Chest
Volume 117, Issue 3, March 2000, Pages 662-671
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Clinical Investigations
COPD
Acute Exacerbation of COPD

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Objectives

To determine the effect of age, severity of lung disease, severity and frequency of exacerbation, steroid use, choice of an antibiotic, and the presence of comorbidity on the outcome of treatment for an acute exacerbation of COPD.

Design

A retrospective chart analysis over 24 months.

Setting

A university Veterans Affairs medical center.

Patients

Outpatients with COPD who were treated with an antibiotic over a period of 24 months for an acute exacerbation of COPD.

Methods

Severity of an acute exacerbation of COPD was defined using the criteria of Anthonisen et al: increased dyspnea, increased sputum volume, and increased sputum purulence. Severity of lung disease was stratified based on FEV1 percent predicted using American Thoracic Society guidelines (stage I, FEV1 ≥ 50%; stage II, FEV1 35 to 49%; stage III, FEV1 < 35%). Treatment outcome was judged successful when the patient had no return visit in 4 weeks for a respiratory problem. Failure was defined as a return visit for persistent respiratory symptoms that required a change of an antibiotic in < 4 weeks.

Results

One-hundred seven patients with COPD (mean age ± SD, 66.9 ± 9.5 years) experienced 232 exacerbations over 24 months. First-line antibiotics (trimethoprim-sulfamethoxazole, ampicillin/amoxicillin, and erythromycin) were used to treat 78% of all exacerbations. Treatment failure was noted in 12.1% of first exacerbations and 14.7% of all exacerbations, with more than half the failures requiring hospitalization. Host factors that were independently associated with treatment failure included the following: FEV1 < 35% (46.4% vs 22.4%; p = 0.047), use of home oxygen (60.7% vs 15.6%; p < 0.0001), frequency of exacerbation (3.8 ± 2.0 vs 1.6 ± 0.91; p < 0.001), history of previous pneumonia (64.3% vs 35.1 p < 0.007), history of sinusitis (28.6% vs 8.8%; p < 0.009) and use of maintenance steroids (32.1% vs 15.2% p = 0.052). Using stepwise logistic regression analysis to identify the top independent variables, the use of home oxygen (p = 0.0002) and frequency of exacerbation (p < 0.0001) correctly classified failures in 83.3% of the patients. Surprisingly, age, the choice of an antibiotic, and the presence of any one or more comorbidity did not affect the treatment outcome.

Conclusion

The results of our study suggest that patient host factors and not antibiotic choice may determine treatment outcome. Prospective studies in appropriately stratified patients are needed to validate these findings.

Section snippets

Study Design and Patient Selection

This study was a retrospective collection of data over 24 months in outpatients with COPD who were treated with an antibiotic for an acute exacerbation of COPD. Patients were initially screened from the pharmacy records for an ongoing antibiotic study in acute exacerbation of COPD. Patients who were either receiving an inhaled or an oral bronchodilator, or both, and had received an antibiotic prescription were identified from the pharmacy records. Between January 1995 and June 1997, a total of

Results

One hundred seven patients with COPD experienced a total of 232 acute exacerbations over a period of 24 months. Demographic and baseline clinical characteristics are listed in Table 1. The age (mean ± SD) was 66.9 ± 9.5 years. Ninety-five patients (88.8%) were either current smokers or ex-smokers. Sixty-four patients (61.5%) had moderate (stage II) to severe (stage III) airflow obstruction. Twenty-nine patients (27.1%) were using home oxygen, 21 patients (19.6%) were on maintenance steroids, 45

Correlation of Initial Antibiotic Choice With Treatment Outcome: The frequency of antibiotic use and success rate respectively for different antibiotics in all 232 exacerbations were as follows: trimethoprim-sulfamethoxazole, 50.4% and 86.3%; ampicillin/amoxicillin, 19.4% and 84.4%; erythromycin, 9.5% and 81.8%; amoxicillin-clavulanic acid, 8.6% and 80%; azithromycin, 4.5% and 91%; first generation cephalosporins, 3.5% and 75%; and other antibiotics (ciprofloxacin, cefixime, cefuroxime, and doxycycline), 3.8% and 100%. Overall, first-line antibiotics were used in 182 exacerbations (78%), while the newer second-line antibiotics were used in only 50 exacerbations (22%). Although, a small subgroup of patients who were treated with the newer antibiotics had a 100% success rate, the numbers were too small for any meaningful correlation. Overall, the choice of an antibiotic did not affect the treatment outcome.

Analysis of 28 patients who experienced 34 failures demonstrated that the use of first-line antibiotics in the failure group was 76.5% (26/34) and was similar when compared to the successful group 78% (56/72; p = 0.653). The success rate with first-line antibiotics in this group of 28 patients was 68.2% (56/82) and similar to the success rate with second-line antibiotics 63.6% (14/22). Similarly, analysis of 30 patients with FEV1 < 35% demonstrated that the use of first-line antibiotics was

Treatment Outcome Factors: The treatment outcome factors for all exacerbations are listed in Table 3. Factors that were independently associated with treatment failure included the following: FEV1 < 35% (46.4% vs 22.4%; p = 0.047), use of home oxygen (60.7% vs 15.6%; p < 0.0001); frequency of exacerbation over 24 months (3.8 ± 2.0 vs 1.6 ± 0.9; p < 0.001), history of previous pneumonia (64.3% vs 35.1%; p = 0.007), history of sinusitis (28.6% vs 8.8%; p < 0.009), and the use of maintenance steroids (32.1% vs 15.2%; p = 0.052). The average cumulative steroid dosage (milligrams per day) over 24 months was also significantly higher in the group of patients who had at least one failure as compared to patients with no failure (12.1 ± 8.2 vs 5.1 ± 3.7 mg; p = 0.017). Surprisingly, age and the presence of any one, two, or more than two comorbidities did not affect the treatment outcome.

A subgroup analysis of the 18 patients who were hospitalized demonstrated a significantly lower FEV1 < 35% (67% vs 10%; p < 0.006) and a more frequent use of home oxygen (78% vs 30%; p < 0.020) when compared to the 10 patients who failed but did not require hospitalization. Pathogens recovered from sputum cultures in these hospitalized patients included Moraxella catarrhalis,1Haemophilus influenzae,1 and Pseudomonas aeruginosa.1 There was no significant difference in the treatment outcome

Discussion

The outcome of any given treatment is generally dependent on the severity of illness, host factors, and the specific treatment given.3, 1213 Host factors that may affect the treatment outcome in acute exacerbation of COPD include age, severity of underlying lung disease, and the presence of comorbidity.5, 6 The results from our study in this group of COPD patients demonstrate that patients who had severe underlying lung disease and had greater frequency and severity of exacerbation were more

ACKNOWLEDGMENT

The authors greatly appreciate the assistance of Mike Caldwell, RRT, and Chris Harvey, RRT, for retrieving charts and data entry, and Mona Coburn and Cindy Hanneman for secretarial assistance.

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    Presented at the International Assembly of American College of Chest Physicians, Toronto, Canada, November 10, 1998.

    Dr. Dewan is the recipient of a research grant from Bayer Pharmaceuticals, Inc. and serves on their speaker's bureau.

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