The Economic Impact of Exacerbations of Chronic Obstructive Pulmonary Disease and Exacerbation Definition: A Review

ABSTRACT

Chronic obstructive pulmonary disease (COPD) poses a significant economic burden on society, and a substantial portion is related to exacerbations of COPD. A literature review of the direct and indirect costs of COPD exacerbations was performed. A systematic search of the MEDLINE database from 1998–2008 was conducted and supplemented with searches of conference abstracts and article bibliographies. Articles that contained cost data related to COPD exacerbations were selected for in-depth review. Eleven studies examining healthcare costs associated with COPD exacerbations were identified. The estimated costs of exacerbations vary widely across studies: $88 to $7,757 per exacerbation (2007 US dollars). The largest component of the total costs of COPD exacerbations was typically hospitalization. Costs were highly correlated with exacerbation severity. Indirect costs have rarely been measured. The wide variability in the cost estimates reflected cross-study differences in geographic locations, treatment patterns, and patient populations. Important methodological differences also existed across studies. Researchers have used different definitions of exacerbation (e.g., symptom- versus event-based definitions), different tools to identify and measure exacerbations, and different classification systems to define exacerbation severity. Unreported exacerbations are common and may influence the long-term costs of exacerbations. Measurement of indirect costs will provide a more comprehensive picture of the burden of exacerbations. Evaluation of pharmacoeconomic analyses would be aided by the use of more consistent and comprehensive approaches to defining and measuring COPD exacerbations.     

Prulifloxacin vs Levofloxacin for Exacerbation of COPD after Failure of Other Antibiotics

The chronic course and evolution of chronic obstructive pulmonary disease (COPD) is often characterized by periods of exacerbation of symptoms, which have a negative impact on the quality of life of patients, as well as on the evolution of COPD, and represent a significant cause of medical intervention and hospitalization. Very few data are available on the efficacy of rescue antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to previous treatment. The aim of this study was to evaluate the efficacy of two fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR study is a randomized, single-blind, non-inferiority comparison between levofloxacin and prulifloxacin. Primary end-point was “therapeutic success” at Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at least three points of a global score of symptomatology (maximum score = 15). 258 patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A very high proportion of patients in the two groups had therapeutic success at Day-10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat; 94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7 days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in 17.8% of patients treated with levofloxacin and 14.2% of those receiving prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in the treatment of AECOPD resistant to other antibiotics.     

Hospitalized Acute Exacerbation of COPD Impairs Flow and Nitroglycerin-Mediated Peripheral Vascular Dilation

Vascular function, as measured by flow mediated dilation (FMD) and nitroglycerin mediated dilation (NMD), is impaired in COPD. Increases in systemic inflammatory mediators during acute exacerbations of COPD (AECOPD) may further impair vascular function and may account for the increased prevalence of cardiovascular disease in COPD patients. Similarly it may account for the increased morbidity and mortality in COPD patients hospitalized with acute exacerbations. We hypothesized that FMD and NMD would be impaired during AECOPD requiring hospitalization and that vascular function would improve upon AECOPD resolution. We used FMD and NMD to evaluate vascular function in 19 patients hospitalized with AECOPD. FMD and NMD were repeated approximately three months later in 8 of these patients. In these eight patients significant improvements were observed in FMD (2.6 ± 1.5% vs 5.1 ± 2.4%, p = 0.04) and NMD (5.0 ± 2.6% vs 13.3 ± 4.5, p = 0.02) after resolution of their exacerbation. We conclude that endothelial and vascular smooth muscle function is markedly impaired during AECOPD requiring hospitalization and improves following resolution. The systemic vascular impairment that occurs during AECOPD may partially explain the observed increased in cardiac morbidity and mortality that occur in this population.     

