Effect of long-acting beta-agonists on the frequency of COPD exacerbations: a meta-analysis

What is Known and Objective: Inhaled long‐acting beta‐agonists have been licensed for the treatment of chronic obstructive pulmonary disease (COPD) since the late 1990s, and they improve lung function and symptoms of dyspnoea. However, the evidence that long‐acting beta‐agonists alone can reduce the rate of COPD exacerbations is not conclusive. This meta‐analysis was performed to evaluate their effect on the frequency of exacerbations. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane trials database were searched for the review. Randomized controlled trials of greater than or equal to 24 weeks’ treatment duration comparing long‐acting beta‐agonists (LABAs) with placebo were reviewed. Studies were pooled to yield odds ratios (ORs) with 95% confidence intervals (CIs). Results and Discussion: Seventeen randomized controlled trials (11871 randomized subjects) met the inclusion criteria and were selected for analysis. Salmeterol, formoterol and indacaterol significantly reduced COPD exacerbations compared with placebo. Salmeterol significantly reduced COPD exacerbations with both study arms exposed or not exposed to inhaled corticosteroids (ICS). The summary ORs were 0·79 (95% CI: 0·67–0·92; P < 0·01) and 0·80 (95% CI: 0·65–0·99; P = 0·04), respectively. However, when both arms were not exposed to ICS, there was no significant reduction in exacerbations with formoterol compared with placebo. The 'summary OR was 0·93 (95% CI: 0·75–1·15; P = 0·50). What is New and Conclusion: Long‐acting beta‐agonists reduce the frequency of COPD exacerbations. Salmeterol, formoterol and indacaterol significantly reduced COPD exacerbations compared with placebo. Salmeterol but not formoterol decreased exacerbations significantly in the absence of ICS.     

Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation

Objective. Patients with chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations associated with increased morbidity and mortality. One potential group of enzymes causing tissue destruction in this disease includes neutrophil proteinase elastase (NE), collagenase‐2 (matrix metalloproteinase‐8 (MMP‐8)) and gelatinase B (MMP‐9). We investigated the activity of NE and the levels of MMP‐8 and MMP‐9 in a longitudinal setting at and after COPD exacerbation using a non‐invasive technique, i.e. induced sputum, to ascertain whether these proteinases play a role in COPD exacerbation. Material and methods. The study included healthy non‐smokers (n = 32), healthy smokers (n = 28), patients with stable COPD (n = 15), COPD patients with acute exacerbations (exa) (n = 10) and their recovery (n = 8) after 4 weeks. NE activity by synthetic peptide substrate and spectrophotometry, MMP‐8 levels by immunofluorometry and MMP‐9 levels by ELISA were analysed from induced sputum supernatants. Results. NE activity and the level of MMP‐8 increased highly significantly in patients with COPD exacerbation compared to stable COPD and controls (NE: p = 0.001 and p<0.0001; MMP‐8: p<0.001 and p<0.0001). Paired samples showed a decrease of these proteinases during the recovery period after exacerbation (p = 0.03, p = 0.04). The proteinase levels correlated not only with the percentage and number of neutrophils but also with the lung function parameters (FEV1/FVC and diffusion capacity). Conclusions. COPD exacerbations are associated with neutrophil recruitment into the airways but also transient activation and/or elevation of tissue destruction proteinases, such as NE and MMP‐8, which can be detected from the induced sputum supernatants of these COPD patients.     

Role of antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease

OBJECTIVE: To define the role of antimicrobial therapy in the treatment of acute bronchitic exacerbations of chronic obstructive pulmonary disease (COPD) through review of placebo-controlled clinical trials. Specificalty, to determine the benefit of antimicrobial therapy on patient outcome. DATA SOURCES: Placebo-controlled dinical trials identified by MEDLINE search (1957-December 1999). STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled clinical trials that included COPD patients with no evidence of pneumonia or underlying asthma were included in the evaluation. DATA SYNTHESIS: The role of antimicrobial agents in the treatment of acute exacerbations of COPD is controversial. Patients with COPD are often chronically colonized with bacteria, and many exacerbations are due to nonbacterial causes. Four placebo-controlled clinical trials and a meta-analysis have demonstrated significant improvements in outcome for patients treated with an antibiotic versus placebo. In contrast, six studies failed to demonstrate statistical differences, possibly due to the small sample size and the subjectivity of outcome measures. Overall, the data suggest that the benefit of antimicrobial therapy in acute exacerbations of COPD may be related to exacerbation severity. CONCLUSIONS: Antimicrobial agents may have a beneficial effect in the treatment of acute exacerbations of COPD in certain patients. Pending further research in this area, we recommend antimicrobial therapy only for COPD patients with acute bronchitic exacerbations characterized by increased dyspnea, sputum volume, and purulence.     

