Your 60yo male patient has COPD (FEV1 50%, FEV1/FVC 60%). He is compliant with his Advair and prn Combivent (with good technique) and stopped smoking 2 years ago. He is enrolled in pulmonary rehab and has a normal resting and ambulatory oxygen saturation. He has had 4 exacerbations in the past year. His other medications include lisinopril and atorvastatin and he has no cardiac history. What should be your next step?
a. Azithromycin 250mg MWF
b. EKG
c. Lung Reduction Surgery
d. Oxygen
Acute exacerbations of COPD portend to further morbidity. Each exacerbation increases the rate of FEV1 decline by an additional 2ml or 7ml per year in non-smokers and smoker respectively. The cost to society is also high. Treatment of COPD includes smoking cessation, pulmonary rehab, anti-cholinergics, beta-agonists, and glucocorticoids. Some patients, despite maximal therapy, may still have uncontrolled disease. Macrolides have anti-inflammatory and immune-modultating effects and may decrease the production of cytokines in the lungs (Role of Macrolide therapy in COPD. Int J Chron Obstruc Pulmon Dis 2008;3:331-50). Thus, these have been studied in COPD.
NEJM published a study in 2011 showing daily use of azithromycin 250mg reduced the frequency of acute exacerbations of COPD (NEJM Article). The median time to the first acute exacerbation was increased by 92 days compared to the placebo group (266 days compared to 174 days). Quality of life was also improved per the St. George's Respiratory Questionnaire. There was no statistically significant difference in mortality. Similar results were found in a trial using erythromycin (Am J Respir Crit Care Med 2008; 178:1139-47).
Long-term use of azithromycin comes with many concerns including prolonged QT (greater than 450), ototoxicity, drug interactions, and possible antibiotic resistance. The risk of torsades is of great concern. It is because of these side-effecs that the GOLD report guidelines stated that despite it's proven efficacy azithromycin is "not recommended because of an unfavorable balance between benefits and side effects" (GOLD Report).
Many expert believe it is still safe and reasonable to add azithromycin if proper baseline screening is done. Important baseline tests include heart-rate, QTc, audiography, LFTs, and medicationreview. If the patient is taking a QTc prolonging agent, has a baseline QTc greater than 450, or has a significant cardiac history (CHF, hx of stroke) then azithromycin is not recommended. Additionally it is not recommended if the patient has an abnormal audiogram or LFTs greater then 3x the ULN. If these tests are normal then it is reasonable to start a trial of azithromycin, but only in those patients who continue to
have frequent COPD exacerbations despite being on maximal therapy (~ 2
or more a year). Expert opinion favors three times a week dosing, despite the trials using a daily dose based on pharmacokinietics of the drug. This may also minimize the side effects. (NEMJ Clinical Therueptucis article). They also recommend repeating EKG, audiography, and labs every three months to monitor for side effects. Some experts suggest obtaining a baseline sputum culture to asses for nontuberculous mycobactermia as well.
Therefore, for this patient the answer is to obtain a baseline EKG and hearing test. If normal, it is reasonable to start azithromycin three times a week with monitoring of side effects.
This case is based on the following article: NEJM Clinical Therapeutics of COPD:
