Mónica Guerrero

Pneumonic and Nonpneumonic Exacerbations of COPD: Inflammatory Response and Clinical Characteristics

BACKGROUND Community-acquired pneumonia (CAP) is a frequent event in patients with COPD, although it is not currently considered an acute exacerbation of COPD (AECOPD). To our knowledge, no studies have compared the inflammatory response of patients with COPD who develop CAP or AECOPD. The aim of our study was to compare clinical and evolutive manifestations and biologic signaling of AECOPD and CAP + COPD. METHODS Prospective data were collected from 249 consecutively hospitalized patients with COPD. Comparative analyses were performed in patients with AECOPD (n = 133) and patients with CAP + COPD (n = 116). Measures of clinical characteristics, blood biomarkers, and evolution were recorded on admission, after 3 and 30 days, and in a follow-up period of 30 days, 90 days, and 1 year. RESULTS Patients with CAP + COPD had higher FEV1 compared with patients with COPD without pneumonia. In-hospital and long-term outcomes (1 year) were similar for both populations. However, patients with AECOPD had more readmissions, and patients with CAP had more prior episodes of pneumonia. At day 1 and day 3, patients with CAP + COPD had significantly (P < .001) higher serum levels of C-reactive protein (CRP), procalcitonin, tumor necrosis factor-α, and IL-6. Repetition of the analyses after stratifying patients based on severity of disease, current inhaled pharmacotherapy, and noninfectious AECOPD cause confirmed higher levels of the same biomarkers in patients with CAP + COPD. Chills, pleuritic pain, sputum purulence, and CRP levels at day 1 were independent clinical predictors of CAP + COPD. CONCLUSIONS Our study confirms that two different clinical and inflammatory profiles exist in hospitalized patients with COPD in response to CAP (stronger response) and AECOPD, although with similar short-term and long-term outcomes.

Original ResearchCOPDPneumonic and Nonpneumonic Exacerbations of COPD: Inflammatory Response and Clinical Characteristics

BACKGROUND Community-acquired pneumonia (CAP) is a frequent event in patients with COPD, although it is not currently considered an acute exacerbation of COPD (AECOPD). To our knowledge, no studies have compared the inflammatory response of patients with COPD who develop CAP or AECOPD. The aim of our study was to compare clinical and evolutive manifestations and biologic signaling of AECOPD and CAP + COPD. METHODS Prospective data were collected from 249 consecutively hospitalized patients with COPD. Comparative analyses were performed in patients with AECOPD (n = 133) and patients with CAP + COPD (n = 116). Measures of clinical characteristics, blood biomarkers, and evolution were recorded on admission, after 3 and 30 days, and in a follow-up period of 30 days, 90 days, and 1 year. RESULTS Patients with CAP + COPD had higher FEV1 compared with patients with COPD without pneumonia. In-hospital and long-term outcomes (1 year) were similar for both populations. However, patients with AECOPD had more readmissions, and patients with CAP had more prior episodes of pneumonia. At day 1 and day 3, patients with CAP + COPD had significantly (P < .001) higher serum levels of C-reactive protein (CRP), procalcitonin, tumor necrosis factor-α, and IL-6. Repetition of the analyses after stratifying patients based on severity of disease, current inhaled pharmacotherapy, and noninfectious AECOPD cause confirmed higher levels of the same biomarkers in patients with CAP + COPD. Chills, pleuritic pain, sputum purulence, and CRP levels at day 1 were independent clinical predictors of CAP + COPD. CONCLUSIONS Our study confirms that two different clinical and inflammatory profiles exist in hospitalized patients with COPD in response to CAP (stronger response) and AECOPD, although with similar short-term and long-term outcomes.

Readmission for Acute Exacerbation within 30 Days of Discharge Is Associated with a Subsequent Progressive Increase in Mortality Risk in COPD Patients: A Long-Term Observational Study

Background and Objective Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge. The prognostic significance of early readmission is not fully understood. The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients. Methods The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge. Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years. Results Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity. Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51–4.05) was the only variable independently associated with 30-day readmission. The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10–5.59). In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5). Conclusion In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death.

Importance of Aspergillus spp. isolation in Acute exacerbations of severe COPD: prevalence, factors and follow-up: the FUNGI-COPD study

BackgroundAcute exacerbations of COPD (AECOPD) are often associated with infectious agents, some of which may be non-usual, including Aspergillus spp. However, the importance of Aspergillus spp. in the clinical management of AECOPD still remains unclear.ObjectivesThe aims of the study were to analyze the prevalence and risk factors associated with Aspergillus spp. isolation in AECOPD, and to investigate the associated clinical outcomes during a 1-year follow-up period.MethodsPatients presenting with an AECOPD requiring hospitalization were prospectively included from four hospitals across Spain. Clinical, radiological and microbiological data were collected at admission and during the follow-up period (1, 6 and 12 months after discharge), and re-admissions and mortality data collected during the follow-up.ResultsA total of 240 patients with severe AECOPD were included. Valid sputum samples were obtained in 144 (58%) patients, and in this group, the prevalence of Aspergillus spp. isolation was 16.6% on admission and 14.1% at one-year follow-up. Multivariate logistic-regression showed that AECOPD in the previous year (OR 12.35; 95% CI, 1.9-29.1; p < 0.001), concurrent isolation of pathogenic bacteria (OR 3.64; 95% CI 1.65-9.45, p = 0.001) and concomitant isolation of Pseudomonas aeruginosa (OR 2.80; 95% IC, 1.81-11.42; p = 0.001) were the main risk factors for Aspergillus spp. isolation.ConclusionsThe main risk factors for Aspergillus spp. isolation were AECOPD in the previous year and concomitant isolation of Pseudomonas aeruginosa. However, although Aspergillus spp. is often isolated in sputum samples from patients with AECOPD, the pathogenic and clinical significance remains unclear.

