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Background We investigate the long-term effects of SARS-CoV on patients’ lung and immune systems 15 years post-infection. SARS-CoV-2 pandemic is ongoing however, another genetically related beta-coronavirus SARS-CoV caused an epidemic in 2003–2004. Methods We enrolled 58 healthcare workers from Peking University People’s Hospital who were infected with SARS-CoV in 2003. We evaluated lung damage by mMRC score, pulmonary function tests, and chest CT. Immune function was assessed by their serum levels of globin, complete components, and peripheral T cell subsets. ELISA was used to detect SARS-CoV-specific IgG antibodies in sera. Results After 15 years of disease onset, 19 (36.5%), 8 (34.6%), and 19 (36.5%) subjects had impaired DL (CO), RV, and FEF25–75, respectively. 17 (30.4%) subjects had an mMRC score ≥ 2. Fourteen (25.5%) cases had residual CT abnormalities. T regulatory cells were a bit higher in the SARS survivors. IgG antibodies against SARS S-RBD protein and N protein were detected in 11 (18.97%) and 12 (20.69%) subjects, respectively. Subgroup analysis revealed that small airway dysfunction and CT abnormalities were more common in the severe group than in the non-severe group (57.1% vs 22.6%, 54.5% vs 6.1%, respectively, p Conclusions SARS-CoV could cause permanent damage to the lung, which requires early pulmonary rehabilitation. The long-lived immune memory response against coronavirus requires further studies to assess the potential benefit. Trial registration ClinicalTrials.gov, NCT03443102. Registered prospectively on 25 January 2018

Objectives Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections represent severe threats to public health worldwide. The aim of this study was to assess potential synergistic interaction between tigecycline and aminoglycosides via in vitro and in vivo studies. Methods Antibiotic resistance profiles and molecular characteristics of 168 CR-KP clinical isolates were investigated by susceptibility testing, PCR and MLST. Chequerboard tests and time–kill assays were performed for 20 CR-KP isolates to evaluate in vitro synergistic effects of tigecycline combined with aminoglycosides. A tissue-cage infection model of rats was established to evaluate in vivo synergistic effects. Different doses of tigecycline and aminoglycosides alone or in combination were administered for 7 days via tail vein injection. Antibiotic efficacy was evaluated in tissue-cage fluid and emergence of resistance was screened. Results The chequerboard tests showed that this combination displayed synergistic or partial synergistic activity against CR-KP. The time–kill assays further demonstrated that strong synergistic effects of such a combination existed against isolates that were susceptible to both drugs but for resistant isolates no synergy was observed if clinical pharmacokinetics were taken into consideration. The in vivo study showed that the therapeutic effectiveness of combination therapies was better than that of monotherapy for susceptible isolates, suggesting in vivo synergistic effects. Furthermore, combinations of tigecycline with an aminoglycoside showed significant activity in reducing the occurrence of tigecycline-resistant mutants. Conclusions Compared with single drugs, tigecycline combined with aminoglycosides could exert synergistic effects and reduce the emergence of tigecycline resistance. Such a combination might be an effective alternative when treating CR-KP infections in clinical practice.

Abstract An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1–7), and the ACE2/angiotensin-(1–7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help attenuate organ injuries. Graphical abstract SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.

Background T helper (Th) cell cytokine imbalances have been associated with the pathophysiology of chronic obstructive pulmonary disease (COPD), including the Th1/Th2 and Th17/T regulatory cells (Treg) paradigms. Clarifying cytokine profiles during COPD acute exacerbation (AE) and their relationships with clinical manifestations would help in understanding the pathogenesis of disease and improve clinical management. Materials and Methods Eighty seven patients admitted to the hospital with AEs of COPD were included in this study, and follow-up was conducted after discharge (every 30 days, for a total of 120 days). Sputum samples of patients at different time points (including at admission, discharge, and follow-up) were collected, and sputum cytokine profiling (12 cytokines in total) was performed using a Luminex assay. Results According to the cytokine profiles at admission, patients were divided into three clusters by a k-means clustering algorithm, namely, Th1high Th17high (n=26), Th1lowTh17low (n=56), and Th1high Th17low (n=5), which revealed distinct clinical characteristics. Patients with Th1high Th17low profile had a significantly longer length of non-invasive ventilation time and length of hospital stay than patients with Th1high Th17high profile (7 vs 0 days, 22 vs 11 days, respectively, p < 0.05), and had the highest AE frequency. Sputum levels of Th17 cytokines (IL-17A, IL-22, and IL-23) during AE were negatively correlated with AE frequency in the last 12 months (r = -0.258, -0.289 and -0.216, respectively, p < 0.05). Moreover, decreased sputum IL-17A levels were independently associated with increased AE frequency, with an OR (95% CI) of 0.975 (0.958-0.993) and p = 0.006. Conclusion Th1/Th17 imbalance during AE is associated with the severity of COPD. Decreased Th17 cytokine expression is correlated with increased AE frequency. The Th1/Th17 balance may be a specific target for the therapeutic manipulation of COPD.

A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.

The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and 78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003 (9.40 ± 7.83)% to 2004 (3.20 ± 4.78)% (P 1/FVC%, t = 2.21, P = 0.04) and mid-flow of maximum expiration (FEF25%–75%, t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 20.23)% (P = 0.000 2), then declined slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible.

Summary Purpose Prognostic biomarkers help triage initial patients and inform targeted therapy selection. Here, we explored the role of progranulin (PGRN)—implicated in processes ranging from inflammation to neurodegeneration—in patients with community-acquired pneumonia (CAP). Methods A prospective observational cohort study was conducted during 2017. Patients who required invasive mechanical ventilation and/or had septic shock and were discharged from the hospital were cohort II. Those who died at the hospital were cohort III. Remaining patients discharged from the hospital were cohort I. The primary endpoint was that patients progressed to served as cohort II; the secondary endpoint was that patients progressed to served as cohort III. Serum PGRN levels were detected by ELISA. Results A total of 280 patients constituted the study cohort. 194 (69.3%) were categorized into cohort I, 61 (21.8%) were categorized into cohort II, and 25 (8.9%) were categorized into cohort III. Serum PGRN levels were increased in CAP patients, independently of etiology. Adjusting for clinical parameters, the odds ratios (95%CI) of cohort III and combined cohort II–III were 34.968 (3.743–326.692) and 3.741 (1.496–9.351), respectively, comparing lowest-to-highest quartile PGRN levels. PGRN exhibited high accuracy in predicting 30-day mortality, with AUC 0.862. PGRN combined with CURB-65 or PSI significantly improved prediction performance. Cox proportional regression analysis showed PGRN was an independent predictor for 30-day mortality risk. Cox survival curves confirmed PGRN ≥89.51 ng/mL had a significantly higher mortality rate than PGRN Conclusion Higher PGRN levels at admission were associated with higher odds of poor prognosis. PGRN can improve the prognostic power of CURB-65 or PSI, so PGRN could be apparently a prognostic biomarker for assisting triage of CAP patients.

