[Analysis of the efficacy and safety of dual immunotherapy in patients with driver gene and programmed death ligand-1 double negative advanced non-small cell lung cancer].

Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage ⅢC and 47 cases (77.0%) classified as stage Ⅳ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.

[New characteristics of COVID-19 caused by the Omicron variant in Guangzhou].

We investigated the types of novel coronavirus strains present during the Omicron epidemic from late 2022 to early 2023, COVID-19 co-infections with other pathogens, and clinical characteristics of patients with novel coronavirus infections. Adult patients hospitalized due to SARS CoV-2 infection in six hospitals in Guangzhou city were included in the study from November 2022 to February 2023. Clinical information was collected and analyzed, and bronchoalveolar lavage fluid was obtained for pathogen detection using a variety of techniques, including standard methods and mNGS, tNGS. The results showed that the main strain circulating in Guangzhou was Omicron BA.5.2, and the overall detection rate of potentially pathogenic pathogens combined with Omicron COVID-19 infection was 49.8%. In patients with severe COVID-19 infection, special attention should be paid to aspergillosis and combined Mycobacterium tuberculosis infection. In additon, Omicron strain infection could cause viral sepsis, which led to a worse prognosis for COVID-19 patients. Diabetic patients with SARS-CoV-2 infection did not benefit from glucocorticoid treatment, and caution was necessary when using glucocorticoids. These findings highlighted some new features of severe Omicron coronavirus infection that should be noted.

[Pulmonary rehabilitation guidelines in the principle of 4S for patients infected with 2019 novel coronavirus (2019-nCoV)].

A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.

[The composition and antimicrobial resistance of isolates from lower respiratory tract and blood in hospitalized patients in respiratory ward: a multicenter national study in China].

Objective: To investigate the species and antimicrobial resistance of bacterial pathogens isolated from hospitalized patients in respiratory ward in China. Methods: This was a multicenter retrospective study based on a national epidemiological network called China Antimicrobial Resistance Surveillance System (CARSS). The non-repetitive strains isolated from lower respiratory tract and blood samples in 91 hospitals from seven geographic regions of CARSS were reviewed. The distribution of specimen type, hospital level (secondary and tertiary hospital), patient age group [geriatric (>65 years old), adult (15 to 65 years old), pediatric (28 days to 14 years old ) and newborn group (≤28 days)] and ward type (respiratory intensive care unit and general respiratory ward) were analyzed for MRSA, PRSP, CREC, CRKP, CRPA, CRAB, ESBL-EC and ESBL-KP. The categorical variables were analyzed by chi-square test using SPSS 16.0 statistical software. P<0.05 was regarded as statistically significant. Results: A total of 50 417 non-repetitive isolates [42 751 isolates from lower respiratory tract (LRT), 2 649 isolates from blood and 5 017 isolates from other samples (urine and secretions)] from 48 752 inpatients (without illness type information) were enrolled in the study. 90.2% (45 491/50 417) isolates were obtained from 63 tertiary hospitals. According to patients' age, all cases were divided into 4 groups, i. e. geriatric(46.0%, 23 177/50 417), adult(29.9%, 15 092/50 417), pediatric(24.0%, 12 112/50 417) and newborn group(0.0%, 36/50 417). All isolates were obtained from respiratory intensive care unit (6.2%, 3 129/50 417) or general respiratory wards (93.8%, 47 288/50 417). The majority of bacterial pathogens were isolated from lower respiratory and blood culture samples, which accounted for 90.0% of all the samples (45 400/50 417). Sputum accounted for 81.6% (41 131/50 417) of samples, and the leading 4 isolates were K. pneumonia (18.9%, 7 784/41 131), P. aeruginosa (13.6%, 5 580/41 131), A. baumanni (11.3%, 4 644/41 131) and S. pneumonia (11.1%, 4 564/41 131). Blood samples accounted for 5.3% (2 649/50 417) of the samples, with the leading 4 bacteria being coagulase-negative staphylococcus (42.0%, 1 112/2 649), E. coli (18.3%, 484/2 649), K. pneumonia (7.4%, 194/2 649) and S. aureus (4.9%, 131/2 649). The species distribution of pathogens isolated from bronchoalveolar lavage fluid (BALF), which accounted for 3.2% (1 620/50 417) of the samples, was similar to that of sputum, and the leading 4 bacteria were P. aeruginosa (22.0%, 360/1 620), K. pneumonia (14.8%, 239/1 620), A. baumanni (11.9%, 193/1 620) and S. pneumonia (9.6%, 155/1 620). The prevalence of CRKP, CRPA and CRAB in tertiary hospitals [5.2% (384/7 439), 23.8% (1 260/5 304) and 53.5% (2 259/4 224), respectively] was significantly higher than that in secondary hospitals [2.5% (24/973), 12.8% (101/787) and 33.9% (109/322), respectively] (all P<0.01). In comparison, the prevalence of ESBL-EC in secondary hospitals (63.9%, 145/227) was higher than that in tertiary ones (55.0%, 1 141/2 074) (P=0.011). The prevalence of ESBL-EC and ESBL-KP in pediatric group [68.2% (283/415) and 55.3% (183/331), respectively] was higher than that in geriatric group [54.2% (684/1 263) and 27.1% (625/2 303), respectively] and adult group [51.1% (317/620) and 15.1% (272/1 804), respectively] (all P<0.001). Conclusions: In China, the predominant bacterial pathogens in the respiratory wards were Enterobacteriaceae and non-fermentative bacteria. High prevalence of ESBL-EC and ESBL-KP isolated from lower repiratory tract was revealed in primary hospitals and pediatric patients.

