Chest
Volume 119, Issue 4, April 2001, Pages 1190-1209
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Special Report
Management of Acute Exacerbations of COPD: A Summary and Appraisal of Published Evidence

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Study objectives

To critically review the available data on the diagnostic evaluation, risk stratification, and therapeutic management of patients with acute exacerbations of COPD.

Design, setting, and participants

English-language articles were identified from the following databases: MEDLINE (from 1966 to week 5, 2000), EMBASE (from 1974 to week 18, 2000), Health Star (from 1975 to June 2000), and the Cochrane Controlled Trials Register (2000, issue 1). The best available evidence on each subtopic then was selected for analysis. Randomized trials, sometimes buttressed by cohort studies, were used to evaluate therapeutic interventions. Cohort studies were used to evaluate diagnostic tests and risk stratification. Study design and results were summarized in evidence tables. Individual studies were rated as to their internal validity, external validity, and quality of study design. Statistical analyses of combined data were not performed.

Measurement and results

Limited data exist regarding the utility of most diagnostic tests. However, chest radiography and arterial blood gas sampling appear to be useful, while short-term spirometry measurements do not. In terms of the risk of relapse and the risk of death after hospitalization for an acute exacerbation, there are identifiable clinical variables that are associated with these outcomes. Therapies for which there is evidence of efficacy include bronchodilators, corticosteroids, and noninvasive positive-pressure ventilation. There is also support for the use of antibiotics in patients with more severe exacerbations. Based on limited data, mucolytics and chest physiotherapy do not appear to be of benefit, and oxygen supplementation appears to increase the risk of respiratory failure in an identifiable subgroup of patients.

Conclusions

Although suggestions for appropriate management can be made based on available evidence, the supporting literature is spotty. Further high-quality research is needed and will require an improved, generally acceptable, and transportable definition of the syndrome “acute exacerbation of COPD” and improved methods for observing and measuring outcomes.

Section snippets

COPD

In the United States at present, > 16 million adults areafflicted with COPD, a slowly progressive condition that typicallybecomes symptomatic in the fifth and sixth decade of life. As the USpopulation ages, the prevalence of this disease is expected toclimb.2 COPD currently accounts for approximately 110,000 deaths per year, making it, after heart disease, cancer, and stroke, the fourth leading cause of death. Nonasthma COPD in the United States annually accounts for 16,367,000 office visits,

What Is an Acute Exacerbation of COPD?

In evaluating the published literature, and in developing practiceguidelines, we have attempted to adhere to a generally accepted anduseful concept of an acute exacerbation or flareof COPD. Unfortunately, many definitions exist, many authors employsubstantively different criteria, and many studies poorly describetheir inclusion criteria. As a generalization, however, most publisheddefinitions embrace some combination of the following three clinicalfindings: worsening of dyspnea; increase in

Identification of Topics for Literature Search

Topics to be covered in this article and in the practiceguideline were determined through a consensus process that involvedboth the ACP-ASIM/ACCP expert panel and the technical advisory panel ofthe Evidence-Based Practice Center at Duke University (Durham, NC). Thetopic list was generated to address the following three questions: (1)what information is available to aid clinicians in predicting theclinical course of a patient with an acute exacerbation?; (2) whatinformation is available about

Approach to the Patient With an Acute Exacerbation of COPD

In the following section, we discuss our recommendations andfindings for the following three domains of care for patients withacute exacerbations of COPD: risk stratification of patients(specifically, data on predictors of outpatient relapse) and predictorsof inpatient mortality; choice of diagnostic tests; and benefits andrisks of therapeutic interventions, including mucus clearancestrategies, bronchodilating agents, corticosteroids, antibiotics, oxygen, and noninvasive mechanical ventilation.

Prediction of Outpatient Relapse

Based on 10 studies that evaluated patients with acuteexacerbations of COPD in emergency departments (7 studies) and in theoutpatient setting (3 studies), we concluded that certaincharacteristics are associated with patients returning for moretreatment rather than with those experiencing gradual improvement(Table 7). The ability to identify patients at high risk for relapseshould improve decisions about hospital admissions and follow-upappointments. Several investigators have confirmed that

General Approach

Many assessment techniques frequently are used in evaluatingpatients with acute exacerbations of COPD. These include measuringroutine laboratory values, performing a physical examination, obtainingan ECG, assessing cardiac function, and instituting an empiric trial of diuretics. We found no published evidence that could help us todetermine the utility of these approaches. For another commonly usedassessment (arterial blood gas sampling), we found indirect evidence ina number of studies

Bronchodilating Agents

Based on 14 randomized studies, we concluded the following: thatshort-acting β-agonist-type and anticholinergic-type inhaledbronchodilators have comparable effects on spirometry and a greatereffect than all parenterally administered bronchodilators(ie, parenteral methylxanthines and sympathomimetics); thatthe toxicity profile of the methylxanthine agents makes thempotentially harmful; and that there may be an additional benefit insome patients when a second bronchodilating agent is administered

Research Priorities

In a disease held responsible for 5% of all deaths in the United States, enormous disability, and $18 billion dollars in annualhealth-care costs, the paucity of primary data on therapeuticsis startling. We found that in more than 40 years of research, fewerthan 1,100 patients had been enrolled in randomized, placebo-controlledtrials of antibiotics, fewer than 650 patients had been enrolled instudies of corticosteroids vs placebo (before the 1999 SCOPPE trial, the count was less than 400), and

ACKNOWLEDGMENT

We gratefully acknowledge the assistance of thecombined ACP-ASIM and ACCP expert panel, the Evidence-Based Center peerreview and technical advisory panels, and the efforts of Ruth E. Goslin, MAT, and Rebecca N. Gray, DPhil.

References (128)

  • CL Emerman et al.

