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PURPOSE Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768 ). METHODS Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment. RESULTS A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively. CONCLUSION Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.

The pandemic coronavirus disease 2019 (COVID-19) has rapidly spread to all countries worldwide. The emergence of its variants has exacerbated this problem. To date, many variants have been identified across the viral genome; the variants of concern are the focus of attention due to their higher transmissibility and resistance to vaccines, especially the delta variant. The delta variant has become the dominant severe acute respiratory syndrome novel coronavirus (SARS-CoV-2) variant worldwide, causing severe panic as it is highly infectious. A better understanding of these variants may help in the development of possible treatments and save more lives. In this study, we summarize the characteristics of the variants of concern. More importantly, we summarize the results of previous studies on the delta variant. The delta variant has a high transmissibility rate and increases the risk of hospitalization and death. However, it is partially sensitive to vaccines. In addition, nonpharmaceutical interventions are valuable during epidemics. These interventions can be used against the delta variant, but managing this variant should still be taken seriously.

BackgroundTo compare whether the general population, especially those without characteristic symptoms, need spirometry screening for chronic obstructive pulmonary disease (COPD).MethodsResidents aged > 40 years old in Minhang, Shanghai, China, filled out screening questionnaires and underwent spirometry. The structured questionnaire integrating COPD population screening and COPD screening questionnaire was designed to obtain data on demographic characteristics, risk factors of COPD, respiratory symptoms, lifestyle habits, and comorbidities. We assessed the correlations between variables and COPD and the impact factors of FEV1% predicted.ResultsA total of 1,147 residents were included with a newly diagnosed mild to moderate COPD prevalence of 9.4% (108/1,147); half of the patients (54/108) were asymptomatic. Multivariate analysis did not reveal any significant differences in symptoms or lifestyle factors between newly diagnosed COPD patients and non-COPD participants. However, according to the generalized linear model, older age (β = −0.062, p < 0.001), male sex (β = −0.031, p = 0.047), and respiratory symptoms (β = −0.025, p = 0.013) were associated with more severe airflow limitation.ConclusionNewly diagnosed COPD patients had few differences compared with the general population, which suggests that a targeted case finding strategy other than general screening was currently preferred. More attention should be paid to respiratory symptoms when making a diagnosis and exploring new therapies and interventions for COPD in the early stage.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has brought a huge threat to public health and the global economy. Rapid identification and isolation of SARS-CoV-2-infected individuals are regarded as one of the most effective measures to control the pandemic. Because of its high sensitivity and specificity, nucleic acid testing has become the major method of SARS-CoV-2 detection. A deep understanding of different diagnosis methods for COVID-19 could help researchers make an optimal choice in detecting COVID-19 at different symptom stages. In this review, we summarize and evaluate the latest developments in current nucleic acid detection methods for SARS-CoV-2. In particular, we discuss biosensors and CRISPR-based diagnostic systems and their characteristics and challenges. Furthermore, the emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis are systematically introduced and discussed. Considering the disease dynamics, we also recommend optional diagnostic tests for different symptom stages. From sample preparation to results readout, we conclude by pointing out the pain points and future directions of COVID-19 detection.

Clarifying the pathogenesis of asthma and/or identifying the specific pathway underlying oral asthma tolerance (OT) would be of great significance. In our previous study, promyelocytic leukemia zinc finger (PLZF), which reportedly regulates memory phenotypes, was found to promote ovalbumin (OVA)-induced OT. Therefore, this study aimed to explore the regulatory effects of PLZF on memory phenotypes in asthma and OT mouse models. We found that Zbtb16 (encoding PLZF) and PLZF

The role of normal gut microbiota in asthma or ovalbumin (OVA)-induced asthma tolerance (OT) remains unclear. Here, we established mouse models of asthma and OT followed by 2 weeks of antibiotic treatment, to clear the gut microbiota. Antibiotic treatment was found to alleviate allergic asthma accompanied with a reduction of invariant natural killer (iNKT) cells. By RNA-seq analysis, we found that β-adrenergic receptor (ADRB) genes, including

Airway remodeling is a remarkable pathological characteristic of chronic obstructive pulmonary disease (COPD), and long noncoding RNAs have been demonstrated to participate in COPD development and pathogenesis. Here, we investigate the role of long noncoding RNA

A 52-year-old woman presented with respiratory symptoms of productive cough and shortness of breath. She had suffered from repeated pneumonia. The CT scans revealed chronic sinusitis, tree bud signs in pulmonary imaging, and situs inversus. She received a primary diagnosis of Kartagener syndrome of primary ciliary dyskinesia (PCD) and a genetic examination was performed. Compound heterozygous mutations in dynein axonemal heavy chain 9 (DNAH9) were identified, which encoded outer dynein arms (ODAs) components. DNAH9 mutations are relatively rare events in PCD, and this is the first report of PCD patients with DNAH9 mutations in the Chinese population. Further, a literature review of mutations in PCD was conducted.

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastaticPatients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment.A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60;Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for

The immune system generates memory cells on infection with a virus for the first time. These memory cells play an essential role in protection against reinfection. Tissue-resident memory T (TRM) cells can be generated in situ once attacked by pathogens. TRM cells dominate the defense mechanism during early stages of reinfection and have gradually become one of the most popular focuses in recent years. Here, we mainly reviewed the development and regulation of various TRM cell signaling pathways in the respiratory tract. Moreover, we explored the protective roles of TRM cells in immune response against various respiratory viruses, such as Respiratory Syncytial Virus (RSV) and influenza. The complex roles of TRM cells against SARS-CoV-2 infection are also discussed. Current evidence supports the therapeutic strategies targeting TRM cells, providing more possibilities for treatment. Rational utilization of TRM cells for therapeutics is vital for defense against respiratory viruses.

