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Rationale: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic. Objectives: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. Methods: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived cells, cell cultures, and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. Measurements and Main Results: We identified biallelic pathogenic variants in WAP four-disulfide core domain 2 (WFDC2) in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and, thus, secretion of mature WFDC2. Conclusions:WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background There is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result. Methods Three standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study. Results The rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83–0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was

Background: There is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result. Methods: Three standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study. Results: The rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83–0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72–0.83). Conclusion: The simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result. [ABSTRACT FROM AUTHOR]

ObjectiveRespiratory infections are a common cause of acute exacerbations in patients with chronic airway disease, however, environmental factors such as air pollution can also contribute to these exacerbations. The study aimed to determine the correlation between pollutant levels and exacerbation risks in areas exposed to environmental pollution sources.MethodsFrom 2015 to 2016, a total of 788 patients with chronic airway diseases were enrolled in a study. Their medical records, including hospital visits due to acute exacerbations of varying severity were analyzed. Additionally, data on daily pollutant levels from the Air Quality Monitoring Network from 2014 to 2016 was also collected and analyzed.ResultsPatients with chronic airway disease and poor lung function (FEV1 < 50% or obstructive ventilatory defect) have a higher risk of severe acute exacerbations and are more likely to experience more than two severe acute exacerbations within a year. The study found that in areas exposed to environmental pollution sources, there is a significant correlation between NO2, O3, and humidity with the main causes of severe acute exacerbation. When the levels of NO2 were higher than 16.65 ppb, O3 higher than 35.65 ppb, or humidity higher than 76.95%, the risk of severe acute exacerbation in patients with chronic airway disease increased.ConclusionAcute exacerbations of chronic airway disease can be triggered by both the underlying disease state and the presence of air pollution. Computer simulations and early warning systems should be developed to predict acute exacerbations of chronic airway disease based on dynamic changes in air pollution.

Shubing Chen,&ast; Yongyi Peng,&ast; Beilan Shen, Liping Zhong, Zhongping Wu, Jinping Zheng, Yi Gao State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Gao; Jinping Zheng, Email misstall2@163.com; jpzhenggy@163.comPurpose: To develop and internally validate a nomogram for predicting the risk of incorrect inhalation techniques in patients with chronic airway diseases.Methods: A total of 206 patients with chronic airway diseases treated with inhaled medications were recruited in this study. Patients were divided into correct (n=129) and incorrect (n=77) cohorts based on their mastery of inhalation devices, which were assessed by medical professionals. Data were collected on the basis of questionnaires and medical records. The least absolute shrinkage and selection operator method (LASSO) and multivariate logistic regression analyses were conducted to identify the risk factors of incorrect inhalation techniques. Then, calibration curve, Harrell’s C-index, area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA) and bootstrapping validation were applied to assess the apparent performance, clinical validity and internal validation of the predicting model, respectively.Results: Seven risk factors including age, education level, drug cognition, self-evaluation of curative effect, inhalation device use instruction before treatment, post-instruction evaluation and evaluation at return visit were finally determined as the predictors of the nomogram prediction model. The ROC curve obtained by this model showed that the AUC was 0.814, with a sensitivity of 0.78 and specificity of 0.75. In addition, the C-index was 0.814, with a Z value of 10.31 (P< 0.001). It was confirmed to be 0.783 by bootstrapping validation, indicating that the model had good discrimination and calibration. Furthermore, analysis of DCA showed that the nomogram had good clinical validity.Conclusion: The application of the developed nomogram to predict the risk of incorrect inhalation techniques during follow-up visits is feasible.Keywords: inhalation technique, incorrect, chronic airway disease, nomogram, predictors

Abstract Respiratory self-care places considerable demands on patients with chronic airways disease (AD), as they must obtain, understand and apply information required to follow their complex treatment plans. If clinical and lifestyle information overwhelms patients’ HL capacities, it reduces their ability to self-manage. This review outlines important societal, individual, and healthcare system factors that influence disease management and outcomes among patients with asthma and chronic obstructive pulmonary disease (COPD)—the two most common ADs. For this review, we undertook a comprehensive literature search, conducted reference list searches from prior HL-related publications, and added insights from international researchers and scientists with an interest in HL. We identified methodological limitations in currently available HL measurement tools in respiratory care. We also summarized the issues contributing to low HL and system-level cultural incompetency that continue to be under-recognized in AD management and contribute to suboptimal patient outcomes. Given that impaired HL is not commonly recognized as an important factor in AD care, we propose a three-level patient-centered model (strategies) designed to integrate HL considerations, with the goal of enabling health systems to enhance service delivery to meet the needs of all AD patients.

