Changes in inflammatory markers following treatment of acute exacerbations of obstructive pulmonary disease.

The aim ofthe study was to investigate changes in inflammatory markers following emergency treatment of obstructive pulmonary disease. The study comprised 43 patients. After acute treatment, they were given either 30 mg of prednisolone p.o. or 1600 microg of inhaled budeson de daily for 1 week. Over the following 3 weeks, all the patients were given 1600 microg of inhaled budesonide daily. Blood samples for measurements of eosinophil cationic protein (S-ECP), eosinophil peroxidase (S-EPO), total eos nophil count (B-Eos), myeloperoxidase (S-MPO) and human neutrophil lipocaline (HNL) were taken and spirometry was performed before emergency treatment and after 1 and 4 weeks. There was no difference in the improvement in forced expiratory volume in 1 sec (FEV1) between patients given prednisolone or budesonide. Patients with an improvement in FEV1 of >20% of baseline after 1 and 4 weeks displayed a larger decrease in eosinophil markers. The correlation between deltaFEV1 and deltaS-ECP was r= -0.37, P < 0.05, deltaS-EPO -0.40, P < 0.01 and deltaB-Eos -0.44, P < 0.01, after 4 weeks. This correlation was highly significant in patients who had smoked < or = 5 pack-years, while the correlation was not significant in patients with a longer smoking history and chronic airflow limitation (best FEV <80% of predicted). We conclude that the change in eosinophil markers is correlated to the improvement in lung function in non-smokers or short-term smokers following the emergency treatment of obstructive pulmonary disease. This study indicates that following eosinophil markers is more useful in patients with asthma than patients with COPD.     

Role of viruses in exacerbations of chronic obstructive pulmonary disease

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.     

Management of acute exacerbations in chronic obstructive pulmonary disease

An acute exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by an acute worsening of symptoms accompanied by lung infection. In severe cases, an acute exacerbation may cause respiratory failure and death. Successful management of acute exacerbation of COPD in either the inpatient or outpatient setting requires attention to a number of key issues. In this review, issues regarding the management of acute exacerbations of COPD are discussed. An inhaled beta-2 agonist along with the inhaled anticholinergic bronchodilator are recommended. Antibiotic therapy has been demonstrated to improve clinical recovery and physical outcomes. It should be directed against the most commonly occurring pathogens and, in more severe cases, coverage against Gram-negative bacteria is considered. Short course of systemic steroids does provide benefit in hospitalized patients. Supplemental oxygen is appropriate for all patients with hypoxemia. Ventilatory support treatment may be necessary, noninvasive ventilatory assistance being preferable early in the course of the acute episode. In a high number of cases, endotracheal intubation may be avoided. Promoting smoking cessation and the use of influenzae and pneumococcal vaccination may help decrease frequency of episodes of these exacerbations.     

Pathogen-directed therapy in acute exacerbations of chronic obstructive pulmonary disease

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of this chronic lung disorder. These events can be caused by a large number of infectious and noninfectious agents and are associated with an increased local and systemic inflammatory response. Their frequency and severity have been linked to progressive deterioration in lung function and health status. Infectious pathogens ranging from viral to atypical and typical bacteria have been implicated in the majority of episodes. Most therapeutic regimens to date have emphasized broad, nonspecific approaches to bronchoconstriction and pulmonary inflammation. Increasingly, therapy that targets specific etiologic pathogens has been advocated. These include clinical and laboratory-based methods to identify bacterial infections. Further additional investigation has suggested specific pathogens within this broad class. As specific antiviral therapies become available, better diagnostic approaches to identify specific pathogens will be required. Furthermore, prophylactic therapy for at-risk individuals during high-risk times may become a standard therapeutic approach. As such, the future will likely include aggressive diagnostic algorithms based on the combination of clinical syndromes and rapid laboratory modalities to identify specific causative bacteria or viruses.     

