Implementing AHRQ Effective Health Care Reviews

Helping Clinicians Make Better Treatment Choices

Therapies for COPD Exacerbations in Adults

 

Am Fam Physician. 2020 May 1;101(9):557-559.

Author disclosure: No relevant financial affiliations.

Key Clinical Issue

What are the benefits and harms of pharmacologic and nonpharmacologic treatments for exacerbations of chronic obstructive pulmonary disease (COPD) in adults?

Evidence-Based Answer

In adults with exacerbations of COPD, antibiotic therapy increases the clinical cure rate and decreases the clinical failure rate. (Strength of Recommendation [SOR]: A, based on consistent, good-quality patient-oriented evidence.) Systemic corticosteroid therapy improves dyspnea and reduces the clinical failure rate. (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) Titrated oxygen reduces mortality when compared with high flow oxygen. (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) Resistance training improves dyspnea and quality of life. (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) Early pulmonar y rehabilitation initiated during hospitalization improves dyspnea.1 (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

COPD affects 10% of the global population. In the United States, it affects 15 million people, is the fourth leading cause of death, and costs the health care system $32 billion each year.1 COPD is a chronic disease marked by exacerbations that impact quality of life and are potentially fatal. This Agency for Healthcare Research and Quality (AHRQ) review was conducted to evaluate the effectiveness and harms of pharmacologic and nonpharmacologic treatments for COPD exacerbations in adults.1

The review included 98 randomized controlled trials (RCTs) encompassing 13,401 patients. When compared with placebo, antibiotic therapy improved the clinical cure rate (three RCTs with 683 patients; odds ratio [OR] = 2.03; 95% CI, 1.47 to 2.80) and decreased the clinical failure rate by the end of the intervention (two RCTs with 405 patients; OR = 0.54; 95% CI, 0.34 to 0.86). Clinical cure was defined as improvement in signs and symptoms; clinical failure was defined as a lack of improvement in signs and symptoms or the need for additional treatment. There were no differences in clinical failure rates at the longest follow-up, hospital readmissions at 30 days, repeat exacerbations at 30 days, or adverse events. Multiple comparisons among antibiotics, doses, and durations were mostly insufficient for showing an improvement in clinical cure and failure rates, repeat exacerbations, and mortality.

In general, systemic corticosteroids were more effective than placebo in improving dyspnea on a numeric scale (two RCTs with 154 patients; standardized mean difference = 0.40; 95% CI, 0.07 to 0.70) and reducing clinical failure rate at the end of the intervention (two RCTs with 217 patients; OR = 0.01; 95% CI, 0.00 to 0.13). Some evidence indicated that total adverse events were higher with systemic corticosteroids compared with placebo (rate ratio = 1.55; 95% CI, 1.14 to 2.10), but there was no difference in serious adverse events such as gastrointestinal bleeding, hypertension, or psychiatric disorders. The evidence was insufficient to compare different corticosteroids with respect to dyspnea, clinical failure, and death. Evidence was insufficient to compare different routes of administration and duration of corticosteroid use. The evidence was insufficient to determine the effects of other pharmacologic agents, including inhaled antibiotics, inhaled corticosteroids, magnesium, and mucolytics.

