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Subcutaneous emphysema is a possible but infrequent consequence of dental procedures. We present the case of a 6-year-old healthy boy transferred from a dental clinic immediately after local anaesthesia for tooth extraction, due to sudden orbital and facial swelling. On physical examination, oedema of the left upper eyelid with fine crepitus on palpation and left hemiface oedema with local pain were observed. Ophthalmologic observation was normal. CT scan of the face and orbits documented extensive infiltration of the subcutaneous tissue planes of the left face by air, with extension to the external part of the body of the mandible, retromaxillary fat, masticatory muscle spaces, parapharyngeal space and adjacent to the orbital roof. After completing initial evaluation, the dentist confirmed the use of an air-driven device during local anaesthesia administration. The patient improved with conservative treatment. Early recognition of this condition is essential to provide an adequate clinical assessment with exclusion of possible life-threatening complications.

Emphysematous cystitis (EC) is a rare severe urinary tract infection characterised by pockets of air in and around the urinary bladder wall caused by gas-forming organisms. Common predisposing factors are chronic infection, immunosuppression, diabetes and neurogenic bladder. The presentation may vary from mild illness to severe life-threatening cystitis. We report two cases of incidental detection of EC diagnosed on imaging for the evaluation of unrelated symptoms. Although asymptomatic, this lethal disease still warrants prompt recognition and treatment with broad-spectrum antibiotics and urinary bladder drainage to prevent severe morbidity and mortality.

RationaleCOPD has been associated repeatedly with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways. This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterisation and examine how these differences may relate to altered biological pathways.Methods213 patients with moderate-to-severe COPD in a clinically stable state were recruited and clinically characterised, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster.ResultsFour clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV), with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that three of the four clusters were enriched in Rage (receptor for advanced glycation end-products) and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterisation of clusters ranged from 1) better functional capacity and health status and fewer comorbidities; 2) more underweight, osteoporosis and static hyperinflation; 3) more metabolically deranged; and 4) older subjects with worse functional capacity and higher comorbidity load.ConclusionsThese new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.

Emphysematous pancreatitis (EP) is a subtype of infected pancreatic necrosis (IPN) characterized by presence of gas in (peri)pancreatic necrosis. However, the impacts of EP on outcomes of IPN are still controversial.A prospective database of consecutive patients with IPN in a tertiary hospital was post-hoc analyzed. Patients were assigned to EP and non-EP groups to perform a comprehensive comparison.A total of 178 patients with IPN were enrolled and the overall mortality was 30.9%. EP accounted for 20.8% (n = 37) of cases and was significantly associated with higher incidences of Escherichia coli (45.9 versus 18.4%, P = 0.001) and Klebsiella pneumoniae (56.8 versus 33.3%, P = 0.009) infection. There was scarcely any disparity in clinical characteristics and outcomes between IPN patients with and without EP. However, patients with early-onset EP defined as air bubble signs occurring within 2 weeks from disease onset were significantly older and have higher prevalence of history of diabetes, and they were also associated with significantly higher mortality (57.1 versus 8.7%, P = 0.015) compared with late-onset patients.The clinical outcomes of EP might be like those of non-emphysematous infection. However, when EP occurs within 2 weeks from disease onset, it is highly lethal.

Jonas Alexander Leppig,1 Lan Song,2 Dorothea C Voigt,1 Felix W Feldhaus,1 Christoph Ruwwe-Gloesenkamp,3 Jacopo Saccomanno,3 Bianca C Lassen-Schmidt,4 Konrad Neumann,5 Katja Leitner,6 Ralf H Hubner,3 Felix Doellinger1 1Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany; 2Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; 4Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany; 5Institute of Biometrics and Clinical Epidemiology, Charité Universitätsmedizin Berlin, Berlin, Germany; 6Department of Internal Medicine, Kantonsspital Aarau AG, Aarau, SwitzerlandCorrespondence: Jonas Alexander Leppig, Department of Radiology, Charité Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin, 13353, Germany, Tel + 49 30 450 627 283, Fax + 49 30 450 527 911, Email Jonas-Alexander.Leppig@charite.dePurpose: To investigate changes in quantitative CT analysis (QCT) and pulmonary function tests (PFT) in pulmonary emphysema patients who required premature removal of endobronchial valves (EBV).Patients and Methods: Our hospital’s medical records listed 274 patients with high-grade COPD (GOLD stages 3 and 4) and pulmonary emphysema who were treated with EBV to reduce lung volume. Prior to intervention, a complete evaluation was performed that included quantitative computed tomography analysis (QCT) of scans acquired at full inspiration and full expiration, pulmonary function tests (PFT), and paraclinical findings (6-minute walking distance test (6MWDT) and quality of life questionnaires). In 41 of these 274 patients, EBV treatment was unsuccessful and the valves had to be removed for various reasons. A total of 10 of these 41 patients ventured a second attempt at EBV therapy and underwent complete reevaluation. In our retrospective study, results from three time points were compared: Before EBV implantation (BL), after EBV implantation (TP2), and after EBV explantation (TP3). QCT parameters included lung volume, total emphysema score (TES, ie, the emphysema index) and the 15th percentile of lung attenuation (P15) for the whole lung and each lobe separately. Differences in these parameters between inspiration and expiration were calculated (Vol. Diff (%), TES Diff (%), P15 Diff (%)). The results of PFT and further clinical tests were taken from the patient’s records.Results: We found persistent therapy effect in the target lobe even after valve explantation together with a compensatory hyperinflation of the rest of the lung. As a result of these two divergent effects, the volume of the total lung remained rather constant. Furthermore, there was a slight deterioration of the emphysema score for the whole lung, whereas the TES of the target lobe persistently improved.Conclusion: Interestingly, we found evidence that, contrary to our expectations, unsuccessful EBV therapy can have a persistent positive effect on target lobe QCT scores.Keywords: chronic obstructive pulmonary disease, pulmonary emphysema, endobronchial valves, lung volume reduction, computed tomography, pulmonary function test

Chest drains are placed after surgery to enable lung re-expansion. However, there remains little guidance on optimal placement. This study aims to identify the ideal size and position for chest drain insertion with regards to post-operative outcomes.383 patients undergoing lobectomy in 1-year had their chest drain size and x-ray position noted (1 (apical), 2 (mid-zone) or 3 (basal)). Primary outcome was residual air space on immediate post-operative x-ray. Secondary outcomes were length of drain in situ (72 versus ≥72 h), persisting pleural effusion, surgical emphysema, post-operative pneumonia (POP), and length of hospital stay (5 versus ≥5 days). Fisher's exact analysis for the primary outcome and binary logistic regression analysis for all outcomes were used. Results presented as odds ratios (OR±95%CI).Univariate analysis for residual air space showed increased risk in area 2 (OR = 1.61, p = 0.041) and 3 (OR = 2.59, p = 0.0043) compared with area 1. Multivariate analysis for residual air space showed increased risk in area 2 (OR = 2.39, p 0.001) and 3 (OR = 2.86, p 0.001) compared with area 1. Drain size had no impact on residual air space in univariate or multivariate analysis. Multivariate analysis showed area 2 drains remained in situ for72 h (OR = 1.49, p = 0.017), had persisting effusions (OR = 2.03, p = 0.004) and POP (OR = 2.10, p = 0.023) compared with area 1. This risk is magnified further for drains in area 3. Drains ≥28F had reduced risk of surgical emphysema (OR = 0.23, p = 0.027) in multivariate analysis.A ≥28F, apical chest drain reduces the risk of post-operative complications, allowing early removal and discharge.