Clinical efficacy and safety of Chinese herbal medicine versus placebo for the treatment of chronic obstructive pulmonary disease: A systematic review and meta-analysis

ObjectiveRandomized clinical trials and published meta-analyses assessing the clinical effectiveness of Chinese herbal medicine (CHM) on the treatment of stable chronic obstructive pulmonary disease (COPD) yielded inconsistent results in terms of disease outcomes, in which the design of placebo-controlled studies can contribute to the heterogeneity. This study aimed to evaluate the efficacy and safety of CHM compared to placebo on the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD.MethodsNine electronic databases were searched from inception to October 1, 2019 to identify placebo controlled randomized trials of CHM for the treatment of stable COPD and studies in English or Chinese were included. The primary outcomes were symptom score (CAT score), quality of life (SGRQ) and frequency of acute exacerbations. The secondary outcomes included lung function, clinical total effective rate and adverse events. The selection of studies, data extraction and coding and assessment of risk of bias of the included studies were conducted by two reviewers independently. Mean difference (MD) was used to analyze continuous variable and relative risk ratio (RR) for dichotomous data.ResultsA total of eleven studies involving 1223 patients were included. While maintaining routine western pharmacotherapies (WP), CHM had significant advantage over the treatment of placebo in improving CAT score (MD -3.93; 95 %CI -6.01 to -1.85) and SGRQ score (MD -6.20; 95 %CI -10.13 to -2.28), reducing the frequency of acute exacerbations (MD -0.78; 95 %CI -1.40 to -0.16) and improving clinical effective rate (RR 1.29; 95 %CI 1.14 to 1.45), but had no significant effect on improving FEV₁%pred (MD 8.18; 95 %CI -4.22 to 20.58). High heterogeneity was found for the changes in exacerbation frequency and FEV₁%pred. No serious adverse events related to CHM were reported.ConclusionsThis meta-analysis of placebo-controlled RCTs demonstrated that the use of CHM in addition to WP could alleviate clinical symptoms, improve quality of life and clinical efficiency and reduce the frequency of exacerbations, which could be an alternative approach for treatment adjustment of COPD. CHM was a relatively safe treatment. These findings need to be verified in future with high-quality clinical trials.     

布地奈德雾化治疗在COPD急性加重期的应用

目的　观察布地奈德雾化治疗在慢性阻塞性肺病 (COPD)急性加重期的临床疗效。方法　 60例COPD急性加重期住院患者随机分为 3组 ,分别给予布地奈德雾化治疗、泼尼松龙口服和空白对照治疗。观察 3组患者在第 2 4、72小时和第 7天的临床表现、肺功能和动脉血气变化以及副作用情况。结果　布地奈德组和泼尼松龙组的呼吸困难评分、FEV1 和动脉血气的改善程度均明显优于空白对照组 ,而布地奈德组和泼尼松龙组间无显著性差异。布地奈德组的副作用明显少于泼尼松龙组 ,与空白对照组相仿。结论　布地奈德雾化治疗是COPD急性加重期激素治疗的有效选择。     

The neutrophil‐to‐lymphocyte ratio as a marker of chronic obstructive pulmonary disease and its exacerbations: A systematic review and meta‐analysis

Introduction

The main white blood cell populations, neutrophils and lymphocytes, are involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta‐analysis of studies investigating the relationship between the neutrophil to lymphocyte ratio (NLR, a marker of subclinical inflammation), presence of COPD, and its exacerbations.