C-Reactive Protein at Discharge, Diabetes Mellitus and ≥1 Hospitalization During Previous Year Predict Early Readmission in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Abstract Recurrent hospitalizations in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients have clinical and economic consequences; particularly those readmitted soon after discharge. The aim of our observational study was to determine predictors of early readmission to hospital (30 days from discharge). Prospective data on 125 hospitalized AECOPD patients were collected over a 30-month period at two Spanish university hospitals. Based on readmission after discharge, patients were divided into non-readmitted (n = 96) and readmitted (n = 29). Measures of serum inflammatory biomarkers were recorded on admission to hospital, at day 3 and at discharge; data on clinical, laboratory, microbiological and severity features were also recorded. In a multivariate model, C-reactive protein (CRP) at discharge ≥7.6 mg/L, presence of diabetes and ≥1 hospitalization for AECOPD during previous year were significant risk factors for predicting readmission. Presence of all 3 risk factors perfectly identified the readmitted patients (positive and negative predictive values of 1.000; 95% CI, 1.00–1.00). A combination of 3 readily available clinical and biochemical parameters is accurate in identifying hospitalized AECOPD patients at risk for early readmission.

Predicting In-Hospital Treatment Failure (≤7 days) in Patients with COPD Exacerbation Using Antibiotics and Systemic Steroids.

Abstract Although pharmacological treatment of COPD exacerbation (COPDE) includes antibiotics and systemic steroids, a proportion of patients show worsening of symptoms during hospitalization that characterize treatment failure. The aim of our study was to determine in-hospital predictors of treatment failure (≤ 7 days). Prospective data on 110 hospitalized COPDE patients, all treated with antibiotics and systemic steroids, were collected; on the seventh day of hospitalization, patients were divided into treatment failure (n = 16) or success (n = 94). Measures of inflammatory serum biomarkers were recorded at admission and at day 3; data on clinical, laboratory, microbiological, and severity, as well data on mortality and readmission, were also recorded. Patients with treatment failure had a worse lung function, with higher serum levels of C-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), interleukin (IL) 8, and IL-10 at admission, and CRP and IL-8 at day 3. Longer length of hospital stay and duration of antibiotic therapy, higher total doses of steroids and prevalence of deaths and readmitted were found in the treatment failure group. In the multivariate analysis, +1 mg/dL of CRP at admission (OR, 1.07; 95% CI, 1.01 to 1.13) and use of penicillins or cephalosporins (OR, 5.63; 95% CI, 1.26 to 25.07) were independent variables increasing risk of treatment failure, whereas cough at admission (OR, 0.20; 95% CI, 0.05 to 0.75) reduces risk of failure. In hospitalized COPDE patients CRP at admission and use of specific class of antibiotics predict in-hospital treatment failure, while presence of cough has a protective role.

Inhaled corticosteroids do not influence the early inflammatory response and clinical presentation of hospitalized subjects with COPD exacerbation.

BACKGROUND: Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids. METHODS: Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded. RESULTS: At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P < .01). All clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13–8.63, P = .02). CONCLUSIONS: Our study demonstrates a lack of inhaled corticosteroid influence in the early systemic inflammatory response to and clinical presentation of COPD exacerbation.

Relation Between Chronic Obstructive Pulmonary Disease and Antibiotics

Chronic obstructive pulmonary disease (COPD) constitutes a major health problem. Recurrent acute exacerbations are characteristic of the course of COPD (AECOPD) associated with significant healthcare costs and contribute to the progress of the disease. Given that almost half of AECOPD is caused by bacteria, administration of antibacterial agents is recommended for patients with severe exacerbations or severe underlying COPD. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients. It is unclear whether antibiotics should be provided as prophylactic agents in COPD patients although ongoing trials are reexamining the question of whether the antiinflammatory action of antibiotics such as macrolides can be useful in preventing exacerbations. In addition, nowadays, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids.

Readmission in COPD patients: should we consider it a marker of quality of care or a marker of a more severe disease with a worse prognosis?

In the January edition of the European Respiratory Journal, we read with interest the paper by Hartl et al. [1], which evaluated, from the European COPD Audit, patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the mortality risk during hospitalisation and in the post-discharge period of 90 days. Moreover, the authors evaluate the risk of readmission in a period of 90 days from discharge. Readmission in COPD patients: a marker of quality of care or a more severe disease with a worse prognosis? http://ow.ly/ZwIpW

Acute exacerbations of COPD: risk factors for failure and relapse

Acute exacerbations are a leading cause of worsening COPD in terms of lung function decline, quality of life, and survival. They also have a relevant economic burden on the health care system. Determining the risk factors for acute exacerbation and early relapse could be a crucial element for a better management of COPD patients. This review analyzes the current knowledge and underlines the main risk factors for recurrent acute exacerbations. Comprehensive evaluation of COPD patients during stable phase and exacerbation could contribute to prevent treatment failure and relapses.