Background Visual assessment remains the standard for evaluating emphysema at CT; however, it is time consuming, is subjective, requires training, and is affected by variability that may limit sensitivity to longitudinal change. Purpose To evaluate the clinical and imaging significance of increasing emphysema severity as graded by a deep learning algorithm on sequential CT scans in cigarette smokers. Materials and Methods A secondary analysis of the prospective Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study participants was performed and included baseline and 5-year follow-up CT scans from 2007 to 2017. Emphysema was classified automatically according to the Fleischner emphysema grading system at baseline and 5-year follow-up using a deep learning model. Baseline and change in clinical and imaging parameters at 5-year follow-up were compared in participants whose emphysema progressed versus those who did not. Kaplan-Meier analysis and multivariable Cox regression were used to assess the relationship between emphysema score progression and mortality. Results A total of 5056 participants (mean age, 60 years ± 9 [SD]; 2566 men) were evaluated. At 5-year follow-up, 1293 of the 5056 participants (26%) had emphysema progression according to the Fleischner grading system. This group demonstrated progressive airflow obstruction (forced expiratory volume in 1 second [percent predicted]: -3.4 vs -1.8), a greater decline in 6-minute walk distance (-177 m vs -124 m), and greater progression in quantitative emphysema extent (adjusted lung density: -1.4 g/L vs 0.5 g/L; percentage of lung voxels with CT attenuation less than -950 HU: 0.6 vs 0.2) than those with nonprogressive emphysema (

Guoyan Tang,1,&ast; Fengyan Wang,1,&ast; Zhenyu Liang,1,&ast; Cuixia Liang,2,&ast; Jinling Wang,3,&ast; Yuqiong Yang,1 Wanyi Tang,1,4 Weijuan Shi,1 Guoqiang Tang,3 Kai Yang,5 Zihui Wang,1 Qiasheng Li,1 Hualin Li,1 Jiaxuan Xu,1 Deyan Chen,2 Rongchang Chen5 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Neusoft Medical Systems Co., Ltd, Shenyang, People’s Republic of China; 3Qingyuan Chronic Disease Prevention Hospital, Qingyuan Occupational Disease Prevention Hospital, Qingyuan, People’s Republic of China; 4Qingyuan People’s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchang Chen, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China, Email chenrc@vip.163.com Zhenyu Liang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email 490458234@qq.comBackground: Pulmonary vascular alteration is an important feature of chronic obstructive pulmonary disease (COPD), which is characterized by distal pulmonary vascular pruning in angiography. We aimed to further investigate the clinical relevance of pulmonary vasculature in COPD patients using non-contrast computed tomography (CT).Methods: Seventy-one control subjects and 216 COPD patients completed the questionnaires, spirometry, and computed tomography (CT) scans within 1 month and were included in the study. Small pulmonary vessels represented by percentage of cross-sectional area of pulmonary vessels smaller than 5 mm2 or 5– 10 mm2 to the total lung fields (%CSA< 5 or %CSA5– 10, respectively) were measured using ImageJ software. Spearman correlation was used to investigate the relationship between %CSA< 5 and airflow limitation. A receiver operating characteristic (ROC) curve was built to evaluate the value of %CSA< 5 in discriminating COPD patients from healthy control subjects. Segmented regression was used to analyze the relationship between %CSA< 5 and %LAA-950 (percentage of low-attenuation areas less than − 950 HU).Results: We found a significant correlation between %CSA< 5 and forced expiratory volume in one second (FEV1) percentage of predicted value (%pred) (r = 0.564, P < 0.001). The area under the ROC curve for the value of %CSA< 5 in distinguishing COPD was 0.816, with a cut-off value of 0.537 (Youden index J, 0.501; sensitivity, 78.24%; specificity, 71.83%). Since the relationship between %CSA< 5 and %LAA-950 was not constant, performance of segmented regression was better than ordinary linear regression (adjusted R2, 0.474 vs 0.332, P < 0.001 and P < 0.001, respectively). As %CSA< 5 decreased, %LAA-950 slightly increased until an inflection point (%CSA< 5 = 0.524) was reached, after which the %LAA-950 increased apparently with a decrease in %CSA< 5.Conclusion: %CSA< 5 was significantly correlated with both airflow limitation and emphysema, and we identified an inflection point for the relationship between %CSA< 5 and %LAA-950.Keywords: computed tomography, pulmonary vascular pruning, airflow limitation, emphysema, chronic obstructive pulmonary disease

To compare an artificial intelligence (AI)-based prototype and subjective grading for predicting disease severity in patients with emphysema.Our IRB approved HIPAA-compliant study included 113 adults (71±8 years; 47 females, 66 males) who had both non-contrast chest CT and pulmonary function tests performed within a span of 2 months. The disease severity was classified based on the forced expiratory volume in 1 second (FEV1 as % of predicted) into mild, moderate, and severe. 2 thoracic radiologists (RA), blinded to the clinical and AI results, graded severity of emphysema on a 5-point scale suggested by the Fleischner Society for each lobe. The whole lung scores were derived from the summation of lobar scores. Thin-section CT images were processed with the AI-Rad Companion Chest prototype (Siemens Healthineers) to quantify low attenuation areas (LAA- 950 HU) in whole lung and each lobe separately. Bronchial abnormality was assessed by both radiologists and a fully automated software (Philips Healthcare).Both AI (AUC of 0.77; 95% CI: 0.68 - 0.85) and RA (AUC: 0.76, 95% CI: 0.65 - 0.84) emphysema quantification could differentiate mild, moderate, and severe disease based on FEV1. There was a strong positive correlation between AI and RA (r = 0.72 - 0.80; p0.001). The combination of emphysema and bronchial abnormality quantification from radiologists' and AI assessment could differentiate between different severities with AUC of 0.80 - 0.82 and 0.87, respectively.The assessed AI-prototypes can predict the disease severity in patients with emphysema with the same predictive value as the radiologists.

A 22-year-old woman with a history of type 1 diabetes mellitus (DM) presented with nausea, vomiting and epigastric discomfort for 3 days. On presentation, she had blood pressure of 80/50 mm Hg and a heart rate of 120 bpm. No significant findings were noted on systemic physical examination. She

A 66-year-old man with rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) presented to our hospital with exertional dyspnoea. He smoked three packs a day for 34 years until he was diagnosed with RA and COPD at the age of 54. He still smokes a half pack a day. RA was in

It has long been thought that small-cell lung cancer (SCLC) is a central type of tumor that is located in the proximal bronchi and the mediastinum. However, several studies reported that SCLC exhibited several types of spread pattern on computed tomography (CT). The aim of this study is to investigate the relationship between CT images and clinical characteristics in patients with SCLC.We retrospectively reviewed the CT images of 92 SCLC patients and classified them into six types of spreading patterns: central, peripheral, lymphangitic spread (LYM), pleural dissemination (PLE), lobar replacement (LOB), and air-space consolidation (AC). We also evaluated the correlation between primary tumor location and the clinical characteristics of patients.The most common type of imaging pattern was peripheral (n = 40, 44%), with the next most common type being central (n = 27, 29%). Atypical types of SCLC, such as LYM (n = 2, 2%), PLE (n = 4, 4%), LOB (n = 8, 9%), and AC (n = 11, 12%), were also recognized in our study. The prevalence of emphysema and interstitial lung disease (ILD) was significantly higher in the peripheral type than in the central type (p = 0.0056 and p = 0.0403, respectively). Meanwhile, no survival difference was seen between the central type and the peripheral type (median months 17.9 vs. 21.9, respectively, p = 0.720).The peripheral type of tumor was correlated with higher prevalence of emphysema and ILD in SCLC. Our result suggests different mechanisms of development and tumor characteristics according to tumor location.

