Long-term associations of PM1 versus PM2.5 and PM10 with asthma and asthma-related respiratory symptoms in the middle-aged and elderly population.

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study.

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

The roles of bacteria and viruses in COPD-Bronchiectasis association: A prospective cohort study.

BACKGROUND: Exacerbations are implicated in bronchiectasis and COPD, which frequently co-exist [COPD-Bronchiectasis association (CBA)]. We aimed to determine the bacterial and viral spectrum at stable-state and exacerbation onset of CBA, and their association with exacerbations and clinical outcomes of CBA as compared with bronchiectasis. METHODS: We prospectively collected spontaneous sputum from adults with CBA, bronchiectasis with (BO) and without airflow obstruction (BNO) for bacterial culture and viral detection at stable-state and exacerbations. RESULTS: We enrolled 76 patients with CBA, 58 with BO, and 138 with BNO (711 stable and 207 exacerbation visits). Bacterial detection rate increased from BNO, CBA to BO at steady-state (P = 0.02), but not at AE onset (P = 0.91). No significant differences in viral detection rate were found among BNO, CBA and BO. Compared with steady-state, viral isolations occurred more frequently at exacerbation in BNO (15.8 % vs 32.1 %, P = 0.001) and CBA (19.5 % vs 30.6 %, P = 0.036) only. In CBA, isolation of viruses, human metapneumovirus and bacteria plus viruses was associated with exacerbation. Repeated detection of Pseudomonas aeruginosa (PA) correlated with higher modified Reiff score (P = 0.032) in CBA but not in BO (P = 0.178). Repeated detection of PA yielded a shorter time to the first exacerbation in CBA [median: 4.3 vs 11.1 months, P = 0.006] but not in BO (median: 8.4 vs 7.6 months, P = 0.47). CONCLUSIONS: Isolation of any viruses, human metapneumovirus and bacterialplus viruses was associated with CBA exacerbations. Repeated detection of PA confers greater impact of future exacerbations on CBA than on BO.

Association between coffee and caffeine intake and risk of COPD: Findings based on NHANES 2007-2012.

BACKGROUND: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. OBJECTIVES: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012. METHODS: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. RESULTS: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. CONCLUSIONS: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms.

Clinical Characteristics and Outcomes of the Phenotypes of COPD-Bronchiectasis Association.

INTRODUCTION: Although COPD may frequently co-exist with bronchiectasis [COPD-bronchiectasis associated (CBA)], little is known regarding the clinical heterogeneity. We aimed to identify the phenotypes and compare the clinical characteristics and prognosis of CBA. METHODS: We conducted a retrospective cohort study involving 2928 bronchiectasis patients, 5158 COPD patients, and 1219 patients with CBA hospitalized between July 2017 and December 2020. We phenotyped CBA with a two-step clustering approach and validated in an independent retrospective cohort with decision-tree algorithms. RESULTS: Compared with patients with COPD or bronchiectasis alone, patients with CBA had significantly longer disease duration, greater lung function impairment, and increased use of intravenous antibiotics during hospitalization. We identified five clusters of CBA. Cluster 1 (N=120, CBA-MS) had predominantly moderate-severe bronchiectasis, Cluster 2 (N=108, CBA-FH) was characterized by frequent hospitalization within the previous year, Cluster 3 (N=163, CBA-BI) had bacterial infection, Cluster 4 (N=143, CBA-NB) had infrequent hospitalization but no bacterial infection, and Cluster 5 (N=113, CBA-NHB) had no hospitalization or bacterial infection in the past year. The decision-tree model predicted the cluster assignment in the validation cohort with 91.8% accuracy. CBA-MS, CBA-BI, and CBA-FH exhibited higher risks of hospital re-admission and intensive care unit admission compared with CBA-NHB during follow-up (all P<0.05). Of the five clusters, CBA-FH conferred the worst clinical prognosis. CONCLUSION: Bronchiectasis severity, recent hospitalizations and sputum culture findings are three defining variables accounting for most heterogeneity of CBA, the characterization of which will help refine personalized clinical management.

SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl- concentration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl- transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl- transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl- concentration ([Cl-]i) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl-]i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

Effects of occupational exposure to dust, gas, vapor and fumes on chronic bronchitis and lung function.

Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide, and therefore the identification of the modifiable risk factors [such as exposure to vapors, gases, dust and fumes (VGDF)] for accelerate disease progression has important significance. Methods: We conducted COPD surveillance in six cities of southern China between 2014 and 2019. We recorded the diagnosis of chronic bronchitis, respiratory symptoms, occupational exposure to VGDF and other covariates by using a structured questionnaire. Logistic regression and multivariate linear regression model were adopted for analysis. We performed sensitivity analyses based on two methods of propensity score (PS) methods to evaluate the robustness of our results. Results: A total of 7,418 participants were included. Cough [odds ratios (ORs): 1.60, 95% confidence interval (CI): 1.22 to 2.08] and phlegm (OR: 1.49, 95% CI: 1.19 to 1.85) correlated significantly with exposure to dust. There was an increased risk of cough (OR: 1.53, 95% CI: 1.11 to 2.07) for occupational exposure to gas/vapor/fume. Dual exposure to dust and gas/vapor/fume was associated with a significantly increased risk of chronic bronchitis (OR: 1.74, 95% CI: 1.20 to 2.52), cough (OR: 1.43, 95% CI: 1.15 to 1.79) and phlegm (OR: 1.49, 95% CI: 1.24 to 1.79). In 5,249 participants with complete data of spirometry, gas/vapor/fume was associated with a decreased ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC) (ß: -1.05, 95% CI: -1.85 to -0.26) and maximal mid-expiratory flow (MMEF) (ß: -0.15, 95% CI: -0.23 to -0.07). Dual exposure to dust and gas/vapor/fume was significantly associated with decreased FEV1/FVC (ß: -0.74, 95% CI: -1.28 to -0.20) and MMEF (ß: -0.06, 95% CI: -0.12 to -0.01). Results of sensitivity analysis were not materially changed. Conclusions: VGDF exposure is associated with chronic bronchitis, respiratory symptoms and decreased lung function, suggesting that VGDF contributes to the pathogenesis and progression of COPD.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Smoking cessation in Chinese patients undergoing thoracic surgery: A multicenter prospective observational study.

INTRODUCTION: The multicenter CHAMPION study aimed to assess the impact of smoking cessation on post-operative complications (PCs) and smoking cessation patterns in Chinese patients undergoing lung surgery. METHODS: Patients undergoing elective lung surgery were prospectively enrolled from three major tertiary centers in China. Patients were categorized as smokers or quitters before surgery. Baseline characteristics and smoking status were analyzed. The incidence of PCs and pulmonary PCs (PPCs), smoking relapse rate, and causes within six months post-operatively were investigated. The questionnaire was conducted in all patients and 30 healthcare professionals (HCPs), regarding the awareness and effectiveness of smoking cessation methods. RESULTS: Of the 276 enrolled patients, 213 (77.2%) were smokers and 63 (22.8%) were quitters; 76.4% were diagnosed with primary lung cancer. PCs occurred in 13.8% of patients, with similar proportions in smokers (14.1%) and quitters (12.7%). PPCs occurred in 9.8% of patients with no significant differences between smokers and quitters (9.4% vs 11.1%, p=0.70). At six months, 9.2% of patients relapsed, with a lower rate in quitters compared to smokers (3.3% vs 11.0%, p=0.01). HCPs exhibited higher awareness of smoking cessation methods than patients. Perceived effectiveness of smoking cessation methods from the patients were low. CONCLUSIONS: In patients undergoing lung surgery with a low risk of PCs, active smoking does not significantly increase the risk of PCs or PPCs relative to quitters, suggesting that there is likely no need to postpone lung surgery for those who have not yet quit smoking. However, further large-scale studies are necessary to confirm these findings.

Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

BACKGROUND: Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. OBJECTIVE: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. METHODS: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry. RESULTS: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria-virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). CONCLUSION: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.

Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study.

BACKGROUND: Clinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. METHODS: This was a post hoc analysis of the 24-month Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. RESULTS: Of the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49-0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. CONCLUSIONS: Tiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Differential airway resistome and its correlations with clinical characteristics in Haemophilus- or Pseudomonas-predominant microbial subtypes of bronchiectasis.

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.

Venovenous extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: A comparative cohort study in China.

Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been demonstrated to be effective in treating patients with virus-induced acute respiratory distress syndrome (ARDS). However, whether the management of ECMO is different in treating H1N1 influenza and coronavirus disease 2019 (COVID-19)-associated ARDS patients remains unknown. Methods: This is a retrospective cohort study. We included 12 VV-ECMO-supported COVID-19 patients admitted to The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Eighth People's Hospital, and Wuhan Union Hospital West Campus between January 23 and March 31, 2020. We retrospectively included VV-ECMO-supported patients with COVID-19 and H1N1 influenza-associated ARDS. Clinical characteristics, respiratory mechanics including plateau pressure, driving pressure, mechanical power, ventilatory ratio (VR) and lung compliance, and outcomes were compared. Results: Data from 25 patients with COVID-19 (n=12) and H1N1 (n=13) associated ARDS who had received ECMO support were analyzed. COVID-19 patients were older than H1N1 influenza patients (P=0.004). The partial pressure of arterial carbon dioxide (PaCO2) and VR before ECMO initiation were significantly higher in COVID-19 patients than in H1N1 influenza patients (P <0.001 and P=0.004, respectively). COVID-19 patients showed increased plateau and driving pressure compared with H1N1 subjects (P=0.013 and P=0.018, respectively). Patients with COVID-19 remained longer on ECMO support than did H1N1 influenza patients (P=0.015). COVID-19 patients who required ECMO support also had fewer intensive care unit and ventilator-free days than H1N1. Conclusions: Compared with H1N1 influenza patients, COVID-19 patients were older and presented with increased PaCO2 and VR values before ECMO initiation. The differences between ARDS patients with COVID-19 and influenza on VV-ECMO detailed herein could be helpful for obtaining a better understanding of COVID-19 and for better clinical management.