[Hemoptysis in adults with bronchiectasis: correlation with disease severity and exacerbation risk].

Objective: To investigate the association between hemoptysis and disease severity and risks of acute exacerbations in patients with bronchiectasis. Methods: Between September 2012 and January 2014, we recruited 148 patients (56 males, 92 females, mean age: 44.6 years) with clinically stable bronchiectasis, who were classified into hemoptysis group (36 males, 70 females, mean age: 45.6 years) and non-hemoptysis group (20 males, 22 females, mean age: 41.8 years). We inquired the past history, and evaluated chest imaging characteristics, lung function, cough sensitivity assessed using capsaicin cough challenge tests, and airway inflammation. We also performed a 1-year follow-up to evaluate whether patients with hemoptysis would have greater risk of having acute exacerbations. Results: In the hemoptysis group, median 24-hour sputum volume was 20.0 ml, median Bronchiectasis Severity Index (BSI) was 7.0, median bronchiectatic lobes was 4.0, median chest CT score was 7.0, the geometric mean for eliciting 5 coughs following capsaicin cough sensitivity (C5) was 77 µmol/L, 67 cases (63%) had cystic bronchiectasis and 52 cases (49%) had pulmonary cavity shown on chest CT, and 35 cases (33%) had Pseudomonas aeruginosa colonization. In the non-hemoptysis group, median 24-hour sputum volume was 5.0 ml, median BSI was 4.0, median bronchiectatic lobes was 3.0, median chest CT score was 5.0, 15 cases (36%) had cystic bronchiectasis and 10 cases (24%) had pulmonary cavity, the geometric mean for C5 was 212 µmol/L, and 4 cases (10%) had Pseudomonas aeruginosa colonization. All the above parameters differed significantly between the hemoptysis and the non-hemoptysis group (P<0.05). In the hemoptysis group, 29 patients with pulmonary cavity (27%) had reported the use of intravenous antibiotics, and 44 cases (42%) had at least one hospitalization within the previous 2 years. In the non-hemoptysis group, 8 cases (19.0%) had reported the use of intravenous antibiotics, and 8 cases (19.0%) reported hospitalization within 2 years. A prior history of hemoptysis was associated with a greater risk of experiencing bronchiectasis exacerbations during follow-up, after adjusting for age, sex, smoking status and BSI (62 cases in the hemoptysis group, 18 cases in the non-hemoptysis group, χ(2)=16.06, P=0.03). In a multivariate model, cystic bronchiectasis was the sole risk factor for hemoptysis; 67 cases which accounted for 63% of patients in the hemoptysis group and 15 cases which accounted for 36% of patients in the non-hemoptysis group, odds ratio: 2.84, 95% confidence interval: 1.00-8.14, P=0.05 . Conclusions: In this study, 72% of bronchiectasis patients had experienced hemoptysis, which was associated with the severity of bronchiectasis. Patients with a prior history of hemoptysis had a greater risk of acute exacerbations during follow-up than those without.