Emphysematous pyelonephritis (EP) is a severe necrotizing infection of the renal parenchyma which is associated with significant case mortality. We sought to identify the incidence and predictive risk factors associated with EP mortality.Two electronic databases, PubMed and Web of Science, were searched from their inception until June 06, 2021 for relevant articles. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines.Of the 1080 retrieved abstracts, 79 underwent full-text review and 45 studies were included in the final analysis, comprising a total cohort of 1303 patients and 177 mortalities. The pooled prevalence of mortality among the patients with EP disease was 13%. Our analysis found a significantly decreasing trend in mortality rates, an increasing trend in minimally invasive intervention and decreasing trends in emergency nephrectomy in the EP studies from 1985 to 2020. Significant risk factors that were associated with a negative impact on survival of EP patients included sepsis (OR = 15.99), shock (OR = 15.57), disturbance of consciousness (OR = 12.11), thrombocytopenia (OR 7.85), acute renal failure (OR = 5.41), Wan classification I (OR = 4.57), emergency nephrectomy (OR = 3.73), Huang-Tseng classification III-IV (OR = 2.4) and medical management alone (OR = 2.04). Female sex (OR = 0.52) and minimally invasive intervention (OR = 0.47) (percutaneous nephrostomy or ureteral stent placement) were associated with decreased mortality rates.Our study results demonstrated several significant risk factors that could help guide treatment to reduce the mortality risk of EP patients. Clinically, early treatment with a combination of minimally invasive intervention and appropriate medical management may be protective for reducing mortality risk in EP patients.

Objectives This study aimed to evaluate the association between visual emphysema and the presence of lung nodules, and Lung-RADS category with low-dose CT (LDCT). Methods Baseline LDCT scans of 1162 participants from a lung cancer screening study (Nelcin-B3) performed in a Chinese general population were included. The presence, subtypes, and severity of emphysema (at least trace) were visually assessed by one radiologist. The presence, size, and classification of non-calcified lung nodules (≥ 30 mm3) and Lung-RADS category were independently assessed by another two radiologists. Multivariable logistic regression and stratified analyses were performed to estimate the association between emphysema and lung nodules, Lung-RADS category, after adjusting for age, sex, BMI, smoking status, pack-years, and passive smoking. Results Emphysema and lung nodules were observed in 674 (58.0%) and 424 (36.5%) participants, respectively. Participants with emphysema had a 71% increased risk of having lung nodules (adjusted odds ratios, aOR: 1.71, 95% CI: 1.26–2.31) and 70% increased risk of positive Lung-RADS category (aOR: 1.70, 95% CI: 1.09–2.66) than those without emphysema. Participants with paraseptal emphysema (n = 47, 4.0%) were at a higher risk for lung nodules than those with centrilobular emphysema (CLE) (aOR: 2.43, 95% CI: 1.32–4.50 and aOR: 1.60, 95% CI: 1.23–2.09, respectively). Only CLE was associated with positive Lung-RADS category (p = 0.02). CLE severity was related to a higher risk of lung nodules (ranges aOR: 1.44–2.61, overall p < 0.01). Conclusion In a Chinese general population, visual emphysema based on LDCT is independently related to the presence of lung nodules (≥ 30 mm3) and specifically CLE subtype is related to positive Lung-RADS category. The risk of lung nodules increases with CLE severity. Key Points • Participants with emphysema had an increased risk of having lung nodules, especially smokers. • Participants with PSE were at a higher risk for lung nodules than those with CLE, but nodules in participants with CLE had a higher risk of positive Lung-RADS category. • The risk of lung nodules increases with CLE severity.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world, and has no radical treatment. Inhibition of amiloride-sensitive epithelial sodium ion channel (ENaC) has now been considered as a potential therapeutic target against COPD. One possible modulator of ENaC is AMP-activated protein kinase (AMPK), a key molecule that controls a wide variety of cellular signals; however, little is known about whether metformin, a clinically available AMPK activator, has a protective role against ENaC-associated chronic pulmonary phenotypes, such as emphysema and pulmonary dysfunction. We first used ENaC-overexpressing human bronchial epithelial cells (β/γENaC-16HBE14o-) and identified that Metformin significantly reduced ENaC activity. Consistently, in vivo treatment of ENaC-overexpressing COPD mouse model (C57BL/6-βENaC-Tg mice) showed improvement of emphysema and pulmonary dysfunction, without any detrimental effect on non-pulmonary parameters (blood glucose level etc.). Bronchoalveolar lavage fluid (BALF) and lung tissue analyses revealed significant suppression in the infiltration of neutrophils as well as the expression of inflammatory markers (KC), neutrophil gelatinase (MMP9) and macrophage elastase (MMP12) in metformin-treated C57BL/6-βENaC-Tg mice. Overall, the present study demonstrates that metformin directly inhibits ENaC activity in vitro and provides the first evidence of therapeutical benefit of Metformin for COPD with higher ENaC activity.

Pharmacologic therapeutics for advanced emphysema have limited benefit. Bronchoscopic lung volume reduction with endobronchial valves (EBVs) have reported improvements in lung function, breathlessness, and quality of life through randomized clinical trials, with less morbidity as comparted to Surgical Lung volume Reduction. We here present a Meta-analysis and systematic review of bronchoscopic lung volume reduction in advanced chronic obstructive lung disease patients.PubMed (NLM), Embase (Elsevier), and Web of Science (Clarivate Analytics) search was conducted using a combination of keywords and subject headings. The search was confined to the last 15 years and was completed on October 23, 2020. Only placebo-controlled randomized control trials of emphysema patients with EBV were included. Quality assessment was done by 2 independent reviewers.Nine studies were included for the meta-analysis with a total number of 1383 patients of whom 888 received EBV and 495 standard of care (SOC) medications. Our Metanalysis show statistically significant improvement in forced expiratory volume in first second, percentage forced expiratory volume in first second, St. George's respiratory questionnaire, and 6-minute walk distance in EBV group compared with SOC. Residual volume had statistically significant reduction after EBV placement compared with SOC. These differences continued to be present during short-term (=6 mo) and long-term follow-up (=6 mo). These improvements were even higher when the EBV patients'. Collateral ventilation was negative/fissure was intact (CV-/FI90%). The rate of hemoptysis and pneumothorax was higher in the EBV group compared with SOC, however, did not lead to increased fatal outcomes.In conclusion, EBV has favorable effects on patients' outcomes in patients who have heterogeneous emphysema particularly with no collateral ventilation.

Air pollution, especially at chronic exposure to high concentrations, is a respiratory risk factor for the development of chronic obstructive pulmonary disease (COPD). E-cadherin, a cell–cell adhesion protein, is involved in the integrity of the alveolar epithelium. Causes of E-cadherin decreases in emphysematous areas with pulmonary cell damage related to COPD are not well understood. We aimed to determine the molecules causing the decrease of E-cadherin and interactions between these molecules. In emphysematous and non-emphysematous areas of lungs from COPD patients (n = 35), levels of E-cadherin, HDACs, Snail, Zeb1, active-β-catenin, p120ctn, and Kaiso were determined by using Western Blot. The interactions of HDAC1, HDAC2, and p120ctn with transcription co-activators and Kaiso were examined by co-immunoprecipitation experiments. The methylation status of the CDH1 promoter was investigated. E-cadherin, Zeb1, Kaiso, and active-β-catenin were decreased in emphysema, while HDAC1, HDAC2, and p120ctn2 were increased. Snail, Zeb1, Twist, active-β-catenin, Kaiso, and p120ctn co-precipitated with HDAC1 and HDAC2. E-cadherin, Kaiso, and active-β-catenin co-precipitated with p120ctn. HDAC1–Snail and HDAC2–Kaiso interactions were increased in emphysema, but p120ctn-E-cadherin interaction was decreased. The results show that HDAC1–Snail and HDAC2–Kaiso interactions are capable of decreasing the E-cadherin in emphysema. The decreased interaction of p120ctn/E-cadherin leads to E-cadherin destruction. The decreased E-cadherin and its induced degradation in pneumocytes cause impaired repair and disintegrity of the epithelium. Approaches to suppress HDAC1–Snail and HDAC2–Kaiso interactions may help the protection of alveolar epithelial integrity by increasing the E-cadherin stability in pneumocytes.