Respiratory self-care places considerable demands on patients with chronic airways disease (AD), as they must obtain, understand and apply information required to follow their complex treatment plans. If clinical and lifestyle information overwhelms patients' HL capacities, it reduces their ability to self-manage. This review outlines important societal, individual, and healthcare system factors that influence disease management and outcomes among patients with asthma and chronic obstructive pulmonary disease (COPD)—the two most common ADs. For this review, we undertook a comprehensive literature search, conducted reference list searches from prior HL-related publications, and added insights from international researchers and scientists with an interest in HL. We identified methodological limitations in currently available HL measurement tools in respiratory care. We also summarized the issues contributing to low HL and system-level cultural incompetency that continue to be under-recognized in AD management and contribute to suboptimal patient outcomes. Given that impaired HL is not commonly recognized as an important factor in AD care, we propose a three-level patient-centered model (strategies) designed to integrate HL considerations, with the goal of enabling health systems to enhance service delivery to meet the needs of all AD patients. [ABSTRACT FROM AUTHOR]

This study investigated the effect of influenza vaccination on prevention of acute attacks in elderly patients with chronic airway disease and provides evidence for the prevention and control strategy of chronic airway disease in the elderly population. A total of 348 elderly patients in Linquan County, Anhui Province, China, who were also in stationary phases of chronic airway disease and were vaccinated with either the tetravalent or trivalent influenza vaccine were selected. The number of patients with acute attacks, the number of outpatients with acute attacks, the number of outpatients, the number of inpatients, the total cost of patients, the cost of outpatients, the cost of hospitalization, and the length of hospitalization were collected before vaccination and after a one-year follow-up. There was no significant difference in age and sex ratio among the two vaccination groups. The ratios of acute attacks, outpatient visits, and hospitalizations and number of outpatient visits, number of hospitalizations, total medical expenses, outpatient expenses, and hospitalization expenses were significantly higher before vaccination than those after vaccination in both the trivalent-vaccination group and tetravalent-vaccination group. Additionally, there was no significant difference in the length of stay between before and after vaccination in either the trivalent-vaccination group or tetravalent-vaccination group. The protection effect between the trivalent-vaccination group and tetravalent-vaccination group was not significant. Influenza vaccination can effectively prevent the acute attack of chronic airway disease and delay the progress of chronic airway disease. [ABSTRACT FROM AUTHOR]

Persistent respiratory bacterial infections are a clinical burden in several chronic inflammatory airway diseases and are often associated with neutrophil infiltration into the lungs. Following recruitment, dysregulated neutrophil effector functions such as increased granule release and formation of neutrophil extracellular traps (NETs) result in damage to airway tissue, contributing to the progression of lung disease. Bacterial pathogens are a major driver of airway neutrophilic inflammation, but traditional management of infections with antibiotic therapy is becoming less effective as rates of antimicrobial resistance rise. Bacteriophages (phages) are now frequently identified as antimicrobial alternatives for antimicrobial resistant (AMR) airway infections. Despite growing recognition of their bactericidal function, less is known about how phages influence activity of neutrophils recruited to sites of bacterial infection in the lungs. In this review, we summarize current in vitro and in vivo findings on the effects of phage therapy on neutrophils and their inflammatory mediators, as well as mechanisms of phage-neutrophil interactions. Understanding these effects provides further validation of their safe use in humans, but also identifies phages as a targeted neutrophil-modulating therapeutic for inflammatory airway conditions.

Background/Objective: To assess whether and how the use of scientifically established Web-based training videos for teaching correct inhalation technique in patients with chronic airway diseases has become accepted among the wider population. Methods: The viewing trends of 141 freely available YouTube videos (full playing time, 01:31–04:37 min:s) provided by the German Respiratory League, covering a broad range of internationally prescribed devices, were analyzed over a 10-year period. Specific emphasis was placed both on German and international videos. Results: The total number of views was 3,350,678. Non-German videos (English, Russian, Turkish, Greek, Arabic, Farsi, and Slovakian) accounted for 23.2% of the views. The number of views steadily increased between 2011 and 2020 with a mean annual increase of 54.0% (range 24.5/119.9%) compared to the respective previous year. By 2020, the incidence of views per 100,000 German inhabitants was 725 for German videos only and 1,030 for all videos. In terms of the annual trend, there were two peak viewing periods, namely in spring and late fall, while the lowest amount of views occurred in summer. Conclusion: This study highlights the rising impact of Web-based training videos used for teaching the correct use of inhalation devices, with a steady increase in the number of annual views and a clear seasonal peaking of views in spring and late fall. [ABSTRACT FROM AUTHOR]

