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PURPOSE Early detection is significant to reduce lung cancer-related death. Computer-aided detection system (CADs) can help radiologists to make an early diagnosis. In this paper, we propose a novel 3D gray density coding feature (3D GDC) and fuse it with extracted geometric features. The fusion feature and random forest are used for benign-malignant pulmonary nodule classification on Chest CT. METHODS First, a dictionary model is created to acquire codebook. It is used to obtain feature descriptors and includes 3D block database (BD) and distance matrix clustering centers. 3D BD is balanced and randomly selecting from benign and malignant pulmonary nodules of training data. Clustering centers is got by clustering the distance matrix, which is the distance between every two blocks in 3D BD. Then, feature descriptor is obtained by coding the pulmonary nodule with codebook, and 3D GDC feature is the result of histogram statistics on feature descriptor. Second, geometric features are extracted for fusion feature. Finally, random forest is performed for benign-malignant pulmonary nodule classification with fusion feature of the 3D gray density coding feature and the geometric features. RESULTS We verify the effectiveness of our method on the public LIDC-IDRI dataset and the private ZSHD dataset. For LIDC-IDRI dataset, compared with other state-of-the-art methods, we achieve more satisfactory results with 93.17 ± 1.94% for accuracy and 97.53 ± 1.62% for AUC. As for private ZSHD dataset, it contains a total of 238 lung nodules from 203 patients. The accuracy and AUC achieved by our method are 90.0% and 93.15%. CONCLUSIONS The results show that our method can provide doctors with more accurate results of benign-malignant pulmonary nodule classification for auxiliary diagnosis, and our method is more interpretable than 3D CNN methods, which can provide doctors with more auxiliary information.

Lung cancer is one of the most prevalent and lethal cancers worldwide (1). The traditional treatments include surgery, chemotherapy, radiotherapy and interventional therapy. The survival of lung cancer patients has dramatically been prolonged in recent years with the availability of targeted therapies, antiangiogenic agents and immune checkpoint inhibitors (ICIs). Meanwhile, technologies for the molecular detection of lung cancer have also advanced rapidly: the detection of single driver genes has evolved to cover combined multi-gene analysis, and whole exome sequencing (WES) has increasingly been applied in the clinical setting. In addition, life support technologies, including ventilators, artificial liver, and artificial kidney as well as extracorporeal membrane oxygenation (ECMO), have further matured, providing powerful forms of life support for patients with various acute and critical diseases. However, most clinical studies have only enrolled patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores from 0 to 1, with few patients having PS scores of 2; patients with a PS score of 3 or 4 have been typically excluded. Therefore, due to the lack of high-quality evidence, supportive care is recommended for patients with a PS score of 3 to 4 in the current guidelines. In the real-world, however, approximately 25% of lung cancer patients present with PS score of 3 or 4 (2) or attain scores between 3 and 4 during the course of treatment. Certain patients with high PS scores can benefit from individualized anti-tumor treatment plus appropriate life-support techniques. In 2017, the Lung Cancer Research Team at the First Affiliated Hospital of Guangzhou Medical College & Institute of Respiratory Diseases for the first time pioneered the concept of “advanced severe lung cancer” (3) and argued that standardized therapy for chronic obstructive pulmonary disease (COPD) plus anti-tumor therapy can improve both quality of life and prognosis in patients with lung cancer combined with COPD. The authors also found that the early detection of lung cancer driver genes and timely targeted therapy can be successful in treating patients with advanced severe lung adenocarcinoma with a PS score of 4 (4). In 2019, the concept of advanced severe lung cancer was further developed in a featured article (5) that indicated “Advanced severe lung cancer: does not refer to end-stage lung cancer but rather to stage IIIB, IIIC and IV lung cancers with a PS score of 2–4, which can result from a variety of factors related to the disease itself or anti-tumor drugs and which are highly likely to benefit from the currently available systemic anti-tumor therapies”. In recent years, with the advances in lung cancer diagnosis and treatment techniques and life support technologies, more clinical studies have enrolled patients with a PS score of 2, and some real-world studies have enrolled patients with PS scores of 3–4. Even for patients with early-stage lung cancer, studies have shown that patients with poor PS scores and co-morbidities have a reduced chance of undergoing surgery and an increased mortality rate (6); nevertheless, survival benefit may still be obtained through surgical modifications combined with individualized and multidisciplinary treatment (7). Therefore, the concept of severe lung cancer should not be limited to advanced lung cancer, but applied to all lung cancer patients. In particular, due to the increase in treatment options as well as substantially prolonged survival, the majority of patients may have a PS score between 2 and 4 for a certain period of time due to a variety of reasons. How to provide timely and reasonable treatment for these lung cancer patients has become a critically important real-world research topic. Therefore, we invited lung cancer experts at home and abroad to consider this issue, and this group has reached the following consensus.

Objective: The expression and function of platinum transporters affect drug tissue concentration and therapeutic effects. We had previously characterized functional variant of platinum intake transporter SLC31A1 gene. We aimed to investigate the association of platinum efflux transporter gene ABCG2 polymorphism and combined ABCG2 and SLC31A1 polymorphisms with clinical outcomes of NSCLC patients receiving platinum-based chemotherapy. Methods: We genotyped thirteen tagging and functional SNPs of ABCG2 in 1004 patients, and assessed their association with response, toxicity and survival using unconditional logistic regression and Cox proportional hazards regression analyses respectively. Results: Nonsynonymous rs2231142 (odds ratio [OR] 2.07; 95 % confidence interval [CI] 1.26-3.63), rs1871744 (OR 0.60; 95 % CI 0.42-0.87) and their haplotype and diplotype were associated with objective response. Rs4148157 was associated with shorter overall survival (Log-rank P = 0.002; hazard ratio [HR] 1.22; 95 % CI 1.05-1.42). Furthermore, the combined SLC31A1 rs2233914 and ABCG2 rs1871744 genotype was significantly associated with poor response (OR 0.31; 95 % CI 0.17-0.56; P interaction = 0.003). And the combined genotypes of the functional rs10759637 of SLC31A1 and the nonsynonymous rs2231142 (Log-rank P = 5.20×10-5; HR 1.47; 95 % CI 1.19-1.81; P interaction = 0.007) or linked rs4148157 of ABCG2 were significantly associated with poor survival. Conclusion: This study reveals divergent association of ABCG2 polymorphism with response and survival of NSCLC patients receiving platinum-based chemotherapy, demonstrates the combined effects of functional variants of ABCG2 and SLC31A1 on clinical outcomes, and highlights pharmacogenetic relevance of platinum transporter genes interaction.

