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Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults with bronchiectasis with Pseudomonas aeruginosa infection. Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection? This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29. The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in P aeruginosa density (adjusted mean difference, 1.74 log 10 colony-forming units/g; 95% CI, 1.12-2.35; P <.001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95% CI, 5.72-10.11; P <.001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups. TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection. ClinicalTrials.gov; No. NCT03715322; URL: www.clinicaltrials.gov [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The anatomic location of small airways, the distribution of airway cartilage, and their correlation with ageing have not been well elucidated. The objective of this article was to explore the morphologic characteristics of small airways in vivo, and how airway structural changes correlate with age using endobronchial optical coherence tomography (EB-OCT).Methods: We recruited 112 subjects with peripheral pulmonary nodules. Participants underwent CT scan, spirometry, and EB-OCT measurements. We measured the airway internal diameter, the inner area (Ai), the airway wall area percentage (Aw%), and the thickness of airway cartilage. EB-OCT airway structural characteristics at different age intervals were analyzed, and the association between airway morphology and age was evaluated.Results: Of the small airways, 47.3% originated from the seventh generation of bronchi. Cartilage was uniformly present in the third to sixth generation of bronchi, despite a decreasing proportion of cartilage from the seventh to ninth generation of bronchi (92.4%, 54.5%, and 26.8%, respectively). The thickness of airway cartilage progressively decreased with older age. In subjects 40 to 54 years of age, Ai from the third to sixth generation correlated positively with age (r = 0.577, P < .001). Both Ai from the third to sixth generation and Ai from the seventh to ninth generation correlated negatively with age in subjects 55 to 69 years of age (r = -0.374, P = .021 and r = -0.410, P = .011). Aw% from the third to sixth generation and Aw% from the seventh to ninth generation did not correlate significantly with age.Conclusions: Small airways are mainly located at the seventh generation, where cartilaginous structures are present despite reduced distribution in more distal airways, and the thickness decreased in older age. Reduction in luminal area of medium-to-small airways might be the morphologic changes associated with ageing (ie, > 55 years of age). [ABSTRACT FROM AUTHOR]

Abstract: Background: Anxiety and depression might frequently affect bronchiectasis patients, but data in Chinese patients, including their association with disease severity assessed with Bronchiectasis Severity Index (BSI) and FACED score, are limited. Objective: To investigate the rate, risk factors, association with disease severity and impact of anxiety and depression on health‐related quality of life (HRQoL) in adult outpatients with steady‐state bronchiectasis. Methods: This cross‐sectional study included 163 outpatients (102 females; mean age, 45.8 years) and 80 healthy subjects (47 females; mean age, 47.1 years). Demographic, clinical indices, radiology, spirometry, aetiology, sputum bacteriology, Hospital Anxiety and Depression Scales (HADS), Pittsburgh Sleep Quality Index (PSQI) and St. George's Respiratory Questionnaire (SGRQ) were assessed. Results: Patients with steady‐state bronchiectasis had a higher rate of depression (HADS‐depression >7) (30.1% vs 10.0%, P = .001) and anxiety (HADS‐anxiety >7; 39.9% vs 6.3%, P < .001) compared with healthy subjects. Notably, no significant differences in the rate of anxiety and depression were found across different disease severity, assessed with BSI and FACED score (all P > .05). In multivariate model, factors associated with anxiety included younger age (OR = 1.05), education below college graduate (OR = 4.55) and sleep disturbance (PSQI ≥ 6; OR = 2.95); whereas sleep disturbance was the sole factor associated with depression (OR = 5.98). Patients with either depression or anxiety had more markedly impaired HRQoL affecting most domains than those without. Conclusions: Anxiety and depression are common in bronchiectasis and can negatively affect HRQoL, but not related to disease severity. Prompt assessment and treatment of these mental disorders, regardless of bronchiectasis severity, are advocated and might improve HRQoL. [ABSTRACT FROM AUTHOR]

Background: Mosaicism and hyperinflation are common pathophysiologic features of bronchiectasis. The magnitude of ventilation heterogeneity might have been affected by the degree of hyperinflation. Some studies have evaluated the discriminative performance of lung clearance index (LCI) in bronchiectasis patients, but the additive diagnostic value of hyperinflation metrics to LCI is unknown. Objective: To compare LCI and the ratio of residual volume to total lung capacity (RV/TLC), along with the LCI normalized with RV/TLC, in terms of discriminative performance, correlation and concordance with clinical variables in adults with bronchiectasis. Methods: Measurement items included chest high-resolution computed tomography, multiple-breath nitrogen washout test, spirometry, and sputum culture. We analyzed bronchodilator responses by stratifying LCI and RV/TLC according to their median levels (LCIHigh/RV/TLCHigh, LCILow/RV/TLCHigh, LCIHigh/RV/TLCLow, and LCILow/RV/TLCLow). Results: Data from 127 adults with clinically stable bronchiectasis were analyzed. LCI had greater diagnostic value than RV/TLC in discriminating moderate-to-severe from mild bronchiectasis, had greater concordance in reflecting clinical characteristics (including the number of bronchiectatic lobes, radiological severity score, and the presence of cystic bronchiectasis). Normalization of LCI with RV/TLC did not contribute to greater discriminative performance or concordance with clinical variables. The LCI, before and after normalization with RV/TLC, correlated statistically with age, sex, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, and ventilation heterogeneity (all P<0.05). Different bronchodilator responses were not significant among the four subgroups of bronchiectasis patients, including those with discordant LCI and RV/TLC levels. Conclusion: LCI is superior to RV/TLC for bronchiectasis assessment. Normalization with RV/TLC is not required. Stratification of LCI and RV/TLC is not associated with significantly different bronchodilator responses. [ABSTRACT FROM AUTHOR]

As of 28 February 2022, China has vaccinated 87.64% of the whole population with at least two doses of SARS-CoV-2 vaccines, with 40.32% completing the third-dose boosting vaccination. The community-based dynamic zeroing policy has played a pivotal role in minimizing the number of laboratory-confirmed cases and deaths in mainland China. The transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the culprit pathogen of coronavirus disease 2019 (COVID-19), has resulted in more than 0.43 billion cases and 6 million deaths globally. [Extracted from the article]

