Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Serum procalcitonin as a diagnostic biomarker in dogs with bacterial respiratory diseases.

BACKGROUND: Procalcitonin (PCT) is a useful biomarker in humans in the identification of bacterial respiratory infections. OBJECTIVES: The aim of this study was to investigate the utility of serum PCT measurements as a diagnostic biomarker in canine bacterial lower respiratory tract diseases. METHODS: PCT concentrations were measured in serum samples with an ELISA method previously validated for dogs. All dogs underwent thorough clinical examinations, and the diagnosis of respiratory disease was based on clinical and laboratory findings, diagnostic imaging, as well as cytology and bacterial culture of respiratory samples. PCT concentrations between different cohorts of dogs were compared with an ANOVA-model. RESULTS: Sixty-two privately owned dogs with respiratory diseases, 25 with bacterial pneumonia (BP), 17 with bacterial bronchitis caused by Bordetella bronchiseptica (BB), and 20 with chronic bronchitis (CB) as well as 44 healthy controls were included in the study. Serum PCT concentrations in dogs with bacterial respiratory diseases (BP mean 51.8 ng/L ± standard deviation [SD] 40.6 ng/L and BB mean 61.4 ng/L ± SD 35.3 ng/L) were not significantly different when compared with dogs with a non-bacterial respiratory disease (CB mean 89.7 ± SD 73.5 ng/L) or healthy dogs (mean 51.0 ng/L ± SD 37.5 ng/L, p > .05 in all comparisons). CONCLUSIONS: These results indicate that despite being a valuable diagnostic, prognostic, and follow-up marker in humans with pneumonia, serum PCT concentrations are not elevated in dogs with bacterial respiratory diseases and, therefore, cannot be used as a diagnostic biomarker in dogs.

Associations of obesity with chronic inflammatory airway diseases and mortality in adults: a population-based investigation.

BACKGROUND: The association between obesity and respiratory diseases has been confirmed. However, few studies have reported the relationship between obesity and the risk and mortality of chronic inflammatory airway disease (CIAD). The aim of this study was to reveal the association between obesity and the risk of CIAD, and mortality in patients with CIAD. METHODS: The study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 among adults aged 20 years and above. All participants were grouped according to body mass index (BMI) and waist circumference (WC) levels to study the relationship between obesity and CIAD. Multivariate logistic regression analysis was utilized to examine the connection between CIAD and obesity in a cross-sectional study. The association between obesity and all-cause mortality in individuals with CIAD was examined using multiple cox regression models and smooth curve fitting in a prospective cohort study. RESULTS: When stratified based on BMI in comparison to the normal weight group, the ORs with 95%CIs of CIAD for underweight and obesity were 1.39 (1.01-1.93) and 1.42 (1.27-1.58), respectively. The OR with 95%CI of CIAD for obesity was 1.20 (1.09-1.31) when stratified according to WC. Additionally, underweight was associated with a higher mortality (HR = 2.44, 95% CI = 1.31-4.55), whereas overweight (HR = 0.58,95% CI = 0.39-0.87) and obesity (HR = 0.59,95% CI = 0.4-0.87) were associated with a lower mortality (P for trend < 0.05). There was a non-linear association between BMI and all-cause mortality (P for non-linear = 0.001). An analysis of a segmentation regression model between BMI and all-cause mortality revealed a BMI turning point value of 32.4 kg/m2. The mortality of CIAD patients was lowest when BMI was 32.4 kg/m2. When BMI ≤ 32.4 kg/m2, BMI was inversely associated with all-cause mortality in patients with CIAD (HR: 0.92, 95%CI:0.88-0.97). However, when BMI > 32.4 kg/m2, there was no association between BMI and all-cause mortality (HR:1.02, 95%CI:0.97-1.06). CONCLUSION: Compared to normal weight, underweight and obesity were associated with the increased risk of CIAD. Underweight was associated with increased all-cause mortality, while overweight was associated with reduced all-cause mortality. There was a non-linear association between BMI and all-cause mortality in patients with CIAD. The all-cause mortality was lowest when BMI was 32.4 kg/m2.