Background Patients with anaplastic lymphoma kinase-rearranged (ALK+) non–small cell lung cancer (NSCLC) treated with crizotinib inevitably relapse, with brain as common site of progression. Patients and methods ASCEND-6, a phase 1/2, single-arm study, included adult Chinese patients with stage IIIB or IV ALK+ NSCLC pretreated with crizotinib as the last therapy (irrespective of prior chemotherapies [≤2]). Primary endpoints were pharmacokinetics (PK), safety, and tolerability. Key secondary endpoint was overall response rate (ORR; investigator assessed). Results Of the 103 enrolled patients, all received prior crizotinib, 70 % received ≥1 prior chemotherapy regimen, and 63.1 % had brain metastases at baseline. In the phase 1 component, 20 patients completed a 5-day PK run-in period. Median Tmax (n = 16) was ∼6 h; geometric means of AUC0–24 h (n = 16) and Cmax (n = 16) at steady state were 22,000 ng*h/mL and 1080 ng/mL, respectively. In the final analysis, median follow-up time was 34 months (range: 27.8–40.6). The ORR was 41.7 % (95 % confidence interval [CI]: 32.1–51.9), and median progression-free survival was 7.2 months (95 % CI: 4.1–7.5). Median overall survival was 17.5 months (95 % CI: 10.8–24.3). Most frequent adverse events, regardless of study drug relationship (mostly grade 1/2), were diarrhea (74.8 %), vomiting (62.1 %), alanine transaminase increased (59.2 %), aspartate transaminase increased (58.3 %), and nausea (58.3 %). Conclusions Ceritinib PK in Chinese patients is consistent with those observed in the global ASCEND-1 study. Ceritinib was well tolerated and showed durable responses in Chinese patients with ALK+ NSCLC who progressed after crizotinib and ≤2 prior lines of chemotherapy.

Yan Liu,1,* Chi Zhang,2,* Chengyu Li,1 Chunxue Bai,3 Hongcai Shang1 1Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute for Brain Disorders, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongcai ShangKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, 5 Haiyuncang, Dongcheng District, Beijing 100700, People’s Republic of ChinaEmail shanghongcai@126.comBackground: There were few studies on the case mortality of severe community-acquired pneumonia (CAP) in elderly people. Improved outcomes with XueBiJing (XBJ) injection vs placebo have been shown in overall trial populations. We investigated the efficacy and safety of XBJ vs placebo in subjects with severe CAP stratified by age (< 65 and ≥ 65 years).Methods: This post hoc analysis of a large randomized trial compared data from elderly and nonelderly patients with XBJ, 100 mL, q 12 h, or a visually indistinguishable placebo for five-to-seven days.Results: Among subjects ≥ 65 years (n=291), 23 (16.0%) XBJ recipients and 41 (27.9%) placebo recipients (P=0.014) died within 28 days. Among subjects < 65 years (n=360), XBJ still had lower mortality (XBJ 15.6% vs placebo 22.8%; P=0.082), without significantly statistical difference. Total duration of ICU stay and the time of mechanical ventilation were similar in both groups (P> 0.05). XBJ also had a favorable safety profile, with no clinically relevant differences between the two groups. The overall incidence of adverse events was similar in both groups.Conclusion: XBJ was safe and effective for reduction in 28-day mortality among elderly patients with severe CAP. Additional confirmatory trials involving elderly patients are needed to further confirm the present results.Trial Registration: http://www.chictr.org.cn/index.aspx. ChiCTR-TRC-13003534.Keywords: severe community-acquired pneumonia, randomized controlled trial, post hoc analysis, 28-day mortality rate, XueBiJing injection

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities., For patients with acute COVID-19 pneumonia who require oxygen support, the International Task Force made suggestions for remdesivir and dexamethasone, but against hydroxychloroquine. Post-discharge management of COVID-19 survivors is a research priority. https://bit.ly/32B96uI

Pulmonary nodules risk classification in adenocarcinoma is essential for early detection of lung cancer and clinical treatment decision. Improving the level of early diagnosis and the identification of small lung adenocarcinoma has been always an important topic for imaging studies. In this study, the authors propose a deep convolutional neural network (CNN) with scale-transfer module (STM) and incorporate multi-feature fusion operation, named STM-Net. This network can amplify small targets and adapt to different resolution images. The evaluation data were obtained from the computed tomography (CT) database provided by Zhongshan Hospital Fudan University (ZSDB). All data have a pathological label and their lung adenocarcinomas risk are classified into four categories: atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma. The authors' deep learning network STM-Net was trained and tested for the risk stage prediction. The accuracy and the average area under the receiver operating characteristic curve achieved by their method are 95.455% and 0.987 for the ZSDB dataset. The experimental results show that STM-Net largely boosts classification accuracy on the pulmonary nodules classification compared with state-of-the-art approaches. The proposed method will be an effective auxiliary to help physicians diagnosis pulmonary nodules risk classification in adenocarcinoma in early-stage.

Background Tyrosine kinase inhibitors (TKIs), such as gefitinib, are widely used as standard treatments for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. However, the subsequent inevitable drug resistance has become a major challenge in clinical treatment. The aim of this study was to investigate the role of tissue-type plasminogen activator (PLAT) in gefitinib resistance in NSCLC. Methods The function of PLAT was determined using gefitinib-resistant cells and a nude mouse model. The gene knockdown was achieved by Lentivirus based RNA silence technique. Expression of relevant genes and proteins, cell viability, proliferation, apoptosis, cell cycle, reactive oxygen species levels, mitochondrial membrane potential and differential gene expression was detected by RT-qPCR, western blot, cell counting kit-8 assay, EdU incorporation, flow cytometry, JC-1 dye assay and complementary DNA arrays. The effects of PLAT knockdown on tumorigenesis was analyzed in vivo. Results Gefitinib-resistant cells expressed higher levels of PLAT and that knockdown of PLAT in resistant cells restored gefitinib sensitivity. Tumor proliferation was limited in vivo following PLAT knockdown. Moreover, PLAT knockdown affected mitochondrial function, caused caspase activation and cell cycle arrest, and activated TNF-α signaling, leading to apoptosis of gefitinib-resistant PC9 cells. Conclusions Our results suggest that PLAT reduces apoptosis of NSCLC cells and knockdown of PLAT enhances anticancer effect of gefitinib by upregulating TNF-α signaling.

An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.

The Internet of Things (IoT) includes three core procedures: full spectrum perception, reliable transmission, and intelligent processing. It can be applied for the prevention and control of SARI (severe acute respiratory infection). By combining sensors, information technology, artificial intelligence, and available dynamic networking devices, IoT could realize long-distance communication between hospitals, patients, and medical devices, which could ultimately improve current medical conditions.

