Search

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.

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.

Haiyan Ge,1,* Xuanqi Liu,1,* 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*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: 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.

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.

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: 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.

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

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 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.

Background Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease. Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD. However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD. Methods miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR. Degeneration of lung tissue, necrosis, infiltration and neutrophil cells were assessed with H&E and flow cytometry. Interleukin (IL)-6 and IL-8 levels were determined by an enzyme-linked immunosorbent assay and qRT-PCR. Luciferase reporter assay and correlation analyses were used to confirm and measure the levels between miR-181c and its target CCN1. Results We showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked (p

To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) — lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor — SB431542 and/or JAK2/STAT3 inhibitor — JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days. In co-culture systems, MFs secreted high levels of IL-6, while cancer cells produced high levels of TGF-β. Recombinant IL-6 and MF-CM activated STAT3 and upregulated TGF-β in cancer cells. In contrast, cancer cell-CM or TGF-β stimulated MFs to produce IL-6. Blockade of JAK2/STAT3 and TGF-β signaling by specific inhibitors significantly inhibited cell proliferation in vitro and tumor growth in vivo of lung cancer cells. Our study demontrated that the TGF-β and IL-6/JAK2/STAT3 signaling pathways form a positive feedback signaling loop that mediated the interactions between MFs and lung cancer cells. Targeted inhibiton of this signaling loop could be a new approach for lung cancer prevention and therapy.

Background and Aims Lung cancer is a multifactorial disease. Xeroderma pigmentosum group D (XPD) and X-ray repair cross-complementing 1 (XRCC1) genes are 2 important susceptibility genes related to lung cancer. In this study, we explored the correlation between genetic polymorphisms in XPD and XRCC1 and the risk of non-small cell lung cancer (NSCLC) in the East Chinese Han population. We also investigated risk factors associated with non-small cell lung cancer in this population. Methods We conducted a case control study in 120 NSCLC patients and 120 healthy controls. The NSCLC patients were further divided into three subgroups, squamous carcinoma, adenocarcinoma and other type of cancer, according to tumor histology. No patients had undergone any treatment. Polymerase chain reaction and restriction fragment length polymorphism technologies were applied to detect the distribution of XPD-751, XRCC1-194 and XRCC1-399 genes in all patients. Results The results showed significant gene frequency differences for all three genes between patients with NSCLC and control patients. Significantly different frequencies of XPD-751-Gln, XRCC-194-Trp and XRCC1-399-Gln mutant alleles were observed between the two groups. XPD-751SNP and XRCC1-194SNP frequencies varied among the three lung cancer groups, while the frequency of XRCC1-399SNP did not differ significantly. Conclusions The results suggested that genetic polymorphisms in XPD-751, XRCC1-194 and XRCC1-399 were related to the risk of NSCLC, among which XPD-751SNP was responsible for adenocarcinoma, while XRCC1-194SNP was closely linked to squamous carcinoma. Smoking and XRCC1-194SNP were risk factors of NSCLC.

Background: To compare 5-day regimen of levofloxacin 750 mg IV daily with 7–14-day conventional regimen of levofloxacin 500 mg intravenous to oral (IV/PO) daily for treatment of community-acquired pneumonia (CAP) in Chinese population. Methods: This was a non-inferiority study to assess the difference of clinical efficacy at the end of treatment (EOT) between two regimens. Adult CAP patients with CURB-65 score 0–2 were enrolled from 17 hospitals in China from November 2012 to July 2014. The subjects were randomized into levofloxacin 750 or 500 mg group and the clinical data were collected. Sputum and blood specimens were sent for bacterial culture. The urinary antigen of Streptococcus pneumoniae ( S. pneumoniae ) was detected as well. At EOT, the clinical efficacy (primary endpoint), microbiological efficacy and safety were evaluated. Results: A total of 457 patients were enrolled. Intent-to-treat (ITT) for primary endpoint analysis and per-protocol set (PPS) populations were 448 and 427 patients respectively. The therapeutic durations were 4.86 and 10.35 days and the mean drug exposure was 3,641.4 and 5,169.6 mg in 750 and 500 mg groups respectively. The clinical efficacy rate was 91.40% (202/221) in 750 mg group and 94.27% (214/227) in 500 mg group (ITT, P=0.2449). The difference in clinical efficacy rate was −2.87 (95% CI: −7.64, 1.90) between the two groups. The non-inferiority hypothesis of two groups was tenable (Δ=10%). The bacterial eradication rate was 100.00% in both groups. The most common drug-related clinical adverse events were injection site and gastrointestinal reactions. The most common drug-related laboratory abnormalities were WBC decrease and ALT/AST elevation. No statistical difference was found between two groups (P>0.05). Conclusions: The 5-day regimen of levofloxacin 750 mg daily is non-inferior to 7–14-day conventional regimen of 500 mg daily in clinical efficacy for treatment of mild to moderate Chinese CAP population. The short course regimen allows the reduction of antimicrobial drug exposure and is well tolerated.

