scholarly journals Effects of corticosteroids on COPD lung macrophage phenotype and function

2020 ◽  
Vol 134 (7) ◽  
pp. 751-763 ◽  
Author(s):  
Andrew Higham ◽  
Tom Scott ◽  
Jian Li ◽  
Rosemary Gaskell ◽  
Aisha Baba Dikwa ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Corticosteroid Treatment ◽  
Therapeutic Benefit ◽  
Chronic Obstructive ◽  
Macrophage Phenotype ◽  
Lung Macrophages ◽  
Lung Macrophage ◽  
Copd Patients ◽  
Gene And Protein Expression ◽  
And Function

Abstract The numbers of macrophages are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. COPD lung macrophages have reduced ability to phagocytose microbes and efferocytose apoptotic cells. Inhaled corticosteroids (ICSs) are widely used anti-inflammatory drugs in COPD; however, their role beyond suppression of cytokine release has not been explored in COPD macrophages. We have examined the effects of corticosteroids on COPD lung macrophage phenotype and function. Lung macrophages from controls and COPD patients were treated with corticosteroids; effects on gene and protein expression of CD163, CD164, CD206, MERTK, CD64, CD80 and CD86 were studied. We also examined the effect of corticosteroids on the function of CD163, MERTK and cluster of differentiation 64 (CD64). Corticosteroid increased CD163, CD164, CD206 and MERTK expression and reduced CD64, CD80 and CD86 expression. We also observed an increase in the uptake of the haemoglobin–haptoglobin complex (CD163) from 59 up to 81% and an increase in efferocytosis of apoptotic neutrophils (MERTK) from 15 up to 28% following corticosteroid treatment. We observed no effect on bacterial phagocytosis. Corticosteroids alter the phenotype and function of COPD lung macrophages. Our findings suggest mechanisms by which corticosteroids exert therapeutic benefit in COPD, reducing iron available for bacterial growth and enhancing efferocytosis.

scholarly journals Short-term responses to high-dose inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease with a fractional nitric oxide concentration over 35 parts per billion: A single-centre pre–post study

2020 ◽  
Vol 4 (1) ◽  
pp. 012-017
Author(s):  
Shiroshita Akihiro ◽  
Tanaka Yu ◽  
Nakashima Kei ◽  
Shiraishi Atsushi ◽  
Matsui Hiroki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhaled Corticosteroids ◽  
Corticosteroid Treatment ◽  
Exhaled Nitric Oxide ◽  
Chronic Obstructive ◽  
Inhaled Corticosteroid ◽  
Fractional Exhaled Nitric Oxide ◽  
Copd Patients ◽  
Oxide Concentration ◽  
Nitric Oxide Concentration

Introduction: There is currently no strategy for identifying chronic obstructive pulmonary disease (COPD) patients whose pulmonary function could benefit from inhaled corticosteroids. We investigated whether a 28-day regime of inhaled corticosteroids improved pulmonary function test results among COPD patients with a fractional exhaled nitric oxide concentration > 35 parts per billion. Methods: This single-centre one-arm pre–post trial included COPD patients with a fractional exhaled nitric oxide concentration > 35 parts per billion treated at our institution from September 2018 to August 2019. Patients were administered budesonide (200 μg, 8 puffs daily) for 28 days. The primary outcome measure was the difference between the forced expiratory volume in 1 s (FEV1) at baseline and after 28 days of inhaled corticosteroid treatment. Secondary outcomes included differences in COPD Assessment Test scores, %FEV1, and that between the percent forced vital capacity (%FVC) at baseline and after 28 days of treatment. Results: Twenty patients completed the 28-day inhaled corticosteroid regime. The mean difference in FEV1 between day 1 and day 28 was 340 mL (95% confidence interval: −100 to 770 mL; p = 0.122). The mean differences in secondary outcomes were: %FVC, −0.16% (95% confidence interval [CI]: −2.84 to 2.53%; p = 0.905); %FEV1, 1.63% (95%CI: −4.56 to 7.81%; p = 0.589); COPD Assessment Test score, −2.50 (95%CI: −5.72 to 0.72; p = 0.121). Conclusion: The 28-day course of inhaled corticosteroids yielded no significant difference in FEV1 for COPD patients with a fractional exhaled nitric oxide concentration > 35 parts per billion. Trial registration: University Hospital Medical Information Network Center, UMIN000034005. Registered 3 September 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000038557

scholarly journals Circulating eosinophil levels do not predict severe exacerbations in COPD: a retrospective study

2018 ◽  
Vol 4 (3) ◽  
pp. 00022-2018 ◽  
Author(s):  
Yochai Adir ◽  
Omar Hakrush ◽  
Michal Shteinberg ◽  
Sonia Schneer ◽  
Alvar Agusti
Keyword(s):  
Functional Data ◽  
Inhaled Corticosteroids ◽  
Corticosteroid Treatment ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Index Event ◽  
Copd Patients ◽  
Clinical Stability