[Lower airway abnormalities in patients with allergic rhinitis].

Objective: To investigate the characteristics of lower airway abnormalities in allergic rhinitis(AR) patients without asthma. Methods: Between June 2008 and December 2012, 377 consecutive AR patients and 264 healthy subjects were recruited. All subjects underwent meticulous history taking, nasal examination, allergen skin prick test, blood routine test, serum total immunoglobin E assay, induced sputum cell count and differentials, measurement of fractional exhaled nitric oxide (FeNO) and bronchial challenge test. Results: The positive rates in AR patients was 12.2%(46/377) for bronchial provocation test, 49.2%(185/377) for FeNO, 39.0%(147/377) for sputum eosinophilia, 15.6%(40/377) for peripheral blood eosinophilia and 55.4%(209/377) for increased serum total IgE levels, which were consistently and statistically higher than those of healthy controls(P<0.01). The levels of FeNO [35.0 (21.8, 65.9)ppb], induced sputum eosinophil percentage [2.0 (0.0, 7.5)%], peripheral blood eosinophil percentage [2.9 (1.8, 4.5)%] and serum total IgE [178.4 (63.1, 384.0)kU/L] in AR patients were also higher(P<0.01). Compared with healthy controls, patients with AR demonstrated lower levels of FEV1/FVC%, MMEFpred%, MEF75 pred%, MEF25pred% (all P<0.05). Statistical analysis showed that FeNO, ratio of induced sputum eosinophil percentage and peripheral blood eosinophil percentage had significant correlations with each other(P<0.01), the r value being 0.247, 0.235, 0.355 respectively. Conclusion: AR without asthma is characterized by lower airway inflammation, small airway impairment and bronchial hyperreactivity, features similar to those of asthma.

Cough reflex sensitivity is increased in guinea pigs with parainfluenza virus infection.

The purpose of this study was to investigate for the change in cough reflex sensitivity (CRS) caused by parainfluenza virus type 3 (PIV3) infection. Guinea pigs were randomized into a vehicle control, an asthma control, or 1 of 4 PIV3-inoculated groups (referred to as postinfection day [PID] 6, 12, 28, and 42 groups). Evidence of viral protein and nucleic acid within the lung confirmed successful PIV3 infection. Plethysmography was used to assess CRS and airway reaction and airway inflammation was assessed via bronchoalveolar lavage fluid cytology and lung histopathology. Compared with the vehicle control group, CRS was significantly increased in all PID groups (P <.05) in concert with an obvious airway hyperresponsiveness in the PID 6 group. Though a small increase in CRS in the asthma control group was noted, it was not significant compared to the vehicle control group. Total cell counts from the bronchoalveolar lavage fluid of all PIV3-inoculated groups increased markedly and the number of lymphocytes was significantly increased in the PID 6 and PID 12 groups. The lung pathology of PIV3-inoculated animals showed airway inflammation without pneumonia in the acute infectious phase. The temporal and spatial variation of CRS may be the essential mechanism of cough caused by PIV3.