Rationale It remains unknown whether long-term ozone exposure can impair lung function. Objectives To investigate the associations between long-term ozone exposure and adult lung function in China. Methods Lung function results and diagnosis of small airways dysfunction (SAD) were collected from a cross-sectional study, China Pulmonary Health Study (N=50,991). We used multivariate linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trend. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and main results We observed each 1-standard deviation (SD, 4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 mL/s [95% confidence interval (CI): 8.8, 19.6] decrease in forced expiratory flow at 75th percentile of vital capacity and a 29.5 mL/s (95% CI: 19.6, 39.5) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI: 1.06, 1.11) for a 1-SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with a decreased ratio of expiratory volume in 1 second to forced vital capacity (FEV1/FVC) but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusion We found independent associations of long-term ozone exposure with impaired small airways function and higher SAD risks, while the associations with airflow obstruction were weak. COPD patients appear to be more vulnerable.

BACKGROUND: Patients with consistent lung pure ground-glass nodules (pGGNs) have a high incidence of lung adenocarcinoma that can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Regular follow-up is recommended for AIS and MIA, while surgical resection should be considered for IAC. This study sought to develop a multi-parameter prediction model to increase the diagnostic accuracy in discriminating between IAC and AIS or MIA. METHODS: The training data set comprised consecutive patients with lung pGGNs who underwent resection from January to December 2017 at the Zhongshan Hospital. Of the 370 resected pGGNs, 344 were pathologically confirmed to be AIS, MIA, or IAC and were included in the study. The 26 benign pGGNs were excluded. We compared differences in the clinical features (e.g., age and gender), the content of serum tumor biomarkers, the computed tomography (CT) parameters (e.g., nodule size and the maximal CT value), and the morphologic characteristics of nodules (e.g., lobulation, spiculation, pleura indentation, vacuole sign, and normal vessel penetration or abnormal vessel) between the pathological subtypes of AIS, MIA, and IAC. An abnormal vessel was defined as “vessel curve” or “vessel enlargement”. Statistical analyses were performed using the chi-square test, analysis of variance (ANOVA), and rank test. The IAC prediction model was constructed via a multivariate logistical regression. Our prediction model for lung pGGNs was further validated in a data set comprising consecutive patients from multiple medical centers in China from July to December 2018. In total, 345 resected pGGNs were pathologically diagnosed as lung adenocarcinoma in the validation data set. RESULTS: In the training data set, patients with pGGNs ≥10 mm in size had a high incidence (74.5%) of IAC. The maximal CT value of IAC [–416.1±121.2 Hounsfield unit (HU)] was much higher than that of MIA (–507.7±138.0 HU) and AIS (–602.6±93.3 HU) (P

Supplemental Digital Content is available in the text., Objectives: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. Design: Prospective, randomized, controlled study. Setting: Thirty-three hospitals in China. Patients: A total of 710 adults 18–75 years old with severe community-acquired pneumonia. Interventions: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. Measurements and Main Results: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9–21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4–15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]). Conclusions: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.

According to multiple studies, the objective response rate of PD‐1/PD‐L1 inhibitors in the second‐line treatment of unscreened non‐small cell lung cancer (NSCLC) is only approximately 20%. Predictive biomarkers of treatment efficacies are still under investigation. In selected NSCLC patients with PD‐L1 expression ≥ 50%, the response rate of pembrolizumab in first‐line treatment can reach 44.8%. Moreover, patients with a higher tumor mutation burden (TMB) tend to achieve a better response with nivolumab. Besides PD‐L1 expression and TMB, taking all these indicators into consideration would hypothetically maximize the clinical response in a specific subgroup of patients. Our study aims to accumulate large and complete samples and clinical data to verify the biomarkers and their cutoff values related to the efficacy of PD‐1/PD‐L1 inhibitors in Chinese NSCLC patients, and to construct a comprehensive predictive model by combining multi‐omics data with contemporary machine learning techniques. NSCLC patients administered treatment of anti‐PD‐1/PD‐L1 antibodies or a combination with other drugs have been enrolled. The estimated enrollment is 250 participants. A sophisticated predictive model of immunotherapy response in the Chinese population has not yet been developed. It is clinically and practically imperative to comprehensively evaluate the possible indicators of Chinese NSCLC patients through multiple test platforms, such as next generation sequencing, PCR, or immunohistochemistry. This study is registered in the Chinese Clinical Trial Registry (ChiCTR1900021395).

To investigate the efficacy and safety of nintedanib versus placebo in Chinese patients with idiopathic pulmonary fibrosis (IPF). The INPULSIS® trials consisted of two replicate, randomized, placebo-controlled, double-blind trials comparing nintedanib 150 mg bid with placebo over a 52-week treatment period. The primary endpoint was annual rate of decline in forced vital capacity (FVC); key secondary endpoints were change from baseline in Saint George’s Respiratory Questionnaire’s total score and time to first investigator-reported acute exacerbation. Data from both trials were pooled for the Chinese subgroup analyses. A total of 101 Chinese patients (nintedanib/placebo: 61/40) were treated. The demographic characteristics were generally balanced between treatment arms. Over 52 weeks, the rate of decline in FVC was lower in nintedanib-treated patients compared with placebo-treated patients in the Chinese subgroup [− 126.43 vs. − 229.82 mL/year; ∆ = 103.39 mL/year (95% confidence interval, CI: − 19.40 to 226.18)]. The proportion of patients with adverse events (AEs) over 52 weeks was similar between treatment arms. The most commonly reported AEs with nintedanib treatment were gastrointestinal symptoms (diarrhoea, nausea, and vomiting). Nintedanib is clinically efficacious in Chinese patients with IPF with approximately 50% reductions in the rate of decline in FVC, demonstrating slowed disease progression. Similar to the overall INPULSIS® population, nintedanib has a favourable benefit/risk profile in Chinese patients with IPF. NCT01335464, NCT01335477. Boehringer Ingelheim. Plain language summary available for this article.

Aim: In order to improve stable COPD patients’ management and reduce exacerbation, we established an Internet of Things based COPD managing system in Qingpu District Shanghai City. Methods: This system is composed of a clinical information database, a 1 M box, a handheld portable spirometer and mobile APPs. This database could collect the exacerbation treatment data from Zhongshan Hospital Qingpu Branch, the largest tertiary healthcare provider in local area, and the follow-up data of stable patients from the 11 primary hospitals through a 1 M box. The lung function data could be tested and uploaded in a real-time way by the handheld portable spirometer. Different smart-phone APPs were developed for the patients and physicians to establish direct communication to improve the disease control. Notably, the clinical data of patients was classified, transferred and stored in an anonymous and encrypted way to preserve the privacy. Results: After starting use in August 2016, 537 inpatients and 13,665 out patients’ follow-up data were recorded in this system automatically.3838 COPD patients were brought to COPD management using this system including 2857 male and 981 female patients. Physicians in Qingpu Branch and primary hospitals endeavored to provide homogenized management for those patients. Conclusions: This IOT system facilitated the collection, storage, transmission and analysis of most COPD patient’s follow-up and exacerbation data, which could be of great potential to improve the management of COPD in local area. Keywords: Internet of Things, COPD, Managing system