Background Adenosine monophosphate (AMP) may reflect airway inflammation and hyperresponsiveness, but relationship between AMP and histamine (His, a conventional stimulus) bronchial provocation test (BPT) in asthma is not fully elucidated. Objectives To compare both BPTs and determine their utility in reflecting changes of asthmatic symptoms. Methods BPTs were performed in a cross-over fashion, at 2-4 day intervals. Cumulative doses eliciting 20% FEV1fall (PD20FEV1), diagnostic performance and adverse events (AEs) were compared. Patients with PD20FEV1 lower than geometric mean were defined as responders, otherwise poor responders. Patients with uncontrolled and partly controlled asthma, who maintained their original inhaled corticosteroids therapy, underwent reassessment of airway responsiveness and asthmatic symptoms 3 and 6 months after. Results Nineteen uncontrolled, 22 partly controlled and 19 controlled asthmatic patients and 24 healthy subjects were recruited. Lower PD20FEV1 geometric means were associated with poorer asthma control in His-BPT (0.424 μmol vs 1.684 μmol vs 3.757 μmol), but not AMP-BPT (11.810 μmol vs 7.781 μmol vs 10.220 μmol). Both BPTs yielded similar overall diagnostic performance in asthma (area under curve: 0.842 in AMP-BPT vs 0.850 in His-BPT). AEs, including wheezing and tachypnea, were similar and mild. Ten patients with uncontrolled and 10 partly controlled asthma were followed-up. At months 3 and 6, we documented an increase in PD20FEV1-AMP and PD20FEV1-His, which did not correlate with reduction asthmatic symptom scores. This overall applied in responders and poor responders of AMP-BPT and His-BPT. Conclusion Despite higher screening capacity of well-controlled asthma, AMP-BPT confers similar diagnostic performance and safety with His-BPT. AMP-BPT might not preferentially reflect changes asthmatic symptoms. [ABSTRACT FROM AUTHOR]

In China, where air pollution has become a major threat to public health, public awareness of the detrimental effects of air pollution on respiratory health is increasing-particularly in relation to haze days. Air pollutant emission levels in China remain substantially higher than are those in developed countries. Moreover, industry, traffic, and household biomass combustion have become major sources of air pollutant emissions, with substantial spatial and temporal variations. In this Review, we focus on the major constituents of air pollutants and their impacts on chronic respiratory diseases. We highlight targets for interventions and recommendations for pollution reduction through industrial upgrading, vehicle and fuel renovation, improvements in public transportation, lowering of personal exposure, mitigation of the direct effects of air pollution through healthy city development, intervention at population-based level (systematic health education, intensive and individualised intervention, pre-emptive measures, and rehabilitation), and improvement in air quality. The implementation of a national environmental protection policy has become urgent. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines (CPGs) have been developed to provide health-care practitioners with the best possible evidence, but the quality of these CPGs varies greatly.Objective: The goal of this study was to systematically evaluate the quality of cough CPGs and identify gaps limiting evidence-based practice.Methods: Systematic searches were conducted to identify cough CPGs in guideline databases, developers' Websites, and Medline. Four reviewers independently evaluated eligible guidelines by using the Appraisal of Guidelines for Research and Evaluation II assessment tool. Agreement among reviewers was measured by using the intraclass correlation coefficient. The number of recommendations, strength of recommendation, and levels of evidence were determined.Results: Fifteen cough CPGs were identified. An overall high degree of agreement among reviewers was observed (intraclass correlation coefficient, 0.82 [95% CI, 0.79-0.85]). The quality ranged from good to acceptable in the scope and purpose (mean, 72%; range, 54%-93%) and clarity and presentation (mean, 68%; range, 50%-90%) domains but not in stakeholder involvement (mean, 36%; range, 18%-90%), rigor of development (mean, 36%; range, 9%-93%), applicability (mean, 23%; range, 9%-83%), and editorial independence domains (mean, 24%; range, 0-96%). Seven guidelines (46.7%) were considered "strongly recommended" or "recommended with modifications" for clinical practice. More than 70% of recommendations were based on nonrandomized studies (Level C, 30.4%) and expert opinion (Level D, 41.3%).Conclusions: The quality of cough CPGs is variable, and recommendations are largely based on low-quality evidence. There is significant room for improvement to develop high-quality guidelines, which urgently warrants first-class research to minimize the vital gaps in the evidence for formulation of cough CPGs. [ABSTRACT FROM AUTHOR]

Background and Aims Correlation between fractional exhaled nitric oxide ( FeNO) and responsiveness to inhaled leukotriene D4 ( LTD4) and methacholine ( MCh) might be different. This study aims to determine the correlation between FeNO and airway responsiveness to LTD4 and MCh, and to compare the airway responsiveness to inhaled LTD4 and MCh and FeNO in non-smokers, patients without rhinitis and non-smokers without rhinitis. Methods In this cross-over study, asthmatic patients and healthy subjects underwent LTD4 and MCh inhalation challenge at a 2- to 14-day interval. The FeNO was measured by using NIOX MINO, a portable instrument, at the initial visit, before spirometry and inhalation challenge tests. Subgroup analyses were performed in asthmatic patients based on the categorisation of never-smoker group, non-rhinitis group and never-smoker without rhinitis group. Results Of 62 asthmatic patients enrolled, 43 did not have self-reported rhinitis (asthmatic patients without rhinitis), 56 were never-smokers (asthmatic non-smokers), giving rise to 37 non-smokers who did not have rhinitis (asthmatic non-smokers without rhinitis). Twenty-one healthy subjects were enrolled. Overall, Log10 FeNO correlated with Log10 PD20 FEV1- MCh but not Log10 PD20 FEV1- LTD4 or Log10( LTD4/ MCh potency ratio). Reduced FeNO was associated with significantly higher Log10 PD20 FEV1- MCh but not Log10 PD20 FEV1- LTD4, except for non-smokers. Compared with all asthmatic patients, asthmatic non-smokers without rhinitis were characterised by markedly reduced levels of Log10 PD20 FEV1- MCh but not Log10 PD20 FEV1- LTD4. The difference in all parameters did not reach statistical significance among asthmatic patients without rhinitis, asthmatic non-smokers and asthmatic non-smokers without rhinitis. Conclusion FeNO correlates with airway responsiveness to inhaled MCh but not LTD4, in asthmatic patients, particularly in asthmatic non-smokers without rhinitis. [ABSTRACT FROM AUTHOR]