The lethal chronic airway infection of the cystic fibrosis (CF) patients is predisposed by colonization of specific CF-philic pathogens or the CF microbiomes, but key processes and reasons of the microbiome settlement in the patients are yet to be fully understood, especially their survival and metabolic dynamics from normal to diseased status under treatment. Here, we report our meta-analysis results on CF airway microbiomes based on metabolic networks reconstructed from genome information at species level. The microbiomes of CF patients appear to engage much more redox-related activities than those of controls, and by constructing a large dataset of anti-oxidative stress (anti-OS) genes, our quantitative evaluation of the anti-OS capacity of each bacterial species in the CF microbiomes confirms strong conservation of the anti-OS responses within genera and also shows that the CF pathogens have significantly higher anti-OS capacity than commensals and other typical respiratory pathogens. In addition, the anti-OS capacity of a relevant species correlates with its relative fitness for the airways of CF patients over that for the airways of controls. Moreover, the total anti-OS capacity of the respiratory microbiome of CF patients is collectively higher than that of controls, which increases with disease progression, especially after episodes of acute exacerbation and antibiotic treatment. According to these results, we propose that the increased OS in the airways of CF patients may play an important role in reshaping airway microbiomes to a more resistant status that favors the pre-infection colonization of the CF pathogens for a higher anti-OS capacity.

Community-acquired pneumonia (CAP) is a lower respiratory tract infection. It is one of the commonest infectious diseases and the third leading cause of death worldwide. However, the epidemiological profiles of CAP in southeastern China are unknown. Data of inpatients and outpatients diagnosed with CAP from January 1, 2015 to December 31, 2020 were obtained from the National Healthcare Big Data in Fuzhou (Fuzhou Database). This database covers medical data from 37 hospitals and 159 community health service stations. The incidence rate, treatment pattern, and direct medical costs of CAP were assessed using clinical data. A total of 8,156,237 patients were enrolled, with a mean age of 33.72 ± 20.88 years. The overall incidence rate of CAP was 3.13 (95% confidence interval [CI]: 3.11–3.15) per 1000 person-years (PY), with 15.97 (95% CI: 15.85–16.08) per 1000 PY in children below 5 years old and 2.62 (95% CI: 2.57–2.66) per 1000 PY in the elderly ≥60 years. The cost per outpatient was $242.83 ± 341.62, and the cost per inpatient was $4,530.4 ± 9,151.68. The three most used therapeutic drugs in patients with CAP are cefotaxime, moxifloxacin, and azithromycin. In addition, despite the ability of both imported and domestic pneumococcal conjugate vaccines to reduce the incidence rate of CAP, the current vaccination coverage rates were relatively low. We suggest that more attention should be paid to the disease burden of CAP, especially due to its great economic burden in China.

In February 2020, an inpatient in Peking University People's Hospital (PKUPH), China, was confirmed positive for the novel coronavirus. In this case, 143 hemodialysis patients were labeled as close contacts and required to be placed under the hospital-based group medical quarantine (HB-GMQ) for 2 weeks by the authorities. After the case was reported, false or misleading information about the case flourished on social media platforms, which led to infodemic. Under this context, PKUPH adopted patient-centered humanistic care to implement the HB-GMQ, through the synergy of administrative, healthcare, logistical, and other measures under the model of patient-centered care of the Massachusetts Medical Society (MMS). As a result, all the patients tided over the HB-GMQ with no COVID-19 infection and no unanticipated adverse events, and all met the criteria for lifting the HB-GMQ. According to the questionnaires taken during the HB-GMQ, a high level of satisfaction was found among the quarantined and no symptomatic increase of anxiety and depression in the patients before and during the HB-GMQ, by comparing the Zung self-rating anxiety scale (SAS) and self-rating depression scale (SDS) conducted in December 2019 and on the 12th day of the HB-GMQ. This article is to brief on PKUPH's experience in implementing patient-centered humanistic care tailored to hemodialysis patients under the HB-GMQ, and to validate the hypothesis that patient-centered humanistic care is effective and helpful to help them tide over the HB-GMQ, so as to shed light on how to implement the HB-GMQ and cope with the HB-GMQ-induced problems in other hospitals.

BackgroundThe c-mesenchymal–epithelial transition factor (C-MET) is an oncogene encoding a tyrosine kinase receptor that plays an important role in tumor growth and metastasis. The National Comprehensive Cancer Network (NCCN) guidelines have approved carbatinib/crizotinib for advanced non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping.MethodsIn June 2020, the Department of Respiratory and Critical Care Medicine of Peking University People’s Hospital admitted a 72-year-old male patient with lung adenocarcinoma (LADC) with a history of interstitial lung disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis. Genetic examination by next-generation sequencing showed an intergenic fusion of MET, and crizotinib was administered on August 14, 2020. Follow-up showed that tumor volume was significantly reduced. However, crizotinib was discontinued in November 2020 because of the patient’s worsening interstitial lung disease, and CT scans showed continued partial response (PR) for 5 months. In April 2021, right lower lobe mass progressed, and disease progression was considered.ConclusionThis was the first case of a patient with LADC with MET intergenic fusion who significantly benefited from crizotinib. Even after crizotinib was discontinued for 5 months, the patient continued exhibiting PR, suggesting that MET intergenic fusion may have carcinogenic activity in LADC and was sensitive to crizotinib.