Patients with nontuberculous mycobacterial lung disease (NTM-LD) have increased mortality. The impact of NTM species on the risk of mortality remains unclear, especially that of death by non-cancer causes. We conducted a retrospective cohort study from 2006 to 2018 in a tertiary-care hospital in Taiwan. We enrolled patients who fulfilled the microbiological diagnostic criteria of NTM-LD. The mortality causes within 8 years after diagnosis were identified, and the Cox proportional hazard regression was performed for risk factors of mortality. A total of 1,652 subjects with NTM-LD were included. Among them, 723 (43.8%) were infected by Mycobacterium avium complex (MAC), 408 (24.7%) by M. abscessus complex (MABC), 120 (7.3%) by Mycobacterium kansasii (MK), 304 (18.4%) by other rapid-growing mycobacteria (RGM), and 97 (5.9%) by other slow-growing mycobacteria (SGM) groups. The 8-year all-cause mortality was 45.2% for all and the highest in the MK-LD group (59.2%), followed by the MABC-LD and MAC-LD groups. The adjusted hazard ratios were 2.20 (95% confidence interval: 1.40-3.46) in the MK-LD, 1.85 (1.54-2.22) in the MABC-LD, and 1.65 (1.12-2.41) in the MAC-LD groups for all-cause mortality, compared with the SGM group. Kaplan--Meier survival curves showed that all-cause mortality, non-cancer mortality, and mortality due to chronic airway diseases were significantly correlated with NTM species (log-rank p = 0.0031, < 0.001, and 0.001, respectively). High 8-year mortality rates were found in patients with NTM-LDs according to different NTM species. Notably, the difference was significant in non-cancer mortality causes, especially in chronic airway diseases. [ABSTRACT FROM AUTHOR]

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OBJECTIVE: To investigate the irrational prescription of patients with chronic airway disease in Hebei General Hospital(hereinafter referred to as “our hospital”), and explore the main factors of irrational prescription and formulate rationale improvement measures, so as to promote the clinical rational drug use. METHODS: Prescriptions of outpatients with chronic airway disease in our hospital from Jul. 2019 to Jun. 2020 were extracted to evaluate the rationality of drug use. Pareto analysis method was used to analyze the irrational prescription, find the main reason of irrational drug use and provide active intervention. The improvement of irrational prescription was compared before intervention(from Jul. 2019 to Jun. 2020) and after intervention(from Jul. 2020 to Jun. 2021). RESULTS: A total of 28 471 outpatient prescriptions with chronic airway disease from Jul. 2019 to Jun. 2020 were retrieved, and 2 635 irrational prescriptions were screened(9. 26%). There were 12 kinds of problems in irrational prescriptions, including 3 primary factors (no indication of drug use, incomplete clinical diagnosis and unsuitable drug selection), 3 secondary factors (unsuitable drug frequency, improper single dosage and improper course of treatment) and 6 general factors. After effective intervention for the main factors for 1 year, compared with before intervention, the proportion of irrational prescriptions and irrational rate of prescriptions decreased significantly after intervention, the success intervention rate of unreasonable prescriptions increased significantly, and the satisfaction of outpatient clinicians increased significantly, with statistically significant difference(P<0. 05). CONCLUSIONS: Pareto analysis method can be used to analyze irrational prescription of patients with chronic airway disease in our hospital, so as to scientifically and intuitively grasp the primary and secondary factors of irrational prescriptions, give play to the specialty of clinical pharmacists, and take targeted measures to actively intervene and promote the rational drug use. [ABSTRACT FROM AUTHOR]

This study investigated the effect of influenza vaccination on prevention of acute attacks in elderly patients with chronic airway disease and provides evidence for the prevention and control strategy of chronic airway disease in the elderly population. A total of 348 elderly patients in Linquan County, Anhui Province, China, who were also in stationary phases of chronic airway disease and were vaccinated with either the tetravalent or trivalent influenza vaccine were selected. The number of patients with acute attacks, the number of outpatients with acute attacks, the number of outpatients, the number of inpatients, the total cost of patients, the cost of outpatients, the cost of hospitalization, and the length of hospitalization were collected before vaccination and after a one-year follow-up. There was no significant difference in age and sex ratio among the two vaccination groups. The ratios of acute attacks, outpatient visits, and hospitalizations and number of outpatient visits, number of hospitalizations, total medical expenses, outpatient expenses, and hospitalization expenses were significantly higher before vaccination than those after vaccination in both the trivalent-vaccination group and tetravalent-vaccination group. Additionally, there was no significant difference in the length of stay between before and after vaccination in either the trivalent-vaccination group or tetravalent-vaccination group. The protection effect between the trivalent-vaccination group and tetravalent-vaccination group was not significant. Influenza vaccination can effectively prevent the acute attack of chronic airway disease and delay the progress of chronic airway disease.