BACKGROUND: Poor control of asthma results from many factors, partly due to inadequate knowledge towards asthma among patients. It is necessary to know patients’ knowledge level before education. However, there is no accepted instrument to evaluate knowledge of asthma in Chinese patients with asthma. The study aims to develop a Chinese version of Patient-completed Asthma Knowledge Questionnaire (PAKQ) to assess its reliability, validity, and responsiveness for testing its clinical application in Chinese adult patients with asthma. METHODS: After translation, back-translation, and cross-cultural adaptation of the PAKQ into Chinese version, a survey of patients with asthma (n=464) in China was conducted. Demographics and clinical data were collected in addition to questionnaires concerning cognition of asthma, education, history, and asthma control test score. The PAKQ was then completed. 14±4 days after the initial assessment, the participants completed the retested questionnaire and again completed the questionnaire immediately after education. The reliability and the construct validity were evaluated. The optimal cut-off points for predicting disease knowledge among asthma patients were determined using the Youden index method. RESULTS: The Chinese version of PAKQ showed high internal consistency (Cronbach’s alpha =0.888) at baseline and an acceptable 2-week test-retest reliability (ICC =0.932, r=0.874). On the basis of large modification indices (>10), this four-factor questionnaire was found to fit the data satisfactorily (χ(2)/df =1.695, RMSEA =0.039, GFI =0.856, CFI =0.885, and SRMR =0.058). Paired t-tests showed significant changes on pre-educational and post-educational tests (t=22.83, df=463, P

Establishment of immune tolerance is crucial to protect humans against asthma. Promyelocytic leukemia zinc finger (PLZF) is an emerging suppressor of inflammatory responses. CCL21-CCR7 signaling mediates tolerance development. However, whether PLZF and CCL21-CCR7 are required for the development of asthma tolerance is unknown. Here, we found that Zbtb16 (coding PLZF) and Ccl21 were upregulated in OVA-induced asthma tolerance (OT) lungs by RNA-seq. PLZF physically interacted with GATA3 and its expression was higher in GATA3+ Th2 cells and ILC2s in OT lungs. Zbtb16-knockdown in lymphocytes promoted the differentiation of CD3e+ CD4+ T cells, particularly those producing IL-4 and IL-5. Moreover, iNKT cells with high expression of PLZF were recruited into the lungs via draining lymph nodes during tolerance. Blockade of CCL21-CCR7 signaling in OT mice decreased the PLZF+ cell population, abolished CCR7-induced PLZF+ iNKT recruitment to the lungs, enhanced Th2responses and exacerbated lung pathology. In OT mice, respiratory syncytial virus (RSV) infection impeded PLZF+ cell and CCR7+ PLZF+ iNKT cellrecruitment to the lungs and increased airway resistance. Collectively, these results indicate that PLZF could interact with GATA3 and restrain differentiation of IL-4- and IL-5-producing T cells, iNKT cells with high PLZF expression are recruited to the lungs via CCL21-CCR7 signaling to facilitate the development of asthma tolerance.

COVID-19 has become a global pandemic and requires the whole world to respond together. There is no specific antiviral treatment recommended at present for COVID-19. The patients must receive the supportive care to help relieve the symptoms and ensure appropriate infection control. Whether or not to use corticosteroids clinically caused controversy. This article has summarized previous researches about the using of corticosteroids in other viral pneumonia, related clinical data in COVID-19, and recommendations in Chinese guideline.

Background Despite the release of a national guideline in 2016, the actual practices with respect to adult community-acquired pneumonia (CAP) remain unknown in China. We aimed to investigate CAP patient management practices in Shanghai to identify potential problems and provide evidence for policy making. Methods A short-period, 5-day prospective cross-sectional study was performed with sampled pulmonologists from 36 hospitals, encompassing all the administrative districts of Shanghai, during January 8-12, 2018. The medical information was recorded and analyzed for the patients with the diagnosis of CAP who were cared for by 46 pulmonologists during the study period. Results Overall, 435 patients were included in the final analysis, and 94.3% had a low risk of death in terms of CRB-65 criteria (C: disturbance of consciousness, R: respiratory rate, B: blood pressure, 65: age). When diagnosed with CAP, 70.1% of patients were not evaluated using the CURB-65 score (CRB-65 + U: urea nitrogen), but most patients (95.4%) were evaluated using CRB-65. Time to achieve clinical stability was longer in patients with hypoxemia than in those without hypoxemia (8.42±6.36 vs. 5.53±4.12 days, P=0.004). Overall, 84.4% of patients with a CRB-65 score of 0 were administered antibiotics intravenously, and 19.4% were still hospitalized after excluding hypoxemia and comorbidities. The average duration of antibiotic treatment was 10.4±4.9 days. Overall, 72.6% of patients received antibiotics covering atypical pathogens whose time to clinical stability was significantly shortened compared with those without coverage, but the antibiotic duration was similar and not correspondingly shortened. Conclusions CRB-65 seems to be more practical than CURB-65 for the initial evaluation of CAP in the context of local practice, and oxygenation assessment should be included in the evaluation of severity. Overtreatment may be relatively common in patients at low risk of death, including unreasonable hospitalization, intravenous administration, and antibiotic duration.

Shuang Yang,1,2,* Xin Yin,3,* Yanan Zhang,4 Hanwei Zhao,4 Zixuan Zheng,2 Junqing Li,2 Xiaoying Hu,1 Juan Xie,2 Zhijun Jie,2 Na Wang,3 Jindong Shi2 1Department of General Medicine, Jiangchuan Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 4Department of General Medicine, Zhuanqiao Community Healthcare Service Center of Minhang District, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jindong Shi, Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China, Tel +86 18918168579, Email shijindong@5thhospital.com Na Wang, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 13564748559, Email na.wang@fudan.edu.cnPurpose: To evaluate the screening efficacy of a self-designed questionnaire for chronic obstructive pulmonary disease (COPD) and the potential gender disparity in its efficacy.Patients and Methods: A screening questionnaire, the COPD Screening Questionnaire-Minhang (COPD-MH), was designed with reference to the self-scored COPD population screener (COPD-PS) and the COPD screening questionnaire (COPD-SQ), incorporating characteristics of the local population in Shanghai, China. The revised questionnaire included only five questions. Each question scored 0– 4, with a highest total score of 20. The COPD-PS and COPD-SQ comprised 5 and 7 questions, respectively. Their scoring criteria were not consecutive integers and, thus, not easily counted. The COPD-MH focused on symptoms, and each item was set the same answers for convenience. Screening for COPD was conducted among residents over 40 years old in a community in Shanghai using the three aforementioned questionnaires. Each participant also received spirometry tests. A receiver operator characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to assess the validity of each questionnaire.Results: A total of 1197 community residents in Minhang District completed the screening. A total of 1023 participants were finally included in analysis with a detected prevalence of 12.4% for COPD. The best cut-off values for the COPD-PS, COPD-SQ, and COPD-MH were 4, 16, and 7 points, respectively. The AUCs for these three questionnaires were > 0.5, but the sensitivity of the COPD-MH was higher than those of the COPD-PS and COPD-SQ. The sensitivity of COPD-MH was 80.77% for males and 77.5% for females. The COPD-MH had higher diagnostic efficiency and higher sensitivity with gender-specific cut-off values.Conclusion: The COPD-MH is comparable to and less time-consuming than the existing screening methods for COPD. Gender-related factors affect the optimal cut-off values of the COPD screening questionnaire, and rectifying this can improve the practical screening efficacy.Keywords: chronic obstructive pulmonary disease, screening questionnaire, gender, spirometry, ROC curve