Multiple genetic and environmental factors impact the pathogenesis of asthma. ADAM33 (a disintegrin and metalloproteinase domain 33) represents a novel susceptibility gene for asthma in several diverse populations. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of the ADAM33 gene associate with asthma susceptibility and severity in the Chinese Han population.A total of 224 subjects were enrolled, including 74 normal controls and 150 asthmatic patients. The asthmatic enrollees were further categorized into high- or low-severity groups according to the percentage of forced expiratory volume in 1 second of predicted value, symptoms, nighttime awakening, requirement for short-acting β2-agonist, and interference with normal activities. Six SNPs (F + 1, ST + 4, S1, S2, T1, and T2) in ADAM33 were genotyped using the polymerase chain restriction fragment length polymorphism method.Three SNPs (F + 1, T1, and T2) of ADAM33 were found to have significant associations with asthma in the study population (p = .0058-.0067). The allele frequencies of two SNPs (F + 1, T1) in both the low- and high-severity groups were significantly different from the allele frequency in the control group. The allelic frequency of the T2 SNP was significantly different from that of the control group only in the high-severity group (p = .0081). Haplotype analysis demonstrated that the frequency of 7575G, 12433T, and 12462C (GTC haplotype) is higher in healthy controls than amongst asthma patients (78.4% vs. 61.8%, p = .0004).Polymorphisms of the ADAM33 gene associate with asthma susceptibility in the east China Han population, and the genetic association is stronger in high-severity asthmatics.

Objective: The aim of this study is to explore whether RSV infection could break immune tolerance inducing to asthma, and to clarify the role of IL-17 in RSV breakingimmune tolerance. Methods: Establishing a mice model of immune tolerance by oral feeding with OVA, and infected with RSV before arousing airway high reactivity. Neutralizing IL-17A before infected with RSV. After the last challenge with OVA the mice were analyzed for AHR, eosinophil infiltration, levels of cytokines, IgE production, percentage of Th2 and Th17 cell, and lung histology. Results: After RSV infection, the Tol group developed the re-emergence of symptoms of asthma, such as increased airway pressure, elevated serum IgE and total number of inflammatory cells in BALF compared with non-infected tolerance group. Quantitative PCR showed that in Tol+RSV group, the mRNA expressions of IL-4,IL-5,IL-13 and IL-17A were significantly up-regulated, especially IL-17A. Pathological results showed that inflammatory responses of the lung reappeared again. Th2, Th17 subsets of hilar lymph nodes in infected mice and non-infected were 2.45±0.06% and 2.19%±0.05% respectively, significantly higher than control group (P Conclusion: Early RSV infection could break immune tolerance of oral OVA and re-induced asthma, which might be due to Th17/IL-17A up-regulation. IL-17 Ab could inhibit the damaging effects of early RSV infection to immune tolerance mice.

