Exploring the mechanism of Lianhuaqingwen (LHQW) in treating chronic bronchitis based on network pharmacology and experimental validation.

BACKGROUND: Lianhuaqingwen (LHQW) has been used in the treatment of chronic bronchitis, but the precise mechanism through which LHQW exhibits its anti-inflammatory effects in this context is not yet fully understood. The aim of this study was to investigate the active ingredients and signaling pathways responsible for LHQW's effectiveness in managing chronic bronchitis. METHODS: The research leveraged the TCMSP database to determine the active compounds and drug targets of LHQW. In parallel, the GeneCards, DrugBank, and PharmGkb databases were used to uncover targets pertinent to chronic bronchitis. To discern the potential mechanisms by which LHQW's active ingredients might treat chronic bronchitis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Network pharmacology facilitated the construction of a drug-active ingredient-disease target network, aiding in forecasting the core targets for chronic bronchitis treatment by LHQW. Subsequently, molecular docking techniques alongside in vitro experiments were applied to confirm the interactions between the active ingredients and the primary targets. RESULTS: A total of 157 active ingredients, 225 potential drug targets, and 594 bronchitis-related targets were derived from various databases. Following this, 76 potential gene targets were pinpointed by integrating drug and related targets. GO and KEGG enrichment analyses were employed to identify key pathways involved in LHQW's mechanism for treating chronic bronchitis. By constructing a protein-protein interaction (PPI) network for the 76 potential gene targets, four core targets (TNF, IL6, IFNG, and STAT3) were identified as primarily involved in responses to lipopolysaccharide, the TNF pathway, and the JAK-STAT pathway. Molecular docking results revealed a favorable affinity between multiple active ingredients of LHQW and the four core targets, suggesting that the therapeutic effects are mediated through the inhibition of inflammatory responses and signaling pathways. Interestingly, quercetin, an active ingredient of LHQW, was observed to bind to all four core targets simultaneously. Furthermore, cell experiment and western blot analysis indicated that both LHQW and quercetin exhibit anti-inflammatory effects by targeting the four core proteins and the JAK-STAT pathways. CONCLUSION: This research emphasizes the diverse active ingredients, targets, channels, and pathways of LHQW in the treatment of chronic bronchitis, providing important perspectives for the creation of novel therapeutic drugs and clinical uses.

Assessment of wood smoke induced pulmonary toxicity in normal- and chronic bronchitis-like bronchial and alveolar lung mucosa models at air-liquid interface.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has the highest increased risk due to household air pollution arising from biomass fuel burning. However, knowledge on COPD patho-mechanisms is mainly limited to tobacco smoke exposure. In this study, a repeated direct wood smoke (WS) exposure was performed using normal- (bro-ALI) and chronic bronchitis-like bronchial (bro-ALI-CB), and alveolar (alv-ALI) lung mucosa models at air-liquid interface (ALI) to assess broad toxicological end points. METHODS: The bro-ALI and bro-ALI-CB models were developed using human primary bronchial epithelial cells and the alv-ALI model was developed using a representative type-II pneumocyte cell line. The lung models were exposed to WS (10 min/exposure; 5-exposures over 3-days; n = 6-7 independent experiments). Sham exposed samples served as control. WS composition was analyzed following passive sampling. Cytotoxicity, total cellular reactive oxygen species (ROS) and stress responsive NFkB were assessed by flow cytometry. WS exposure induced changes in gene expression were evaluated by RNA-seq (p ≤ 0.01) followed by pathway enrichment analysis. Secreted levels of proinflammatory cytokines were assessed in the basal media. Non-parametric statistical analysis was performed. RESULTS: 147 unique compounds were annotated in WS of which 42 compounds have inhalation toxicity (9 very high). WS exposure resulted in significantly increased ROS in bro-ALI (11.2%) and bro-ALI-CB (25.7%) along with correspondingly increased NFkB levels (bro-ALI: 35.6%; bro-ALI-CB: 18.1%). A total of 1262 (817-up and 445-down), 329 (141-up and 188-down), and 102 (33-up and 69-down) genes were differentially regulated in the WS-exposed bro-ALI, bro-ALI-CB, and alv-ALI models respectively. The enriched pathways included the terms acute phase response, mitochondrial dysfunction, inflammation, oxidative stress, NFkB, ROS, xenobiotic metabolism of AHR, and chronic respiratory disorder. The enrichment of the 'cilium' related genes was predominant in the WS-exposed bro-ALI (180-up and 7-down). The pathways primary ciliary dyskinesia, ciliopathy, and ciliary movement were enriched in both WS-exposed bro-ALI and bro-ALI-CB. Interleukin-6 and tumor necrosis factor-α were reduced (p < 0.05) in WS-exposed bro-ALI and bro-ALI-CB. CONCLUSION: Findings of this study indicate differential response to WS-exposure in different lung regions and in chronic bronchitis, a condition commonly associated with COPD. Further, the data suggests ciliopathy as a candidate pathway in relation to WS-exposure.

