Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai / 医学前沿

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Diagnostic efficacy of joint detection of Xpert MTBRIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid for smear-negative pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To investigate the diagnostic value of joint detection of Mycobacterium tuberculosis rifampicin resistance gene (Xpert MTB/RIF), Mycobacterium tuberculosis ribonucleic acid (TB-RNA) and Mycobacterium tuberculosis deoxyribonucleic acid (TB-DNA) in bronchoalveolar lavage fluid for smear-negative pulmonary tuberculosis. Methods A total of 806 patients with suspected smear-negative pulmonary tuberculosis admitted to our hospital from May 2020 to July 2022 were selected, 506 patients diagnosed as bacterial negative pulmonary tuberculosis by clinical, X-ray and sputum samples were classified as bacterial negative pulmonary tuberculosis group, and the other 300 patients with non-tuberculous pulmonary disease were classified as non-tuberculous pulmonary disease group. XpertMTB/RIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid of all patients were detected. With clinical, X-ray and sputum specimen examination of mycobacterium tuberculosis as the gold standard, the diagnostic efficacy of alveolar lavage solution Xpert MTB/RIF, TB-RNA and TB-DNA alone and in combination was analyzed. Results The positive detection rates of Xpert MTB/RIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid of the smear-negative pulmonary tuberculosis group and the non-tuberculosis pulmonary disease group were 69.96% (354/506) and 2.67% (8/300), 61.46% (311/506) and 5.00% (15/300), and 63.64% (322/506) and 8.00% (24/300), respectively. The rates in the smear-negative pulmonary tuberculosis group were higher than those in the non-tuberculosis lung disease group, and the differences were statistically significant (χ2=342.005, 246.930, 235.687, P<0.01). Compared with the gold standard, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of Xpert MTB/RIF in the diagnosis of smear-negative pulmonary tuberculosis were 69.96%, 97.33%, 80.15%, 97.79% and 65.77%, respectively; those values of TB-RNA were 61.46%, 95.00%, 73.95%, 95.40% and 59.38%, respectively; those values of TB-DNA were 63.64%, 92.00%, 74.19%, 93.06% and 60.00%, respectively; those values of combined diagnosis with Xpert MTB/RIF, TB-RNA and TB-DNA were 61.26%, 100.00%, 75.68%, 100.00% and 60.48%, respectively; the specificity and positive predictive value of combined detection were higher than those of single detection (P<0.05). Conclusions The joint detection of Xpert MTB/RIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid can improve the diagnostic efficacy of smear-negative pulmonary tuberculosis and is worthy of clinical promotion and application.

Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai / 医学前沿

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Diagnosis of Pneumocystis jirovecii pneumonia by cytological examination of bronchoalveolar lavage fluid combined with metagenomic next-generation sequencing / 中国热带医学

@#Abstract：Objective To investigate the morphological features of the Pneumocystis jirovecii, in order to facilitate early detection and rapid diagnosis of this rare pathogen from a morphology point of view by laboratory technicians. By analyzing the laboratory features and application value of different pathogen detection methods in the diagnosis of Pneumocystis jirovecii pneumonia, we aim to provide the most reliable diagnostic basis for rapid diagnosis of Pneumocystis jirovecii pneumonia.Methods A retrospective analysis was conducted on the test results of bronchoalveolar lavage fluid samples from a comprehensive hospital in Zhangqiu District, Jinan City, Shandong Province, and a hospital in Changde City from April 2022 to October 2022. Five confirmed cases of Pneumocystis jirovecii pneumonia were detected. Its clinical manifestations, laboratory results, and morphological characteristics of pathogens under different stains were analyzed to discuss the advantages and disadvantages of different detection methods. Results Cytological examination of bronchoalveolar lavage fluid found the trophozoites and cysts of Pneumocystis jirovecii by Wright's-Giemsa staining in 4 cases (80%), and the cysts of Pneumocystis jirovecii by Silver hexamine staining in 4 cases (80%), while the metagenomic next-generation sequencing confirmed all the 5 positive results. All 5 patients had different degrees of reduction in the absolute count of peripheral blood lymphocytes, and the serum lactic dehydrogenase and (1-3)-β-D-Glucan were increased. Among the 5 patients in this study, 4 were treated with sulfamethoxazole combined with caspofungin, and 1 was treated with sulfamethoxazole. Three patients were cured and discharged from hospital after treatment, but two died. Conclusions The method of Wright's-Giemsa staining for the cytological examination of bronchoalveolar lavage fluid to find Pneumocystis jirovecii has the unique and irreplaceable advantages as silver staining. Metagenomic next-generation sequencing can further increase the positive detection rate of Pneumocystis jirovecii. The combination of cytological examination of bronchoalveolar lavage fluid with metagenomic nextgeneration sequencing is a powerful diagnostic method for rapid diagnosis of Pneumocystis jirovecii pneumonia, which can diagnose accurately and reduce missed diagnosis.