Viral pathogens in acute exacerbations of chronic obstructive pulmonary disease

The objective of this study is to determine the prevalence of respiratory syncytial virus (RSV) and other viral respiratory pathogens in emergency department (ED) patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD patients presenting to the ED with <10 days of AECOPD symptoms were eligible. We used PCR to test nasal swabs for common viral respiratory pathogens. We completed viral studies on 76 patients from two EDs. Patients had a mean age of 72 years, and were 68% male, 99% white, and 29% current smokers. Influenza vaccination was reported by 87%. Viruses were detected in 19 of 76 patients (25%). These included RSV A (2) and B (4); parainfluenza 1 (1), 2 (0), and 3 (2); influenza A (3) and B (0); rhinovirus (4); and human metapneumovirus (3). A putative viral etiology was identified in 25% of AECOPD presenting for emergency care, of which approximately one-third were RSV-related.     

In-hospital mortality following acute exacerbations of chronic obstructive pulmonary disease

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent cause of hospitalization in the United States. Previous studies of selected populations of patients with COPD have estimated in-hospital mortality to range from 4% to 30%. Our objective was to obtain a generalizable estimate of in-hospital mortality from acute exacerbation of COPD in the United States and to identify predictors of in-hospital mortality using administrative data. METHODS: We performed a cross-sectional study utilizing the 1996 Nationwide Inpatient Sample, a data set of all hospitalizations from a 20% sample of nonfederal US hospitals. The study population included 71 130 patients aged 40 years or older with an acute exacerbation of COPD at hospital discharge. The primary outcome assessed was in-hospital mortality. RESULTS: In-hospital mortality for patients with an acute exacerbation of COPD was 2.5%. Multivariable analyses identified older age, male sex, higher income, nonroutine admission sources, and more comorbid conditions as independent risk factors for in-hospital mortality. CONCLUSIONS: Mortality during hospitalization in this nationwide sample of patients with acute exacerbations of COPD was lower than that of previous studies of select populations. This estimate should provide optimism to both clinicians and patients regarding prognoses from COPD exacerbations requiring hospitalization. Our results indicate that the use of administrative data can help to identify subsets of patients with acute exacerbations of COPD that are at higher risk of in-hospital mortality.     

Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease

The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD.Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses.A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population.In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.     

慢性阻塞性肺疾病急性加重期患者的血浆生物标志物变化

COPD是目前全球致残和致死率较高的疾病之一.COPD急性加重(AECOPD)与肺功能加速减损、生命质量降低及病死率增高密切相关.AECOPD导致患者反复住院,并构成疾病费用的主要部分~([1-2]).     

Role of corticosteroids in acute exacerbations of chronic obstructive pulmonary disease

Systemic corticosteroid therapy for patients with exacerbations of chronic obstructive pulmonary disease has become increasingly commonplace over the past two decades. This practice was controversial because a number of small clinical trials provided inconclusive evidence about efficacy. Experience from recent trials indicates that systemic cortico-steroids are modestly effective in this setting. Systemic corticosteroids administered to hospitalized patients reduces the absolute treatment rate by about 10%, increases the forced expiratory volume in 1 second (FEV(1)) by about 100 mL, and shortens the hospital stay by 1 to 2 days. Treatment should not extend longer than 2 weeks. The optimal starting dose is not known. Hyperglycemia and possibly an increased rate of secondary infections are expected complications of treatment.     

Pathogenesis and treatment of acute exacerbations of chronic obstructive pulmonary disease

Once thought to be a mere nuisance, exacerbations are now recognized as a major contributor to the morbidity and mortality associated with chronic obstructive pulmonary disease. This recognition has led to research using new investigative tools that has substantially enhanced our understanding of the pathogenesis of exacerbations. Several overlapping etiologies can precipitate the symptom complex of an exacerbation. Treatment of exacerbations requires the use of several therapeutic modalities with the goal of restoring the patient to baseline. Results of recent clinical trials and observational studies have allowed a refinement of the approach to treatment of exacerbations. These include a rational, stratified approach to the use of antibiotics and several trials substantiating the use of systemic corticosteroids. Relapse or failure rates of 20 to 33% have been described in the treatment of acute exacerbation, with these treatment failures contributing substantially to the costs associated with exacerbations. Improved treatment based on enhanced understanding and good clinical evidence should lead to better outcomes in this common clinical entity.     