Pleural effusion (PE) is commonly observed in advanced lung cancer and was suggested to contain both cell-free tumor DNA and tumor cells. Molecular profiling of PE represents a minimally invasive approach of detecting tumor driver mutations for clinical decision making, especially when tumor tissues are not available. The objective of this study is to investigate the efficacy and precision of detecting gene alterations in PE samples to address the feasibility in clinical use. Methods: Sixty-three metastatic lung cancer patients with (n=30, cohort 1) or without (n=33, cohort 2) matched tumor tissues were enrolled in this study. PE and plasma samples of each patient were collected simultaneously. Supernatant and cell precipitate of PE were processed separately to extract cfDNA (PE-cfDNA) and sediment DNA (sDNA). All samples were subjected to targeted next-generation sequencing (NGS) of 416 cancer-related genes. Results: PE supernatants contain more abundant tumor DNA than PE sediments and plasma samples, suggested by higher mutant allele frequencies (MAF) and elevated mutation detection rate in PE-cfDNA (98.4% vs. 90.5% in PE sDNA vs. 87% in plasma cfDNA). In Cohort 1 with matched tumor tissue, tumor mutational burden (TMB) of PE-cfDNA was similar as tumor tissues (6.4 vs. 5.6), but significantly higher than PE sDNA (median TMB: 3.3) and plasma cfDNA (median TMB: 3.4). Ninety-three percent (27 out of 29) of tissue-determined driver mutations were detected in PE-cfDNA, including alterations in ALK, BRAF, EGFR, ERBB2, KRAS, NF1, PIK3CA, and RET, while only 62% were captured in plasma cfDNA. PE-cfDNA also has the highest detection rate of EGFR driver mutations in the full cohort (71% vs. 68% in PE sDNA vs. 59% in plasma cfDNA). Mutation detection from cytological negative and hemorrhagic PE is challenging. Comparatively, PE-cfDNA demonstrated absolute superiority than PE sDNA in such a scenario, suggesting that it is an independent source of tumor DNA and therefore less influenced by the abundance of tumor cells. Conclusion: Genomic profiling of PE-cfDNA offers an alternative, and potentially more meticulous approach in assessing tumor genomics in advanced lung cancer when tumor tissue is not available. Our data further demonstrate that in hemorrhagic or cytologically negative PE samples, PE-cfDNA has higher mutation detection sensitivity than sDNA and plasma cfDNA, and therefore is a more reliable source for genetic testing.

Background: Chronic obstructive pulmonary disease (COPD) has become a leading cause of morbidity and mortality in China, with tobacco smoke, air pollution, and occupational biohazards being the major risk factors. Objectives: The REACH trial is a multicenter, prospective, randomized controlled trial undertaken in China to assess the safety and effectiveness of the Spiration® Valve System (SVS) compared to standard medical care in COPD patients with severe emphysema. Methods: Patients with severe airflow obstruction, hyperinflation, and severe dyspnea with interlobar fissure integrity were evaluated for enrollment. A total of 107 subjects were randomized in a 2: 1 allocation ratio to either the treatment group (SVS valves and medical management) or the control group (medical management alone). Results: The 3-month primary endpoint showed statistically significant improvement in forced expiratory volume in 1 s in the treatment group compared to the control group (0.104 ± 0.18 vs. 0.003 ± 0.15 L, p = 0.001), with the difference being durable through 6 months. Statistically significant target lobe volume reduction was achieved at 3 months (mean change 684.4 ± 686.7 mL) and through 6 months (757.0 ± 665.3 mL). Exercise function and quality of life measures improved in the treatment group, but showed a deterioration in the control group. The serious adverse event (SAE) rate was 33% in the treatment group and 24.2% in the control group. The predominance of SAEs were acute exacerbations of COPD in both groups. There was 1 death in the control group and no deaths in the treatment group. Conclusion: The SVS represents a novel approach for the treatment of severe emphysema with a clinically acceptable risk-benefit profile.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25–75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 μg/m3 to 92 μg/m3 (average: 53 μg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30–28.33), FVC (17.45 mL, 95% CI: 7.16–27.74), PEF (86.64 mL/s, 95% CI: 59.77–113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64–47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

BackgroundLung cancer screening using low-dose computed tomography (LDCT) often leads to unnecessary biopsy because of the low specificity among patients with pulmonary nodules ≤10 mm. Circulating genetically abnormal cells (CACs) can be used to discriminate lung cancer from benign lung disease. To examine the diagnostic value of CACs in detecting lung cancer for patients with malignant pulmonary nodules ≤10 mm.MethodsIn this prospective study, patients with pulmonary nodules ≤10 mm who were detected at four hospitals in China from January 2019 to January 2020 were included. CACs were detected using fluorescence in-situ hybridization. All patients were confirmed as lung cancer or benign disease by further histopathological examination. Multivariable logistic regression models were established to detect the presence of lung cancer using CACs and other associated characteristics. Receiver operating characteristic analysis was used to evaluate the performance of CACs for lung cancer diagnosis.ResultsOverall, 125 patients were included and analyzed. When the cutoff value of CACs was >2, the sensitivity and specificity for lung cancer were 70.5 and 86.4%. Male (OR = 0.330, P = 0.005), maximum solid nodule (OR = 2.362, P = 0.089), maximum nodule located in upper lobe (OR = 3.867, P = 0.001), and CACs >2 (OR = 18.525, P < 0.001) met the P < 0.10 criterion for inclusion in the multivariable models. The multivariable logistic regression model that included the dichotomized CACs (>2 vs. ≤2) and other clinical factors (AUC = 0.907, 95% CI = 0.842–0.951) was superior to the models that only considered dichotomized CACs or other clinical factors and similar to the model with numerical CACs and other clinical factors (AUC = 0.913, 95% CI = 0.850–0.956).ConclusionCACs presented a significant diagnostic value in detecting lung cancer for patients with pulmonary nodules ≤10 mm.

Background The impact of corticosteroid therapy on outcomes of patients with coronavirus disease 2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. Methods In this single-center retrospective observational study, patients with ARDS caused by COVID-19 between January 20, 2020, and February 24, 2020, were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. Results A total of 382 patients [60.7 ± 14.1 years old (mean ± SD), 61.3% males] were analyzed. The median of sequential organ failure assessment (SOFA) score was 2.0 (IQR 2.0–3.0). Of these cases, 94 (24.6%) patients had invasive mechanical ventilation. The number of patients received systemic corticosteroids was 226 (59.2%), and 156 (40.8%) received standard treatment. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. Conclusion In this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS.

