Chronic Obstructive Pulmonary Disease Phenotypes Research Articles

Bronchodilator responsiveness in chronic obstructive pulmonary disease: prevalence, significance, and clinical implications.

Bronchodilator responsiveness (BDR) is often considered a key feature distinguishing asthma from chronic obstructive pulmonary disease (COPD). However, recent evidence suggests that BDR alone may not be a reliable discriminator between these conditions. There is still no consensus on BDR definitions and testing protocols. Additionally, it remains unclear whether BDR is linked to a specific COPD phenotype or influences treatment responses. Our review of recent literature attempts to clarify some of these issues. A significant proportion of COPD patients demonstrate BDR, but the variability in testing procedures and definitions makes it challenging to draw any definite conclusion. There is no evident association between BDR and specific COPD characteristics. A few studies suggest that BDR may be associated with marginally better treatment response and disease outcomes in COPD. The impact of recent changes in BDR definitions on clinical practice remains to be fully understood. There is still no clear, clinically relevant threshold to define BDR. BDR is an unreliable discriminator to differentiate asthma from COPD and is not consistently linked to any specific COPD phenotype, treatment response, or disease outcomes. Further research is needed to refine the definitions and implications of BDR in COPD.

Clinical application and challenges of thermal vapor lung volume reduction

There are major clinical challenges in the management of chronic obstructive pulmonary disease (COPD). Recent studies suggest that thermal vapor lung volume reduction may be an important interventional method in the treatment of emphysema phenotype of COPD. In this article, we reviewed and summarized the research and development, the current situation of clinical application, and the clinical challenges of thermal vapor lung volume reduction, to provide further clinical evidence for the standardized application of thermal vapor lung volume reduction.

Impact of HHIP gene polymorphisms on phenotypes, serum IL-17 and IL-18 in COPD patients of the Chinese Han population

BackgroundGenetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population.MethodsA case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders.ResultsOur study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes.ConclusionThis study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes.Trial registrationwww.chictr.org.cn ID: ChiCTR2300071579 2023-05-18.

Rationale and design of healthy at home for COPD: an integrated remote patient monitoring and virtual pulmonary rehabilitation pilot study

Chronic obstructive pulmonary disease (COPD) is a common, costly, and morbid condition. Pulmonary rehabilitation, close monitoring, and early intervention during acute exacerbations of symptoms represent a comprehensive approach to improve outcomes, but the optimal means of delivering these services is uncertain. Logistical, financial, and social barriers to providing healthcare through face-to-face encounters, paired with recent developments in technology, have stimulated interest in exploring alternative models of care. The Healthy at Home study seeks to determine the feasibility of a multimodal, digitally enhanced intervention provided to participants with COPD longitudinally over 6 months. This paper details the recruitment, methods, and analysis plan for the study, which is recruiting 100 participants in its pilot phase. Participants were provided with several integrated services including a smartwatch to track physiological data, a study app to track symptoms and study instruments, access to a mobile integrated health program for acute clinical needs, and a virtual comprehensive pulmonary support service. Participants shared physiologic, demographic, and symptom reports, electronic health records, and claims data with the study team, facilitating a better understanding of their symptoms and potential care needs longitudinally. The Healthy at Home study seeks to develop a comprehensive digital phenotype of COPD by tracking and responding to multiple indices of disease behavior and facilitating early and nuanced responses to changes in participants’ health status. This study is registered at Clinicaltrials.gov (NCT06000696).

Personalized COPD Care: The Future of Precision-Based Therapies.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by long-standing respiratory symptoms and airflow limitation. It is a major contributor to respiratory disease-related deaths and currently ranked as the sixth leading cause of mortality in the United States. Approved pharmacological therapies for the stable disease primarily consist of inhaled short and long-acting bronchodilators, inhaled corticosteroids, azithromycin, and roflumilast. In recent years, significant progress has been made in the management of COPD through the identification of different COPD phenotypes and endotypes, which allows for a more personalized treatment approach. While earlier studies investigating targeted therapies were less promising, recent data on drugs targeting type 2 inflammatory pathways have shown promising results in carefully selected patients. In this article, we will review the available data on targeted therapies as well as the ongoing clinical studies of novel targeted therapies for COPD. Understanding and implementing these advancements hold promise for improving outcomes and quality of life for individuals living with COPD.