Both COPD and emphysema are associated with an increased incidence of lung cancer, but the impacts of these comorbidities on lung cancer prognosis are still unclear. Herein, we conducted a meta-analysis to clarify whether the presence of these comorbidities indicates poor survival in patients with lung cancer. A comprehensive search was conducted using PubMed, Embase, Web of Science, ASCO Abstracts and Cochrane library for articles published before 1 June 2015. Papers referenced by the obtained articles were also reviewed. Main outcomes were overall survival ( OS) and disease-free survival ( DFS) in patients with lung cancer. Pooled hazard ratio ( HR) and 95% confidence intervals ( CIs) were calculated using random-effects models. Subgroup and sensitivity analyses were also conducted. Of 58 full texts reviewed, 26 met our inclusion criteria that were derived from 21 and seven studies examining the impacts of COPD and emphysema on survival of lung cancer, respectively. Meta-analyses revealed that concomitant COPD was associated with poorer OS ( HR, 1.17; 95% CI: 1.10-1.25, n = 20), which was independent of tumour staging, diagnostic criteria of COPD or location, and DFS ( HR, 1.52; 95% CI: 1.04-2.23, n = 6) with high heterogeneity ( I2 = 78%). The presence of emphysema in patients with lung cancer predicted worse OS ( HR, 1.66; 95% CI: 1.25-2.22, n = 7), but not poorer DFS. The presence of COPD and emphysema are robust predictors of poor survival in patients with lung cancer. Early detection of these diseases should be taken into account for lung cancer surveillance and management. [ABSTRACT FROM AUTHOR]

Background and objective The triplet of airway infection, inflammation and bronchial wall destruction associated with excessive matrix metalloproteinases ( MMP) release and imbalance of tissue inhibitor metalloproteinase-1 ( TIMP-1) is implicated in bronchiectasis. We sought to determine the associations between sputum MMP ( MMP-8, MMP-9) and TIMP-1 and the severity of bronchiectasis; the utility of MMP in predicting risks of future bronchiectasis exacerbations ( BE); and the changes in MMP levels during BE. Methods We recruited 102 patients with stable bronchiectasis and 22 healthy subjects. For bronchiectasis patients, baseline measurements consisted of sputum inflammation and MMP measurements, bacterial culture, spirometry and chest high-resolution computed tomography ( HRCT). Bronchiectasis patients were followed up for 1 year to determine the frequency of BE. Changes in MMP levels during BE were assessed in 36 bronchiectasis patients. Results Sputum MMP-8, MMP-9 and MMP-9/ TIMP-1 ratio in bronchiectasis patients were significantly increased compared with healthy subjects. MMP-8 and MMP-9 levels, but not TIMP-1, were positively correlated with clinical measures, including HRCT scores, spirometry and B ronchiectasis S everity I ndex. Seventy-nine bronchiectasis patients were included in survival analyses of BE. Lower levels of baseline MMP-9 were associated with reduced risks of and a longer time to the first BE during follow-up. MMP-8 and MMP-9, but not TIMP-1 or MMP-9/ TIMP-1 ratio, were significantly heightened during BE. Conclusions Sputum MMP might be useful biomarkers for the assessment of bronchiectasis severity and the prediction of future risks of BE. Our results provide the rationales for the future clinical application of MMP inhibitors. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence supports the notion of “one airway, one disease.” Objective: To determine whether chronic rhinosinusitis (CRS) poses adverse impacts on Chinese adults with bronchiectasis. Methods: We enrolled 148 consecutive adults with clinically stable bronchiectasis. CRS diagnosed based on the 2012 EP3OS criteria. We systematically evaluated the bronchiectasis etiology, radiology, lung function, sputum bacteriology, airway inflammatory biomarkers, Bronchiectasis Severity Index, cough sensitivity and healthcare resource utilization. All patients were prospectively followed-up for 1 year to examine the frequency of bronchiectasis exacerbations (BEs). Results: Forty-seven patients (31.8%) were diagnosed as having CRS. Bronchiectasis etiologies did not vary statistically between CRS and no-CRS group. There was a trend towards non-statistically higher Bronchiectasis Severity Index [6.4±3.4 vs. 5.0(6.0), P = 0.19], a higher proportion of patients with BEs needing hospitalization before enrollment (48.9% vs. 29.7%, P = 0.13), poorer FVC [78.2±19.8% vs. 82.2(16.8)%, P = 0.54] and FEV1 [68.2±24.8% vs. 74.8(21.2)%, P = 0.29], a higher prevalence of Pseudomonas aeruginosa isolated (36.2% vs. 26.7%, P = 0.27) or colonized in sputum (36.2% vs. 21.8%, P = 0.12) and greater capsaicin cough sensitivity [C2: 3.9(123.0) μmol/L vs. 11.7(123.0) μmol/L, P = 0.81; C5: 62.5(996.0) μmol/L vs. 250.0(973.0) μmol/L, P = 0.32]. Patients with CRS had significantly greater risks of experiencing BEs during follow-up (P = 0.02 for negative binominal regression test). Conclusion: Chinese adults with bronchiectasis appear to have a lower prevalence of CRS than that in western countries. There was a trend towards greater adverse impacts on bronchiectasis in patients with CRS. Studies with greater sample sizes might help to resolve this issue. In future clinical practice, physicians should be vigilant to the screening of concomitant CRS in bronchiectasis so as to better improve patient’s healthcare. Our findings may be of clinical significance in that proper treatment of upper airway symptoms due to CRS will be the prevention of infection or re-infection of the tracheobronchial tree, which should be addressed for the future management of bronchiectasis. [ABSTRACT FROM AUTHOR]