Purpose Available biomarkers lack sensitivity for an early lung cancer. Circulating genetically abnormal cells (CACs) occur early in tumorigenesis. To determine the diagnostic value of CACs in blood detected by 4-color fluorescence in situ hybridization (FISH) for lung cancer. Methods This was a prospective study of patients with pulmonary nodules ≤ 30 mm detected between 10/2019 and 01/2020 at four tertiary hospitals in China. All patients underwent a pathological examination of lung nodules found by imaging and were grouped as malignant and benign. CACs were detected by 4-color FISH. Patients were divided into the training and validation cohorts. Receiver operating characteristics analysis was used to analyze the diagnosis value of CACs. Results A total of 205 participants were enrolled. Using a cut-off value of ≥ 3, blood CACs achieved areas under the curve (AUCs) of 0.887, 0.823, and 0.823 for lung cancer in the training and validation cohorts, and all patients, respectively. CACs had high diagnostic values across all tumor sizes and imaging lesion types. CACs were decreased after surgery (median, 4 vs. 1, P P P Conclusion CACs might have a high value for the early diagnosis of lung cancer. These findings might need to be validated in future studies. Evidence suggested homology in genetic aberrations between the CACs and the tumor cells.

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic acute infectious disease, especially with the features of possible asymptomatic carriers and high contagiousness. It causes acute respiratory distress syndrome and results in a high mortality rate if pneumonia is involved. Currently, it is difficult to quickly identify asymptomatic cases or COVID-19 patients with pneumonia due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans, which facilitates the spread of the disease at the community level, and contributes to the overwhelming of medical resources in intensive care units.GoalThis study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist global frontline doctors to efficiently and precisely diagnose asymptomatic COVID-19 patients and cases who had a false-negative RT-PCR test result.MethodsWith online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan Unversity (approval number B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. These patients had SARS-CoV-2 RT-PCR test results and chest CT scans, both of which were used as the gold standard for the diagnosis of COVID-19 and COVID-19 pneumonia. In particular, the dataset included 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, and 122 asymptomatic cases who had positive RT-PCR test results, amongst whom 31 cases were diagnosed. We also integrated the function of a survey in nCapp to collect user feedback from frontline doctors.FindingsWe applied the statistical method of a multi-factor regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are fast and accessible: ‘Residing or visiting history in epidemic regions’, ‘Exposure history to COVID-19 patient’, ‘Dry cough’, ‘Fatigue’, ‘Breathlessness’, ‘No body temperature decrease after antibiotic treatment’, ‘Fingertip blood oxygen saturation ≤93%’, ‘Lymphopenia’, and ‘C-reactive protein (CRP) increased’. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). To ensure the sensitivity of the model, we used a cutoff value of 0.09. The sensitivity and specificity of the model were 98.0% (95% CI: 96.9%, 99.1%) and 17.3% (95% CI: 15.0%, 19.6%), respectively, in the training dataset, and 96.5% (95% CI: 95.1%, 98.0%) and 18.8% (95% CI: 16.4%, 21.2%), respectively, in the validation dataset. In the subset of the 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, the model predicted 132 cases, accounting for 96.4% (95% CI: 91.7%, 98.8%) of the cases. In the subset of the 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, the model predicted 59 cases, accounting for 95.2% (95% CI: 86.5%, 99.0%) of the cases. Considering the specificity of the model, we used a cutoff value of 0.32. The sensitivity and specificity of the model were 83.5% (95% CI: 80.5%, 86.4%) and 83.2% (95% CI: 80.9%, 85.5%), respectively, in the training dataset, and 79.6% (95% CI: 76.4%, 82.8%) and 81.3% (95% CI: 78.9%, 83.7%), respectively, in the validation dataset, which is very close to the published AI model.The results of the online survey ‘Questionnaire Star’ showed that 90.9% of nCapp users in WeChat mini programs were ‘satisfied’ or ‘very satisfied’ with the tool. The WeChat mini program received a significantly higher satisfaction rate than other platforms, especially for ‘availability and sharing convenience of the App’ and ‘fast speed of log-in and data entry’.DiscussionWith the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic patients and avoid misdiagnoses of cases with false-negative RT-PCR results. These patients require timely isolation or close medical supervision. By applying the model, medical resources can be allocated more reasonably, and missed diagnoses can be reduced. In addition, further education and interaction among medical professionals can improve the diagnostic efficiency for COVID-19, thus avoiding the transmission of the disease from asymptomatic patients at the community level.

Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Background There were a few studies on the case mortality of severe community-acquired pneumonia (CAP) in elderly people. Improved outcomes with XueBiJing (XBJ) Injection versus placebo have been shown in overall trial populations. We investigated the efficacy and safety of XBJ versus placebo in subjects with severe CAP stratified by age ( 0.05). XBJ also had a favorable safety profile, with no clinically relevant differences between two groups. The overall incidence of adverse events was similar in both groups. Conclusions XBJ was safe and effective for reduction in 28-day mortality among elderly patients with severe CAP. Additional trials involving elderly patients are needed to further confirm the present results.

Summary Background Small airway dysfunction is a common but neglected respiratory abnormality. Little is known about its prevalence, risk factors, and prognostic factors in China or anywhere else in the world. We aimed to estimate the prevalence of small airway dysfunction using spirometry before and after bronchodilation, both overall and in specific population subgroups; assess its association with a range of lifestyle and environmental factors (particularly smoking); and estimate the burden of small airway dysfunction in China. Methods From June, 2012, to May, 2015, the nationally representative China Pulmonary Health study invited 57 779 adults to participate using a multistage stratified sampling method from ten provinces (or equivalent), and 50 479 patients with valid lung function testing results were included in the analysis. We diagnosed small airway dysfunction on the basis of at least two of the following three indicators of lung function being less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50%, and FEF 75%. Small airway dysfunction was further categorised into pre-small airway dysfunction (defined as having normal FEV1 and FEV1/forced vital capacity [FVC] ratio before bronchodilator inhalation), and post-small airway dysfunction (defined as having normal FEV1 and FEV1/FVC ratio both before and after bronchodilator inhalation). Logistic regression yielded adjusted odds ratios (ORs) for small airway dysfunction associated with smoking and other lifestyle and environmental factors. We further estimated the total number of cases of small airway dysfunction in China by applying present study findings to national census data. Findings Overall the prevalence of small airway dysfunction was 43·5% (95% CI 40·7–46·3), pre-small airway dysfunction was 25·5% (23·6–27·5), and post-small airway dysfunction was 11·3% (10·3–12·5). After multifactor regression analysis, the risk of small airway dysfunction was significantly associated with age, gender, urbanisation, education level, cigarette smoking, passive smoking, biomass use, exposure to high particulate matter with a diameter less than 2·5 μm (PM2·5) concentrations, history of chronic cough during childhood, history of childhood pneumonia or bronchitis, parental history of respiratory diseases, and increase of body-mass index (BMI) by 5 kg/m2. The ORs for small airway dysfunction and pre-small airway dysfunction were similar, whereas larger effect sizes were generally seen for post-small airway dysfunction than for either small airway dysfunction or pre-small airway dysfunction. For post-small airway dysfunction, cigarette smoking, exposure to PM2·5, and increase of BMI by 5 kg/m2 were significantly associated with increased risk, among preventable risk factors. There was also a dose-response association between cigarette smoking and post-small airway dysfunction among men, but not among women. We estimate that, in 2015, 426 (95% CI 411–468) million adults had small airway dysfunction, 253 (238–278) million had pre-small airway dysfunction, and 111 (104–126) million had post-small airway dysfunction in China. Interpretation In China, spirometry-defined small airway dysfunction is highly prevalent, with cigarette smoking being a major modifiable risk factor, along with PM2·5 exposure and increase of BMI by 5 kg/m2. Our findings emphasise the urgent need to develop and implement effective primary and secondary prevention strategies to reduce the burden of this condition in the general population. Funding Ministry of Science and Technology of China; National Natural Science Foundation of China; National Health Commission of China.

Background The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we introduced a model to describe and monitor the immune status of sepsis and explored its prognostic value. Methods A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at day 1 and 3. Serum cytokines levels (TNF-α, IL-2R, IL-6, IL-8 and IL-10) and CD14 + monocyte HLA-DR expression were measured to serve as immune markers. Cut-off values were acquired from ROC curves and serum cytokine level higher than or HLA-DR level lower than cut point was defined as “positive”, otherwise defined as “negative”. Classification of each immune status, namely SIRS, CARS and MARS, was defined by numbers of positive immune markers levels. Changes of immune status from day 1 to 3 were classified into four groups which were Stabilization (SB), Deterioration (DT), Remission (RM) and Non-remission (NR). Results A total of 174 septic patients were enrolled including 50 non-survivors. In univariate analysis, serum levels of TNF-α, IL-2R, IL-6, IL-8 and IL-10 and HLA-DR expression at day 1 and 3 were associated with prognosis. Multivariate analysis discovered IL-10 and HLA-DR expression at day 3 were independent prognostic factors. Patients with MARS at day 1 had the highest mortality rate up to 58.7% among three immune status classifications, so did the patient with MARS at day 3 with mortality rate up to 69.2%. Immune status of 46.1% patients changed from day 1 to 3. Among four groups of immune status changes, DT had the highest mortality rate up to 77.8% followed by NR, RM and SB with mortality rate of 64.7%, 42.9% and 11.2% respectively. Conclusions Patients with severe immune disorder defined as MARS or deterioration of immune status defined as DT have the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers levels has prognostic values and worthy of further investigation. Trail Registration: ChiCTR-OCC-14005202 (Chinese Clinical Trial Registry), Registered 09 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=4373

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

The most significant characteristics of the pulmonary injuries induced by ischemia-reperfusion (IR) include robust inflammatory response, alveolar epithelial cells damage, and increased vascular permeability, which are also the main risk factors for related death, especially in the process of trauma, pulmonary embolism, lung transplantation, and cardiopulmonary bypass. Many factors are involved in this multistep pathophysiologic process directly or indirectly, including reactive oxygen species, immune cells, complement system, proinflammatory cytokines, and other factors. Several preclinical studies have effectively prevented or improved this devastating organ injury, involving the use of various antioxidants, anti-inflammatory agents, mesenchymal stromal cells, and ventilation with gaseous molecules; however, the majority of these have not been translated into clinical use yet. Meanwhile, some randomized controlled trials involving lung IR injury have some limitations. In the future, further studies and ongoing clinical trials are needed to be conducted to reveal the complex mechanism of lung IR injury and develop novel and effective therapeutic approaches.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) have been shown to improve ALI, and the imbalance of regulatory T cells (Tregs) and Th17 cells is associated with mortality in ALI/ARDS patients. However, whether administration of lung-resident MSC (LRMSC) improves lung injury and regulates the balance of Tregs and Th17 cells remains unknown. An ALI animal model was induced by LPS, and PBS or LRMSC were administered via tail vein after 4 h. LRMSC were subsequently detected in the lungs by a live imaging system (Berthold LB983, Germany). Lung morphology; lung wet-to-dry weight ratio; and total protein concentration, inflammatory cells, and cytokines in bronchoalveolar lavage fluid (BALF) and plasma were determined. The percentage of Tregs in lung and spleen, and of Th17 cells in lung and blood, were also evaluated. The results showed that LRMSC not only attenuated histopathological damage but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration and inflammatory cells in BALF. LRMSC also decreased inflammatory cytokines in both BALF and plasma and increased KGF-2 and surfactant protein C (SPC) expression in the lung. Flow cytometry revealed the upregulation of Tregs and the downregulation of Th17 cells, and the increase in the ratio of Tregs and Th17 cells. The live imaging system showed that LRMSC migrated to and were retained in the injured area. In conclusion, the results indicated that administration of LRMSC attenuates LPS-induced ALI via upregulating the balance of Tregs and Th17 cells.

Objective: To conduct a preliminary study of the hierarchical diagnosis and treatment of patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) using the Internet of Things (IoT) medical technology and to explore the feasibility of the hierarchical diagnosis, treatment, and management of OSAHS patients using IoT medicine in primary hospitals. Methods: The IoT technology and a remote medical monitoring system were used to observe and compare the respiratory and sleep parameters before and after a three-month intervention in 47 patients with OSAHS who met the diagnostic criteria and were selected in the Kashgar region. All parameters were compared based on the severity (mild, moderate, and severe) of OSAHS. Results: The Epworth Sleepiness Scale (ESS) score, apnea–hypopnea index (AHI), and nighttime minimum oxygen saturation (lowest SaO2min) improved in patients with OSAHS from before to after treatment ([Formula: see text]). The improvements were more profound in OSAHS patients with cardiovascular disease such as hypertension. Conclusion: The IoT medical technology can help to hierarchically diagnose, treat, and manage patients with OSAHS. It is feasible for primary hospitals in rural regions to use the IoT technology for the hierarchical diagnosis and treatment of OSAHS patients.

