scholarly journals Dysregulation of the CD163-Haptoglobin Axis in the Airways of COPD Patients

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 2
Author(s):  
Andrew Higham ◽  
James M. Baker ◽  
Natalie Jackson ◽  
Rajesh Shah ◽  
Simon Lea ◽  
...  

Pulmonary iron levels are increased in chronic obstructive pulmonary disease (COPD) patients. Iron causes oxidative stress and is a nutrient for pathogenic bacteria. Iron may therefore play an important role in the pathophysiology of COPD. The CD163-haptglobin axis plays a central role in the regulation of iron bioavailability. The aim of this study was to examine dysregulation of the CD163-haptglobin axis in COPD. We measured soluble CD163 (sCD163) and haptoglobin levels in sputum supernatants by enzyme-linked immunosorbent assay (ELISA) and sputum macrophage CD163 and haptoglobin expression by flow cytometry in COPD patients and controls. SCD163 levels were lower in COPD patients compared to controls (p = 0.02), with a significant correlation to forced expiratory volume in 1 s (FEV1)% predicted (rho = 0.5, p = 0.0007). Sputum macrophage CD163 expression was similar between COPD patients and controls. SCD163 levels and macrophage CD163 expression were lower in COPD current smokers compared to COPD ex-smokers. Haptoglobin levels were not altered in COPD patients but were regulated by genotype. Macrophage CD163 and haptolgobin expression were significantly correlated, supporting the role of CD163 in the cellular uptake of haptoglobin. Our data implicates a dysfunctional CD163-haptoglobin axis in COPD, which may contribute to disease pathophysiology, presumably due to reduced clearance of extracellular iron.

2021 ◽  
Author(s):  
Tai Joon An ◽  
Yeun Jie Yoo ◽  
Jeong Uk Lim ◽  
Wan Seo ◽  
Chan Kwon Park ◽  
...  

Abstract Background: The importance of evaluating the diaphragm muscle in chronic obstructive pulmonary disease (COPD) is widely accepted. However, the role of diaphragm ultrasound (DUS) in COPD is not fully understood. We set this study to evaluate the role of DUS for distinguishing the status of COPD. Methods: COPD patients who underwent DUS were enrolled between March 2020 and November 2020. The diaphragm thickening fraction (TFmax) and diaphragm excursion (DEmax) during maximal deep breathing were measured. Patients were divided into exacerbation and stable groups. Demographics, lung function, and DUS findings were compared between the two groups. Receiver operating characteristic (ROC) curve and univariate/multivariate logistic regression analyses were performed.Results: Fifty-five patients were enrolled. The exacerbation group had a lower body mass index (BMI) (20.9 vs. 24.2, p = 0.003), lower TFmax (94.8 ± 8.2% vs. 158.4 ± 83.5%, p = 0.010), and lower DEmax (30.8 ± 11.1 mm vs. 40.5 ± 12.5 mm, p = 0.007) compared to stable group. The areas under the TFmax (0.745) and DEmax (0.721) curves indicated fair results for distinguishing exacerbation. The patients were divided into low and high TFmax and DEmax groups based on calculated cut-off values. Low TFmax (odds ratio [OR] 8.40; 95% confidence interval [CI] 1.55–45.56) and low DEmax (OR 11.51; 95% CI 1.15–115.56) were associated with exacerbation after adjusting for age, sex, BMI, forced vital capacity and forced expiratory volume in 1 sec.Conclusion: TFmax and DEmax distinguished exacerbation from stable status. We describe the DUS cut-off values for determining an exacerbation status in this study.


2021 ◽  
Vol 4 (1) ◽  
pp. 61
Author(s):  
Rexel Kuatama ◽  
Louis Fabio Jonathan Jusni ◽  
Christa Karina

Background: Chronic Obstructive Pulmonary Disease (COPD) is the third highest leading cause of early death amongst other non-communicable diseases characterized by irreversible limitations of airflow. Current reliable classification relies on forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) measured on spirometry. In order to provide more effective and individualized management, new markers are needed. Accumulating studies has shown the role of miRNA in the pathogenesis of COPD and the progression of the disease. Aim: This review aims to provide overview of the diagnostic capabilities of miRNA and identify gaps of knowledge for further studies. Method: A review based on Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) was conducted with the database from Pubmed, Science Direct, and Proquest. Outcome: A total of nine studies has reported  diagnostic accuracies of miRNA in distinguishing COPD and normal, COPD and AECOPD, and other subtypes of COPD Conclusion: Retrospective diagnostic analyses of miRNAs have shown several promising AUC and need to be followed up with reliable prospective designs. Further diagnostics studies, in particular those with clinical values, need to be conducted.