Background: Air pollution exposure can increase the risk of development and exacerbation of chronic airway disease (CAD). We set out to assess CAD patients in Benin, Cameroon and The Gambia and to compare their measured exposures to air pollution., Methodology: We recruited patients with a diagnosis of CAD from four clinics in the three countries. We collected epidemiological, spirometric and home air pollution data., Results: Of the 98 adults recruited, 56 were men; the mean age was 51.6 years (standard deviation ±17.5). Most (69%) patients resided in cities and ever smoking was highest in Cameroon (23.0%). Cough, wheeze and shortness of breath were reported across the countries. A diagnosis of asthma was present in 74.0%; 16.3% had chronic obstructive pulmonary disease and 4.1% had chronic bronchitis. Prevalence of airflow obstruction was respectively 77.1%, 54.0% and 64.0% in Benin, Cameroon, and Gambia. Across the sites, 18.0% reported >5 exacerbations. The median home particulate matter less than 2.5 μm in diameter (PM 2.5 ) was respectively 13.0 μg/m 3 , 5.0 μg/m 3 and 4.4 μg/m 3 . The median home carbon monoxide (CO) exposures were respectively 1.6 parts per million (ppm), 0.3 ppm and 0.4 ppm. Home PM 2.5 differed significantly between the three countries ( P < 0.001) while home CO did not., Conclusion: Based on these results, preventive programmes should focus on ensuring proper spirometric diagnosis, good disease control and reduction in air pollution exposure., Competing Interests: Conflicts of interest: none declared., (© 2024 The Authors.)

Objective: To compare therapeutic response between Montelukast versus Montelukast plus inhaled corticosteroid (Budesonide) in children having mild persistent asthma. Study Design: Randomized Controlled Trial. Setting: Department of Pediatrics Medicine, National Institute of Child Health, Karachi. Period: 1st April 2016 to 30th September 2016. Material & Methods: Children aged 2 years to 14 years having mild persistent asthma for more than 6 months were included. After treatment Good response was considered when, forced expiratory volume in first second (FEV1) became >7.5% from baseline. Group A was given montelukast as monotherapy once daily and Group B was given Montelukast along with inhaled corticosteroid (Budesonide. At 6 weeks followup change in FEV1 was recorded. Result: Mean age of the patients in montelukast alone (Group A) was 6.77+/-2.16 years while in montelukast with Inhaled Corticosteroid (Group B) was 6.97+/-2.17 years. Duration of disease in Group A was 18.32+/-6.12 months while in montelukast with ICS group was 18.50 +/-6.08 months. Baseline FEV1 in Group A was 81.83+/-0.85% while in Group B was 82.05 +/-0.63%. Males were higher with 131 (61.8%). Family history was positive in 82 (38.70%) patients. After 6 weeks mean FEV1 was 89.49 +/-0.87% in Group A while in Group B was 89.53+/-0.86%. Overall good responses were found in 21 (9.09%) patients. In Group A, good response was found in 5 (4.7%) patients while in Group B was in 16 (15.1%) with significant p-value. Conclusion: In our study montelukast along with inhaled steroids had better response than montelukast alone in mild persistent asthma. [ABSTRACT FROM AUTHOR]

• The prevalence of fungal disease is increasing in CF and non-CF bronchiectasis. • Effective management of fungal disease requires an understanding of the mycobiome. • Culture methods alone are inadequate for the accurate diagnosis of fungal disease. • Our study provides a framework to characterize fungal airway disease using NGS. • NGS can improve detection and clinical management of fungal infections. The prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and non-CF bronchiectasis. Next generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls. ITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with non-CF bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20.4%), whereas in non-CF bronchiectasis sputum Candida albicans (21.8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp. , Exophiala spp., Candida parapsilosis or Scedosporium spp. This study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases. [ABSTRACT FROM AUTHOR]