Methods

A comprehensive literature search was conducted in Pubmed, Web of Science and Scopus databases; two investigators independently reviewed suitable studies.

Results

Nine studies, from 247 initially identified, were included in the meta‐analysis. Seven studies, in 775 COPD patients with stable disease and 496 healthy controls, showed a significant increase in NLR values in stable COPD (standardised mean difference, SMD, 0.773, 95% CI 0.410‐1.136; P < 0.001). Furthermore, in six studies in 527 COPD patients with acute exacerbation and 620 COPD patients with stable disease, NLR values were significantly higher in patients with exacerbations (random effects SMD 0.850, 95% CI 0.549‐1.151; P < 0.001).

Conclusions

Our meta‐analysis showed that NLR values are significantly higher in stable COPD patients when compared to healthy individuals, although the magnitude of the difference is reduced after trim and fill adjustment, and in patients with COPD exacerbations when compared to patients with stable disease. Further studies, in larger cohorts, are needed to confirm whether the NLR is a useful tool in discriminating between COPD patients with stable disease, those with acute exacerbations, and subjects without the disease.     

Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study

Introduction: Statins have diverse anti‐inflammatory effects in addition to their lipid‐lowering ability. This study assesses the rate of chronic obstructive pulmonary disease (COPD) exacerbation and intubations in patients taking statins. Methods: This is a retrospective cohort study of 185 patients with COPD exacerbation, with a 1‐year follow‐up. Outcomes examined were repeat hospitalisation and intubations for COPD exacerbation. Baseline characteristics for which the p‐value was ≤ 0.10 were considered as covariates for inclusion in a multivariate model. Results: The statin group had fewer episodes of exacerbation and required intubation fewer times than the subjects not receiving statins (p < 0.0001 for both outcomes). Unadjusted odds ratios (OR) for no statin use vs. statin use were 9.54 (95% CI: 4.54–20.02) for exacerbation and 10.47 (CI: 4.56–24.01) for intubation. The OR, adjusted for the use of angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers (ORa), were 2.35 (CI: 1.01–5.50) for non‐statin users exhibiting an exacerbation and 10.36 (CI: 2.77–38.76) for this group requiring intubation, compared with statin users. Similarly, ORa for long‐acting β₂ agonists as a covariate were 3.01 (CI: 1.46–6.10) for exacerbation and 8.89 (CI: 3.67–21.32) for intubation. Time to outcome during the observation period was reduced by statins with the hazard ratio (HR) for exacerbation of 0.19 (CI: 0.06–0.14); HR for statins reducing intubation was 0.14 (95% CI: 0.10–0.30). Conclusions: These data suggest that the use of statins may be associated with lower incidence of both exacerbations and intubations in patients with COPD.     

Respiratory care year in review 2010: part 1. asthma, COPD, pulmonary function testing, ventilator-associated pneumonia

The purpose of this paper is to review the recent literature related to asthma, COPD, pulmonary function testing, and ventilator-associated pneumonia. Topics covered related to asthma include genetics and epigenetics; exposures; viruses; diet, obesity and exercise; exhaled nitric oxide; and drug therapy (β agonists, macrolides, tiotropium and monteleukast). Topics covered related to COPD include childhood disadvantage factors and COPD; vitamin D deficiency and COPD; β-blockers and COPD; corticosteroid therapy during COPD exacerbations; oxygen administration during pre-hospital transport of patients with COPD exacerbation; and prognosis of patients admitted to the hospital for COPD exacerbation. Topics related to pulmonary function testing include methods and techniques; predicted values; natural history, pulmonary function in health and disease; and the COPD controversy. Finally, the paper includes the following topics related to ventilator-associated pneumonia: the tube, the intubation route, and the cuff; mechanical ventilation; the bundle; and cost. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.     