Background To explore the risk factors for prolonged ventilation after thymectomy in patients with thymoma associated with myasthenia gravis (TAMG). Methods We reviewed the records of 112 patients with TAMG after thymectomy between January 2010 and December 2019 in Peking University People’s Hospital. Demographic, pathological, preoperative data and the Anesthesia, surgery details were assessed with multivariable logistic regression analysis to predict the risk of prolonged ventilation after thymectomy. A nomogram to predict the probability of post-thymectomy ventilation was constructed with R software. Discrimination and calibration were employed to evaluate the performance of the nomogram. Results By multivariate analysis, male, low vital capacity (VC), Osserman classification (IIb, III, IV), total intravenous anesthesia, and long operation time were identified as the risk factors and entered into the nomogram. The nomogram showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0. 835 (95% confidence interval [CI], 0.757–0.913). The calibration plot indicated that the nomogram-predicted probabilities compared very well with the actual probabilities (Hosmer–Lemeshow test: P = 0.921). Conclusion The nomogram is a valuable predictive tool for prolonged ventilation after thymectomy in patients with TAMG.

Objective:As the number of recovering COVID-19 patients increases worldwide, the persistence of symptoms and signs through the post-acute phase indicates an urgent need for prolonged follow-up care. To explore existing data about post-acute COVID-19 syndrome, this meta-analysis assesses the prevalence of persistent manifestations in multiple systems and abnormalities in lung function, as well as their related risks in patients with various severities.Methods:Articles about discharged COVID-19 patients (published from January 1, 2020 to February 23, 2021) were obtained by searching four databases. Cohort studies with follow-up periods >1 month post-discharge or >2 months post-admission were included.Results:A total of 4,478 COVID-19 patients from 16 cohort studies were included in this meta-analysis. Fatigue or weakness (47%) were the most prevalent physical effects of post-acute COVID-19 syndrome, while psychosocial (28%) symptoms were the most common manifestations among several systems. Abnormalities in lung function of recovering patients, i.e., DLCO Conclusions:Our research indicates that patients recovering from COVID-19 manifest long-term, multi-system symptoms, and the adverse effects on psychosocial health and lung functions were the most extensive and persistent. These findings together may facilitate much needed in-depth study of clinical treatments for long-term, post-acute phase symptoms that affect a great number of recovering COVID-19 patients.

Purpose: Viral load of Torque Teno virus (TTV) is elevated in immunosuppressed patients. The weakened immune response is typical in chronic obstructive pulmonary disease (COPD) patients. However, the relationship between TTV and COPD is still unknown.Patients and Methods: We enrolled 91 patients admitted to hospitals with acute exacerbation of COPD (AECOPD) between January 2017 and August 2017 (ClinicalTrials.gov ID, NCT03236480). Sputum samples were gathered during hospitalization and the 120-day follow-up. TTV distribution and genogroups were assessed, and the associations between viral loads and clinical parameters were analyzed.Results: TTV DNA was detected in 95.6% of COPD patients, and the viral load was nearly invariable at the stable and exacerbation states. Most TTV DNA-positive patients carried four distinct genotypes. Sputum load of TTV was positively associated with RV/TLC (r = 0.378, p = 0.030), and negatively correlated with FEV1/pre and FEV1/FVC (r = −0.484, −0.432, p = 0.011, 0.024, respectively). Neutral correlation between the TTV DNA load and COPD assessment test (CAT) scores (r = 0.258, p = 0.018) was observed.Conclusion: Sputum loads of TTV DNA could be a novel indicator for lung function and disease severity assessment in COPD patients.

Background: The value of procalcitonin (PCT) in the diagnosis of bacterial infections and for determining antibiotic usage among patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is currently unclear. Methods: We systematically reviewed the literature and selected studies that evaluated PCT as a biomarker for predicting bacterial infection and compared PCT-based protocols to determine its application in the initiation or discontinuation of antibiotics. Guidance for systematic reviews from Cochrane and the GRADE were followed to perform this study. Data were pooled and analyzed by using a random-effects or a fixed-effects model based on the heterogeneity. Results: The pooled sensitivity and specificity of PCT in diagnosing respiratory bacterial infections were 0.60 and 0.76, respectively, with the area under the summary receiver operating characteristic curve of 0.77. Subgroup analysis showed that the sensitivity and specificity of PCT for patients in ICU were 0.48 and 0.69, respectively. PCT-based protocols decreased antibiotic prescription (relative risk = 0.66, 95% CI: 0.62–0.71) and total antibiotic exposure (mean difference = −2.60, 95% CI: −4.48–0.72), without affecting clinical outcomes such as treatment failure, length of hospitalization and rates of re-exacerbation or overall mortality. Conclusions: PCT has a moderate ability to distinguish bacterial respiratory infection in patients with AECOPD. PCT-guided algorithm can reduce unnecessary administration of antibiotics without increasing adverse outcomes. However, for patients requiring admission in the ICU, PCT may have a poor diagnostic value, and the PCT-guided algorithm may not effectively and safely reduce the antibiotic exposure.

Circular RNAs (circRNAs) have been reported as effective diagnostic and therapeutic biomarkers in many diseases, but the potential of using this easy-to-monitor and highly stable materials for diagnosing Community-acquired pneumonia (CAP) remains unexplored. Here, aiming to identify potential CAP-related circRNAs in peripheral blood and seeking to deepen the understanding of how circRNA-miRNA-mRNA regulatory networks may contribute to CAP, we applied microarrays profiling analysis and identified 8296 differentially expressed (DE) circRNAs between patients with CAP (n = 6) and healthy controls (n = 6). Subsequently, we validated the accumulation trends for the top 100 DE circRNAs based on qPCR in an independent validation cohort (30 patients vs 30 controls), and ultimately identified a panel of four circRNAs that perform extremely well as sensitive and specific biomarkers for diagnosing CAP: hsa_circ_0018429 (area under the curve [AUC] = 0.8216), hsa_circ_0026579 (AUC = 0.7733), hsa_circ_0125357 (AUC = 0.7730), and hsa_circ_0099188 (AUC = 0.6978); combined as a panel (AUC = 0.8776). In addition, hsa_circ_0026579 exhibited good performance in differentiating viral from bacterial or mixed infection, with an AUC of 0.863. We also identified 10 miRNAs that most likely to interact with these four circRNAs, and then predicted 205 mRNA target genes. The KEGG pathway enrichment analysis suggested highly plausible functional implications related to inflammation and to virus-infection-related signaling pathways (such as HTLV-1 infection and hepatitis B infection). Thus, we generated a genetic network of potential CAP-related regulatory interactions that should inform future hypothesis-driven research into the causes and potential treatment of this widespread and frequently fatal disease.

