Chronic Obstructive Pulmonary Disease Phenotypes Research Articles

MicroRNA Monitoring in Human Alveolar Macrophages from Patients with Smoking-Related Lung Diseases: A Preliminary Study

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports a role of the immune system, mainly played by alveolar macrophages (AMs), in key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore their involvement in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine the expressions of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, a bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group, suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insights for diagnosis or pharmacological treatment.

Chronic obstructive pulmonary disease (COPD) and COPD-like phenotypes.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. Historically, two COPD phenotypes have been described: chronic bronchitis and emphysema. Although these phenotypes may provide additional characterization of the pathophysiology of the disease, they are not extensive enough to reflect the heterogeneity of COPD and do not provide granular categorization that indicates specific treatment, perhaps with the exception of adding inhaled glucocorticoids (ICS) in patients with chronic bronchitis. In this review, we describe COPD phenotypes that provide prognostication and/or indicate specific treatment. We also describe COPD-like phenotypes that do not necessarily meet the current diagnostic criteria for COPD but provide additional prognostication and may be the targets for future clinical trials.

Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype

BackgroundThe aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. Material and methodsWe retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. ResultsFrom 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (−39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16–7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08–17.42]; p = 0.04). ConclusionsOur study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.

Respiratory Oscillometry and Functional Performance in Different COPD Phenotypes.

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. 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 Glittre‑ADL test, handgrip strength and respiratory pressures. 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). 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.

Phenotyping of COPD with MRI in comparison to same-day CT in a multi-centre trial.

A prospective, multi-centre study to evaluate concordance of morphologic lung MRI and CT in chronic obstructive pulmonary disease (COPD) phenotyping for airway disease and emphysema. A total of 601 participants with COPD from 15 sites underwent same-day morpho-functional chest MRI and paired inspiratory-expiratory CT. Two readers systematically scored bronchial wall thickening, bronchiectasis, centrilobular nodules, air trapping and lung parenchyma defects in each lung lobe and determined COPD phenotype. A third reader acted as adjudicator to establish consensus. Inter-modality and inter-reader agreement were assessed using Cohen's kappa (im-κ and ir-κ). The mean combined MRI score for bronchiectasis/bronchial wall thickening was 4.5/12 (CT scores, 2.2/12 for bronchiectasis and 6/12 for bronchial wall thickening; im-κ, 0.04-0.3). Expiratory right/left bronchial collapse was observed in 51 and 47/583 on MRI (62 and 57/599 on CT; im-κ, 0.49-0.52). Markers of small airways disease on MRI were 0.15/12 for centrilobular nodules (CT, 0.34/12), 0.94/12 for air trapping (CT, 0.9/12) and 7.6/12 for perfusion deficits (CT, 0.37/12 for mosaic attenuation; im-κ, 0.1-0.41). The mean lung defect score on MRI was 1.3/12 (CT emphysema score, 5.8/24; im-κ, 0.18-0.26). Airway-/emphysema/mixed COPD phenotypes were assigned in 370, 218 and 10 of 583 cases on MRI (347, 218 and 34 of 599 cases on CT; im-κ, 0.63). For all examined features, inter-reader agreement on MRI was lower than on CT. Concordance of MRI and CT for phenotyping of COPD in a multi-centre setting was substantial with variable inter-modality and inter-reader concordance for single diagnostic key features. MRI of lung morphology may well serve as a radiation-free imaging modality for COPD in scientific and clinical settings, given that its potential and limitations as shown here are carefully considered. • In a multi-centre setting, MRI and CT showed substantial concordance for phenotyping of COPD (airway-/emphysema-/mixed-type). • Individual features of COPD demonstrated variable inter-modality concordance with features of pulmonary hypertension showing the highest and bronchiectasis showing the lowest concordance. • For all single features of COPD, inter-reader agreement was lower on MRI than on CT.