Sex hormone alterations and systemic inflammation in chronic obstructive pulmonary disease

Objective: Decreased anabolic hormone levels are described in chronic obstructive pulmonary disease (COPD), leading to important clinical consequences. The aim of this study was to evaluate the alterations in sex hormone levels in men with COPD to compare with age‐matched control subjects, the determinants of these alterations, the relationship between hypogonadism and markers of systemic inflammation [interleukin‐6 (IL‐6) and tumour necrosis factor alpha (TNF‐α)] and the androgen status during an acute exacerbation of COPD. Methods: A total of 103 COPD patients and 30 control subjects were admitted to the study. 83 stable COPD patients and 30 control subjects were evaluated as outpatients. 20 patients with COPD exacerbation were hospitalised and evaluated before discharge and after 1 month. Results: Testosterone and dehydroepiandrosteronesulphate (DHEAS) levels of both COPD groups were lower than that of the control group. Luteinizing hormone (LH), follicle stimulating hormone (FSH) levels were increased during exacerbation. Testosterone and DHEAS levels increased and LH decreased in follow‐up measurements of COPD exacerbation group. Testosterone and DHEAS levels were lower in severe COPD [forced expiratory volume in 1 s (FEV₁) < 50%], in patients with severe hypoxaemia (PaO₂ < 60 mmHg) and in hypercapnic patients. Circulating IL‐6 and TNF‐α concentrations were higher in both stable and exacerbation phase COPD groups than controls. There was no correlation between sex hormones and TNF‐α or IL‐6. Conclusion: The alterations in sex hormone levels in COPD are particularly related to FEV₁, hypoxaemia and hypercapnia. There are significant differences in hormone levels during stable and exacerbation phases of COPD; the hormonal changes are marked during exacerbation and partially regress after 1 month when the disease is stabilised.     

Exacerbations of chronic obstructive pulmonary disease

Exacerbations of chronic obstructive pulmonary disease (COPD) cause morbidity, hospital admissions, and mortality, and strongly influence health-related quality of life. Some patients are prone to frequent exacerbations, which are associated with considerable physiologic deterioration and increased airway inflammation. About half of COPD exacerbations are caused or triggered primarily by bacterial and viral infections (colds, especially from rhinovirus), but air pollution can contribute to the beginning of an exacerbation. Type 1 exacerbations involve increased dyspnea, sputum volume, and sputum purulence; Type 2 exacerbations involve any two of the latter symptoms, and Type 3 exacerbations involve one of those symptoms combined with cough, wheeze, or symptoms of an upper respiratory tract infection. Exacerbations are more common than previously believed (2.5-3 exacerbations per year); many exacerbations are treated in the community and not associated with hospital admission. We found that about half of exacerbations were unreported by the patients, despite considerable encouragement to do so, and, instead, were only diagnosed from patients' diary cards. COPD patients are accustomed to frequent symptom changes, and this may explain their tendency to underreport exacerbations. COPD patients tend to be anxious and depressed about the disease and some might not seek treatment. At the beginning of an exacerbation physiologic changes such as decreases in peak flow and forced expiratory volume in the first second (FEV(1)) are usually small and therefore are not useful in predicting exacerbations, but larger decreases in peak flow are associated with dyspnea and the presence of symptomatic upper-respiratory viral infection. More pronounced physiologic changes during exacerbation are related to longer exacerbation recovery time. Dyspnea, common colds, sore throat, and cough increase significantly during prodrome, indicating that respiratory viruses are important exacerbation triggers. However, the prodrome is relatively short and not useful in predicting onset. As colds are associated with longer and more severe exacerbations, a COPD patient who develops a cold should be considered for early therapy. Physiologic recovery after an exacerbation is often incomplete, which decreases health-related quality of life and resistance to future exacerbations, so it is important to identify COPD patients who suffer frequent exacerbations and to convince them to take precautions to minimize the risk of colds and other exacerbation triggers. Exacerbation frequency may vary with the severity of the COPD. Exacerbation frequency may or may not increase with the severity of the COPD. As the COPD progresses, exacerbations tend to have more symptoms and take longer to recover from. Twenty-five to fifty percent of COPD patients suffer lower airway bacteria colonization, which is related to the severity of COPD and cigarette smoking and which begins a cycle of epithelial cell damage, impaired mucociliary clearance, mucus hypersecretion, increased submucosal vascular leakage, and inflammatory cell infiltration. Elevated sputum interleukin-8 levels are associated with higher bacterial load and faster FEV(1) decline; the bacteria increase airway inflammation in the stable patient, which may accelerate disease progression. A 2-week course of oral corticosteroids is as beneficial as an 8-week course, with fewer adverse effects, and might extend the time until the next exacerbation. Antibiotics have some efficacy in treating exacerbations. Exacerbation frequency increases with progressive airflow obstruction; so patients with chronic respiratory failure are particularly susceptible to exacerbation.     