    Effect of different albuterol dosing regimens in the treatment of acute exacerbation of chronic obstructive pulmonary disease

    Ann Emerg Med

    (1997)
  • JJ Seidenfeld et al.

    Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease

    Ann Emerg Med

    (1984)
  • M Shrestha et al.

    Decreased duration of emergency department treatment of chronic obstructive pulmonary disease exacerbations with the addition of ipratropium bromide to β-agonist therapy

    Ann Emerg Med

    (1991)
  • DM Patrick et al.

    Severe exacerbations of COPD and asthma: incremental benefit of adding ipratropium to usual therapy

    Chest

    (1990)
  • AS Rebuck et al.

    Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room

    Am J Med

    (1987)
  • CL Emerman et al.

    Risk of toxicity in patients with elevated theophylline levels

    Ann Emerg Med

    (1990)
  • RB Berry et al.

    Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD

    Chest

    (1989)
  • AC Jasper et al.

    Cost-benefit comparison of aerosol bronchodilator delivery methods in hospitalized patients

    Chest

    (1987)
  • GP Maguire et al.

    Comparison of a hand-held nebulizer with a metered dose inhaler-spacer combination in acute obstructive pulmonary disease

    Chest

    (1991)
  • JR Turner et al.

    Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction

    Chest

    (1988)
  • MJ Bullard et al.

    Early corticosteroid use in acute exacerbations of chronic airflow obstruction

    Am J Emerg Med

    (1996)
  • CL Emerman et al.

    A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD

    Chest

    (1989)
  • L Davies et al.

    Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial

    Lancet

    (1999)
  • DG Berry et al.

    Exacerbations of chronic bronchitis: treatment with oxytetracycline

    Lancet

    (1960)
  • EC Fear et al.

    Antibiotic regimes in chronic bronchitis

    Br J Dis Chest

    (1962)
  • A Pines et al.

    Antibiotic regimens in moderately ill patients with purulent exacerbations of chronic bronchitis

    Br J Dis Chest

    (1972)
  • RC Bone et al.

    Controlled oxygen administration in acute respiratory failure in chronic obstructive pulmonary disease: a reappraisal

    Am J Med

    (1978)
  • JH Langlands

    Double-blind clinical trial of bromhexine as a mucolytic drug in chronic bronchitis

    Lancet

    (1970)
  • J Bott et al.

    Randomised controlled trial of nasal ventilation in acute ventilatory failure because of chronic obstructive airways disease

    Lancet

    (1993)
  • Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Report No. 19

    (2000)
  • The National Lung Health Education Program

    Strategies in preserving lung health and preventing COPD and associated diseases

    Chest

    (1998)
  • Statistical abstract of the United States 1997; US Department of Commerce, Bureau of the Census

    (1997)
  • Healthcare cost and utilization project: nationwide inpatient sample for 1997

  • TL Petty et al.

    Building a national strategy for the prevention and management of and research in chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute Workshop Summary; Bethesda, Maryland, August 29–31, 1995

    JAMA

    (1997)
  • NR Anthonisen et al.

    Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease

    Ann Intern Med

    (1987)
  • DW Gump et al.

    Role of infection in chronic bronchitis

    Am Rev Respir Dis

    (1976)
  • CD Beaty et al.

    Chlamydia pneumoniae, strain TWAR, infection in patients with chronic obstructive pulmonary disease

    Am Rev Respir Dis

    (1991)
  • CB Smith et al.

    Interactions between viruses and bacteria in patients with chronic bronchitis

    J Infect Dis

    (1976)
  • T Schaberg et al.

    An analysis of decisions by European general practitioners to admit to hospital patients with lower respiratory tract infections

    Thorax

    (1996)
  • J Schwartz

    Air pollution and hospital admissions for the elderly in Detroit, Michigan

    Am J Respir Crit Care Med

    (1994)
  • AF Connors et al.

    Outcomes following acute exacerbation of severe chronic obstructive lung disease: the SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments)

    Am J Respir Crit Care Med

    (1996)
  • TA Seemungal et al.

    Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2000)
  • TA Seemungal et al.

    Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (1998)
  • AI Mushlin et al.

    The necessary length of hospital stay for chronic pulmonary disease

    JAMA

    (1991)
  • RH Burk et al.

    Acute respiratory failure in chronic obstructive pulmonary disease: immediate and long-term prognosis

    Arch Intern Med

    (1973)
  • MG Seneff et al.

    Hospital and 1-year survival of patients admitted to ICUs with acute exacerbation of chronic obstructive pulmonary disease

    JAMA

    (1995)
  • AF Connors et al.

    Effect of inspiratory flow rate on gas exchange during mechanical ventilation

    Am Rev Respir Dis

    (1981)
  • H Peach et al.

    Follow-up study of disability among elderly patients discharged from hospital with exacerbations of chronic bronchitis

    Thorax

    (1981)
  • AW Wu et al.

    Predicting future functional status for seriously ill hospitalized adults: the SUPPORT prognostic model

    Ann Intern Med

    (1995)
  • M Weinberger et al.

    Does increased access to primary care reduce hospital readmissions?

    N Engl J Med

    (1996)
  • Cited by (0)

    This article is based on research conducted by investigators at Memorial Sloan-Kettering Cancer Center, New York, NY, under contractwith the ACP–ASIM and the ACCP, and by investigators at Duke University, Durham, NC, under contract with the Agency for Healthcare Research and Quality (contract No. 290–97-0014).

    This paper also appeared in Annals of Internal Medicine 2001; 134:600–620

    The authors of this article are responsible for its contents, includingany clinical or treatment recommendations. No statement in this articleshould be construed as an official position of the Agency for Healthcare Research and Quality of the US Department of Health and Human Services.

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