Lung Tissue Multi-Layer Network Analysis Uncovers the Molecular Heterogeneity of COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using a novel multi-layer approach may unravel mechanisms associated with clinical characteristics. METHODS: We profiled mRNA, miRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer) we built a patient network based on molecular similarity. The three networks were used to build a multi-layer network, and optimization of multiplex-modularity was employed to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features. RESULTS: We identified five patient communities in the multi-layer network which were molecularly distinct and related to clinical characteristics, such as FEV1 and blood eosinophils. Two communities (C#3 and C#4) had both similarly low FEV1 values and emphysema, but were molecularly different: C#3, but not C#4, presented B and T cell signatures and a downregulation of secretory (SCGB1A1/SCGB3A1) and ciliated cells. A machine learning model was set up to discriminate C#3 and C#4 in our cohort, and to validate them in an independent cohort. Finally, using spatial transcriptomics we characterized the small airway differences between C#3 and C#4, identifying an upregulation of T/B cell homing chemokines, and bacterial response genes in C#3. CONCLUSIONS: A novel multi-layer network analysis is able to identify clinically relevant COPD patient communities. Patients with similarly low FEV1 and emphysema can have molecularly distinct small airways and immune response patterns, indicating that different endotypes can lead to similar clinical presentation.

Chronic Bronchitis in Children and Adults: Definitions, Pathophysiology, Prevalence, Risk Factors, and Consequences.

The complex nature of chronic bronchitis (CB) and changing definitions have contributed to challenges in understanding its aetiology and burden. In children, CB is characterised by persistent airway inflammation often linked to bacterial infections and is therefore termed "protracted bacterial bronchitis" (PBB). Longitudinal studies suggest that CB in childhood persists into adulthood in a subgroup. It can also be associated with future chronic respiratory diseases including asthma, bronchiectasis, and chronic obstructive pulmonary disease (COPD). Adult CB is traditionally associated with smoking, occupational exposures, and lower socioeconomic status. The interplay between risk factors, childhood CB, adult CB, and other chronic respiratory diseases is intricate, requiring comprehensive longitudinal studies for a clearer understanding of the natural history of CB across the lifespan. Such longitudinal studies have been scarce to date given the logistic challenges of maintaining them over time. In this review, we summarise current evidence on the evolution of the definitions, pathophysiology, risk factors, and consequences of childhood and adulthood chronic bronchitis.

Combined association of urinary volatile organic compounds with chronic bronchitis and emphysema among adults in NHANES 2011-2014: The mediating role of inflammation.

Evidence on the association of volatile organic compounds (VOCs) with chronic bronchitis (CB) and emphysema is spare and defective. To evaluate the relationship between urinary metabolites of VOCs (mVOCs) with CB and emphysema, and to identify the potential mVOC of paramount importance, data from NHANES 2011-2014 waves were utilized. Logistic regression was conducted to estimate the independent association of mVOCs with respiratory outcomes. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen a parsimonious set of CB- and emphysema-relevant mVOCs that were used for further co-exposure analyses of weight quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Mediation analysis was employed to detect the mediating role of inflammatory makers in such associations. In single exposure analytic model, nine mVOCs were individually and positively associated with CB, while four mVOCs were with emphysema. In WQS regression, positive association between LASSO selected mVOCs and CB was identified (OR = 1.82, 95% CI: 1.25 to 2.69), and N-acetyl-S-(4-hydroxy-2-butenyl)-l-cysteine (MHBMA3) weighted the highest. Results from BKMR further validated such combined association and the significance of MHBMA3. As for emphysema, significantly positive overall trend of mVOCs was only observed in BKMR model and N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) contributed most to the mixed effect. White blood cell count (WBC) and lymphocyte number (LYM) were mediators in the positive pattern of mVOCs mixture with CB, while association between mVOCs mixture and emphysema was significantly mediated by LYM and segmented neutrophils num (NEO). This study demonstrated that exposure to VOCs was associated with CB and emphysema independently and combinedly, which might be partly speculated that VOCs were linked to activated inflammations. Our findings shed novel light on VOCs related respiratory illness, and provide a new basis for the contribution of certain VOCs to the risk of CB and emphysema, which has potential public health implications.

Respiratory Oscillometry and Functional Performance in Different COPD Phenotypes.