The role of chest computed tomography in the evaluation and management of chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: The purpose of this review is to compile recent data on the clinical associations of computed tomography (CT) scan findings in the literature and potential avenues for implementation into clinical practice. RECENT FINDINGS: Airways dysanapsis, emphysema, chronic bronchitis, and pulmonary vascular metrics have all recently been associated with poor chronic obstructive pulmonary disease (COPD) outcomes when controlled for clinically relevant covariables, including risk of mortality in the case of emphysema and chronic bronchitis. Other authors suggest that CT scan may provide insight into both lung parenchymal damage and other clinically important comorbidities in COPD. SUMMARY: CT scan findings in COPD relate to clinical outcomes. There is a continued need to develop processes to best implement the results of these studies into clinical practice.

Bronchoscopic interventions for chronic bronchitis.

PURPOSE OF REVIEW: Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased rate of COPD exacerbations and hospital admissions, a more rapid decline in lung function and reduced life expectancy. Despite optimal medical therapy, chronic bronchitis remains difficult to treat. Interventional bronchoscopic procedures offer novel therapeutic approaches to this highly symptomatic condition. RECENT FINDINGS: A characteristic feature of chronic bronchitis is the presence of an abnormal epithelium with excessive mucus producing cells, parasympathetic overactivity, and airway inflammation. Metered cryospray and bronchial rheoplasty are designed to target this abnormal epithelium to reduce mucus production and inflammation. Targeted lung denervation aims to reduce parasympathetic overactivity, which may drive mucus hypersecretion. Here, we review the available evidence to determine the safety and efficacy across the bronchoscopic interventions. SUMMARY: Interventional bronchoscopy is a rapidly expanding field and its application in the treatment of chronic bronchitis has been recognized by the Global initiative for chronic Obstructive Lung Disease (GOLD). The outcomes from the latest clinical trials will guide future treatment approaches in patients with difficult to treat chronic bronchitis.

Chronic respiratory symptoms following deployment-related occupational and environmental exposures among US veterans.

OBJECTIVES: Characterise inhalational exposures during deployment to Afghanistan and Southwest Asia and associations with postdeployment respiratory symptoms. METHODS: Participants (n=1960) in this cross-sectional study of US Veterans (Veterans Affairs Cooperative Study 'Service and Health Among Deployed Veterans') completed an interviewer-administered questionnaire regarding 32 deployment exposures, grouped a priori into six categories: burn pit smoke; other combustion sources; engine exhaust; mechanical and desert dusts; toxicants; and military job-related vapours gas, dusts or fumes (VGDF). Responses were scored ordinally (0, 1, 2) according to exposure frequency. Factor analysis supported item reduction and category consolidation yielding 28 exposure items in 5 categories. Generalised linear models with a logit link tested associations with symptoms (by respiratory health questionnaire) adjusting for other covariates. OR were scaled per 20-point score increment (normalised maximum=100). RESULTS: The cohort mean age was 40.7 years with a median deployment duration of 11.7 months. Heavy exposures to multiple inhalational exposures were commonly reported, including burn pit smoke (72.7%) and VGDF (72.0%). The prevalence of dyspnoea, chronic bronchitis and wheeze in the past 12 months was 7.3%, 8.2% and 15.6%, respectively. Burn pit smoke exposure was associated with dyspnoea (OR 1.22; 95% CI 1.06 to 1.47) and chronic bronchitis (OR 1.22; 95% CI 1.13 to 1.44). Exposure to VGDF was associated with dyspnoea (OR 1.29; 95% CI 1.14 to 1.58) and wheeze (OR 1.18; 95% CI 1.02 to 1.35). CONCLUSION: Exposures to burn pit smoke and military occupational VGDF during deployment were associated with an increased odds of chronic respiratory symptoms among US Veterans.

Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial.

Rationale: CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction is associated with mucus accumulation and worsening chronic obstructive pulmonary disease (COPD) symptoms. Objectives: The aim of this phase IIb dose-finding study was to compare a CFTR potentiator, icenticaftor (QBW251), with placebo in patients with COPD and chronic bronchitis. Methods: Patients with COPD on triple therapy for at least three months were randomized to six treatment arms (icenticaftor 450, 300, 150, 75, or 25 mg or placebo twice daily [b.i.d.]) in a 24-week, multicenter, parallel-group, double-blind study. The primary endpoint was change from baseline in trough FEV1 after 12 weeks. Secondary endpoints included change from baseline in trough FEV1 and Evaluating Respiratory Symptoms in COPD (E-RS) total and cough and sputum scores after 24 weeks. Multiple comparison procedure-modeling was conducted to characterize dose-response relationship. Rescue medication use, exacerbations, and change in serum fibrinogen concentration after 24 weeks were assessed in exploratory and post hoc analyses, respectively. Measurements and Main Results: Nine hundred seventy-four patients were randomized. After 12 weeks of icenticaftor treatment, no dose-response relationship for change from baseline in trough FEV1 was observed; however, it was observed for E-RS cough and sputum score. A dose-response relationship was observed after 24 weeks for trough FEV1, E-RS cough and sputum and total scores, rescue medication use, and fibrinogen. A dose of 300 mg b.i.d. was consistently the most effective. Improvements for 300 mg b.i.d. versus placebo were also seen in pairwise comparisons of these endpoints. All treatments were well tolerated. Conclusions: The primary endpoint was negative, as icenticaftor did not improve trough FEV1 over 12 weeks. Although the findings must be interpreted with caution, icenticaftor improved trough FEV1; reduced cough, sputum, and rescue medication use; and lowered fibrinogen concentrations at 24 weeks. Clinical trial registered with www.clinicaltrials.gov (NCT04072887).

Serum IL-8 as a Determinant of Response to Phosphodiesterase-4 Inhibition in Chronic Obstructive Pulmonary Disease.

Rationale: Phosphodiesterase-4 (PDE4) inhibitors have demonstrated increased efficacy in patients with chronic obstructive pulmonary disease who had chronic bronchitis or higher blood eosinophil counts. Further characterization of patients who are most likely to benefit is warranted. Objective: To identify determinants of response to the PDE4 inhibitor tanimilast. Methods: A PDE4 gene expression signature in blood was developed by unsupervised clustering of the ECLIPSE study dataset (ClinicalTrials.gov ID: NCT00292552; Gene Expression Omnibus Series ID: GSE76705). The signature was further evaluated using blood and sputum transcriptome data from the BIOMARKER study (NCT03004417; GSE133513), enabling validation of the association between PDE4 signaling and target biomarkers. Predictivity of the associated biomarkers against clinical response was then tested in the phase-2b PIONEER tanimilast study (NCT02986321). Measurements and Main Results: The PDE4 gene expression signature developed in the ECLIPSE dataset classified subgroups of patients associated with different PDE4 signaling in the BIOMARKER cohort with an area under the receiver operator curve of 98%. In the BIOMARKER study, serum IL-8 was the only variable that was consistently associated with PDE4 signaling, with lower levels associated with higher PDE4 activity. In the PIONEER study, the exacerbation rate reduction mediated by tanimilast treatment increased up to twofold in patients with lower IL-8 levels; 36% versus 18%, reaching statistical significance at ⩽20 pg/ml (P = 0.035). The combination with blood eosinophils ⩾150 µl-1 or chronic bronchitis provided further additive exacerbation rate reduction: 45% (P = 0.013) and 47% (P = 0.027), respectively. Conclusions: Using selected heterogeneous datasets, this analysis identifies IL-8 as an independent predictor of PDE4 inhibition, as tanimilast had a greater effect on exacerbation prevention in patients with chronic obstructive pulmonary disease who had lower baseline serum IL-8 levels. Testing of this biomarker in other datasets is warranted. Clinical trial registered with www.clinicaltrials.gov (NCT00292552 [Gene Expression Omnibus Series ID: GSE76705], NCT03004417 [GSE133513], and NCT02986321).