2021 ◽  
Vol 10 (2) ◽  
pp. 269
Author(s):  
Elisabetta Zinellu ◽  
Alessandro G. Fois ◽  
Elisabetta Sotgiu ◽  
Sabrina Mellino ◽  
Arduino A. Mangoni ◽  
...  

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.


2015 ◽  
Vol 3 (4) ◽  
pp. 151-154 ◽  
Author(s):  
Gautam Rawal ◽  
Sankalp Yadav

AbstractCachexia and muscle wasting is a frequent but partly reversible complication in patients with chronic obstructive pulmonary disease (COPD), and affects the disease progression and prognosis. Weight loss in COPD is a consequence of increased energy requirements unbalanced by dietary intake. Nutritional supplement therapy has been shown to be effective for maintaining and improving the muscle strength and exercise tolerance in poorly nourished COPD patients, thereby decreasing morbidity and mortality. This mini review discusses the role of nutritional supplement therapy in the treatment of COPD.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217072
Author(s):  
Enya Daynes ◽  
Neil Greening ◽  
Sally J Singh

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by symptomatic dyspnoea and reduced exercise tolerance, in part as a result muscle weakness, for which inspiratory muscle training (IMT) may be useful. Excess mucus hypersecretion commonly coexists in COPD and may lead to reduce ventilation, further impacting on breathlessness. Devices for sputum clearance may be employed to aid mucus expectoration. This trial aimed to explore the effectiveness of a combined IMT and high-frequency airway oscillating (HFAO) device in the management of dyspnoea.MethodsThis was a double-blinded, randomised sham-controlled trial which recruited symptomatic patients with COPD. Patients were randomised to either a HFAO device (Aerosure) or sham device for 8 weeks, three times a day. The primary outcome was the Chronic Respiratory Questionnaire dyspnoea (CRQ-D) domain. Pre-specified subgroup analyses were performed including those with respiratory muscle weakness, excessive sputum and frequent exacerbators.Results104 participants (68% men, mean (SD) age 69.75 years (7.41), forced expiratory volume in 1 s per cent predicted 48.22% (18.75)) were recruited to this study with 96 participants completing. No difference in CRQ-D was seen between groups (0·28, 95% CI −0.19 to 0.75, p=0.24), though meaningful improvements were seen over time in both groups (mean (SD) HFAO 0.45 (0.78), p<0.01; sham 0.73 (1.09), p<0.01). Maximal inspiratory pressure significantly improved in the HFAO group over sham (5.26, 95% CI 0.34 to 10.19, p=0.05). Similar patterns were seen in the subgroup analysis.ConclusionThere were no statistical differences between the HFAO and the sham group in improving dyspnoea measured by the CRQ-D.Trial registration numberISRCTN45695543.


2019 ◽  
Vol 8 (7) ◽  
pp. 962 ◽  
Author(s):  
Tinè ◽  
Biondini ◽  
Semenzato ◽  
Bazzan ◽  
Cosio ◽  
...  

Blood eosinophils measurement, as proxy for tissue eosinophils, has become an important biomarker for exacerbation risk and response to inhaled corticosteroids (ICS) in Chronic Obstructive Pulmonary Disease (COPD). Its use to determine the pharmacological approach is recommended in the latest COPD guidelines. The potential role of blood eosinophils is mainly based on data derived from post-hoc and retrospective analyses that showed an association between increased blood eosinophils and risk of exacerbations, as well as mitigation of this risk with ICS. Yet other publications, including studies in real life COPD, do not confirm these assumptions. Moreover, anti-eosinophil therapy targeting interleukin (IL)-5 failed to reduce exacerbations in COPD patients with high blood eosinophils, which casts significant doubts on the role of eosinophils in COPD. Furthermore, a reduction of eosinophils might be harmful since COPD patients with relatively high eosinophils have better pulmonary function, better life quality, less infections and longer survival. These effects are probably linked to the role of eosinophils in the immune response against pathogens. In conclusion, in COPD, high blood eosinophils are widely used as a biomarker for exacerbation risk and response to ICS. However, much is yet to be learned about the reasons for the high eosinophil counts, their variations and their controversial effects on the fate of COPD patients.


