acids, desmosine, and isodesmosine. By protecting elastic fibers from enzymatic and oxidative damage, aerosolized HA could alter the natural history of pulmonary emphysema, thereby reducing the risk of respiratory failure.

Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.

Overdiagnosing giant bullous emphysema as metastatic adenocarcinoma: a case report.

BACKGROUND: Giant bullous emphysema is characterized by large bullae occupying at least one-third of the hemithorax and leading to compression of the surrounding lung parenchyma. Overdiagnosis can occur because of the atypical appearance of hyperplastic type II pneumocytes, which may be mistaken for malignant cells. CASE PRESENTATION: A 48-year-old male with a history of smoking and occupational exposure presented with dyspnea and drowsiness. Initial chest X-ray revealed a tension pneumothorax, and subsequent chest CT revealed extensive bullous emphysema and lung cancer in the right middle lobe (RML). Pathologic examination initially indicated resected bullae to metastatic adenocarcinoma, but upon review, it was determined that the reactive alveolar cells were misdiagnosed as malignant. CONCLUSIONS: This case emphasizes the need for thorough histopathological assessment and prudent interpretation of atypical cellular morphology.

Computed Tomography Spectrum of Complications in Usual Interstitial Pneumonia Pattern in a Tertiary Care Hospital: A Descriptive Cross- sectional Study.

INTRODUCTION: Idiopathic pulmonary fibrosis is the most prevalent form of interstitial lung disease, which presents as usual interstitial pneumonia on histopathology and imaging. It leads to significant lung scarring, damage, and fibrosis and is associated with a high degree of mortality, repeated hospital admissions, and oxygen dependence. Many complications are associated with idiopathic pulmonary fibrosis, which further increases the morbidity of patients. High-resolution computed tomography chest is the imaging modality of choice for usual interstitial pneumonia tracking its progression, evaluating treatment response, and detecting potential complications. METHODS: This descriptive cross-sectional study was approved by the Institutional Ethics Committee (Reference number: IEC-INT/2023/Study-1256). Departmental computed tomography report database from November, 2017 to June, 2018 was reviewed and scans with imaging features consistent with the 'usual interstitial pneumonia' pattern were identified. Total sampling method was used and two independent radiologists, blinded to the patient's clinical information, reviewed the high-resolution computed tomography chest scans to assess for imaging features of usual interstitial pneumonia and associated complications. Data was collected and analyzed using Microsoft Excel. RESULTS: There were 65 patients reported as unusual interstitial pneumonia pattern. Emphysema and pneumothorax were identified in 4 (6.15%) and 1 (1.53%) scans, respectively. Two (3.08%) scans showed features of pulmonary arterial hypertension. Ten (15.38%) scans exhibited findings consistent with co-existent or superimposed pulmonary infection. Additionally, features of lung malignancy were identified in high-resolution computed tomography scans of 5 (7.69%) patients. CONCLUSIONS: Patients with UIP often experience severe lung scarring, and frequent complications, and require regular chest CT scans to monitor disease progression and identify potential complications.

Blood eosinophil count correlates with alveolar damage in emphysema-predominant COPD.

BACKGROUND: Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes. METHODS: Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens. RESULTS: The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls. CONCLUSIONS: Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall.

The severity assessment and nucleic acid turning-negative-time prediction in COVID-19 patients with COPD using a fused deep learning model.

BACKGROUND: Previous studies have shown that patients with pre-existing chronic obstructive pulmonary diseases (COPD) were more likely to be infected with coronavirus disease (COVID-19) and lead to more severe lung lesions. However, few studies have explored the severity and prognosis of COVID-19 patients with different phenotypes of COPD. PURPOSE: The aim of this study is to investigate the value of the deep learning and radiomics features for the severity evaluation and the nucleic acid turning-negative time prediction in COVID-19 patients with COPD including two phenotypes of chronic bronchitis predominant patients and emphysema predominant patients. METHODS: A total of 281 patients were retrospectively collected from Hohhot First Hospital between October 2022 and January 2023. They were divided to three groups: COVID-19 group of 95 patients, COVID-19 with emphysema group of 94 patients, COVID-19 with chronic bronchitis group of 92 patients. All patients underwent chest computed tomography (CT) scans and recorded clinical data. The U-net model was pretrained to segment the pulmonary involvement area on CT images and the severity of pneumonia were evaluated by the percentage of pulmonary involvement volume to lung volume. The 107 radiomics features were extracted by pyradiomics package. The Spearman method was employed to analyze the correlation of the data and visualize it through a heatmap. Then we establish a deep learning model (model 1) and a fusion model (model 2) combined deep learning with radiomics features to predict nucleic acid turning-negative time. RESULTS: COVID-19 patients with emphysema was lowest in the lymphocyte count compared to COVID-19 patients and COVID-19 companied with chronic bronchitis, and they have the most extensive range of pulmonary inflammation. The lymphocyte count was significantly correlated with pulmonary involvement and the time for nucleic acid turning negative (r=-0.145, P < 0.05). Importantly, our results demonstrated that model 2 achieved an accuracy of 80.9% in predicting nucleic acid turning-negative time. CONCLUSION: The pre-existing emphysema phenotype of COPD severely aggravated the pulmonary involvement of COVID-19 patients. Deep learning and radiomics features may provide more information to accurately predict the nucleic acid turning-negative time, which is expected to play an important role in clinical practice.