Background Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Antibiotics are losing their effectiveness due to the emerging infectious diseases, the scarcity of novel antibiotics, and the contributions of antibiotic misuse and overuse to resistance. Characterization of the lipidomic response to pneumonia and exploring the “lipidomic phenotype” can provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments. Methods Lipid profiles of bronchoalveolar lavage fluid (BALF) samples were generated through untargeted lipidomic profiling analysis using high-performance liquid chromatography with mass spectrometry (HPLC-MS). Principal component analysis (PCA) was applied to identify possible sources of variations among samples. Partitioning clustering analysis (k-means) was employed to evaluate the existence of distinct lipidomic clusters. Results PCA showed that BALF lipidomes differed significantly between CAP (n = 52) and controls (n = 68, including 35 healthy volunteers and 33 patients with non-infectious lung diseases); while no clear separation was found between severe CAP and non-severe CAP cases. Lactosylceramides were the most prominently elevated lipid constituent in CAP. Clustering analysis revealed three separate lipid profiles; subjects in each cluster exhibited significant differences in disease severity, incidence of hypoxemia, percentages of phagocytes in BALF, and serum concentrations of albumin and total cholesterol (all p

To investigate the expression and clinical significance of secretory mucins in patients with interstitial lung disease (ILD). The bronchoalveolar lavage fluid (BALF) concentrations of mucins (MUCs) from 27 patients with ILD, 6 patients with lung cancer, 8 patients with pleural effusion and 9 patients with bronchiectasis were determined by ELISA. The concentration of MUC5AC was significantly increased in patients with ILD (12.84±15.02 ng/mL) compared with patients with pleural effusion (4.33±2.51 ng/mL), lung cancer (8.02±5.57 ng/mL) or bronchiectasis (6.08±2.40 ng/mL) (p1)/forced vital capacity (r=−0.761, p=0.000), FEV1 predicted value (FEV1/pred) (r=−0.668, p=0.002), and diffusing capacity (r=−0.606, p=0.006). Secretory mucins MUC5AC, MUC2 and IL-8 were highly expressed in ILD. MUC5AC level was closely correlated with the amount of inflammatory cells in BALF and the lung function parameters.

Purpose. Studying the cytokine profiles in influenza A pneumonia could be helpful to better understand the pathogenesis of the disease and predict its prognosis. Patients and Methods. Patients with influenza A pneumonia (including 2009H1N1, H1N1, H3N1, and H7N1) hospitalized in six hospitals from January 2017 to October 2018 were enrolled (ClinicalTrials.gov ID, NCT03093220). Sputum samples were collected within 24 hours after admission and subsequently analyzed for cytokine profiles using a Luminex assay. Results. A total of 35 patients with influenza A pneumonia were included in the study. The levels of IL-6, IFN-γ, and IL-2 were increased in patients with severe influenza A pneumonia (n =10) ( P = 0.002 , 0.009, and 0.008, respectively), while those of IL-5, IL-25, IL-17A, and IL-22 were decreased compared to patients with nonsevere pneumonia ( P = 0.0001 , 0.009, 0.0001, and 0.006, respectively). The levels of IL-2 and IL-6 in the nonsurvivors ( n = 5 ) were significantly higher than those in the survivors ( P = 0.043 and 0.0001, respectively), while the levels of IL-5, IL-17A, and IL-22 were significantly lower ( P = 0.001 , 0.012, and 0.043, respectively). The IL-4/IL-17A ratio has the potential to be a good predictor ( AUC = 0.94 , P < 0.05 , sensitivity = 88.89 % , specificity = 92.31 % ) and an independent risk factor (OR, 95% CI: 3.772, 1.188-11.975; P < 0.05 ) for intermittent positive pressure ventilation (n = 9). Conclusion. Significant dysregulation of cytokine profiles can be observed in patients with severe influenza A pneumonia.

Community-acquired pneumonia (CAP) is a respiratory disease frequently requiring hospital admission, and a significant cause of death worldwide. This study aimed to investigate the prognostic value of clinical indicators. A prospective, multi-center study was conducted (January 2017–December 2018) where patient demographic and clinical data were recorded (N = 366). The 30-day mortality rate was 5.46%. Cox Regression analyses showed that serum albumin (ALB) and respiratory rate (RR) were independent prognostic variables for 30-day survival in patients with CAP. Albumin negatively correlated with the Pneumonia Severity Index (PSI) and CURB-65 scores using Pearson and Spearman tests. Survival curves showed that a RR >24 breaths/min or ALB ≤30 g/L were associated with a significantly higher risk of mortality. The area-under-the-curve (AUC) for predicting 30-day mortality in patients with CAP was 0.762, 0.763, 0.790, and 0.784 for ALB, RR, PSI, and CURB-65, respectively. The AUC for the prediction of 30-day mortality using ALB combined with PSI, CURB-65 scores, and RR was 0.822 (95% CI 0.731–0.912), 0.847 (95% CI 0.755–0.938), and 0.847 (95% CI 0.738–0.955), respectively. Albumin and RR were found to be reliable prognostic factors for CAP. This combination showed equal predictive value when compared to adding ALB assessment to PSI and CURB-65 scores, which could improve their prognostic accuracy.

Early diagnosis and prognosis of patients with community-acquired pneumonia (CAP) are still difficult clinical challenges. This study aimed to investigate the role of lysophosphatidylethanolamine acyltransferase (LPEAT) in CAP and to evaluate the effectiveness of this enzyme as an indicator of disease severity and risk of death in CAP. This retrospective, multi-center study was conducted in 2017. A total of 267 patients with CAP were included. Of these 267 patients, 175 patients had non-severe CAP (non-SCAP) and 92 patients had severe CAP (SCAP). In addition, we recruited 15 healthy volunteers and 42 hospitalized disease controls in our study. The demographic and clinical characteristics were recorded for all participants. Admission levels of LPEAT were determined by quantitative enzyme-linked immunosorbent assay. Admission levels of LPEAT in patients with SCAP were significantly higher, particularly in non-survivors and were not affected by the causative etiology. Furthermore, when the patients were stratified according to PSI and CURB-65 scores, the patients with high severity scores had higher LPEAT levels upon admission than patients with low severity scores. LPEAT also performed well in predicting SCAP in patients with CAP. Moreover, LPEAT could predict the 30-day mortality rate of patients with CAP, and combining LPEAT with the clinical severity score further improved the accuracy of mortality prediction. Elevated LPEAT levels can reliably predict the severity of illness in patients with CAP at the time of admission. Adding LPEAT to clinical scoring methods could improve prognostic accuracy. Trial registration ClinicalTrials.gov, NCT03093220. Registered on March 28th, 2017.