Neural respiratory drive in patients with COPD during exercise tests.

BACKGROUND: It is unknown whether neural drive is comparable in constant rate and incremental exercise tests. Few data have previously been available to address this question because of the lack of reliable methods to assess neural respiratory drive in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aims of this study are to determine whether neural respiratory drive during constant rate exercise differs from that during incremental exercise and to determine whether neural respiratory drive was maximal at the end of exhaustive exercise tests. METHODS: We studied sixteen patients with moderate-severe COPD (mean ± SD FEV(1) 29 ± 10%). Both diaphragmatic electro-myogram (EMG) and transdiaphragmatic pressure were recorded with a combined multipair electrode balloon catheter during incremental and constant (80% of maximal oxygen consumption derived from a prior incremental exercise test) treadmill exercise. Minute ventilation and oxygen uptake were also measured. RESULTS: Root mean square (RMS) of the diaphragmatic EMG increased gradually without a plateau during incremental exercise, whereas the RMS increased initially and reached a plateau during constant work rate exercise. The RMS of the diaphragmatic EMG at the end of exercise was similar for both incremental and constant work rate exercise (176 ± 42 µV vs. 184 ± 39 µV); these values were 70 and 73% of maximal values recorded over the study. CONCLUSIONS: The pattern of increase in neural respiratory drive during incremental exercise is different to that observed during constant work rate exercise, but both exercise protocols are terminated when the patients achieve a similar but submaximal drive.

How well do questionnaires perform compared with physical examination in detecting flexural eczema? Findings from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

BACKGROUND: Questionnaires are widely used in epidemiological studies to measure eczema symptom prevalence, but there are concerns regarding their accuracy if used as a diagnostic tool. OBJECTIVES: To compare the performance of a validated eczema symptom questionnaire and a standardized skin examination protocol employed in the second phase of the International Study of Asthma and Allergies in Childhood (ISAAC). METHODS: A total of 30,358 schoolchildren aged 8-12 years from 18 countries were examined for flexural eczema. Parents also completed an eczema symptom questionnaire. We compared prevalence estimates at the population level based on the questionnaire vs. physical examination. We also compared the skin examination and the ISAAC questionnaire in making a diagnosis of flexural eczema. RESULTS: The point prevalences for flexural eczema at centre level based on a single examination were lower than the questionnaire-based 12-month period prevalences (mean centre prevalence 3.9% vs. 9.4%). Correlation between prevalences of both outcome measures was high (r = 0.77, P < 0.001). At the individual level, questionnaire-derived symptoms of 'persistent flexural eczema in the past 12 months' missed < 10% of cases of flexural eczema detected on physical examination. However, between 33% and 100% of questionnaire-based symptoms of 'persistent flexural eczema in the past 12 months' were not confirmed on examination. CONCLUSIONS: ISAAC questionnaire-derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used.

Effect of propofol on twitch diaphragmatic pressure evoked by cervical magnetic stimulation in patients.

BACKGROUND: Several studies have demonstrated the inhibitory effect of propofol on diaphragmatic contractility in laboratory animals, but there have been few studies in humans. We have investigated the effect of a single bolus injection of propofol on twitch diaphragmatic pressure (TwPdi) evoked by cervical supramaximal magnetic stimulation, and its impact on diaphragmatic contractility. METHODS: In 16 patients scheduled for elective operation, TwPdi was evoked bilaterally at the cervical phrenic nerves with supramaximal magnetic stimulations using a 140 mm diameter magnetic coil. Changes of TwPdi were monitored dynamically before and during general anaesthesia induced by single bolus of propofol 2 mg kg (-1). During the study, all patients breathed 100% oxygen by a face mask, maintaining Sp(O(2)) > or = 99% and PE'(CO(2)) 4.6-5.2 kPa. RESULTS: TwPdi declined after administration of propofol with gradual recovery. Compared with baseline [20.6 (6.0) cm H(2)O], TwPdi decreased by 23.3% (P<0.001) to [15.8 (6.4) cm H(2)O]. When the patients regained awareness, TwPdi returned to [19.1 (6.1) cm H(2)O], close to baseline (P=0.063). The time from starting the propofol infusion to the lowest TwPdi was [240 (86) s]. Total time course of stimulation lasted [363 (89) s]. CONCLUSIONS: A single bolus propofol depressed TwPdi evoked by cervical magnetic stimulation, demonstrating inhibitory effects of propofol on diaphragmatic contractility in patients during general anaesthesia.