Clinical characteristics of children with lobar pneumonia and the distribution of pathogens in bronchoalveolar lavage fluid / 中国热带医学

@#Abstract: Objective　To analyze the clinical characteristics of children with lobar pneumonia and the distribution of pathogens in bronchoalveolar lavage fluid (BALF) collected from these patients, hence providing a scientific basis for their precise diagnosis and treatment. Methods　A total of 115 children diagnosed with lobar pneumonia from August 2019 to August 2022 at Suining Central Hospital were screened as the research subjects. The clinical manifestations and occurrence of complications in the patients were investigated. All the children underwent bronchoalveolar lavage after admission, and BALF samples were collected. Fluorescence quantitative PCR was adopted to detect and analyze the distribution and clinical characteristics of Streptococcus pneumoniae (SP) and other related pathogenic microorganisms in BALF specimens. Results Among the 115 pediatric patients with lobar pneumonia, the occurrence of manifestations or complications including involvement of ≥2 lung lobes, myocardial damage, pleural effusion, abnormal liver function, digestive system involvement, nervous system involvement, rash, renal function impairment, and lung atelectasis were observed in 46, 46, 39, 33, 18, 17, 11, 5, and 4 cases, respectively. The pathogen positivity rate in the BALF samples of the 115 patients was 87.0% (100/115), with 81 cases of single infection and 19 cases of mixed infection. A total of 121 strains of pathogens were isolated, including 83 strains of Mycoplasmal pneumonia (MP) (accounting for 68.6%) and SP(13.2%). The differences in the detection rates of HI, MP, RSV strains among different age groups were statistically significant (χ2=8.834, 19.454, 10.284, P<0.05), while the differences in the infection rates of SP, KP, CP, and ADV were not statistically significant (χ2=3.393, 2.67, 0.565, 0.097, P>0.05). The MP pneumonia group showed significantly higher incidence of complications such as pleural effusion, nervous system involvement, and abnormal liver function than the non-MP pneumonia group (χ2=3.925, 4.195, and 4.513, P<0.05). The highest pathogen detection rate was in winter, accounting for 33.91%. Conclusions MP is the most common pathogen in BALF of children with lobar pneumonia. There is variation in the pathogen detection rate among different age groups and seasons. Those with combined infections were more prone to complications, which is worthy of attention by clinicians.

Application of metagenomic next-generation sequencing of bronchoalveolar lavage fluid in the diagnosis and treatment of refractory pneumonia in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children.@*METHODS@#A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (n=80) and traditional testing (n=80). All children received the tests of inflammatory markers and pathogen tests after admission. Traditional pathogenicity tests included microbial culture (sputum specimen collected by suction tube), nucleic acid detection of respiratory pathogens, and serological test (mycoplasma, tuberculosis, and fungi). For the mNGS group, BALF specimens were collected after bronchoscopy and were sent to the laboratory for mNGS and microbial culture. The two groups were analyzed and compared in terms of the detection of pathogens and treatment.@*RESULTS@#Compared with the traditional testing group, the mNGS group had a significantly higher detection rate of pathogens (92% vs 58%, P<0.05), with more types of pathogens and a higher diagnostic rate of mixed infections. Compared with the traditional testing group, the mNGS group had a significantly higher treatment response rate and a significantly lower incidence rate of complications during hospitalization (P<0.05). Treatment was adjusted for 68 children in the mNGS group according to the results of mNGS, with a treatment response rate of 96% (65/68) after adjustment.@*CONCLUSIONS@#Compared with traditional pathogen tests, BALF mNGS can significantly improve the detection rate of pathogens and find some rare pathogens. In clinical practice, when encountering bottlenecks during the diagnosis and treatment of children with RTP, it is advisable to promptly perform the mNGS to identify the pathogens.

Application of body temperature rinse in percutaneous transforaminal endoscopic lumbar discectomy through intervertebral approach / 中国骨伤