The outbreak of coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has now become a global pandemic. SARS-CoV-2 uses angiotensin-converting enzyme (ACE) 2 as the receptor for entry into host cells. The virus can attack organs with high ACE2

COVID-19 pandemic has become a major public health problem globally. Fever is the most common symptom. Besides fever, GI symptoms has also been reported in patients with COVID-19, such as diarrhoea, nausea, vomiting and abdominal pain and affect up to 28% of patients.1–5 Several previous studies assessed the association between GI symptoms and disease severity and yielded inconsistent results.1 2 6 In this retrospective cohort study, we explored whether GI symptoms and fever increased the risk of severe illness or death in patients with COVID-19. We analysed 29 393 laboratory-confirmed COVID-19 patients diagnosed before 21 March 2020 in cities outside of Wuhan in mainland China. The study was supported by the National Health Commission of China. The final data of follow-up were 17 April 2020. We excluded clinically diagnosed cases who were not laboratory confirmed and patients who were not discharged from hospital by 17 April 2020. The diagnosis of laboratory-confirmed COVID-19 case, severe cases (including critical cases) and death was conducted by local healthcare workers according to the national diagnosis and treatment protocol for COVID-19 released by the National Health Commission.7 The definition of having …

Background A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)–CoV-2, has infected >75 000 individuals and spread to >20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung. Methods We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS–CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison. Results The median number of intrahost variants was 1–4 in SARS–CoV-2–infected patients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS–CoV-2–infected patients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. Conclusion SARS–CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection has posed a severe threat to global public health It is unclear how t

Background This study aimed to determine whether community-acquired pneumonia (CAP) had a metabolic profile and whether this profile can be used for disease severity assessment. Methods A total of 175 individuals including 119 CAP patients and 56 controls were enrolled and divided into two cohorts. Serum samples from a discovery cohort (n = 102, including 38 non-severe CAP, 30 severe CAP, and 34 age and sex-matched controls) were determined by untargeted ultra-high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomics. Selected differential metabolites between CAP patients versus controls, and between the severe CAP group versus non-severe CAP group, were confirmed by targeted mass spectrometry assays in a validation cohort (n = 73, including 32 non-severe CAP, 19 severe CAP and 22 controls). Pearson’s correlation analysis was performed to assess relationships between the identified metabolites and clinical severity of CAP. The area under the curve (AUC), sensitivity and specificity of the metabolites for predicting the severity of CAP were also investigated. Results The metabolic signature was markedly different between CAP patients and controls. Fifteen metabolites were found to be significantly dysregulated in CAP patients, which were mainly mapped to the metabolic pathways of sphingolipid, arginine, pyruvate and inositol phosphate. The alternation trends of five metabolites among the three groups including sphinganine, p-Cresol sulfate, dehydroepiandrosterone sulfate (DHEA-S), lactate and l-arginine in the validation cohort were consistent with those in the discovery cohort. Significantly lower concentrations of sphinganine, p-Cresol sulfate and DHEA-S were observed in CAP patients than in controls (p 65 years (CURB-65), pneumonia severity index (PSI) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, while DHEA-S inversely correlated with the three scoring systems. Combining lactate, sphinganine and DHEA-S as a metabolite panel for discriminating severe CAP from non-severe CAP exhibited a better AUC of 0.911 (95% confidence interval 0.825–0.998) than CURB-65, PSI and APACHE II scores. Conclusions This study demonstrates that serum metabolomics approaches based on the LC-MS/MS platform can be applied as a tool to reveal metabolic changes during CAP and establish a metabolite signature related to disease severity. Trial registration ClinicalTrials.gov, NCT03093220. Registered retrospectively on 28 March 2017. Electronic supplementary material The online version of this article (10.1186/s13054-018-2049-2) contains supplementary material, which is available to authorized users.

Background Acute respiratory infections (ARIs) are a great public health challenge globally. The prevalence of respiratory viruses in patients with ARIs attending at different hospital settings is fully undetermined. Methods Laboratory-based surveillance for ARIs was conducted at inpatient and outpatient settings of 11 hospitals in North China. The first 2–5 patients with ARIs were recruited in each hospital weekly from 2012 through 2015. The presence of respiratory viruses was screened by PCR assays. The prevalence of respiratory viruses was determined and compared between patients at different hospital settings. Results A total of 3487 hospitalized cases and 6437 outpatients/Emergency Department (ED) patients were enrolled. The most commonly detected viruses in the hospitalized cases were respiratory syncytial virus (RSV, 33.3%) in children less than two years old, adenoviruses (13.0%) in patients 15–34 years old, and influenza viruses (IFVs, 9.6%) in patients ≥65 years. IFVs were the most common virus in outpatient/ED patients across all age groups (22.7%). After controlling for the confounders caused by other viruses and covariates, adenoviruses (adjusted odds ratio [aOR]: 3.97, 99% confidence interval [99% CI]: 2.19–7.20) and RSV (aOR: 2.04, 99% CI: 1.34–3.11) were independently associated with increased hospitalization in children, as well as adenoviruses in adults (aOR: 2.14, 99% CI: 1.19–3.85). Additionally, co-infection of RSV with IFVs was associated with increased hospitalization in children (aOR: 12.20, 99% CI: 2.65–56.18). Conclusions A substantial proportion of ARIs was associated with respiratory viruses in North China. RSV, adenoviruses, and co-infection of RSV and IFVs were more frequent in hospitalized children (or adenoviruses in adults), which might predict the severity of ARIs. Attending clinicians should be more vigilant of these infections. Electronic supplementary material The online version of this article (10.1186/s12879-018-2982-3) contains supplementary material, which is available to authorized users.