Whether the level of circulating eosinophils in chronic obstructive pulmonary disease (COPD) patients can predict the risk of exacerbations of COPD (ECOPD) or response to treatment is debated. Here, we evaluate the prevalence of elevated eosinophils in COPD patients and its relationship with severe ECOPD requiring hospitalisation.We retrospectively reviewed the charts of COPD patients hospitalised in our centre between January 1, 2005 and November 30, 2015 because of ECOPD or other reasons (controls). In a second analysis, the ECOPD patients were divided into two subgroups based on having ECOPD in the next year after the index event or not. Circulating eosinophils, both during clinical stability and hospitalisation, as well as clinical and functional data and the relation to recurrent exacerbations were analysed.We studied 992 COPD patients (318 ECOPD patients and 674 controls). Among ECOPD patients, 121 had one or more ECOPD during the year after the index event. The prevalence of eosinophils ≥2% was 72% in ECOPD patients and 71% in controls (p=0.93). Among ECOPD patients, eosinophil levels ≥2%, ≥4% or ≥300 cells·μL−1, either when clinically stable or during hospitalisation, did not show a significant association with the rate of recurrent severe exacerbations. The severity of airflow limitation was associated with recurrent exacerbations, but inhaled corticosteroid treatment was not.The majority of COPD patients have circulating eosinophils >2% and a significant association with the risk of severe ECOPD or response to inhaled corticosteroids was not demonstrated.

Current opportunities of inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease

2021 ◽  
Vol 31 (1) ◽  
pp. 75-87
Author(s):  
I. V. Leshchenko ◽  
A. S. Meshcheryakova
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Fixed Combination ◽  
Chronic Obstructive ◽  
Delivery Device ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Long Acting ◽  
Blood Eosinophils

Chronic obstructive pulmonary disease (COPD) is the leading cause of death in the structure of respiratory diseases. The problem of rational pharmacotherapy of COPD have attracted attention of the medical scientific society for many years. The understanding of the pathogenesis of the disease has deepened and approaches to the therapy have changed. Some COPD patients need regular fixed-combination therapy: long-acting bronchodilators (LABD) and inhaled corticosteroids (ICS) in order to prevent exacerbations and reduce the severity of symptoms of the disease. Blood eosinophils count is one of criteria for choosing regular therapy. The appearance of fixed triple combinations of ICS/LABD increased the effectiveness of COPD therapy, and a new delivery device for fixed combination of budesonide/formoterol makes it possible to use ICS successfully in the most severe patients.

scholarly journals The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages

2018 ◽  
Vol 12 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Stanislas Grassin-Delyle ◽  
Charlotte Abrial ◽  
Hélène Salvator ◽  
Marion Brollo ◽  
Emmanuel Naline ◽  
...  
Keyword(s):  
Human Lung ◽  
Macrophage Phenotype ◽  
Chemokine Production ◽  
Lung Macrophages ◽  
Cytokines And Chemokines ◽  
M1 Macrophage ◽  
Microbial Infections ◽  
Selective Agonists ◽  
And Function ◽  
Subtype Selective

Background: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. Methods: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. Results: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. Conclusions: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype.

scholarly journals Inhaled Corticosteroids and the Pneumonia Risk in Patients With Chronic Obstructive Pulmonary Disease: A Meta-analysis of Randomized Controlled Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong Chen ◽  
Jian Sun ◽  
Qiang Huang ◽  
Yongqi Liu ◽  
Mengxin Yuan ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
Controlled Trials ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Obstructive Pulmonary Disease ◽  
Randomized Controlled ◽  
Copd Patients ◽  
Baseline Characteristics

Background: Whether all types of inhaled corticosteroids (ICSs) would increase the pneumonia risk in patients with chronic obstructive pulmonary disease (COPD) remains controversial. We aimed to assess the association between ICSs treatment and pneumonia risk in COPD patients, and the impact of medication details and baseline characteristics of patients on the association.Methods: Four databases (PubMed, Embase, Cochrane Library, and Clinical Trials.gov) were searched to identify eligible randomized controlled trials (RCTs) comparing ICSs treatment with non-ICSs treatment on the pneumonia risk in COPD patients. Pooled results were calculated using Peto odds ratios (Peto ORs) with corresponding 95% confidence intervals (CIs).Results: A total of 59 RCTs enrolling 103,477 patients were analyzed. All types of ICSs significantly increased the pneumonia risk (Peto OR, 1.43; 95% CI, 1.34–1.53). Subgroup analysis showed that there was a dose-response relationship between ICSs treatment and pneumonia risk (low-dose: Peto OR, 1.33; 95% CI, 1.22–1.45; medium-dose: Peto OR, 1.50; 95% CI, 1.28–1.76; and high-dose: Peto OR, 1.64; 95% CI, 1.45–1.85). Subgroup analyses based on treatment durations and baseline characteristics (severity, age, and body mass index) of patients were consistant with the above results. Subgroup analysis based on severity of pneumonia showed that fluticasone (Peto OR, 1.75; 95% CI, 1.44–2.14) increased the risk of serious pneumonia, while budesonide and beclomethasone did not.Conclusions: ICSs treatment significantly increased the risk of pneumonia in COPD patients. There was a dose-response relationship between ICSs treatment and pneumonia risk. The pneumonia risk was related with COPD severity.