Role of bacteria in acute exacerbations of chronic obstructive pulmonary disease

Background and study objective

Infections are major causes of acute exacerbations of chronic obstructive pulmonary disease (COPD) which result in significant mortality and morbidity. The primary aim of the study was to determine the microbiological spectrum including atypical agents in acute exacerbations. The secondary aim was to evaluate resistance patterns in the microorganisms.

Methods

The sputum culture of 75 patients admitted to our clinic from January 1, 1999 to December 31, 2002 was evaluated prospectively, for aerobic Gram-positive and Gram-negative bacteria, and serologically for Chlamydophila pneumoniae and Mycoplasma pneumoniae. Sensitivity patterns in potentially pathogenic microorganisms (PPMs) were also investigated.

Results

An infectious agent was identified in 46 patients, either serologically or with sputum culture. Pathogens most commonly demonstrated were: Haemophilus influenzae (30%), Chlamydophila pneumoniae (17%), and Mycoplasma pneumoniae (9%). Mixed infections were diagnosed in 9 patients. PPMs showed a high resistance rate to commonly used antibiotics.

Conclusion

We have shown that microorganisms causing acute exacerbations of COPD are not only typical bacteria (46%) but also atypical pathogens (26%), with unpredictable high rates. Typical agents showed a high resistance to commonly used antibiotics.     

Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the airways and lung parenchyma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (1) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically stable state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected from patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time point for soluble markers associated with neutrophilic inflammation; myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8). Serologic assays on acute and convalescent sera were performed for respiratory viruses, and induced sputum was also subject to quantitative bacterial cultures, viral cultures, and polymerase chain reaction (PCR) for detection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 15-mo study period. TNF-alpha and IL-8 were significantly elevated in the sputum of patients during acute COPD exacerbation compared with when they were clinically stable (p = 0.01 and p = 0.05, respectively). Concentrations of these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract infections. Patients with documented infection did not demonstrate greater increases in sputum levels of inflammatory cytokines during exacerbations compared with patients without demonstrable infection. We conclude that markers of airway neutrophilic inflammation increase at the time of acute COPD exacerbation and then decline 1 mo later, and that this acute inflammatory response appears to occur independently of a demonstrable viral or bacterial airway infection.     

Aminophylline for acute exacerbations of chronic obstructive pulmonary disease. A controlled trial

Study Objective: To determine the efficacy of intravenous aminophylline in the treatment of patients hospitalized for exacerbation of chronic obstructive pulmonary disease. Design: Randomized, double-blind, placebo-controlled trial during the first 72 hours of hospitalization. Patients: Thirty patients admitted from the emergency room or walk-in clinic with the primary diagnosis of an exacerbation of chronic obstructive pulmonary disease. Twenty-eight patients completed the study; 2 patients, 1 receiving placebo and 1 receiving aminophylline, were removed from the study because of respiratory failure requiring mechanical ventilation. Interventions: Patients received either intravenous aminophylline or placebo, in addition to nebulized, inhaled 0.3 mL of a 5% solution every 6 hours; methylprednisolone, 0.5 mg/kg body weight every 6 hours intravenously; ampicillin, 500 mg orally every 6 hours (tetracycline or trimethoprim-sulfamethoxazole were substituted in penicillin-allergic patients); and supplemental oxygen as needed. Aminophylline infusion rates were adjusted by an unblinded investigator to achieve theophylline levels of 72 to 83 mumol/L. Changes were also made in placebo infusion rates to maintain the double-blind design. Measurements and Main Results: The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) before and after metaproterenol inhalation were measured twice daily by a blinded investigator, who also administered a verbal dyspnea index with a scale of 1 to 10 and questioned patients regarding possible side effects of treatment (tremor, palpitations, nausea, or vomiting). Arterial blood gas measurements at 72 hours were compared with those obtained on admission. Significant improvements in FEV1 and FVC measured before and after metaproterenol treatment and in dyspnea occurred over time in both treatment groups (p less than 0.05 for all measurements). However, there were no significant differences between the placebo and aminophylline groups in any of the spirometric measurements or the dyspnea indices (p greater than 0.5 in all five analyses). The mean increases (+/- SE) in Po2 of 1.9 (+/- 0.5) kPa with placebo and 1.7 (+/- 0.7) kPa with aminophylline and the mean decreases in PCO2 of 0.5 (+/- 0.4) kPa with placebo and 1.2 (+/- 0.4) kPa with aminophylline were not significantly different (p greater than 0.6 for PO2, p greater than 0.2 for PCO2).(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease

Our understanding of the pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased considerably in the past decade. Several new lines of evidence support bacterial causation of about half the exacerbations. Contrary to previous data, recent studies with improved methodology have demonstrated that exacerbations do contribute to the loss of lung function in COPD. Another interesting new observation is that colonization by bacterial pathogens may not be innocuous, and in fact may lead to airway inflammation and contribute to pathogenesis of COPD. Evidence that bacteria cause exacerbations, that exacerbations contribute to loss of lung function, and that chronic colonization by bacteria may be harmful, has emphasized the potential importance of appropriate antibiotics in the treatment of exacerbations. An unfortunate paucity of data does not allow evidence-based recommendations to be made for optimal choice of antibiotics for exacerbations of COPD. Emerging data that antibiotics differ in unconventional measures of efficacy such as time to next exacerbation, improvement in health-related quality of life, and bacteriologic eradication will help us make concrete recommendations in the future.     

N-acetylcysteine and exacerbations of chronic obstructive pulmonary disease

Oxidative stress may play a role in chronic obstructive pulmonary disease (COPD) exacerbations. There is heterogeneity in the literature with regard to the impact of antioxidant therapy on COPD exacerbation frequency. Clinical trials of N-acetylcysteine in COPD were identified in unrestricted searches of MEDLINE, CINAHL, International Pharmaceutical Abstracts and the Cochrane Register. Randomized, controlled trials which reported exacerbations over a treatment period > or =3 months were selected. Two observers independently extracted data regarding exacerbation number over the treatment period in subjects allocated to either N-acetylcysteine or placebo. Data were analyzed using inverse-variance weighted random effects meta-analysis methodology. Meta-analysis of data from 8 trials (randomized n = 2,214) indicated that N-acetylcysteine significantly reduced the odds of experiencing one or more exacerbations over the treatment period (odds ratio = 0.49, 95% confidence interval [0.32-0.74], p = 0.001). Treatment effect was not reduced in studies which enrolled >50% active smokers (odds ratio = 0.36 [0.24-0.55], p < 0.001), although a greater effect was observed with exclusion of subjects using concurrent inhaled corticosteroids (odds ratio = 0.42 [0.32-0.54], p < 0.0001), suggesting that inhaled steroids attenuate the effect of N-acetylcysteine. The use of N-acetylcysteine significantly reduces the odds of exacerbation in patients with COPD, an effect possibly attenuated by inhaled steroids but not smoking. This analysis suggests treatment with N-acetylcysteine may be beneficial in a subset of patients with COPD.     

Pharmacotherapeutic approaches to preventing acute exacerbations of chronic obstructive pulmonary disease

The significance of acute exacerbations in chronic obstructive pulmonary disease (AECOPDs) is increasingly appreciated. AECOPDs result in significant morbidity and mortality and are a significant driver of health care costs. Frequent AECOPDs are associated with poor quality of life and more rapid decline in lung function. As such, reducing their frequency or severity is a key paradigm of COPD therapy. Bronchodilators alone and in combination with inhaled corticosteroids are the current standards of care and decrease AECOPDs. Prevention of infection with chronic macrolide antibiotics or pulsed quinolones has demonstrated some promise. Vaccination against Streptococcus pneumonia and influenza is likely beneficial. Therapeutics with antiinflammatory properties, including phosphodiesterase enzyme 4 inhibitors and HMG-CoA reductase inhibitors, may reduce AECOPD frequency. Inhibiting the formation of reactive oxidant species has also been studied, with varying results. Antioxidants, including N-acetylcysteine and S-carbomethylcysteine, may reduce exacerbation frequency, but further investigation is needed. As new therapies are developed, it will be helpful to know in which patient phenotypes they are most effective and how they compare in efficacy and side-effect profiles with inhaled coricosteroids, bronchodilators, or their combination.