Background and objectives In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. Materials and methods In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. Results Of the 2729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26-2.29) with an age at diagnosis of RA of 57.3 ± 13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. Conclusions We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.

Background: Penetrating trauma to the oropharynx is a rare problem in children. Although the majority of cases heal with no long-term consequences it can result in fatal complications. In this case report we discuss how a spoon-related oropharyngeal trauma case was treated. Case: A 7-year-old child fell facedown while eating ice cream, the spoon became inserted in his. A vertical 3-4 cm laceration in the midline of the posterior wall of the pharynx was discovered. There was subcutaneous and retropharyngeal air values extending into the upper mediastinum in his computed tomography scan. While the patient was intubated and monitored in the pediatric intensive care unit. Broad-spectrum antibiotics were initiated to prevent infectious complications. As his subcutaneous emphysema regressed, he was successfully extubated.Conclusion: In penetrating trauma of the oropharynx; to avoid fatal complications, early commencement of antibiotic therapy, and close monitoring of the in the intensive care unit is vital.

Tomography; Emphysema; Outcomes Tomografía; Enfisema; Resultados Tomografia; Emfisema; Resultats

Objective. To analyze the risk factors of pulmonary infection in patients with type 2 diabetes mellitus (T2DM) and its implications for clinical intervention. Methods. One hundred and twenty-five patients with type 2 diabetes treated in our hospital from January 2019 to November 2021 were divided into simple T2DM group ( n = 80 ) and infection group ( n = 45 ) according to whether they were complicated with pulmonary infection or not. Sputum samples of patients with infection were collected and identified by bacterial culture. The general conditions (age, sex, body mass index, course of disease, and length of stay), pulmonary complications (chronic bronchitis, emphysema, and obstructive pulmonary disease,), blood glucose control (fasting blood glucose and glycosylated hemoglobin), and treatment (use of hormones and antibiotics and invasive operation) were compared between the two groups. Univariate and multivariate analyses were used to screen the risk factors of pulmonary infection in patients with T2DM. Results. A total of 45 patients were found to be infected in this study. 68 pathogenic bacteria were detected in the sputum samples, of which 42 were Gram-negative (61.76%), 22 were Gram-positive (35.35%), and 4 were fungi (5.88%). Gram-negative bacteria were mainly Klebsiella pneumoniae, accounting for 25.00%, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. Gram-positive bacteria were mainly Staphylococcus aureus, accounting for 17.65%, followed by Streptococcus pneumoniae and Staphylococcus haemolyticus. The main fungi were Candida albicans (4.41%). The age, the course of T2DM, and the duration of hospitalization in the coinfection group were significantly higher than those in the T2DM group ( P < 0.05 ). There was no significant difference in other indexes ( P > 0.05 ). The number of patients with chronic bronchitis, emphysema, and obstructive pulmonary disease in the coinfection group was significantly higher than that in the T2DM group. The fasting blood glucose and glycosylated hemoglobin in the coinfection group were significantly higher than those in the T2DM group. The number of patients using hormone and antimicrobial agents and invasive operation in the coinfection group was higher than that in the simple T2DM group, and the difference was statistically significant ( P < 0.05 ). Multivariate analysis showed that age, course of T2DM, length of hospital stay, complicated pulmonary disease, glycosylated hemoglobin, use of hormones and antibiotics, and invasive operation were all risk factors of pulmonary infection in patients with T2DM ( P < 0.05 ). Conclusion. Gram-negative bacteria are the main pathogens of T2DM complicated with pulmonary infection. Drug sensitivity test should be combined to understand the drug resistance of pathogenic bacteria and use drugs reasonably to patients. Among them, advanced age, long course of T2DM, long hospital stay, complicated pulmonary disease, high level of glycosylated hemoglobin, use of hormones and antibiotics, and invasive operation were all risk factors of pulmonary infection in patients with T2DM. In clinical treatment, under the premise of using insulin to control blood sugar in an appropriate range, antibiotics should be used reasonably, pulmonary complications should be treated actively, pulmonary ventilation function should be improved, and invasive operation should be avoided as far as possible, which can effectively prevent the occurrence of T2DM complicated with pulmonary infection.

Lung diseases affect the lives of billions of people worldwide, and 4 million people, each year, die prematurely due to this condition. These pathologies are characterized by specific imagiological findings in CT scans. The traditional Computer-Aided Diagnosis (CAD) approaches have been showing promising results to help clinicians; however, CADs normally consider a small part of the medical image for analysis, excluding possible relevant information for clinical evaluation. Multiple Instance Learning (MIL) approach takes into consideration different small pieces that are relevant for the final classification and creates a comprehensive analysis of pathophysiological changes. This study uses MIL-based approaches to identify the presence of lung pathophysiological findings in CT scans for the characterization of lung disease development. This work was focus on the detection of the following: Fibrosis, Emphysema, Satellite Nodules in Primary Lesion Lobe, Nodules in Contralateral Lung and Ground Glass, being Fibrosis and Emphysema the ones with more outstanding results, reaching an Area Under the Curve (AUC) of 0.89 and 0.72, respectively. Additionally, the MIL-based approach was used for EGFR mutation status prediction - the most relevant oncogene on lung cancer, with an AUC of 0.69. The results showed that this comprehensive approach can be a useful tool for lung pathophysiological characterization.

Neuropeptide Y (NPY) is a neuropeptide widely expressed in not only the central nervous system but also immune cells and the respiratory epithelium. Patients with chronic obstructive pulmonary disease (COPD) reportedly exhibit decreased NPY expression in the airway epithelium, but the involvement of NPY in the pathophysiology of COPD has not been defined. We investigated the role of NPY in elastase-induced emphysema. NPY-deficient (NPY−/−) mice and wild-type (NPY+/+) mice received intratracheal instillation of porcine pancreas elastase (PPE). The numbers of inflammatory cells and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates were determined along with quantitative morphometry of lung sections. Intratracheal instillation of PPE induced emphysematous changes and increased NPY levels in the lungs. Compared with NPY+/+ mice, NPY−/− mice had significantly enhanced PPE-induced emphysematous changes and alveolar enlargement. Neutrophilia seen in BAL fluid of NPY+/+ mice on day 4 after PPE instillation was also enhanced in NPY−/− mice, and the enhancement was associated with increased levels of neutrophil-related and macrophage-related chemokines and IL-17A as well as increased numbers of type 3 innate lymphoid cells in the airways. Treatment with NPY significantly reduced PPE-induced emphysematous changes. Conversely, treatment with a NPY receptor antagonist exacerbated PPE-induced emphysematous changes. These observations indicate that NPY has protective effects against elastase-induced emphysema and suggest that targeting NPY in emphysema has potential as a therapeutic strategy for delaying disease progression.

Most pulmonary conditions reduce FVC, but studies of patients with combined pulmonary fibrosis and emphysema demonstrate that reductions in FVC are less than expected when these two conditions coexist clinically.Do interstitial lung abnormalities (ILAs), chest CT imaging findings that may suggest an early stage of pulmonary fibrosis in individuals with undiagnosed disease, affect the association between emphysema and FVC?Measures of ILA and emphysema were available for 9,579 and 5,277 participants from phases 1 (2007-2011) and 2 (2012-2016) of the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study (COPDGene), respectively. ILA were defined by Fleischner Society guidelines. Adjusted linear regression models were used to assess the associations and interactions among ILA, emphysema, measures of spirometry, and lung function.ILA were present in 528 (6%) and 580 (11%) of participants in phases 1 and 2 of COPDGene, respectively. ILA modified the association between emphysema and FVC (P .0001 for interaction) in both phases. In phase 1, in those without ILA, a 5% increase in emphysema was associated with a reduction in FVC (-110 mL; 95% CI, -121 to -100 mL; P .0001); however, in those with ILA, it was not (-11 mL; 95% CI, -53 to 31; P = .59). In contrast, no interaction was found between ILA and emphysema on total lung capacity or on diffusing capacity of carbon monoxide.The presence of ILA attenuates the reduction in FVC associated with emphysema.