Mice with lymphatic dysfunction develop pathogenic lung tertiary lymphoid organs that model an autoimmune emphysema phenotype of COPD.

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development of emphysema. TLOs in CLEC2-deficient mice were rich in plasma cells and were a source of a broad array of autoantibodies. Chronic cigarette smoke exposure increased the size and number of lung TLOs in CLEC2-deficient mice and was associated with increased markers of antigen presentation and maturation, leading to increased autoantibody deposition. Using lung tissue from patients with COPD, we found an increase in lymphatic markers in patients with an emphysema phenotype and autoreactive TLOs compared with patients with COPD without emphysema that lack prominent TLOs. Taken together, these results demonstrate that emphysema in mice with lymphatic dysfunction can be partially rescued by blocking TLO formation and that these TLOs are the source of autoantibodies that are exacerbated by cigarette smoke. Our work suggests that lymphatic dysfunction in mice may recapitulate some aspects of an autoimmune emphysema phenotype that is seen in a subset of patients with COPD.NEW & NOTEWORTHY The lymphatic vasculature has been implicated in the pathogenesis of lung disease but remains understudied. Here, the authors use a mouse model to show that lymphatic dysfunction leads to a phenotype of emphysema that is characterized by lung tertiary lymphoid organs that are autoreactive and pathogenic. Analysis of human tissue showed increased lymphatic markers in autoimmune emphysema with prominent TLOs, compared with other COPD phenotypes.

N-acetylcysteine – a drug for basic and symptomatic therapy of chronic bronchitis/chronic obstructive pulmonary disease

Prevention and successful treatment of the disease exacerbations are crucial for patients with chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). At present, a sufficient number of efforts are being made to improve both prevention of exacerbations in patients with stable disease progression and treatment of the exacerbations. According to international and domestic recommendations, mucolytic drugs are among the key therapies for both bronchitis phenotype of COPD and chronic bronchitis, the main clinical manifestation of which is a long-term productive cough. The aim of the review is to analyze modern literature data that reflect the role of N-acetylcysteine (NAC) in prevention of exacerbations during the stable course and treatment of exacerbations of chronic bronchitis and COPD.

Association of the gut microbiome and different phenotypes of COPD and asthma: a bidirectional Mendelian randomization study.

Mounting evidence has revealed the association between gut microbiota and both chronic obstructive pulmonary disease (COPD) and asthma; however, the causal association between gut microbiota and specific disease phenotypes remains to be determined. This study employed bidirectional two-sample Mendelian randomization (MR) analyses to investigate the potential causal relationship between gut microbiota and these conditions. The research utilized genome-wide association study (GWAS) data from the MiBioGen consortium for gut microbiota and the integrative epidemiology unit (IEU) Open GWAS for these conditions. Four MR analysis methods were employed: the inverse variance weighted (IVW) test, MR-Egger, weighted median, and weighted mode methods. The IVW method results are considered the primary findings. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy analysis, and leave-one-out analysis, were used to enhance robustness. Our MR study identified eight gut microbiota taxa potentially associated with the risk of different types of COPD and asthma. These include two taxa for early-onset COPD: Streptococcaceae [odds ratio (OR) = 1.315, 95% confidence interval (CI) = 1.071-1.616, P = 0.009] and Holdemanella (OR = 1.199, 95% CI = 1.063-1.352, P = 0.003); three for later-onset COPD: Acidaminococcaceae (OR = 1.312, 95% CI = 1.098-1.567, P = 0.003), Holdemania (OR = 1.165, 95% CI = 1.039-1.305, P = 0.009), and Marvinbryantia (OR = 0.814, 95% CI = 0.697-0.951, P = 0.009); one for allergic asthma: Butyricimonas (OR = 0.794, 95% CI = 0.693-0.908, P = 0.001); and two for non-allergic asthma: Clostridia (OR = 1.255, 95% CI = 1.043-1.511, P = 0.016) and Clostridiales (OR = 1.256, 95% CI = 1.048-1.506, P = 0.014).IMPORTANCEIndividuals with diverse phenotypes of chronic obstructive pulmonary disease (COPD) and asthma exhibit different responses to the conventional "one treatment fits all" approach. Recent research has revealed the significant role of the gut-lung axis in both COPD and asthma. However, the specific impact of gut microbiota on different subtypes of these conditions remains poorly understood. Our study has identified eight gut microbiota that may be associated with the risk of different types of COPD and asthma. These findings provide evidence suggesting a potential causal relationship between gut microbiota and various phenotypes of COPD and asthma. This offers a new perspective on the origins of different disease phenotypes and points toward future exploration of phenotype-specific and personalized therapies.