Background and objectives To improve lung nodule classification efficiency, we propose a lung nodule CT image characterization method. We propose a multi-directional feature extraction method to effectively represent nodules of different risk levels. The proposed feature combined with pattern recognition model to classify lung adenocarcinomas risk to four categories: Atypical Adenomatous Hyperplasia (AAH), Adenocarcinoma In Situ (AIS), Minimally Invasive Adenocarcinoma (MIA), and Invasive Adenocarcinoma (IA). Methods First, we constructed the reference map using an integral image and labelled this map using a K-means approach. The density distribution map of the lung nodule image was generated after scanning all pixels in the nodule image. An exponential function was designed to weight the angular histogram for each component of the distribution map, and the features of the image were described. Then, quantitative measurement was performed using a Random Forest classifier. The evaluation data were obtained from the LIDC-IDRI database and the CT database which provided by Shanghai Zhongshan hospital (ZSDB). In the LIDC-IDRI, the nodules are categorized into three configurations with five ranks of malignancy (“1” to “5”). In the ZSDB, the nodule categories are AAH, AIS, MIA, and IA. Results The average of Student's t-test p-values were less than 0.02. The AUCs for the LIDC-IDRI database were 0.9568, 0.9320, and 0.8288 for Configurations 1, 2, and 3, respectively. The AUCs for the ZSDB were 0.9771, 0.9917, 0.9590, and 0.9971 for AAH, AIS, MIA and IA, respectively. Conclusion The experimental results demonstrate that the proposed method outperforms the state-of-the-art and is robust for different lung CT image datasets.

The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defined as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be considered by individuals and governments while addressing several SDGs. Background: The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defned as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be consid‑ ered by individuals and governments while addressing several SDGs. Results: The concept of the Nature Step has evolved from innovative research indicating, how changed lifestyle in urban surroundings reduces contact with biodiverse environments, impoverishes microbiota, afects immune regulation and increases risk of NCDs. The Nature Step calls for strengthening connections to nature. Physical activity in natural environments should be promoted, use of fresh vegetables, fruits and water increased, and consumption of sugary drinks, tobacco and alcohol restricted. Nature relatedness should be part of everyday life and especially emphasized in the care of children and the elderly. Taking “nature” to modern cities in a controlled way is possible but a challenge for urban planning, nature conservation, housing, trafc arrangements, energy production, and impor‑ tantly for supplying and distributing food. Actions against the well-known respiratory risk factors, air pollution and smoking, should be taken simultaneously. Conclusions: In Finland and elsewhere in Europe, successful programmes have been implemented to reduce the burden of respiratory disorders and other NCDs. Unhealthy behaviour can be changed by well-coordinated actions involving all stakeholders. The growing public health concern caused by NCDs in urban surroundings cannot be solved by health care alone; a multidisciplinary approach is mandatory

SLC31A1 is the major transporter for platinum drug intake, its expression correlates with drug disposition and response. In 1004 Chinese NSCLC patients with platinum-based chemotherapy, we investigated the association between SLC31A1 polymorphisms and clinical outcomes. Heterozygotes of rs10759637 at 3'UTR was associated with severe thrombocytopenia (odds ratio [OR]: 2.69; P = 0.012) and shorter overall survival (hazard ratio [HR]: 1.24; P = 0.005). Variant homozygote of rs2233914 was correlated with longer overall survival (hazard ratio [HR]: 0.73; P = 0.008). Haplotype and diplotype of these linked SNPs were associated with hematologic toxicities. In stratification analyses, rs10759637 and rs2233914 consistently correlated with overall survival in specific subgroups such as men, smoker, patients older than 58 years, or with ECOG PS 0-1, or with squamous cell carcinoma. rs10759637 could change the local structure of 3'UTR harboring putative binding sites for hsa-miR-29, whose transfection into 16HBE cells resulted in remarkable suppression of gene expression. The rs10759637 variant significantly correlated with lowered luciferase activity in reporter assays and decreased expression of SLC31A1 transcript in tumorous tissues. The study thereby identified functional polymorphism of SLC31A1 that modulates miRNA-3'UTR interaction and gene expression as potential pharmacogenetic biomarker for clinical outcomes of platinum-based chemotherapy in NSCLC patients.

Summary Background Although exposure to cigarette smoking and air pollution is common, the current prevalence of chronic obstructive pulmonary disease (COPD) is unknown in the Chinese adult population. We conducted the China Pulmonary Health (CPH) study to assess the prevalence and risk factors of COPD in China. Methods The CPH study is a cross-sectional study in a nationally representative sample of adults aged 20 years or older from ten provinces, autonomous regions, and municipalities in mainland China. All participants underwent a post-bronchodilator pulmonary function test. COPD was diagnosed according to 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Findings Between June, 2012, and May, 2015, 57 779 individuals were invited to participate, of whom 50 991 (21 446 men and 29 545 women) had reliable post-bronchodilator results and were included in the final analysis. The overall prevalence of spirometry-defined COPD was 8·6% (95% CI 7·5–9·9), accounting for 99·9 (95% CI 76·3–135·7) million people with COPD in China. Prevalence was higher in men (11·9%, 95% CI 10·2–13·8) than in women (5·4%, 4·6–6·2; p 3 (1·85, 1·23–2·77) or 75 μg/m 3 or higher (2·00, 1·36–2·92), underweight (body-mass index 2 ; 1·43, 1·03–1·97), sometimes childhood chronic cough (1·48, 1·14–1·93) or frequent cough (2·57, 2·01–3·29), and parental history of respiratory diseases (1·40, 1·23–1·60). A lower risk of COPD was associated with middle or high school education (OR 0·76, 95% CI 0·64–0·90) and college or higher education (0·47, 0·33–0·66). Interpretation Spirometry-defined COPD is highly prevalent in the Chinese adult population. Cigarette smoking, ambient air pollution, underweight, childhood chronic cough, parental history of respiratory diseases, and low education are major risk factors for COPD. Prevention and early detection of COPD using spirometry should be a public health priority in China to reduce COPD-related morbidity and mortality. Funding Ministry of Health and Ministry of Science and Technology of China.

Background Limited evidence concerns the associations between ambient temperature and lung function and the results are mixed. Objective To evaluate the associations between temperature variations and daily fluctuations in pulmonary function in chronic obstructive pulmonary disease (COPD) patients. Methods We designed a time-series panel study of 28 male urban COPD patients with repeated daily lung function measurements from December 2012 to May 2013 in Shanghai, China. We used a linear mixed-effect model combined with a distributed lag model to estimate the cumulative effects of temperature on morning/evening pulmonary function tests (PFTs), including peak expiratory flow (PEF) and forced expiratory volume in 1-s (FEV1), while adjusting for within-subject correlations, individual characteristics, time trends and air pollution levels. Results We obtained a total of 8618 pairs of morning PFTs and 8528 pairs of evening PFTs. The associations between daily mean temperature and PEF were inverted U-shaped with both low and high temperatures significantly reducing morning and evening PEF. Compared with the referent temperature (16 °C), the low temperature (1st percentile, − 1 °C) would result in cumulative decreases of 32.20 L/min in morning PEF and 21.15 L/min in evening PEF over lags of two weeks. The corresponding decrements at the same lag associated with high temperature (99th percentile, 25 °C) were 38.10 L/min in morning PEF and 27.08 L/min in evening PEF. There were no statistically significant changes in morning or evening FEV1. Conclusions This time-series panel study provided robust evidence that both low and high temperatures were significantly associated with decrements in pulmonary function, particularly in PEF.