Incidental respiratory disease-related findings are frequently observed on low-dose CT (LDCT) lung cancer screenings. This study analyzed data from the National Lung Screening Trial (NLST) to assess the relationship between such findings and respiratory disease mortality (RDM), excluding lung cancer.Are incidental respiratory findings on LDCT scanning associated with increased RDM?Subjects in the NLST LDCT arm received three annual screens. Trial radiologists noted findings related to possible lung cancer, as well as respiratory-related incidental findings. Demographic characteristics, smoking history, and medical history were captured in a baseline questionnaire. Kaplan-Meier curves were used to assess cumulative RDM. Multivariate proportional hazards models were used to assess risk factors for RDM; in addition to incidental CT scan findings, variables included respiratory disease history (COPD/emphysema, and asthma), smoking history, and demographic factors (age, race, sex, and BMI).Of 26,722 subjects in the NLST LDCT arm, 25,002 received the baseline screen and a subsequent LDCT screen. Overall, 59% were male, 26.5% were aged ≥ 65 years at baseline, and 10.6% reported a history of COPD/emphysema. Emphysema on LDCT scanning was reported in 30.7% of subjects at baseline and in 44.2% at any screen. Of those with emphysema on baseline LDCT scanning, 18% reported a history of COPD/emphysema. Median mortality follow-up was 10.3 years. There were 3,639 deaths, and 708 were from respiratory diseases. Among subjects with no history of COPD/emphysema, 10-year cumulative RDM ranged from 3.9% for subjects with emphysema and reticular opacities to 1.1% for those with neither condition; the corresponding range among subjects with a COPD/emphysema history was 17.3% (both) to 3.7% (neither). Emphysema on LDCT imaging was associated with a significantly elevated RDM hazard ratio (2.27; 95% CI, 1.92-2.7) in the multivariate model. Reticular opacities (including honeycombing/fibrosis/scar) also had a significantly elevated hazard ratio (1.39; 95% CI, 1.19-1.62).Incidental respiratory disease-related findings observed on NLST LDCT screens were frequent and associated with increased mortality from respiratory diseases.

Chronic obstructive pulmonary disease (COPD) is primarily caused by inhalation of cigarette smoke and is the third leading cause of death worldwide. Pulmonary surfactant, a complex of phospholipids and proteins, plays an essential role in respiration by reducing the surface tension in the alveoli. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is an enzyme that catalyzes the biosynthesis of surfactant lipids and is expressed in type 2 alveolar epithelial cells. Its dysfunction is suggested to be involved in various lung diseases; however, the relationship between LPCAT1 and COPD remains unclear. To investigate the role of LPCAT1 in the pathology of COPD, we analyzed an elastase-induced emphysema model using Lpcat1 knockout (KO) mice. In Lpcat1 KO mice, elastase-induced emphysema was significantly exacerbated with increased apoptotic cells, which was not ameliorated by supplementation with dipalmitoylphosphatidylcholine, which is a major component of the surfactant synthesized by LPCAT1. We subsequently evaluated the effects of cigarette smoking on primary human type 2 alveolar epithelial cells (hAEC2s) and found that cigarette smoke extract (CSE) downregulated the expression of Lpcat1. Furthermore, RNA sequencing analysis revealed that the apoptosis pathway was significantly enriched in CSE-treated primary hAEC2s. Finally, we downregulated the expression of Lpcat1 using small interfering RNA, which resulted in enhanced CSE-induced apoptosis in A549 cells. Taken together, cigarette smoke-induced downregulation of LPCAT1 can promote the exacerbation of pulmonary emphysema by increasing the susceptibility of alveolar epithelial cells to apoptosis, thereby suggesting that Lpcat1 is a novel therapeutic target for irreversible emphysema.

In some noisy low dose CT lung cancer screening images, we noticed that the CT density values of air were increased and the visibility of emphysema was distinctly decreased. By examining histograms of these images, we found that the CT density values were truncated at -1024 HU. The purpose of this study was to investigate the effect of pixel value truncation on the visibility of emphysema using mathematical models.Assuming CT noise follows a normal distribution, we derived the relationship between the mean CT density value and the standard deviation (SD) when the pixel values below -1024 HU are truncated and replaced by -1024 HU. To validate our mathematical model, 20 untruncated phantom CT images were truncated by simulation, and the mean CT density values and SD of air in the images were measured and compared with the theoretical values. In addition, the mean CT density values and SD of air were measured in 100 cases of real clinical images obtained by GE, Siemens, and Philips scanners, respectively, and the agreement with the theoretical values was examined. Next, the contrast-to-noise ratio (CNR) between air (-1000 HU) and lung parenchyma (-850 HU) was derived from the mathematical model in the presence and absence of truncation as a measure of the visibility of emphysema. In addition, the radiation dose ratios required to obtain the same CNR in the case with and without truncation were also calculated.The mathematical model revealed that when the pixel values are truncated, the mean CT density values are proportional to the noise magnitude when the magnitude exceeds a certain level. The mean CT density values and SD measured in the images with pixel values truncated by simulation and in the real clinical images acquired by GE and Philips scanners agreed well with the theoretical values from our mathematical model. In the Siemens images, the measured and theoretical values agreed well when a portion of the truncated values were replaced by random values instead of simply replacing by -1024 HU. The CNR of air and lung parenchyma was lowered by truncating CT density values compared to that of no truncation. Furthermore, it was found that higher radiation dose was required to obtain the same CNR with truncation as without. As an example, when the noise SD was 60 HU, the radiation dose required for the GE and Philips truncation method was about 1.2 times higher than that without truncation, and that for the Siemens truncation method was about 1.4 times higher.It was demonstrated mathematically that pixel value truncation causes a brightening of the mean CT density value and decreases the CNR of emphysema. Our results indicate that it is advisable to turn off truncation at -1024 HU, especially when scanning at low and ultra-low radiation doses in the thorax.

From the identification of a specific lung disease caused by coal dust exposure in miners in 1831 until the demonstration of the association of that exposure to risk of emphysema in 1984, there was continuous argument about the harmfulness of coal dust. Ill health in miners was attributed variously to tuberculosis, quartz exposure or cigarette smoking. An acceptance that coal dust was harmful only started with investigative radiology and pathology in the 1920s, and physiology in the 1950s. Most of the early investigations were in South Wales, the centre of the most important coal field in Great Britain. Among the investigators was Professor Jethro Gough who, with his technician James Wentworth, introduced a technique for making thick sections of whole, inflated lungs on paper backing. Here, we describe this method and its central role in understanding the relationships between coal dust exposure, pneumoconiosis, emphysema and lung dysfunction in miners.

Cigarette smoke (CS) is known to cause impaired mitophagy and mitochondrial dysregulation in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. Mitochondrial complexes and dynamics are affected by acute CS exposure in lung epithelium and mouse lung. We hypothesize that chronic CS exposure (4 months) will induce lung mitochondrial dysregulation and abnormal mitophagy. In this study, we employed the mitoQC reporter mice, a mitochondrial reporter strain, which can reflect the mitophagy based on the fluorescence-tagged mitochondria. Chronic CS exposure induced lung inflammatory cell infiltration, airspace enlargement, and lung cellular senescence. We showed the higher occurrence of mitophagy in the lung cells by CS exposure, associated with more mitochondrial fluorescence signals (GFP(+)/mCherry(+)). After chronic CS exposure, the mitochondrial complexes and function related genes were inhibited, while protein levels of complexes I and III slightly changed. Additionally, chronic CS exposure down-regulated most of the mitochondrial dynamic markers at gene expression level, included mitochondrial fusion/fission and mitochondrial translocate/transfer markers. For the markers related to mitophagy, Pink1 and Parkin, decreased gene and protein levels of Parkin, and decreased gene expression of Pink1, were identified in the CS exposure group. Hence, CS-induced mitophagy is mediated by Pink1-Parkin independent mechanism. Thus, we have shown that chronic CS exposure induced mitophagy, which is observed using a state-of-the art mitoQC reporter mice, as well as the dysregulated mitochondrial complexes and dynamics. Our results suggested that dysregulated mitochondrial function and dynamics are associated with CS-induced lung injury and phenotypic development of chronic lung diseases, such as COPD/ emphysema.