Clinical significance of chronic bronchitis in different racial groups.

BACKGROUNDS: Limited data are available on racial differences in the clinical features of chronic bronchitis (CB) patients with chronic obstructive pulmonary disease (COPD). In this study, we aimed to compare clinical features among CB patients of different races. We also analyzed the clinical significance of CB, defined classically and based on the COPD Assessment Test (CAT), to validate the CAT-based definition. METHODS: We analyzed patient data extracted from the Korean COPD Subgroup Study (KOCOSS) cohort (2012-2021) and US Genetic Epidemiology of COPD (COPDGene) study (2008-2011). We compared clinical characteristics among CB and non-CB patients of three different races using two CB definitions. RESULTS: In this study, 3,462 patients were non-Hispanic white (NHW), 1,018 were African American (AA), and 1,793 were Asian. The proportions of NHW, AA, and Asian patients with CB according to the classic definition were 27.4%, 20.9%, and 10.7%, compared with 25.2%, 30.9%, and 23.0% according to the CAT-based definition, respectively. The risk of CB prevalence was highest in NHW and lowest in Asian COPD patients. Among all races, CB patients were more likely to be current smokers, have worse respiratory symptoms and poorer health-related quality of life (HrQoL), and to have decreased lung function and exercise capacity. Most of these characteristics showed similar associations with the outcomes between the two definitions of CB. A binominal regression model revealed that CB patients of all races had an increased risk of future exacerbations according to both CB definitions, except for Asian patients with classically defined CB. CONCLUSIONS: The presence of CB was associated with worse respiratory symptoms, HrQoL, exercise capacity and lung function, and more exacerbations, regardless of race or CB definition. The CAT-based definition may be more useful for assessing the risk of future exacerbations in Asian COPD patients.

Contribution of small airway inflammation to the development of COPD.

BACKGROUND: Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD. METHODS: A total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO50, FeNO200, and calculated CaNOdual. Both FeNO200 and CaNOdual were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD. RESULTS: Exhaled NO levels (FnNO, FeNO50, FeNO200, and CaNOdual) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO50, FeNO200, and CaNOdual) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO200 was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNOdual (AUC ROC = 0.707) in COPD. FeNO200 was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO50 and FeNO200. CONCLUSION: The complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.

The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma: a study protocol.

BACKGROUND: Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an 'add-on' test in asthma diagnostics [2, 3]. METHODS AND ANALYSIS: This multi-center prospective study (Trial number: NCT06230458) compares the 'standard asthma diagnostic work-up' (spirometry with reversibility and BPT) to the 'new asthma diagnostics work-up' (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. ETHICS AND DISSEMINATION: The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. LIMITATIONS: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.

Assessing the effectiveness of mitigating pesticide-related disease risk among pesticide-spraying drone operators in Taiwan.