Differential miRNA Profiling Reveals miR-4433a-5p as a Key Regulator of Chronic Obstructive Pulmonary Disease Progression via PIK3R2- mediated Phenotypic Modulation.

In this study, a high-throughput sequencing technology was used to screen the differentially expressed miRNA in the patients with "fast" and "slow" progression of chronic obstructive pulmonary disease (COPD). Moreover, the possible mechanism affecting the progression of COPD was preliminarily analyzed based on the target genes of candidate miRNAs. The "fast" progressive COPD group included 6 cases, "slow" and Normal progressive COPD groups included 5 cases each, and COPD group included 3 cases. The peripheral blood samples were taken from the participants, followed by total RNA extraction and high throughput miRNA sequencing. The differentially expressed miRNAs among the progressive COPD groups were identified using bioinformatics analysis. Then, the candidate miRNAs were externally verified. In addition, the target gene of this miRNA was identified, and its effects on cell activity, cell cycle, apoptosis, and other biological phenotypes of COPD were analyzed. Compared to the Normal group, a total of 35, 16, and 7 differentially expressed miRNAs were identified in the "fast" progressive COPD, "slow" progressive COPD group, and COPD group, respectively. The results were further confirmed using dual-luciferase reporter assay and transfection tests with phosphoinositide- 3-kinase, regulatory subunit 2 (PIK3R2) as a target gene of miR-4433a-5p; the result showed a negative regulatory correlation between the miRNA and its target gene. The phenotype detection showed that the activation of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway might participate in the progression of COPD by promoting the proliferation of inflammatory A549 cells and inhibiting cellular apoptosis. MiR-4433a-5p can be used as a marker and potential therapeutic target for the progression of COPD. As a target gene of miR-4433a-5p, PIK3R2 can affect the progression of COPD by regulating phenotypes, such as cellular proliferation and apoptosis.

Impact of N-Acetylcysteine on Mucus Hypersecretion in the Airways: A Systematic Review.

Mucus clearance is crucial for airway protection, and its dysfunction leads to chronic obstructive pulmonary disease (COPD) characterized by mucus hypersecretion (MHS) and impaired clearance. MUC5AC and MUC5B mucin proteins are key components of airway mucus, with MUC5AC being particularly responsive to environmental stimuli, making it a potential COPD biomarker. N-acetylcysteine (NAC) is a mucolytic agent with known effects on mucus viscosity and clearance, but its precise mechanisms in COPD remain unclear. This systematic review evaluated the impact of NAC on MHS in the airways, reporting significant inhibitory effects on MUC5AC and MUC5B gene and protein expression, as well as a reduction in the number of goblet cells. NAC has demonstrated efficacy in vitro and in animal models of MHS, including COPD models, but data on human bronchial tissue are lacking. This systematic review suggests that NAC acts as a mucolytic and a mucoregulator, directly inhibiting mucus secretion and goblet cell hyperplasia. Given the critical role of MHS in COPD progression, exacerbations, and mortality, these findings highlight the potential of NAC as a targeted therapy for hypersecretion COPD phenotypes. However, further studies are needed to confirm the results of this systematic review, even in human bronchial tissue, to provide translatable evidence in clinical settings. Understanding the intimate mechanism of NAC versus MHS regulation may pave the way for more effective treatments targeting airway mucus dysfunction in COPD, ultimately improving patient outcomes and reducing morbidity and mortality associated with chronic mucus hypersecretion.