Emphysematous pyelonephritis is a life-threatening infection of the kidney and surrounding tissues associated with a high mortality rate. The aim of this study was to determine predictive factors for mortality and intensive care unit admission in patients with emphysematous pyelonephritis, and to propose a therapeutic algorithm based on current literature and our experience.A retrospective study was done including patients with emphysematous pyelonephritis in a single center in the north of Mexico from 2011 to 2016. Demographic, clinical, microbiological and biochemical parameters, therapeutic management, and outcomes were assessed. Factors associated with admission to intensive care unit and mortality were determined. Comparison was assessed using XA total of 63 patients were included, of which 55 (87.3%) were females, with a mean age of 55.5 ± 12.2 years. The most common comorbidities were diabetes and hypertension. Escherichia coli was the most common isolated microorganism (51.7%) and extended-spectrum beta-lactamase-producing agents were reported in 31.7%. Conservative therapy was provided to 38.7%, double J stent 42.9%, open/percutaneous drainage 12.7%, and nephrectomy 25.3%. Overall mortality and intensive care admission were 20.6% and 36.5%, respectively. In the multivariate analysis, hemodynamic instability (P = .005), qSOFA ≥ 2 (P = .003), hypoalbuminemia (P = .02), and early nephrectomy (P = .002) were associated with intensive care admission. Huang scale 4 (P = .006) and early nephrectomy (P = .001) were associated to mortality.Emphysematous pyelonephritis is a life-threatening disease and evidence of management is based in small case series due to the low incidence of this condition. Hemodynamic instability, hypoalbuminemia, qSOFA ≥ 2, Huang scale ≥3, and early nephrectomy are associated with poor prognosis.

Jiaxin Liu,1 Zixiao Zhang,1 Yue Yang,1 Tingting Di,2 Yan Wu,1 Tao Bian1 1Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China; 2Department of Respiratory Medicine, First People’s Hospital of Nantong, Nantong, Jiangsu, 226006, People’s Republic of ChinaCorrespondence: Tao Bian; Yan Wu, Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China, Email btaophd@sina.com; wuyanyangting@163.comBackground: Macrophage polarization plays an important role in the pathogenesis of COPD emphysema. Changes in macrophage polarization in COPD remain unclear, while polarization and ferroptosis are essential factors in its pathogenesis. Therefore, this study investigated the relationship between macrophage polarization and ferroptosis in COPD emphysema.Methods: We measured macrophage polarization and the levels of matrix metalloproteinases (MMPs) in the lung tissues of COPD patients and cigarette smoke (CS)-exposed mice. Flow cytometry was used to determine macrophage (THP-M cell) polarization changes. Ferroptosis was examined by FerroOrange, Perls’ DAB, C11-BODIPY and 4-HNE staining. Nuclear receptor coactivator 4 (NCOA4) was measured in the lung tissues of COPD patients and CS-exposed mice by western blotting. A cell study was performed to confirm the regulatory effect of NCOA4 on macrophage polarization.Results: Increased M2 macrophages and MMP9 and MMP12 levels were observed in COPD patients, CS-exposed mice and THP-M cells cocultured with CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased NCOA4 levels and ferroptosis were confirmed in COPD. Treatment with NCOA4 siRNA and the ferroptosis inhibitor ferrostatin-1 revealed an association between ferroptosis and M2 macrophages. These findings support a role for NCOA4, which induces an increase in M2 macrophages, in the pathogenesis of COPD emphysema.Conclusion: In our study, CS led to the dominance of the M2 phenotype in COPD. We identified NCOA4 as a regulator of M2 macrophages and emphysema by mediating ferroptosis, which offers a new direction for research into COPD diagnostics and treatment.Keywords: NCOA4, ferroptosis, macrophage polarization, MMP9, MMP12, COPD

Basic fibroblast growth factor (bFGF) induces regeneration and neovascularization of the lungs. We conducted this study to demonstrate the regeneration of emphysematous lungs achieved by gelatin sheets that slowly release bFGF into the visceral pleura in a canine model.Porcine pancreatic elastase was used to induce bilateral lower lobe pulmonary emphysema in dogs. Slow-release bFGF gelatin sheets were attached to the visceral pleura of the left lower lobe via thoracotomy. The subjects were divided into two groups: one treated with gelatin sheets containing slow-release bFGF (bFGFThe MLI was significantly shorter in the bFGFAttaching gelatin sheets with slow-release bFGF to the visceral pleura induced lung regeneration and vascularization in a canine pulmonary emphysema model.

Chin-Hsiao Tseng1– 3 1Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3National Institute of Environmental Health Sciences, Zhunan, TaiwanCorrespondence: Chin-Hsiao Tseng, Tel/Fax +886 2 2388 3578, Email ccktsh@ms6.hinet.netBackground: Pioglitazone’s effect on chronic obstructive pulmonary disease (COPD) has rarely been studied.Purpose: This retrospective observational study investigated whether the use of pioglitazone would affect the risk of COPD in patients with type 2 diabetes mellitus.Patients and Methods: The Taiwan’s National Health Insurance database was used to enroll 9487 matched pairs of ever users and never users of pioglitazone based on propensity score from a cohort of 350,536 patients. The enrolled patients had a new diagnosis of type 2 diabetes mellitus between 1999 and 2008 and were not having a diagnosis of COPD before January 1, 2009. They were then followed up for COPD, starting from January 1, 2009 until December 31, 2011. Diagnosis of COPD was based on the codes of 491 for chronic bronchitis and 492 for emphysema based on the International Classification of Diseases, Ninth Revision, Clinical Modification. Cox regression was used to estimate hazard ratios. The interactions between pioglitazone and COPD risk factors including pneumonia, pulmonary tuberculosis and tobacco abuse were also investigated.Results: In 9487 never users and 9487 ever users of pioglitazone, the case numbers of incident COPD were 359 and 295, respectively. The respective incidence rates of COPD were 1484.73 and 1167.61 per 100,000 person-years. The overall hazard ratio (95% confidence interval) for COPD that compared ever to never users was 0.778 (0.667– 0.908). The hazard ratios for the tertiles of cumulative duration of pioglitazone therapy (cutoffs: < 11.0, 11.0– 19.6 and > 19.6 months) to never users were 0.904 (0.729– 1.121), 0.727 (0.578– 0.914) and 0.715 (0.570– 0.896), respectively. No interactions between pioglitazone and COPD risk factors including pneumonia, pulmonary tuberculosis and tobacco abuse were noted.Conclusion: Pioglitazone use is associated with a significantly lower risk of COPD.Keywords: chronic bronchitis, emphysema, pharmacoepidemiological study, risk factors, Taiwan, thiazolidinediones

Purpose This study aims to develop and validate a parametric response mapping (PRM) methodology to accurately identify diseased regions of the lung by using variable thresholds to account for alterations in regional lung function between the gravitationally-independent (anterior) and gravitationally-dependent (posterior) lung in CT images acquired in the supine position. Methods 34 male Sprague-Dawley rats (260-540 g) were imaged, 4 of which received elastase injection (100 units/kg) as a model for emphysema (EMPH). Gated volumetric CT was performed at end-inspiration (EI) and end-expiration (EE) on separate groups of free-breathing (n = 20) and ventilated (n = 10) rats in the supine position. To derive variable thresholds for the new PRM methodology, voxels were first grouped into 100 bins based on the fractional distance along the anterior-to-posterior direction. Lower limits of normal (LLN) for x-ray attenuation in each bin were set by determining the smallest region that enclosed 98% of voxels from healthy, ventilated animals. Results When utilizing fixed thresholds in the conventional PRM methodology, a distinct posterior-anterior gradient was seen, in which nearly the entire posterior region of the lung was identified as HEALTHY, while the anterior lung was labeled as significantly less so (t(29) = -3.27, p = 0.003). In both cohorts, %SAD progressively increased from posterior to anterior, while %HEALTHY lung decreased in the same direction. After applying our PRM methodology with variable thresholds to the same rat images, the posterior-anterior trend in %SAD quantification was removed from all rats and the significant increase of diseased lung in the anterior was removed. Conclusions The PRM methodology using variable thresholds provides regionally specific markers of %SAD and %EMPH by correcting for alterations in regional lung function associated with the naturally occurring vertical gradient of dependent vs. non-dependent lung density and compliance.