OBJECTIVE@#To investigate the effects of two types of temperature rinses on body temperature, inflammatory cytokine levels, and bleeding volume in percutaneous endoscopic lumbar discectomy.@*METHODS@#Eighty patients underwent percutaneous endoscopic lumbar discectomy from January 2018 to December 2020 were selected and divided into experimental group (40 cases) and control group(40 cases). In experimental group, there were 19 males and 21 females, aged (38.8±9.8) years old;7patients on L4,5 and 33 patients on L5S1;Body msss index(BMI) was (27.8±7.2) kg·m-2. In contral group, there were 18 males and 22 females, aged (41.5±10.9) years old, 5 patients on L4,5 and 35 patients on L5S1;BMI was (26.4±6.2) kg·m-2. The patients in the control group were received normal saline rinse at room temperature, and the patients in the experimental group were received normal saline rinse heated to 37 ℃. Body temperature, chills, nausea, vomiting, and other adverse reactions were recorded. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in two groups were recorded before and 2 hours after operation. Visual analogue scale (VAS) was used to evaluate the degree of lumbar pain in two groups before and 2 hours after surgery. Fibrinolytic-coagulation indexes with preoperative and 2 hours after surgery, including the D-dimer (DD), fibrinogen degradation products (FDP), activated partial thrombin time (APTT) and prothrombin time (PT) were recorder. Operation time and blood loss in two groups were recorded.@*RESULTS@#The body temperature of both groups showed a downward trend, while the body temperature of the control group was lower than that of the experimental group. The levels of TNF-α, IL-6 and IL-10 in two groups were increased 2 hours after surgery compared with those before surgery(P<0.05), while the levels in experimental group were lower than those in control group(P<0.05). Postoperative VAS in experimental group 2.19±1.13 was significantly lower than that in the control group 3.38±1.35(P<0.05). The levels of DD and FDP at 2 hours after surgery in both groups were higher than those before surgery (P<0.05), while the levels of DD and FDP in the experimental group were higher than those in the control group (P<0.05). There was no significant difference in APTT and PT levels between two groups after operation (P>0.05). The blood loss in the experimental group of (45.2±14.1) ml was lower than that in the control group of (59.52±15.6) ml. The operation time of experimental group (46.7±13.8) min was less than that of control group (58.3±15.2) min(P<0.05).@*CONCLUSION@#Body temperature rinse can reduce the incidence of adverse reactions, alleviate local inflammatory reactions, reduce intraoperative blood loss and shorten the operation time.

Metabolomics of nasal lavage fluid in patients with allergic rhinitis treated by Xiaoqinglong Decoction / 中国中药杂志

This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including β-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.

Structural characteristics of lower respiratory tract microflora in patients with pneumoconiosis / 中华劳动卫生职业病杂志

Objective: To explore the composition of bacteria in lower respiratory tract of patients with pneumoconiosis and dust exposure, and to compare and analyze the difference and correlation between them. Methods: From May 2020 to January 2021, a prospective multicenter cross-sectional study was conducted to select patients with pneumoconiosis who underwent bronchoalveolar lavage treatment at the Respiratory and Critical Care Medical Department of the 920th Hospital of the Joint Support Force and the Respiratory Department of Tongren Hospital in Kunming, as well as the population of dust recipients. A total of 24 patients with pneumoconiosis (pneumoconiosis group) were included, and 16 dust exposed individuals (dust exposed group) were used as controls. Two groups of patients' alveolar lavage fluid were collected. The 16SrRNA gene V3-V4 sequencing technology and bioinformatics analysis platform were used to measure and analyze the differences in microbial structure composition and associations between bacterial communities. Results: Compared with the dust exposed group, the top 5 bacterial phyla in the alveolar lavage fluid level of patients with pneumoconiosis were the same, followed by Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria. Compared with the dust exposure group, the pneumoconiosis group patients belong to the top 5 genera of horizontal flora abundance, which are different. The dust exposure group is respectively: Pseudomonas, Proctor, Streptococcus, Achromobacter, and Neisseria. The pneumoconiosis group is respectively: Pseudomonas, Achromobacter, Streptococcus, Ralstonia, and Proctor. The Alpha diversity analysis results showed that compared with the dust exposed group, the level of bacterial diversity in the pneumoconiosis group was difference (P<0.05), and there was no statistically significant difference in bacterial evenness (P>0.05) ; Beta diversity showed differences in microbial community structure between the two groups (P<0.05 ). Single factor microbial association network analysis showed that there was a high correlation between Firmicutes and Bacteroidetes in the pneumoconiosis and dust exposed groups and other species, showing a positive correlation; The correlation between Proteobacteria and other species is high, showing a negative correlation. Conclusion: The structure and relative abundance of bacteria in lower respiratory tract were different between patients with pneumoconiosis and dust exposure, and the diversity of bacteria in lower respiratory tract increased in patients with pneumoconiosis, which may be related to disease status.

Clinical and bronchoscopy characteristics of Mycoplasma pneumoniae pneumonia in children with 23S rRNA resistance gene positive in bronchoalveolar lavage fluid / 中华实用儿科临床杂志