Cell-free DNA levels associate with COPD exacerbations and mortality

The question addressed by the studyGood biological indicators capable of predicting chronic obstructive pulmonary disease (COPD) phenotypes and clinical trajectories are lacking. Because nuclear and mitochondrial genomes are damaged and released by cigarette smoke exposure, plasma cell-free mitochondrial and nuclear DNA (cf-mtDNA and cf-nDNA) levels could potentially integrate disease physiology and clinical phenotypes in COPD. This study aimed to determine whether plasma cf-mtDNA and cf-nDNA levels are associated with COPD disease severity, exacerbations, and mortality risk.Materials and methodsWe quantified mtDNA and nDNA copy numbers in plasma from participants enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE, n = 2,702) study and determined associations with relevant clinical parameters.ResultsOf the 2,128 participants with COPD, 65% were male and the median age was 64 (interquartile range, 59–69) years. During the baseline visit, cf-mtDNA levels positively correlated with future exacerbation rates in subjects with mild/moderate and severe disease (Global Initiative for Obstructive Lung Disease [GOLD] I/II and III, respectively) or with high eosinophil count (≥ 300). cf-nDNA positively associated with an increased mortality risk (hazard ratio, 1.33 [95% confidence interval, 1.01–1.74] per each natural log of cf-nDNA copy number). Additional analysis revealed that individuals with low cf-mtDNA and high cf-nDNA abundance further increased the mortality risk (hazard ratio, 1.62 [95% confidence interval, 1.16–2.25] per each natural log of cf-nDNA copy number).Answer to the questionPlasma cf-mtDNA and cf-nDNA, when integrated into quantitative clinical measurements, may aid in improving COPD severity and progression assessment.

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.

Assessing Chronic Obstructive Pulmonary Disease (COPD) Mortality and Morbidity: A Review

From PubMed, referencing articles over the previous 4 years, 146 articles addressing morbidity and mortality of chronic obstructive pulmonary disease (COPD) were reviewed. The major topics covered in this article include the epidemiology of COPD, spirometry with ATS/ERS and GOLD staging, scoring Indices (BODE, ADO, FODEP), trajectories in the development of COPD, pathophysiology of COPD, classification of COPD phenotypes, pharmacotherapy of COPD, causes of Acute Exacerbation of COPD (AECOPD), CT Lung imaging in COPD, and COPD comorbidities. All studies are referenced allowing for greater exploration into given areas of interest (76 ref.).

Respiratory Microbiome Profiles Associated With Distinct Inflammatory Phenotype and Clinical Indexes in Chronic Obstructive Pulmonary Disease.

Respiratory microbiome studies have fostered our understanding of the various phenotypes and endotypes of heterogeneous chronic obstructive pulmonary disease (COPD). This study aimed to identify microbiome-driven clusters that reflect the clinical features and dominant microbiota of COPD. This cross-sectional study included 32 patients with stable COPD between December 2019 and December 2020 from the outpatient clinic of the China-Japan Friendship Hospital. Sputum samples were tested for 16S rRNA. Patients were classified according to the species level using an unsupervised clustering method to compare the inflammatory phenotypes of 2 clusters and analyze the correlation between the main bacteria and clinical indicators in each cluster. Patients were further divided into 2 clusters according to microorganisms. Neutrophils in cluster 1 were significantly increased compared with cluster 2. Cluster 1 was predominantly Bacteroides, while cluster 2 was dominated by Prevotella and Fusobacterium at the genus level. Fusobacterium was negatively correlated with the COPD Assessment Test (CAT) score, and Bacteroides were positively correlated with the number of acute exacerbations of COPD. This study found that differential flora was negatively associated with CAT scores and the number of acute exacerbations of COPD. This microbiome-driven, unbiased clustering method for COPD can help identify new endotype-related COPD phenotypes.

T3 Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model.

Chronic obstructive pulmonary disease (COPD) is a complex pulmonary condition characterized by bronchitis, emphysema, and mucus stasis. Due to the variability in symptoms among patients, traditional approaches to treating COPD as a singular disease are limited. This led us to focus on phenotype/endotype classifications. In this study, we explore the potential therapeutic role of thyroid hormone (T3) by using mouse models: emphysema-dominant elastase-induced COPD and airway-dominant C57BL/6-βENaC-Tg to represent different types of the disease. Here, we showed that intratracheal T3 treatment (40, 80 μg/kg, i.t., every other day) resulted in significant improvements regarding emphysema and the enhancement of respiratory function in the elastase-induced COPD model. T3-dependent improvement is likely linked to the up-regulation of Ppargc1a, a master regulator of mitochondrial biogenesis, and Gclm, a factor associated with oxidative stress. Conversely, neither short- nor long-term T3 treatments improved COPD pathology in the C57BL/6-βENaC-Tg mice. Because the up-regulation of extrathyroidal T3-producing enzyme Dio2, which is also considered a marker of T3 requirement, was specifically observed in elastase-induced COPD lungs, these results demonstrate that exogenous T3 supplementation may have therapeutic potential for acute but not chronic COPD exacerbation. Moreover, this study highlights the relevance of considering not only COPD phenotypes but also COPD endotypes (expression levels of Ppargc1a and/or Dio2) in the research and development of better treatment approaches for COPD.