To improve the identification and subsequent intervention of COVID-19 patients at risk for ICU admission, we constructed COVID-19 severity prediction models using logistic regression and artificial neural network (ANN) analysis and compared them with the four existing scoring systems (PSI, CURB-65, SMARTCOP, and MuLBSTA). In this prospective multi-center study, 296 patients with COVID-19 pneumonia were enrolled and split into the General-Ward-Care group (N = 238) and the ICU-Admission group (N = 58). The PSI model (AUC = 0.861) had the best results among the existing four scoring systems, followed by SMARTCOP (AUC = 0.770), motified-MuLBSTA (AUC = 0.761), and CURB-65 (AUC = 0.712). Data from 197 patients (training set) were analyzed for modeling. The beta coefficients from logistic regression were used to develop a severity prediction model and risk score calculator. The final model (NLHA2) included five covariates (consumes alcohol, neutrophil count, lymphocyte count, hemoglobin, and AKP). The NLHA2 model (training: AUC = 0.959; testing: AUC = 0.857) had similar results to the PSI model, but with fewer variable items. ANN analysis was used to build another complex model, which had higher accuracy (training: AUC = 1.000; testing: AUC = 0.907). Discrimination and calibration were further verified through bootstrapping (2000 replicates), Hosmer-Lemeshow goodness of fit testing, and Brier score calculation. In conclusion, the PSI model is the best existing system for predicting ICU admission among COVID-19 patients, while two newly-designed models (NLHA2 and ANN) performed better than PSI, and will provide a new approach for the development of prognostic evaluation system in a novel respiratory viral epidemic.

Smoking is an essential facet of the pathogenesis of chronic obstructive pulmonary disease (COPD), which is typically characterized by inflammation and cellular senescence of alveolar epithelial cells. In this study, we investigated the function and fundamental mechanism of a novel circular RNA XPO1 (circXPO1) in cigarette smoke (CS)-induced inflammation and cellular senescence of alveolar epithelial cells. We found that circXPO1 was overexpressed in the lungs of CS-exposed mice and the CS extract (CSE)-treated alveolar epithelial cell line MLE12. Suppression of circXPO1 inhibited CSE-induced inflammatory cytokine production and cellular senescence. In vivo assays also demonstrated that circXPO1 knockdown attenuates CS-induced inflammation and senescence in the mouse lungs. Mechanistically, circXPO1 can directly bind to miR-23b-3p, preventing miR-23b-3p from binding to its target TGF-β-activated kinase 1/MAP3K7 binding protein 3 (TAB3)mRNA. In addition, under CSE conditions, miR-23b-3p overexpression recapitulated the prophylactic effects of circXPO1 knockdown. Inhibition of miR-23b-3p attenuated the function of circXPO1 knockdown in CSE-treated MLE12 cells. These results reveal that circXPO1 plays a role in the pathogenesis of COPD by modulating TAB3 through sponging miR-23b-3p.

Background Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by incomplete reversible airflow limitation, which is associated with emphysema and chronic inflammation. Oxidative/antioxidant imbalance is one of the mechanisms of the current pathogenesis of COPD and several recent studies have attempted to uncover genetic causes of COPD and its progression. GST, HO-1, and SOD-3 are important susceptibility genes related to COPD. Methods A total of 300 blood samples were included in two groups: Control group and COPD group. We genotyped 4 single nucleotide polymorphisms (SNPs) from these 3 genes in 150 COPD patients and 150 controls to analyze genetic polymorphisms and interactions with COPD-related quantitative traits using correlation analysis and multivariate logistic regression analysis. Results The results indicated that genotype distributions and allele frequencies of GSTP1, HO-1, and SOD-3 were significantly different between the COPD and the control group, while there is no correlation between the polymorphism of GSTP1, HO-1, SOD3, and the different stages of COPD. Furthermore, multivariate logistic regression analysis indicated that COPD GSTP1-exon5 SNP and HO-1 (GT)n SNP are high-risk factors for COPD and there was interaction between GSTP1 exon5 SNPS and HO-1 (GT)n SNP. More important, the genotypes, AG, GG of GSTP1 exon5 and L/M*S, L/L of HO-1 (GT)n associated with increased 8-iso-prostaglandin F (2 alpha) (8-iso-PGF2) and malondialdehyde (MDA) concentration and decreased catalase (CAT) activity. Conclusion Collectively, this study shows that genetic polymorphisms of GSTP1, HO-1, and SOD-3 are associated with COPD susceptibility.

Influenza pandemics with different extent occur every year in the world. It can cause high morbidity and mortality, arouse fear panic in public, and attract extensive attention worldwide. This paper reviews the research progress in epidemiological characteristics, detection methods, pathogenesis, treatment and prophylactic measures of influenza in China. It will be helpful for us to understand the current situation of influenza.