scholarly journals Reassessing the Role of Eosinophils as a Biomarker in Chronic Obstructive Pulmonary Disease

2019 ◽  
Vol 8 (7) ◽  
pp. 962 ◽  
Author(s):  
Tinè ◽  
Biondini ◽  
Semenzato ◽  
Bazzan ◽  
Cosio ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Real Life ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Exacerbation Risk ◽  
Blood Eosinophils

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.

scholarly journals Cost-Effectiveness of Combination Therapy for Chronic Obstructive Pulmonary Disease

2008 ◽  
Vol 15 (8) ◽  
pp. 437-443 ◽  
Author(s):  
Anderson Chuck ◽  
Philip Jacobs ◽  
Irvin Mayers ◽  
Darcy Marciniuk
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cost Effectiveness ◽  
Combination Therapy ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Life Years

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.

scholarly journals Biological Age in COPD Patients Reveals an Accelerated Lung Aging

2021 ◽  
Author(s):  
Manuela Campisi ◽  
Filippo Liviero ◽  
Piero Maestrelli ◽  
Gabriella Guarnieri ◽  
Sofia Pavanello
Keyword(s):  
Inhaled Corticosteroids ◽  
Blood Parameters ◽  
Biological Age ◽  
Biological Aging ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
New Finding ◽  
New Research ◽  
Research Challenge

Abstract Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, shows striking clinical aging-associated features of lung. We tested the hypothesis that lung biological aging in COPD is accelerated. Biological aging was assessed by mitotic telomere length (TL) and non-mitotic age-dependent methylation changes in specific CpGs (DNAmAge) of lung cells, obtained from induced sputum, and peripheral blood leucocytes in 18 COPD patients (72.4±7.7 years; 50% males), clinically appraised by lung function and blood parameters. DNAmAge (67.4±5.80 vs 61.6±5.40 years; p=0.0003), AgeAcc (-4.5±5.02 vs -10.8±3.50 years; p=0.0003) and TL attrition (1.05±0.35 vs 1.48±0.21 T/S; p=0.0341) are higher in lung than blood in the same patients. Blood DNAmAge (r=0.927245; p=0.0026) and AgeAcc (r=0.916445; p=0.0037), but not TL, highly correlate with that of lung. Therefore, blood can be a proxy indicator of lung biological age. Multiple regression analyses show that both blood DNAmAge and AgeAcc decrease (i.e., younger) in patients with combined inhaled corticosteroids (ICS) therapy (p=0.0494 and p=0.0553) and FEV1% enhancement (p=0.0254; p=0.0296). In conclusion, the new finding, that lung of COPD patients is remarkably biologically older than blood, opens new research challenge on novel therapeutic approaches to counteract this key aspect of the disease.

scholarly journals Maintenance inhaler therapy preferences of patients with asthma or chronic obstructive pulmonary disease: a discrete choice experiment

Thorax ◽  
2020 ◽  
Vol 75 (9) ◽  
pp. 735-743 ◽  
Author(s):  
Tommi Tervonen ◽  
Natalia Hawken ◽  
Nicola A Hanania ◽  
Fernando J Martinez ◽  
Sebastian Heidenreich ◽  
...  
Keyword(s):  
Discrete Choice Experiment ◽  
Discrete Choice ◽  
Patient Preferences ◽  
Choice Experiment ◽  
Inhaled Corticosteroids ◽  
Symptom Relief ◽  
Chronic Obstructive ◽  
Onset Of Action ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

BackgroundA variety of maintenance inhaler therapies are available to treat asthma and COPD. Patient-centric treatment choices require understanding patient preferences for the alternative therapies.MethodsA self-completed web-based discrete choice experiment was conducted to elicit patient preferences for inhaler device and medication attributes. Selection of attributes was informed by patient focus groups and literature review.ResultsThe discrete choice experiment was completed by 810 patients with asthma and 1147 patients with COPD. Patients with asthma most valued decreasing the onset of action from 30 to 5 min, followed by reducing yearly exacerbations from 3 to 1. Patients with COPD most and equally valued decreasing the onset of action from 30 to 5 min and reducing yearly exacerbations from 3 to 1. Both patients with asthma and patients with COPD were willing to accept an additional exacerbation in exchange for a 15 min decrease in onset of action and a longer onset of action in exchange for a lower risk of adverse effects from inhaled corticosteroids. Patients with asthma and COPD valued once-daily over twice-daily dosing, pressurised inhalers over dry powder inhalers and non-capsule priming over single-use capsules, although these attributes were not valued as highly as faster onset of action or reduced exacerbations.ConclusionsThe most important maintenance inhaler attributes for patients with asthma and COPD were fast onset of symptom relief and a lower rate of exacerbations. Concerns about safety of inhaled corticosteroids and device convenience also affected patient preferences but were less important.

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