OBJECTIVES: The purpose of this study was to evaluate the risk of pesticide poisoning, liver and renal failure, dermatitis, respiratory problems, hypersensitivity pneumonitis, keratitis, and epilepsy among pesticide-spraying personnel and to assess the effectiveness of a new method of aerial pesticide application in reducing this risk. METHODS: A total of 2268 pesticide spraying operators (1651 ground-based field crop operators and 617 aerial pesticide spraying drone operators) who passed the national certification examination between 2010 and 2020 in Taiwan were included. Ground-based operators served as the positive control group, while 2463 farmer controls were matched from the Farmers' Health Insurance database as the negative control group. Data from the National Health Insurance Research Database were used to track possible pesticide-related disease cases. Logistic regression was employed to calculate odds ratios and 95% confidence intervals (95% CI). RESULTS: Drone operators had significantly reduced risks of dermatitis, asthma and chronic bronchitis compared to ground-based operators. This was observed in allergic contact dermatitis (OR = 0.40, 95% CI: 0.24-0.68), unspecified contact dermatitis (OR = 0.58, 95% CI: 0.35-0.97), asthma (OR = 0.27, 95% CI: 0.12-0.60), and chronic bronchitis (OR = 0.24, 95% CI: 0.06-0.93), after adjusting for age, sex, working areas, and licensing years. However, no significant differences were found when comparing drone operators to matching farmers. CONCLUSIONS: Aerial pesticide spraying using drones may contribute to a decreased risk of dermatitis, asthma and chronic bronchitis, suggesting potential health benefits for operators. Further field pesticide exposure surveys are recommended to validate these findings and assess health risk indicators.

Chronic conditions and incident and persistent depressive symptoms among ageing adults in rural South Africa.

The study aimed to assess associations between chronic diseases and incident and persistent depressive symptoms (DSs) in a cohort study of ageing adults in South Africa. Participants in the baseline survey (in 2014/2015) were 5,059 persons (≥40 years) and at follow-up 4,176 (in 2018/2019). DSs were measured with the Center for Epidemiological Studies Depression scale. Logistic regression was used to estimate the associations between chronic conditions and incident and persistent DS. The prevalence of DS at baseline was 15.5%, incident DS (without DS and/or PTSD at baseline) was 25.1% and persistent DS (DS at both baseline and follow-up) was 4.8%. In unadjusted logistic regression analysis, diabetes had higher odds of incident DS. Participants with baseline heart attack/stroke/angina, dyslipidemia, tuberculosis, chronic bronchitis, kidney disease and three or more chronic conditions had a higher probability of persistent DS. In conclusion, of the eight chronic conditions evaluated, only diabetes (in unadjusted analysis) was associated with incident DS, and five chronic conditions (heart attack/stroke/angina, dyslipidaemia, tuberculosis, chronic bronchitis and kidney disease) and three or more chronic conditions were associated with persistent DS.

From pre-COPD to COPD: a Simple, Low cost and easy to IMplement (SLIM) risk calculator.

BACKGROUND: The lifetime risk of developing clinical COPD among smokers ranges from 13% to 22%. Identifying at-risk individuals who will develop overt disease in a reasonable timeframe may allow for early intervention. We hypothesised that readily available clinical and physiological variables could help identify ever-smokers at higher risk of developing chronic airflow limitation (CAL). METHODS: Among 2273 Lovelace Smokers' Cohort (LSC) participants, we included 677 (mean age 54 years) with normal spirometry at baseline and a minimum of three spirometries, each 1 year apart. Repeated spirometric measurements were used to determine incident CAL. Using logistic regression, demographics, anthropometrics, smoking history, modified Medical Research Council dyspnoea scale, St George's Respiratory Questionnaire, comorbidities and spirometry, we related variables obtained at baseline to incident CAL as defined by the Global Initiative for Chronic Obstructive Lung Disease and lower limit of normal criteria. The predictive model derived from the LSC was validated in subjects from the COPDGene study. RESULTS: Over 6.3 years, the incidence of CAL was 26 cases per 1000 person-years. The strongest independent predictors were forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.75, having smoked ≥30 pack-years, body mass index (BMI) ≤25 kg·m2 and symptoms of chronic bronchitis. Having all four predictors increased the risk of developing CAL over 6 years to 85% (area under the receiver operating characteristic curve (AUC ROC) 0.84, 95% CI 0.81-0.89). The prediction model showed similar results when applied to subjects in the COPDGene study with a follow-up period of 10 years (AUC ROC 0.77, 95% CI 0.72-0.81). CONCLUSION: In middle-aged ever-smokers, a simple predictive model with FEV1/FVC, smoking history, BMI and chronic bronchitis helps identify subjects at high risk of developing CAL.