Background and objective Aetiologies of bronchiectasis in mainland China and their comparisons with those in western countries are unknown. We aimed to investigate bronchiectasis aetiologies in Guangzhou, southern China, and to determine ethnic or geographic differences with reports from western countries. Methods Consecutive patients with steady-state bronchiectasis were randomly recruited. Past history was meticulously extracted. Patients underwent physical examination, saccharine test, humoral immunity assays, gastroesophageal reflux scoring and sputum culture. Fiberoptic bronchoscopy, total immunoglobin E ( IgE) and A spergillus fumigatus-specific IgE measurement, 24-h gastroesophageal pH monitoring and miscellaneous screening tests were performed, if indicated. This entailed comparisons on aetiologies with literature reports. Results We enrolled 148 patients (44.6 ± 13.8 years, 92 females), most of whom had mild to moderate bronchiectasis. Idiopathic (46.0%), post-infectious (27.0%) and immunodeficiency (8.8%) were the most common aetiologies. Miscellaneous aetiologies consisted of asthma (5.4%), gastroesophageal reflux (4.1%), aspergillosis (2.7%), congenital lung malformation (2.0%), Kartagener syndrome (1.4%), rheumatoid arthritis (1.4%), chronic obstructive pulmonary disease (0.7%), Young's syndrome (0.7%), yellow nail's syndrome (0.7%), eosinophilic bronchiolitis (0.7%) and foreign bodies (0.7%). No notable differences in clinical characteristics between idiopathic and known aetiologies were found. Ethnic or geographic variations of aetiologies were overall unremarkable. Conclusions Idiopathic, post-infectious and immunodeficiency constitute major bronchiectasis aetiologies in Guangzhou. Clinical characteristics of patients between known aetiologies and idiopathic bronchiectasis were similar. Ethnicity and geography only account for limited differences in aetiologic spectra. These findings will offer rationales for early diagnosis and management of bronchiectasis in future studies and clinical practice in China. [ABSTRACT FROM AUTHOR]

Background: Although viral infections are a major cause of exacerbations in patients with chronic airway diseases, their roles in triggering bronchiectasis exacerbations in adults remain unclear. Therefore, we prospectively investigated the incidence and clinical impacts of viral infection in adults with bronchiectasis exacerbations.Methods: The study cohort of 119 adults with bronchiectasis was followed up prospectively for 12 months. Nasopharyngeal swabs and sputum samples were assayed for 16 respiratory viruses, using polymerase chain reaction assays. Symptoms, spirometry, quality of life, bacterial cultures, and inflammatory markers were assessed during steady-state bronchiectasis and exacerbations.Results: A total of 100 exacerbations were captured from 58 patients during 1-year follow-up. Respiratory viruses were found more frequently in nasopharyngeal swabs and sputum during bronchiectasis exacerbations (49 of 100, 49.0%) than during steady state (11 of 58, 18.9%; P < .001). The most common viruses found in patients experiencing exacerbations were coronavirus (19 of 65, 39.2%), rhinovirus (16 of 65, 24.6%), and influenza A/B viruses (16 of 65, 24.6%). Virus-positive exacerbations were associated with a greater increase in markers of systemic and airway inflammation (serum IL-6 and tumor necrosis factor-α; sputum IL-1β and tumor necrosis factor-α) compared with virus-negative exacerbations, but the differences in spirometric indexes, quality of life, and bacterial density were unremarkable. In receiver operating characteristics analysis, serum interferon-γ-induced protein 10 yielded an area under curve of 0.67 (95% CI, 0.53-0.77; P = .018). Furthermore, a greater proportion of patients with virus-positive exacerbations received IV antibiotics.Conclusions: Prevalence of viral infections, detected by polymerase chain reaction assay, is higher in cases of bronchiectasis exacerbations than in steady-state bronchiectasis, suggesting that respiratory viruses play crucial roles in triggering bronchiectasis exacerbations. The potential mechanisms of virus-induced bronchiectasis exacerbations merit further investigations.Trial Registry: ClinicalTrials.gov; No.: NCT01801657; www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

The article presents a study on delineation of six-minute walk distance (6MWD) test to assess exercise tolerance in Chinese adults suffering from clinically stable bronchiectasis and factors that are associated with reduced 6MWD. Topics discussed include identification of lower levels of 6MWD in older age patients, increased quality of life in patients with high 6MWD, lower 6MWD due to cystic bronchiectasis and perceived dyspnea and reduced diffusing capacity being 6MWD's independent factors.

Introduction The convenient measure to predict efficacy of leukotriene receptor antagonist is lacking. Objectives To determine if leukotriene D4 inhalation challenge predicts short-term efficacy of montelukast in asthma. Methods In this open-labelled 28-day trial, 45 patients with asthma were allocated to leukotriene-sensitive and leukotriene-insensitive group to receive montelukast monotherapy (10 mg, once daily) based on the positive threshold of leukotriene D4 inhalation challenge test (4.800 nmol). Miscellaneous measurements comprised fractional exhaled nitric oxide, methacholine inhalation challenge, Asthma Control Test and Asthma Quality of Life Questionnaire. Peak expiratory flow was self-monitored throughout the treatment. End point assessments were performed 3 to 5 days after montelukast withdrawal. (Registration: ) Results Twenty-three patients in leukotriene-sensitive group and 10 leukotriene-insensitive group completed the study. Both groups differed neither in 28-day peak expiratory flow rate nor in maximal weekly peak expiratory flow (both P > 0.05). However, minimal weekly peak expiratory flow was significantly higher in leukotriene-insensitive group throughout the treatment course (all P < 0.05) except for week 1 ( P > 0.05). Both groups did not differ statistically in the post-treatment improvement in forced expiratory volume in 1 s ( FEV1) predicted% prior to inhalation challenge, fractional exhaled nitric oxide or the airway responsiveness to leukotriene D4 or methacholine (all P > 0.05). There was a marked increase in Asthma Control Test score and the symptom score of Asthma Quality of Life Questionnaire in both groups (both P < 0.05). The overall significance of Logistic regression model was unremarkable ( P = 0.467). Conclusion Responsiveness to inhaled leukotriene D4 alone might not be sufficient to predict the short-term efficacy of montelukast monotherapy in patients with asthma. [ABSTRACT FROM AUTHOR]

