Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD

The impact of blood eosinophilia in chronic obstructive pulmonary disease (COPD) remains controversial.To evaluate the prevalence and stability of a high level of blood eosinophils (≥300 cells·μL–1) and its relationship to outcomes, we determined blood eosinophils at baseline and over 2 years in 424 COPD patients (forced expiratory volume in 1 s (FEV1) 60% predicted) and 67 smokers without COPD from the CHAIN cohort, and in 308 COPD patients (FEV1 60% predicted) in the BODE cohort. We related eosinophil levels to exacerbations and survival using Cox hazard analysis.In COPD patients, 15.8% in the CHAIN cohort and 12.3% in the BODE cohort had persistently elevated blood eosinophils at all three visits. A significant proportion (43.8%) of patients had counts that oscillated above and below the cut-off points, while the rest had persistent eosinophil levels <300 cells·μL–1. A similar eosinophil blood pattern was observed in controls. Exacerbation rates did not differ in patients with and without eosinophilia. All-cause mortality was lower in patients with high eosinophils compared with those with values <300 cells·μL–1 (15.8% versus 33.7%; p=0.026).In patients with COPD, blood eosinophils ≥300 cells·μL–1 persisting over 2 years was not a risk factor for COPD exacerbations. High eosinophil count was associated with better survival.

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Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma

Metabolites ◽

10.3390/metabo9080157 ◽

2019 ◽

Vol 9 (8) ◽

pp. 157 ◽

Cited By ~ 2

Author(s):

Eitan Halper-Stromberg ◽

Lucas Gillenwater ◽

Charmion Cruickshank-Quinn ◽

Wanda Kay O’Neal ◽

Nichole Reisdorph ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Cell Metabolism ◽

Lavage Fluid ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Exacerbations ◽

False Discovery ◽

Copd Patients ◽

Clinical Covariates

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.

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INDACO project: a pilot study on incidence of comorbidities in COPD patients referred to pneumology units

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2013.504 ◽

2013 ◽

Vol 8 ◽

Author(s):

Giorgio Fumagalli ◽

Fabrizio Fabiani ◽

Silvia Forte ◽

Massimiliano Napolitano ◽

Paolo Marinelli ◽

...

Keyword(s):

Pilot Study ◽

Inhaled Corticosteroids ◽

Chronic Obstructive Lung Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Exacerbations ◽

Copd Patients ◽

High Prevalence ◽

Global Initiative ◽

The Impact

Background: Chronic Obstructive Pulmonary Disease (COPD) is often associated with comorbidities, especially cardiovascular, that have a heavy burden in terms of hospitalization and mortality. Since no conclusive data exist on the prevalence and type of comorbidities in COPD patients in Italy, we planned the INDACO observational pilot study to evaluate the impact of comorbidities in patients referred to the outpatient wards of four major hospitals in Rome. Methods: For each patient we recorded anthropometric and anamnestic data, smoking habits, respiratory function, GOLD (Global initiative for chronic Obstructive Lung Disease) severity stage, Body Mass Index (BMI), number of acute COPD exacerbations in previous years, presence and type of comorbidities, and the Charlson Comorbidity Index (CCI). Results: Here we report and discuss the results of the first 169 patients (124 males, mean age 74±8 years). The prevalence of patients with comorbidities was 94.1% (25.2% of cases presented only one comorbidity, 28.3% two, 46.5% three or more). There was a high prevalence of arterial hypertension (52.1%), metabolic syndrome (20.7%), cancers (13.6%) and diabetes (11.2%) in the whole study group, and of anxiety-depression syndrome in females (13%). Exacerbation frequency was positively correlated with dyspnea score and negatively with BMI. Use of combination of bronchodilators and inhaled corticosteroids was more frequent in younger patients with more severe airways obstruction and lower CCI. Conclusions: These preliminary results show a high prevalence of comorbidities in COPD patients attending four great hospitals in Rome, but they need to be confirmed by further investigations in a larger patients cohort.

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Serum Albumin Concentrations in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10020269 ◽

2021 ◽

Vol 10 (2) ◽

pp. 269

Author(s):

Elisabetta Zinellu ◽

Alessandro G. Fois ◽

Elisabetta Sotgiu ◽

Sabrina Mellino ◽

Arduino A. Mangoni ◽

...

Keyword(s):

Systematic Review ◽

Chronic Obstructive Pulmonary Disease ◽

Serum Albumin ◽

Pulmonary Disease ◽

Meta Analysis ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Standard Mean Difference ◽

Copd Patients

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.

