Tuesday, August 30, 2011

Once Daily Azithromycin in COPD Disease Management To Prevent Emergency Room Visits?

Chronic obstructive pulmonary disease or "COPD" is a chronic lung condition that is almost always caused by years of tobacco abuse.  Once COPD is present, patients are prone to episodic "exacerbations."  These are characterized by  progressively worse coughing, wheezing and shortness of breath over the course of several days.  If the flare is severe enough, it can force people to the emergency room.  The Disease Management Care Blog has treated such patients countless times, often at 2 in the morning. Treatment usually consists of  a mix of antibiotics, glucocorticosteroids and airway-opening inhalants. Patients often have to be hospitalized for several days.

The business case for "COPD disease management" is reducing emergency room visits and the hospitalizations that often follow.  Patients can learn how to spot an evolving exacerbation early, notify their primary care physician and start antibiotics, steroids and inhalers described above while still at home.  The logic is that early intervention can reduce the likelihood of ending up in the emergency room.  In addition, COPD disease management provides tobacco cessation programs for patients who (unbelievably) continue to smoke and also promotes the use of various types of inhalers that can reduce the incidence of exacerbations.

But suppose you could further tweak your COPD disease management program with another care option that could further  prevent exacerbations from happening in the first place?

That's the logic behind the study by Albert et al, titled "Azithromycin for Prevention of Exacerbations of COPD," that was recently published in the New England Journal.  Many DMCB readers are probably already aware that azithromycin is a "macrolide" antibiotic chemically related to erythromycin marketed under the brand name "Zithromax."  It turns out, however, that this drug also has important effects on white cell function and inflammation. That made researchers wonder if azithromycin would benefit a variety of chronic inflammatory-infectious lung diseases, including COPD.

This study went from from March of 2006 to June of 2010.  Persons over age 40 years with a diagnosis of COPD (a history of tobacco use plus confirmatory breathing tests) with either a hospitalization or emergency room visit involving glucocorticosteroids or oxygen were recruited from 17 participating institutions.   1577 persons were screened for participation and 1142 entered the study with 570 assigned to the daily antibiotic at a dose of 250 mg a day every day for one year, while 572 were assigned to a matching placebo. 12 and 13 individuals, respectively dropped out and 32 and 28, respectively, withdrew from the study. 495 and 502 completed the study. 80% of the study subjects were remained on optimal inhaler therapy during the course of the study.

After one year, 317 (57%) of the persons assigned to the antibiotic had had an exacerbation versus 380 (68%) in the placebo group.   Persons on the antibiotic went longer without exacerbations and had fewer of them.  The number needed to treat (NNT) was impressively low at 2.9.  There was no difference in overall side effects (3% vs. 4%) except for a decrease in hearing based on audiogram testing (25% vs. 20%).  There was no difference in death rates from any cause between the two groups. Patients were cultured for the presence of azithromycin-resitant organisms and persons assigned to the drug had a rate of 81% vs. 41% in the placebo group.

An accompanying editorial in the same issue of the Journal endorses the use of daily azithromycin, stating the findings of Alpert et al "tip the scales toward the benefits of azithromycin treatment."

The DMCB's impression?

In addition to all of the other interventions used in disease management for COPD, azithromycin appears to be a once-a-day treatment that can reduce exacerbations that can lead to fewer  emergency room visits.  It's hard to argue with a large randomized clinical trial like this.

The study was limited to patients who had previously experienced a severe exacerbation.  There is no evidence, therefore, that daily azithomycin should be used in patients with milder disease.

Azithromycin can effect hearing and the QT interval on EKG.  It makes sense to get an EKG  and a hearing test before starting the drug.

Patients may be at risk for future infections with azithromycin resistant infections once the year is out.  The risk may be worth it.

Since azithromycin is an antibiotic, patients may need to pay for the drug "out of pocket" or with a pharmacy co-pay.  Patients may be reluctant to do that, but it may still be worth it.

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