Linyun Zhu,1 Zhenhua Ni,2 Xuming Luo,1 Zhuhua Zhang,1 Shiqiang Wang,1 Ziyu Meng,1 Xiandong Gu,1 Xiongbiao Wang1 1Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 2Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China Purpose: Chronic bronchitis is thought to occur in elderly patients, and smoking seems to be an important risk factor. The outcomes related to the age of onset in patients with chronic bronchitis are still unclear. Patients and methods: A retrospective study was conducted on deceased patients whose diagnosis included bronchitis from 2010 to 2016. Patients were separated into two groups according to the age of onset (Group I, age ≤50 years old; Group II, age >50 years old). Information regarding disease course, smoking history, death age, number of admissions per year, Hugh Jones Index, and self-reported comorbidities of the patients was recorded. Results: The courses of chronic cough and sputum were 33.38±7.73 years and 14.44±8.60 years in Group I and Group II, respectively (p

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]

The adverse effects of polluted air on human health have been increasingly appreciated worldwide. It is estimated that outdoor air pollution is associated with the death of 4.2 million people globally each year. Accumulating epidemiological studies indicate that exposure to ambient fine particulate matter (PM2.5), one of the important air pollutants, significantly contributes to respiratory mortality and morbidity. PM2.5 causes lung damage mainly by inducing inflammatory response and oxidative stress. In this paper, we reviewed the research results of our group on the effects of PM2.5 on chronic obstructive pulmonary disease, asthma, and lung cancer. And recent research progress on epidemiological studies and potential mechanisms were also discussed. Reducing air pollution, although remaining a major challenge, is the best and most effective way to prevent the onset and progression of respiratory diseases.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is characterised by chronic airway inflammation and concomitant systemic inflammation and associated with various comorbidities. Though cardiovascular complications have been most widely discussed, many studies over past two decades have identified stroke and carotid atherosclerosis to be associated with COPD. Some studies have postulated carotid atherosclerosis as a risk factor for impending stroke as well as a marker for cardiovascular complications. Aim: To evaluate carotid atherosclerosis in terms of carotid wall thickness (intima media thickness) in patients of COPD in absence of identifiable risk factors for carotid atherosclerosis. Materials and Methods: Patients admitted for acute exacerbation of COPD were screened for presence of carotid atherosclerois. Sixty seven patients were selected for study after meeting the inclusion criteria and after stabilisation of exacerbation were investigated by Color Doppler study of neck vessels and pulmonary function test. Distribution of data was tested for normalcy upon which parametric tests were used. Pearson correlation and one-way Anova tests were used using SPSS software. Results: Study included subjects more than 45 years (N=67). Mean age was 61.91±9.07 (Median=63.00). Airflow limitation was found to be of Grade IV in 55.2%, Grade III in 22.4% and Grade II in 22.4% of cases. Mean Carotid Intima Media Thickness (CIMT) was 1.19±0.35 mm. Strong inverse and significant correlation between FEV1-% Predicted (N=67, Mean 42.3, SD=14) and CIMT was found (Correlation coefficient (R) -0.696, p-value

Objective: Respiratory infections are a common cause of acute exacerbations in patients with chronic airway disease, however, environmental factors such as air pollution can also contribute to these exacerbations. The study aimed to determine the correlation between pollutant levels and exacerbation risks in areas exposed to environmental pollution sources., Methods: From 2015 to 2016, a total of 788 patients with chronic airway diseases were enrolled in a study. Their medical records, including hospital visits due to acute exacerbations of varying severity were analyzed. Additionally, data on daily pollutant levels from the Air Quality Monitoring Network from 2014 to 2016 was also collected and analyzed., Results: Patients with chronic airway disease and poor lung function (FEV1 < 50% or obstructive ventilatory defect) have a higher risk of severe acute exacerbations and are more likely to experience more than two severe acute exacerbations within a year. The study found that in areas exposed to environmental pollution sources, there is a significant correlation between NO 2 , O 3 , and humidity with the main causes of severe acute exacerbation. When the levels of NO 2 were higher than 16.65 ppb, O 3 higher than 35.65 ppb, or humidity higher than 76.95%, the risk of severe acute exacerbation in patients with chronic airway disease increased., Conclusion: Acute exacerbations of chronic airway disease can be triggered by both the underlying disease state and the presence of air pollution. Computer simulations and early warning systems should be developed to predict acute exacerbations of chronic airway disease based on dynamic changes in air pollution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chou, Chen, Peng, Chen and Cheng.)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is characterised by chronic airway inflammation and concomitant systemic inflammation and associated with various comorbidities. Though cardiovascular complications have been the most widely discussed, many studies over past two decades have identified stroke and carotid atherosclerosis to be associated with COPD. Some studies have postulated carotid atherosclerosis as a risk factor for impending stroke as well as a marker for cardiovascular complications. Aim: To evaluate carotid atherosclerosis in terms of carotid wall thickness (intima media thickness) in patients of COPD in absence of identifiable risk factors for carotid atherosclerosis. Materials and Methods: Patients admitted for acute exacerbation of COPD were screened for presence of carotid atherosclerois. Sixty seven patients were selected for study after meeting the inclusion criteria and after stabilisation of exacerbation were investigated by Color Doppler study of neck vessels and pulmonary function test. Distribution of data was tested for normalcy upon which parametric tests were used. Pearson correlation and one-way Anova tests were used using SPSS software. Results: Study included subjects more than 45 years (N=67). Mean age was 61.91±9.07 (Median=63.00). Airflow limitation was found to be of Grade IV in 55.2%, Grade III in 22.4% and Grade II in 22.4% of cases. Mean Carotid Intima Media Thickness (CIMT) was 1.19±0.35 mm. Strong inverse and significant correlation between FEV1-% Predicted (N=67, Mean 42.3, SD=14) and CIMT was found (Correlation coefficient (R) -0.696, p-value <0.001). FEV1/FVC % (N=67, Mean=58.4, SD=8.1). No significant correlation was seen with Body Mass Index (BMI) and Total Blood Cholesterol. Conclusion: Our study concluded that carotid atherosclerosis, quantified as CIMT, is inversely correlated to severity of airflow limitation in patients with COPD. The correlation is significant and studied in absence of factors which are known to be independent risk factors for atherosclerosis. [ABSTRACT FROM AUTHOR]