Background The world’s first reported patient infected with avian influenza H7N9 was treated at the Fifth People’s Hospital of Shanghai. Shortly thereafter, several other cases emerged in the local area. Here, we describe the detailed epidemiological and clinical data of 6 cases of avian influenza H7N9. Methods and Findings We analyzed the epidemiologic and clinical data from clustered patients infected with H7N9 in the Minhang District of Shanghai during a 2-week period. Of the 6 patients, 2 were from a single family. In addition, 3 patients had a history of contact with poultry; however, all 6 patients lived in the proximity of 2 food markets where the H7N9 virus was detected in chickens and pigeons. The main symptoms were fever, cough, and hemoptysis. At onset, a decreased lymphocyte count and elevated creatine kinase, lactate dehydrogenase, procalcitonin, and C-reactive protein levels were observed. As the disease progressed, most patients developed dyspnea and hypoxemia. Imaging studies revealed lung consolidation and multiple ground-glass opacities in the early stage, rapidly extending bilaterally. All patients were treated with oseltamivir tablets beginning on days 3–8 after onset. The main complications were as follows: acute respiratory distress syndrome (ARDS; 83.3%), secondary bacterial infection (66.7%), pleural effusion (50%), left ventricular failure (33.3%), neuropsychiatric symptoms (33.3%), and rhabdomyolysis (16.7%). Of the 6 patients, 4 died of ARDS, with 2 patients recovering from the infection. Conclusions An outbreak of H7N9 infection occurred in the Minhang District of Shanghai that easily progressed to acute respiratory distress syndrome. Two cases showed family aggregation, which led us to identify the H7N9 virus and indicated that human transmission may be involved in the spread of this infection.

In March 2013, a novel avian-origin influenza A (H7N9) virus was isolated from throat swabs of 2 patients at the Fifth People's Hospital of Shanghai, China. Subsequently, 4 more patients infected by H7N9 were identified. Of the 6 patients, 4 died of acute respiratory distress syndrome. Here, we report the first case of a patient who recovered from pneumonia induced by H7N9 infection. The patient presented with fever, cough, and blood in sputum. Laboratory tests showed a low level of leukocytes, hypoxaemia, and increased levels of creatine kinase and lactate dehydrogenase. Imaging showed multiple areas of segmental ground-glass opacity in the right lung. Oseltamivir and antibiotics were administered. Supplemental oxygen helped relieve symptoms. Approximately 2 weeks after treatment, the patient finally recovered. A follow-up chest computed tomography scan taken 8 weeks later revealed that the ground-glass opacity was clearly absorbed. Therefore, timely intervention with oseltamivir and supplemental oxygen may be very important in the treatment of H7N9 infection.

A disintegrin and metalloprotease domain 33 (ADAM33) has been identified as an asthma susceptibility gene, which is associated with small-airway remodeling. However, the role of ADAM33 in the development of allergic airway inflammation is unclear. The present study used an established murine model of allergen-induced chronic airway inflammation, which was sensitized and then challenged by nebulized 2.5% ovalbumin (OVA) for 8 weeks (30 min/day, three times a week). The expression of ADAM33 mRNA detected by real time RT-PCR was significantly enhanced in the lung tissue of mice with OVA challenge, as compared with the group challenged with saline. This OVA-challenged model showed significant Th2-biased airway inflammation as well as airway remodeling with features of sub-epithelial fibrosis and mucus hyper-secretion. Furthermore, in vitro studies showed that IL-4 and IL-13 could significantly up-regulate the expression of ADAM33 mRNA in human fibroblasts in a concentration- and time-dependent manner as compared to normal controls. These results support the note that Th2 cytokines can up-regulate the expression of ADAM33 mRNA and ADAM33 may play an important role in the development of airway remodeling in allergen-induced chronic airway inflammation.

The dysregulation of microRNAs (miRNAs) is crucially implicated in the development of various cancers. In this study, we explored the biological role of miR-141 in non-small cell lung cancer (NSCLC). miR-141 expression was significantly up-regulated in NSCLC tissues, and its overexpression accelerated NSCLC cell proliferation in vitro and tumor growth in vivo. We subsequently identified the antagonists of PI3K/AKT signaling, PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, as direct targets of miR-141. Re-introduction of PHLPP1 and PHLPP2 abrogated miR-141-induced proliferation of NSCLC cells. Together, the results of this study suggest that miR-141 and its targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis, and provide potential therapeutic targets for NSCLC treatment.