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Domiciliary Cough Monitoring for the Prediction of COPD Exacerbations

Lung ◽

10.1007/s00408-021-00435-9 ◽

2021 ◽

Vol 199 (2) ◽

pp. 131-137

Author(s):

Michael G. Crooks ◽

Albertus C. den Brinker ◽

Susannah Thackray-Nocera ◽

Ralph van Dinther ◽

Caroline E. Wright ◽

...

Keyword(s):

Automated System ◽

Chronic Obstructive ◽

Service Utilisation ◽

Alert System ◽

Obstructive Pulmonary Disease ◽

Prospective Longitudinal Study ◽

Copd Exacerbations ◽

Cough Frequency ◽

Copd Patients ◽

Prospective Longitudinal

Abstract Introduction Acute exacerbations of COPD (AE-COPD) are a leading cause of health service utilisation and are associated with morbidity and mortality. Identifying the prodrome of AE-COPD by monitoring symptoms and physiological parameters (telemonitoring) has proven disappointing and false alerts limit clinical utility. We report objective monitoring of cough counts around AE-COPD and the performance of a novel alert system identifying meaningful change in cough frequency. Methods This prospective longitudinal study of cough monitoring included chronic obstructive pulmonary disease (COPD) patients experienced in telemonitoring that had two or more AE-COPD in the past year. Participants underwent cough monitoring and completed a daily questionnaire for 90 days. The automated system identified deteriorating trends in cough and this was compared with alerts generated by an established telemonitoring questionnaire. Results 28 patients [median age 66 (range 46–86), mean FEV-1% predicted 36% (SD 18%)] completed the study and had a total of 58 exacerbations (43 moderate and 15 severe). Alerts based on cough monitoring were generated mean 3.4 days before 45% of AE-COPD with one false alert every 100 days. In contrast, questionnaire-based alerts occurred in the prodrome of 88% of AE-COPD with one false alert every 10 days. Conclusion An alert system based on cough frequency alone predicted 45% AE-COPD; the low false alert rate with cough monitoring suggests it is a practical and clinically relevant tool. In contrast, the utility of questionnaire-based symptom monitoring is limited by frequent false alerts.

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Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

European Respiratory Review ◽

10.1183/16000617.00002215 ◽

2015 ◽

Vol 24 (137) ◽

pp. 451-461 ◽

Cited By ~ 81

Author(s):

Mario Cazzola ◽

Luigino Calzetta ◽

Clive Page ◽

Josè Jardim ◽

Alexander G. Chuchalin ◽

...

Keyword(s):

Relative Risk ◽

Airway Obstruction ◽

Chronic Bronchitis ◽

Meta Analysis ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Regular Treatment ◽

Copd Exacerbations ◽

Copd Patients ◽

High Doses

In order to clarify the possible role of N-acetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD), we have carried out a meta-analysis testing the available evidence that NAC treatment may be effective in preventing exacerbations of chronic bronchitis or COPD and evaluating whether there is a substantial difference between the responses induced by low (≤600 mg per day) and high (>600 mg per day) doses of NAC.The results of the present meta-analysis (13 studies, 4155 COPD patients, NAC n=1933; placebo or controls n=2222) showed that patients treated with NAC had significantly and consistently fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75, 95% CI 0.66–0.84; p<0.01), although this protective effect was more apparent in patients without evidence of airway obstruction. However, high doses of NAC were also effective in patients suffering from COPD diagnosed using spirometric criteria (relative risk 0.75, 95% CI 0.68–0.82; p=0.04). NAC was well tolerated and the risk of adverse reactions was not dose-dependent (low doses relative risk 0.93, 95% CI 0.89–0.97; p=0.40; high doses relative risk 1.11, 95% CI 0.89–1.39; p=0.58).The strong signal that comes from this meta-analysis leads us to state that if a patient suffering from chronic bronchitis presents a documented airway obstruction, NAC should be administered at a dose of ≥1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient.

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

Russian Pulmonology ◽

10.18093/0869-0189-2021-31-1-75-87 ◽

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.