Purpose: Chronic obstructive pulmonary disease (COPD) phenotypes may introduce different characteristics that need to be known to improve treatment. Respiratory oscillometry provides a detailed analysis and may offer insight into the pathophysiology of COPD. In this paper, we used this method to evaluate the differences in respiratory mechanics of COPD phenotypes. Patients and Methods: This study investigated a sample of 83 volunteers, being divided into control group (CG = 20), emphysema (n = 23), CB (n = 20) and asthma-COPD overlap syndrome (ACOS, n = 20). These analyses were performed before and after bronchodilator (BD) use. Functional capacity was evaluated using the Glittre­ADL test, handgrip strength and respiratory pressures. Results: Initially it was observed that oscillometry provided a detailed description of the COPD phenotypes, which was consistent with the involved pathophysiology. A correlation between oscillometry and functional capacity was observed (r=-0.541; p = 0.0001), particularly in the emphysema phenotype (r = -0.496, p = 0.031). BD response was different among the studied phenotypes. This resulted in an accurate discrimination of ACOS from CB [area under the receiver operating curve (AUC) = 0.84] and emphysema (AUC = 0.82). Conclusion: These results offer evidence that oscillatory indices may enhance the comprehension and identification of COPD phenotypes, thereby potentially improving the support provided to these patients.

N-acetylcysteine Treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: Distinct Meta-analyses.

INTRODUCTION: N-acetylcysteine (NAC) is a mucolytic agent with antioxidant properties. Oxidative stress is a key pathogenic mechanism in chronic respiratory conditions such as COPD and chronic bronchitis (CB). In these meta-analyses we investigated the efficacy of NAC in subjects with COPD or CB, the latter being a potential pre-COPD condition (CB/pre-COPD). METHODS: The meta-analyses were conducted according to PRISMA guidelines. Exacerbations were assessed using total number of exacerbations. Improvement in patients' respiratory symptoms and/or patients quality of life (QoL) were measured by validated tools or assessed at the end of the study. RESULTS: Twenty studies were included, of which seven evaluated NAC in patients with symptoms of CB/pre-COPD as entry criterion. NAC treated patients showed a significant reduction of the incidence of exacerbations as compared to placebo both in COPD (IRR=0.76; 95% confidence interval (CI) 0.59-0.99) and CB/pre-COPD (IRR=0.81; 95% CI 0.69-0.95). Sensitivity analyses in studies with duration higher than 5 months, confirmed the overall results. CB/pre-COPD patients treated with NAC were significantly more likely to experience an improvement in symptoms and/or QoL compared to placebo (odds ratio (OR)=3.47; 95% CI 1.92-6.26). A similar trend was observed in the few COPD studies evaluable. Sensitivity analyses showed a significant association of NAC with improvement in symptoms and/or QoL both in CB/pre-COPD and COPD patients. CONCLUSIONS: These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD. PROSPERO registry no. CRD42023468154.

Eucalyptol, limonene and pinene enteric capsules attenuate airway inflammation and obstruction in lipopolysaccharide-induced chronic bronchitis rat model via TLR4 signaling inhibition.

BACKGROUND: Chronic bronchitis (CB), a type of chronic obstructive pulmonary disease (COPD), poses a significant global health burden owing to its high morbidity and mortality rates. Eucalyptol, limonene and pinene enteric capsules (ELPs) are clinically used as expectorants to treat various respiratory diseases, including CB, but their acting mechanisms remain unclear. In this study, we investigated the anti-CB effects of ELP in a rat model of lipopolysaccharide (LPS)-induced CB. The molecular mechanisms underlying its inhibitory effects on airway inflammation were further explored in LPS-stimulated Beas-2B cells. METHODS: ELP was characterized using gas chromatography. The production of inflammatory mediators in bronchoalveolar lavage fluid (BALF) was determined using an enzyme-linked immunosorbent assay. The expression of MUC5AC, MUC5B, and p-p65 in the lung tissue was measured using immunohistochemical staining. The gene expression of inflammatory mediators was determined using qRT-PCR. The expression levels of the target proteins were detected by western blotting. Nuclear localization of p65 was determined using an immunofluorescence assay. RESULTS: Compared to the CB model rats, ELP-treated rats showed reduced airway resistance, inflammation, and goblet cell hyperplasia. In BALF, ELP decreased the levels of inflammatory mediators, including TNF-α, IL-6, MIP-1α, and CCL5. ELP also suppressed LPS-induced elevation of MUC5AC, MUC5B, and p-p65 in the lung tissue. The metabolic pathway changes caused by LPS challenge were improved by ELP treatment. In LPS-exposed Beas-2B cells, ELP treatment inhibited the expression of TNFA, IL6, CCL5, MCP1, and MIP2A and decreased the phospho-levels of toll-like receptor 4 (TLR4) signaling-related proteins, including p-p38, p-JNK, p-ERK, p-TBK1, p-IKKα/ß, p-IκB, p-p65, and p-c-Jun. ELP also hindered the nuclear translocation of p65, c-Jun, and IRF3. CONCLUSIONS: This study showed that ELP has a potential therapeutic effect in LPS-induced CB rat model, possibly by suppressing TLR4 signaling. These results justify the clinical use of ELP for the treatment of pulmonary inflammatory diseases.

