Macrolides to Prevent Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease
Macrolides to Prevent Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease
The purpose of this study is to determine whether macrolide therapy is effective in treating
 patients hospitalized with asthma exacerbations or chronic obstructive pulmonary disease
 (COPD)exacerbations. We hypothesize that compared to placebo, maintenance therapy with
 macrolides, when added to usual care, a) improves respiratory symptoms, b) improves quality
 of life, c) reduces airway inflammation, d) reduces airflow obstruction, and e) decreases the
 rate of re-exacerbations.
Asthma and chronic obstructive pulmonary disease (COPD) are the two most common obstructive
 lung diseases. Chronic airway inflammation and episodic worsening of respiratory symptoms and
 airflow obstruction (exacerbations) occur in asthma and COPD. Despite major advances in the
 development of therapies for these respiratory disorders, asthma and COPD exacerbations are
 common and result in substantial morbidity and mortality. Moreover, patients hospitalized for
 asthma or COPD exacerbations are at high risk for near fatal and fatal re-exacerbations after
 discharge home. These observations highlight the need for novel therapies to prevent asthma
 and COPD exacerbations. The role of macrolide antibiotics (e.g., azithromycin,
 clarithromycin, erythromycin) in treating bacterial infections is well established. Recent
 pre-clinical evidence also suggests that macrolides may posses distinct anti-inflammatory
 properties and even anti-viral properties. These exciting observations have led to research
 evaluating the use of maintenance therapy with macrolides in patients with asthma and COPD.
 Small studies in clinically stable asthma or COPD suggest that maintenance macrolide therapy
 (e.g., use for 6 weeks), when added to usual care, may attenuate airway inflammation, reduce
 respiratory symptoms, and improve lung function. However, there are no studies that have
 evaluated the potential benefits of initiating maintenance macrolide therapy during asthma or
 COPD exacerbations. We hypothesize that initiating maintenance macrolide therapy in
 hospitalized patients with asthma or COPD exacerbations will, when added to usual medical
 care, accelerate the improvement in airflow obstruction, respiratory symptoms, and quality of
 life and reduce the risk of re-exacerbations after discharge home. The objective of this
 pilot study is to evaluate the feasibility of the study protocol (recruitment, retention, and
 adherence to study procedures and medications), as well as collect preliminary data about the
 proportion of exacerbations due to bacterial or viral infections and estimate potential
 effect sizes for clinically important outcomes (respiratory symptoms, quality of life,
 airflow obstruction, airway inflammation, and rate of re-exacerbations). To achieve these
 objectives, we propose a 48 week randomized, double-blind, placebo-controlled crossover
 clinical trial (24 weeks azithromycin, 24 weeks placebo) in adults hospitalized for asthma or
 COPD exacerbations to the Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center.
Inclusion Criteria:

 -  Physician-diagnosis of asthma, COPD exacerbation, or undifferentiated asthma/COPD
 exacerbation

 -  Admitted to the inpatient medical service at Johns Hopkins Hospital or Johns Hopkins
 Bayview Medical Center

 -  Evidence of airflow obstruction on spirometry (FEV1/FVC<70%)

 -  Age 18 years or older

 Exclusion Criteria:

 -  History of allergy or other contraindication to macrolides (azithromycin,
 erythromycin, clarithromycin)

 -  Treatment with any macrolide in the 4 weeks prior to study entry

 -  Elevated AST or ALT (2 or more times the upper limit of normal) on current admission

 -  Elevated alkaline phosphatase (>1.25 times the upper limit of normal) on current
 admission

 -  Elevated total serum bilirubin (more than upper limit of normal) on current admission

 -  Previous participation in this study

 -  Patients prescribed digoxin (azithromycin may increase digoxin levels)

 -  Patients prescribed warfarin (azithromycin may increase INR in patients on warfarin)

 -  Patients prescribed pimozide (azithromycin may increase risk of arrhythmias)

 -  Patient unable to provide consent (e.g., language difficulty or history of dementia)

 -  Patient to be discharged to a location other than home (e.g., other hospital,
 long-term care facility)