Neural respiratory drive during apnoeic events in obstructive sleep apnoea.

For a given neural drive, oesophageal pressure during apnoeic episodes may differ from that during airflow, since inspiratory airflow and increased lung volume both reduce pressure generation. It was, therefore, hypothesised that diaphragm electromyography (EMG) may provide additional data to oesophageal pressure when used for the assessment of neural drive in patients with obstructive sleep apnoea, whose breathing is associated with variable airflow and changes in lung volume. Neural respiratory drive was assessed using diaphragm EMG recorded from multipair oesophageal electrodes in 12 patients with obstructive sleep apnoea. Oesophageal pressure was also recorded. The mean+/-sd inspiratory oesophageal pressure swing was 11.0+/-3.7 cmH(2)O during wakefulness, 38.2+/-15.7 cmH(2)O at the end of the apnoea and reduced to 28.5+/-10.4 cmH(2)O at the beginning of arousal. The mean peak inspiratory diaphragm EMG signal was 21.8+/-6.5 muV during wakefulness, 38.6+/-14.0 muV at the end of the apnoea and further increased to 59.6+/-32.0 muV at the beginning of arousal. It was concluded that the pattern of neural drive assessed by oesophageal pressure differs from that measured by diaphragm electromyography during apnoeic events and, therefore, that diaphragm electromyography may be a useful adjunct to measurement of oesophageal pressure for the assessment of neural drive in patients with obstructive sleep apnoea.

Prior SO2 exposure promotes airway inflammation and subepithelial fibrosis following repeated ovalbumin challenge.

BACKGROUND: Exposure to allergens or air pollutants often leads to asthma exacerbations associated with aggravation of airway inflammation. Although, repeated allergen challenge often induces chronic allergic airway inflammation (CAAI) and airway remodelling, yet, the effects of brief exposure to air pollutants such as SO(2) on development of CAAI and airway remodelling remain to be clarified. OBJECTIVE: The aim of the experiment was to investigate the effects of acute neutrophilic airway inflammation induced by brief exposure to SO(2) on development of CAAI and subepithelial fibrosis (SEF) in a murine model of asthma. METHODS: Acute airway inflammation was induced by brief exposure to 50 p.p.m. SO(2) (1 h/d, 3 days). CAAI and SEF in BALB/c mice were induced by repeated challenge with ovalbumin (OVA) for 5 or 9 weeks with or without prior exposure to SO(2). Bronchoalveolar lavage fluid (BALF) eosinophilia as index of CAAI, BALF endothelin-1 (ET-1) and TGF-beta1 levels, morphometric evaluation of fibrotic area beneath subbasement membrane and lung hydroxyproline content (Hyp) as indexes of SEF were monitored. RESULTS: Exposure to SO(2) led to acute neutrophilic inflammation and epithelial sloughing with profound elevation of BALF ET-1. Repeated OVA challenge resulted in CAAI and SEF along with elevation of Hyp, increase of fibrotic area beneath subbasement membrane and elevation of BALF TGF-beta1. Preceding SO(2) exposure exaggerated BALF eosinophilia, facilitated and enhanced SEF with more significant elevation of BALF ET-1 and TGF-beta1 levels compared with OVA-challenged mice without prior exposure to SO(2). The increase of Hyp was positively correlated with elevation of BALF TGF-beta1 during CAAI (r=0.842, P<0.01). CONCLUSION: This data demonstrated that SEF developed in parallel with severity and time course of CAAI following repeated OVA challenge. SO(2)-induced acute epithelial injury and neutrophilic inflammation could enhance CAAI and promote SEF, probably through overexpression of ET-1 and TGF-beta1.