Background and purpose While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials. Materials and methods In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol. We assessed the forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0–3) response and trough FEV1 response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg. Treatment-emergent adverse events were recorded throughout treatment and ≤21 days after study medication. Results In the East Asian population, 1,152 patients were randomized (5,163 overall). After 24 weeks, FEV1 AUC0–3 and trough FEV1 responses were greater (P, Video abstract

e20581 Background: Small-cell lung cancer (SCLC) is an aggressive disease with rapid progression rate and high metastatic potential that accounts for 15% of all lung cancers. Early-stage SCLC is usually asymptomatic; therefore, the majority of the SCLC patients were diagnosed in advanced stages. Although some radiological features were reported with advanced stages SCLC by CT scans, diagnosis of early stages SCLC from CT images has remained challenging since the radiological features are not distinct. Neuron-specific enolase (NSE) is commonly used in the clinical setting as a biomarker for SCLC, but the sensitivity of the test did not meet the needs. Here, we proposed a study using Circulating Genetically Abnormal Cells (CAC) to improve the diagnosis rate of SCLC in the early stages. Methods: A series of 26 stage I SCLC patients were enrolled from October 2019 to October 2020. All participants were having newly discovered pulmonary nodules ≤ 30mm when enrolled in the study, with no previous cancer history. Before the histopathological examination, 10 ml of peripheral blood were collected from each patient for CAC test, by using a 4 color FISH–based assay to detect the genetic abnormalities of 3p22.1, 3q29, 10q22.3, and CEP10 in the chromosome. Besides, NSE was performed on all participants. Both tests were intended to evaluate the malignant risk of lung nodules. Results: Confirmed by histopathological exam, 69% patients were diagnosed with SCLC located on the central part of the lung, and 31% patients were found to have peripheral-type SCLC. 88% of the patients in the overall cohort were smokers or past smokers, and only 12% participants had a family history of cancer. For Immunohistochemistry tests, the numbers of participants with positive CD56, TTF-1, CgA, CK, Syn and Ki-67 ≥ 60% are 65%, 58%, 12%, 42%, 50% and 69%, respectively. For diagnostic performance, the sensitivity of CAC in the over-all cohort is 73.08% (95%CI: 52.21%-88.43%), compared with 50.00% (95%CI: 29.93%- 70.07%) for NSE. CAC has achieved 77.78% (95%CI: 52.36% - 93.59%) and 62.5% (95%CI：24.49% - 91.48%) sensitivity in the centra and peripheral group. For NSE, the sensitivity of these two groups were 55.56% (95%CI: 30.76% - 78.47%) and 37.5% (95%CI: 8.52% - 75.51%). Conclusions: Compared with NSE, CAC is more sensitive to stage I SCLC, especially for SCLC that arising in central locations. This non-invasive method can be a complementary diagnostic tool with LDCT for smokers aged ≥65 with newly discovered pulmonary nodules. Clinical trial information: ChiCTR1900026233.

BACKGROUND The authors built a model for lung cancer diagnosis previously based on the blood biomarkers progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin 19 fragment (CYFRA21-1). In the current study, they examined whether modification of the model to include relevant clinical information, risk factors, and low-dose chest computed tomography screening would improve the performance of the biomarker panel in large cohorts of Chinese adults. METHODS The current study was a large-scale multicenter study (ClinicalTrials.gov identifier NCT01928836) performed in a Chinese population. A total of 715 participants were enrolled from 5 regional centers in Beijing, Henan, Nanjing, Shanghai, and Chongqing between October 2012 and February 2014. Serum biomarkers ProGRP, CEA, SCC, and CYFRA21-1 were analyzed on the ARCHITECT i2000SR. Relevant clinical information was collected and used to develop a patient risk model and a nodule risk model. RESULTS The resulting patient risk model had an area under the receiver operating characteristic (ROC) curve of 0.7037 in the training data set and 0.7190 in the validation data set. The resulting nodule risk model had an area under the ROC curve of 0.9151 in the training data set and 0.5836 in the validation data set. Moreover, the nodule risk model had a relatively higher area under the ROC curve (0.9151 vs 0.8360; P = 0.001) compared with the American College of Chest Physician model in patients with lung nodules. CONCLUSIONS Both the patient risk model and the nodule risk model, developed for the early diagnosis of lung cancer, demonstrated excellent discrimination, allowing for the stratification of patients with different levels of lung cancer risk. These new models are applicable in high-risk Chinese populations. Cancer 2018;124:262-70. © 2017 American Cancer Society.

// Fanglei Liu 1 , Chunxue Bai 1 and Zhongliang Guo 2 1 Department of Respiratory Medicine, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China 2 Department of Respiratory Medicine, Dongfang Hospital Affiliated to Tongji University, Shanghai, China Correspondence to: Zhongliang Guo, email: guozhongliangshzs@163.com Keywords: small cell lung cancer, osteopontin, prognosis, proliferation, epithelial-mesenchymal transition Received: May 30, 2017 Accepted: June 26, 2017 Published: July 26, 2017 ABSTRACT Osteopontin (OPN) is known to be overexpressed in numerous carcinomas. Although abundant OPN has been reported to be correlated with poor survival in non-small cell lung cancer (NSCLC) but their clinical and prognostic significance in SCLC remains unknown. In this study, RNA-sequencing was used to obtain gene expression data in SCLC tissue samples and OPN expression levels were then investigated using qPCR, immunohistochemical and Western blot. We found OPN was one of the most upregulated genes. Besides, the correlation of OPN with tumor clinicopathological characteristics was evaluated and we found OPN was associated with advanced tumor stages. In addition, Kaplan-Meier survival analysis and Cox analyses revealed OPN expression was an independent predictor for overall survival (OS) (P= 0.013) and progression-free survival (PFS) (P=0.008). A high level of OPN was correlated with pT classification and pN classification (P

Airway mucus hypersecretion is a frequent symptom associated with acute and chronic airway disease. Inhibition of mucus production or promotion of mucolysis not only relieved symptoms but also improved disease outcomes. There are numerous available mucoactive medicines for prescription, and how to select them properly for different diseases is important for clinical practice. So far, there is no one consensus or guideline reported. A group of Chinese pulmonary physicians worked together to complete this consensus based on literature review, summarized mechanism and usage of each classical mucoactive medicine. In general, antioxidant mucoactive medicines play an important role in chronic airway disease, including but not limited to airway mucus clearance, reduced acute exacerbation and improved pulmonary function.