Haiyan Ge,1,&ast; Xuanqi Liu,1,&ast; Wenchao Gu,2 Xiumin Feng,3,4 Fengying Zhang,5 Fengfeng Han,6 Yechang Qian,7 Xiaoyan Jin,8 Beilan Gao,9 Li Yu,10 Hong Bao,11 Min Zhou,12 Shengqing Li,13 Zhijun Jie,14 Jian Wang,15 Zhihong Chen,16 Jingqing Hang,5 Jingxi Zhang,3 Huili Zhu1 1Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Respiratory Medicine, Pudong New District People’s Hospital, Shanghai, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to Navy Military Medical University, Shanghai, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Changji Branch of First Affiliated Hospital of Xinjiang Medical University, Xinjiang, People’s Republic of China; 5Department of Respiratory Medicine, Putuo District People’s Hospital, Shanghai, People’s Republic of China; 6Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 7Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People’s Republic of China; 8Department of Respiratory Medicine, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 9Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China; 10Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 11Department of Respiratory Medicine Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 13Department of Respiratory and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 14Department of Respiratory Medicine, Shanghai Fifth’s Hospital, Fudan University, Shanghai, People’s Republic of China; 15Department of Respiratory Medicine, Shanghai Ninth’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 16Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huili Zhu Email zhuhuili001@126.comJingxi Zhang Email jingxizhang2000@126.comBackground: Chronic obstructive pulmonary disease (COPD) often coexists with multiple comorbidities which may have a significant impact on acute exacerbations of patients. At present, what kind of comorbidities affects acute exacerbations and how comorbidities lead to poor prognosis are still controversial. The purpose of our study is to determine the impact of comorbidities on COPD exacerbation and establish an acute exacerbation risk assessment system related to comorbidities.Methods: A total of 742 COPD patients participated in the Shanghai COPD Investigation on Comorbidity Program (SCICP, ChiCTR2000030911). Finally, the baseline information of 415 participants and one-year follow-up data were involved in the analysis. We collected hemogram indices, pulmonary function tests and acute exacerbation of COPD with regular medical follow-up. Q-type cluster analysis was used to determine the clusters of participants. Receiver operating characteristic (ROC) analysis was constructed to assess the ability of indicators in predicting acute exacerbations.Results: Almost 65% of the population we investigated had at least one comorbidity. The distribution and incidence of comorbidities differed between exacerbation group and non-exacerbation group. Three comorbidity clusters were identified: (1) respiratory, metabolic, immune and psychologic disease (non-severe cases); (2) cardiovascular and neoplastic disease (severe cases); (3) less comorbidity. Different sub-phenotypes of COPD patients showed significant distinction in health status. Anxiety (OR=5.936, P=0.001), angina (OR=10.155, P=0.025) and hypertension (OR=3.142, P=0.001) were found to be independent risk factors of exacerbation in a year. The novel risk score containing BODEx and four diseases showed great prognostic value of COPD exacerbation in developing sample.Conclusion: Our study detailed the major interaction between comorbidities and exacerbation in COPD. Noteworthily, a novel risk score using comprehensive index – BODEx – and comorbidity parameters can identify patients at high risk of acute exacerbation.Keywords: chronic obstructive pulmonary disease, exacerbation, comorbidity, risk score

Background: The COVID-19 pandemic is a significant health threat. Health care worker (HCWs) are at a significant risk of infection which may cause high levels of psychological distress. The aim of this study was to investigate the psychological impact of the COVID-19 on HCWs and factors which were associated with these stresses during the first outbreak in Shanghai.Methods: Between February 9 and 21, 2020, a total of 3,114 frontline HCWs from 26 hospitals in Shanghai completed an online survey. The questionnaire included questions on their sociodemographic characteristics, 15 stress-related questions, and General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis was applied to the 15 stress-related questions which produced four distinct factors for evaluation. Multiple linear regression models were performed to explore the association of personal characteristics with each score of the four factors. Binary logistic analysis was used to explain the association of personal characteristics and these four factors with the GHQ-12.Results: There were 2,691 valid surveys received. The prevalence of emotional distress (defined as GHQ-12 ≥ 12) was noted in 47.7% (95%CI:45.7–49.6%) HCWs. Females (OR = 1.43, 95%CI:1.09–1.86) were more likely to have a psychological distress than males. However, HCWs who work in secondary hospitals (OR = 0.71, 95% CI:0.58–0.87) or had a no contact history (OR = 0.45, 95%CI: 0.35–0.58) were less likely to suffer psychological distress. HCWs who were nurses, married, and had a known contact history were highly likely to have anxiety. HCWs working at tertiary hospitals felt an elevated anxiety regarding the infection, a lack of knowledge, and less protected compared to those who worked at secondary hospitals.Conclusions: Our study shows that the frontline HCWs had a significant psychosocial distress during the COVID-19 outbreak in Shanghai. HCWs felt a lack of knowledge and had feelings of being not protected. It is necessary for hospitals and governments to provide additional trainings and psychological counseling to support the first-line HCWs.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammatory processes, and exacerbation of COPD represents a critical moment in the progression of COPD. Several biomarkers of inflammation have been proposed to have a predictive function in acute exacerbation. However, their use is still limited in routine clinical practice. The purpose of our study is to explore the prognostic efficacy of novel inflammatory hemogram indexes in the exacerbation among stable COPD patients.Method: A total of 275 stable COPD patients from the Shanghai COPD Investigation Comorbidity Program were analyzed in our study. Blood examinations, especially ratio indexes like platelet–lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio [systemic immune-inflammation index (SII)], and monocyte × neutrophil/lymphocyte ratio [systemic inflammation response index (SIRI)], lung function test, CT scans, and questionnaires were performed at baseline and routine follow-ups. Clinical characteristics and information of exacerbations were collected every 6 months. The relationship between hemogram indexes and diverse degrees of exacerbation was assessed by logistic regression. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the ability of hemogram indexes to predict exacerbation of COPD. Furthermore, the discrimination and accuracy of combined indexes were measured by ROC and calibration curve.Result: There was a significant positive correlation between PLR levels and total exacerbation of COPD patients in a stable stage in a year. Also, the predictive ability of PLR exceeded any other ratio indexes, with an AUC of 0.66. SII and SIRI ranked second only to PLR, with an AUC of 0.64. When combining PLR with other indexes (sex, COPD year, and St. George's Respiratory Questionnaire scores), they were considered as the most suitable panel of index to predict total exacerbation. Based on the result of the ROC curve and calibration curve, the combination shows optimal discrimination and accuracy to predict exacerbation events in COPD patients.Conclusion: The hemogram indexes PLR, SII, and SIRI were associated with COPD exacerbation. Moreover, the prediction capacity of exacerbation was significantly elevated after combining inflammatory hemogram index PLR with other indexes, which will make it a promisingly simple and effective marker to predict exacerbation in patients with stable COPD.

