Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells.

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68+ AMφ-like cells were spatially organized on the luminal epithelial surface of alveolar hLOs. Bleomycin-treated alveolar hLOs showed upregulated expression of fibrosis-related markers and extracellular matrix deposits in the alveolar sacs. Alveolar hLOs also showed structural alterations such as excessive tissue fraction under bleomycin treatment. Therefore, we suggest that micro-CT analyzable PSC-derived alveolar hLOs are a promising in vitro model to predict lung toxicity manifestations, including fibrosis.

Changes in concentrations and characteristics of asbestos fibers dispersed from corrugated asbestos cement sheets due to stabilizer treatment.

Asbestos management in Korea has, to date, focused exclusively on dismantlement and removal; however, the effective management of asbestos in public facilities and rural dwellings is also critical. This study compares eight different asbestos stabilization treatments and their effectiveness in reducing asbestos fiber dispersion from weathered corrugated asbestos cement sheets (CACS) under different wind conditions. The effectiveness of the different asbestos stabilizers was assessed in order to identify the characteristics of fibers dispersed from treated CACS samples. The impact of wind speed on the concentration and composition of the dispersed fibers was also evaluated. For all wind speeds, the concentration of the fibers dispersed from the CACS samples that were treated with stabilizers decreased relative to the untreated CACS. These results show that asbestos concentrations were considerably reduced following stabilizer treatment and that treated CACS dispersed fewer asbestos fibers relative to untreated CACS. The results of this study will be useful for the development of strategies regarding the appropriate management of asbestos in public buildings.

Quantitative CT-based structural alterations of segmental airways in cement dust-exposed subjects.

BACKGROUND: Dust exposure has been reported as a risk factor of pulmonary disease, leading to alterations of segmental airways and parenchymal lungs. This study aims to investigate alterations of quantitative computed tomography (QCT)-based airway structural and functional metrics due to cement-dust exposure. METHODS: To reduce confounding factors, subjects with normal spirometry without fibrosis, asthma and pneumonia histories were only selected, and a propensity score matching was applied to match age, sex, height, smoking status, and pack-years. Thus, from a larger data set (N = 609), only 41 cement dust-exposed subjects were compared with 164 non-cement dust-exposed subjects. QCT imaging metrics of airway hydraulic diameter (Dh), wall thickness (WT), and bifurcation angle (θ) were extracted at total lung capacity (TLC) and functional residual capacity (FRC), along with their deformation ratios between TLC and FRC. RESULTS: In TLC scan, dust-exposed subjects showed a decrease of Dh (airway narrowing) especially at lower-lobes (p < 0.05), an increase of WT (wall thickening) at all segmental airways (p < 0.05), and an alteration of θ at most of the central airways (p < 0.001) compared with non-dust-exposed subjects. Furthermore, dust-exposed subjects had smaller deformation ratios of WT at the segmental airways (p < 0.05) and θ at the right main bronchi and left main bronchi (p < 0.01), indicating airway stiffness. CONCLUSIONS: Dust-exposed subjects with normal spirometry demonstrated airway narrowing at lower-lobes, wall thickening at all segmental airways, a different bifurcation angle at central airways, and a loss of airway wall elasticity at lower-lobes. The airway structural alterations may indicate different airway pathophysiology due to cement dusts.

Clinical features of infectious endophthalmitis in South Korea: a five-year multicenter study.