Advances in molecular mechanism and treatment of chronic mucus hypersecretion

Chronic obstructive pulmonary disease (COPD) is one of the chronic diseases with high morbidity and mortality in China, which imposes heavy economic burden on society. Research has shown that chronic mucus hypersecretion (CMH) is an independent risk factor for persistent clinical symptoms, poor quality of life, rapid decline in lung function, acute exacerbation and increased hospitalization rate in COPD patients. CMH is a clinical phenotype of COPD with specific pathological and physiological changes. At present, the formation mechanism of CMH is not clear. There is a lack of specific and effective targeted treatments. This article aimed to review the latest research findings on CMH at home and abroad from the overview, impact on COPD patients, molecular mechanisms of formation, current treatment status and progress, and discuss potential targets for CMH treatment, to provide new ideas and directions for improving CMH and treating COPD.

Clinical efficacy of a triple combination of budesonide/ glycopyrronium bromide/formoterol in the treatment of chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterized by persistent airflow limitation, caused by chronic inflammation in response to exposure to inhaled damaging particles or gases. Exacerbations of COPD lead to the progression of symptoms, worsening lung function, reduced physical tolerance, and, as a result, contribute to an increase mortality. Therefore, the prevention of exacerbations is a primary objective in the management of COPD. The foundation of COPD therapy involves prescribing long-acting bronchodilators, and for some patients, the use of anti-inflammatory agents, such as inhaled corticosteroids (ICS). ICS are used in combination with long-acting beta2-agonists (LABA) or as part of triple therapy (ICS/LABA/ LAMA). The choice of triple therapy depends on the patient’s exacerbation history, severity of symptom, level of peripheral blood eosinophilia, risk of infectious complications, and the presence of a concomitant diagnosis of bronchial asthma. Triple therapy offers advantages in terms of improving lung function, disease symptoms, reducing exacerbation frequency, and significantly decreasing mortality compared to other inhaled therapy options for COPD. A significant advantage of this therapy has been shown in patients with eosinophilic COPD. Currently, three combined inhalation medications containing ICS/LABA/LAMA are available for COPD treatment in our country. This review provides basic information on the clinical efficacy and safety profile of one of them, budesonide/glycopyrronium bromide/formoterol, in patients with various COPD phenotypes.

Clinical phenotypes of COPD and their impact on quality of life: A cross-sectional study

BackgroundA Chronic Obstructive Pulmonary Disease (COPD) phenotype is a single or group of disease characteristics that describe differences between individuals based on clinically important factors such as symptoms, exacerbations, morbidity, and treatment responses. Many studies estimated the prevalence of various phenotypes, but very few studies looked into their quality of life. We aimed to estimate the prevalence of different COPD phenotypes and their disease-specific Health-Related Quality of Life (HRQoL). Materials and methodsThe prospective study, with a sample size of 136, was conducted between May 2021 and December 2022 in a tertiary teaching institute. Based on their clinical features, COPD patients were classified into 4 different clinical phenotypes, and their disease-specific quality of life was assessed using St. George Respiratory Questionnaire-COPD(SGRQ-c) and COPD Assessment Test (CAT) questionnaires. ResultsAmong 136 COPD patients, the frequency of Non-Exacerbator (NE), Exacerbator Emphysema (EEM), Exacerbator Chronic Bronchitis (ECB), and Asthma COPD overlap (ACO) phenotypes was 79(58.1 %), 16(11.8 %), 31(22.8 %), and 10(7.4 %) respectively. Based on the SGRQ-c score, the ECB and EEM phenotypes had a significantly poorer Quality of life (QoL) when compared with NE(P<0.0001), ACO(P=0.011), phenotypes. Similarly, ECB and EEM phenotypes had significantly poorer QoL when compared to NE(P<0.0001), and ACO(P=0.015), based on the CAT score. ECB and EEM patients also had the worst scores in all individual CAT items and SGRQ-c components. ConclusionNE was the most common followed by ECB phenotype. ECB and EEM phenotypes recorded the poorest quality of life without any significant differences among them. Further research is needed in the future to determine whether phenotype-specific therapies can produce better clinical outcomes.