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Periodontal Health and Chronic Obstructive Pulmonary Disease (COPD) Exacerbations: A Systematic Review

10.21203/rs.3.rs-138210/v1 ◽

2021 ◽

Author(s):

Niamh Kelly ◽

Lewis Winning ◽

Christopher Irwin ◽

Fionnuala Lundy ◽

Dermot Linden ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Chronic Obstructive Pulmonary Disease ◽

Risk Of Bias ◽

Chronic Obstructive ◽

Periodontal Health ◽

Obstructive Pulmonary Disease ◽

Copd Exacerbations ◽

Copd Patients

Abstract BackgroundA growing body of evidence suggests a role for oral bacteria in lung infections. This systematic review aimed to analyse the association between poor periodontal health and the frequency of chronic obstructive pulmonary disease (COPD) exacerbations. MethodsPubMed, Embase, Web of Science, CINAHL and Medline were searched for studies published until May 2020, with no language restriction. Studies reporting periodontal condition, or periodontal treatment outcomes, with data on the frequency of exacerbations of COPD, were identified. The primary outcome was the frequency of exacerbations and secondary outcomes included quality of life and hospitalisation. Studies were assessed for eligibility and quality by two assessors independently.Results Searches identified 532 records and 8 met the inclusion criteria. The data from intervention studies showed reduction in the frequency of exacerbations following periodontal treatment. Data from observational studies suggest association of worse plaque scores with exacerbation but not pocket depth or clinical attachment loss. Better periodontal health was also associated with reduced frequency of COPD exacerbations, hospitalisations and improved quality of life in COPD patients. Due to the high heterogeneity no meta-analysis was performed. The quality of some of the included studies was low and there was evidence of high risk of bias.ConclusionThe data supports possible association between poor periodontal health, the frequency of exacerbations and quality of life in COPD patients. The evidence is limited by high risk of bias suggesting need for well-designed and adequately powered randomised control trials.The PROSPERO registration number CRD42020180328

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A NEW PERSPECTIVE ON BRONCHIAL ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE OVERLAP: POTENTIAL DIAGNOSTIC CRITERIA

Wiadomości Lekarskie ◽

10.36740/wlek202007131 ◽

2020 ◽

Vol 73 (7) ◽

pp. 1480-1483

Author(s):

Tetyana O. Pertseva ◽

Lyudmyla I. Konopkina ◽

Alina O. Babenko

Keyword(s):

Allergic Inflammation ◽

Chronic Obstructive ◽

Bronchial Obstruction ◽

Obstructive Pulmonary Disease ◽

Total Ige ◽

Copd Patients ◽

Group 2 ◽

New Perspective ◽

High Level ◽

Blood Eosinophils

The aim: The aim of the research was to analyze the results of observation and examination of COPD patients in order to identify a group of individuals with potential asthma overlap. Materials and methods: We have conducted a two-stage dynamic investigation of 43 COPD patients during 3–8 years. The patients were divided into two groups: group 1 counted 30 individuals who presented with at least one episode of reversible bronchial obstruction (RBO) during the observation; group 2 – 13 individuals who presented with nonreversible bronchial obstruction (nonRBO). At the first stage, we conducted a clinical observations analysis and studied lung function examination records; at the second stage, we calculated the markers of allergic inflammation. Results: It was revealed that around 70% of COPD patients have occasional episodes of RBO. It was established that the level of blood eosinophils in these patients on the whole is rather low even in people with intermittent RBO, and the total IgE level appeared to be significantly higher in patients with intermittent RBO comparing to the level of this marker in patients who have nonRBO. Conclusions: COPD patients with intermittent RBO and high level of total IgE level form a group with potential asthma overlap.

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Randomised controlled trial to investigate the use of high-frequency airway oscillations as training to improve dyspnoea (TIDe) in COPD

Thorax ◽

10.1136/thoraxjnl-2021-217072 ◽

2021 ◽

pp. thoraxjnl-2021-217072

Author(s):

Enya Daynes ◽

Neil Greening ◽

Sally J Singh

Keyword(s):

Muscle Weakness ◽

High Frequency ◽

Controlled Trial ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Registration Number ◽

Randomised Controlled ◽

Double Blinded

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.

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LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis

Therapeutic Advances in Respiratory Disease ◽

10.1177/1753466620937194 ◽

2020 ◽

Vol 14 ◽

pp. 175346662093719

Author(s):

Ching-Yi Chen ◽

Wang-Chun Chen ◽

Chi-Hsien Huang ◽

Yi-Ping Hsiang ◽

Chau-Chyun Sheu ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Meta Analysis ◽

Similar Efficacy ◽

Fixed Dose ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Exacerbations ◽

Copd Patients ◽

History Of ◽

Long Acting

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

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