 Enlarge     Print

CLINICAL BOTTOM LINE

Comparison of Treatments for COPD Exacerbation: Critical Outcomes

ComparatorOutcomeNumber of trials and participantsFindingsStrength of evidence

Antibiotic therapy

Placebo

Clinical cure rate at end of intervention

3 RCTs with 683 patients

OR = 2.03; 95% CI, 1.47 to 2.80 Improvement

● ● ○

Placebo

Clinical failure rate at end of intervention

2 RCTs with 405 patients

OR = 0.54; 95% CI, 0.34 to 0.86 Improvement

● ● ○

Placebo

Clinical failure rate at longest follow-up

2 RCTs with 570 patients

OR = 0.82; 95% CI, 0.58 to 1.14 No change

● ○ ○

No antibiotics

30-day hospital readmission

1 RCT with 194 patients

OR = 1.72; 95% CI, 0.68 to 4.36 No change

● ○ ○

Placebo or no antibiotics

Repeat exacerbation at 30 days

2 RCTs with 229 patients

OR = 1.69; 95% CI, 0.78 to 3.68 No change

● ○ ○

Placebo or no antibiotics

Adverse events

Multiple studies

No change

● ○ ○

Systemic corticosteroids

Placebo

Dyspnea

2 RCTs with 154 patients

SMD = 0.40; 95% CI, 0.07 to 0.70 Improvement

● ○ ○

Placebo

Clinical failure rate at end of intervention

2 RCTs with 217 patients

OR = 0.01; 95% CI, 0.00 to 0.13 Improvement

● ○ ○

Placebo

Serious adverse events

2 RCTs

Rate ratio = 0.73; 95% CI, 0.27 to 1.97 No change

● ○ ○

Placebo

Total adverse events

4 RCTs

Rate ratio = 1.55; 95% CI, 1.14 to 2.10 More adverse events

● ● ○

Resistance training

No resistance training

Dyspnea

1 RCT with 60 patients

WMD = −2.11; 95% CI, −3.50 to −0.72 Improvement

● ○ ○

No resistance training

Quality of life at end of intervention

1 RCT with 60 patients

WMD = 18.70; 95% CI, 5.06 to 32.34 Improvement

● ○ ○

Whole-body vibration

No whole-body vibration

Quality of life

1 RCT with 49 patients

WMD = −12.02; 95% CI, −21.41 to −2.63 Improvement

● ○ ○

Titrated oxygen

High flow oxygen

Mortality at longest follow-up

1 RCT with 214 patients

OR = 0.36; 95% CI, 0.14 to 0.88 Improvement

● ○ ○

Vitamin D supplementation

Placebo

Quality of life at longest follow-up

1 RCT with 70 patients

WMD = −4.67; 95% CI, −6.00 to −3.35 Improvement

● ○ ○


Strength of evidence scale

● ● ● High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change the confidence in the estimate of effect.

● ● ○ Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change the confidence in the estimate of effect and may change the estimate.

● ○ ○ Low: Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.

○ ○ ○ Insufficient: Evidence either is unavailable or does not permit a conclusion

COPD = chronic obstructive pulmonary disease; OR = odds ratio; RCT = randomized controlled trial; SMD = standardized mean difference; WMD = weighted mean difference.

Adapted from Dobler CC, Marrow AS, Farah MH, et al. Pharmacologic and nonpharmacologic therapies in adult patients with exacerbation of COPD: a systematic review. Comparative Effectiveness Review No. 221. (Prepared by the Mayo Clinic Evidence-Based Practice Center under contract no. 290-2015-00013-I.) AHRQ publication no. 19(20)-EHC024-EF. Rockville, Md.: Agency for Healthcare Research and Quality; October 2019. Accessed January 24, 2020. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/cer-221-copd-final-report.pdf

CLINICAL BOTTOM LINE

Comparison of Treatments for COPD Exacerbation: Critical Outcomes

ComparatorOutcomeNumber of trials and participantsFindingsStrength of evidence

Antibiotic therapy

Placebo

Clinical cure rate at end of intervention

3 RCTs with 683 patients

OR = 2.03; 95% CI, 1.47 to 2.80 Improvement

● ● ○

Placebo

Clinical failure rate at end of intervention

2 RCTs with 405 patients

OR = 0.54; 95% CI, 0.34 to 0.86 Improvement

● ● ○

Placebo

Clinical failure rate at longest follow-up

2 RCTs with 570 patients

OR = 0.82; 95% CI, 0.58 to 1.14 No change

● ○ ○

No antibiotics

30-day hospital readmission

1 RCT with 194 patients

OR = 1.72; 95% CI, 0.68 to 4.36 No change

● ○ ○

Placebo or no antibiotics

Repeat exacerbation at 30 days

2 RCTs with 229 patients

OR = 1.69; 95% CI, 0.78 to 3.68 No change

● ○ ○

Placebo or no antibiotics

Adverse events

Multiple studies

No change

● ○ ○

Systemic corticosteroids

Placebo

Dyspnea

2 RCTs with 154 patients

SMD = 0.40; 95% CI, 0.07 to 0.70 Improvement

● ○ ○

Placebo

Clinical failure rate at end of intervention

2 RCTs with 217 patients

OR = 0.01; 95% CI, 0.00 to 0.13 Improvement

● ○ ○

Placebo

Serious adverse events

2 RCTs

Rate ratio = 0.73; 95% CI, 0.27 to 1.97 No change

● ○ ○

Placebo

Total adverse events

4 RCTs

Rate ratio = 1.55; 95% CI, 1.14 to 2.10 More adverse events

● ● ○

Resistance training

No resistance training

Dyspnea

1 RCT with 60 patients

WMD = −2.11; 95% CI, −3.50 to −0.72 Improvement

● ○ ○

No resistance training

Quality of life at end of intervention

1 RCT with 60 patients

WMD = 18.70; 95% CI, 5.06 to 32.34 Improvement

● ○ ○

Whole-body vibration

No whole-body vibration

Quality of life

1 RCT with 49 patients

WMD = −12.02; 95% CI, −21.41 to −2.63 Improvement

● ○ ○

Titrated oxygen

High flow oxygen

Mortality at longest follow-up

1 RCT with 214 patients

OR = 0.36; 95% CI, 0.14 to 0.88 Improvement

● ○ ○

Vitamin D supplementation

Placebo

Quality of life at longest follow-up

1 RCT with 70 patients

WMD = −4.67; 95% CI, −6.00 to −3.35 Improvement

● ○ ○


Strength of evidence scale

● ● ● High: High confidence that the evidence reflects the true effect. Further research is very unlikely to change the confidence in the estimate of effect.