BACKGROUND: To investigate clinical features of infectious endophthalmitis over five years in a South Korean population. METHODS: Medical records of consecutive patients diagnosed with infectious endophthalmitis at eight institutions located in Gyeongsangnam-do and Pusan city between January 1, 2004 and July 31, 2010 were reviewed. RESULTS: A total of 197 patients were diagnosed and treated. An average of 30.0 infectious endophthalmitis per year was developed. The annual incidence rate of postoperative endophthalmitis during 2006~2009 was 0.037%. The ratios of male to female and right to left were 50.2%: 49.8 % and 54.8%: 43.2%, respectively. Eighth decade and spring were the peak age (36.6%) and season (32.0%) to develop the infectious endophthalmitis. The most common past history in systemic disease was hypertension (40.4%), followed by diabetes (23.4%). Cataract operation (60.4%) was the most common cause, among which most of them was uneventful phacoemulsification (95.9%). Corneal laceration (51.6%) and liver abscess (42.9%) were the most common causes of traumatic and endogenous endophthalmitis, respectively. The percentages of patients with initial and final visual acuity less than counting fingers were 62.6% and 35.2%, respectively. Treatment with vitrectomy with or without intravitreal antibiotics injection was administered to 72.6% of patients, while 17.3% received intravitreal antibiotics only. CONCLUSIONS: Our study revealed that the development of infectious endophthalmitis was related with seasonal variation and increased during our study period. Pars plana vitrectomy was preferred for the treatment of infectious endophthalmitis in South Korea.

Multimodal imaging using optical coherence tomography and endolaryngeal ultrasonography in a new rabbit VX2 laryngeal cancer model.

BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) provides ultrahigh-resolution imaging of tissues within a depth of a few millimeters, whereas ultrasonography provides good imaging further below the surface. We aimed to develop a minimally invasive rabbit model of VX2 laryngeal cancer, suitable for these two imaging modalities through a transoral approach. We also sought to study the utility of combined OCT and endolaryngeal ultrasonography (EUS) for evaluation of early and advanced laryngeal cancer, using this model. MATERIALS AND METHODS: VX2 tumor suspension was inoculated into the vocal folds of ten rabbits by injection through the trans-thyrohyoid membrane. The tumor model was characterized by rigid laryngoscopy and the tumor generation rate was 80% (8/10). Correlation between frequency-domain OCT and high-frequency EUS were used to visualize laryngeal tumors in the area of protruding mass formation in four rabbits, one week after injection (group A) and the remaining four rabbits two weeks after injection (group B). RESULTS: A small submucosal tumor was observed with rigid laryngoscopy in group A, and pathologic evaluation showed that the tumor was close to the basement membrane of the vocal fold mucosa, but had not invaded. OCT confirmed that the lining of the mucosa and basement membrane of the vocal fold was not broken, but the mucosa had thinned at the most elevated ridge. However, these lesions were not detected by EUS, and the overall shape of the tumor could not be clearly identified by EUS. A large tumor filling the laryngeal lumen was observed with rigid laryngoscopy in group B, and nearly the entire vocal fold, including the paraglottic space, was found to be involved on pathologic analysis. Distinguishing between normal structures and tumor was difficult using OCT; however, EUS confirmed the overall shape, size, and extent of the tumor, and the paraglottic space and thyroid cartilage were shown to be intact. CONCLUSIONS: This study is the first experimental trial, assessing the value of multimodal imaging using OCT and EUS in a rabbit VX2 laryngeal tumor model. Combining OCT and EUS helped to identify changes in laryngeal mucous membranes, and could potentially be used to identify laryngeal tumors and predict how tumors progress. This combined modality could help in determining tumor extent, assisting in diagnosis, and establishing a treatment plan for laryngeal cancer.

Asbestos: use, bans and disease burden in Europe.