Proteobacteria community compositions correlate with bronchiectasis severity.

BACKGROUND: Proteobacteria contributes to airway inflammation and poor clinical outcomes in bronchiectasis. OBJECTIVE: To compare sputum Proteobacteria compositions according to bronchiectasis severity. METHODS: Sputum samples collected from 106 patients with stable bronchiectasis and 17 healthy subjects were split for 16srRNA sequencing and biomarker measurement. Pairwise changes in Proteobacteria compositions among 22 of 106 patients during stability, exacerbations and convalescence were compared. Patients were stratified based on the Bronchiectasis Severity Index (BSI). RESULTS: Respectively 44, 34 and 28 patients had mild, moderate and severe bronchiectasis. A higher BSI was associated with a greater relative abundance of Proteobacteria and lower Shannon-Wiener diversity index, Simpson diversity index and bacterial richness. Similar findings applied at genera levels. Proteobacteria and Pseudomonas were the major phylum and genus, respectively, contributing to community similarity in moderate-to-severe bronchiectasis. These significant correlations were not observed in those in whom Pseudomonas aeruginosa was not isolated. Proteobacteria abundance correlated with lung function, but not sputum inflammatory biomarkers in severe bronchiectasis. Proteobacteria compositions in severe bronchiectasis were less likely to change significantly during exacerbations and convalescence. CONCLUSION: Proteobacteria compositions (particularly culturable Pseudomonas abundance) were correlated with bronchiectasis severity. Proteobacteria and Pseudomonas contributed most to community similarity in patients with a higher BSI, indicating microbial targets for interventions in severe bronchiectasis.

National epidemiology of carbapenem-resistant and extensively drug-resistant Gram-negative bacteria isolated from blood samples in China in 2013.

Although antimicrobial resistance poses a great challenge to clinicians in China, there are limited antimicrobial resistance data on Gram-negative bacteria nationwide. We investigated the phenotypic characteristics of carbapenem-resistant Escherichia coli (CREC) and Klebsiella pneumoniae (CRKP) as well as extensively drug-resistant strains of Pseudomonas aeruginosa (XDRPA) and Acinetobacter baumannii (XDRAB) isolated from blood cultures in China. Data were collected on 24113 isolates from the China surveillance of antimicrobial resistance program in 2013, which comprised 208 hospitals located in all seven administrative regions of China. Minimum inhibitory concentrations (MICs) for common antimicrobials were determined by commercial automated systems available at local hospitals, and associations with geographic and clinical distributions was further studied. The overall prevalence of CREC, CRKP, XDRAB and XDRPA strains was 1.0, 5.5, 13.7 and 4.2%, respectively. Except for CREC, which did not differ greatly by region, the prevalence of the remaining three strains varied significantly across regions. The highest prevalence of CRKP (10.6%) and XDRAB (13.1%) were found in the pediatric group, and higher prevalence of all four target strains was found in the intensive care unit. For imipenem, 55.8% of CREC and 22.9% of CRKP strains had MICs of ≤4 µg/mL, while 97.4% XDRAB and 84% XDRPA isolates had MICs of ≥16 µg/mL. All CREC, CRKP and 81.2% of XDRAB strains were susceptible to tigecycline, with MIC90 values of 0.5, 2 and 4 µg/mL, respectively. In conclusion, a high prevalence of CRKP and XDRAB has emerged in China, especially in children and in the intensive care unit.

Unsupervised learning technique identifies bronchiectasis phenotypes with distinct clinical characteristics.

