Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

COVID-19 vaccine uptake and hesitancy in Chinese patients with asthma.

OBJECTIVE: Both patients and physicians may be hesitant toward vaccination in patients with asthma, which may result in lower vaccine uptake. The aim of this work was to investigate the vaccination rate, the adverse reactions, as well as the factors associated with vaccine acceptance and hesitancy toward COVID-19 vaccination among asthmatic patients in Beijing. METHODS: A multi-center, cross-sectional face-to-face survey was conducted in patients with asthma consecutively recruited from December 2021 to April 2022. The survey included asthma status, COVID-19 vaccine uptake and adverse reactions, and knowledge of and attitude toward COVID-19 vaccination. RESULTS: A total of 261 patients were enrolled. The rate of COVID-19 vaccination during the study period was 73.6%, as compared to 87.64% in the general population in China. Patients who were currently working, had received other vaccines in the past, and had had no adverse reactions to other vaccines, showed a higher rate of COVID-19 vaccination. Patients believing that the vaccination of family members and colleagues had a positive impact on their decision to get vaccinated, were more likely to get the COVID-19 vaccines. The COVID-19 vaccination rate was lower in those with poorly monitored asthma and those using biologic therapies. The adverse effects of COVID-19 vaccines in asthmatic patients were similar to those in the general population. CONCLUSION: The COVID-19 vaccination rate in asthmatic patients was lower than the general population in China. Active measures should be taken to control asthma and increase vaccination rates in these patients.

COVID-19 Control in Community Hospitals: Experience From Four Community Hospitals in Beijing, China.

By September 20, 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been pandemic in 237 countries and regions, resulting in 228,506,698 confirmed cases and 4,692,361 deaths. At the same time, a total of 1123 cases of COVID-19 had been confirmed in Beijing, China. Peking University Shougang Hospital has 4 community hospitals with 174 staff members, covering 230,000 residents in Shijingshan district, Beijing. The community hospitals were the basic units of China's healthcare system for public health services, as the main battlefield for screening and controlling of COVID-19. We reported our experience about the prevention of SARS-CoV-2. We suggest that community hospitals should change their process for admitting patients. While the screening of suspected cases of COVID-19 is vital, patients with suspected infections should be isolated immediately.

The Current Status of Vaccine Uptake and the Impact of COVID-19 on Intention to Vaccination in Patients with COPD in Beijing.

Background: SARS-CoV-2 tends to cause more severe disease in patients with COPD once they are infected. We aimed to investigate the rates of influenza, pneumococcal and COVID-19 vaccination uptake in patients with COPD and to determine whether the COVID-19 pandemic and widespread vaccination against COVID-19 had any impact on the intention to accept influenza vaccines in these patients. Methods: We conducted a multi-center and cross-sectional survey in seven tertiary hospitals in Beijing and consecutively recruited outpatients with COPD from June 1st to July 30th, 2021. The survey included patient's clinical characteristics, uptake of influenza, pneumococcal and COVID-19 vaccination, vaccine knowledge, attitude towards vaccines, and the change of intention to receive influenza vaccination after COVID-19 epidemic and COVID-19 vaccination in Beijing. Results: A total of 264 patients were enrolled. The rate of COVID-19 vaccination during the study period was 39.0%. The rates of influenza vaccination in the past season and pneumococcal vaccination in the past year were 22.7% and 5.7%, respectively. Of the patients who had not received COVID-19 vaccination (n = 161), only 16.2% reported that COVID-19 vaccination was recommended by clinicians, while 23.5% had no knowledge regarding COVID-19 vaccination. About 51.1% of the patients reported that their intention to receive influenza vaccination was influenced by the COVID-19 pandemic. COVID-19 vaccination was independently associated with a positive change in intention to receive influenza vaccination. Conclusion: The coverage rate of COVID-19 vaccination among patients with COPD in Beijing was 39.0%, and that of influenza and pneumococcal vaccination was very low. The COVID-19 pandemic and the COVID-19 vaccination campaign showed a significant, positive impact on patients with COPD in terms of influenza vaccination. Improving awareness of the effectiveness and safety of vaccines among both healthcare professionals and patients could increase vaccination coverage in patients with COPD.

Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a systemic condition that is too complex to be assessed by lung function alone. Metabolomics has the potential to help understand the mechanistic underpinnings that contribute to COPD pathogenesis. Since blood metabolomics may be affected by sex and body mass index (BMI), the aim of this study was to determine the metabolomic variability in male smokers with and without COPD who have a narrow BMI range. Methods: We compared the quantitative proton nuclear magnetic resonance acquired serum metabolomics of a male Chinese Han population of non-smokers without COPD, and smokers with and without COPD. We also assessed the impact of smoking status on metabolite concentrations and the associations between metabolite concentrations and inflammatory markers such as serum interleukin-6 and histamine, and blood cell differential (%). Metabolomics data were log-transformed and auto-scaled for parametric statistical analysis. Mean normalized metabolite concentration values and continuous demographic variables were compared by Student's t-test with Welch correction or ANOVA with post-hoc Tukey's test, as applicable; t-test p-values for metabolomics data were corrected for false discovery rate (FDR). A Pearson association matrix was built to evaluate the relationship between metabolite concentrations, clinical parameters and markers of inflammation. Results: Twenty-eight metabolites were identified and quantified. Creatine, glycine, histidine, and threonine concentrations were reduced in COPD patients compared to non-COPD smokers (FDR ≤15%). Concentrations of these metabolites were inversely correlated with interleukin-6 levels. COPD patients had overall dampening of metabolite concentrations including energy-related metabolic pathways such as creatine metabolism. They also had higher histamine levels and percent basophils compared to smokers without COPD. Conclusion: COPD is associated with alterations in the serum metabolome, including a disruption in the histidine-histamine and creatine metabolic pathways. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in COPD.Trial registration www.clinicaltrials.gov, NCT03310177.

Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.

Although broad knowledge of influenza viral pneumonia has been established, the significance of non-influenza respiratory viruses in community-acquired pneumonia (CAP) and their impact on clinical outcomes remains unclear, especially in the non-immunocompromised adult population.Hospitalised immunocompetent patients with CAP were prospectively recruited from 34 hospitals in mainland China. Respiratory viruses were detected by molecular methods. Comparisons were conducted between influenza and non-influenza viral infection groups.In total, 915 out of 2336 adult patients with viral infection were enrolled in the analysis, with influenza virus (28.4%) the most frequently detected virus, followed by respiratory syncytial virus (3.6%), adenovirus (3.3%), human coronavirus (3.0%), parainfluenza virus (2.2%), human rhinovirus (1.8%) and human metapneumovirus (1.5%). Non-influenza viral infections accounted for 27.4% of viral pneumonia. Consolidation was more frequently observed in patients with adenovirus infection. The occurrence of complications such as sepsis (40.1% versus 39.6%; p=0.890) and hypoxaemia (40.1% versus 37.2%; p=0.449) during hospitalisation in the influenza viral infection group did not differ from that of the non-influenza viral infection group. Compared with influenza virus infection, the multivariable adjusted odds ratios of CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) ≥3, arterial oxygen tension/inspiratory oxygen fraction <200 mmHg, and occurrence of sepsis and hypoxaemia for non-influenza respiratory virus infection were 0.87 (95% CI 0.26-2.84), 0.72 (95% CI 0.26-1.98), 1.00 (95% CI 0.63-1.58) and 1.05 (95% CI 0.66-1.65), respectively. The hazard ratio of 90-day mortality was 0.51 (95% CI 0.13-1.91).The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza respiratory viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza respiratory viruses.