Objective The present study compared the effectiveness of asthma control test (ACT)-guided treatment vs. usual care (UC) in patients with asthma from China. Methods This prospective, phase IV, multicenter, cluster-randomized, open-label 24-week study was conducted in China; patients were randomized to either ACT-guided treatment or UC group. The patients recorded peak expiratory flow, symptoms, and medication in a diary card every day and completed ACT at every clinic visit. For the UC group, patients completed ACT after the physician's treatment decision. Results In total, 83.6% patients (n = 443/530; ACT: n = 209, UC: n = 234) completed the study. A significantly higher proportion of patients (adjusted OR [95% CI]: 7.87 (1.29, 48.11; p = 0.027) responded to the treatment and had ACT total score ≥20 or demonstrated an improvement of >3 points in ACT total score in ≥1 post-baseline assessment in the ACT-guided treatment vs. UC group. A higher proportion of patients had an ACT total score ≥20 and an improvement of >3 points in ACT total score at Week 24 in the ACT-guided treatment vs. the UC group (adjusted OR (95% CI):2.28 (1.07, 4.85; p = 0.036). A significant difference (p = 0.005) in change from baseline in ACT total score was observed in ACT-guided treatment vs. UC group at Week 24. The mean annual exacerbation rate was similar in both the groups. Conclusions ACT-guided treatment was more effective in achieving ACT total score ≥20 or showing an improvement of >3 points in the ACT total score and well tolerated compared with UC treatment in the 24-week treatment period. Trial registration Clinical trials.gov Identifier: NCT02868281, https://clinicaltrials.gov/ ; GlaxoSmithKline study ID: 201097, https://www.gsk-studyregister.com/ .

OBJECTIVE To investigate the epidemiology, clinical features, treatment and outcome of Noninvasive ventilation (NIV)-treated acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in secondary hospitals of Shanghai. METHOD Relying on Shanghai alliances for respiratory diseases, a retrospective observational study was performed in 34 secondary hospitals of Shanghai. The AECOPD patients treated with NIV and admitted to the respiratory department or respiratory intensive care unit were recruited between December 1, 2016, and November 30, 2017. RESULTS There were 555 patients finally recruited in this study. The age was 75.8 ± 9.6 years old and 380 patients (68.5%) were male. 70.5% of all patients had respiratory acidosis (pH

Background To investigate whether the administration of hydrogen/oxygen mixture was superior to oxygen in improving symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods This prospective, randomized, double-blind, controlled clinical trial in 10 centres enrolled patient with AECOPD and a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 6 points. Eligible patients were randomly assigned (in a 1:1 ratio) to receive either hydrogen/oxygen mixture or oxygen therapy. Primary endpoint was the change from baseline in BCSS score at day 7. Adverse events (AEs) were recorded to evaluate safety. Results Change of BCSS score in Hydrogen/oxygen group was larger than that in Oxygen group (− 5.3 vs. − 2.4 point; difference: − 2.75 [95% CI − 3.27 to − 2.22], meeting criteria for superiority). Similar results were observed in other time points from day 2 through day 6. There was a significant reduction of Cough Assessment Test score in Hydrogen/oxygen group compared to control (− 11.00 vs. − 6.00, p Conclusions The trial demonstrated that hydrogen/oxygen therapy is superior to oxygen therapy in patient with AECOPD with acceptable safety and tolerability profile. Trial registration: Name of the registry: U.S National Library of Medicine Clinical Trials; Trial registration number: NCT04000451; Date of registration: June 27, 2019-Retrospectively registered; URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/study/NCT04000451?term=04000451&draw=2&rank=1.

Disorders of immune tolerance may lead to allergic asthma. Group 2 innate lymphoid cells (ILC2s) and inflammatory ILC2s (iILC2s) are key players in asthma. The vagus nerve innervating the airways releases acetylcholine or neuropeptides (i.e. calcitonin gene-related peptide) via pulmonary C-fibers (PCFs), which could regulate ILC2 activity upon binding the α7 nicotinic acetylcholine receptor (α7nAChR, coded by Chrna7) or neuropeptide receptors. Whether and how α7nAChR and PCFs regulate asthma and the formation of asthma tolerance via ILC2s or iILC2s are poorly understood. We used vagotomized, PCF degeneration and Chrna7 knockout mice to investigate ovalbumin (OVA)-induced asthma and oral OVA feeding-induced asthma tolerance. Our results revealed that vagotomy could generally suppress lung ILC2s and iILC2s, which mitigated allergic asthma responses but disrupted asthmatic tolerance. Removal of neuropeptides by PCF degeneration also reduced lung ILC2s and iILC2s, attenuating asthma responses, but did not affect asthma tolerance. In comparison, deletion of Chrna7 increased resident ILC2s and trafficking iILC2s in the lung, worsened allergic inflammation and disrupted oral tolerance. Mechanistically, deletion of Chrna7 in asthma-tolerant conditions upregulated T helper 2 cytokine- (Il4, Il13 and Il25) and sphingosine-1-phosphate (S1P)-related genes (S1pr1 and Sphk1). Blockade of S1P reduced iILC2 recruitment into asthmatic lungs. Our work is the first to demonstrate that vagal-α7nAChR signaling engaging with iILC2s and S1P not only alleviates asthma but also facilitates asthma tolerance. These findings may provide a novel therapeutic target for attenuating asthma by enhancing asthmatic tolerance.