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

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

Epigenome-Wide Association Studies of COPD and Lung Function: A Systematic Review.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. This systematic review synthesizes evidence from epigenome-wide association studies (EWAS) related to COPD and lung function. METHODS: Systematic literature search on PubMed, Embase and CINAHL databases, identified 1947 articles that investigated epigenetic changes associated with COPD/lung function; 17 of them met our eligibility criteria from which data was manually extracted. Differentially methylated positions (DMPs) and/or annotated genes, were considered replicated if identified by ≥2 studies with a p<1 x 10-4. RESULTS: Ten studies profiled DNA methylation changes in blood and 7 in respiratory samples, including surgically resected lung tissue (n=3), small airways epithelial brushings (n=2), bronchoalveolar lavage (n=1) and sputum (n=1). Main results showed: (1) high variability in study design, covariates and effect sizes, which prevented a formal meta-analysis; (2) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; (3) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and, (4) in COPD vs. control studies, 123 genes (2.6% of total) were shared between ≥1 blood and ≥1 respiratory sample and associated with chronic inflammation, ion transport and coagulation. CONCLUSIONS: There is high heterogeneity across published COPD/lung function EWAS studies. A few genes (n=123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research.

Susceptible Young Adults and Development of COPD Later in Life.

RATIONALE: Chronic obstructive pulmonary disease (COPD) has its origin in early life, and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposes a pre-disease state "pre-COPD". OBJECTIVE: We tested the hypothesis that susceptible young adults identified with chronic bronchitis and subtle lung function impairment will develop COPD later in life. METHODS: We followed random non-obstructive individuals aged 20-50years from two population-based cohorts from different smoking eras, the Copenhagen General Population Study from 2003(N=5497) and Copenhagen City Heart Study from 1976-78(N=2609), for 10 and 25years for development of COPD(forced expiratory volume in one second[FEV1]/forced vital capacity[FVC]<0.70) and COPD GOLD 2-4 (additionally FEV1<80% predicted). MEASUREMENTS AND MAIN RESULTS: After 10 years follow-up, 28% developed COPD and 13% COPD GOLD 2-4 in individuals susceptible to COPD compared to 8% and 1% in those without any susceptibility to COPD. Correspondingly, after 25years, 22% versus 13% developed COPD and 20% versus 8% developed COPD GOLD 2-4. More than half of incident COPD cases developed from a susceptible state. Compared to those without susceptibility to COPD, multivariable adjusted odds ratios in those susceptible to COPD were 3.42(95% confidence interval:2.78-4.21) for COPD and 10.1(6.77-15.2) for COPD GOLD 2-4 after 10years, and 1.54(1.23-1.93) and 2.12(1.64-2.73) after 25years. The ability of a COPD risk score consisting of the susceptibility state to COPD with smoking and asthma as risk factors to predict COPD later in life was high. CONCLUSIONS: Our study suggests the existence of a pre-disease state of COPD, which can be used for early identification of susceptible individuals at risk for COPD later in life.

Mechanism of Tonifying Spleen-lung Recipe in the Treatment of Chronic Bronchitis Based on Network Pharmacology and Observational Data.

BACKGROUND: Chronic bronchitis is a type of common chronic inflammatory respiratory disease, which is mainly characterized by chronic cough and expectoration. Clinical practice and experimental research have shown that the modified tonifying spleen-lung method has significant preventive and therapeutic effects on chronic lung diseases, but the mechanism of TSLR in the treatment of chronic bronchitis are not yet clear. OBJECTIVE: To explore the mechanism of tonifying spleen-lung recipe (TSLR) in the treatment of chronic bronchitis (CB) through network pharmacology combined with observational studies. MATERIALS AND METHODS: The effective components, core targets and signaling pathways of TSLR in the treatment of chronic bronchitis were obtained using network pharmacology. One hundred and thirty-seven elderly CB patients were selected as the observational group who were treated by TSLR, and 67 no-CB cases from the Physical Examination Center were selected as the control group. We compared the levels of inflammatory parameters between patients before and after TSLR treatment, and after treatment group with the control group were also compared. RESULTS: The key effective components of TSLR selected by network pharmacology included quercetin, kaempferol, luteolin, and nobiletin, and the core targets involved HSP90AA1, AKT1, JUN, MAPK1, IL6, MAPK3, MAPK14, STAT1, NFKB1, and CDKN1. KEGG pathway enrichment analysis revealed that the TNF signaling pathway, PI3K-AKT and AGE-RAGE signaling pathways might play a key role in the treatment of CB. The observation study demonstrated that compared with the control group, the levels of WBC, NEU, NLR, PCT, and CRP in the research group after TSLR treatment were increased. Although the levels of WBC, NEU, NLR, and PCT in the research group after TSLR treatment were higher than those in the control group, the above indicators trend tended towards the control group, and there was no significant difference in CRP indicators between the control group and after treatment group. CONCLUSION: TSLR had a good therapeutic effect on chronic bronchitis patients, which might be related to the fact that the natural active components in TSLR inhibit inflammation by regulating the expression of proteins related to PI3K-AKT and TNF signaling pathways.