A prospective study of salvational intervention with ICS/LABA for reducing chronic obstructive pulmonary disease exacerbation under severe air pollution (SIRCAP) in Beijing: protocol of a multi-center randomized controlled trial.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality all over the world. Acute exacerbation of COPD (AECOPD) not only accelerates the progression of disease, but also causes hospital administration and death events. Epidemiologic studies have shown air pollution is a high risk factor of AECOPD. However, there are rare technics or treatment strategies recommended to reduce severe air pollution related AECOPD. METHODS: This is a multi-center, prospective, randomized and standard treatment parallel control clinical trial. Seven hundred sixty-four stable COPD patients in group B, C and D according to GOLD 2017 will be recruited and equally divided into two parallel groups, salvational intervention (SI group) and control group (CT group). Original treatments for participants include tiotropium (18µg once q.d), budesonide/formoterol (160µg/4.5µg once or twice b.i.d) or budesonide/formoterol (160µg/4.5µg once or twice b.i.d) with tiotropium (18µg once q.d). The savational intervention for SI group is routine treatment plus budesonide/formoterol (160µg/4.5µg once b.i.d) from the first day after severe air pollution (air quality index, AQI ≥200) to the third day after AQI < 200. CT group will maintain the original treatment. The intervention will last for 2 years. Primary outcome is the frequency of AECOPD per year and the secondary outcomes include the incidence of unplanned outpatient visits, emergency visits, hospitalization, medical cost and mortality associated with AECOPD per year. DISCUSSION: The salvational intervention is a novel strategy for COPD management under severe air pollution. Results of the present study will provide reference information to guide clinical practice in reducing the air pollution related exacerbation of COPD. TRIAL REGISTRATION: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03083067 ) in 17 March, 2017.

Is hypercapnia associated with poor prognosis in chronic obstructive pulmonary disease? A long-term follow-up cohort study.

OBJECTIVES: To assess whether hypercapnia may predict the prognosis in chronic obstructive pulmonary disease (COPD). DESIGN: Prospective cohort study comparing the survival of patients with COPD and normocapnia to those with chronic hypercapnia. SETTING: Patients with consecutive COPD were enrolled between 1 May 1993 and 31 October 2006 at two medical centres. Follow-up was censored on 31 October 2011. PARTICIPANTS: A total of 275 patients with stable COPD and aged 40-85 years were enrolled. Diagnosis of hypercapnia was confirmed by blood gas analysis. Patients with near-terminal illness or comorbidities that affect PaCO2 (obstructive sleep apnoea, obesity-related hypoventilation, or neuromuscular disease) were excluded. The outcome of 98 patients with normocapnia and 177 with chronic hypercapnia was analysed. OUTCOME MEASURES: Overall survival. RESULTS: Median survival was longer in patients with normocapnia than in those with hypercapnia (6.5 vs 5.0 years, p=0.016). Multivariate COX regression analysis indicated that age (HR=1.043, 95% CI 1.012 to 1.076), Charlson Index, which is a measure of comorbidity (HR=1.172, 95% CI 1.067 to 1.288), use of medication (HR=0.565, 95% CI 0.379 to 0.842), body mass index (BMI) (HR=0.922, 95% CI 0.883 to 0.963), PaCO2 (HR=1.026, 95% CI 1.011 to 1.042), Cor pulmonale (HR=2.164, 95% CI 1.557 to 3.006), non-invasive positive-pressure ventilation (NPPV) (HR=0.615, 95% CI 0.429 to 0.881) and per cent of forced expiratory volume in 1 s (FEV1%) (HR=0.979, 95% CI 0.967 to 0.991), were independent risk factors for mortality. CONCLUSIONS: Increased age, Charlson Index, chronic hypercapnia and Cor pulmonale, and decreased FEV1%, use of medication, BMI and NPPV, were associated with a poor prognosis in patients with COPD.

