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                  The New England Journal of Medicine   
   
                          Resident e-Bulletin   
   
      TEACHING TOPICS from the New England Journal of Medicine   
   
   
                  Teaching Topics | August 25, 2011   
   
   
Azithromycin to Prevent COPD Exacerbations: What was the effect of    
daily azithromycin treatment on the frequency of exacerbations in    
this study?   
   
Primary Immune Thrombocytopenia: What is the initial approach to    
managing patients with primary immune thrombocytopenia?   

   
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TEACHING TOPIC   
Azithromycin to Prevent COPD Exacerbations   
   
ORIGINAL ARTICLE,   
Azithromycin for Prevention of Exacerbations of COPD,   
(http://www.nejm.org/doi/full/10.1056/NEJMoa1104623?query=BUL)   
R.K. Albert and Others   
CME Exam | Comments   
   
   
Acute exacerbations of chronic obstructive pulmonary disease (COPD)    
result in frequent visits to physicians' offices and emergency rooms    
and numerous hospitalizations and days lost from work.   
   
   
Clinical Pearls   
   
- How do acute exacerbations of COPD affect patient outcomes?   
   
Patients who have acute exacerbations of COPD, as compared with    
patients with COPD who do not have acute exacerbations, have an    
increased risk of death, a more rapid decline in lung function, and    
reduced quality of life.   
   
- What was the effect of daily azithromycin treatment on the frequency    
of exacerbations in this study?   
   
The frequency of exacerbations was 1.48 exacerbations per    
patient-year in the azithromycin group, as compared with 1.83 per    
patient-year in the placebo group (P=0.01), and the hazard ratio for    
having an acute exacerbation of COPD per patient-year in the    
azithromycin group was 0.73 (95% CI, 0.63 to 0.84) (P<0.001).   
   
Table 2. Effect of Treatment for Chronic Obstructive Pulmonary    
Disease (COPD) on Hospitalization Rates, Emergency Department or    
Urgent Care Visits, and Unscheduled Office Visits.   
(http://www.nejm.org/action/showImage?doi=10.1056/NEJMoa1104623&iid=t02&query=BUL)   
   
   
Morning Report Questions   
   
Q: How did daily treatment with azithromycin affect antibiotic    
resistance patterns among treated patients?   
   
A: Cultures from 68% of the participants in the azithromycin group and    
70% in the placebo group who were not colonized with selected    
respiratory pathogens at the time of enrollment but who became    
colonized during the course of the study were available for    
susceptibility testing (P=0.76), and the incidence of resistance to    
macrolides was 81% and 41% in the two groups, respectively (P<0.001).   
   
Q: What adverse event was significantly more frequent among patients    
treated with azithromycin as compared to placebo in this study?   
   
A: No significant differences were observed in the frequency of serious    
adverse events or of adverse events leading to discontinuation of the    
study drug, but an audiogram-confirmed hearing decrement occurred in    
142 of the participants receiving azithromycin (25%), as compared    
with 110 of those receiving placebo (20%) (P=0.04).   
   
   
TEACHING TOPIC   
Primary Immune Thrombocytopenia   
   
CLINICAL THERAPEUTICS,   
Thrombopoietin-Receptor Agonists for Primary Immune Thrombocytopenia,   
(http://www.nejm.org/doi/full/10.1056/NEJMct1014202?query=BUL)   
P. Imbach and M. Crowther   
CME Exam   
   
   
Immune thrombocytopenia is a disorder that is characterized by    
immune-mediated platelet destruction and impaired platelet production    
resulting in a platelet count of less than 100,000 per cubic    
millimeter and varying degrees of bleeding risk.   
   
   
Clinical Pearls   
   
- Does platelet count correlate with bleeding risk in patients with    
primary immune thrombocytopenia?   
   
Bleeding in immune thrombocytopenia is rare in patients who have a    
platelet count of more than 50,000 per cubic millimeter. The bleeding    
risk at lower platelet counts varies greatly from none to very    
severe, although spontaneous, life-threatening or fatal bleeding is    
generally confined to patients with a platelet count of less than    
10,000 to 20,000 per cubic millimeter.   
   
- What is the initial approach to managing patients with primary immune    
thrombocytopenia?   
   
Initial treatment for immune thrombocytopenia is generally a course    
of glucocorticoids, intravenous immune globulin, or both. The only    
second-line treatment that has been shown to produce sustained    
increases in the platelet count is splenectomy. Rituximab is widely    
used as a second-line agent, although the median duration of response    
with this agent is only 10.5 months.   
   
Figure 1. Structure of Romiplostim and Eltrombopag and the Cellular    
Mechanisms of Action.   
(http://www.nejm.org/action/showImage?doi=10.1056/NEJMct1014202&iid=f01&query=BUL)   
   
   
Morning Report Questions   
   
Q: What is the efficacy of the thrombopoietin-receptor agonists,    
romiplostim?   
   
A: Romiplostim is administered subcutaneously once weekly. In an ongoing    
open-label extension study involving 292 patients treated with    
romiplostim, 94.5% achieved a platelet count of at least 50,000 per    
cubic millimeter during the study.   
   
Q: What is the efficacy of the thrombopoietin-receptor agonist,    
eltrombopag?   
   
A: Eltrombopag is given orally daily. In an ongoing open-label extension    
study involving 299 patients who completed a previous eltrombopag    
study, 87% of patients achieved a platelet count of at least 50,000    
per cubic millimeter during treatment.   
   
   
QUOTE OF THE WEEK   
   
"Among selected subjects with COPD, azithromycin taken daily for 1    
year, when added to usual treatment, decreased the frequency of    
exacerbations and improved quality of life but caused hearing    
decrements in a small percentage of subjects."   
   
R.K. Albert and Others, Original Article, "Azithromycin for    
Prevention of Exacerbations of COPD"   
(http://www.nejm.org/doi/full/10.1056/NEJMoa1104623?query=BUL)   
   
   
IMAGE CHALLENGE   
   
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