Summary Background The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. Methods We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74–6·33; p

Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population.From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS).Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires.Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.

Age significantly determined the clinical features and prognosis of the disease. The prognosis was worse in patients older than 60 years, calling for clinicians to pay more attention to patients on this special age.https://bit.ly/34DTI05

Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1β) and pro-IL-1β protein level, but significantly decreased secretion of IL-1β, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1β in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1β secretion.

Background: Systematic assessment of the impact of age on the clinical characteristics and outcomes of coronavirus disease 2019 (COVID -19) is crucial for clini

Background: The outbreak of novel coronavirus disease 2019 (COVID-19) has led to increasing international concern. Effective screening strategy and early recognition of the disease are crucial to limiting spread of this worldwide challenge. Methods: Fever clinics of 25 hospitals evenly distributed in 16 Districts of Shanghai were selected. All patients visiting the fever clinics from the begin of the outbreak of Shanghai (17 January 2020) to 16 February were enrolled. A standardized procedure for COVID-19 screening was presented and all the suspected cases were monitored and analyzed till they were confirmed or excluded. Findings: Among 53617 patients who visiting fever clinics, 1004 (1·87%) were considered as suspected cases, with 188 (0·35% of all patients, 18·73% of suspected cases) diagnosed as confirmed cases finally. Compared with the excluded cases, confirmed cases were older and the highest temperatures were relatively lower (p

Background The microbial etiology and mortality risk factors of ventilator-associated pneumonia (VAP) have not been investigated extensively in Shanghai. Methods VAP cases were identified from the patients hospitalized during the period from 1 January 2013 to 30 December 2017 in Shanghai. The relevant data were reviewed and analyzed retrospectively. Results One hundred ninety-four VAP cases were included in this analysis. The overall mortality rate was 32.47%. The respiratory pathogens isolated from these patients included 212 bacterial strains and 54 fungal strains. The leading pathogens were Acinetobacter baumannii (33.96%), Klebsiella pneumoniae (23.58%), Pseudomonas aeruginosa (19.81%), and Staphylococcus aureus (7.08%). Candida colonization was associated with higher mortality of VAP patients compared to those without Candida colonization (45.45% vs 28.67%, P < .05). The VAP patients with Candida colonization also showed higher prevalence of P. aeruginosa, carbapenem-resistant P. aeruginosa (CRPA), K. pneumoniae, carbapenem-resistant K. pneumoniae (CRKP), A. baumannii, and carbapenem-resistant A. baumannii (CRAB) (P < .05). VAP nonsurvivors had higher prevalence of CRPA, K. pneumoniae, CRAB, and Candida than VAP survivors (P < .05). Multivariate analysis showed that prior antibiotic use was a significant risk factor for Candida colonization, while hypertension and length of hospital stay were significant risk factors of VAP mortality (P < .05). Conclusions The top pathogens of VAP patients in Shanghai tertiary teaching hospitals are A. baumannii, K. pneumoniae, and P. aeruginosa, with high prevalence of carbapenem resistance. Carbapenem-resistant bacterial pathogens and Candida may predict poor outcome.

Background Persistent cough and large amounts of purulent sputum affects many bronchiectasis patients. No studies have evaluated the efficacy and safety of bronchoscopic airway clearance therapy and bronchoalveolar lavage (B-ACT) for non-cystic fibrosis bronchiectasis patients with acute exacerbation. Methods A randomised controlled trial was conducted to explore the efficacy and safety of B-ACT among 189 bronchiectasis inpatients from February 1, 2018 to February 28, 2019. The primary outcome was the time to first acute exacerbation. Secondary outcomes included changes of health-related scores, length of hospital stay, hospitalization expenses and incidences of adverse events. Findings B-ACT therapy significantly prolonged the median days to first acute exacerbation when compared with control group (198 vs 168 days, HR 0·555 (0·322-0·958), p=0·012; effect size(r)= 0·94). Further analysis showed that B-ACT therapy was more beneficial for these patients with severe disease and greater symptoms. COPD Assessment Test (CAT) scores improved significantly on the third day (5·45 vs 4·85, 0·60 (0·09-1·11), p=0·023), and Leicester Cough Questionnaire (LCQ) scores improved obviously on the third and seventh days (1·53 vs 1·23, 0·30 (0·05-0·55), p=0·044; 1·66 vs 1·32, 0·34 (0·08-0·60), p=0·022; respectively) after B-ACT therapy. Adverse events associated with B-ACT were mostly transient and mild. Differences of the lengths of hospital stay and hospitalization expenses in both group was not significant. Interpretation B-ACT therapy significantly prolonged the time to first acute exacerbation after discharge, highlighting the importance of B-ACT therapy focused on symptom improvements in preventing exacerbation. Funding National Natural Science Foundation of China. Trial registry ClinicalTrials.gov; No.:NCT03643302; URL: www.clinicaltrials.gov .

BACKGROUND: Toward the end of December 2019, a novel type of coronavirus (2019-nCoV) broke out in Wuhan, China. Here, the hematological characteristics of patients with severe and critical 2019-nCoV pneumonia in intensive care unit (ICU) were investigated, which may provide the necessary basis for its diagnosis and treatment. METHODS: We collected data on patients with confirmed 2019-nCoV pneumonia in the ICU of Leishenshan Hospital in Wuhan from February 25 to April 2, 2020. Real-time reverse-transcription polymerase chain reaction was used to confirm the presence of 2019-nCoV, and various hematological characteristics were analyzed. RESULTS: All patients tested positive for 2019-nCoV using nasopharyngeal swabs or sputum after admission, and interstitial pneumonia findings were noted on chest computed tomography. Sex, age and comorbidities were not significantly different between the severe and critical groups. In terms of prognosis, the survival rate of patients in the severe group reached 100%, whereas that of patients in the critical group was only 13.33% after positive treatment. Furthermore, lymphocyte percentage, blood urea nitrogen, calcium, D-dimer, myohemoglobin, procalcitonin, and IL-6 levels were high-risk factors for disease progression in critical patients. Finally, lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels were closely associated with patient prognosis. CONCLUSIONS: 2019-nCoV pneumonia should be considered a systemic disease. Patients with more complications were more likely to develop critical disease. Lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels can be monitored to prevent progression critical disease.

