Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Effect of continuing the use of renin-angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis.

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population. METHODS: We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes. RESULTS: Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28-0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5-0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46-0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98). CONCLUSION: Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022.

The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China): Protocol of a prospective multicenter observational study.

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.

Metagenomic Next-Generation Sequencing for Diagnosing Infections in Lung Transplant Recipients: A Retrospective Study.

Background: Accurate identification of pathogens is essential for the diagnosis and control of infections. We aimed to compare the diagnostic performance of metagenomic next-generation sequencing (mNGS) and conventional detection methods (CDM) in lung transplant recipients (LTRs). Methods: We retrospectively analyzed 107 LTRs with suspected infection of pulmonary, blood, central nervous system or chest wall between March 2018 and November 2020. Bronchoalveolar lavage fluid and other body fluids were subject to pathogen detection by both mNGS and CDM. Results: Of the 163 specimens, 84 (51.5%) tested positive for both mNGS and culture, 19 (11.7%) of which were completely consistent, 44 (27.0%) were partially congruent, and 21 (12.9%) were discordant (kappa = .215; p = .001). Compared with CDM, mNGS detected a higher diversity of pathogens. Moreover, the turn-around time was significantly shorter for mNGS compared with culture (2.7 ± .4 vs. 5.5 ± 1.6 days, p < .001). As an auxiliary method, treatment strategies were adjusted according to mNGS findings in 31 cases (29.0%), including eight patients with non-infectious diseases, who were finally cured. Conclusion: mNGS can identify pathogens with a shorter turn-around time and therefore provide a more accurate and timely diagnostic information to ascertaining pulmonary infections. mNGS might have a role in differentiating infectious from non-infectious lung diseases in LTRs.

Sporadic Dissemination of tet(X3) and tet(X6) Mediated by Highly Diverse Plasmidomes among Livestock-Associated Acinetobacter.

The emergence of high-level tigecycline resistance mediated by plasmid-borne tet(X) genes greatly threatens the clinical effectiveness of tigecycline. However, the dissemination pattern of plasmid-borne tet(X) genes remains unclear. We here recovered tet(X)-positive Acinetobacter isolates from 684 fecal and environmental samples collected at six livestock farms. Fifteen tet(X)-positive Acinetobacter isolates were identified, mainly including 9 tet(X3)- and 5 tet(X6)-positive Acinetobacter towneri isolates. A clonal dissemination of tet(X3)-positive A. towneri was detected in a swine farm, while the tet(X6)-positive A. towneri isolates mainly disseminated sporadically in the same farm. A tet(X3)-carrying plasmid (pAT181) was self-transmissible from a tigecycline-susceptible A. towneri strain to Acinetobacter baumannii strain ATCC 17978, causing 64- to 512-fold increases in the MIC values of tetracyclines (including tigecycline). Worrisomely, pAT181 was stably maintained and increased the growth rate of strain ATCC 17978. Further identification of tet(X) genes in 10,680 Acinetobacter genomes retrieved from GenBank revealed that tet(X3) (n = 249), tet(X5)-like (n = 61), and tet(X6) (n = 53) were the prevalent alleles mainly carried by four species, and most of them were livestock associated. Phylogenetic analysis showed that most of the tet(X3)- and tet(X6)-positive isolates disseminated sporadically. The structures of the tet(X3), and tet(X6) plasmidomes were highly diverse, and no epidemic plasmids were detected. However, cross-species and cross-region transmissions of tet(X3) might have been mediated by several plasmids in a small proportion of strains. Our study implies that horizontal plasmid transfer may be insignificant for the current dissemination of tet(X3) and tet(X6) in Acinetobacter strains. Continuous surveillance for tet(X) genes in the context of One Health is necessary to prevent them from transmitting to humans. IMPORTANCE Recently identified plasmid-borne tet(X) genes have greatly challenged the efficiency of tigecycline, a last-resort antibiotic for severe infection, while the dissemination pattern of the plasmid-borne tet(X) genes remains unclear. In this study, we identified a clonal dissemination of tet(X3)-positive A. towneri isolates on a swine farm, while the tet(X6)-positive A. towneri strains mainly disseminated sporadically on the same farm. Of more concern, a tet(X3)-carrying plasmid was found to be self-transmissible, resulting in enhanced tigecycline resistance and growth rate of the recipient. Further exploration of a global data set of tet(X)-positive Acinetobacter genomes retrieved from GenBank revealed that most of the tet(X3)- and tet(X6)-positive isolates shared a highly distant relationship, and the structures of tet(X3) and tet(X6) plasmidomes exhibited high mosaicism. Notably, some of the isolates belong to Acinetobacter species that are opportunistic pathogens and have been identified as sources of nosocomial infections, raising concerns about transmission to humans in the future. Our study evidenced the sporadic dissemination of tet(X3) and tet(X6) in Acinetobacter strains and the necessity of continuous surveillance for tet(X) genes in the context of One Health.

Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD.

OBJECTIVES: To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease. METHODS: This retrospective study included anti-MDA5 antibody positive ILD subjects in the First Affiliated Hospital of Guangzhou Medical University from November 2017 to March 2019. Independent predictors for 180-day mortality were measured by Cox regression analysis. Patients were divided into 3 groups: Group 1 (non-cyclophosphamide (CTX)/RTX) (n = 10), Group 2 (CTX only) (n = 19) and Group 3 (RTX with/without CTX) (n = 11). The 180-day mortality was compared among 3 groups with Kaplan-Meier analysis. Post-RTX serological parameters as well as adverse events were evaluated. RESULTS: Forty patients were included with the mean age of 51.3 years. Elevated IL-10 level and CD4+/8+ ratio were considered as risk factors of 180-day mortality. Kaplan-Meier analysis showed a trend toward decrease, albeit non-significant, in 180-day mortality in Group 3 (P = 0.26). The administration of 100 mg RTX brought down B cell within 7 days that lasted for 180 days. There were 7 and 6 infection events observed within 2 months of CTX/RTX treatment in Group 2 and 3, with 5 and 2 fatal cases respectively. Cytomegalovirus infection accounted for half infection events in Group 3. CONCLUSION: We found a pronounced and prolonged B cell depletion following 100 mg RTX infusion and RTX add-on may be effective in anti-MDA5 positive ILD patients. However, infection, especially opportunistic infection, should be concerned during the treatment.

El papel de las bacterias y los virus en la exacerbación de bronquiectasia: un estudio prospectivo / The roles of bacteria and viruses in bronchiectasis exacerbation: a prospective study

Contexto: Las exacerbaciones son eventos cruciales durante la progresión de la bronquiectasia. OBJETIVOS: Analizar las asociaciones entre el aislamiento de bacterias, virus y virus y bacterias juntas y las exacerbaciones de las bronquiectasias. MÉTODOS: En este estudio prospectivo se incluyó a 108 pacientes a los que se siguió cada 3-6 meses y al comienzo de las exacerbaciones entre marzo de 2017 y noviembre de 2018. La muestra de esputo espontáneo se dividió para la detección de bacterias (cultivo de rutina) y virus (reacción en cadena de la polimerasa cuantitativa). Se evaluaron los síntomas y la función pulmonar durante las exacerbaciones. RESULTADOS: La mediana de la tasa de exacerbación fue de 2,0 (rango intercuartil: 1,0-2,5) por paciente/año. En cualquier visita, los aislamientos de virus (V+) tuvieron lugar con mayor frecuencia durante el inicio de las exacerbaciones (odds ratio [OR]: 3,28; intervalo de confianza del 95% [IC 95%]: 1,76-6,12), al igual que el aislamiento de nuevas bacterias (NB+) (OR: 2,52; IC 95%: 1,35-4,71) y los aislamientos de bacterias y virus juntos (OR: 2,24; IC 95%: 1,11-4,55). Mientras que la coriza parecía más común en las exacerbaciones con V+ que en las exacerbaciones sin aislamientos de patógenos y en aquellas con NB+, los síntomas de las vías respiratorias inferiores fueron más graves en las exacerbaciones con NB+ (p < 0,05). Los niveles de interleucina-1β en el esputo fueron más altos en las exacerbaciones con NB+ que en las exacerbaciones sin aislamiento de patógenos, y aquellas con V+ (ambos p < 0,05). De manera significativa, más síntomas de coriza se correlacionaron con aislamientos de bacterias y virus juntos durante las exacerbaciones (p = 0,019). Comparados con los V+ en solitario, los aislamientos de bacterias con y sin virus tienden a producir síntomas más graves en las vías respiratorias inferiores, pero no alteran los niveles de citocinas en el esputo durante las exacerbaciones. CONCLUSIONES: Los aislamientos de virus, el aislamiento de nuevas bacterias y el aislamiento de bacterias y virus juntos están asociados a las exacerbaciones de las bronquiectasias. Los síntomas de las exacerbaciones pueden proporcionar información a los médicos sobre los posibles patógenos responsables

BACKGROUND: Exacerbations are crucial events during bronchiectasis progression. OBJECTIVES: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. METHODS: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. RESULTS: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P < .05). Sputum interleukin-1β levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P < .05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P = .019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. CONCLUSIONS: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens

The Role of Epstein-Barr Virus in Adults With Bronchiectasis: A Prospective Cohort Study.