Temporal Exploration of COPD Phenotypes: Insights from the COPDGene and SPIROMICS Cohorts.

Chronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships. Cross-sectional data from 8,972 tobacco-exposed COPDGene participants, with and without COPD, were used to train a model with EPGA, using thirty clinical, physiologic and CT features. Principal component analysis (PCA) was used to reduce data dimensionality to six principal components. An elastic principal tree was fitted to the reduced space. 4,585 participants from COPDGene Phase 2 were used to test longitudinal trajectories. 2,652 participants from SPIROMICS tested external reproducibility. Our analysis used cross-sectional data to create an elastic principal tree, where the concept of time is represented by distance on the tree. Six clinically distinct tree segments were identified that differed by lung function, symptoms, and CT features: 1) Subclinical (SC); 2) Parenchymal Abnormality (PA); 3) Chronic Bronchitis (CB); 4) Emphysema Male (EM); 5) Emphysema Female (EF); and 6) Severe Airways (SA) disease. Cross-sectional SPIROMICS data confirmed similar groupings. 5-year data from COPDGene mapped longitudinal changes onto the tree. 29% of patients changed segment during follow-up; longitudinal trajectories confirmed a net flow of patients along the tree, from SC towards Emphysema, although alternative trajectories were noted, through airway disease predominant phenotypes, CB and SA. This novel analytic methodology provides an approach to defining longitudinal phenotypic trajectories using cross sectional data. These insights are clinically relevant and could facilitate precision therapy and future trials to modify disease progression.

Proteomic networks and related genetic variants associated with smoking and chronic obstructive pulmonary disease

BackgroundStudies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with interconnections that may not be captured when considering single molecular features.MethodsLeveraging proteomic data from 3,173 COPDGene Non-Hispanic White (NHW) and African American (AA) participants, we applied sparse multiple canonical correlation network analysis (SmCCNet) to 4,776 proteins assayed on the SomaScan v4.0 platform to derive sparse networks of proteins associated with current vs. former smoking status, airflow obstruction, and emphysema quantitated from high-resolution computed tomography scans. We then used NetSHy, a dimension reduction technique leveraging network topology, to produce summary scores of each proteomic network, referred to as NetSHy scores. We next performed a genome-wide association study (GWAS) to identify variants associated with the NetSHy scores, or network quantitative trait loci (nQTLs). Finally, we evaluated the replicability of the networks in an independent cohort, SPIROMICS.ResultsWe identified networks of 13 to 104 proteins for each phenotype and exposure in NHW and AA, and the derived NetSHy scores significantly associated with the variable of interests. Networks included known (sRAGE, ALPP, MIP1) and novel molecules (CA10, CPB1, HIS3, PXDN) and interactions involved in COPD pathogenesis. We observed 7 nQTL loci associated with NetSHy scores, 4 of which remained after conditional analysis. Networks for smoking status and emphysema, but not airflow obstruction, demonstrated a high degree of replicability across race groups and cohorts.ConclusionsIn this work, we apply state-of-the-art molecular network generation and summarization approaches to proteomic data from COPDGene participants to uncover protein networks associated with COPD phenotypes. We further identify genetic associations with networks. This work discovers protein networks containing known and novel proteins and protein interactions associated with clinically relevant COPD phenotypes across race groups and cohorts.

Role of quantitative planar lung perfusion scintigraphy and tomography in identifying target lobes in patients with emphysematous phenotype of advanced chronic obstructive pulmonary disease: a retrospective cross-sectional study.