Background: Characteristics of lung function impairment in bronchiectasis is not fully understood. Objectives: To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy). Methods: We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence. Results: In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV1 being 50%pred or less; and the only variable associated with reduced DLCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV1 during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV1 and DLCO reduction at baseline. Conclusion: Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV1. Changes of other spirometric parameters were less significant during exacerbations. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Cough hypersensitivity has been common among respiratory diseases. Objective: To determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis. Methods: We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5). Results: Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all P<0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 µmol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35–7.83, P<0.01), HRCT total score between 7–12 (OR: 2.57, 95%CI: 1.07–6.173, P = 0.04), BSI between 5–8 (OR: 4.05, 95%CI: 1.48–11.06, P<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48–12.93, P<0.01). Conclusion: Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. Objectives: To compare the diagnostic value of RDR and PD, by conducting leukotriene D (LTD-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. Methods: Healthy subjects and asthmatic patients underwent LTD-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20 % fall in forced expiratory volume in one second (PDFEV) and the RDR, defined as FEV fall (%) at the final step divided by the corresponding provocative dosage. Results: Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. LogRDR was positively correlated with logPDFEV in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PDFEV and higher RDR (both P < 0.05). The differences in PDFEV and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with logPDFEV, the logRDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤25th percentile) was associated with higher baseline FEV ( P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PDFEV led to an increased diagnostic value compared with either parameter alone. Conclusions: RDR is a surrogate of PDFEV for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants. [ABSTRACT FROM AUTHOR]

Background: A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis. Methods: We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events. Results: Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75–0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, −6.56; 95% CI, −11.99 to −1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, −11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy. Conclusions: Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background: Although interleukin-10 (IL-10) is a potent inhibitor of allergic diseases, the association between promoter −1082/−819/−592 polymorphisms and asthma susceptibility remains inconclusive. We sought to determine if IL-10 promoter −1082/−819/−592 polymorphisms contribute to asthma susceptibility and are associated with phenotypes of atopic asthma. Methods: Systematic computerized searches were performed. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by using random-effect and fixed-effect models, based on between-study heterogeneity. Subgroup analyses were performed according to age, ethnicity, and atopy. Publication bias was detected by funnel plot using Egger's test. Results: A total of 4,716 asthmatic patients and 5,093 controls were included. The asthma susceptibility correlated significantly with IL-10 promoter gene −1082 polymorphism [OR (95 % CI) 1.26 (1.02, 1.55) for AA vs. AG + GG] and −592 polymorphism [OR (95 % CI) 1.12 (1.07, 1.34) for AC + AA vs. CC] (both P < 0.05), but not with −819 polymorphism ( P > 0.05). Subgroup analyzes suggested that the AA versus AG + GG genotype of −1082A/G polymorphism and AC + AA versus CC genotype of −592A/C polymorphism contributed significantly to increased asthma susceptibility in adults [OR (95 % CI) 1.39 (1.03, 1.87) for −1082A/G and 1.53 (1.25, 1.87) for −592A/C polymorphism]. The Asian population [OR (95 % CI) 1.35 (1.1, 1.7) for −1082A/G and 1.4 (1.12, 1.64) for −592A/C polymorphism] and subjects with atopic asthma [OR (95 % CI) 1.49 (1.18, 1.88) for −1082A/G and 1.23 (1.01, 1.48) for −592A/C polymorphism] also had an increased susceptibility of asthma. No publication bias was detected. Conclusions: IL-10 promoter −1028A/G, −592A/C polymorphisms and their haplotypes, but not −819T/C polymorphism, correlate with asthma susceptibility. [ABSTRACT FROM AUTHOR]

Keywords: coronavirus; COVID-19; laboratory testing; prevention; therapy; transmission EN coronavirus COVID-19 laboratory testing prevention therapy transmission 657 658 2 05/28/20 20200601 NES 200601 The outbreak of coronavirus disease 2019 (Covid-19) has been rapidly spreading, causing a pandemic globally. We must ensure opportunities to develop targeted therapies to Covid-19 and other coronavirus diseases do not cease when the current outbreak is over. Coronavirus, COVID-19, laboratory testing, prevention, therapy, transmission. [Extracted from the article]

The authors convey their response to a feedback about their study on the effects of cellulose powder (CP) on human nasal epithelium. Topics mentioned include the failure of the experimental design to extrapolate the findings based on the dosing schemes, the impact of intranasal CP on minimizing ciliary beat frequency, and the administration of CP as a maintenance therapeutic approach.

See related Letter [ABSTRACT FROM AUTHOR]

Patients with mild asthma had already developed airway remodeling (wall thickening without notable airway luminal narrowing) from the 3rd to 9th generation. Keywords: airway remodeling; asthma; bronchodilation; optical coherence tomography EN airway remodeling asthma bronchodilation optical coherence tomography 646 649 4 02/01/22 20220201 NES 220201 ACKNOWLEDGMENTS We thank Prof. Zheng Jing-ping, Prof. Gao Yi, Prof. Xie Yan-qing, Dr. [Extracted from the article]

We hypothesized that exposure to polluting fuels for cooking was associated with abnormality of glucose metabolism and diabetes mellitus (DM) in south urban China. 3414 residents were surveyed in 14 urban areas of Guangdong Province in 2018. We recorded polluting fuels for cooking exposure, different DM status (DM, prediabetes), fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and other covariates by using a structured questionnaire. We conducted logistic regression model and multivariate linear regression model based on propensity‐score method (inverse probability of weighting) to examine the effect of polluting fuels for cooking exposure on DM and glucose metabolism. Exposure to polluting fuels for cooking was associated with DM (odds ratio: 2.57, 95% confidence interval: 1.71 to 3.86) and prediabetes (odds ratio: 1.98, 95% confidence interval: 1.52 to 2.58) in both the adjusted and unadjusted models (all p < 0.05). Exposure to polluting fuels for cooking was significantly associated with an increase of FBG (β: 0.30 mmol/L, 95% confidence interval: 0.22 to 0.38 mmol/L). Sensitivity analysis showed that the results were not substantially changed. There was an increased risk of DM, prediabetes and high levels of FBG, OGTT, and HbA1c among participants aged ≥ 40 years with exposure to polluting fuels for cooking. We demonstrated that exposure to polluting fuels for cooking was associated with higher levels of FBG, which contributed to the increased risk of DM and prediabetes in middle‐aged elderly Chinese population living in urban areas. [ABSTRACT FROM AUTHOR]