OBJECTIVE: To analyse national data on asbestos use and related diseases in the European Region of the World Health Organization (WHO). METHODS: For each of the 53 countries, per capita asbestos use (kg/capita/year) and age-adjusted mortality rates (deaths/million persons/year) due to mesothelioma and asbestosis were calculated using the databases of the United States Geological Survey and WHO, respectively. Countries were further categorized by ban status: early-ban (ban adopted by 2000, n = 17), late-ban (ban adopted 2001-2013, n = 17), and no-ban (n = 19). FINDINGS: Between 1920-2012, the highest per capita asbestos use was found in the no-ban group. After 2000, early-ban and late-ban groups reduced their asbestos use levels to less than or equal to 0.1 kg/capita/year, respectively, while the no-ban group maintained a very high use at 2.2 kg/capita/year. Between 1994 and 2010, the European Region registered 106,180 deaths from mesothelioma and asbestosis, accounting for 60% of such deaths worldwide. In the early-ban and late-ban groups, 16/17 and 15/17 countries, respectively, reported mesothelioma data to WHO, while only 6/19 countries in the no-ban group reported such data. The age-adjusted mortality rates for mesothelioma for the early-ban, late-ban and no-ban groups were 9.4, 3.7 and 3.2 deaths/million persons/year, respectively. Asbestosis rates for the groups were 0.8, 0.9 and 1.5 deaths/million persons/year, respectively. CONCLUSION: Within the European Region, the early-ban countries reported most of the current asbestos-related deaths. However, this might shift to the no-ban countries, since the disease burden will likely increase in these countries due the heavy use of asbestos.

Time-Sequential Monitoring of the Early Mesothelial Reaction in the Pleura after Cryoinjury.

(1) Background: An early mesothelial reaction of the pleura, leading to fibrosis, has been reported in animals after chemical or heavy metal exposure. However, the visual monitoring of early time-sequential mesothelial reaction-associated cryoinjury has not been fully investigated. Therefore, this study aimed to evaluate and visualize the early mesothelial reactions seen following cryoinjury using rabbit pleura. (2) Methods: We monitored the early mesothelial reaction in rabbit pleurae after cryoinjury using optical coherence tomography (OCT), in real-time, which was then compared with pathological images. Due to the penetration limit of OCT, we made a thoracic window to image the parietal and visceral pleurae in vivo. We also used an innovative technique for capturing the microstructure in vivo, employing a computer-controlled intermittent iso-pressure breath hold to reduce respiratory motion, increasing the resolution of OCT. We organized three sample groups: the normal group, the sham group with just a thoracic window, and the experimental group with a thoracic window and cryotherapy. In the experimental group, localized cryoinjury was performed. The mesothelial cells at the level of pleura of the cryotherapy-injured site were visualized by OCT within the first 30 min and then again after 2 days at the same site. (3) Results: In the experimental group, focal thickening of the parietal pleura was observed at the site of cryoinjury using OCT after the first injury, and it was then confirmed pathologically as focal mesothelial cell proliferation. Two days after cryoinjury, diffuse mesothelial cell proliferation in the parietal pleura was noted on the reverse side around the cryoinjured site in the same rabbit. In the sham group, no pleural reaction was found. The OCT and pathological examinations revealed different patterns of mesothelial cell reactions between the parietal and visceral pleurae: the focal proliferation of mesothelial cells was found in the parietal pleura, while only a morphological change from flat cells to cuboidal cells and a thickened monolayer without proliferation of mesothelial cells were found in the visceral pleural. (4) Conclusions: An early mesothelial reaction occurs following cryoinjury to the parietal and visceral pleurae.

Longitudinal long term follow up investigation on the carcinogenic impact of polyhexamethylene guanidine phosphate in rat models.

Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar-alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar-alveolar hyperplasia progression, although bronchiolar-alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.

Transcriptional characterization of Wnt pathway during sequential hepatic differentiation of human embryonic stem cells and adipose tissue-derived stem cells.

Human embryonic stem cells (hESs) and adipose-derived stem cells (hADSCs) are able to differentiate into hepatocytes. However, a role of Wnt signaling in hepatic differentiation of stem cells is unclear. This study characterized the transcriptional expression pattern of Wnt signaling genes during the sequential hepatocytes differentiation of hES and hADSC. The sequential hepatocytes differentiation of hES and hADSC was induced by three steps including induction, differentiation and maturation steps with the treatment of cytokines. Hepatocytes differentiation was more efficient in hES than hADSC in terms of the expression of hepatocyte-specific genes and the cellular uptake of ICG. The expression of WNT2B, WNT5A, and WISP1 increased at late hepatic differentiation of hES, but the expression of DKK1 and CCND1 decreased during early hepatic differentiation of hES. During hepatic differentiation of hADSC, the expression of WNT2B and WISP1 decreased, but the expression of WNT5B and DKK1 increased at late hepatic differentiation. These results showed that Wnt signaling appears to be activated in hepatic differentiation of hES, but repressed in hepatic differentiation of hADSC in a time-dependent manner, which suggests the differential regulation of Wnt signaling for hepatic differentiation of hES and hADSC.