BACKGROUND: Epstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression. METHODS: We collected induced sputum in healthy controls and spontaneous sputum at 3-6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction. RESULTS: We collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P = .001), but not viral loads (mean log10 load, 4.45 vs 4.76; P = .266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P = .393) nor load (mean log10 load, 4.34 vs 4.45; P = .580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1ß (P = .002), CXC motif chemokine-8 (P = .008), and tumor necrosis factor-α levels (P = .005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P < .05) than those without. Detection of EBV DNA was unrelated to influenza virus and opportunistic bacteria (all P > .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous. CONCLUSIONS: Patients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression.

The Interactions of Airway Bacterial and Fungal Communities in Clinically Stable Asthma.

Dysbiotic airway microbiota play important roles in the inflammatory progression of asthma, and exploration of airway microbial interactions further elucidates asthma pathogenesis. However, little is known regarding the airway bacterial-fungal interactions in asthma patients. We conducted a cross-sectional survey of the sputum bacterial and fungal microbiota from 116 clinically stable asthma patients and 29 healthy controls using 16S rRNA gene and ITS1 sequencing. Compared with healthy individuals, asthma patients exhibited a significantly altered microbiota and increased bacterial and fungal alpha diversities in the airway. Microbial genera Moraxella, Capnocytophaga, and Ralstonia (bacteria) and Schizophyllum, Candida, and Phialemoniopsis (fungi) were more abundant in the asthma airways, while Rothia, Veillonella and Leptotrichia (bacteria) and Meyerozyma (fungus) were increased in healthy controls. The Moraxellaceae family and their genus Moraxella were significantly enriched in asthma patients compared with healthy controls (80.5-fold, P = 0.007 and 314.7-fold, P = 0.027, respectively). Moreover, Moraxellaceae, along with Schizophyllum, Candida, and Aspergillus (fungal genera), were positively associated with fungal alpha diversity. Correlation networks revealed 3 fungal genera (Schizophyllum, Candida, and Aspergillus) as important airway microbes in asthma that showed positive correlations with each other and multiple co-exclusions with other common microbiota. Moraxellaceae members were positively associated with asthma-enriched fungal taxa but negatively related to several healthy-enriched bacterial taxa. Collectively, our findings revealed an altered microbiota and complex microbial interactions in the airways of asthma patients. The Moraxellaceae family and their genus Moraxella, along with 3 important fungal taxa, showed significant interactions with the airway microbiota, providing potential insights into the novel pathogenic mechanisms of asthma.

The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study.

BACKGROUND: Exacerbations are crucial events during bronchiectasis progression. OBJECTIVES: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. METHODS: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. RESULTS: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P<.05). Sputum interleukin-1ß levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P<.05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P=.019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. CONCLUSIONS: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens.

Scutellarin protects against myocardial ischemia-reperfusion injury by suppressing NLRP3 inflammasome activation.

BACKGROUND: Activation of NLRP3 inflammasome plays a key role in cardiac dysfunction for acute myocardial ischemia-reperfusion injury. Scutellarin (Scu) is a flavonoid purified from Erigeron breviscapus. Whether Scu has any influence on the activation of NLRP3 inflammasome in cardiomyocytes remains unknown. PURPOSE: We aimed to examine the therapeutic effect of Scu on cardiomyocyte ischemia-reperfusion (I/R) injury and its effect on NLRP3 inflammasome in rats with acute myocardial I/R injury and anoxia/reoxygenation (A/R)-induced H9c2 injuries. METHODS: Heart injuries were induced through 30 min of ischemia followed by 24 h of reperfusion. Scu was intraperitoneally administered 15 min before vascular ligation. Effects of Scu on cardiac injury were detected by echocardiograms, TTC staining, and histological and immunohistochemical analyses. The effects of Scu on biochemical parameters were analyzed. H9c2 cells were pretreated with different concentrations of Scu for 6 h before A/R exposure. Afterward, cell viability, LDH release, and Hoechst 33342 and peromide iodine double staining were determined. Western blot analyses of proteins, including those involved in autophagy, NLRP3, mTOR complex 1 (mTORC1), and Akt signaling, were conducted. RESULTS: In vivo study revealed that Scu improved diastolic dysfunction, ameliorated myocardium structure abnormality, inhibited myocyte apoptosis and inflammatory response, and promoted autophagy. Scu reduced NLRP3 inflammasome activation, inhibited mTORC1 activity, and increased Akt phosphorylation. In vitro investigation showed the same results. The Scu-mediated NLRP3 inflammasome and mTORC1 inhibition and cardioprotection were abolished through the genetic silencing of Akt by siRNA. CONCLUSIONS: The cardioprotective effect of Scu was achieved through its anti-inflammatory effect. It suppressed the activation of NLRP3 inflammasome. In addition, inflammasome restriction by Scu was dependent on Akt activation and mTORC1 inhibition.