Pulmonary and Systemic Immune Profiles Following Lung Volume Reduction Surgery and Allogeneic Mesenchymal Stromal Cell Treatment in Emphysema.

Emphysema in patients with chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation. Preclinical studies suggest that lung volume reduction surgery (LVRS) and mesenchymal stromal cell (MSC) treatment dampen inflammation. We investigated the effects of bone marrow-derived MSC (BM-MSC) and LVRS on circulating and pulmonary immune cell profiles in emphysema patients using mass cytometry. Blood and resected lung tissue were collected at the first LVRS (L1). Following 6-10 weeks of recovery, patients received a placebo or intravenous administration of 2 × 106 cells/kg bodyweight BM-MSC (n = 5 and n = 9, resp.) in week 3 and 4 before the second LVRS (L2), where blood and lung tissue were collected. Irrespective of BM-MSC or placebo treatment, proportions of circulating lymphocytes including central memory CD4 regulatory, effector memory CD8 and γδ T cells were higher, whereas myeloid cell percentages were lower in L2 compared to L1. In resected lung tissue, proportions of Treg (p = 0.0067) and anti-inflammatory CD163- macrophages (p = 0.0001) were increased in L2 compared to L1, while proportions of pro-inflammatory CD163+ macrophages were decreased (p = 0.0004). There were no effects of BM-MSC treatment on immune profiles in emphysema patients. However, we observed alterations in the circulating and pulmonary immune cells upon LVRS, suggesting the induction of anti-inflammatory responses potentially needed for repair processes.

Vanishing lung syndrome a rare cause of dwindling of lungs in children with pulmonary tuberculosis.

Vanishing lung syndrome (VLS) or idiopathic giant bullous disease is a rare condition characterized by giant emphysematous bullae, classically presenting as a slowly enlarging bulla that compresses normal lung parenchyma and causes mediastinal shift, leading to increasing dyspnea and reduced exercise tolerance. Intermittent sudden worsening of symptoms may be seen because of secondary pneumothorax due to rupture of these bullae. Here we present three cases of vanishing lung syndrome in children due to tuberculosis (TB). Reports on VLS due to TB are bare minimum. In contrast to most of the published case reports, our cases had a moderate to rapid progression, bilateral extensive bullae and isoniazid which has been traditionally thought to be the causative factor was not used in one of our patients. All three are female patients arising new horizons of research regarding whether there is any sex predominance.

Efficacy and safety of simultaneous combined Zephyr and Spiration valve therapy in patients with advanced pulmonary emphysema.

BACKGROUND: Endoscopic lung volume reduction with valves is a minimally invasive treatment strategy for patients with severe pulmonary emphysema. Two valve systems are currently available: Zephyr and Spiration valves. As these can be implanted simultaneously in the same procedure, the question arose as to the effect on lung function, exercise capacity and subjective disease perception after combined valve treatment. METHODS: We conducted a retrospective analysis of 108 patients with combined, simultaneous treatment of Zephyr and Spiration valves. The decision on which and how many valves to implant was based on the individual patient anatomy. Effects on lung function, exercise capacity and atelectasis formation as well as complications were evaluated 90- and 180-days post-treatment (90d-FU and 180d-FU). RESULTS: At 90d-FU (n = 90), the mean change was 86.7 ± 183.7 mL for FEV1 and -645.3 ± 1276.5 mL for RV, with responder rates of 39.8 % and 46.5 %, respectively. Complete atelectasis occurred in 16.7 % and partial atelectasis in 25.5 % of patients. Six-minute walking distance increased by 27.00 m [-1.50 - 68.50m]. The rates of pneumothorax (10.2 %) 6 months after treatment were not higher than in randomized controlled trials (RCTs). Likely due to the inclusion of high-risk patients, there was a higher incidence of severe COPD exacerbation (21.3 %) and pneumonia (12.0 %) compared to RCTs. CONCLUSIONS: The combined implantation of Zephyr and Spiration valves resulted in significant clinical and functional improvements with an acceptable risk profile. Therefore, the ability to combine both valve types in severe emphysema could be a promising option in endoscopic lung volume reduction.

Citrullination, a novel posttranslational modification of elastin, is involved in COPD pathogenesis.