慢性阻塞性肺疾病患者血清中微量元素浓度变化及作用

目的探讨慢性阻塞性肺疾病(COPD)患者中微量元素铜和锌与炎症介质的关系。方法 2010年11月-2011年3月间测量15例COPD急性加重期患者入院时及治疗后和13例健康者为对照组的血清铜、锌、C反应蛋白(CRP)、白介素-6(IL-6),血浆中金属硫蛋白,以及氧化应激产物丙二醛的浓度变化。并对铜、锌浓度变化与CRP、IL-6进行相关分析。结果 COPD组血清中铜浓度、CRP、IL-6水平高于对照组(P<0.05),同时急性加重期患者血清中铜的浓度、CRP、IL-6水平以及丙二醛值高于缓解期患者(P<0.05)。而急性加重期患者血清中锌浓度低于缓解期组和对照组(P<0.05)。血浆中抗氧化物质金属硫蛋白在三组间差异无统计学意义(P>0.05)。在微量元素与炎症因子的相关分析中发现,铜与CRP(r=0.602,P<0.001)、IL-6(r=0.533,P<0.001)呈正相关,锌与IL-6呈负相关(r=0.336,P<0.05)。结论在COPD氧化应激发病机制中,铜可能发挥促氧化应激的作用,而锌可能发挥抗氧化应激的作用。微量元素稳态的紊乱有可能是COPD急性加重的危险因素。     

Clinical characteristics of neutrophilic,eosinophilic and mixed-type exacerbation phenotypes of COPD

BackgroundChronic obstructive pulmonary disease (COPD) comprises a significant number of emergency department (ED) presentations, and hematological phenotypes may have prognostic significance. The aim of this study was to investigate the effect of hematological phenotypes on serious outcomes in COPD exacerbations.MethodsA prospective cohort study was carried out in patients with COPD exacerbation presenting to the ED. The patients were classified into three groups, including neutrophilic, eosinophilic, and mixed-type (including neutrophilic and eosinophilic features) COPD exacerbation. Outcome measures were defined as mortality, hospitalization, and need for intensive care unit (ICU) care within three months, and these outcomes were compared among groups.ResultsA total of 173 COPD patients were assessed for eligibility, and 147 of them were included in the final analysis. The study population consisted of 90 patients with neutrophilic exacerbation (61.2%), 26 patients with eosinophilic exacerbation (17.7%), and 31 patients with mixed-type exacerbation (21.1%). The neutrophilic exacerbation group was older, was more often tachycardic and desaturated, and had more sputum production compared with the eosinophilic exacerbation group. Mortality was seen in 35 patients in the neutrophilic exacerbation group (38.9%), whereas 5 patients in the eosinophilic group (19.2%) and 6 patients in the mixed-type group (19.4%) died (p = .044). No difference was observed among groups in terms of hospital and ICU admission.ConclusionCOPD exacerbations with neutrophilic phenotypes presented to the ED with more serious clinical findings compared with eosinophilic exacerbations. This may also have a possible effect on mortality.     

Exacerbations worsen the quality of life of chronic obstructive pulmonary disease patients in primary healthcare