BACKGROUND: Unsupervised learning technique allows researchers to identify different phenotypes of diseases with complex manifestations. OBJECTIVES: To identify bronchiectasis phenotypes and characterise their clinical manifestations and prognosis. METHODS: We conducted hierarchical cluster analysis to identify clusters that best distinguished clinical characteristics of bronchiectasis. Demographics, lung function, sputum bacteriology, aetiology, radiology, disease severity, quality-of-life, cough scale and capsaicin sensitivity, exercise tolerance, health care use and frequency of exacerbations were compared. RESULTS: Data from 148 adults with stable bronchiectasis were analysed. Four clusters were identified. Cluster 1 (n = 69) consisted of the youngest patients with predominantly mild and idiopathic bronchiectasis with minor health care resource use. Patients in cluster 2 (n = 22), in which post-infectious bronchiectasis predominated, had the longest duration of symptoms, greater disease severity, poorer lung function, airway Pseudomonas aeruginosa colonisation and frequent health care resource use. Cluster 3 (n = 16) consisted of elderly patients with shorter duration of symptoms and mostly idiopathic bronchiectasis, and predominantly severe bronchiectasis. Cluster 4 (n = 41) constituted the most elderly patients with moderate disease severity. Clusters 2 and 3 tended to have a greater risk of bronchiectasis exacerbations (P = 0.06) than clusters 1 and 4. CONCLUSION: Identification of distinct phenotypes will lead to greater insight into the characteristics and prognosis of bronchiectasis.

Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003.

BACKGROUND: An epidemic of severe acute respiratory syndrome (SARS) has been associated with an outbreak of atypical pneumonia originating in Guangdong Province, People's Republic of China. We aimed to identify the causative agent in the Guangdong outbreak and describe the emergence and spread of the disease within the province. METHODS: We analysed epidemiological information and collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong in mid-February, 2003. We did virus isolation, serological tests, and molecular assays to identify the causative agent. FINDINGS: SARS had been circulating in other cities of Guangdong Province for about 2 months before causing a major outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS coronavirus (CoV), was isolated from specimens from three patients with SARS. Viral antigens were also directly detected in nasopharyngeal aspirates from these patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their convalescent sera. Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world. INTERPRETATION: SARS CoV is the infectious agent responsible for the epidemic outbreak of SARS in Guangdong. The virus isolated from patients in Guangdong is the prototype of the SARS CoV in other regions and countries.

Sputum bacteriology in steady-state bronchiectasis in Guangzhou, China.

BACKGROUND: The impact of potentially pathogenic micro-organisms (PPMs) on Chinese patients with steady-state bronchiectasis is unknown. METHODS: Peripheral blood and sputum were sampled to determine inflammatory markers and sputum bacterial density. Spirometry and diffusing capacity were measured. Quality of life was assessed using the St George's Respiratory Questionnaire. RESULTS: Of 144 patients with steady-state bronchiectasis, Pseudomonas aeruginosa was isolated in 44 cases (30.6%). Compared with other PPMs, P. aeruginosa had a more pronounced influence on airway inflammation and spirometry, but not on systemic inflammation or quality of life. The impact of PPMs other than P. aeruginosa on clinical indices was similar. Bacterial density was not correlated with most clinical parameters. Factors associated with PPM isolation included bronchiectasis symptoms for ⩾ 10 years (OR 2.13) and ⩾ 4 bronchiectatic lobes (OR 2.82). Having ⩾ 4 exacerbations within 2 years (OR 2.18) and cystic bronchiectasis (OR 2.23) was associated with the colonisation of PPMs, i.e., isolating an identical PPM on at least two occasions within 1 year. CONCLUSION: In patients with steady-state bronchiectasis in Guangzhou, P. aeruginosa is the most common organism causing heightened airway inflammation and poor lung function. PPM isolation or colonisation should be suspected in case of longer duration of symptoms, multilobar bronchiectasis, frequent exacerbation and cystic bronchiectasis.