Objective:To investigate clinical and bronchoscopy characteristics of Mycoplasma pneumoniae pneumonia in children with 23S rRNA resistance gene positive in bronchoalveolar lavage fluid(BALF), and find clinical indicators that can identify Mycoplasma pneumoniae drug resistance early.Methods:The clinical data of 61 hospita-lized children diagnosed with Mycoplasma pneumoniae pneumonia as subjects from October 2017 to June 2018 in the Department of Pediatric Respiratory Medicine of Shengjing Hospital Affiliated to China Medical University were analyzed retrospectively.Bronchoscopy was performed on each subject and the BALF was taken and used to detect the 2063 site mutation of the 23S rRNA V region gene in BALF, and they were divided into drug-resistant gene positive group and drug-resistant gene negative group.The clinical manifestations, relevant laboratory data, imaging data, and bronchoscopy findings in different load groups were compared.Statistical methods such as t test, rank sum test, χ2 test, Fisher′ s exact probability method, and multivariate Logistic regression analysis were used to analyze the data. Results:Among the 61 children, 38 cases (62.30%) were in the drug resistance gene positive group, and 23 cases (37.70%) were in the drug resistance gene negative group.There were no significant differences in gender and age between the two groups (all P>0.05). The days of hospitalization and fever in the children with positive drug resistance genes were longer than those in the negative drug resistance gene groups, and they were more likely to have refractory mycoplasma pneumoniae pneumonia(RMPP) and extra pulmonary complications, with statistically significant differences ( P<0.05), but there were no significant differences in hypoxemia ( P>0.05). There were significant differences in white blood cell(WBC), C-reactive protein(CRP), procalcitonin(PCT), D-Dimer (D-D) and interleukin-6 (IL-6) between the two groups (all P<0.05). Except that the WBC level in the drug-resistant gene-positive group was lower than that in the drug-resistant gene-negative group, the rest of the test results indicated that the drug-resistant gene-positive group was higher than the drug-resistant gene-negative group.There were no significant differences in the concentrations of serum lactate dehydrogenlase(LDH)and IL-6 in BALF ( P>0.05). In this study, Logistic regression analysis was performed on several statistically significant laboratory indicators.It was found that WBC was more sensitive to identify drug resistance genes, and the optimal critical value was 8.55×10 9/L.The specificity of D-D in identifying drug resistance genes was higher, and the optimal cut-off value was 523 μg/L.In the drug resistance gene positive group, 35 cases (92.11%) showed extensive lung consolidation/atelectasis on imaging, and the drug resistance gene negative group was 13 cases (56.52%), with statistically significant differences ( P<0.05). The drug resistance gene-positive group mainly showed mucosal erosion, necrosis, phlegm plug/plastic phlegm plug and bronchitis stenosis, with a total of 19 cases (50.00%). In the drug resistance gene negative group, the main manifestations of mucosal longitudinal wrinkle, flocculent and viscous secretions were 14 cases (60.88%), with statistically significant differences ( P<0.05). Conclusions:The point mutation of 23S rRNA V region gene is closely related to the clinical characteristics of children with Mycoplasma pneumoniae pneumonia.Children with A2063G mutation are more prone to have RMPP and extrapulmonary complications, and their imaging manifestation and bronchoscopy are more severe.The levels of leukocytes and D-D in the blood have significance for the early identification of drug resistance.The systemic excessive immune inflammatory response caused by Mycoplasma pneumoniae pneumonia with drug-resistant gene positive needs to be valued.

Analysis of drug resistance gene in Mycoplasma pneumoniae and 13 pathogens in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia / 中华实用儿科临床杂志

Objective:To investigate drug resistance gene in Mycoplasma pneumoniae(MP) and the distribution of 13 respiratory pathogens in bronchoalveolar lavage fluid(BALF) of children with Mycoplasma pneumoniae pneumonia(MPP).Methods:A total of 100 BALF of children with MPP in Peking University Third Hospital and Peking University First Hospital from January 2018 to January 2019 were collected.Fluorogenic quantitative PCR was used to detect nucleic acid and it′s drug resistance gene of MP and multiple PCR method was adopted to detect influenza A virus, influenza A virus-H 1N 1, influenza A virus-H 3N 2, influenza B, human parainfluenza virus, adenovirus, human bocavirus, human rhinovirus, Chlamydia pneumoniae, human metapneumovirus, MP, human coronavirus, and respi-ratory syncytial virus gene, and the results were compared by using Chi square test. Results:In 100 BALF samples, MP and drug resistance gene were detected by fluorogenic quantitative PCR.Totally, 83 cases (83.00%) were MP positive and 78 cases (93.98%) were drug resistant.All of them had the point mutations A2063G in V region of 23S rRNA domain.A total of 13 kinds of respiratory pathogens were detected by multiplex PCR method, and 89 cases (89.00%) were positive.Totally, 79 cases (79.00%) were MP positive, of which 74 cases (74.00%) detected only MP, and 5 cases (5.00%) detected MP combined with other pathogens.Other pathogens were detected in 10 cases (10.00%). The virus detection rate of 0-4 years old group was higher than that of >4-6 years old group ( P=0.042) and >6 years old group ( P=0.002), and the differences were statistically significant. Conclusions:MP can be detected in most BALF samples of MPP children, the drug resistance phenomenon is serious, and the main point mutation is A2063G.There were other respiratory pathogens and 2 or 3 pathogens were detected in a small number of BALF samples.