Asbestos exposure during home renovation in New South Wales.

OBJECTIVE: Asbestos exposure is causally associated with the development of malignant mesothelioma (MM), which is increasingly being reported after exposure to asbestos fibro sheeting in Australia. In this study, we investigate self-reported non-occupational asbestos exposure during home renovation in New South Wales. DESIGN AND SETTING: Cross-sectional mailed questionnaire examining renovation activity, tasks undertaken during renovation and self-reported exposure to asbestos among respondents and their family members in NSW between January and June 2008. PARTICIPANTS: 10 000 adults aged 18-99 years, randomly selected from the NSW electoral roll. We received 3612 responses, while 365 questionnaires did not reach addressees, giving an overall response rate of 37.5%. MAIN OUTCOME MEASURES: Differences in self-reported asbestos exposure between do-it-yourself (DIY) and non-DIY renovators. RESULTS: 1597 participants (44.2%) had renovated their home and among these, 858 participants (53.7%) self-reported as DIY renovators. Of these, 527 (61.4%) reported asbestos exposure during home renovations, 337 (39.3%) reported that their partner had been exposed to asbestos during renovations, and 196 (22.8%) reported that their children had been exposed. More than 20% of renovators planned to further renovate their current homes within the next 5 years. CONCLUSIONS: Self-reported asbestos exposure during home renovation is common. This preventable exposure could place adults and children at risk of MM many years into the future. Although such exposure is self-reported and ideally should be verified, this study identifies a potentially important problem in NSW.

Potential years of life lost (PYLL) caused by asbestos-related diseases in the world.

BACKGROUND: We applied the well-established, but rather under-utilized, indicator of Potential Years of Life Lost (PYLL) to estimate the global burden of mesothelioma and asbestosis. METHODS: We analyzed all deaths caused by mesothelioma and asbestosis that were reported by 82 and 55 countries, respectively, to the World Health Organization (WHO) from 1994 to 2010. RESULTS: The 128,015 and 13,885 persons who died of mesothelioma and asbestosis, potentially lost a total of 2.18 million and 180,000 years of life (PYLL), or, an annual average PYLL of 201,000 years and 17,000 years, respectively. The average PYLL per decedent were 17.0 and 13.0 years for mesothelioma and asbestosis, respectively. CONCLUSIONS: The current burden of asbestos-related diseases (ARDs) in terms of PYLL is substantial. The future burden of ARDs can be eliminated by stopping the use of asbestos.

Computed tomography-based imaging biomarker identifies coal workers' pneumoconiosis.

Rationale: The increase in the incidence and the diagnostic limitations of pneumoconiosis have emerged as a public health concern. This study aimed to conduct a computed tomography (CT)- based quantitative analysis to understand differences in imaging results of pneumoconiosis according to disease severity. Methods: According to the International Labor Organization (ILO) guidelines, coal workers' pneumoconiosis (CWP) are classified into five categories. CT images were obtained only at full inspiration and were quantitatively evaluated for airway structural variables such as bifurcation angle (θ), hydraulic diameter (Dh), wall thickness (WT), and circularity (Cr). Parenchymal functional variables include abnormal regions (emphysema, ground-glass opacities, consolidation, semi consolidation, and fibrosis) and blood vessel volume. Through the propensity score matching method, the confounding effects were decreased. Results: Category 4 demonstrated a reduced θ in TriLUL, a thicker airway wall in both the Trachea and Bronint compared to Category 0, and a decreased Cr in Bronint. Category 4 presented with higher abnormal regions except for ground-glass opacity and a narrower pulmonary blood vessel volume. A negative correlation was found between abnormal areas with lower Hounsfield units (HU) than the normal lung and the ratio of forced expiratory volume in 1 s/forced vital capacity, with narrowed pulmonary blood vessel volume which is positively correlated with abnormal areas with upper HU than the normal lung. Conclusion: This study provided valuable insight into pneumoconiosis progression through a comparison of quantitative CT images based on severity. Furthermore, as there has been paucity of studies on the pulmonary blood vessel volume of the CWP, in this study, a correlation between reduced pulmonary blood vessel volume and regions with low HU values holds significant importance.