Mucosal tolerance is induced early in life and is an important mechanism of protection from diseases, such as asthma. Respiratory syncytial virus (RSV) is a main cause of bronchiolitis and pneumonia in infants. Clinical studies have found that there is a strong association between RSV infection in infancy and later development of asthma, but the underlying mechanisms are unclear. A mouse model of immune tolerance induced by oral feeding of ovalbumin(OVA) was successfully established in our previous studies. We found that RSV infection could break the oral immune tolerance state.RSV infection increased the mRNA expression of IL-17A and IL-17A/Foxp3(the transcription factor forkhead box P3) in OT mice, but the mRNA expression of IL-4 and other T helper(Th)2 cytokines did not change significantly. As detected by flow cytometry analysis, RSV infection elevated Th17 cell levels and correspondingly decreased Regulatory T(Treg) cell levels in the hilar lymph nodes (HLNs) and mesenteric lymph nodes (MLNs), but there were no significant differences in the spleen or peripheral blood.We hypothesized that an imbalance in Th cells played an important role in RSV infection compromising asthma tolerance.RSV infection disrupted asthma tolerance by increasing the Th17/Treg ratio rather than the Th1/Th2 ratio'.Therefore, altering the Th17/Treg ratio has been identified as a potential therapeutic target in asthma caused by RSV or another virus.

Asthma tolerance can be induced by breast-feeding or oral feeding with ovalbumin (OVA). Anergy or deletion of specific T cells and generation of T regulatory cells might contribute to this process. However, whether respiratory syncytial virus (RSV) infection would affect asthma tolerance is not very clear. Here, we first established asthma and oral tolerance mouse models and then analyzed airway hypersensitivity and asthma-related genes in the lung, CCR6-expressing IL-17A+ cells in the lungs, hilar or mesenteric lymph nodes (HLN or MLN) among control, asthmatic, tolerized, RSV infection, and RSV-infected asthmatic and tolerized groups. We also administrated CCL20 or IL-17A neutralizing antibody to RSV-infected tolerized mice to test whether RSV infection would mobilize CCR6-expressing IL-17A+ cells from MLN to the infected lungs. We found that tolerized mice infected with RSV developed asthma-like responses manifested by increasing airway hypersensitivity, exacerbating peribronchial inflammation, elevating lung asthma-related genes (Il17a, Mu5ac, and Gob5), accumulating CCR6-expressing IL-17A+ cells in the lungs and HLN with a reduction of this cell population in MLN. CCL20-CCR6 co-expression in RSV-infected tolerized MLN was reduced. Neutralization of CCL20 reduced CD3+CD4+CCR6+ cells in the RSV-infected tolerized HLN. Neutralization of IL-17A mitigated the compromising effects of RSV infection on asthma tolerance. Taken together, RSV infection impairs asthma tolerance by recruiting IL-17A-producing cells via CCR6-CCL20 signaling. The findings provide novel insight into exacerbation and therapeutic strategy of asthma under RSV infection.

Objective: To investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection. Methods: This study included all consecutive patients who were admitted for a diagnosis of AECOPD during June 2013 to May 2015. 31 stable COPD patients and 31 healthy controls were also recruited. Oropharyngeal samples were assessed, PCR for respiratory viruses were performed. Patients were divided into AECOPD virus-positive (+) group and AECOPD virus-negative (-) group according to viral detection. Luminex was used to detect the concentrations of inflammatory cytokines in the serum. Results: A total of 264 patients were included with a mean age of 75 ± 0.5 years. There were 72 patients (27.3%) identified with viral positive, of whom two patients were detected with double viral infections (FluA+FluB and RSVA+HRV, respectively). The rate of viral detection was associated with season, highest in winter. Comparisons of clinical characteristics showed no significant differences between AECOPD virus+ group and AECOPD virus- group. However, serum concentrations of interferon-inducible protein-10 (IP-10) and interferon-gamma (IFN-γ) in virus+ AECOPD patients were significantly higher than those in the virus- AECOPD, stable COPD and healthy control groups (P

Background Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by incomplete reversible airflow limitation, which is associated with emphysema and chronic inflammation. Oxidative/antioxidant imbalance is one of the mechanisms of the current pathogenesis of COPD and several recent studies have attempted to uncover genetic causes of COPD and its progression. GST, HO-1, and SOD-3 are important susceptibility genes related to COPD. Methods A total of 300 blood samples were included in two groups: Control group and COPD group. We genotyped 4 single nucleotide polymorphisms (SNPs) from these 3 genes in 150 COPD patients and 150 controls to analyze genetic polymorphisms and interactions with COPD-related quantitative traits using correlation analysis and multivariate logistic regression analysis. Results The results indicated that genotype distributions and allele frequencies of GSTP1, HO-1, and SOD-3 were significantly different between the COPD and the control group, while there is no correlation between the polymorphism of GSTP1, HO-1, SOD3, and the different stages of COPD. Furthermore, multivariate logistic regression analysis indicated that COPD GSTP1-exon5 SNP and HO-1 (GT)n SNP are high-risk factors for COPD and there was interaction between GSTP1 exon5 SNPS and HO-1 (GT)n SNP. More important, the genotypes, AG, GG of GSTP1 exon5 and L/M*S, L/L of HO-1 (GT)n associated with increased 8-iso-prostaglandin F (2 alpha) (8-iso-PGF2) and malondialdehyde (MDA) concentration and decreased catalase (CAT) activity. Conclusion Collectively, this study shows that genetic polymorphisms of GSTP1, HO-1, and SOD-3 are associated with COPD susceptibility.

