Therapeutics

Review: Inuenza vaccination and Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute ex-
acerbations of COPD: American College of Chest Physicians and
inhaled therapies prevent acute Canadian Thoracic Society Guideline. Chest. 2015;147:894-942.

exacerbations in COPD
Clinical impact ratings:

Question months of follow-up and were published in English. 8 guidelines

In patients with chronic obstructive pulmonary disease (COPD), and 53 systematic reviews were included. Grade 1A (a strong
do nonpharmacologic, inhaled, or oral therapies prevent acute recommendation based on high-quality evidence) and 1B (a
exacerbations? strong recommendation based on moderate-quality evidence)
recommendations are presented in this abstract.
Review scope Main results
Included studies assessed the effects of nonpharmacologic treat-
ments (including vaccinations), maintenance inhaled therapy, or The main results are in the Table.
oral therapy in adults > 40 years of age who had spirometry- Conclusion
conrmed COPD (FEV1/ FVC < 0.70) and were previous or current In patients with chronic obstructive pulmonary disease, inuenza
smokers. Outcomes included COPD exacerbations. vaccination and inhaled therapies prevent acute exacerbations.
Review methods Sources of funding: American College of Chest Physicians and
Separate searches were conducted for each specic nonphar- Canadian Thoracic Society.
macologic, inhaled, and oral therapy. For each treatment cate-
gory, MEDLINE and Cochrane CENTRAL were searched for sys- For correspondence: Dr. G.J. Criner, Temple University School of
tematic reviews published between 2007/2008 and 2013, and Medicine, Philadelphia, PA, USA. E-mail gerard.criner@tuhs
Guidelines International Network Library and National Guideline .temple.edu.
Clearinghouse (Jan 2013) were searched for relevant guide- Commentary
lines. Relevant systematic reviews were updated, using their
original search strategies, which always included MEDLINE and The guideline by Criner and colleagues is atypical in that it fo-
Cochrane CENTRAL and often other major bibliographic data- cuses on a single disease outcome (exacerbations) rather than
bases and reference lists. The search for oral therapies included COPD as a whole. As a result, the recommendations have evalu-
primary database searches for specic therapies that did not ated interventions out of their full context and may seem odd
have relevant systematic reviews. Included studies had 3 unless the guideline's narrow focus is considered. For example,
it assigned smoking cessation the weakest recommendation
grade, despite acknowledging that it is the only evidence-based
intervention that alters the natural history of COPD, and recom-
Interventions to prevent acute exacerbations in chronic mended pulmonary rehabilitation only within 4 weeks of an exacer-
obstructive pulmonary disease (COPD)* bation, while noting that rehabilitation at any time is the most effec-
Recommendation (Grade) Evidence
tive therapy known for improving quality of life in COPD.
Vaccination The guideline found that long-acting muscarinic antagonists
In patients with COPD, administer an- Meta-analysis of 180 patients showed that
(LAMAs) alone, inhaled corticosteroids (ICSs)/long-acting 2-
nual inuenza vaccination to prevent inactivated inuenza vaccine reduced the agonists (LABAs), LAMA/LABA, or triple therapy (ICS/LABA/
acute exacerbation (1B). number of exacerbations per patient com- LAMA) are each effective in preventing exacerbations and bet-
pared with placebo (WMD 0.37, 95% CI
0.64 to 0.11). ter than other inhaled options. If exacerbations were the only
Maintenance inhaled therapy issue, monotherapy would seem to be favored based on cost,
side effects, and simplicity, but in practice other therapeutic
In patients with moderate to severe Meta-analyses showed that LABAs re-
COPD, use LABAs to prevent moderate duced risk for moderate (OR 0.73, CI goals dictate choices. For example, other guidelines preferen-
to severe acute exacerbations (1B). 0.61 to 0.87, 7 studies, n = 3375) or se- tially support LAMA/LABA-containing regimens in patients more
vere (OR 0.73, CI 0.56 to 0.95, 7 studies,
n = 2859) exacerbations compared with limited by dyspnea (1) or ICS-containing regimens in patients
placebo. with the asthmaCOPD overlap syndrome (2).
In patients with moderate to severe Meta-analysis of 22 studies (n = 22 309) Although the strongest efcacy and safety evidence favored in-
COPD, use LAMAs to prevent moder- found that tiotropium, delivered by Han-
ate to severe acute exacerbations (1A). diHaler or Respimat system, prevented haled therapies, weaker evidence supported such oral therapies
exacerbations more than placebo (OR as macrolides, phosphodiesterase type 4 inhibitors, theophyl-
0.78, CI 0.70 to 0.87).
line, and N-acetylcysteine, which may be helpful when inhaled
In patients with moderate to severe Meta-analysis of 2 studies (n = 1073)
COPD, use LAMAs rather than short- found that tiotropium prevented exacer- options alone are insufcient. The guideline also found evi-
acting muscarinic antagonists to pre- bations compared with ipratropium (OR dence for benet from combined education and case manage-
vent moderate to severe acute exacer- 0.71, CI 0.52 to 0.95).
bations (1A). ment, but not for either method alone. The studies evaluated for
this method had health professionals contact patients at least
In patients with stable moderate to very Existing national and international guide-
severe COPD, use maintenance combi- lines recommend combination therapy. monthly, and hence the guideline specically endorses it, but
nation ICS/LABA rather than placebo the true optimal contact interval is unknown.
(1B) or ICS monotherapy (1B) to pre-
vent acute exacerbations.
This guideline was constructed with great methodological rigor
Oral therapy and attention to mitigation of competing interests. The result is
In patients with an acute COPD exacer- Meta-analysis showed that treatment of likely the most robust and credible COPD guideline to date.
bation, do not use systemic corticoste- exacerbations with systemic corticoste-
roids for the sole purpose of prevent- roids for 6 mo after an exacerbation did Matthew B. Stanbrook, MD, PhD
ing hospitalization for subsequent not prevent subsequent exacerbations
acute exacerbations beyond the rst within 6 months compared with placebo University Health Network, University of Toronto
30 d after an exacerbation (1A). (OR 1.6, CI 0.34 to 7.51).
Toronto, Ontario, Canada
In patients with moderate to severe 1 study showed that statins did not differ
COPD and high risk for exacerbations, from placebo for exacerbations (1.36 vs
do not use statins to prevent acute ex- 1.39 per person/y, P = 0.54). References
acerbations (1B).
1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global
Strategy for the Diagnosis, Management and Prevention of COPD 2015.
*ICS = inhaled corticosteroid; LABA = long-acting 2-agonist; LAMA = long-acting
muscarinic antagonist; OR = odds ratio; WMD = weighted mean difference; other www.goldcopd.org (accessed 16 July 2015).
denitions in Glossary. 2. Global Initiative for Asthma (GINA), Global Initiative for Chronic Obstructive
Grade 1A (strong recommendation based on high-quality evidence) and 1B (strong Lung Disease (GOLD). Diagnosis of diseases of chronic airow limitation:
recommendation based on moderate-quality evidence) recommendations and asthma, COPD and asthma-COPD overlap syndrome (ACOS) (updated 2015).
evidence. www.ginasthma.org/local/uploads/les/ACOS_2015.pdf (accessed 16 July 2015).

15 Sep 2015 Annals of Internal Medicine ACP Journal Club JC3 2015 American College of Physicians
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