The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study.

Background: Exacerbations are crucial events during bronchiectasis progression. Objectives: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. Methods: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. Results: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P < .05). Sputum interleukin-1ß levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P < .05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P = .019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. Conclusions: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens.

Contexto: Las exacerbaciones son eventos cruciales durante la progresión de la bronquiectasia. Objetivos: Analizar las asociaciones entre el aislamiento de bacterias, virus y virus y bacterias juntas y las exacerbaciones de las bronquiectasias. Métodos: En este estudio prospectivo se incluyó a 108 pacientes a los que se siguió cada 3-6 meses y al comienzo de las exacerbaciones entre marzo de 2017 y noviembre de 2018. La muestra de esputo espontáneo se dividió para la detección de bacterias (cultivo de rutina) y virus (reacción en cadena de la polimerasa cuantitativa). Se evaluaron los síntomas y la función pulmonar durante las exacerbaciones. Resultados: La mediana de la tasa de exacerbación fue de 2,0 (rango intercuartil: 1,0-2,5) por paciente/año. En cualquier visita, los aislamientos de virus (V+) tuvieron lugar con mayor frecuencia durante el inicio de las exacerbaciones (odds ratio [OR]: 3,28; intervalo de confianza del 95% [IC 95%]: 1,76-6,12), al igual que el aislamiento de nuevas bacterias (NB+) (OR: 2,52; IC 95%: 1,35-4,71) y los aislamientos de bacterias y virus juntos (OR: 2,24; IC 95%: 1,11-4,55). Mientras que la coriza parecía más común en las exacerbaciones con V+ que en las exacerbaciones sin aislamientos de patógenos y en aquellas con NB+, los síntomas de las vías respiratorias inferiores fueron más graves en las exacerbaciones con NB+ (p < 0,05). Los niveles de interleucina-1ß en el esputo fueron más altos en las exacerbaciones con NB+ que en las exacerbaciones sin aislamiento de patógenos, y aquellas con V+ (ambos p < 0,05). De manera significativa, más síntomas de coriza se correlacionaron con aislamientos de bacterias y virus juntos durante las exacerbaciones (p = 0,019). Comparados con los V+ en solitario, los aislamientos de bacterias con y sin virus tienden a producir síntomas más graves en las vías respiratorias inferiores, pero no alteran los niveles de citocinas en el esputo durante las exacerbaciones. Conclusiones: Los aislamientos de virus, el aislamiento de nuevas bacterias y el aislamiento de bacterias y virus juntos están asociados a las exacerbaciones de las bronquiectasias. Los síntomas de las exacerbaciones pueden proporcionar información a los médicos sobre los posibles patógenos responsables.

Sputum Exosomal microRNAs Profiling Reveals Critical Pathways Modulated By Pseudomonas aeruginosa Colonization In Bronchiectasis.