Characteristics of inflammatory phenotypes in patients with chronic obstructive pulmonary disease: a cross-sectional study

BackgroundThe relationship between airway inflammation in chronic obstructive pulmonary disease (COPD) and clinical characteristics remains unclear. This study aimed to investigate the airway inflammatory phenotypes in COPD and their association...

Оценка температуры выдыхаемого воздуха у пациентов с различным течением хронической обструктивной болезни легких

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an important medical problem of modern society. COPD is characterized by a heterogeneous course due to individual trajectories of pulmonary function decline, differences in the frequency of exacerbations and comorbidity. The exhaled air temperature is a parameter associated with the activity of local inflammation in the respiratory tract in COPD and, accordingly, the nature of the course of the disease. AIM: To study peak values of exhaled air temperature in patients with heterogeneous COPD. MATERIALS AND METHODS: The exhaled air temperature was assessed in patients with COPD phenotype with frequent exacerbations in comparison with patients with stable COPD and rare exacerbations and a group of healthy individuals. RESULTS: It was shown that the peak values of exhaled air temperature decreased in patients with COPD with rare exacerbations compared with healthy controls (p &lt; 0.01), but increased in patients with COPD with a phenotype of frequent exacerbations compared with both the control group (p &lt; 0.01) and COPD with rare exacerbations (p &lt; 0.01). CONCLUSION: The stable course of COPD with rare exacerbations is characterized by a decrease in the values of the exhaled air temperature compared with the healthy control, while in COPD patients with the phenotype of frequent exacerbations, the exhaled air temperature increased compared with the healthy control.

Risk factors for chronic obstructive pulmonary disease (COPD) in a tertiary health institution in Lagos, Nigeria

Objective: To describe the clinical characteristics and identifiable risk factors for Chronic Obstructive Pulmonary Disease (COPD) in a real-world clinical setting.Design: Cross-sectional study among patients with COPD.Setting: The Respiratory clinic of the Lagos University Teaching Hospital.Participants: Consecutive patients with spirometry confirmed COPD on follow-up for ≥3 months. There were 79 participants.Intervention: NoneMain outcome measure: COPD risk factors, disease severity, comorbidities, and the severity of airflow limitation.Results: The mean age of the participants was 63.3± 12.4 years, and 47 (59.5) were male. There was a high symptom burden (73.4% had COPD assessment test (CAT) score &gt;10), 33 (41.8%) and 4 (5.1%) had GOLD 3 and GOLD 4 airflow limitation, respectively. Risk factors were identified for 96.2% of the participants: history of asthma in 37 (46.8%), tobacco smoking 22 (27.8%), occupational exposure 15 (19%), biomass exposure 5 (6.6%), post-tuberculosis 3 (3.8%), old age (3.8%), and prematurity 1 (1.3%). Fifty-nine (74.7%) had Asthma COPD Overlap (ACO). There were no significant associations between the risk factors and disease severity. Participants with ACO had lower lung function and a high frequency of allergic rhinitis.Conclusion: Asthma was the most commonly identifiable risk factor for COPD, underscoring asthma risk reduction and management optimisation as priorities toward COPD burden mitigation. Future studies need to validate these findings and identify the predominant COPD phenotypes in our setting.

Radiation phenotypes of chronic obstructive pulmonary disease in patients with type 2 diabetes mellitus

The relevance of the work is due to the lack of systematic data on the features of lung damage in patients with chronic obstructive pulmonary disease (COPD) and type II diabetes mellitus (DM2).Aim: To identify the main radiation phenotypes of lung tissue damage in patients with chronic obstructive pulmonary disease and type II diabetes mellitus.Material and Methods. We conducted a one-stage observational study, with the analysis of clinical data, laboratory and instrumental studies (pulmonary function tests, computed tomography), in patients with chronic obstructive pulmonary disease in combination with type II diabetes mellitus (57 people).Results. In patients with a combination of COPD and type II diabetes mellitus, the predominance of predominantly bronchitic type of COPD over emphysematous was revealed, with the presence of statistically significant links between a number of patterns (the presence of air trapping, bronchiolitis) and laboratory results (the number of eosinophils in the blood, the number of leukocytes in the blood and sputum, the number of macrophages in sputum, levels of IL-33, TNF-α, CRP, IFN-γ/IL-4 ratio), which may reflect the influence of different pathogenetic aspects of inflammation on the formation of structural changes in the lung tissue).Conclusion. For patients with a combination of chronic obstructive pulmonary disease and type II diabetes mellitus, the presence of a bronchitic COPD phenotype with the absence of confluent and destructive forms of pulmonary emphysema is more characteristic. The wide prevalence of the bronchitic COPD phenotype in patients with concomitant type 2 diabetes mellitus may be due to predominant changes in the small airways, the development of microangiopathy, as well as an infectious factor, since patients with type 2 diabetes mellitus, in general, are more susceptible to infections, including respiratory.