Predictors of exacerbation frequency in chronic obstructive pulmonary disease.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are sporadic, acute worsening of symptoms. Identifying predictors of exacerbation frequency may facilitate medical interventions that reduce exacerbation frequency and severity. The objective of this study was to determine predictors of exacerbation frequency and mortality. METHODS: A total of 227 COPD patients were enrolled in a prospective clinical study between January 2000 and December 2011. Reported exacerbations were recorded for the year preceding enrollment and annually thereafter, and patients were grouped by median annual exacerbation frequency into those experiencing infrequent exacerbations (less than one exacerbation annually) and frequent exacerbations (one or more exacerbation annually). Patients experiencing frequent exacerbations were further divided into those experiencing moderately frequent exacerbations (fewer than two exacerbations per year) and severely frequent exacerbations (two or more exacerbations per year). The rate of clinical relapse and survival was recorded over a 10-year period. The mean of follow-up time was 5.15 years per patient. RESULTS: For patients experiencing infrequent, moderately frequent, and severely frequent exacerbations, median exacerbations in the year preceding enrollment were 0.0, 0.5, 1.0, respectively, and more frequent exacerbations correlated with lower baseline forced expiratory volume in one second (FEV1) (0.81 L, 0.75 L, and 0.66 L, respectively), higher comorbidity (70.7%, 75.0%, and 89.4%, respectively), and greater NPPV use during hospitalization (16.4%, 35.9% and 51.1%, respectively). FEV1 declined and mortality increased with increasing exacerbation frequency. CONCLUSIONS: Exacerbation frequency can be used to generate discreet patient subpopulations, supporting the hypothesis that multiple COPD phenotypes exist and can be used in patient risk stratification.

[The clinical application of bi-level positive airway pressure noninvasive ventilator for home mechanical ventilation via tracheostomy in patients with amyotrophic lateral sclerosis].

OBJECTIVE: To study the feasibility of the bi-level positive airway pressure (BiPAP) non-invasive ventilator used in home mechanical ventilation for long-term tracheostomy-mechanical ventilation (TMV) in patients with amyotrophic lateral sclerosis (ALS). METHODS: Sixteen patients (12 men and 4 women, mean age 59 years) with ALS were selected for this study at Respiratory Department of the Shougang Hospital, Peking University from January 2002 to March 2008. After the disease had been controlled by anti-infective therapy and comprehensive treatment, the patients received TMV, through the improved ("Xiang's" connection) non-invasive BiPAP ventilator connected with tracheotomy tube, and on-going home mechanical ventilation (HMV). The blood gas was evaluated during invasive ventilation and non-invasive ventilation before discharge. Family members of the patients were trained for the use of non-invasive ventilators. The use of ventilators and the patients' condition were regularly followed and the survival rate calculated. Statistical analysis was carried out by using one-way ANOVA. RESULTS: There was no statistical difference in the blood gas before the use of non-invasive ventilator, 2 h and 1 d after the use of non-invasive ventilator, and before discharge, PaCO2 [(36+/-10), (42+/-11), (41+/-10), (42+/-11) mm Hg (1 mm Hg=0.133 kPa)], PaO2 [(84+/-11), (81+/-12), (87+/-14), (86+/-12) mm Hg], SaO2 [(96.7+/-1.3)%, (96.5+/-0.8)%, (96.8+/-1.2)%, (96.5+/-1.0)%] respectively, (F=1.21, 0.59, 0.97, 0.41, respectively, all P>0.05). All patients had no complaint of uncomfortable use, no intolerance to ventilators, and no ventilator breakdown. Fifteen patients were alive at the end of the follow-up (July 31, 2008). The mean time of using non-invasive ventilator was 39 months (range 4 to 66 months). CONCLUSION: For ALS patients who need long-term ventilation support, the use of BiPAP non-invasive ventilators is a safe and effective alternative for invasive ventilators.