In China, there are an estimated 30 million people with asthma, a condition that remains poorly controlled in many patients. The INITIAL study (NCT02143739) was a 12-week, multicentre, prospective, observational study comprising 45 centres across Northern and Southern China that aimed to assess asthma severity among newly diagnosed patients as well as their prescribed medications and response to treatment. The primary objective was to evaluate asthma severity using Global Initiative for Asthma (GINA) 2006 research criteria. Secondary objectives included the distribution of asthma medication by GINA severity category and evaluation of GINA 2012-defined control levels. Medications were prescribed as per usual clinical practice. At baseline, among 4491 patients, 3.9%, 12.0%, 22.6% and 61.6% had intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Inhaled corticosteroid/long-acting β2 agonist was the most common initial therapy in 90.2% of patients. GINA 2012-defined controlled asthma levels increased in all groups, rising from 6.1% at baseline to 43.0%, 53.8% and 67.8% at Weeks 4, 8 and 12, respectively. Most patients presented with severe persistent asthma. Newly diagnosed patients with asthma could benefit from at least 3 months of regular treatment followed by long-term pharmacological management.

BACKGROUND: Chest computed tomography (CT) has been found to have high sensitivity in diagnosing novel coronavirus pneumonia (NCP) at the early stage, giving it an advantage over nucleic acid detection during the current pandemic. In this study, we aimed to develop and validate an integrated deep learning framework on chest CT images for the automatic detection of NCP, focusing particularly on differentiating NCP from influenza pneumonia (IP). METHODS: A total of 148 confirmed NCP patients [80 male; median age, 51.5 years; interquartile range (IQR), 42.5–63.0 years] treated in 4 NCP designated hospitals between January 11, 2020 and February 23, 2020 were retrospectively enrolled as a training cohort, along with 194 confirmed IP patients (112 males; median age, 65.0 years; IQR, 55.0–78.0 years) treated in 5 hospitals from May 2015 to February 2020. An external validation set comprising 57 NCP patients and 50 IP patients from 8 hospitals was also enrolled. Two deep learning schemes (the Trinary scheme and the Plain scheme) were developed and compared using receiver operating characteristic (ROC) curves. RESULTS: Of the NCP lesions, 96.6% were >1 cm and 76.8% were of a density

INTRODUCTION Cough is among the most common symptoms for patients to seek medical attention. OBJECTIVES The purpose of this study is to evaluate the association between fractional exhaled nitric oxide (FeNO) cutoff values (25 ppb) and risk factors related to cough, hoping to evaluate the feasibility of the FeNO cut point values (25 ppb) for clinical prediction of cough in etiology. METHODS In 107 adult patients with acute, subacute, or chronic cough, the FeNO, forced expiratory volume for 1 second (FEV1), forced vital capacity (FVC), blood routine (white blood cell and neutrophil), immunoglobulin E (IgE), lymphocyte eosinophils, and hemoglobin were measured. The Student's t-test was used to test the differences of FeNO levels compared with FEV1/FVC, lymphocyte, and hemoglobin level. For evaluating the correlation of FeNO levels with IgE, eosinophil, blood routine, pulmonary infection, and smoking status, the chi-square test was performed. RESULTS FeNO cutoff value (25 ppb) significantly correlated with serum IgE (P

BACKGROUND AND AIMS Genetic predisposition and environmental factors impact the development of lung cancer. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of the IL-17A and IL-17F genes with lung cancer risk in Chinese Han population. METHODS A total of 678 subjects were enrolled, including 320 lung cancer patients and 358 healthy controls. Six SNPs of IL-17A (rs2275913, rs3748067 and rs3819025) and IL-17F (rs763780, rs1266828 and rs12203582) were genotyped using the polymerase chain reaction (PCR) and ligase detection reaction (LDR). RESULTS The distribution of IL-17A alleles and A and AA genotype for rs2275913 had a significant association with lung cancer risk (OR: 1.26, 95% confidence interval = 1.01-1.56 and OR: 2.08, 95% confidence interval = 1.311-3.31, respectively). In the subgroup analysis, people carrying homozygous variants of rs2275913 and rs12203582 were more likely to develop lung cancer both in adenocarcinoma (OR: 2.33, 95% confidence interval = 1.34-4.05; OR: 1.84, 95% confidence interval = 1.04-3.25) and advanced (OR: 2.35, 95% confidence interval = 1.46-3.80; OR: 1.74, 95% confidence interval = 1.06-2.87) groups. Although no interaction was found between variants of rs2275913 and rs12203582 and tobacco smoking (P > 0.05), smokers carrying homozygous variants of rs2275913 and rs12203582 are at high risk of lung cancer, while no relationship were found among non-smokers. No significant associations between rs3748067, rs3819025, rs763780 and rs1266828 polymorphisms and lung cancer risk were observed. CONCLUSIONS Polymorphisms of both IL-17A and IL-17F may increase lung cancer risk in Chinese population, and are associated differently with subtypes of clinical-pathologic features and tobacco smoking history of lung cancer patients. SNPs of IL-17A and IL-17F predict lung cancer risk.

Respiratory syncytial virus (RSV) infection induces activation and imbalance of the immune system; however, the role of T helper 17 cells (Th17) in the response to RSV infection remains unclear. Interleukin-23 (IL-23) is a key cytokine in Th17 cell differentiation. The aim of this study was to explore the function of IL-23 in determining the distribution of Th lymphocyte subsets (Th1, Th2, and Th17) after RSV infection in vitro. Human bronchial epithelial cell line BEAS-2B was infected with mock or RSV at various multiplicities of infection (MOI) and transcript expression of IL-6, IL-23p19, and transforming growth factor (TGF-β) was detected by real-time polymerase chain reaction; IL-6, IL-23, and TGF-β in the supernatant were measured by enzyme-linked immunosorbent assay. The Th subset distribution in lymphocytes was determined by flow cytometry after co-culture with supernatants from mock and 72-hr RSV infection cultures. The role of IL-23 in lymphocytes was assessed by specific receptor blockade (IL-23R) prior to co-culture with supernatants from RSV-infected BEAS-2B cells, followed by flow cytometry to analyze Th subset differentiation. Cytokine expression increased after RSV infection. IL-23R blockade suppressed the differentiation of Th1, Th2, and Th17 cells in the presence of supernatants from RSV-infected BEAS-2B cells. RSV infection may induce cytokine secretion, thus inducing Th1, Th2, and Th17 differentiation via an IL-23R-dependent process.