Acute exacerbations of chronic airway disease are common occurrences that cause a major burden of illness. Acute exacerbations are associated with impaired health status, increased lung function decline, hospitalization and increased risk of death. Exacerbation avoidance is a major priority. Despite this goal, exacerbations continue to occur and the need for effective models of care that optimize patient outcomes are urgently needed. 'Treatable Traits' is an approach to personalized medicine that has been proposed for the management of airway diseases. The treatable traits approach allows for the recognition of clinically important, identifiable and treatable disease characteristics, followed by targeted and individualized treatment interventions to address each trait. We review the literature relating to treatable traits in airway diseases; in particular, those traits that can predict exacerbations and approaches to management that aim to prevent exacerbations by using a treatable traits model of care. We propose this approach as a potentially useful model of care to both prevent and manage acute exacerbations. [ABSTRACT FROM AUTHOR]

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Background and Aims: Inhaled corticosteroids (ICSs) are crucial antiinflammatory medications for chronic airway diseases. Studies investigating the relationship between ICSs and fractures in Asian populations are scant. We investigated whether ICSs increased the risk of low-energy fractures in patients with chronic airway diseases. Methods: We used the Longitudinal Health Insurance Database to select patients aged 20 years and older with chronic airway diseases (asthma and COPD) between 2000 and 2011 as the base cohort. We identified ICS users and ICS non-users matched by propensity score method at 1:1 ratio. Cox proportional hazard regression models were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for factors associated with the risk of fracture. Results: A total of 1,182 ICS users and 1,182 controls were enrolled. After adjustment for age, gender, annual exacerbation number of acute respiratory events, comorbidity and medications, the risk of fracture was 1.10 for ICS users (aHR=1.20; 95% CI=1.10-1.31) compared with ICS non-users. The ICS users exhibited significantly 1.63-fold risk of hip fracture and 1.24-fold risk of ulna and radius fracture than did the ICS non-users. Patients with medium and high doses of ICS use were associated with significantly increased risks of fracture (aHR=1.48, 95% CI=1.25-1.76 for medium dose and aHR=1.55, 95% CI=1.39-1.72 for high dose) compared with those in ICS non-users. Conclusions: Patients with medium and high doses of ICS use are associated with an increased risk of fracture. [ABSTRACT FROM AUTHOR]

Studies of human airway virome are relatively recent and still very limited. Culture-independent microbial techniques showed growing evidence of numerous viral communities in the respiratory microbial ecosystem. The significance of different acute respiratory viruses is already known in the pathogenesis of chronic conditions, such as asthma, cystic fibrosis (CF), or chronic obstructive lung disease (COPD), and their exacerbations. Viral pathogens, such as influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, or rhinovirus, have been associated with impaired immune response, acute exacerbations, and decrease in lung function in chronic lung diseases. However, more data have attributed a role to Herpes family viruses or the newly identified Anelloviridae family of viruses in chronic diseases, such as asthma, idiopathic pulmonary fibrosis (IPF), or CF. Impaired antiviral immunity, bacterial colonization, or used medication, such as glucocorticoids or antibiotics, contribute to the imbalance of airway microbiome and may shape the local viral ecosystem. A specific part of virome, bacteriophages, frames lung microbial communities through direct contact with its host, the specific bacteria known as Pseudomonas aeruginosa or their biofilm formation. Moreover, antibiotic resistance is induced through phages via horizontal transfer and leads to more severe exacerbations of chronic airway conditions. Morbidity and mortality of asthma, COPD, CF, and IPF remains high, despite an increased understanding and knowledge about the impact of respiratory virome in the pathogenesis of these conditions. Thus, more studies focus on new prophylactic methods or therapeutic agents directed toward viral–host interaction, microbial metabolic function, or lung microbial composition rearrangement.