Preventing COPD: Evidence of Progress

Abstract

Lightweight ambulatory oxygen devices are provided on the assumptions that they enhance compliance and increase activity, but data to support these assumptions are lacking. We studied 22 patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy (14 men, average age = 66.9 y, FEV₁ = 33.6%pred, PaO₂ at rest = 51.7 torr) who were using E-cylinders as their portable oxygen. Subjects were recruited at 5 sites and studied over a 2-week baseline period and for 6 months after randomizing them to either continuing to use 22-lb E-cylinders towed on a cart or to carrying 3.6-lb aluminum cylinders. Utilizing novel electronic devices, ambulatory and stationary oxygen use was monitored continuously over the 2 weeks prior to and the 6 months following randomization. Subjects wore tri-axial accelerometers to monitor physical activity during waking hours for 2–3 weeks prior to, and at 3 and 6 months after, randomization. Seventeen subjects completed the study. At baseline, subjects used 17.2 hours of stationary and 2.5 hours of ambulatory oxygen daily. At 6 months, ambulatory oxygen use was 1.4 ± 1.0 hrs in those randomized to E-cylinders and 1.9 ± 2.4 hrs in those using lightweight oxygen (P = NS). Activity monitoring revealed low activity levels prior to randomization and no significant increase over time in either group. In this group of severe chronic obstructive pulmonary disease patients, providing lightweight ambulatory oxygen did not increase either oxygen use or activity. Future efforts might focus on strategies to encourage oxygen use and enhance activity in this patient group. This trial is registered at ClinicalTrials.gov (NCT003257540).     

Risk Factors of Poor Outcomes after Admission for a COPD Exacerbation: Multivariate Logistic Predictive Models

The aim of this study was to identify a multivariate model to predict poor outcomes after admission for exacerbation of chronic obstructive pulmonary disease (COPD). We performed a multicenter, observational, prospective study. Patients admitted to hospital for COPD were followed up for 3 months. Relevant clinical variables at admission were selected. For each variable, the best cut-offs for the risk of poor outcome were identified using receiver operating characteristic (ROC) curves. Finally, a stepwise logistic regression model was performed. A total of 106 patients with a mean age of 71.1 (9.8) years were included. The mean maximum expiratory volume in the first second (FEV₁)(%) was 45.2%, and the mean COPD assessment test (CAT) score at admission was 24.8 (7.1). At 3 months, 39 (36.8%) patients demonstrated poor outcomes: death (2.8%), readmission (20.8%) or new exacerbation (13.2%). Variables included in the logistic model were: previous hospital admission, FEV₁ < 45%, Charlson ≥ 3, hemoglobin (Hb)<13 g/L, PCO2 ≥ 46 mmHg, fibrinogen ≥ 554 g/L, C-reactive protein (CRP)≥45 mg/L, leukocyte count < 9810 × 10⁹/L, purulent sputum, long-term oxygen therapy (LTOT) and CAT ≥ 31 at admission. The final model showed that Hb < 13 g/L (OR = 2.46, 95%CI 1.09–6.36), CRP ≥ 45 mg/L (OR = 2.91, 95%CI: 1.11–7.49) and LTOT (3.07, 95%CI: 1.07–8.82) increased the probability of poor outcome up to 82.4%. Adding a CAT ≥ 31 at admission increased the probability to 91.6% (AUC = 0.75; p = 0.001). Up to 36.8% of COPD patients had a poor outcome within 3 months after hospital discharge, with low hemoglobin and high CRP levels being the risk factors for poor outcome. A high CAT at admission increased the predictive value of the model.     

[Translated article] Spanish COPD Guidelines (GesEPOC) 2021 Update. Diagnosis and Treatment of COPD Exacerbation Syndrome

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm³. Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment.     

Long-Term Effects of a Maintenance Program After Supervised or Self-Monitored Training Programs in Patients with COPD

The evaluation of a 13-month maintenance program (MP) for 39 severe COPD patients with FEV(1)%pred 44(7)% who, as result of two different 8-week leg exercise training (LET) programs, one supervised at the hospital (group S; n = 20) and the other self-monitored (SM; n = 19), had achieved different levels of exercise tolerance. After LET, patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O(2)max 1.43(0.30) l. min(-1)] vs l.25(0.27) l. min(-1) and endurance-time 16(4) min vs 12 (5) min, respectively). During the MP patients were advised to walk vigorously at least 4 km/day, 4 times/wk. After the MP, while endurance time remained higher than at baseline, it had decreased ( p < 0.01) immediately after LET in both groups and no differences were evident between groups (11(4) min and 10(4), respectively). In contrast, Chronic Respiratory Diseases Questionnaire scores, which had improved significantly after LET in both groups, remained high. Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET. SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance, though "quality of life" can be maintained.     