Elimination of asbestos use and asbestos-related diseases: an unfinished story.

Asbestos is a proven human carcinogen. Asbestos-related diseases (ARDs) typically comprise lung cancer, malignant mesothelioma, asbestosis, pleural plaques, thickening and effusion. International organizations, notably the World Health Organization and the International Labour Organization, have repeatedly declared the need to eliminate ARDs, and have called on countries to stop using asbestos. However, the relevant national-level indicators (e.g., incidence/mortality rates and per capita asbestos use, as well as their interrelationships) indicate that ARDs are increasing and asbestos use is continuing in the world. Lessons learned by industrialized countries in terms of policy and science have led to a growing number of countries adopting bans. In contrast, industrializing countries are faced with a myriad of forces prompting them to continue using asbestos. Full-scale international cooperation will thus be needed, with industrialized countries sharing their experiences and technologies to enable industrializing countries to make smooth transitions to banned states and achieve the goal of eliminating ARDs.

A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels.

BACKGROUND: Malignant mesothelioma (MM) is an aggressive pleural tumor which is difficult to diagnose in its early stages. Thus, biomarkers for MM including soluble mesothelin-related protein (SMRP) are currently an area of intense research interest. However, SMRP is affected by several factors other than malignancy which need to be taken into account in the individual patient. This study aimed to evaluate factors required to adjust SMRP levels for such variables and produce a useful prediction equation for clinical application. METHODS: Serum SRMP levels were measured in 535 subjects formerly exposed to asbestos and silica, including many with asbestos-related disorders (ARDs). Linear regression analyses were used to quantify the strength and " direction " of the relationship between SMRP and several independent variables,and 2 × 2 tables were used to determine the diagnostic accuracy of SMRP levels, taking into account clinical variables. RESULTS: SMRP levels were affected by age and glomerular filtration rate (GFR), which were strong confounders in this study. Body mass index (BMI) was also an initial confounder but lost significance after other factors were taken into account.SMRP was also affected by smoking. Poor sensitivity (15.1 % )for SMRP values among subjects with non-malignant asbestos-related disorders was found when compared to currently healthy subjects with a history of asbestos exposure. CONCLUSIONS: The present study proposes an equation based on age and GFR to improve diagnostic accuracy of SMRP.The poor sensitivity of SMRP found in this study suggests that further work is needed to fi nd new candidate biomarkers for diagnosing early stage MM.

The effects of smoking on the relationship between metabolic syndrome and arterial stiffness.

It has been reported that arterial stiffness assessed by pulse wave velocity (PWV) can predict cardiovascular morbidity and mortality. Metabolic syndrome and smoking are independently associated with increased risk of cardiovascular disease. The purpose of this study was to evaluate the effect of smoking on the relationship between metabolic syndrome and arterial stiffness. We retrospectively enrolled 1,530 men on whom brachial-ankle pulse wave velocity (baPWV) measurement had previously been performed as part of health screening at Kosin University Hospital. We found that PWV was positively correlated with the following variables: age (r = 0.391, P < 0.0001), systolic blood pressure (r = 0.438, P < 0.0001), diastolic blood pressure (r = 0.377, P < 0.0001), low-density lipoprotein (LDL) (r = 0.068, P = 0.008) and high-density lipoprotein (HDL) (r = 0.027, P = 0.287), whereas BMI was negatively correlated, although without statistical significance (r = -0.026, P = 0.309). Among current smokers, PWV decreased with increasing BMI (from 1,387.9 to 1,311.6), and increased with increasing HDL (from 1,342.7 to 1,385.4). On the other hand, among never smokers, PWV increased with increasing BMI (from 1,382.3 to 1,458.8), and decreased with increasing HDL (from 1,391.2 to 1,369.7). PWV was inversely associated with BMI and HDL, and these differences are likely due to smoking.