Plasma exchange plus glucocorticoids in the treatment of immune checkpoint inhibitor-induced myocarditis: A case series and review.

Immune checkpoint inhibitors (ICIs), including antiprogrammed cell-death (PD)-1/anti-PD-ligand (PDL-1) monoclonal antibodies, are effective at improving the prognosis of patients with cancer. Among immune-related adverse events, myocarditis associated with anti-PD-1/anti-PD-L1 antibodies is rare but lacks effective treatment and mortality is very high. In this study, the authors extracted data from the previous 8 years from electronic medical records housed in the hospital information system to identify patients hospitalized with myocarditis putatively caused by anti-PD-1/anti-PD-L1 tumor therapy. Clinical data from these patients are reported. Four patients who developed myocarditis after undergoing treatment with anti-PD-1/anti-PD-L1 antibodies for malignant tumors, all of whom responded favorably to therapy consisting of plasma exchange and glucocorticoids for myocarditis, and all patients improved and were discharged from hospital. Plasma exchange plus systemic glucocorticoids may be effective for treating anti-PD-1/anti-PD-L1 antibody-induced myocarditis in patients with cancer.

Endobronchial optical coherence tomography or computed tomography for evaluating progression of bronchiectasis.

Background: The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis via stratification of the presence (TW+) or absence (TW-) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors. Methods: In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW+ and TW- groups. We ascertained radiological progression at 5 years via CT and EB-OCT. Results: We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW+ group than in the TW-group. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW- group. At 5 years, 53.1% of patients in the TW+ group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW- group (p<0.05). 34 patients in the TW+ group demonstrated marked dilatation of medium-sized and small airways. Higher baseline neutrophil elastase activity and TW+ bronchioles on CT predicted progression of bronchiectasis. Conclusion: Thickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.

Effect of hydrogen/oxygen therapy for ordinary COVID-19 patients: a propensity-score matched case-control study.

BACKGROUND: Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates. METHODS: This retrospective, propensity-score matched (PSM) case-control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed. RESULTS: Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25-2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9-15) versus the oxygen group (13 days; 95% CI, 11-20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days). CONCLUSION: This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.

The airway microbiome mediates the interaction between environmental exposure and respiratory health in humans.

Exposure to environmental pollution influences respiratory health. The role of the airway microbial ecosystem underlying the interaction of exposure and respiratory health remains unclear. Here, through a province-wide chronic obstructive pulmonary disease surveillance program, we conducted a population-based survey of bacterial (n = 1,651) and fungal (n = 719) taxa and metagenomes (n = 1,128) from induced sputum of 1,651 household members in Guangdong, China. We found that cigarette smoking and higher PM2.5 concentration were associated with lung function impairment through the mediation of bacterial and fungal communities, respectively, and that exposure was associated with an enhanced inter-kingdom microbial interaction resembling the pattern seen in chronic obstructive pulmonary disease. Enrichment of Neisseria was associated with a 2.25-fold increased risk of high respiratory symptom burden, coupled with an elevation in Aspergillus, in association with occupational pollution. We developed an individualized microbiome-based health index, which covaried with exposure, respiratory symptoms and diseases, with potential generalizability to global datasets. Our results may inform environmental risk prevention and guide interventions that harness airway microbiome.

Advances in pharmacotherapy for bronchiectasis in adults.

INTRODUCTION: Bronchiectasis has become a growing concern of chronic airway disease because of the enormous socioeconomic burden. Four cardinal interdependent components - impaired airway defense, recurrent airway infections, inflammatory response, and airway damage, in conjunction with the underlying etiology, have collectively played a role in modulating the vicious vortex of the pathogenesis and progression of bronchiectasis. Current pharmacotherapy aims to target at these aspects to break the vicious vortex. AREAS COVERED: The authors retrieve and review, in MEDLINE, Web of Science and ClinicalTrials.gov registry, the studies about pharmacotherapy for bronchiectasis from these aspects: antibiotics, mucoactive medications, bronchodilators, anti-inflammatory drug, and etiological treatment. EXPERT OPINION: Future drug development and clinical trials of bronchiectasis need to pay more attention to the different phenotypes or endotypes of bronchiectasis. There is a need for the development of novel inhaled antibiotics that could reduce bacterial loads, improve quality-of-life, and decrease exacerbation risks. More efforts are needed to explore the next-generation neutrophil-targeted therapeutic drugs that are expected to ameliorate respiratory symptom burden, reduce exacerbation risks, and hinder airway destruction in bronchiectasis.