GOLD COPD DOCUMENT 2023: a brief update for practicing cardiologists.

Many patients seen by cardiologists suffer chronic obstructive pulmonary disease (COPD) in addition to their primary cardiovascular problem. Yet, quite often COPD has not been diagnosed and, consequently, patients have not been treated of their pulmonary disease. Recognizing and treating COPD in patients with CVDs is important because optimal treatment of the COPD carries important benefits on cardiovascular outcomes. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) publishes an annual report that serves as a clinical guideline for the diagnosis and management of COPD around the world and has very recently released the 2023 annual report. Here, we provide a summary of the GOLD 2023 recommendations that highlights those aspects of more interest for practicing cardiologists dealing with patients with CVD who may suffer COPD.

Synergistic effects of COVID-19 and Pseudomonas aeruginosa in chronic obstructive pulmonary disease: a polymicrobial perspective.

This article discusses the connection between the novel coronavirus disease 2019 (COVID-19) caused by the coronavirus-2 (SARS-CoV-2) and chronic obstructive pulmonary disease (COPD). COPD is a multifaceted respiratory illness that is typically observed in individuals with chronic exposure to chemical irritants or severe lung damage caused by various pathogens, including SARS-CoV-2 and Pseudomonas aeruginosa. The pathogenesis of COPD is complex, involving a variety of genotypes and phenotypic characteristics that result in severe co-infections and a poor prognosis if not properly managed. We focus on the role of SARS-CoV-2 infection in severe COPD exacerbations in connection to P.  aeruginosa infection, covering pathogenesis, diagnosis, and therapy. This review also includes a thorough structural overview of COPD and recent developments in understanding its complicated and chronic nature. While COVID-19 is clearly linked to emphysema and chronic bronchitis at different stages of the disease, our understanding of the precise interaction between microbial infections during COPD, particularly with SARS-CoV-2 in the lungs, remains inadequate. Therefore, it is crucial to understand the host-pathogen relationship from the clinician's perspective in order to effectively manage COPD. This article aims to provide a comprehensive overview of the subject matter to assist clinicians in their efforts to improve the treatment and management of COPD, especially in light of the COVID-19 pandemic.

Effects of cannabis smoking on the respiratory system: A state-of-the-art review.

The diminished perception of the health risks associated with the consumption of cannabis (marijuana) lead to a progressive increase in its inhalational use in many countries. Cannabis can be smoked through the use of joints, spliffs and blunts, and it can be vaporised with the use of hookah or e-cigarettes. Delta-9 tetrahydrocannabinol (THC) is the main psychoactive component of cannabis smoke but contains numerous other substances. While the recreational use of cannabis smoking has been legalised in several countries, its health consequences have been underestimated and undervalued. The purpose of this review is to critically review the impact of cannabis smoke on the respiratory system. Cannabis smoke irritates the bronchial tree and is strongly associated with symptoms of chronic bronchitis, with histological signs of airway inflammation and remodelling. Altered fungicidal and antibacterial activity of alveolar macrophages, with greater susceptibility to respiratory infections, is also reported. The association with invasive pulmonary aspergillosis in immunocompromised subjects is particularly concerning. Although cannabis has been shown to produce a rapid bronchodilator effect, its chronic use is associated with poor control of asthma by numerous studies. Cannabis smoking also represents a risk factor for the development of bullous lung disease, spontaneous pneumothorax and hypersensitivity pneumonitis. On the other hand, no association with the development of chronic obstructive pulmonary disease was found. Finally, a growing number of studies report an independent association of cannabis smoking with the development of lung cancer. In conclusion, unequivocal evidence established that cannabis smoking is harmful to the respiratory system. Cannabis smoking has a wide range of negative effects on respiratory symptoms in both healthy subjects and patients with chronic lung disease. Given that the most common and cheapest way of assumption of cannabis is by smoking, healthcare providers should be prepared to provide counselling on cannabis smoking cessation and inform the public and decision-makers.

