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Long-Term Macrolides for COPD Management and Comments on Antiretroviral Therapy - 8/9/2012

posted Jul 29, 2012, 8:04 AM by Rohit Das   [ updated Dec 27, 2012, 7:19 AM by Purnema Madahar ]

Welcome to the NW Daily – a venue to summarize the happenings of our educational conferences and daily activities on our lovely Northwest Floors.

Today, in Resident Journal Club, we went over a very interesting article regarding maintenance management of COPD with long-term macrolide therapy. As a reminder: 

  • Severity of COPD is staged by the “GOLD” criteria, which is based on spirometry. Their delineation ranges from “mild” COPD (Stage 1 – FEV1 ≥ 80% of predicted) to “very severe” COPD (Stage IV, FEV1 <30% predicted). 
  • Smoking cessation and oxygen supplementation (for those with chronic hypoxemia) improve survival 
  • Inhaled medications (anticholinergics being first line, followed by long-acting beta agonists, then inhaled corticosteroids) are mainly used to control symptoms, decrease exacerbation rates, and increase overall quality of life.

Antibiotics in COPD management are a very interesting topic. Acutely, they have been shown to lead to faster clinical improvement during an exacerbation, and in some studies, even improve mortality – though all of this mainly in patients with moderate-severe COPD exacerbation (defined as having 2/3 of dyspnea, increased cough, or change in sputum quanitity/quality).  Recently, there have been observational, and small randomized trials, showing that macrolides may improve LONG-TERM outcomes in COPD. 

  • Aside from their antimicrobial effects, macrolides are also theorized to have anti-inflammatory and immunomodulatory effects. 
  • GERD contributes to airway hyperreactivity, and that macrolide effects on upper GI motility may ameliorate COPD in this fashion as well…all very interesting…

The study we went over was a large, blinded randomized trial looking at Azithromycin 250mg Daily as an addition to management of COPD patients, with 1 year follow up. Their cohorts were diverse, and included a significant amount of patients already on “triple-therapy” and with Stage III-IV COPD. Assessing a primary outcome of time to first COPD exacerbation:

  • There was a significant difference in patients taking Azithromycin versus placebo (174 days vs. 266 days, p < 0.001), with a hazard ratio of 0.73 after adjustment for potential confounders.
  • Conversely, Azithromycin did lead to increased colonization with macrolide resistant organisms and an increased incidence of hearing impairment. 
  • So, macrolide therapy, at least based on this study, may ultimately be a good therapeutic option for our difficult-to-manage pink puffers, but further studies are certainly needed.

At intern noon conference, the HIV pharmacology team talked about HIV medications, the importance of reconciliation, and adverse interactions/effects that we should be aware of. This reminded me of briefly reminding you to refresh your memory about when we’re supposed to START ARVs for HIV-infected patients. Attached is the most recent IAS-USA guidelines, and pay particular attention to Box 1. Based on very recent data (attached NEJM article), we now know that HIV fulfills a paradigm we often see with transmissible infectious illnesses – treatment = prevention. For primarily this reason, ARVs should be offered to all patients with HIV, regardless of CD4 count. Though, keep in mind that the evidence for doing this, from a clinical outcome standpoint, gets stronger with decreasing CD4 count.

Please send me your thoughts and suggestions!!! Until next time…

 

Azithromycin for Prevention of Exacerbation of COPD
Albert et. al., NEJM 2011, Vol. 365: 689-98

Cohen et. al., NEJM 2011, Vol. 365: 483-505

Thompson et. al., JAMA 2012, Col 308: 387-402
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