Distribution and antimicrobial resistance pattern of bacteria isolated from alveolar lavage fluid in pediatric patients with lower respiratory tract infection / 中华传染病杂志

Objective:To analyze the distribution and antimicrobial resistance pattern of bacteria isolated from alveolar lavage fluid in pediatric patients with lower respiratory tract infection from 2016 to 2018.Methods:The alveolar lavage fluid of pediatric patients aged <18 years old with lower respiratory tract infection in ten hospitals from January 2016 to December 2018 were collected, and the pathogenic bacteria were cultured and isolated. The paper diffusion method or minimum inhibitory concentration method was used to conduct drug susceptibility tests for the isolated strains.The distribution of pathogenic bacteria and the source department of the strains were analyzed.Chi-sqare test was used for statistical analysis.Results:Of 1 271 isolates, 606 strains (47.7%) were gram-negative bacteria, 628 strains (49.4%) were gram-positive bacteria, and 37 strains (2.9%) were fungi. The common pathogens were Streptococcus pneumoniae (36.7%, 466/1 271), Acinetobacter baumannii (16.8%, 214/1 271), Staphylococcus aureus (12.7%, 162/1 271), Klebsiella pneumoniae (8.3%, 105/1 271), Haemophilus influenzae (7.4%, 94/1 271), Pseudomonas aeruginosa (6.2%, 79/1 271), Burkholderia cepacia (5.3%, 67/1 271) and Escherichia coli (3.7%, 47/1 271). The main pathogens in the intensive care unit (ICU) were gram-negative bacteria (80.1%, 428/534), among which Acinetobacter baumannii was the most common (3.7%, 199/534). The main pathogens in the non-ICU were gram-positive bacteria (70.8%, 522/737). The detection rates of methicillin-resistant Staphylococcus aureus (MRSA) were 45.1%(23/51) in the ICU and 43.2% (48/111) in the non-ICU, respectively. The detection rates of penicillin-resistant Streptococcus pneumoniae (PRSP) were 10.9%(6/55) in the ICU and 18.5% (76/411) in the non-ICU, respectively. The detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP) were 57.3%(43/75) in the ICU and 33.3%(10/30) in the non-ICU, respectively. The detection rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in the ICU was higher than that in the non-ICU (49.1%(27/55) vs 25.0%(6/24)), and the difference was statistically significant ( χ2=3.98, P=0.046). Eight strains (17.0%) of carbapenem-resistant Escherichia coli were detected, and 164 strains(76.6%) of carbapenem-resistant Acinetobacter baumannii were detected. Seventy-eight Haemophilus influenzae isolates were isolated from non-ICU, and the resistance rate to ampicillin was 57.4%(54/94). Burkholderia cepacia isolates were all isolated from ICU, and the resistance rates to piperacillin-tazobactam, levofloxacin, ciprofloxacin and compound sulfamethoxazole were 13.4%(9/67), 3.0%(2/67), 0(0/67) and 9.0%(6/67), respectively. Conclusions:Streptococcus pneumoniae is still the most common pathogen in pediatric patients with lower respiratory tract infection. Gram-negative bacilli are the main pathogens in pediatric patients with lower respiratory tract infection in the ICU. The dection rates of MRSA, PRSP and carbopenem-resistant gram-negative bacilli are high. And the resistance rate of Haemophilus influenzae to ampicillin is also high. The clinical empirical treatment should be determined according to different clinical background.

Effect of acute exposure to electronic cigarette on bronchoalveolar lavage fluid and pulmonary surfactant protein in mice / 预防医学

Objective@#To assess the effects of acute exposure to electronic cigarette ( e-cigarette ) on leukocyte and total protein levels in bronchoalveolar lavage fluid ( BALF ) and pulmonary surfactant protein expression in a mouse model, so as to provide insights into the elucidation of the mechanism underlying the damages to the respiratory system caused by e-cigarette.@*Methods@#Twenty-one C57BL/6N female mice were randomly divided into the blank control group, the solvent control group and the nicotine group. Mice in the solvent control group and the nicotine group were exposed to the solvent aerosol or e-cigarette aerosol containing 25 mg/mL nicotine for 3 hours daily, while mice in the blank control group were bred in clean air. Following 3-day exposure, mouse BALF and lung specimens were collected. The cell morphology was observed using microscopy following Wright-Giemsa staining and the leukocyte count was estimated in BALF, while the total protein expression was quantified using bicinchoninic acid ( BCA ) assay. In addition, the mRNA expression of pulmonary surfactant protein genes was detected in mouse lung specimens using quantitative real-time PCR ( qPCR ) assay.@*Results@#All mice in three groups grew well without obvious abnormality or death seen. Wright-Giemsa staining showed a higher number of mononuclear macrophages in mouse BALF in the nicotine group than in the blank control group and the solvent control group. The leukocyte counts were ( 2.00±0.77 )×107, ( 1.79±0.99 )×107 and ( 4.00±1.35 )×107 cells/L ( F=9.199, P=0.002 ), and the total protein levels were ( 0.16±0.03 ), ( 0.12±0.02 ) and ( 0.16±0.04 ) mg/mL in mouse BALF in the blank control group, solvent control group and nicotine group ( F=3.610, P=0.048 ), and the relative mRNA expression of pulmonary surfactant protein B (SP-B) and SP-D was 1.00±0.14, 0.82±0.12 and 0.74±0.07 ( F=5.491, P=0.028 ), and 1.00±0.06, 0.90±0.02 and 0.71±0.15 in mouse lung specimens, respectively ( F=10.460, P=0.005 ). The leukocyte count was significantly higher in the nicotine group than in the blank control group and solvent control group (P=0.007, 0.003), and the total protein content was higher in the nicotine group than in the solvent control group ( P=0.060 ), while the relative SP-B mRNA expression was lower in the nicotine group than in the blank control group ( P=0.025 ), and the relative SP-D mRNA expression was lower in the nicotine group than in the blank control group and solvent control group ( P=0.004, 0.041 ).@*Conclusion@#Acute exposure to e-cigarette results in elevated intrapulmonary inflammatory responses, pulmonary capillary barrier impairment and reduced pulmonary surfactant protein expression.