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.

Risk Factors for Chronic Obstructive Pulmonary Disease Exacerbations among Individuals without a History of Recent Exacerbations: A COPDGene Analysis.

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are detrimental events in the natural history of COPD, but the risk factors associated with future exacerbations in the absence of a history of recent exacerbations are not fully understood. Objectives: To identify risk factors for COPD exacerbations among participants in the Genetic Epidemiology of COPD Study (COPDGene) without a history of exacerbation in the previous year. Methods: We identified participants with a smoking history enrolled in COPDGene who had COPD (defined as forced expiratory volume in 1 second [FEV1]/forced vital capacity < 0.70), no exacerbation in the year before their second study site visit, and who completed at least one longitudinal follow-up questionnaire in the following 36 months. We used univariable and multivariable zero-inflated negative binomial regression models to identify risk factors associated with increased rates of exacerbation. Each risk factor's regression coefficient (ß) was rounded to the nearest 0.25 and incorporated into a graduated risk score. Results: Among the 1,528 participants with a smoking history and COPD enrolled in COPDGene without exacerbation in the year before their second study site visit, 508 participants (33.2%) had at least one moderate or severe exacerbation in the 36 months studied. Gastroesophageal reflux disease, chronic bronchitis, high symptom burden (as measured by Modified Medical Research Council Dyspnea Scale and COPD Assessment Test), and lower FEV1% predicted were associated with an increased risk of exacerbation. Each 1-point increase in our graduated risk score was associated with a 25-30% increase in exacerbation rate in the 36 months studied. Conclusions: In patients with COPD without a recent history of exacerbations, gastroesophageal reflux disease, chronic bronchitis, high symptom burden, and lower lung function are associated with increased risk of future exacerbation using a simple risk score that can be used in clinical practice.

Potential systemic effects of acquired CFTR dysfunction in COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, respiratory symptoms, inflammation of the airways, and systemic manifestations of the disease. Genetic susceptibility and environmental factors are important in the development of the disease, particularly exposure to cigarette smoke which is the most notable risk factor. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are the cause of cystic fibrosis (CF), which shares several pathophysiological pulmonary features with COPD, including airway obstruction, chronic airway inflammation and bacterial colonization; in addition, both diseases also present systemic defects leading to comorbidities such as pancreatic, gastrointestinal, and bone-related diseases. In patients with COPD, systemic CFTR dysfunction can be acquired by cigarette smoking, inflammation, and infection. This dysfunction is, on average, about half of that found in CF. Herein we review the literature focusing on acquired CFTR dysfunction and the potential role in the pathogenesis of comorbidities associated with COPD and chronic bronchitis.

Electronic cigarette use and respiratory symptoms in the French population-based Constances cohort.

BACKGROUND: Knowledge about the consequences of electronic cigarette (EC) use on respiratory health is still limited. We aimed to assess whether EC use is associated with the occurrence of asthma symptoms and chronic bronchitis among the French adult population, with a specific focus on never combustible cigarettes (CC) smokers. We further investigated whether the association differed in men and women. METHODS: Constances is a population-based cohort of adults aged 18-69 years at inception. We analyzed baseline data collected in 136,276 participants recruited in 2015-2019. Associations of current and former EC use with respiratory symptoms (asthma symptom score and chronic bronchitis) were assessed, controlling for CC smoking, cannabis use, demographics, education and body mass index (BMI). RESULTS: Increased frequencies of respiratory symptoms were observed in both current and former EC users (for the asthma symptom score, adjusted mean score ratio (aMSR): 1.34 [95 % confidence interval: 1.28-1.41] and 1.39 [1.33-1.45], respectively; for chronic bronchitis, adjusted prevalence ratio (aPR): 1.27 [1.19-1.36] and 1.40 [1.32-1.48], respectively). Among never CC smokers, ever EC use was associated with an increased asthma symptom score in both men and women (aMSR = 1.44 [1.09-1.90] and 1.36 [1.01-1.83], respectively), and with a higher prevalence of chronic bronchitis only in women (aPR = 1.97 [1.27-3.05]). CONCLUSION: EC use is associated with symptoms of asthma and chronic bronchitis, independently of CC smoking and cannabis use. The fact that these associations are observed among individuals who have never smoked tobacco adds further evidence of the deleterious effects of EC on respiratory health.