[The efficacy and safety of long term home noninvasive positive pressure ventilation in patients with stable severe chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the long term efficacy and safety of long term home noninvasive positive pressure ventilation (HNPPV) in stable hypercapnic patients with chronic obstructive pulmonary disease (COPD). METHODS: Forty patients with stable severe COPD [arterial PaCO2>or=55 mm Hg (1 mm Hg=0.133 kPa)] after hospital discharge were divided into 2 groups: the HNPPV group (n=20) with conventional therapy and HNPPV, and the control group (n=20) with conventional therapy only. Parameters before and after 2 year follow-up observation were compared, which included dyspnea grade, scale for accessory muscle use, scoring for emotional disorders, lung function test, arterial blood gases, 6-min walking distance (6MWD), mean pulmonary arterial pressure (mPAP) by electrocardiography, mortality and hospitalization rates. RESULTS: The age, gender, height, weight, dyspnea grade, scale for accessory muscle use, anxiety scores, depression scores, 6MWD, mPAP, arterial PaCO2 and PaO2, FVC, FEV1, and hospitalization rates of the 2 groups on admission were similar (t values were 1.08, 1.15, 1.20, 1.09, 0.86, 0.54, 0.00, 0.00, 0.43, 0.96, 0.76, 0.38, 0.26, 0.24 and 0.87 respectively, all P>0.05). The mortality was reduced slightly by HNPPV but with no statistically significant difference (3/20 and 8/20, respectively, chi2=3.27, P>0.05). After 2 years, the difference of the dyspnea grade, scale for accessory muscle use, anxiety scores, depression scores, arterial PaCO2 and PaO2, 6MWD, mean pulmonary artery pressure, and hospitalization rates in the HNPPV group [2.4+/-0.5, 2.6+/-0.6, 6.9+/-2.1, 6.1+/-1.6, (49.5+/-2.2) mm Hg, (60.8+/-4.7) mm Hg, (213+/-45) m, (30.3+/-2.2) mm Hg, (1.4+/-0.4) times/year] was statistically significant compared to the control group [3.9+/-0.3, 4.8+/-0.4, 11.2+/-2.6, 11.6+/-2.1, (61.5+/-2.3) mm Hg, (52.8+/-2.4) mm Hg, (127+/-23) m, (36.4+/-2.3) mm Hg, (3.9+/-0.3) times/year] (t values were 9.53, 10.83, 4.92, 7.83, 14.07, 5.41, 6.07, 4.81 and 10.22 respectively, all P<0.01). CONCLUSION: Long-term use of home noninvasive positive ventilation in patients with stable severe COPD is effective and safe.

[Long-term follow-up study of moderate chronic obstructive pulmonary disease in elderly patients].

OBJECTIVE: To investigate the prognosis of moderate chronic obstructive pulmonary disease (COPD) in the elderly patients, and to evaluate the factors for long term survival. METHODS: From May 1993, a prospective cohort study was carried out, in which 191 elderly patients with moderate COPD were recruited in Shougang communities, Shijingshan District, Beijing. The general health state, arterial blood gas, pulmonary function test, electrocardiograph, chest X-ray and 6-minute-walk test (6MWT) were recorded. The patients were followed for 12 years. Univariate analysis of survival rate was performed by Kaplan-Meier method. The significance test was done by Log-rank method, and the baseline factors were analyzed using the COX regression model multiplicity. RESULTS: During the 12 years of follow-up, 10 patients were lost because of migration. Twenty-six patients died of non-COPD diseases, while 52 died of COPD. The survival rate was 81.7% (156/191) in 5 years, and 56.9% (103/181) in 12 years. The result with COX multiplicity showed that the important factors for prognosis of the patients were body mass index [BMI, relative risk (RR) = 0.916, 95% confidence intervals (95% CI) = 0.841 - 0.996], forced expired volume in one second (FEV(1), RR = 0.999, 95% CI = 0.998 - 1.000), arterial partial pressure of oxygen (PaO(2), RR = 0.929, 95% CI = 0.892 - 0.967), 6MWT (RR = 0.997, 95% CI = 0.995 - 1.000) and P pulmonale of ECG (RR = 4.081, 95% CI = 1.567 - 10.624). CONCLUSION: The important factors for prognosis of moderate COPD in elderly patients included BMI, FEV(1), PaO(2), 6MWT and P pulmonale in ECG.