Statins and outcome after hospitalization for COPD exacerbation: a prospective study

Background

Retrospective studies have shown that the use of statins is associated with reduced mortality and decreased hospitalizations from COPD, but data from prospective studies are lacking.

Methods

We followed-up prospectively 245 patients admitted to hospital for exacerbations of COPD (ECOPD) with monthly evaluations for one year. The role of statins on outcomes was evaluated by Cox regression analysis after proper adjustments for age, gender, BMI, current smoking status, Charlson comorbidity index and COPD stage. Health-related quality of life (HRQoL) was evaluated by Saint George’s Respiratory Questionnaire.

Results

There was no effect of statins on either 30-day or 1-year mortality. Patients receiving statins presented a lower total number of ECOPD during the 1-year follow up (2.1 ± 2.7 vs. 2.8 ± 3.2 ECOPD/patient respectively, p = 0.037). After proper adjustments, the use of statins was associated with a lower risk for ECOPD [HR: 0.656 (95% CI: 0.454–0.946)] and severe ECOPD [HR: 0.608 (95%CI: 0.381–0.972)]. The group of statins presented better improvement in HRQoL at 2, 6 and 12 months (p < 0.001).

Conclusions

The use of statins in patients hospitalized for ECOPD was associated with a lower risk for subsequent ECOPD and severe ECOPD and improved HRQoL. These data support a possible beneficial role for these agents in COPD.     

Effects of Early Enteral Nutrition on Patients After Emergency Gastrointestinal Surgery: A Propensity Score Matching Analysis

Early postoperative enteral feeding has been demonstrated to improve the outcome of patients who underwent surgery for gastrointestinal (GI) malignancies, trauma, perforation, and/or obstruction. Thus, this study was conducted to assess the efficacy of early postoperative enteral nutrition (EN) after emergency surgery in patients with GI perforation or strangulation.The medical records of 484 patients, admitted between January 2007 and December 2012, were reviewed retrospectively. Patients were divided into 2 groups: the early EN (EEN, N = 77) group and the late EN (LEN, N = 407) group. The morbidity, mortality, length of hospital, and intensive care unit (ICU) stays were compared between the 2 groups. Propensity score matching was performed in order to adjust for any baseline differences.Patients receiving EEN had reduced in-hospital mortality rates (EEN 4.5% vs LEN 19.4%; P = 0.008), pulmonary complications (EEN 4.5% vs LEN 19.4%; P = 0.008), lengths of hospital stay (median: 14.0, interquartile range: 8.0–24.0 vs median: 17.0, interquartile range: 11.0–26.0, P = 0.048), and more 28-day ICU-free days (median: 27.0, interquartile range: 25.0–27.0 vs median: 25.0, interquartile range: 22.0–27.0, P = 0.042) than those receiving LEN in an analysis using propensity score matching. The significant difference in survival between the 2 groups was also shown in the Kaplan–Meier survival curve (P = 0.042). In a further analysis using the Cox proportional hazard ratio after matching on the propensity score, EEN was associated with reduced in-hospital mortality (hazard ratio, 0.03; 95% confidence interval, 0.01–0.49; P = 0.015).EEN is associated with beneficial effects, such as reduced in-hospital mortality rates, pulmonary complications, lengths of hospital stay, and more 28-day ICU-free days, after emergency GI surgery.     

The Workplace Impact of Acute Exacerbations of Chronic Bronchitis (AECB); A Literature Review

Acute exacerbations of chronic bronchitis (AECB) are known to have a substantial economic burden in terms of medical care costs. The objective of this study was to assess workplace‐based costs associated with AECB, including absenteeism and decreased productivity, based on a review of published literature. A secondary goal was to identify factors related to workplace‐based costs in AECB. A literature search was conducted to identify relevant articles assessing one or more aspects of work loss or workplace costs among patients with chronic bronchitis. A review of the identified literature indicates that patients with chronic bronchitis had more days off work; patients whose exacerbations were treated were less likely to have additional exacerbations and had comparatively less work loss. Findings suggest that clinical outcomes and workplace costs are related. While this relationship is clearer in terms of work loss, further exploration is needed to assess decreased productivity and to evaluate this relationship using objective indicators of absenteeism and productivity rather than recall.