Aims: To investigate the evolution of the quality of life of patients with chronic obstructive pulmonary disease (COPD) and quantify the impact of exacerbations on the deterioration of quality of life over 2 years. Methods: Multicentre, observational, prospective 2‐year study carried out in primary care. Patients with COPD were seen every 6 months. All the exacerbations developing during the study period were recorded and the quality of life of these patients was measured with the St. George’s Respiratory Questionnaire (SGRQ). Results: Twenty‐seven physicians participated and collected information on 136 patients with a mean age of 70 years (SD: 9.7) and a mean forced expiratory volume in 1 s (FEV₁) of 48.7% predicted (SD: 14.5%). The mean global score of the SGRQ was 39.6 at the beginning of the study and 37.9 at the end. Patients without exacerbations improved an average of ?5.32 units compared with a worsening of +0.2 among patients with exacerbations (p = 0.023). Among the latter, patients with only one exacerbation improved ?3.8 units (p = 0.012) compared with a worsening of +2.4 in those with two or more exacerbations (p = 0.134). The impact of exacerbations was greater in patients with more preserved pulmonary function, with a change in the SGRQ among patients with or without exacerbations of +0.23 and ?6.17 (p = 0.017), respectively in patients with a FEV₁ > 50%, vs. +0.18 and ?4.39 (p = 0.32) in patients with a FEV₁ ≤ 50%. Conclusions: Exacerbations are associated with a significant worsening in the quality of life of patients with COPD measured with the SGRQ. The degree of impairment depends on the number of exacerbations, being greater in patients with more preserved pulmonary function.     

Gender Differences in Emergency Department Patients with Chronic Obstructive Pulmonary Disease Exacerbation

Objectives: Although more men are diagnosed as having chronic obstructive pulmonary disease (COPD), its prevalence is increasing among women. Little is known about gender differences in exacerbations of COPD. The objective of this study was to determine if acute presentation, management, and outcomes differ among men and women seeking care in the emergency department (ED) for exacerbation of COPD. Methods: This was a secondary analysis of a prospective cohort study of ED patients aged 55 years or older who presented with an exacerbation of COPD. Subjects underwent structured interviews in the ED and two weeks later. Results: The cohort consisted of 397 subjects with COPD, of whom 52% were women. Self-report of COPD only tended to be more common among men (61% of men vs. 52% of women), while mixed COPD/asthma tended to be more common among women (39% vs. 48%; p = 0.10). Despite reporting similar chronic symptom severity, women were less likely than men to use anticholinergic agents before their ED visit (59% vs. 69%; p = 0.04). During the exacerbation, women initiated less home therapy and were less likely to seek emergency care within the first 24 hours of symptom onset (25% vs. 36%; p = 0.01). Although ED care and disposition were similar, post-ED outcomes differed. At two-week follow-up, men were more likely to report an ongoing exacerbation (42% vs. 31%; p = 0.03). Conclusions: Men and women who present to the ED for treatment of an exacerbation of COPD have substantial differences in long-term medication use, self-treatment during exacerbation, delay in emergency care, and post-ED outcomes. Further studies are warranted to confirm and explain these gender-related differences.     

Elevation of cardiac troponins in exacerbation of chronic obstructive pulmonary disease

Objectives: To investigate the prevalence of serum troponin elevation in patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD). Methods: We examined the records of all patients admitted to hospital for treatment of COPD for serum troponin measurement, clinical features of myocardial ischaemia, oxygenation (pulse oximetry, arterial blood gas analysis), spirometry, and duration of admission. Results: Troponin elevation was observed in 58 of 235 (25%) presentations in which troponin was measured. Despite the troponin result, only seven of these 58 patients had been diagnosed with an acute coronary syndrome. New ECG evidence of ischaemia was uncommon. Patients with raised troponins tended to be older (75.7 vs 70.0 years, P = 0.001), had lower pulse oximetry (85.6% vs 89.6%, P = 0.003), were more acidotic (pH 7.34 vs 7.40, P= 0.002) and more hypercapnoeic (pCO₂ 58.0 vs 49.1, P = 0.04). There were no significant differences in serum creatine kinase. Patients with raised troponins had significantly longer admissions (5 vs 3 days, P = 0.001). Conclusions: Serum troponins are commonly raised in acute exacerbations of COPD and appear to reflect the severity of the exacerbation. In the majority of patients there is insufficient evidence to support the diagnosis of an acute coronary syndrome.     