● ● ○ Moderate: Moderate confidence that the evidence reflects the true effect. Further research may change the confidence in the estimate of effect and may change the estimate.

● ○ ○ Low: Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.

○ ○ ○ Insufficient: Evidence either is unavailable or does not permit a conclusion

COPD = chronic obstructive pulmonary disease; OR = odds ratio; RCT = randomized controlled trial; SMD = standardized mean difference; WMD = weighted mean difference.

Adapted from Dobler CC, Marrow AS, Farah MH, et al. Pharmacologic and nonpharmacologic therapies in adult patients with exacerbation of COPD: a systematic review. Comparative Effectiveness Review No. 221. (Prepared by the Mayo Clinic Evidence-Based Practice Center under contract no. 290-2015-00013-I.) AHRQ publication no. 19(20)-EHC024-EF. Rockville, Md.: Agency for Healthcare Research and Quality; October 2019. Accessed January 24, 2020. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/cer-221-copd-final-report.pdf

Resistance training involving the upper and lower body with progressively increased elastic band tension and number of exercise repetitions for nine days was helpful in relieving dyspnea (one RCT with 60 patients; weighted mean difference [WMD] = −2.11 on the 10-point Modified Borg scale, small effect; 95% CI, −3.50 to −0.72) and improving quality of life (one RCT with 60 patients; WMD = 18.70 on the 100-point EQ-5D visual analog scale, small effect; 95% CI, 5.06 to 32.34) when compared with no resistance training. Evidence was insufficient to demonstrate a benefit of resistance training with respect to hospital readmissions and mortality.

Whole-body vibration improved quality of life (one RCT with 49 patients; WMD = −12.02 on the 100-point St. George's Respiratory Questionnaire, small effect; 95% CI, −21.41 to −2.63) when compared with no vibration. Titrated oxygen (to keep oxygen saturation between 88% and 92%) improved prehospital and in-hospital mortality at the longest follow-up (one RCT with 214 patients; OR = 0.36; 95% CI, 0.14 to 0.88) when compared with high flow oxygen. There was no evidence of benefit associated with chest physiotherapy. Early pulmonary rehabilitation initiated during hospitalization for exacerbation was found to improve six-minute walking difference (three RCTs with 253 patients; WMD = 20.02; 95% CI, 12.06 to 28.67), but there was not enough evidence to show a readmission or mortality benefit. There was no significant difference in adverse events between those who received nonpharmacologic therapies and those who did not.

This AHRQ review emphasizes many therapies that family physicians are already using for their patients experiencing COPD exacerbations, such as antibiotics and corticosteroid therapy, while also suggesting that magnesium and mucolytics may not be helpful. Nonpharmacologic therapies such as resistance training and whole-body vibration may be beneficial. The American Academy of Family Physicians is developing a clinical practice guideline based on the AHRQ review. Current guidelines from the U.S. Department of Veterans Affairs/U.S. Department of Defense and the Global Initiative for Chronic Obstructive Lung Disease recommend a five- to seven-day course of antibiotics and systemic corticosteroids with titrating oxygen therapy to maintain a saturation of 88% to 92% for adults with COPD exacerbations.2,3

Editor's Note: AFP SOR ratings are different from the AHRQ Strength of Evidence ratings. Dr. Saguil is a contributing editor for AFP.

The views expressed in this article are the author's and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences, the Department of Defense, or the U.S. government.

Address correspondence to Aaron Saguil, MD, MPH, at aaron.saguil@usuhs.edu. Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.

References

1. Dobler CC, Morrow AS, Farah MH, et al. Pharmacologic and nonpharmacologic therapies in adult patients with exacerbation of COPD: a systematic review. Comparative Effectiveness Review No. 221. (Prepared by the Mayo Clinic Evidence-Based Practice Center under contract no. 290-2015-00013-I.) AHRQ publication no. 19(20)-EHC024-EF. Rockville, Md.: Agency for Healthcare Research and Quality; October 2019. Accessed January 24, 2020. https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/cer-221-copd-final-report.pdf

2. U.S. Department of Veterans Affairs, U.S. Department of Defense. VA/DoD clinical practice guideline for the management of chronic obstructive pulmonary disease. Accessed December 12, 2019. https://www.healthquality.va.gov/guidelines/CD/copd/VADoDCOPDCPG2014.pdf

3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2020 report). Accessed December 12, 2019. https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.1wms.pdf

The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to produce evidence to improve health care and to make sure the evidence is understood and used. A key clinical question based on the AHRQ Effective Health Care Program systematic review of the literature is presented, followed by an evidence-based answer based upon the review. AHRQ's summary is accompanied by an interpretation by an AFP author that will help guide clinicians in making treatment decisions. For the full review go to https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/cer-221-copd-final-report.pdf.

This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

A collection of Implementing AHRQ Effective Health Care Reviews published in AFP is available at https://www.aafp.org/afp/ahrq.

 

 

Copyright © 2020 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


More in Pubmed

MOST RECENT ISSUE


May 1, 2021

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article