Background: Upper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs). Methods: We elucidated localization patterns of FOXJ1 by performing immunofluorescence assays in nasal specimens and cytospin samples from controls and patients with NPs. We also assayed mRNA expression levels of FOXJ1 by using quantitative real-time polymerase chain reaction. Four localization patterns [normal (N), intermediate (I), mislocalization (M), and absence (A)] were defined. A semi-quantitative scoring system was applied for demonstrating FOXJ1 localization in five areas per paraffin section, with individual sections being scored between 0 and 2. Results: FOXJ1 localization score was significantly higher in samples from NPs than in controls (P < 0.001). Elevated FOXJ1 localization scores and down-regulation of FOXJ1 mRNA levels were observed in NPs with co-existing AR or asthma (all P < 0.05). Moreover, FOXJ1 localization scores positively correlated with Lund–Mackay score (r = 0.362, P = 0.007). Of primary cytospin samples, the mean percentage of patients with FOXJ1 localization patterns N, I, M and A was 15.0%, 3.3%, 53.3% and 28.3% in NPs, and 82.5%, 5.0%, 5.0% and 7.5% in controls, respectively (P < 0.001). Conclusions: Aberrant localization of FOXJ1 correlates with the severity and co-existence of AR or asthma in patients with NPs, and might be a novel target for assessment and intervention in NPs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 registrationChiCTR2200056727. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Asthmatic patients with chest tightness as their only presenting symptom (chest tightness variant asthma [CTVA]) have clinical characteristics of eosinophilic airway inflammation similar to those of classic asthma (CA); however, whether CTVA has similar response to antiasthma treatment as compared with CA remains unclear. Objective: The response of 76 CTVA patients to standard asthma treatments with inhaled corticosteroids with long‐acting beta‐agonists was explored in a 52‐week multicenter, prospective, real‐world study. Results: After 52 weeks of treatment with therapy regimens used for CA, the mean 5‐point Asthma Control Questionnaire (ACQ‐5) score decreased markedly from 1.38(first administration) to 0.71 (52 weeks, mean decrease: 0.674, 95%CI: 0.447‐0.900, P<.001).The mean asthma quality‐of‐life questionnaire (AQLQ) score increased from 5.77 (first administration) to 6.20 (52 weeks, mean increase: 0.441, 95% CI 0.258‐0.625, P<.001). Furthermore, at week 52, FVC, FEV1%, the diurnal variation in PEFand the PD20‐FEV1 were significantly improved. Subgroup analysis revealed that the patients at first administration in the responsive group had higher ACQ‐5 scores than those in the nonresponsive group (P <.05). Conclusion: In conclusion, patients with CTVA had a good therapeutic response to the guideline‐recommended routine treatment (containing inhaled corticosteroids). The association between the treatment response and the severity of CTVA suggested that CTVA patients with higher ACQ‐5 scores had better therapeutic effects. [ABSTRACT FROM AUTHOR]

While identifying the underlying aetiology is a key part of bronchiectasis management, the prevalence and impact of identifying the aetiologies on clinical management remain unclear. We aimed to determine the etiological spectrum of bronchiectasis, and how often etiological assessment could lead to the changes in patients' management. A comprehensive search was conducted using MEDLINE (via PubMed) and EMBASE for observational studies published before October 2015 reporting aetiologies in adults with bronchiectasis. Of the 8216 citations identified, 56 studies including 8608 adults with bronchiectasis were relevant for this systematic review. The crude prevalence for the identified aetiologies ranged from 18% to 95%, which possibly resulted from the differences in the geographic regions and diagnostic workup. Post-infective (29.9%), immunodeficiency (5%), chronic obstructive pulmonary disease (3.9%), connective tissue disease (3.8%), ciliary dysfunction (2.5%), allergic bronchopulmonary aspergillosis (2.6%) were the most common aetiologies. In 1577 patients (18.3%), identifying the aetiologies led to changes in patient's management. Aetiologies varied considerably among different geographic regions ( P < 0.001). Intensive investigations of these aetiologies might help change patient's management and therefore should be incorporated into routine clinical practice. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the bronchiectasis etiology of the people in southern China.

Background: Motile ciliary disorder (MCD) has been implicated in chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease.Research Question: What is the characteristic of MCD of the nasal epithelium and the association with disease severity and inflammatory endotypes in adults with bronchiectasis?Study Designs and Methods: In this observational study, we recruited 167 patients with bronchiectasis and 39 healthy controls who underwent brushing of nasal epithelium. A subgroup of patients underwent bronchoscopy for bronchial epithelium sampling (n=13), elective surgery for bronchial epithelium biopsy (n=18), and blood sampling for next-generation sequencing (n=37). We characterized systemic and airway inflammatory endotypes in bronchiectasis. We conducted immunofluorescence assays to profile ultrastructural [dynein axonemal heavy chain 5 (DNAH5), dynein intermediate chain 1 (DNAI1), radial spoke head protein 9 (RSPH9)] and ciliogenesis marker expression (Ezrin).Results: MCD was present in 89.8% of patients with bronchiectasis, 67.6% had secondary MCD and 16.2% had primary plus secondary MCD. Compared with healthy controls, patients with bronchiectasis yielded abnormal staining patterns of DNAH5, DNAI1 and RSPH9 (but not ezrin), which were more prominent in moderate-to-severe bronchiectasis. MCD pattern scores were largely consistent between upper and lower airways, and between large-to-medium and small airways in bronchiectasis. Co-existing nasal diseases and asthma did not significantly confound nasal ciliary ultrastructural marker expression. The propensity of MCD was unaffected by the airway or systemic inflammatory endotypes. MCD, particularly ultrastructural abnormality, was notable in patients with mild bronchiectasis who had blood or sputum eosinophilia.Interpretation: Nasal ciliary markers profiling provides complimentary information to clinical endotyping of bronchiectasis. [ABSTRACT FROM AUTHOR]