Analysis of sputum microbial flora in chronic obstructive pulmonary disease patients with different phenotypes during acute exacerbations.

BACKGROUND: Increasing studies have shown that the imbalance of the respiratory microbial flora is related to the occurrence of COPD, the severity and frequency of exacerbations and mortality.However, it remains unclear how the sputum microbial flora differs during exacerbations in COPD patients manifesting emphysema phenotype, chronic bronchitis with emphysema phenotype and asthma-COPD overlap phenotype. METHODS: Sputum samples were obtained from 29 COPD patients experiencing acute exacerbations who had not received antibiotics or systemic corticosteroids within the past four weeks.Patients were divided into three groups;emphysema phenotype(E);chronic bronchitis with emphysema phenotype(B+E) and asthma-COPD overlap phenotype(ACO).We utilized metagenomic Next Generation Sequencing (mNGS) technology to analyze the sputum microbial flora in COPD patients with different phenotypes during exacerbations. RESULTS: There was no significant difference in alpha diversity and beta diversity among three groups.The microbial flora composition was similar in all three groups during exacerbations except for a significant increase in Streptococcus mitis in ACO.Through network analysis,we found Candidatus Saccharibacteria oral taxon TM7x and Fusobacterium necrophorum were the core nodes of the co-occurrence network in ACO and E respectively.They were positively correlated with some species and play a synergistic role.In B+E,Haemophilus pittmaniae and Klebsiella pneumoniae had a synergistic effect.Besides,some species among the three groups play a synergistic or antagonistic role.Through Spearman analysis,we found the relative abundance of Streptococcus mitis was negatively correlated with the number of hospitalizations in the past year(r = -0.410,P = 0.027).We also observed that the relative abundance of Prevotella and Prevotella melaninogenica was negatively correlated with age(r = -0.534,P = 0.003;r = -0.567,P = 0.001),while the relative abundance of Streptococcus oralis and Actinomyces odontolyticus was positively correlated with age(r = 0.570,P = 0.001;r = 0.480,P = 0.008).In addition,the relative abundance of Prevotella melaninogenica was negatively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio(r = -0.479,P = 0.009;r = -0.555,P = 0.002),while the relative abundance of Streptococcus sanguinis was positively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio (r = 0.450,P = 0.014;r = 0.501,P = 0.006).There was also a significant positive correlation between Oribacterium and blood eosinophil counts(r = 0.491,P = 0.007). CONCLUSION: Overall,we analyzed the sputum microbiota of COPD patients with different phenotypes and its relationship with clinical indicators, and explored the relationships between microbiota and inflammation in COPD.We hope to alter the prognosis of patients by inhibiting specific bacterial taxa related to inflammation and using guide individualized treatment in the future research.

Airway Mucosal Remodeling: Mechanism of Action and Preclinical Data of Pulsed Electric Fields for Chronic Bronchitis and Mucus Hypersecretion.

Patients living with chronic bronchitis (CB) suffer from physical limitations and poor quality of life. In general, treatment options that directly address the mucus hypersecretion component of CB are quite limited. Chronic airway inflammation and the associated hypersecretion and cough that are pathognomonic for CB generally result from long-term exposure to airway irritants such as tobacco use and other environmental insults. This, in turn, results in an increase in the quantity and change in composition of the airway mucosa as a consequence of altered goblet cells, club cells, and submucosal glands. Pulsed electric fields (PEFs) provide a method for eradicating the cellular constituents of tissue with limited impact on the stromal proteins. Preclinical evidence in porcine airways demonstrated that particular PEF waveforms allowed for salutary remodeling of the epithelial and submucosal airway tissue layers and appeared to foster rapid regeneration and recovery of the tissue. Therefore, a therapeutic opportunity might exist whereby the application of a specific form of PEF may result in a reduction of the cellular secretory constituents of the airway while also reducing airway mucosal inflammation. This review discusses the use of such PEF to address the underlying disease processes in CB including challenges around device design, dosing, and appropriate delivery methods. Further, we outline considerations for the transition to human airways along with a brief examination of the initial work treating CB patients, suggesting that the therapy is well tolerated with limited adverse events.