Nuclear factor-kappa B is not involved in titanium dioxide-induced inflammation.

Research over recent years have shown that titanium dioxide (TiO2) nanoparticles (NPs) induce inflammation in various lung, kidney, liver and brain cells. Although the mechanism of inflammation is unclear, existing literature suggests the underlying role of oxidative stress. On the other hand, it has also been shown that nuclear factor-kappa B (NF-kappaB) is activated in response to pro-inflammatory cytokines. In this study we investigated the involvement of NF-kappaB in TiO2-induced inflammation in human lung adenocarcinomic epithelial cells (A549 cells). After 24h of treatment, IL-8 protein release from A549 cells, induced by 10, 50 and 250 microg/ml of P25 TiO2 NPs, were statistically significantly raised, compared to that of the control. This finding corroborates existing literature in that TiO2 NPs induce a dose-dependent increase in the release of IL-8 protein when exposed to A549 cells. However, the binding of NF-kappaB DNA was not affected after 6 h of incubation with P25. Therefore, NF-kappaB DNA binding is not the likely transcription pathway that leads to TiO2-induced inflammation.

Classification of rotator cuff tears in ultrasound images using deep learning models.

Rotator cuff tears (RCTs) are one of the most common shoulder injuries, which are typically diagnosed using relatively expensive and time-consuming diagnostic imaging tests such as magnetic resonance imaging or computed tomography. Deep learning algorithms are increasingly used to analyze medical images, but they have not been used to identify RCTs with ultrasound images. The aim of this study is to develop an approach to automatically classify RCTs and provide visualization of tear location using ultrasound images and convolutional neural networks (CNNs). The proposed method was developed using transfer learning and fine-tuning with five pre-trained deep models (VGG19, InceptionV3, Xception, ResNet50, and DenseNet121). The Bayesian optimization method was also used to optimize hyperparameters of the CNN models. A total of 194 ultrasound images from Kosin University Gospel Hospital were used to train and test the CNN models by five-fold cross-validation. Among the five models, DenseNet121 demonstrated the best classification performance with 88.2% accuracy, 93.8% sensitivity, 83.6% specificity, and AUC score of 0.832. A gradient-weighted class activation mapping (Grad-CAM) highlighted the sensitive features in the learning process on ultrasound images. The proposed approach demonstrates the feasibility of using deep learning and ultrasound images to assist RCTs' diagnosis.

Structural and functional alterations of subjects with cement dust exposure: A longitudinal quantitative computed tomography-based study.

Cement dust exposure (CDE) can be a risk factor for pulmonary disease, causing changes in segmental airways and parenchymal lungs. This study investigates longitudinal alterations in quantitative computed tomography (CT)-based metrics due to CDE. We obtained CT-based airway structural and lung functional metrics from CDE subjects with baseline CT and follow-up CT scans performed three years later. From the CT, we extracted wall thickness (WT) and bifurcation angle (θ) at total lung capacity (TLC) and functional residual capacity (FRC), respectively. We also computed air volume (Vair), tissue volume (Vtissue), global lung shape, percentage of emphysema (Emph%), and more. Clinical measures were used to associate with CT-based metrics. Three years after their baseline, the pulmonary function tests of CDE subjects were similar or improved, but there were significant alterations in the CT-based structural and functional metrics. The follow-up CT scans showed changes in θ at most of the central airways; increased WT at the subgroup bronchi; smaller Vair at TLC at all except the right upper and lower lobes; smaller Vtissue at all lobes in TLC and FRC except for the upper lobes in FRC; smaller global lung shape; and greater Emph% at the right upper and lower lobes. CT-based structural and functional variables are more sensitive to the early identification of CDE subjects, while most clinical lung function changes were not noticeable. We speculate that the significant long-term changes in CT are uniquely observed in CDE subjects, different from smoking-induced structural changes.