Clinical and economic analysis of antimicrobial therapy of chronic obstructive pulmonary disease exacerbations

The aim of the study was to analyse the clinical and economic indicators of the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD). The study focused specifically on antimicrobial therapy and the use of fluoroquinolones in the management of exacerbations. Data on the consumption of antibiotics to treat exacerbations in ambulatory care were derived from IMS Health. Also, an observational, retrospective analysis was carried out of patients who entered the clinical pathway for COPD exacerbations in University Hospitals Leuven. IMS Health data showed that there is a trend towards the increasing use of broad-spectrum penicillins and fluoroquinolones, and decreasing use of tetracyclines in the treatment of COPD exacerbations in ambulatory care in Belgium in the first half of the 2000s. The observational analysis enrolled 267 patients who were hospitalised between October 2000 and October 2005 to manage 359 exacerbations according to the clinical pathway. Median length of stay per exacerbation amounted to 10 days. Mean quality of life associated with an exacerbation was 74 using the Chronic Respiratory Disease Questionnaire. Median costs of hospital treatment amounted to euro5514 (third-party payer reimbursement and patient co-payment) per exacerbation. Treatment costs were driven by hospital stay (75% of total costs), diagnostic and laboratory tests (20%) and medication (5%). Antibiotics played a role in the hospital management of 75% of exacerbations. Fluoroquinolones were used to treat more severe exacerbations. Treatment of acute exacerbations of COPD imposes a significant clinical and economic burden on patients, the healthcare system and the society.     

纤维蛋白原与白蛋白比值对慢阻肺患者急性加重风险的预测价值分析

目的 分析纤维蛋白原与白蛋白比值（FAR）对慢性阻塞性肺疾病（COPD）患者急性加重风险的预测价值。方法 选取2019年11月至2021年11月在我院接受治疗的86例COPD患者作为COPD组,同时选取同期来我院健康体检的40例健康人群作为对照组。根据患者入院前1年急性加重次数将COPD患者分为急性加重风险组（n=36）和无急性加重风险组（n=50）。所有纳入对象入院后均检测血清纤维蛋白原（FIB）、白蛋白（ALB）水平,并计算FAR比值。分析比较各组基本资料、生化指标,采用受试者工作特性曲线（ROC）评估血清FAR比值对COPD患者急性加重风险的预测价值,同时采用多因素Logistic回归分析影响COPD患者急性加重风险的相关因素。结果 COPD组血清FIB、FAR水平均明显高于对照组（P<0.05）,ALB水平明显低于对照组（P<0.05）。急性加重风险组患者血清FIB、FAR水平明显高于无急性加重风险组（P<0.05）,ALB水平明显低于无急性加重风险组（P<0.05）。ROC曲线结果显示,FAR预测COPD患者急性加重风险的曲线下面积为0.806,截断值0.29,敏感度、特异度分别为89.7%、85.3%,FIB曲线下面积为0.658,截断值8.50g/L,敏感度、特异度分别为75.6%、69.9%,ALB曲线下面积为0.689,截断值30.62g/L,敏感度、特异度分别为78.4%、70.2%。多因素logistic回归模型分析结果显示,血清FIB[OR（95%CI）：3.39（1.73~6.42）]、ALB[OR（95%CI）：3.56（1.79~7.06）]、FAR[OR（95%CI）：4.04（1.70~9.59）]均为影响COPD患者出现急性加重风险的相关因素（P<0.05）。结论 FAR比值在COPD患者急性加重风险中升高,是增加COPD患者急性加重风险的相关因素之一,有望作为预测患者出现急性加重风险的有效指标。     

Multidisciplinary COPD disease management program: impact on clinical outcomes

Objectives: We hypothesized performance improvement interventions would improve COPD guideline-recommended care and decrease COPD exacerbations in primary care clinic practices.

Methods: We initiated a performance improvement project in 12 clinics to improve COPD outcomes incorporating physician education, case management, web-based decision support (CareManager^TM), and performance feedback. We collected baseline and one-year follow up data on 242 patients who had COPD with acute exacerbations. We analyzed data by two methods. First, the 12 clinics were cluster randomized to 4 intervention (117 patients) and 8 control (125 patients) clinics which all had access to CareManager^TM but only intervention clinic physicians received case management, academic detailing, and decision support assistance. Exacerbation rates and guideline adherence were compared. Second, data from all 12 clinics were pooled in a quasi-experimental design comparing baseline and post-implementation of CareManager^TM to determine the value of system-wide performance improvement during the study period.