Pneumonia caused by carbapenemase-producing Klebsiella pneumoniae (CP-KP) are increasingly encountered in hospitals worldwide, causing high mortality due to lack of treatment options. The goal of this study was to assess the efficacy of tigecycline and minocycline for CP-KP hospital-acquired pneumonia (HAP) by using Monte Carlo simulation.A total of 164 non-duplicated CP-KP strains were collected from sputum or blood in patients with HAP. The MICs for antimicrobials were determined by the agar dilution method. A 10,000-patient Monte Carlo Simulation based on a PK/PD model incorporating the MICs and population pharmacokinetic parameters were conducted to calculate probability of target attainment (PTA) at each MIC value and total cumulative fraction of response (CFR).The susceptibility rate of tigecycline and minocycline were 79.9% and 41.5%, respectively. At recommended doses, an optimal PTA of 90% was obtained for treating HAP caused by CP-KP with MICs of tigecycline ≤0.5 mg/L or minocycline ≤4 mg/L. The CFR of tigecycline at the recommended dose and double dose (100 mg q12h) were 71.2% and 90.2%, respectively. The CFR of minocycline at recommended dose and double dose (200 mg q12h) was 53.4% and 77.2%, respectively.The findings of this study suggest that the recommended dose of tigecycline was not effective in HAP caused by CP-KP, and a higher CFR indicating a better clinical efficacy can be gained by doubling the dose (100 mg q12h). minocycline (200 mg q12h) might be a potential alternative of tigecycline to against strains with MICs ≤ 8 mg/L.

A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has infected75 000 individuals and spread to20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung.We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS-CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison.The median number of intrahost variants was 1-4 in SARS-CoV-2-infected patients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS-CoV-2-infected patients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.

Background: Human rhinovirus (HRV) is one of the most common viral etiologies detected in community-acquired pneumonia (CAP) adult cases. However, few is known about the characteristics of HRV-associated CAP. To describe the clinical features of HRV-associated CAP in immunocompetent adults admitted to multiple medical centers in mainland China over a 2-year period. Methods: A total of 383 patients admitted to hospitals for CAP were enrolled from 46 medical centers in mainland China between January 2013 and December 2014. Multiplex real-time polymerase chain reaction (RT-PCR) assays for viral detection and DNA-based quantitative loop-mediated isothermal amplification (qLAMP) assays for bacterial detection were implemented to all lower respiratory tract specimens obtained from the patients. Twenty-eight cases (28/383, 7.3%) revealed HRV-positive PCR results. Patients with bronchoalveolar lavage (BAL) HRV-positive PCR results (n=20) were further enrolled and divided into two groups depending on the status of bacterial co-infection (viral group, n=12; viral-Bacterial group, n=8). Demographic, clinical and microbiological data were reviewed and compared in detail. Results: Cases with HRV-infection were remarkably correlated with respiratory failure (14/20) and most of them (13/14) received mechanical ventilation. Fever (17/20), productive cough (15/20) and dyspnea (6/20) were common symptoms while flu-like symptoms were rarely observed in the cohort. Streptococcus pneumoniae (3/8), Klebsiella pneumoniae (3/8) and Mycoplasma pneumoniae (2/8) were most frequently identified bacterium in the viral-bacterial group. Compared with the viral group, higher incidence of septic shock (3/8 vs . 1/12, P=0.255), longer ICU length of stay (LOS) (10.0 vs . 6.5 days, P=0.686), longer hospital LOS (18.5 vs . 13.0 days, P=0.208) and higher 28-day mortality (2/8 vs . 2/12, P=1) were observed in the Viral-Bacterial group, although without statistically significant difference. Conclusions: HRV is a common etiology in CAP among China adults, especially in severe CAP. Clinicians should be vigilant considering of the poor outcome. Highly qualified multiplex PCR techniques with invasive sampling are needed to increase the detection rate.

The emergence of multidrug- and extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. Thus, alternatives to conventional antibiotics for management of severe A. baumannii infections is urgently needed. In our previous study, we found that a capsule depolymerase Dpo48 could strip bacterial capsules, and the non-capsuled A. baumannii were significantly decreased in the presence of serum complement in vitro. Here, we further explored its potential as a therapeutic agent for controlling systemic infections caused by extensively drug-resistant A. baumannii. Prior to mammalian studies, the anti-virulence efficacy of Dpo48 was first tested in a Galleria mellonella infection model. Survival rate of Dpo48-pretreated bacteria or Dpo48 treatment group was significantly increased compared to the infective G. mellonella without treatment. Furthermore, the safety and therapeutic efficacy of Dpo48 to mice were evaluated. The mice treated with Dpo48 displayed normal serum levels of TBIL, AST, ALT, ALP, Cr, BUN and LDH, while no significant histopathology changes were observed in tissues of liver, spleen, lung, and kidney. Treatment with Dpo48 could rescue normal and immunocompromised mice from lethal peritoneal sepsis, with the bacterial counts in blood, liver, spleen, lung, and kidney significantly reduced by 1.4–3.3 log colony-forming units at 4 h posttreatment. Besides, the hemolysis and cytotoxicity assays showed that Dpo48 was non-homolytic to human red blood cells and non-toxic to human lung, liver and kidney cell lines. Overall, the present study demonstrated the promising potential of capsule depolymerases as therapeutic agents to prevent antibiotic-resistant A. baumannii infections.

[This corrects the article DOI: 10.21037/jtd.2017.10.107.].

Background: It is important to achieve the definitive pathogen identification in hospital-acquired pneumonia (HAP), but the traditional culture results always delay the target antibiotic therapy. We assessed the method called quantitative loop-mediated isothermal amplification (qLAMP) as a new implement for steering of the antibiotic decision-making in HAP. Methods: Totally, 76 respiratory tract aspiration samples were prospectively collected from 60 HAP patients. DNA was isolated from these samples. Specific DNA fragments for identifying 11 pneumonia-related bacteria were amplified by qLAMP assay. Culture results of these patients were compared with the qLAMP results. Clinical data and treatment strategies were analyzed to evaluate the effects of qLAMP results on clinical data. McNemar test and Fisher′s exact test were used for statistical analysis. Results: The detection of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Stenotrophomonas maltophilia, Streptococcus pneumonia, and Acinetobacter baumannii by qLAMP was consistent with sputum culture (P > 0.05). The qLAMP results of 4 samples for Haemophilus influenzae, Legionella pneumophila, or Mycoplasma pneumonia (MP) were inconsistent with culture results; however, clinical data revealed that the qLAMP results were all reliable except 1 MP positive sample due to the lack of specific species identified in the final diagnosis. The improvement of clinical condition was more significant (P < 0.001) in patients with pathogen target-driven therapy based on qLAMP results than those with empirical therapy. Conclusion: qLAMP is a more promising method for detection of pathogens in an early, rapid, sensitive, and specific manner than culture.