2010 ◽  
Vol 11 (4) ◽  
pp. 249-253 ◽  
Author(s):  
Ashok A. Ramani ◽  
Anthony A. Pickston ◽  
James L. Clark ◽  
Courtney A. Clark ◽  
Michael Brown

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, and the incidence and prevalence are rising every decade. The cost of hospital admission is substantial and is the single largest source of expenditure in care of COPD patients. Home-based intervention has been shown to provide long-term cost benefit in a range of chronic illnesses; however, the role of home visits by respiratory therapists (RT) in COPD management has not been evaluated. The aim of this study was to assess the effectiveness of a management pathway in the care of oxygen dependent COPD patients in their homes. Oxygen-dependent COPD patients were enrolled in the management pathway after discharge from the hospital or referred from a provider’s office. At least three home visits were made: the first within 3 days of enrollment, the second in 1 month, and the third 10 months later. Three hundred and twenty-four patients were enrolled in the study. During the study period, the overall hospitalization rate dropped (11% per month at the second visit vs. 2.1% per month at the third visit). The patients’ understanding of the disease improved substantially (21.6% vs. 83.9%), knowledge of medications the patients were taking improved (56.0% vs. 87.0%), and appropriate use of medications increased (52.0% vs. 86.0%). In our community, this RT-led program helped patients’ self-management of COPD in their own homes by increasing understanding of the disease, assisted physicians in monitoring their patients, and reduced hospitalization.


Metabolites ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 157 ◽  
Author(s):  
Eitan Halper-Stromberg ◽  
Lucas Gillenwater ◽  
Charmion Cruickshank-Quinn ◽  
Wanda Kay O’Neal ◽  
Nichole Reisdorph ◽  
...  

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography–mass spectrometry (LC–MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected 7939 and 10,561 compounds in BAL and paired plasma samples, respectively. FEV1/FVC (Forced Expiratory Volume in One Second/Forced Vital Capacity) ratio, emphysema, FEV1 % predicted, and COPD exacerbations associated with 1230, 792, eight, and one BAL compounds, respectively. Only two plasma compounds associated with a COPD phenotype (emphysema). Three BAL co-expression modules associated with FEV1/FVC and emphysema. K-means BAL metabolomic signature clustering identified two groups, one with more airway obstruction (34% of subjects, median FEV1/FVC 0.67), one with less (66% of subjects, median FEV1/FVC 0.77; p < 2 × 10−4). Associations between metabolites and COPD phenotypes are more robustly represented in BAL compared to plasma.


2020 ◽  
Vol 9 (12) ◽  
pp. 3832
Author(s):  
Massa Zantah ◽  
Aloknath Pandya ◽  
Michael R. Jacobs ◽  
Gerard J. Criner

High-flow nasal therapy (HFNT) is a unique system that delivers humidified, heated oxygen-enriched air via nasal cannula at high flow rates. It is a promising therapy for chronic obstructive pulmonary disease (COPD) patients. Several studies have examined the physiologic effects of this therapy in the patient population and have revealed that it improves mucociliary clearance, reduces nasopharyngeal dead space, and subsequently increases CO2 washout. It also improves alveolar recruitment and gas exchange. These mechanisms may explain the promising results observed in recently published studies that examined the role of HFNT in stable COPD patients.


2008 ◽  
Vol 15 (8) ◽  
pp. 437-443 ◽  
Author(s):  
Anderson Chuck ◽  
Philip Jacobs ◽  
Irvin Mayers ◽  
Darcy Marciniuk

BACKGROUND: There is evidence that combination therapy (CT) in the form of long-acting beta2-agonists (LABAs) and inhaled corticosteroids can improve lung function for patients with chronic obstructive pulmonary disease (COPD).OBJECTIVE: To determine the cost-effectiveness of using CT in none, all or a selected group of COPD patients.METHODS: A Markov model was designed to compare four treatment strategies: no use of CT regardless of COPD severity (patients receive LABA only); use of CT in patients with stage 3 disease only (forced expiratory volume in 1 s [FEV1] less than 35% of predicted); use of CT in patients with stages 2 and 3 disease only (FEV1less than 50% of predicted); and use of CT in all patients regardless of severity of COPD. Estimates of mortality, exacerbation and disease progression rates, quality-adjusted life years (QALYs) and costs were derived from the literature. Three-year and lifetime time horizons were used. The analysis was conducted from a health systems perspective.RESULTS: CT was associated with a cost of $39,000 per QALY if given to patients with stage 3 disease, $47,500 per QALY if given to patients with stages 2 and 3 disease, and $450,333 per QALY if given to all COPD patients. Results were robust to various assumptions tested in a Monte Carlo simulation.CONCLUSION: Providing CT for COPD patients in stage 2 or 3 disease is cost-effective. The message to family physicians and specialists is that as FEV1worsens and reaches 50% of predicted values, CT is recommended.


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