Results: In the randomized analysis, baseline demographics were similar. No differences (p = 0.79) occurred in exacerbation rates between intervention and control clinics although both groups had decreased numbers of exacerbations from baseline to follow up (p < 0.05). The pooled data from all 12 clinics demonstrated a reduction (p < 0.05) in mean exacerbations/patient from 2.3 (CI 2.0–2.6) during baseline to 1.4 (CI 1.1–1.7) at one-year follow up. Emergency department visits and hospitalizations/patient decreased (p = 0.003). Patients naïve at study start to depression screening, pneumococcal vaccination, inhaled control medications or smoking cessation had fewer (p < 0.05) exacerbations after these interventions.

Conclusion: We observed no difference in exacerbation rates between clinics receiving case management, academic detailing, and ongoing assistance with decision support and controls. Implementation of a web-based disease management system (CareManager^TM) along with health system-wide COPD performance improvement efforts was associated with fewer COPD exacerbations and increased adherence to guideline recommendations.     

Monitoring micronutrients in cigarette smokers

Smoking is associated with oxidative stress and increased risks of many chronic diseases that both shorten life and impair its quality. Low concentrations of several micronutrients, especially the antioxidants vitamin C and beta-carotene, are also associated with smoking, and there has been much interest in determining whether deficiencies in micronutrients are involved etiologically in smoking-related diseases. The objective of this review was to bring together reports on dietary intakes, biochemical indicators of micronutrient status, and results of some intervention studies on micronutrients where authors had compared outcomes in smokers and non-smokers. The micronutrients discussed are vitamins A, E, and C; the carotenoids; some of the B-vitamin group; and the minerals selenium, zinc, copper, and iron. The data were then examined to determine whether effects on the biochemical markers of micronutrient status were due to differences in dietary intakes between smokers and non-smokers or to the consequences of inflammatory changes caused by the oxidative stress of smoking. It was concluded that although smoking is associated with reduced dietary intake of vitamin C and carotenoid-containing foods, inflammatory changes increase turnover of these micronutrients so that blood concentrations are still lower in smokers than non-smokers even when there is control for dietary differences. In the case of vitamin E, there is some evidence for increased turnover of this nutrient in smokers, but this has little to no influence on blood concentrations, and there are no differences in dietary intake of vitamin E between smokers and non-smokers. Serum concentrations of vitamin A, folate, and vitamin B12 and B6 markers do not appear to be influenced by smoking, although there is some influence of dietary intake on concentrations of these nutrients in the body. In the case of the minerals examined, the main effects on biochemical markers of mineral status were attributed to inflammation and were therefore greater in heavy or long-term smokers. Serum concentrations of selenium and erythrocyte GPx activity were lower in smokers. Erythrocyte CuZn-SOD activity and serum ceruloplasmin concentrations were elevated, while serum zinc concentrations were depressed only in heavy smokers. Lastly, smoking appears to affect iron homeostasis mainly by changing hemoglobin concentrations, which were in general increased. Serum iron, TfR, and ferritin were mostly unaffected by smoking, except in pregnancy where there is evidence of increased erythropoiesis causing lower saturation of plasma transferrin and some evidence of lowering of iron stores.     

COPD exacerbations: causes, prevention, and treatment

The mechanisms of COPD exacerbation are complex. Respiratory viruses (in particular rhinovirus) and bacteria play a major role in the causative etiology of COPD exacerbations. In some patients, noninfective environmental factors may also be important. Data recently published from a large observational study identified a phenotype of patients more susceptible to frequent exacerbations. Many current therapeutic strategies can reduce exacerbation frequency. Future studies may target the frequent exacerbator phenotype, or those patients colonized with potential bacterial pathogens, for such therapies as long-term antibiotics, thus preventing exacerbations by decreasing bacterial load or preventing new strain acquisition in the stable state. Respiratory viral infections are also an important therapeutic target for COPD. Further work is required to develop new anti-inflammatory agents for exacerbation prevention, and novel acute treatments to improve outcomes at exacerbation.