Effects of spray cryotherapy on cough receptors and airway microenvironment in a canine model of chronic bronchitis.

The aim of this study was to explore the effects of spray cryotherapy (SCT) on cough receptors and airway microenvironment in a canine model of chronic bronchitis. We examined the expression of transient receptor potential vanilloid 1/4 (TRPV1/4) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) at the gene and protein levels before and after SCT. In addition, we explored whether TRPV1/4 could regulate inflammatory factors via mediator adenosine triphosphate (ATP). The levels of ATP and cytokines in alveolar lavage fluid and cell supernatant were measured using ELISA. SCT effectively downregulated the expression of TRPV1/4 and SP/CGRP in canine airway tissues with chronic bronchitis and reduced the levels of inflammatory mediators and cytokines that affect cough receptor sensitivity, achieving cough relief. TRPV1/4 - ATP - inflammatory cytokines axis has been demonstrated at the cellular level, which in turn modulate the milieu of the airways and promote the formation of a cough feedback loop. Our study has fully revealed the specific mechanism of SCT in treating cough in a canine model of chronic bronchitis, providing a solid theoretical basis for future clinical treatment.

Contribution of smoking change to 45-year trend in prevalence of chronic bronchitis in Finland.

AIMS: Tobacco smoking has been identified as the most important risk factor of chronic bronchitis. The aim of this study was to assess the contribution of smoking to the trends in prevalence of chronic bronchitis among men and women in Finland. METHODS: For this purpose, we analysed questionnaires included in national FINRISK and FinHealth studies conducted between 1972 and 2017 in 5-year intervals. A total of 26,475 men and 28,684 women aged 30-59 years were included in the analysis. In addition to smoking, age and socioeconomic status were used as risk factors in the logistic regression model. RESULTS: Smoking in Finland has declined from 51% to 23% in men between 1972 and 2017. In women, it increased from 11% in 1972 to 23% in 2002, with a following decrease to 16% in 2017. The prevalence of chronic bronchitis has generally followed the trend of smoking. The population attributable risk was 60% in men and 49% in women. A decrease in chronic bronchitis was observed in male never-smokers. CONCLUSIONS: Smoking is currently declining in Finland in both men and women. As result, the prevalence of chronic bronchitis is declining and it is approaching baseline independent of smoking. The decrease in never-smokers has yet to be explained.

Occupational exposure to fine particulate matter in the reinforced concrete production and its association with respiratory symptoms and lung function.

BACKGROUND: Reinforced concrete production is widespread, but little is known about the occupational exposure to fine particulate matter (PM) in such workplaces, including from metalworking and concrete processing. Therefore, the aim was to characterize exposure to fine PM in the typical workplaces of the whole production cycle and to quantify the risk of respiratory symptoms and lung function in a cohort of reinforced concrete parts production industry. METHODS: At a reinforced concrete parts producing facility in Almaty, we collected 50 personal PM2.5 samples from the main exposure sites and the measured mass concentrations using gravimetric method. Workers also completed questionnaires on a detailed working history, respiratory symptoms (chronic obstructive pulmonary disease (COPD) Assessment Tool (CAT)), followed by spirometry. The association of cumulative dose with CAT score and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was tested with multiple regression. RESULTS: The highest PM2.5 concentrations were found in the concrete-mixing unit (median 1180 µg/m3), followed by metalworking (510 µg/m3), armature workshop (375 µg/m3) and molding site (245 µg/m3), different from the concentrations in the office (29.5 µg/m3), Kruskall-Wallis p < 0.001. Cumulative PM2.5 dose, mg/m3-year (beta 0.10 (95% confidence interval (CI) 0.05; 0.15)) was strongly associated with CAT score, whereas production with FEV1/FVC (beta -4.96 (-8.31; -1.61)), independent of smoking and chronic bronchitis and sex. CONCLUSIONS: Mixing concrete and metalworks pose the greatest risk for worker's health in the reinforced concrete production from the inhalational exposure to aerosol, adversely affecting respiratory health.