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease. Despite optimal medical therapy and pulmonary rehabilitation, bronchoscopic and surgical lung volume reduction may still be necessary. Identifying the target lobe is crucial for the success of these treatments. This study aims to compare the role of quantitative planar lung perfusion scintigraphy (QPLPS) with quantitative lung computed tomography (StratX®), which is used in identifying the target lobe before the Zephyr® endobronchial valve (EBV) placement in patients with the emphysematous phenotype of advanced COPD. A single-center retrospective cross-sectional study was performed in the Department of Pulmonology at the University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital between June 2019 and June 2022. The study included 46 patients with the emphysematous phenotype of advanced COPD, who were all candidates for Zephyr® EBV therapy. The target lobes were assessed using the QPLPS and StratX® and the agreement between the methods was analyzed by the Kappa statistic method. Additionally, demographic characteristics, respiratory function tests, distributions of emphysema, and 6-minute walk test results of patients were recorded. The median age was 67 (42-80) years and 42 (91.3%) were male. In QPLPS, the perfusion percentages were 7.47%±3.31%, 9.59%±2.67%, and 13.32%±2.59% for the 1st, 2nd and 3rd target lobes, respectively while in StratX®, the voxel densities were 68.28%±9.16%, 63.79%±7.42%, and 60.69%±5.35%. In StratX®, the fissure integrity (FI) at the target lobe was 76.25%±21.18%, 84.68%±17.67%, and 86.19%±13.19%, respectively. There was a significant agreement between the methods in identifying the first, second, and third target lobes in all patients (Kappa coefficient: 0.897, 0.700, and 0.522), and also in identifying the first and second target lobes in patients with heterogeneous (Kappa coefficient: 0.879, and 0.735), and homogeneous subgroups (Kappa coefficient: 0.919, and 0.672). There is an agreement between QPLPS and StratX® in identifying the target lobe in patients with severe emphysema, including those with homogeneous diseases. However, StratX® may be preferred, considering that it also predicts FI.

The Clinical Characteristics, Treatment and Prognosis of Tuberculosis-Associated Chronic Obstructive Pulmonary Disease: A Protocol for a Multicenter Prospective Cohort Study in China.

Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation. This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred. The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.

Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways

Ethnopharmacological relevanceSea buckthorn (Hippophae rhamnoides), a traditional Tibetan medicinal herb, exhibits protective effects against cardiovascular and respiratory diseases. Although Sea buckthorn extract (SBE) has been confirmed to alleviate airway inflammation in mice, its therapeutic effect and underlying mechanism on chronic obstructive pulmonary disease (COPD) requires further clarification. Aim of the studyTo elucidate the alleviative effect and molecular mechanism of SBE on lipopolysaccharides (LPS)/porcine pancreatic elastase (PPE)-induced COPD by blocking ferroptosis. MethodsThe anti-ferroptotic effects of SBE were evaluated in human BEAS-2B bronchial epithelial cells using CCK8, RT-qPCR, western blotting, and transmission electron microscopy. Transwell was employed to detect chemotaxis of neutrophils. COPD model was induced by intranasally administration of LPS/PPE in mice and measured by alterations of histopathology, inflammation, and ferroptosis. RNA-sequencing, western blotting, antioxidant examination, flow cytometry, DARTS, CETSA, and molecular docking were then used to investigate its anti-ferroptotic mechanisms. ResultsIn vitro, SBE not only suppressed erastin- or RSL3-induced ferroptosis by suppressing lipid peroxides (LPOs) production and glutathione (GSH) depletion, but also suppressed ferroptosis-induced chemotactic migration of neutrophils via reducing mRNA expression of chemokines. In vivo, SBE ameliorated LPS/PPE-induced COPD phenotypes, and inhibited the generation of LPOs, cytokines, and chemokines. RNA-sequencing showed that p53 pathway and mitogen-activated protein kinases (MAPK) pathway were implicated in SBE-mediated anti-ferroptotic action. SBE repressed erastin- or LPS/PPE-induced overactivation of p53 and MAPK pathway, thereby decreasing expression of diamine acetyltransferase 1 (SAT1) and arachidonate 15-lipoxygenase (ALOX15), and increasing expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Mechanistically, erastin-induced elevation of reactive oxygen species (ROS) was reduced by SBE through directly scavenging free radicals, thereby contributing to its inhibition of p53 and MAPK pathways. CETSA, DARTS, and molecular docking further showed that ROS-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) may be the target of SBE. Overexpression of NOX4 partially impaired the anti-ferroptotic activity of SBE. ConclusionOur results demonstrated that SBE mitigated COPD by suppressing p53 and MAPK pro-ferroptosis pathways via directly scavenging ROS and blocking NOX4. These findings also supported the clinical application of Sea buckthorn in COPD therapy.