Background Association between chronic airway diseases (CAD) and gastroesophageal reflux disease (GERD) is well described, but causality has not yet been conclusively established. This study evaluates the therapeutic significance of laparoscopic Thal fundoplication in children with CAD and diagnosed GERD. Methods We performed a retrospective analysis of 182 neurologically nonimpaired children, all with medically refractory CAD and GERD undergoing laparoscopic Thal fundoplication. The clinical response, ability to wean oral and inhaled medication and satisfaction with postoperative results were evaluated. Results Main symptoms disappeared completely in 68.7% of patients and were markedly improved in a further 22% of patients following surgery. Complete discontinuation of medication was achieved in 70.1–96.4% of cases and reduced in a further 1.8–23.5%. One intraoperative complication occurred (gastric perforation), however no conversion to laparotomy was necessary. Postoperative Dumping Syndrome occurred in 1% of cases and was managed dietetically. Prolonged postoperative dysphagia occurred in 4.3% of patients, but disappeared within 8 weeks in all but one case. Conclusions Our study suggests that Thal fundoplication in neurologically nonimpaired children with CAD and documented GERD is effective and safe. Children unresponsive to preoperative medical management showed significant improvement in airway symptoms together with a marked reduction in the need for medication. We conclude that laparoscopic Thal fundoplication represents a significant treatment worthy of consideration in this group of patients. [ABSTRACT FROM AUTHOR]

Persistent respiratory bacterial infections are a clinical burden in several chronic inflammatory airway diseases and are often associated with neutrophil infiltration into the lungs. Following recruitment, dysregulated neutrophil effector functions such as increased granule release and formation of neutrophil extracellular traps (NETs) result in damage to airway tissue, contributing to the progression of lung disease. Bacterial pathogens are a major driver of airway neutrophilic inflammation, but traditional management of infections with antibiotic therapy is becoming less effective as rates of antimicrobial resistance rise. Bacteriophages (phages) are now frequently identified as antimicrobial alternatives for antimicrobial resistant (AMR) airway infections. Despite growing recognition of their bactericidal function, less is known about how phages influence activity of neutrophils recruited to sites of bacterial infection in the lungs. In this review, we summarize current in vitro and in vivo findings on the effects of phage therapy on neutrophils and their inflammatory mediators, as well as mechanisms of phage-neutrophil interactions. Understanding these effects provides further validation of their safe use in humans, but also identifies phages as a targeted neutrophil-modulating therapeutic for inflammatory airway conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laucirica, Stick, Garratt and Kicic.)

Patients with nontuberculous mycobacterial lung disease (NTM-LD) have increased mortality. The impact of NTM species on the risk of mortality remains unclear, especially that of death by non-cancer causes. We conducted a retrospective cohort study from 2006 to 2018 in a tertiary-care hospital in Taiwan. We enrolled patients who fulfilled the microbiological diagnostic criteria of NTM-LD. The mortality causes within 8 years after diagnosis were identified, and the Cox proportional hazard regression was performed for risk factors of mortality. A total of 1,652 subjects with NTM-LD were included. Among them, 723 (43.8%) were infected by Mycobacterium avium complex (MAC), 408 (24.7%) by M. abscessus complex (MABC), 120 (7.3%) by Mycobacterium kansasii (MK), 304 (18.4%) by other rapid-growing mycobacteria (RGM), and 97 (5.9%) by other slow-growing mycobacteria (SGM) groups. The 8-year all-cause mortality was 45.2% for all and the highest in the MK-LD group (59.2%), followed by the MABC-LD and MAC-LD groups. The adjusted hazard ratios were 2.20 (95% confidence interval: 1.40-3.46) in the MK-LD, 1.85 (1.54-2.22) in the MABC-LD, and 1.65 (1.12-2.41) in the MAC-LD groups for all-cause mortality, compared with the SGM group. Kaplan-Meier survival curves showed that all-cause mortality, non-cancer mortality, and mortality due to chronic airway diseases were significantly correlated with NTM species (log-rank p = 0.0031, < 0.001, and 0.001, respectively). High 8-year mortality rates were found in patients with NTM-LDs according to different NTM species. Notably, the difference was significant in non-cancer mortality causes, especially in chronic airway diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Pan, Wang, Shu and Chang.)