Risk factors analysis of central airway stenosis after lung transplantation / 器官移植

Objective To investigate the risk factors of central airway stenosis after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation in Wuxi People's Hospital Affiliated to Nanjing Medical University from July 2016 to December 2017 were retrospectively analyzed. According to the incidence of central airway stenosis following lung transplantation, all recipients were divided into the stenosis group (n=36) and control group (n=119). The incidence of central airway stenosis after lung transplantation was summarized. The risk factors of central airway stenosis after lung transplantation were assessed by univariate and multivariate logistic regression analyses. Results Among 155 lung transplant recipients, 36 cases (23.2%) developed central airway stenosis. The average incidence time was (53±13) d after lung transplantation. Univariate analysis demonstrated that bilateral lung transplantation, grade 3 primary graft dysfunction (PGD), airway fungal infection, long cold ischemia time, long mechanical ventilation time and long intensive care unit (ICU) stay were the risk factors for central airway stenosis after lung transplantation (all P < 0.05). Multivariate analysis showed that airway fungal infection, long cold ischemia time and long mechanical ventilation time were the independent risk factors for central airway stenosis after lung transplantation (all P < 0.05). Conclusions Airway fungal infection after lung transplantation, long cold ischemia time and long mechanical ventilation time probably lead to central airway stenosis after lung transplantation. Active preventive measures and intimate monitoring should be taken to improve the quality of life of the recipients after lung transplantation.

Analysis of pathogens and drug sensitivity in bronchoalveolar lavage fluid of children with severe community acquired pneumonia in Qingdao area / 中国小儿急救医学

Objective:To analyze the distribution and drug sensitivity of pathogens in bronchoalveolar lavage fluid(BALF)of children with severe community acquired pneumonia(CAP)in Qingdao from 2018 to 2020.Methods:The clinical data of 482 children with severe CAP in Qingdao admitted to Women and Children′s Hospital of Qingdao University were collected.BALF was collected by bronchoscopy for detection of bacteria and mycoplasma.Results:(1)Bacterial infection was detected in 139 cases(27.84%), mycoplasma infection in 119 cases(24.69%), and virus infection in 141 cases(29.25%). (2)The detection rates of bacteria and virus infection in the 1-12 months old group were higher.The detection rate of mycoplasma pneumoniae was the highest in the group over 5 years old.(3)A total of 139 strains were positive in bacterial culture of lavage fluid under bronchoscope: 55 strains(39.57%) of gram-negative bacilli and 84 strains(60.43%) of gram-positive cocci.Streptococcus pneumoniae was the most common gram-positive bacteria.Haemophilus influenzae was the most common gram-negative strain.(4)Streptococcus pneumoniae and Staphylococcus aureus were highly sensitive to amoxicillin clavulanate potassium, vancomycin and linezolid.The resistance rate to erythromycin was high(100%). (5)Haemophilus influenzae, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were highly sensitive to meropenem and cefoperazone sulbactam.They were highly resistant to amoxicillin, ampicillin and cefuroxime(>80%).Conclusion:Severe CAP in Qingdao area is mainly caused by virus and bacteria within 1 year old.Mycoplasma pneumoniae infection is the main cause of children over 5 years old.Respiratory syncytial virus, adenovirus and parainfluenza virus are main causes of virus infection.Streptococcus pneumoniae and haemophilus influenzae are the main pathogens, which are more sensitive to vancomycin, linezolid, meropenem and cefoperazone sulbactam, but resistant to erythromycin and amoxicillin.