GOLD-Grade Specific Disease Characterization and Phenotyping of COPD Using Quantitative Computed Tomography in the Nationwide COSYCONET Multicenter Trial in Germany

Introduction: The aim of this study was to apply quantitative computed tomography (QCT) for GOLD-grade specific disease characterization and phenotyping of air-trapping, emphysema, and airway abnormalities in patients with chronic obstructive pulmonary disease (COPD) from a nationwide cohort study. Methods: As part of the COSYCONET multicenter study, standardized CT in ex- and inspiration, lung function assessment (FEV1/FVC), and clinical scores (BODE index) were prospectively acquired in 525 patients (192 women, 327 men, aged 65.7 ± 8.5 years) at risk for COPD and at GOLD1–4. QCT parameters such as total lung volume (TLV), emphysema index (EI), parametric response mapping (PRM) for emphysema (PRMEmph) and functional small airway disease (PRMfSAD), total airway volume (TAV), wall percentage (WP), and total diameter (TD) were computed using automated software. Results: TLV, EI, PRMfSAD, and PRMEmph increased incrementally with each GOLD grade (p < 0.001). Aggregated WP5–10 of subsegmental airways was higher from GOLD1 to GOLD3 and lower again at GOLD4 (p < 0.001), whereas TD5–10 was significantly dilated only in GOLD4 (p < 0.001). Fifty-eight patients were phenotyped as “non-airway non-emphysema type,” 202 as “airway type,” 96 as “emphysema type,” and 169 as “mixed type.” FEV1/FVC was best in “non-airway non-emphysema type” compared to other phenotypes, while “mixed type” had worst FEV1/FVC (p < 0.001). BODE index was 0.56 ± 0.72 in the “non-airway non-emphysema type” and highest with 2.55 ± 1.77 in “mixed type” (p < 0.001). Conclusion: QCT demonstrates increasing hyperinflation and emphysema depending on the GOLD grade, while airway wall thickening increases until GOLD3 and airway dilatation occur in GOLD4. QCT identifies four disease phenotypes with implications for lung function and prognosis.

Lung Lesions in Exposure to Pesticides and Herbicides (Literature Review and Case Report)

Pesticides (herbicides, insecticides, fungicides, zoocides) are mixtures of substances of chemical or biological origin used to destroy or inhibit the growth of microorganisms, fungi, harmful vegetation, and other living organisms. These organisms damage crop and livestock production, degrade the quality of agricultural products, materials, and goods. Pesticides are classified into organic, and inorganic based on their chemical composition. About 1,000 active ingredients are used in pesticides, of which 310 are considered particularly hazardous. Extensive use of pesticides leads to the destruction of biocenoses and the emergence of various pathological changes in the human body. Among the pesticide ingredients with acute and chronic toxicity, abamectin, aluminum phosphide, beta-cyfluthrin, bifenthrin, chlorpyrifos, deltamethrin, diazinon, fenamiphos, malathion, methomyl, oxamyl, primicarb, propargite, tebuconazole, chlorothalonil, bromoxynil, bromoxynil octanoate, brodifacoum, and others stand out. In conditions of pesticide load on soils, the frequency of allergic and respiratory diseases is steadily increasing. Chronic obstructive pulmonary disease (COPD), caused by smoking and pesticides, leads to loss of working capacity and social activity, as well as significant costs for treatment and rehabilitation. The article discusses the pathogenetic and clinical aspects of the formation of COPD under conditions of synergy (smoking + pesticides). Various clinical phenotypes of COPD are also considered. A clinical case of a patient with COPD caused by smoking and prolonged contact with pesticides (mosplan, zellek-super, goal 2E), which manifested with chronic respiratory failure, multifocal atherosclerosis, and heart failure, is described.

