In primary care, CRP testing reduced antibiotic use in COPD exacerbations without worsening health Clinical impact ratings:   Question In patients attending primary care for acute exacerbation of chronic obstructive pulmonary disease (COPD), does point-of- care C-reactive protein (CRP) testing to guide antibiotic pre- scribing reduce antibiotic use? Methods Design: Randomized controlled trial (PACE study). ISRCTN24346473. Allocation: {Concealed}*.† Blinding: Blinded† {data collectors and analysts}*. Follow-up period: 6 months. Setting: 86 primary care practices in the UK. Patients: 649 of 653 patients ≥ 40 years of age (mean age 68 y, 52% men) who had COPD and presented with acute exacerba- tion of COPD (≥ 1 of increased dyspnea, sputum volume, or sputum purulence). Exclusion criteria included need for hospital admission, severe illness, concurrent infection at another site, or receipt of antibiotic therapy. Intervention: Usual care plus point-of-care CRP testing and guidance (i.e., antibiotics are unlikely to be beneficial if CRP is < 20 mg/L, may be beneficial if CRP is between 20 and 40 mg/L, and are likely to be beneficial if CRP is > 40 mg/L) (n = 325) or usual care alone (n = 324). Outcomes: Primary outcomes were patient-reported antibiotic use for acute exacerbation of COPD at 4 weeks and COPD- related health status (Clinical COPD Questionnaire) at 2 weeks. Patient follow-up: 83% for antibiotic use and 87% for Clinical COPD Questionnaire (primary analysis complete case as ran- domized, intention-to-treat). Main results The main results are in the Table. Conclusion In primary care patients with acute exacerbation of COPD, usual care plus point-of-care CRP testing to guide antibiotic treatment decisions reduced antibiotic use at 4 weeks without adverse effects on health status at 2 weeks. *Information provided by author. †See Glossary. Source of funding: National Institute for Health Research Health Technology Assessment Program. For correspondence: Dr. C. Butler, University of Oxford, Oxford, England, UK. E-mail christopher.butler@phc.ox.ac.uk.  Commentary Acute exacerbations of COPD can be caused by viral infection, environmental factors, changes in medication, and bacterial infec- tion (1). The use of antibiotics for COPD exacerbations has been studied extensively, but debate persists. A recent Cochrane review found small and inconsistent benefits of antibiotics in outpatients with mild to moderate exacerbations; the authors suggested fur- ther studies to determine which patients might benefit most and to reduce unnecessary use of antibiotics, with their risk for side effects and promotion of bacterial resistance (2). Butler and colleagues have answered this challenge and showed that giving providers point-of-care CRP values reduced antibiotic prescriptions by > 20% overall, with clinical outcomes that were at least as good. Nearly one third of patients with CRP levels in the range where guidance recommended against their use still received antibiotics. This raises the question of whether primary care physicians who are more adherent to CRP guid- ance would see similar outcomes in the full range of patients. There is little reason to think that they would not; thus, encour- aging clinicians to adhere to CRP thresholds seems advisable. Point-of-care CRP deserves further testing in emergency depart- ments and potentially in patients with more severe COPD exac- erbations but seems to be ready for wider implementation in primary care settings. The remaining questions have to do with whether patients and providers in other settings will be more, or less, comfortable treating exacerbations without antibiotics on the basis of CRP results. Henry S. Sacks, PhD, MD Icahn School of Medicine at Mount Sinai New York, New York, USA References 1. Anzueto A, Miravitlles M. Chronic obstructive pulmonary disease exacerba- tions: a need for action. Am J Med. 2018;131:15-22. 2. Vollenweider DJ, Frei A, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmo- nary disease. Cochrane Database Syst Rev. 2018;10: CD010257. Usual care plus point-of-care C-reactive protein (CRP) testing vs usual care alone for acute exacerbation of chronic obstructive pulmonary disease (COPD)‡ Outcomes Event rates At 4 wk CRP testing Usual care RRR (95% CI) NNT (CI) Patient-reported antibiotic use for acute exacerbation of COPD 57% 74% 33% (20 to 48) 4 (3 to 7) Mean scores Adjusted mean difference between groups (90% CI) at 2 wk Clinical COPD Questionnaire§ 2.6 2.8 -0.19 (-0.33 to -0.05)|| ‡Abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rate and adjusted odds ratio in article. §Score range 0 to 6; higher score = worse status; minimum important difference = 0.4. ||Criterion for noninferiority: upper limit of the 2-sided 90% CI for the between-group difference excluded 0.3. Therapeutics Butler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med. 2019;381:111-20. doi:10.7326/ACPJ201911190-051 19 Nov 2019 Annals of Internal Medicine ACP Journal Club JC51  2019 American College of Physicians