Natalie E. West, MD Postdoctoral Fellow Pulmonary and Critical Care Medicine July 23, 2010

1. The Effect Of Chronic Macrolide Therapy In Cystic Fibrosis Individuals Infected With Pseudomonas Aeruginosa Natalie E. West, MD Postdoctoral Fellow Pulmonary and Critical Care Medicine July 23, 2010

2. Pulmonary infections are the main complication in Cystic Fibrosis • Cystic Fibrosis (CF) is characterized by • chronic pulmonary infection • intermittent acute pulmonary exacerbations • Most CF exacerbations: • Identified by increased symptoms & decreased lung function (FEV1) • Severe exacerbations require hospitalization and IV antibiotics

3. 38% of CF patients have a severe exacerbation each year CF Foundation Registry Report 2007

4. Acute pulmonary exacerbations decrease lung function in Cystic Fibrosis CF Foundation Registry Report 2007

5. Advancement in therapy has increased survival CF Foundation Registry Report 2007

6. Pseudomonas aeruginosa is pathogenic in Cystic Fibrosis CF Foundation Registry Report 2007

7. Azithromycin therapy has been shown to be beneficial in Pseudomonas treatment • Design: Randomized, placebo-controlled, multicenter trial • Participants: -CF individuals with P. aeruginosa -Age >6, Weight >25kg • Exposure Azithromycin M/W/F • Primary Outcome Change in FEV1 • Results Azithromycin compared to control: Increase in FEV1 by 6.2% f (p=0.009) Decreased exacerbations (p=0.03) 0.7kg weight gain (p=0.02) Saiman, L. JAMA. 2003; 290 (13):1749-56.

8. Azithromycin decreased exacerbations Saiman, L. JAMA. 2003; 290 (13):1749-56.

9. Large scale long term follow-up studies are needed Rate of Macrolide use per CF center CF Foundation Registry Report 2007

10. Our study: Does chronic macrolide therapy improve outcomes? • Hypothesis Chronic macrolide therapy in CF patients with P. aeruginosa results in decreased rates of pulmonary exacerbations requiring hospitalization, compared to those not treated • Specific Aim To evaluate the long term effects of chronic macrolide use in individuals with CF and P. aeruginosa infection, by looking at rates of pulmonary exacerbations requiring hospitalization

11. Long term study using the CF Registry • Design: Longitudinal, 3 year study using the CF Foundation registry • Participants: -CF individuals with P. aeruginosa -Age >6, Weight >25kg • Exposure Macrolide use • Exposure Assessment Patient report • Primary Outcome Exacerbations → hospitalizations • Outcome Assessment Chart Review

12. Statistical Analysis • Multiple Poisson regression for repeated measures • Adjusted for: • FEV1 • Inhaled Tobramycin (TOBI), pulmozyme , hypertonic saline • methicillin-resistant Staphylococcus aureus(MRSA), Burkholderiacepacia. • Incidence rate ratio (IE/IO) calculated

13. Study population similar to general CF population

14. Macrolide therapy led to a decreased exacerbation rate

15. Strengths and Limitations • Strengths • Long term longitudinal data • Aligns RCT and current guidelines • Limitations • Data collected at individual centers, may increase risk of misclassification bias

16. Conclusion • We have shown that macrolide therapy improves outcomes in individuals with CF and P.aeruginosa • We recommend that macrolide therapy should be implemented widely in this population

17. Significance • Large scale, long term study • Potential for improved patient adherence • Potential for improved survival

18. Acknowledgements • My Mentor • Noah Lechtzin, MD • Co-Mentors • Michael Boyle, MD • Christian Merlo, MD • Co-Authors – above plus… • Elliott Dasenbrook, MD • Patrick Sosnay, MD