COPD is associated with increased cardiovascular disease risk independent of phenotype.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide that frequently presents with concomitant cardiovascular diseases. Despite the pathological distinction between individual COPD phenotypes such as emphysema and chronic bronchitis, there is a lack of knowledge about the impact of COPD phenotype on cardiovascular disease risk. Thus, this study aimed to utilize a nationally representative sample to investigate cardiovascular disease prevalence in patients with COPD with emphysema and chronic bronchitis phenotypes. Data from 31,560 adults including 2504 individuals with COPD, collected as part of the National Health and Nutrition Examination Survey (1999-2018), were examined. A significantly increased cardiovascular disease risk, including coronary heart disease, heart failure, myocardial infarction and stroke, was identified in patients with COPD among all disease phenotypes. Particularly, compared to those without COPD, individuals with chronic bronchitis presented with 1.76 (95% CI: 1.41-2.20) times greater odds, individuals with emphysema with 2.31 (95% CI: 1.80-2.96) times greater odds, while those with a concurrent phenotype (combined chronic bronchitis and emphysema) exhibited 2.98 (95% CI: 2.11-4.21) times greater odds of reporting cardiovascular diseases. Our data confirms that patients with COPD present an elevated risk of developing cardiovascular disease among all phenotypes, with the most marked increase being in those with concurrent chronic bronchitis and emphysema phenotypes. These findings emphasize the need for awareness and appropriate cardiovascular screening in COPD.

Association of bronchial disease on CT imaging and clinical definitions of chronic bronchitis in a single-center COPD phenotyping study

IntroductionChronic Bronchitis (CB) represents a phenotype of chronic obstructive pulmonary disease (COPD). While several definitions have been used for diagnosis, the relationship between clinical definitions and radiologic assessment of bronchial disease (BD) has not been well studied. The aim of this study was to evaluate the relationship between three clinical definitions of CB and radiographic findings of BD in spirometry-defined COPD patients. MethodsA cross-sectional analysis was performed from a COPD phenotyping study. It was a prospective observational cohort. Participants had spirometry-defined COPD and available chest CT imaging. Comparison between CB definitions, Medical Research Council (CBMRC), St. George's Respiratory Questionnaire (CBSGRQ), COPD Assessment Test (CBCAT) and CT findings were performed using Cohen's Kappa, univariate and multivariate logistic regressions. ResultsOf 112 participants, 83 met inclusion criteria. Demographics included age of 70.1 ± 7.0 years old, predominantly male (59.0 %), 45.8 ± 30.8 pack-year history, 21.7 % actively smoking, and mean FEV1 61.5 ± 21.1 %. With MRC, SGRQ and CAT definitions, 22.9 %, 36.6 % and 28.0 % had CB, respectively. BD was more often present in CB compared to non-CB patients; however, it did not have a statistically significant relationship between any of the CB definitions. CBSGRQ had better agreement with radiographically assessed BD compared to the other two definitions. ConclusionIdentification of BD on CT was associated with the diagnoses of CB. However, agreement between imaging and definitions were not significant, suggesting radiologic findings of BD and criteria defining CB may not identify the same COPD phenotype. Research to standardize imaging and clinical methods is needed for more objective identification of COPD phenotypes.

Developing Interventions for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an incurable, progressive respiratory disease that may have a significant negative impact on the morbidity and mortality of affected patients. A substantial portion of the world's population is affected by COPD, and despite optimal medical management with medications, supplemental oxygen, and pulmonary rehabilitation, many patients are left debilitated because of this disease. Bronchoscopic treatment modalities offer a less-invasive method for the treatment of refractory COPD compared to surgical interventions and have expanded the potential therapeutic options for these patients. Bronchoscopic lung volume reduction is aimed at decreasing the hyperinflation and air trapping that occur in emphysema, and the most studied and successful intervention is endobronchial valve placement. Endobronchial coils, polymeric sealants, and thermal ablation are other researched alternatives. Additional interventional procedures are being investigated for the treatment of the mucus hypersecretion and cough that are associated with the chronic bronchitis phenotype of COPD and include targeted lung denervation, metered dose spray cryotherapy, deobstruction balloon, and bronchial rheoplasty. This review summarizes the most recent evidence pertaining to available therapies for the management of COPD, including chronic bronchitis, with a particular focus on bronchoscopic interventions.