Neutrophilic inflammation is associated with chronic airway diseases. It has been observed that human neutrophil elastase (HNE), which is secreted by active neutrophils during inflammation, induces both mucin overproduction and goblet cell metaplasia. Several in vitro studies suggest that tumor necrosis factor-α converting enzyme (TACE) regulates the signaling axis that mediates HNE-induced mucin overproduction; however, it is unknown whether TACE performs a similar function in HNE-induced goblet cell metaplasia in vivo. We conducted this study to determine whether the inactivation of Tace gene expression attenuates HNE-induced goblet cell metaplasia in mice. Deletion of Tace is lethal shortly after birth in mice; therefore, we utilized Taceflox/floxR26CreER+/- mice and induced conditional deletion of Tace using a tamoxifen injection. Wild-type mice were given tamoxifen to control for its effect. Tace conditional deletion mice and wild-type mice were exposed to HNE via nasal instillation three times at 3-day intervals, and the lungs were harvested on day 11 after initial HNE exposure. Using periodic acid-Schiff staining and MUC5AC immunohistochemical staining to visualize goblet cells in the lungs, we found that HNE induced goblet cell metaplasia in the wild-type mice and that HNE-induced goblet cell metaplasia was significantly attenuated in the Tace conditional deletion mice. These findings suggest that TACE could be a potential target in the treatment of goblet cell metaplasia in patients with chronic airway diseases. [ABSTRACT FROM AUTHOR]

Objectives: The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases. Methods: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo . Sputum smears were also prepared to count sputum neutrophils. Patients’ symptoms were assessed by a questionnaire that used a visual analogue scale. Results: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 ± 1.8 to 24.4 ± 2.5 (P = 0.0103). Conclusions: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases. [ABSTRACT FROM AUTHOR]

The adverse effects of polluted air on human health have been increasingly appreciated worldwide. It is estimated that outdoor air pollution is associated with the death of 4.2 million people globally each year. Accumulating epidemiological studies indicate that exposure to ambient fine particulate matter (PM2.5), one of the important air pollutants, significantly contributes to respiratory mortality and morbidity. PM2.5 causes lung damage mainly by inducing inflammatory response and oxidative stress. In this paper, we reviewed the research results of our group on the effects of PM2.5 on chronic obstructive pulmonary disease, asthma, and lung cancer. And recent research progress on epidemiological studies and potential mechanisms were also discussed. Reducing air pollution, although remaining a major challenge, is the best and most effective way to prevent the onset and progression of respiratory diseases. [ABSTRACT FROM AUTHOR]

Objective:Immunoglobulin binding factor (IgBF) is known to bind immunoglobulin, to interact with anti-Fcγ-III antibodies and to be present in the lower respiratory tract of normal healthy subjects. In this study, in order to clarify the role of IgBF in vespiratory diseases, we investigated whether IgBF exists in the airway of patients with chronic airway diseases. Methodology: IgBF was measured in the sputum of 28 normal subjects and 59 patients with chronic airway diseases including 37 cases of chronic bronchitis, 18 bronchiectasis, and four diffuse panbronchiolitis by enzyme-linked immunosorbent assay. Results: Immunoglobulin binding factor concentration in the sputum of patients with chronic airway diseases (purulent sputum, 50.2 ± 8.2 μg/mL; mucoid sputum, 88.6 ± 12.8 μg/mL) was higher than that in induced sputum of normal subjects (6.3 ± 5.5 μg/mL; P < 0.001). Immunoglobulin binding factor level in mucoid sputum was significantly higher than that in purulent sputum (P < 0.05). A significant inverse correlation was shown between the IgBF level and the elastase activity in sputum, and the concentration of IgBF purified from seminal plasma was decreased by treatment with neutrophil elastase, indicating that IgBF might be degraded by elastase. In the gel filtration chromatography of both types of sputum, IgBF was eluted in a region corresponding to a molecular weight of 27 kDa as a single peak. Western blot analysis with a monoclonal antibody to IgBF indicated that IgBF in both types of sputum had a molecular weight of 27 kDa under non-reducing conditions and of 16 kDa under reducing conditions. Conclusion: These results demonstrate that a high level of IgBF is present in the respiratory tract of patients with chronic airway diseases and may be related to the pathogenesis of these diseases. [ABSTRACT FROM AUTHOR]