Elastin is an extracellular matrix protein (ECM) that supports elasticity of the lung, and in patients with chronic obstructive pulmonary disease (COPD) and emphysema, the structural changes that reduce the amount of elastic recoil, lead to loss of pulmonary function. We recently demonstrated that elastin is a target of peptidyl arginine deiminase (PAD) enzyme-induced citrullination, thereby leading to enhanced susceptibility of this ECM protein to proteolysis. This study aimed to investigate the impact of PAD activity in vivo and furthermore assessed whether pharmacological inhibition of PAD activity protects against pulmonary emphysema. Using a Serpina1a-e knockout mouse model, previously shown to develop inflammation-mediated emphysema, we validated the involvement of PADs in airway disease. In line with emphysema development, intratracheal administration of lipopolysaccharide in combination with PADs provoked significant airspace enlargement (P < 0.001) and diminished lung function, including loss of lung tissue elastance (P = 0.0217) and increases in lung volumes (P = 0.0463). Intraperitoneal treatment of mice with the PAD inhibitor, BB-Cl-amidine, prevented PAD/LPS-mediated lung function decline and emphysema and reduced levels of citrullinated airway elastin (P = 0.0199). These results provide evidence for the impact of PADs on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.NEW & NOTEWORTHY This study provides evidence for the impact of peptidyl arginine deiminase (PAD) enzymes on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.

Effect of decreased expression of latent TGF-ß binding proteins 4 on the pathogenesis of emphysema as an age-related disease.

PURPOSE: Latent TGF-ß binding protein 4 (LTBP4) is involved in the production of elastin fibers and has been implicated in LTBP4-related cutis laxa and its complication, emphysema-like changes. Various factors have been implicated in the pathogenesis of emphysema, including elastic degeneration, inflammation, cellular senescence, mitochondrial dysfunction, and decreased angiogenesis in the lungs. We investigated the association between LTBP4 and emphysema using human lung fibroblasts with silenced LTBP4 genes. METHODS: Cell contraction, elastin expression, cellular senescence, inflammation, anti-inflammatory factors, and mitochondrial function were compared between the LTBP4 small interfering RNA (siRNA) and control siRNA. RESULTS: Under the suppression of LTBP4, significant changes were observed in the following: decreased cell contractility, decreased elastin expression, increased expression of the p16 gene involved in cellular senescence, increased TNFα, decreased GSTM3 and SOD, decreased mitochondrial membrane potential, and decreased VEGF expression. Furthermore, the decreased cell contractility and increased GSTM3 expression observed under LTBP4 suppression were restored by the addition of N-acetyl-L-cysteine or recombinant LTBP4. CONCLUSION: The decreased elastin expression, cellular senescence, inflammation, decreased antioxidant activity, mitochondrial dysfunction, and decreased VEGF expression under reduced LTBP4 expression may all be involved in the destruction of the alveolar wall in emphysema. Smoking is the most common cause of emphysema; however, genetic factors related to LTBP4 expression and other factors may also contribute to its pathogenesis.

Personalised indication of augmentation therapy for emphysema associated with severe alpha-1 antitrypsin deficiency: a case series.

Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.

Causal inference analysis of the radiologic progression in the chronic obstructive pulmonary disease.

There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber's M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber's M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.

The Use of Bronchial Rheoplasty in Emphysema Patients Previously Treated with Endoscopic Lung Volume Reduction: A Case Series.

Endoscopic lung volume reduction (ELVR) is an established treatment option for patients with severe emphysema. Not all patients are candidates for this type of intervention, and in the context of significant airway secretions, they may be excluded from treatment. Bronchial Rheoplasty (BR) was developed to treat mucus hypersecretion by delivering nonthermal pulsed electric fields to the airway epithelium and submucosa. The literature to date demonstrates that patients treated with BR in clinical studies have a reduction in airway goblet cell hyperplasia as well as substantive clinical improvement in the setting of chronic bronchitis (CB). In this case series, we present four patients treated at three different institutions who had previously undergone ELVR with beneficial outcome. However, over time, these patients subsequently developed worsening clinical issues, including complaints of increased and thickened mucus, along with exacerbations in the setting of a loss of some ELVR-associated benefits. These patients then underwent exploratory treatment with BR with the intent of reducing their secretion burden and potentially restoring the efficacy associated with the initial placement of the airway valves. All BR procedures were well tolerated, and three of the four patients showed substantial improvement in their symptom burden. Airway examinations during the second of the two BR procedures also revealed what appeared to be less airway mucosal inflammation and a decrease in the quantity of airway secretions. Therefore, treatment with BR may have the potential to improve and restore the initial benefits associated with ELVR, thus enhancing long-term outcomes. Further clinical studies with sufficient follow-up are warranted to assess this in a larger cohort of patients, and to determine whether treatment with BR prior to ELVR may make more patients eligible for this treatment through reduction in their secretions and/or symptoms.