Background and Aims: Acute severe asthma, thyroid crisis and acute myasthenia are all medical emergencies that rarely coexistent. Here, we report a young man with severe asthma attack, necessitate invasive mechanical ventilation at the onset, followed by thyroid crisis, rhabdomyolysis, acute kidney injury, thrombocytopenia and progressive myasthenia. The aim of this study is to better understand the relationships among severe asthma, autoimmune thyroiditis and myasthenia. Methods: The case was presented and former literatures were reviewed. Results: This is the first case report of a young patient presented with severe asthma and autoimmune thyroiditis, followed by thyroid storm, multiple organ dysfunction and myasthenia. Neither conventional treatment for asthma or thyroid storm was effective separately. The patient's clinical condition did not improve until after plasmapheresis. Conclusion: Here, we highlighted both the importance of early recognition of thyroid storm and prompt therapies, which likely attenuated organ dysfunction and enabled this patient to recover from the life-threatening attack. Asthmatic patients should be closely controlled when suspected of thyroid disorders, especially those with high levels of anti-thyroid antibodies irrespective of thyroid hormones concentrations.

Background Aerosol delivery via mechanical ventilation has been reported to vary significantly among different intensive care units (ICU). The optimal technique for using each aerosol generator may need to be updated with the available evidence. Methods A 2-week prospective multicenter observational cohort study was implemented to record aerosol delivery for mechanically ventilated adult patients in Chinese ICUs. Our data included the type of aerosol device and its placement, ventilator type, humidification, and aerosolized medication administered. A guide for the optimal technique for aerosol delivery during mechanical ventilation was summarized after a thorough literature review. Results A total of 160 patients (105 males) from 28 ICUs were enrolled, of whom 125 (78.1%) received aerosol therapy via invasive ventilation. Among these 125 patients, 53 received ventilator-integrated jet nebulizer, with 64% (34/53) of them placed the nebulizer close to Y piece in the inspiratory limb. Further, 56 patients used continuous nebulizers, with 84% (47/56) of them placed the nebulizer close to the Y piece in the inspiratory limb. Of the 35 patients who received aerosol therapy via noninvasive ventilation, 30 received single limb ventilators and continuous nebulizers, with 70% (21/30) of them placed between the mask and exhalation port. Only 36% (58/160) of the patients received aerosol treatments consistent with optimal practice. Conclusions Aerosol delivery via mechanical ventilation varied between ICUs, and only 36% of the patients received aerosol treatments consistent with optimal practice. ICU clinicians should be educated on the best practices for aerosol therapy, and quality improvement projects aim to improve the quality and outcome of patients with the optimal technique for aerosol delivery during mechanical ventilation are warranted.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members. Methods We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed. Results Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability. Conclusions SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection., SARS-CoV-2 can be rapidly transmitted from person to person in nosocomial and social settings, despite patients having no symptoms https://bit.ly/34BHtB5

S100A4, a calcium-binding protein, can promote pulmonary fibrosis via fibroblast activation. Due partly to its various cellular origins, the exact role of S100A4 in the development of lung fibrosis remains elusive. Here, we show that in the bronchoalveolar lavage fluid, numbers of S100A4+ macrophages correlated well with S100A4 protein levels and occurrence of idiopathic pulmonary fibrosis (IPF) in patients. A mouse model of bleomycin-induced pulmonary fibrosis demonstrated S100A4+ macrophages as main source for extracellular S100A4 in the inflammatory phase. In vitro studies revealed that extracellular S100A4 could activate both mouse and human lung fibroblasts by upregulation of α-SMA and type I collagen, during which sphingosine-1-phosphate (S1P) increased. Inhibiting the S1P receptor subtypes S1P1/S1P3 abrogated fibroblast activation. Accordingly, absence or neutralization of S100A4 significantly attenuated bleomycin-induced lung fibrosis in vivo. Importantly, adoptive transfer of S100A4+ but not of S100A4- macrophages installed experimental lung injury in S100A4-/- mice that were otherwise not sensitive to fibrosis induction. Taken together, S100A4 released by macrophages promotes pulmonary fibrosis through activation of lung fibroblasts which is associated with S1P. This suggests that extracellular S100A4 or S100A4+ macrophages within the lung as promising targets for early clinical diagnosis or therapy of IPF.

Background Community-acquired pneumonia (CAP) is a major cause of death worldwide and occurs with variable severity. There are few studies focused on the expression of soluble urokinase-type plasminogen activator receptor (suPAR) and syndecan-4 in patients with CAP. Methods A prospective, multi-centre study was conducted between January 2014 and December 2016. A total of 103 patients with severe CAP (SCAP), 149 patients with non-SCAP, and 30 healthy individuals were enrolled. Clinical data were recorded for all enrolled patients. Serum suPAR and syndecan-4 levels were determined by quantitative enzyme-linked immunosorbent assay. The t test and Mann–Whitney U test were used to compare between two groups; one-way analysis of variance and the Kruskal–Wallis test were used to compare multiple groups. Correlations were assessed using Pearson and Spearman tests. Area under the curve (AUCs), optimal threshold values, sensitivity, and specificity were calculated. Survival curves were constructed and compared by log-rank test. Regression analyses assessed the effect of multiple variables on 30-day survival. Results suPAR levels increased in all patients with CAP, especially in severe cases. Syndecan-4 levels decreased in patients with CAP, especially in non-survivors. suPAR and syndecan-4 levels were positively and negatively correlated with severity scores, respectively. suPAR exhibited high accuracy in predicting SCAP among patients with CAP with an AUC of 0.835 (p

Common variable immunodeficiency (CVID) belongs to the primary immunodeficiency disorders (PIDs), presenting a profound heterogeneity in phenotype and genotype, with monogenic or complex causes. Recurrent respiratory infections are the most common clinical manifestations. CVID patients can also develop various autoimmune and lymphoproliferative complications. Genetic testing such as whole exome sequencing (WES) can be utilized to investigate likely genetic defects, helping for better clinical management. We described the clinical phenotypes of three sporadic cases of CVID, who developed recurrent respiratory infections with different autoimmune and lymphoproliferative complications. WES was applied to screen disease-causing or disease-associated mutations. Two patients were identified to have monogenic disorders, with compound heterozygous mutations in LRBA for one patient and a frameshift insertion in NFKB1 for another. The third patient was identified to be a complex form of CVID. Two novel mutations were identified, respectively, in LRBA and NFKB1. A combination of clinical and genetic diagnosis can be more extensively utilized in the clinical practice due to the complexity and heterogeneity of CVID.