Analysis of influencing factors and a predictive model of small airway dysfunction in adults.

BACKGROUND: Small airway dysfunction (SAD) is a widespread but less typical clinical manifestation of respiratory dysfunction. In lung diseases, SAD can have a higher-than-expected impact on lung function. The aim of this study was to explore risk factors for SAD and to establish a predictive model. METHODS: We included 1233 patients in the pulmonary function room of TangDu Hospital from June 2021 to December 2021. We divided the subjects into a small airway disorder group and a non-small airway disorder group, and all participants completed a questionnaire. We performed univariate and multivariate analyses to identify the risk factors for SAD. Multivariate logistic regression was performed to construct the nomogram. The performance of the nomogram was assessed and validated by the Area under roc curve (AUC), calibration curves, and Decision curve analysis (DCA). RESULTS: One. The risk factors for small airway disorder were advanced age (OR = 7.772,95% CI 2.284-26.443), female sex (OR = 1.545,95% CI 1.103-2.164), family history of respiratory disease (OR = 1.508,95% CI 1.069-2.126), history of occupational dust exposure (OR = 1.723,95% CI 1.177-2.521), history of smoking (OR = 1.732,95% CI 1.231-2.436), history of pet exposure (OR = 1.499,95% CI 1.065-2.110), exposure to O3 (OR = 1.008,95% CI 1.003-1.013), chronic bronchitis (OR = 1.947,95% CI 1.376-2.753), emphysema (OR = 2.190,95% CI 1.355-3.539) and asthma (OR = 7.287,95% CI 3.546-14.973). 2. The AUCs of the nomogram were 0.691 in the training set and 0.716 in the validation set. Both nomograms demonstrated favourable clinical consistency. 3.There was a dose‒response relationship between cigarette smoking and SAD; however, quitting smoking did not reduce the risk of SAD. CONCLUSION: Small airway disorders are associated with age, sex, family history of respiratory disease, occupational dust exposure, smoking history, history of pet exposure, exposure to O3, chronic bronchitis, emphysema, and asthma. The nomogram based on the above results can effectively used in the preliminary risk prediction.

Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study.

BACKGROUND: Previous observational studies have found an association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases, but it remains uncertain whether GERD causally influences these diseases. In this study, we aimed to estimate the causal associations between GERD and 5 chronic respiratory diseases. METHODS: 88 GERD-associated single nucleotide polymorphisms (SNPs) identified by the latest genome-wide association study were included as instrumental variables. Individual-level genetic summary data of participants were obtained from corresponding studies and the FinnGen consortium. We applied the inverse-variance weighted method to estimate the causality between genetically predicted GERD and 5 chronic respiratory diseases. Furthermore, the associations between GERD and common risk factors were investigated, and mediation analyses were conducted using multivariable MR. Various sensitivity analyses were also performed to verify the robustness of the findings. RESULTS: Our study demonstrated that genetically predicted GERD was causally associated with an increased risk of asthma (OR 1.39, 95%CI 1.25-1.56, P < 0.001), idiopathic pulmonary fibrosis (IPF) (OR 1.43, 95%CI 1.05-1.95, P = 0.022), chronic obstructive disease (COPD) (OR 1.64, 95%CI 1.41-1.93, P < 0.001), chronic bronchitis (OR 1.77, 95%CI 1.15-2.74, P = 0.009), while no correlation was observed for bronchiectasis (OR 0.93, 95%CI 0.68-1.27, P = 0.645). Additionally, GERD was associated with 12 common risk factors for chronic respiratory diseases. Nevertheless, no significant mediators were discovered. CONCLUSIONS: Our study suggested that GERD was a causal factor in the development of asthma, IPF, COPD and chronic bronchitis, indicating that GERD-associated micro-aspiration of gastric contents process might play a role in the development of pulmonary fibrosis in these diseases.