Analysis of lung cancer-related genetic changes in long-term and low-dose polyhexamethylene guanidine phosphate (PHMG-p) treated human pulmonary alveolar epithelial cells.

BACKGROUND: Lung injury elicited by respiratory exposure to humidifier disinfectants (HDs) is known as HD-associated lung injury (HDLI). Current elucidation of the molecular mechanisms related to HDLI is mostly restricted to fibrotic and inflammatory lung diseases. In our previous report, we found that lung tumors were caused by intratracheal instillation of polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. However, the lung cancer-related genetic changes concomitant with the development of these lung tumors have not yet been fully defined. We aimed to discover the effect of long-term exposure of PHMG-p on normal human lung alveolar cells. METHODS: We investigated whether PHMG-p could increase distorted homeostasis of oncogenes and tumor-suppressor genes, with long-term and low-dose treatment, in human pulmonary alveolar epithelial cells (HPAEpiCs). Total RNA sequencing was performed with cells continuously treated with PHMG-p and harvested after 35 days. RESULTS: After PHMG-p treatment, genes with transcriptional expression changes of more than 2.0-fold or less than 0.5-fold were identified. Within 10 days of exposure, 2 protein-coding and 5 non-coding genes were selected, whereas in the group treated for 27-35 days, 24 protein-coding and 5 non-coding genes were identified. Furthermore, in the long-term treatment group, 11 of the 15 upregulated genes and 9 of the 14 downregulated genes were reported as oncogenes and tumor suppressor genes in lung cancer, respectively. We also found that 10 genes of the selected 24 protein-coding genes were clinically significant in lung adenocarcinoma patients. CONCLUSIONS: Our findings demonstrate that long-term exposure of human pulmonary normal alveolar cells to low-dose PHMG-p caused genetic changes, mainly in lung cancer-associated genes, in a time-dependent manner.

Quantitative computed tomography imaging-based classification of cement dust-exposed subjects with an artificial neural network technique.

BACKGROUND AND OBJECTIVE: Cement dust exposure is likely to affect the structural and functional alterations in segmental airways and parenchymal lungs. This study develops an artificial neural network (ANN) model for identifying cement dust-exposed (CDE) subjects using quantitative computed tomography-based airway structural and functional features. METHODS: We obtained the airway features in five central and five sub-grouped segmental regions and the lung features in five lobar regions and one total lung region from 311 CDE and 298 non-CDE (NCDE) subjects. The five-fold cross-validation method was adopted to train the following classification models:ANN, support vector machine (SVM), logistic regression (LR), and decision tree (DT). For all the classification models, linear discriminant analysis (LDA) and genetic algorithm (GA) were applied for dimensional reduction and hyperparameterization, respectively. The ANN model without LDA was also optimized by the GA method to observe the effect of the dimensional reduction. RESULTS: The genetically optimized ANN model without the LDA method was the best in terms of the classification accuracy. The accuracy, sensitivity, and specificity of the GA-ANN model with four layers were greater than those of the other classification models (i.e., ANN, SVM, LR, and DT using LDA and GA methods) in the five-fold cross-validation. The average values of accuracy, sensitivity, and specificity for the five-fold cross-validation were 97.0%, 98.7%, and 98.6%, respectively. CONCLUSIONS: We demonstrated herein that a quantitative computed tomography-based ANN model could more effectively detect CDE subjects when compared to their counterpart models. By employing the model, the CDE subjects may be identified early for therapeutic intervention.