Lung function impairments, especially airflow obstruction, are important features during acute exacerbation in patients with bronchiectasis. Recognition of the risk factors associated with airflow obstruction is important in the management of these exacerbations. The medical records of adult patients admitted to the Peking University People’s Hospital, Beijing, China, from 2004 to 2011 with a diagnosis of bronchiectasis were reviewed retrospectively. Univariate and multivariate analyses were used to evaluate the risk factors associated with airflow obstruction. Airflow obstruction was found in 55.6% of 156 patients hospitalized with acute exacerbation of bronchiectasis, and the risk factors associated with airflow obstruction included young age (≤14 years old) at diagnosis (odds ratio (OR) = 3.454, 95% confidence interval (CI) 1.709–6.982, p = 0.001) as well as the presence of chronic obstructive pulmonary disease (COPD; OR = 14.677, 95% CI 5.696–37.819, p = 0.001), asthma (OR = 3.063, 95% CI 1.403–6.690, p = 0.005), and wheezing on auscultation (OR = 3.279, 95% CI 1.495–7.194, p = 0.003). The C-reactive protein (13.9 mg/dl vs. 6.89 mg/dl, p = 0.005), partial pressure of arterial oxygen (66.7 ± 8.57 mmHg vs. 89.56 ± 12.80 mmHg, p < 0.001), and partial pressure of arterial carbon dioxide (40.52 ± 2.77 mmHg vs. 42.87 ± 5.39 mmHg, p = 0.02) profiles were different between patients with or without airflow obstruction. In addition, patients colonized with potential pathogenic microorganisms had a decreased diffusing capacity (56.0% vs. 64.7%, p = 0.04). Abnormal pulmonary function was common in hospitalized patients with bronchiectasis exacerbations. Airflow obstruction was correlated with the patient’s age at diagnosis, as well as the presence of combined COPD and asthma, and wheezing on auscultation, which also resulted in more severe systemic inflammation and hypoxemia.

Background A high incidence and mortality of plague in the past two decades occurred in the Qinghai-Tibet Plateau, China. High dose streptomycin (6–8 g/d) remained the first practical strategy for controlling the progressive, vicious clinical circumstances for patients with pneumonic plague in the Plateau, as opposed to the routine dosage recommended by the World Health Organization. To investigate whether patients with pneumonic plague truly required a large dosage of streptomycin in the hypoxic environment of the Tibetan Plateau, we investigated the hypothesis that hypoxic environment would change the pharmacokinetics of streptomycin in vivo. Methods (1) We retrospectively analyzed the data of pneumonic plague patients administered streptomycin from January 1, 2000 to December 31, 2012 in these areas, which came from the database of the Qinghai Center for Disease Control; and (2) We used a persistent hypoxia chamber to simulate the plateau hypoxic environment and fed Sprague Dawley rats in the chambers for one month. Then, we continuously administered hypoxic rats a single loading dose (200 mg/kg) of streptomycin and analyzed its concentrations by high performance liquid chromatography. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. Results (1) There were 32 cases of patients with pneumonic plague in the past two decades totally and 9 of them died (all-cause mortality 28.125%, 9/32), including 7 cases died of delayed diagnosis without treatment of streptomycin, and the only 2 patients received normal dose of streptomycin. (2) The pharmacokinetic behaviors of streptomycin were different between the hypoxic and normal rats. Administration in a hypoxic state resulted in 74.81% and 29.28% decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity compared with those values under normal condition for streptomycin. Conclusions These results indicated that hypoxic condition could significantly decrease the absorption rate and extent of streptomycin. Therefore, patients with pneumonic plague require higher doses of streptomycin to maintain effective drug concentrations in Qing Hai and the Tibetan Plateau.

Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs.

The air pollution in China is a severe problem. The aim of our study was to investigate the impact of air pollutants on acute respiratory outcomes in outpatients. Outpatient data from 2 December 2013 to 1 December 2014 were collected, as well as air pollutant data including ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and particulate matter (PM2.5 and PM10). We screened six categories of acute respiratory outcomes and analyzed their associations with different air pollutant exposures, including upper respiratory tract infection (URTI), acute bronchitis (AB), community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), acute exacerbation of asthma (AE-asthma), and acute exacerbation of bronchiectasis (AEBX). A case-crossover design with a bidirectional control sampling approach was used for statistical analysis. A total of 57,144 patients were enrolled for analysis. PM2.5, PM10, NO2, SO2, and CO exposures were positively associated with outpatient visits for URTI, AB, CAP, and AEBX. PM10, SO2, and CO exposures were positively associated with outpatient visits for AECOPD. Exposure to O3 was positively associated with outpatient visits for AE-asthma, but negatively associated with outpatient visits for URTI, CAP, and AEBX. In conclusion, air pollutants had acute effects on outpatient visits for acute respiratory outcomes, with specific outcomes associated with specific pollutants.

Introduction Heavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear. Methods In our study, human tumor-adjacent bronchial epithelial cells were obtained from 10 cases with smoking-related chronic obstructive pulmonary disease and lung squamous carcinoma and cultured in an established microfluidic chip for continual exposure to cigarette smoke extracts (CSE) to investigate the potential tumor-like transformation and mechanisms. The integrated microfluidic chip included upstream concentration gradient generator and downstream cell culture chambers supplied by flowing medium containing different concentrations of CSE. Results Our results showed that continual exposure to low doses of CSE promoted cell proliferation whereas to high doses of CSE triggered cell apoptosis. Continual exposure to CSE promoted reactive oxygen species production in human epithelial cells in a dose-dependent manner. More importantly, continual exposure to low dose of CSE promoted the epithelial-to-mesenchymal transition process and anchorage-independent growth, and increased chromosome instability in bronchial epithelial cells, accompanied by activating the GRP78, NF-κB, and PI3K pathways. Conclusions The established microfluidic chip is suitable for primary culture of human tumor-adjacent bronchial epithelial cells to investigate the malignant transformation. Continual exposure to low doses of CSE promoted tumor-like transformation of human nontumor bronchial epithelial cells by inducing reactive oxygen species production and activating the relevant signaling.