The TCAV method reduces lung damage in ARDS. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury and cardiac function in experimental emphysema. The TCAV method at EFT/EPF ratio of 25%, compared with EFT/EPF of 75% (frequently used in ARDS), reduced lung inflammation, alveolar heterogeneity and hyperinflation, and pulmonary arterial hypertension in elastase-induced emphysema. TCAV may be a promising and personalized ventilation strategy for patients with emphysema.

Exacerbation of chronic obstructive pulmonary disease (COPD) is associated with disease progression and increased mortality. Periodontal disease is a risk factor for exacerbation of COPD, but little is known about the role of periodontopathic bacteria in this process. Here, we investigated the effects of intratracheal administration of Fusobacterium nucleatum, a periodontopathic bacteria species, on COPD exacerbation in elastase-induced emphysematous mice. The administration of F. nucleatum to elastase-treated mice enhanced inflammatory responses, production of alveolar wall destruction factors, progression of emphysema, and recruitment of mucin, all of which are symptoms observed in patients with COPD exacerbation. Hence, we propose that F. nucleatum may play a role in exacerbation of COPD.

To develop a nomogram based on CT radiomics and clinical features to predict the epidermal growth factor receptor (EGFR) mutations in early-stage lung adenocarcinomas.A retrospective analysis of postoperative patients with pathologically confirmed lung adenocarcinoma, which had been tested for EGFR mutations was performed from January 2015 to December 2015. Patients were randomly assigned to training and validation cohorts. A total of 1,078 radiomics features were extracted. least absolute shrinkage and selection operator (LASSO) regression analysis was applied to select clinical and radiomics features, and to establish predictive models. The radiomics score (rad-score) of each patient was calculated. The discrimination of the model was evaluated with area under the curve.1092 patients (444 men and 648 women; mean age: 59.59±9.6) were enrolled. The radiomics signature consisted of 28 radiomics features and emphysema. The mean validation cohort result of the rad-score for patients with EGFR mutations (0.814±0.988) was significantly higher than those with EGFR wild-type (0.315±1.237; p = 0.001). When combined with clinical features, LASSO regression analysis revealed four radiomics features, emphysema, and three clinical features including sex, age, and histologic subtype as associated with to EGFR mutation status. The nomogram that combined radiomics and clinical features significantly improved the predictive discrimination (AUC: 0.723), which is better than that of the radiomics signature alone (AUC: 0.646).A relationship between selected radiomics features and EGFR mutant lung adenocarcinomas is demonstrated. A nomogram, combining radiomics features and clinical features for EGFR prediction in early-stage lung adenocarcinomas, has shown a moderate discriminatory efficiency and high sensitivity, providing additional information for clinicians.

To evaluate the association of visual emphysema on preoperative CT with respiratory complications and prolonged air leak (PAL) in smokers with normal spirometry who underwent lobectomy for lung cancer.Among patients who underwent lobectomy for lung cancer between 2018 and 2019 at a single center, ever-smokers with normal spirometry were identified retrospectively. Visual emphysema was graded for centrilobular emphysema (CLE) and paraseptal emphysema (PSE), respectively, by two thoracic radiologists. The associations of visual emphysema with PAL and respiratory complications (except PAL) were investigated.In total, 282 patients were evaluated (257 men; mean age, 64.6 ± 9.8 years). Visual emphysema was present in 126 patients (44.7%) (CLE, 26; PSE, 40; combined CLE and PSE, 60). PAL and respiratory complications occurred in 34 (12.1%) and 26 patients (26.9%), respectively. Greater frequency of PAL and respiratory complications were observed in patients with higher grades of CLE (p = 0.002 for PAL; p = 0.039 for respiratory complications) and PSE (p 0.001 for PAL; p 0.001 for respiratory complications). For reader 1 evaluation, the presence of both CLE and PSE was associated with PAL (adjusted odds ratio [OR], 4.94; 95% confidence interval [CI], 1.75-13.95; p = 0.003). For reader 2 evaluation, PSE (adjusted OR, 4.26; 95% CI, 1.22-14.97; p = 0.024) and combined CLE and PSE (adjusted OR, 3.49; 95% CI, 12.1-10.06; p = 0.020) were associated with PAL. The presence of solely CLE was not associated with any adverse outcome (all p 0.05) for both readers.Visual assessment of PSE in smokers with normal spirometry may help identify those who develop PAL after lobectomy.• Visual emphysema was highly prevalent (44.7%) in smokers with normal lung function who underwent lobectomy for lung cancer. • Increasing tendency of postoperative complications was observed as the grade of visual emphysema increased. • The presence of paraseptal emphysema was associated with prolonged air leak.

The aim of this study was to evaluate the impact of contrast enhancement and different virtual monoenergetic image energies on automatized emphysema quantification with photon-counting detector computed tomography (PCD-CT).Sixty patients who underwent contrast-enhanced chest CT on a first-generation, clinical dual-source PCD-CT were retrospectively included. Scans were performed in the multienergy (QuantumPlus) mode at 120 kV with weight-adjusted intravenous contrast agent. Virtual noncontrast (VNC) images as well as virtual monoenergetic images (VMIs) from 40 to 80 keV obtained in 10-keV intervals were reconstructed. Computed tomography attenuation was measured in the aorta. Noise was measured in subcutaneous fat and defined as the standard deviation of attenuation. Contrast-to-noise with region of interest in the ascending aorta and signal-to-noise ratio in the subcutaneous fat were calculated. Subjective image quality (and emphysema assessment, lung parenchyma evaluation, and vessel evaluation) was rated by 2 blinded radiologists. Emphysema quantification (with a threshold of -950 HU) was performed by a commercially available software. Virtual noncontrast images served as reference standard for emphysema quantification.Noise and contrast-to-noise ratio showed a strong negative correlation (r = -0.98; P0.01) to VMI energies. The score of subjective assessment was highest at 70 keV for lung parenchyma and 50 keV for pulmonary vessel evaluation (P0.001). The best trade-off for the assessment of emphysema while maintaining reasonable contrast for pulmonary vessel evaluation was determined between 60 and 70 keV. Overall, contrast-enhanced imaging led to significant and systematic underestimation of emphysema as compared with VNC (P0.001). This underestimation decreased with increasing VMI-energy (r = 0.98; P = 0.003). Emphysema quantification showed significantly (P0.05) increased emphysema volumes with increasing VMI energies, except between 60-70 keV and 70-80 keV. The least difference in emphysema quantification between contrast-enhanced scans and VNC was found at 80 keV.Computed tomography emphysema quantification was significantly affected by intravenous contrast administration and VMI-energy level. Virtual monoenergetic image at 80 keV yielded most comparable results to VNC. The best trade-off in qualitative as well as in quantitative image quality evaluation was determined at 60/70 keV.