Background: Forkhead box J1 (FOXJ1) plays pivotal roles in motile cilia formation. However, it remains unclear whether abnormal expression or localization of FOXJ1 in nasal mucosa tissues is associated with allergic rhinitis (AR), in which impaired mucociliary clearance is implicated. Objective: We sought to investigate the expression and localization of FOXJ1 in inferior turbinate from patients with AR and controls. Methods: We assayed mRNA levels of FOXJ1, DNAI1, DNALI1, and DNAH9 by using whole-genome expression array and quantitative real-time polymerase chain reaction. We elucidated the localization of FOXJ1 by using immunofluorescence assays in paraffin sections and primary single cells. Four patterns of FOXJ1 localization (normal, N; intermediate, I; mislocalization, M; absence, A) were defined. We developed a semiquantitative scoring system to elucidate their localization in 5 areas per paraffin section, with individual sections being assigned a score between 0 and 2. Results: The mRNA levels of FOXJ1, DNAI1, DNALI1, and DNAH9 were significantly reduced in patients with AR compared with controls (all p < 0.05). The median (1st and 3rd quartile) of the FOXJ1 score was 0.4 (0.0 and 0.85) in patients with AR, and 0.2 (0.0 and 0.4) in controls (p < 0.05). For primary cytospin samples, the mean percentages of FOXJ1 localization patterns N, I, M, and A were 46.7, 10.0, 30.0, and 26.7% in patients with AR, and 82.5, 5.0, 5.0, and 7.5% in controls, respectively (p < 0.05). Conclusion: Downregulation and aberrant localization of FOXJ1 may be crucial characteristics of the allergic nasal mucosa. [ABSTRACT FROM AUTHOR]

Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. We also examined the prevalence of viral infection stratified by age, geographic region, type of respiratory secretion, and detection method. Sixty articles were included in the final analysis. During asthma exacerbations, the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%, respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV, BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major virus detected globally, except in Africa. RV could be detected in both the upper and lower airway. Polymerase chain reaction was the most sensitive method for detecting viral infection. Our findings indicate the need to develop prophylactic polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce herd immunity and reduce the healthcare burden associated with virus-induced asthma exacerbations. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) and asthma often coexist. The terminology combined allergic rhinitis and asthma syndrome (CARAS) was introduced to describe patients with combined AR and asthma. The aim of the present study was to evaluate the correlation between eosinophilic inflammation in the upper and lower airways of patients with CARAS. Stable patients with CARAS initially presenting with AR or asthma were recruited. Healthy subjects and patients with AR alone were recruited as controls. Clinical characteristics, including disease history, lung function, nasal airway inspiratory resistance and upper and lower airway eosinophilic inflammation were evaluated and compared. A total of 73 subjects (22 patients with CARAS initially presenting with AR, 15 patients with CARAS initially presenting with asthma, 25 patients with AR alone and 11 healthy subjects) were studied. The nasal symptoms visual analogue scale scores at the week prior to enrollment and nasal airway inspiratory resistances were comparable among the groups. The percentage of predicted forced expiratory volume in 1 sec and percentage of predicted maximal middle expiratory flow in patients with CARAS initially presenting with asthma were significantly lower compared with the other three groups (P<0.05). No significant different in the percentage of eosinophils in the nasal lavage was observed between patients with CARAS and those with AR only; however, it was significantly increased compared with healthy subjects (P<0.05). The fractional concentration of exhaled nitric oxide and percentage of eosinophils in the sputum were significantly increased in patients with CARAS compared with those in the AR only and healthy subject groups (P<0.05). The difference in the percentage of eosinophils in the nasal lavage and sputum between patients with CARAS initially presenting with AR and initially presenting with asthma was not significant; however, a positive correlation between the percentage of eosinophils in the upper and lower airways was present in patients with CARAS initially presenting with AR only (r=0.526, P=0.030). [ABSTRACT FROM AUTHOR]

Accumulating studies have shown that bats could harbor various important pathogenic viruses that could be transmitted to humans and other animals. Extensive metagenomic studies of different organs/tissues from bats have revealed a large number of novel or divergent viruses. To elucidate viral diversity and epidemiological and phylogenetic characteristics, six pooled fecal samples from bats were generated (based on bat species and geographic regions characteristic for virome analysis). These contained 500 fecal samples from six bat species, collected in four geographic regions. Metagenomic analysis revealed a plethora of divergent viruses originally found in bats. Multiple contigs from influenza A virus and coronaviruses in bats shared high identity with those from humans, suggesting possible cross-species transmission, whereas a number of contigs, whose sequences were taxonomically classifiable within Alphapapillomavirus, Betaretrovirus, Alpharetrovirus, Varicellovirus, Cyprinivirus, Chlorovirus and Cucumovirus had low identity to viruses in existing databases, which indicated possible evolution of novel viral species. None of the established caliciviruses and picornaviruses were found in the 500 fecal specimens. Papillomaviruses with high amino acid identity were found in Scotophilus kuhlii and Rhinolophus blythi, challenging the hypotheses regarding the strict host specificity and co-evolution of papillomaviruses. Phylogenetic analysis showed that four bat rotavirus A strains might be tentative G3 strains, according to the Rotavirus Classification Working Group classification. [ABSTRACT FROM AUTHOR]