Background: Pseudomonas aeruginosa (PA) colonization confers poor prognosis in bronchiectasis. However, the biomarkers and biological pathways underlying these associations are unclear. Objective: To identify the roles of PA colonization in bronchiectasis by exploring for sputum exosomal microRNA profiles. Methods: We enrolled 98 patients with clinically stable bronchiectasis and 17 healthy subjects. Sputum was split for bacterial culture and exosomal microRNA sequencing, followed by validation with quantitative polymerase chain reaction. Bronchiectasis patients were stratified into PA and non-PA colonization groups based on sputum culture findings. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to explore biological pathways corresponding to the differentially expressed microRNAs (DEMs) associated with PA colonization. Results: Eighty-two bronchiectasis patients and 9 healthy subjects yielded sufficient sputum that passed quality control. We identified 10 overlap DEMs for the comparison between bronchiectasis patients and healthy subjects, and between PA and non-PA colonization group. Both miR-92b-5p and miR-223-3p could discriminate PA colonization (C-statistic >0.60) and independently correlated with PA colonization in multiple linear regression analysis. The differential expression of miR-92b-5p was validated by quantitative polymerase chain reaction (P<0.05), whereas the differential expression of miR-223 trended towards statistical significance (P=0.06). These DEMs, whose expression levels correlated significantly with sputum inflammatory biomarkers (interleukin-1ß and interleukin-8) level, were implicated in the modulation of the nuclear factor-κB, phosphatidylinositol and longevity regulation pathways. Conclusion: Sputum exosomal microRNAs are implicated in PA colonization in bronchiectasis, highlighting candidate targets for therapeutic interventions to mitigate the adverse impacts conferred by PA colonization.

[Research methods and applications progress on spectrum-effect relationships in study of traditional Chinese medicine].

The application of chemical fingerprint to evaluate the quality of traditional Chinese medicine has been widely accepted and used in many countries. However,only by analyzing the type and content of its chemical components to evaluate the quality of traditional Chinese medicines,the gold standard of quality evaluation by evaluating pharmacodynamic effects is ignored. The study of Chinese medicinal spectrum-effect relationships combining the chemical composition with the pharmacodynamic activity of traditional Chinese medicine,which can evaluate the quality of traditional Chinese medicine from more comprehensive and different angles,has been applied in many fields of traditional Chinese medicine research. This paper mainly summarizes the research methods of the Chinese medicinal spectrum-effect relationships and its application in the field of traditional Chinese medicine study,and provides reference for the research,development and application of the Chinese medicinal spectrum-effect relationships.

Improving mass spectrometry analysis of protein structures with arginine-selective chemical cross-linkers.

Chemical cross-linking of proteins coupled with mass spectrometry analysis (CXMS) is widely used to study protein-protein interactions (PPI), protein structures, and even protein dynamics. However, structural information provided by CXMS is still limited, partly because most CXMS experiments use lysine-lysine (K-K) cross-linkers. Although superb in selectivity and reactivity, they are ineffective for lysine deficient regions. Herein, we develop aromatic glyoxal cross-linkers (ArGOs) for arginine-arginine (R-R) cross-linking and the lysine-arginine (K-R) cross-linker KArGO. The R-R or K-R cross-links generated by ArGO or KArGO fit well with protein crystal structures and provide information not attainable by K-K cross-links. KArGO, in particular, is highly valuable for CXMS, with robust performance on a variety of samples including a kinase and two multi-protein complexes. In the case of the CNGP complex, KArGO cross-links covered as much of the PPI interface as R-R and K-K cross-links combined and improved the accuracy of Rosetta docking substantially.

The Role of Follow-up Evaluation in the Diagnostic Algorithm of Idiopathic Interstitial Pneumonia: A Retrospective Study.

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.

Health Perception and Behaviors in Adults With Bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic debilitating suppurative disease that significantly impacts quality of life. Clinical outcomes like exacerbations, are usually physician centered; however, the patients' experience, health-related behaviors, and expectations have frequently been neglected. In addition, patients' health perceptions may be influenced by their culture. OBJECTIVE: To determine the health perception and behavior in adults with bronchiectasis. METHODS: We performed semi-directive interviews, which were audiotaped, with 60 adults with bronchiectasis between April 2016 and December 2016. Our interview focused on issues related to symptom perception, access to health-care resources and patient-physician communication, medication adherence, outcomes and expectations, quality of life, and social relationships. RESULTS: The subjects with bronchiectasis developed varying patterns of symptom perception (ranging from highly distressing to barely disturbing) and had conflicting opinions on whether and when they should seek health-care services (ranging from active consultations to being totally passive or resistant to seek health care). We observed certain discrepancies between symptom perception and health-related behaviors. Overall, medication adherence was suboptimal, but the subjects were willing to participate in clinical trials and receive complementary alternative medications despite concerns regarding adverse effects of prolonged treatment. There were concerns about the adverse effects of bronchiectasis on fertility and infectiousness to others, although most subjects disregarded these issues. CONCLUSIONS: The diverse symptom perception and health-related behaviors highlighted the need for evaluation and intervention in bronchiectasis. These findings will provide rationales for refining future health care through comprehensive (particularly psychological) interventions worldwide.