Advanced bronchoscopic lung volume reduction treatment (BLVR) is now a routine care option for treating patients with severe emphysema. Patterns of low attenuation clusters indicating emphysema and functional small airway disease (fSAD) on paired CT, which may provide additional insights to the target selection of the segmental or subsegmental lobe of the treatments, require further investigation. The low attenuation clusters (LACS) were segmented to identify the scalar and spatial distribution of the lung destructions, in terms of 10 fractions scales of low attenuation density (LAD) located in upper lobes and lower lobes. The LACs of functional small airway disease (fSAD) were delineated by applying the technique of parametric response map (PRM) on the co-registered CT image data. Both emphysematous LACs of inspiratory CT and fSAD LACs on expiratory CT were used to derive the coefficients of the predictive model for estimating the airflow limitation. The voxel-wise severity is then predicted using the regional LACs on the co-registered CT to indicate the functional localization, namely, the bullous parametric response map (BPRM). A total of 100 subjects, 88 patients with mild to very severe COPD and 12 control participants with normal lung functions (FEV1/FVC % > 70%), were evaluated. Pearson’s correlations between FEV1/FVC% and LAV%HU-950 of severe emphysema are − 0.55 comparing to − 0.67 and − 0.62 of LAV%HU-856 of air-trapping and LAV%fSAD respectively. Pearson’s correlation between FEV1/FVC% and FEV1/FVC% predicted by the proposed model using LAD% of HU-950 and fSAD on BPRM is 0.82 (p

Background: HIV is associated with accelerated decline in lung function and increased risk for chronic obstructive pulmonary disease (COPD). Recently, there has been growing attention toward the impairment in the diffusing capacity of the lungs for carbon monoxide (DLCO), a marker of pulmonary gas exchange, observed among persons living with HIV. Although increased emphysema can contribute to the DLCO impairment observed, other factors may drive this association. Methods: Using cross-sectional data from the Study of HIV in the Etiology of Lung Disease, we studied the association between HIV and DLCO independent of emphysema. We also analyzed the joint influence of HIV and COPD on DLCO impairment. An analysis was conducted among 339 participants (229 with HIV) with lung function and chest CT imaging data. Multivariable regression models were generated with percent predicted DLCO and odds of DLCO impairment as outcomes. Results: After adjusting for confounders, including emphysema severity, HIV was associated with lower DLCO (β −4.02%; P = 0.020) and higher odds of DLCO impairment (odds ratio 1.93; P = 0.017). Even among those without COPD, HIV was independently associated with lower DLCO (β −3.89%; P = 0.049). Compared with HIV-uninfected participants without COPD, those with both HIV and COPD experienced the greatest impairment in DLCO (β −14.81; P < 0.001). Conclusions: HIV is associated with impaired pulmonary gas exchange independent of emphysema severity. Our data also suggest a potentially additive influence between HIV and COPD on DLCO impairment. Further studies should investigate the other factors, including pulmonary vascular disease, which may contribute to DLCO impairment among persons living with HIV.

Lung volume reduction surgery continues to have a high morbidity despite National Emphysema Treatment Trial selection criteria. This study evaluated the association between analytic morphomics on chest computed tomography scans and outcomes after lung volume reduction surgery. In a retrospective review of 85 lung volume reduction surgery patients from 1998-2013, dorsal muscle group area, subcutaneous and visceral fat area, and bone mineral density were assessed using analytic morphomics. Lung density was divided into five levels of increasing density (Lung density 1, emphysema; 2, normal lung; 4-5, scarring). Outcomes including survival, hospital length of stay, readmission at 30 days, and pulmonary complications were analyzed using univariate and multivariable techniques. Pulmonary complications developed in 27.1% (23/85). Mortality at 90 days was 9.4% (8/85). On multivariable analysis, lower bone mineral density (Odds ratio 0.61; 95% confidence interval 0.39-0.95) was associated with decreased survival, longer length of stay (0.83; 0.77-0.89), and readmissions (0.39; 0.15-1.00). Higher lung density 5:lung density 2 volume (1.84; 1.05-3.23), possibly due to scarring, was associated with pulmonary complications and longer length of stay (1.32; 1.23-1.41) while lower subcutaneous fat area:height was associated with readmissions which may reflect decreased metabolic reserve (0.35; 0.13-0.93). Patients with signs of frailty including lower bone mineral density may be at increased risk of adverse outcomes including decreased survival after lung volume reduction surgery. The results of this hypothesis-generating study will need to be confirmed in larger, multicenter trials to determine whether analytic morphomics can improve risk stratification and patient selection.

Background: Lung volume reduction coil (LVR-coil) treatment provides a minimally invasive treatment option for severe emphysema patients which has been studied in multiple clinical trials. Objectives: The aim of the study was to assess the effect of LVR-coil treatment on pulmonary function, quality of life, and exercise capacity using individual participant data. Method: PubMed, Web of Science, and EMBASE were searched until May 17, 2021. Prospective single-arm and randomized controlled trials that evaluated the effect of LVR-coil treatment on forced expiratory volume in 1 s (FEV1), residual volume (RV), St. George Respiratory Questionnaire (SGRQ) total score, and/or 6-min walk distance (6MWD) and were registered in an official clinical trial database were eligible for inclusion. Individual patient data were requested, and a linear mixed effects model was used to calculate overall treatment effects. Results: Eight trials were included in the final analysis, representing 680 individual patients. LVR-coil treatment resulted in a significant improvement in FEV1 at 3- (0.09 L [95% confidence interval (95% CI): 0.06–0.12]) and 6-month follow-up (0.07 L [95% CI: 0.03–0.10]), a significant reduction in RV at 3- (−0.45L [95% CI: −0.62 to −0.28]), 6- (−0.33L [95% CI: −0.52 to −0.14]), and 12-month follow-up (−0.36L [95% CI: −0.64 to −0.08]), a significant reduction in SGRQ total score at 3- (−12.3 points [95% CI: −15.8 to −8.8]), 6- (−10.1 points [95% CI: −12.8 to −7.3]), and 12-month follow-up (−9.8 points [95% CI: −15.0 to −4.7]) and a significant increase in 6MWD at 3-month follow-up (38 m [95% CI: 18–58]). Conclusions: LVR-coil treatment in emphysema patients results in sustained improvements in pulmonary function and quality of life and shorter lived improvements in exercise capacity. Since the owner of this LVR-coil has decided to stop the production and newer generations LVR-coils are currently being developed, these results can act as a reference for future studies and clinical guidance.

Chronic obstructive pulmonary disease (COPD) affects the health of more than 300 million people worldwide; at present, there is no effective drug to treat COPD. Smoking is the most important risk factor, but the molecular mechanism by which smoking causes the disease is unclear. The senescence of lung epithelial cells is related to development of COPD. Regulation of miRNAs is the main epigenetic mechanism related to aging. β-Galactose staining showed that the lung tissues of smokers have a higher degree of cellular senescence, and the expression of miR-125a-5p is high. This effect is obvious for smokers with COPD/emphysema, and there is a negative correlation between miR-125a-5p levels and values for forced expiratory volume in one second (FEV1)/forced vital capacity (FVC). After Balb/c mice were chronically exposed to various concentrations of cigarette smoke (CS), plethysmography showed that lung function was impaired, lung tissue senescence was increased, and the senescence-associated secretory phenotype (SASP) in bronchoalveolar lavage fluid was increased. For mouse lung epithelial (MLE)-12 cells treated with cigarette smoke extract (CSE), Sp1 and SIRT1 levels were low, HIF-1α acetylation levels were high, and cell senescence and secretion of SASP factors were elevated. Down-regulation of miR-125a-5p or up-regulation of Sp1 reversed these effects. In addition, compared with mice exposed to CS, knockdown of miR-125a-5p reduced lung epithelial cell senescence and COPD/emphysema. Therefore, in smoking-induced COPD, elevated miR-125a-5p participates in the senescence of lung epithelial cells through Sp1/SIRT1/HIF-1α. These findings provide evidence related to the pathogenesis of COPD/emphysema caused by chronic smoking.