Clinical characteristics of human cytomegalovirus pneumonia in children and the diagnosis value of detecting human cytomegalovirus DNA in bronchoalveolar lavage fluid / 中国小儿急救医学

Objective:To investigate the clinical features, therapy and prognosis of human cytomegalovirus(HCMV)pneumonia in pediatric patients, and to analyze the diagnosis value of detecting HCMV DNA in bronchoalveolar lavage fluid(BALF)by real-time PCR.Methods:The clinical characteristics of 58 pediatric inpatients who were HCMV DNA positive in BALF were retrospectively reviewed.All the patients were from Shengjing Hospital of China Medical University from January 2015 to December 2019.Clinical, radiologic, laboratory and microbiologic data was collected for each patient.The study cohort was divided into HCMV productive infection and latent infection consisting of 22 and 36 patients respectively, based on the HCMV active infection in lung or not.Receiver operating characteristic(ROC)curve was used to assess utility of detecting HCMV DNA in BALF and establish a threshold for diagnosis.Results:(1)Compared with patients in latent infection group, the children in productive infection group had a lower age of onset( P<0.05), a higher proportion of male( P<0.05), and more prolonged hospitalization stay( P<0.05). Pulmonary rales, hypoxemia and higher AST, CK, LDH in serum were easier to detect in productive infection group( P<0.05). Higher HCMV DNA copies in BALF was also detected( P<0.01). Patients in productive infection group had significantly more exposure to additional oxygen treatment or mechanical ventilation and systemic hormone therapy( P<0.05), while with poorer outcomes( P<0.05). (2) ROC curve analysis showed that the AUC for HCMV DNA in BALF in diagnosis of HCMV pneumonia was 0.708 with a threshold of 8.83×10 3 copies/mL, a sensitivity of 77.27%, and a specificity of 58.33%. Conclusion:Those who are diagnosed HCMV pneumonia have a lower age of onset with higher male proportion.These children suffered severer clinical signs.The patients with HCMV DNA copies higher than 8.83×10 3 copies/mL in BALF would be more likely to be diagnosed as HCMV pneumonia.

The evaluation value of heparin-binding protein levels in bronchoalveolar lavage fluid for severe pneumonia in children / 中国小儿急救医学

Objective:To investigate the value of the level of heparin-binding protein(HBP)in bronchoalveolar lavage fluid(BALF)on the evaluation of severe pneumonia in children.Methods:A total of 94 children with severe pneumonia who underwent bronchoscopy and bronchoalveolar lavage were admitted at Hunan Children′s Hospital, and HBP levels in BALF were detected.According to the etiological results, the patients were divided into non-bacterial infection group(19 cases) and bacterial infection group(75 cases). According to the existence and severity of acute respiratory distress syndrome (ARDS), the cases were divided into non-ARDS group(65 cases), mild ARDS group(23 cases) and moderate to severe ARDS group(6 cases).Results:The HBP level of BALF in the bacterial infection group was higher than that in the non-bacterial infection group, and the difference was statistically significant[ 20.77(5.90, 73.50)ng/mL vs.5.9(5.90, 7.64)ng/mL, Z=12.500, P<0.001]. The HBP level of BALF in the moderate to severe ARDS group[300.00(169.29, 300.00)ng/mL] was significantly higher than those in the non-ARDS group[11.90(5.90, 36.95)ng/mL] and the mild ARDS group[15.13(7.41, 46.44)ng/mL], and the difference was statistically significant( H=14.718, P=0.001). In predicting the presence of bacterial infection in severe pneumonia, the area under the receiver operating characteristic curves of BALF HBP, serum procalcitonin (PCT) and serum C-reactive protein(CRP) were 0.758, 0.737, and 0.732, respectively.When the optimal truncation values of BALF HBP, serum PCT and serum CRP were 8.40 ng/mL, 0.16 ng/mL, and 8.39 mg/L, the predicted sensitivities were 70.7%, 69.3%, 46.7%, and the predicted specificity were 79.0%, 79.0%, 94.7%, respectively. Conclusion:The level of HBP in BALF in children with severe pneumonia increases with the severity of ARDS, and significantly increases in the positive group of bacterial infection, which can be used as one of the auxiliary indicators to evaluate the severity of severe pneumonia and bacterial infection in children.

Effect of donor-derived infection on clinical prognosis of kidney transplant recipients / 器官移植