Does Chronic Obstructive Pulmonary Disease Originate from Different Cell Types?

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung that can initiate COPD pathogenesis, focusing on the susceptibility of macrophages, T and B cells, mast cells, dendritic cells, endothelial cells, and airway epithelial cells. Additional cell types, including fibroblasts, smooth muscle cells, neuronal cells, and other rare cell types not covered here, may also play a role in orchestrating COPD. Here, we discuss current knowledge gaps, such as which cell types drive distinct disease phenotypes and/or stages of the disease and which cells are primarily affected by the genetic variants identified by whole genome-wide association studies. Applying new technologies that interrogate the functional role of a specific cell type or a combination of cell types as well as single-cell transcriptomics and proteomic approaches are creating new opportunities to understand and clarify the pathophysiology and thereby the clinical heterogeneity of COPD.

The Role of Osteopontin in Respiratory Health and Disease.

The biological functions of osteopontin (OPN) are diverse and specific to physiological and pathophysiological conditions implicated in inflammation, biomineralization, cardiovascular diseases, cellular viability, cancer, diabetes, and renal stone disease. We aimed to present the role of OPN in respiratory health and disease. OPN influences the immune system and is a chemo-attractive protein correlated with respiratory disease severity. There is evidence that OPN can advance the disease stage associated with its fibrotic, inflammatory, and immune functions. OPN contributes to eosinophilic airway inflammation. OPN can destroy the lung parenchyma through its neutrophil influx and fibrotic mechanisms, linking OPN to at least one of the two major chronic obstructive pulmonary disease phenotypes. Respiratory diseases that involve irreversible lung scarring, such as idiopathic pulmonary disease, are linked to OPN, with protein levels being overexpressed in individuals with severe or advanced stages of the disorders and considerably lower levels in those with less severe symptoms. OPN plays a significant role in lung cancer progression and metastasis. It is also implicated in the pathogenesis of pulmonary hypertension, coronavirus disease 2019, and granuloma generation.

Plasma Proteomics Study Between the Frequent Exacerbation and Infrequent Exacerbation Phenotypes of Chronic Obstructive Pulmonary Disease.

Frequent exacerbation (FE) and infrequent exacerbation (IE) are two phenotypes of chronic obstructive pulmonary disease (COPD), of which FE is associated with a higher incidence of exacerbation and a serious threat to human health. Because the pathogenesis mechanisms of FE are unclear, this study aims to identify FE-related proteins in the plasma via proteomics for use as predictive, diagnostic, and therapeutic biomarkers of COPD. A cross-sectional study was conducted in which plasma protein profiles were analyzed in COPD patients at stable stage, and differentially expressed proteins (DEPs) were screened out between the FE and IE patients. FE-related DEPs were identified using data-independent acquisition-based proteomics and bioinformatics analyses. In addition, FE-related candidates were verified by enzyme-linked immunosorbent assay. In this study, 47 DEPs were screened out between the FE and IE groups, including 20 upregulated and 27 downregulated proteins. Key biological functions (eg, neutrophil degranulation, extracellular exosome, protein homodimerization activity) and signaling pathways (eg, arginine and proline metabolism) were enriched in association with the FE phenotype. Receiver operating characteristic (ROC) analysis of the 11 combined DEPs revealed an area under the curve of 0.985 (p <0.05) for discriminating FE from IE. Moreover, correlation and ROC curve analyses indicated that creatine kinase, M-type (CKM) and fat storage-inducing transmembrane protein 1 (FITM1) might be clinically significant in patients with the FE phenotype. In addition, plasma expression levels of CKM and FITM1 were validated to be significantly decreased in the FE group compared with the IE group (CKM: p <0.01; FITM1: p <0.05). In this study, novel insights into COPD pathogenesis were provided by investigating and comparing plasma protein profiles between the FE and IE patients. CKM, FITM1, and a combinative biomarker panel may serve as useful tools for assisting in the precision diagnosis and effective treatment of the FE phenotype of COPD.