Background: Although FEV1 remains the gold standard for staging COPD, the association between airway remodeling and airflow limitation remains unclear. Endobronchial optical coherence tomography (EB-OCT) was performed to assess the association between disorders of large and medium to small airways and COPD staging. We also evaluated small airway architecture in heavy smokers with normal FEV1 (SNL) and healthy never-smokers.Methods: We recruited 48 patients with COPD (stage I, n = 14; stage II, n = 15; stage, III-IV, n = 19), 21 SNL, and 17 healthy never-smokers. A smoking history inquiry, as well as spirometry, chest CT, bronchoscopy, and EB-OCT were performed. Mean luminal diameter (Dmean), inner luminal area (Ai), and airway wall area (Aw) of third- to ninth-generation bronchi were measured using EB-OCT.Results: Patients with more advanced COPD demonstrated greater abnormality of airway architecture in both large and medium to small airways, followed by SNL and never-smokers. Abnormality of airway architecture and EB-OCT parameters in SNL were comparable to those in stage I COPD. FEV1% predicted correlated with Dmean and Ai of seventh- to ninth-generation bronchi in COPD; however, neither Dmean nor Ai of third- to sixth-generation bronchi correlated with FEV1% in stage I and stage II COPD and in SNL.Conclusions: FEV1-based COPD staging partially correlates with small airway disorders in stage II-IV COPD. Small airway abnormalities detected by EB-OCT correlate with FEV1-based staging in COPD and identify early pathologic changes in healthy heavy smokers. [ABSTRACT FROM AUTHOR]

Background Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). Objectives To determine the efficacy and safety of para -toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. Methods Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. Results In full-analysis set ( N = 88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%–69.5%), bronchoscopy: 48.9% (95%CI: 38.1%–59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%–54.2%), bronchoscopy: 29.6% (95%CI: 20.3%–40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16–0.53 liters), FEV 1 (mean difference: 0.27 liters, 95%CI: 0.07–0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9–74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6·9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9–10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). Conclusion PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We sought to investigate the association between household exposure to biomass fuel and metabolic syndrome (MetS) and its components including blood pressure, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG) and waist circumference among females in southern rural China. We surveyed 1664 residents in the Chronic Disease and Risk Factors Surveillance , conducted in 14 districts of Guangdong province. We recorded the use of biomass fuel, MetS and its components, and other covariates by using a structured questionnaire. Logistic regression model and multivariate linear regression model were adopted for analysis. Exposure to biomass fuel was significantly associated with an increase of systolic blood pressure (SBP) (β: 2.15, 95% confidence interval: 0.13 to 4.17) and FBG (β: 0.19, 95% confidence interval: 0.01 to 0.37) in the adjusted and unadjusted models (all P < 0.05). Among participants with exposure to biomass fuel, being overweight or obese was associated with an increased risk of having hypertension (odds ratio: 3.19, 95% confidence interval: 2.13 to 4.76) and higher FBG levels (odds ratio: 2.10, 95% confidence interval: 1.46 to 3.02). Exposure to biomass fuel was significantly associated with a decrease of the prevalence of central obesity (P < 0.05). However, exposure to biomass fuel was not associated with MetS, diastolic blood pressure and TG (all P > 0.05). Exposure to biomass fuel is associated with an increase in blood pressure and FBG levels, but not MetS per se. Efforts should be made to protect females in southern rural China from the adverse effects associated with biomass fuel pollution. • This is the first study delineating the association between biomass fuel and multiple MetS components. • Biomass fuel was associated with increased blood pressure and FBG. • Overweight or obese women who were exposed to biomass fuel had a higher risk of hypertension. • Higher FBG associated with biomass fuel exposure was detected in overweight or obese participants. • Biomass fuel exposure was not associated with the development of MetS. [ABSTRACT FROM AUTHOR]

Background: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.Methods: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.Results: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy.Conclusion: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions. [ABSTRACT FROM AUTHOR]

We sought to investigate the association between active cigarette smoking (ex‐ and current smokers) with or without exposure to biomass fuels and respiratory symptoms/lung function in middle‐aged adults and the elderly. In the chronic obstructive pulmonary disease surveillance conducted in six cities of Guangdong province, China, we surveyed 1986 residents aged 40‐93 years. We recorded respiratory symptoms, smoking status, use of biomass fuel, and other covariates by using a structured questionnaire. All models were adjusted for second‐hand smoking. Active smoking with or without exposure to biomass fuels was significantly associated with wheezing, chronic cough, and phlegm (all P <.05). Active smoking alone with or without exposure to biomass fuels was associated with 2.5% and 0.6% reduction in the mean forced vital capacity predicted, 6.8% and 4.2% reduction in the mean forced expiratory volume in one second predicted, and 9.0% and 4.7% reduction in the mean maximal mid‐expiratory flow predicted compared with the exposure to neither smoking nor biomass fuels, respectively. However, exposure to biomass fuel alone was associated with neither greater lung function impairment nor respiratory symptoms except for chronic cough. Efforts should be made to protect home owners and their family from adverse effects of indoor air pollution. [ABSTRACT FROM AUTHOR]

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-1β (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. [ABSTRACT FROM AUTHOR]

Background: Factors attributable to the level of fraction of exhaled nitric oxide (FeNO) in different age groups of asthmatic children are still lack of report. Objective: To evaluate factors associated with FeNO and the response of FeNO to inhaled steroid in different age groups of asthmatic children with allergic rhinitis. Methods: Asthmatic children aged 5 to 12 years were recruited. FeNO, lung function and bronchial hyperresponsiveness (BHR) to methacholine, skin prick testing to a panel of aeroallergens, total immunoglobulin E (T‐IgE) in serum and eosinophils in blood were tested. Correlations between FeNO and the measured parameters were assessed. FeNO was measured again after the treatment of combined inhaled corticosteroid and long‐acting beta‐agonist (ICS/LABA) for 4 weeks. Changes in FeNO between different age groups were compared. Results: A total of 121 eligible subjects were enrolled in and completed this study. Asthmatic children aged 10 to 12 years old had significantly higher FeNO than those between 8 and 9 years and 5 to 7 years of children (both P < 0.01). Greater height/age (P < 0.01) and higher level of total allergen IgE (P < 0.01) are associated with a higher value of FeNO. After 4 weeks of treatment with ICS/LABA, asthma control test scores were significantly increased in all age groups (P < 0.01), while the level of FeNO significantly decreased in the elder age group only (P < 0.01). Conclusions: Height and T‐IgE are well correlated with FeNO in asthmatic children aged 5 to 12 years. Measurement of FeNO is more suitable for evaluating the efficacy of ICS/LABA in elder asthmatic children. [ABSTRACT FROM AUTHOR]