Differences in the Quantitative HRCT Characteristics of Patients with Asthma, COPD and Asthma-COPD Overlap and Their Relationships with Pulmonary Function.

Purpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma-COPD overlap (ACO) and explored their relationships with airflow limitation. Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of -860 HU to -950 HU (RVC-860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships. Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC-860 to -950 levels decreased in the following order: ACO, COPD, and asthma. RVC-860 to -950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC-860 to -950 in ACO patients. Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.

Improved diagnostic yield of peripheral pulmonary malignant lesions with emphysema using a combination of radial endobronchial ultrasonography and rapid on-site evaluation.

BACKGROUND: This is a retrospective cohort study from a single center of Chest Medical District of Nanjing Brain Hospital Affiliated to Nanjing Medical University, Jiangsu Province, China. It was aim to evaluate the diagnostic value of radial endobronchial ultrasound (R-EBUS) combination with rapid on-site evaluation (ROSE) guided transbronchial lung biopsy (TBLB) for peripheral pulmonary lesions in patients with emphysema. METHODS: All 170 patients who underwent PPLs with emphysema received an R-EBUS examination with or without the ROSE procedure, and the diagnostic yield, safety, and possible factors influencing diagnosis were analyzed between the two groups by the SPSS 25.0 software. RESULTS: The pooled and benign diagnostic yields were not different in the two groups (P = 0.224, 0.924), but the diagnostic yield of malignant PPLs was significantly higher in the group with ROSE than the group without ROSE (P = 0.042). The sensitivity of ROSE was 79.10%, the specificity, 91.67%, the positive predictive value, 98.15%, and the negative predictive value, 84.62%. The diagnostic accuracy, was 95.52%. In the group of R-EBUS + ROSE, the procedural time and the number of times of biopsy or brushing were both significantly reduced (all P<0.05). The incidence of pneumothorax (1.20%) and bleeding (10.84%) in the group of R-EBUS + ROSE were also less than those in the group of R-EBUS (P<0.05). The lesion's diameter ≥ 2 cm, the distance between the pleura and the lesion ≥ 2 cm, the positive air bronchograms sign, the location of the ultrasound probe within the lesion, and the even echo with clear margin feature of lesion ultrasonic image, these factors are possibly relevant to a higher diagnostic yield. The diagnostic yield of PPLs those were adjacent to emphysema were lower than those PPLs which were away from emphysema (P = 0.048) in the group without ROSE, however, in the group of R-EBUS + ROSE, there was no such difference whether the lesion is adjacent to emphysema or not (P = 0.236). CONCLUSION: Our study found that the combination of R-EBUS and ROSE during bronchoscopy procedure was a safe and effective modality to improve diagnostic yield of PPLs with emphysema, especially for malignant PPLs. The distance between the pleura and the lesion ≥ 2 cm, the positive air bronchograms sign, the location of the ultrasound probe within the lesion, and the even echo with clear margin feature of lesion ultrasonic image, these factors possibly indicated a higher diagnostic yield. Those lesions' position is adjacent to emphysema may reduce diagnostic yield but ROSE may make up for this deficiency.

Differential lung gene expression identified Zscan2 and Bag6 as novel tissue repair players in an experimental COPD model.

Chronic obstructive pulmonary disease is a common chronic lung disease with an ever-increasing incidence. Despite years of drug research and approvals, we are still not able to halt progress or restore normal lung function. Our previous studies have demonstrated that liver growth factor-LGF has an effect on the repair of the affected tissue in a mouse model of cigarette smoke exposure, but by what pathways it achieves this is unknown. The present study aimed to identify differentially expressed genes between emphysematous mice treated with LGF to identify potential therapeutic targets for the treatment of pulmonary emphysema. The emphysema mouse model was induced by prolonged exposure to cigarette smoke. To determine the gene expression profile of the lung in smokers treated or not with LGF, lung messenger RNA gene expression was assessed with the Agilent Array platform. We carried out differentially expressed gene analysis, functional enrichment and validated in treated mouse lung samples. The treated group significantly improved lung function (~35%) and emphysema level (~20%), consistent with our previous published studies. Microarray analysis demonstrated 290 differentially expressed genes in total (2.0-fold over or lower expressed). Injury repair-associated genes and pathways were further enhanced in the lung of LGF treated mice. The expression trends of two genes (Zscan2 and Bag6) were different in emphysematous lungs treated with LGF compared to untreated lungs. Therefore, Zscan2 and Bag6 genes could play a role in regulating inflammation and the immune response in the lung that undergoes partial lung regeneration. However, further studies are necessary to demonstrate this causal relationship.

Anticancer Effects of Spiperone in C57BL/6 Mice with Emphysema and Lung Carcinoma.

The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.