Objective To evaluate the effect of donor-derived infection (DDI) on clinical prognosis of kidney transplant recipients. Methods Clinical data of 82 donors from donation after citizen's death and 148 kidney transplant recipients were retrospectively analyzed. According to the culture results of the lavage fluid of donor kidney, all recipients were divided into the lavage fluid culture of donor kidney positive group (positive group, n=92) and lavage fluid culture of donor kidney negative group (negative group, n=56). All recipients were assigned into the DDI group (n=19) and non-DDI group (n=129) according to whether they developed DDI or not. The distribution and composition ratio of positive strains in the lavage fluid of donor kidney were analyzed. The incidence of postoperative infection and other complications was assessed in the recipients. Perioperative conditions of the recipients were statistically compared between the DDI and non-DDI groups. The treatment efficacy and clinical prognosis of DDI recipients were evaluated. Results Among 148 recipients, 92 obtained positive culture results in the lavage fluid of donor kidney. A total of 131 pathogenic strains were isolated, including 41.2% (54/131) of Gram-positive cocci, 48.9% (64/131) of Gram-negative bacilli and 9.9%(13/131) of fungi. Among 148 recipients, 52 cases were infected. And 45% (41/92) and 20% (11/56) of the recipients were infected in the positive and negative group, respectively. Statistical significance was noted between two groups (P=0.002). Surgical site was the most common infection site in 52 infected recipients, followed by the urinary system. Nineteen recipients developed DDI with an incidence rate of 12.8% and fatality of 16%. Compared with the non-DDI recipients, DDI recipients had significantly higher graft loss rate and fatality, and longer postoperative hospital stay (all P < 0.05). Eight cases presented with carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, after treatment with tigecycline and/or polymyxin and carbapenems, 3 cases died, and 3 underwent kidney graft resection. In the other 8 recipients with CRKP infection, 2 cases were treated with ceftazidime-avibactam (CAZ-AVI) alone, 3 treated with CAZ-AVI combined with carbapenems, and 3 initially treated with tigecycline combined with carbapenems followed by CAZ-AVI for salvage treatment. After corresponding treatment, the recipients achieved long-term survival. Conclusions DDI may lead to severe complications, while early specific antibacterial treatment plays a positive role.

Diagnostic value of detection of pathogens in bronchoalveolar lavage fluid by metagenomics next-generation sequencing in organ transplant patients with pulmonary infection / 中华危重病急救医学

Objective:To evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) in detecting pathogens in bronchoalveolar lavage fluid (BALF) for pulmonary infection in solid organ transplant patients in intensive care unit (ICU).Methods:A retrospective study was conducted, the BALF samples from 46 patients with post organ transplant pneumonia/suspected pneumonia admitted to the Department of Critical Care Medicine of the First Affiliated Hospital of University of Science and Technology of China from August 2018 to August 2021 were collected, all tested by simultaneous mNGS and conventional comprehensive microbial test (CMT), and the results of CMT were used as the reference standard to compare the differences in the diagnostic value of mNGS and CMT for pulmonary infections in solid organ transplant patients, and to analyze the diagnostic value of mNGS for mixed infections.Results:① Pneumonia pathogens: a total of 31 pathogens were detected in 35 patients, including bacteria (16 species), fungi (9 species) and viruses (6 species). Among them, 25 pathogens were detected by mNGS and CMT, and only 19 pathogens were detected by mNGS. Among the microorganisms isolated by mNGS method, the detection rates of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae were higher [51.4%(18/35), 42.9% (15/35), 31.4% (11/35), respectively]; Candida albicans, Aspergillus and Pneumocystis carinii were the most commonly detected fungi [31.4% (11/35), 22.9% (8/35), 22.9% (8/35), respectively]; 20 patients were positive for the virus, and the most commonly detected viruses were cytomegalovirus, herpesvirus and EB virus [28.6% (10/35), 20.0% (7/35), 17.1% (6/35), respectively]. In addition, one case of Brucella was detected by mNGS.② Diagnostic efficiency: as far as bacterial detection is concerned, 20 cases of negative results were obtained by CMT detection of 35 samples included in the study, and a total of 10 cases of positive results were obtained by mNGS detection of negative samples; the percentage of mNGS positive samples was significantly higher than that of CMT positive samples [odds ratio ( OR) = 5.5, 95% confidence interval (95% CI) = 1.2-24.8, P = 0.02]. When compared with CMT, the sensitivity and specificity of mNGS were 93.3% and 50.0%, and the positive predictive value (PPV) and negative predictive value (NPV) were 58.3%, 91.1%. As far as fungal detection was concerned, there was no significant difference in the percentage of positive samples between the two methods ( OR = 1.5, 95% CI = 0.5-4.2, P = 0.60); the sensitivity and specificity of mNGS were 72.2% and 64.7%, and the PPV and NPV were 68.4%, 68.8%; CMT test of the 35 included samples produced 17 negative results, and mNGS test of the negative samples produced 6 positive results. A total of 20 patients tested positive for the virus by mNGS. In addition, 23 patients (65.7%) were diagnosed with pulmonary mixed infection. Conclusion:The use of mNGS to detect pathogens in BALF can improve the sensitivity and specificity of bacterial identification of pulmonary infection in critically ill organ transplant patients, and mNGS has obvious advantages in detecting virus and identifying mixed infections.

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma, chronic obstructive pulmonary diseases and respiratory infections, and systemic diseases such as diabetes. Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit. The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration, but also enhance the clinical benefits to the patients with improved therapeutic outcomes. This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines. It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure, which is followed by recent advances in various strategies to overcome these barriers. Finally, the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.