1. HIGH DOSES OF VITAMIN D TO REDUCE EXACERBATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A RANDOMIZED TRIAL An Lehouck, PhD; Chantal Mathieu, MD, PhD; Claudia Carremans, MS; Femke Baeke, PhD; Jan Verhaegen, MD, PhD; Johan Van Eldere, MD, PhD; Brigitte Decallonne, MD, PhD; Roger Bouillon, MD, PhD; Marc Decramer, PhD; and Wim Janssens, MD, PhD

2. Background & Objective  COPD is defined as an abnormal inflammatory response of the airways that block airflow and make breathing difficult.  Vitamin D deficiency is present in 60-75% of patients with COPD.

3. Background & Objective  Background: Low serum Vitamin D (25- hydroxyvitamin D, or 25-[OH]D) levels associated with lower FEV 1 and increased airway inflammation.  Objective: To investigate whether high doses of Vitamin D supplementation could reduce occurrence of COPD exacerbations/flare-ups.

4. Methods: Study design and participants  Single-center, double-blind, randomized, placebo- controlled trial in Belgium over 1.5 year period  182 patients with moderate to severe COPD recruited

5. Methods: Study design and participants  Inclusion Criteria:  Have COPD diagnosis  50+ years of age  Current/former smokers  Had less than 80% predicted FEV 1  Exclusion Criteria:  Hx of hypercalcemia, sarcoidosis, or active cancer  Those being treated with Vitamin D supplements for newly diagnosed osteoporosis  Those on long-term antibiotics with anti-inflammatory functions

6. Methods: Randomization and Masking  First, 1 group received low dose Vitamin D (400-880 IU/day) at baseline for osteoporosis; one group not receiving low dose Vitamin D  Then, participants randomly assigned to blocks of 20 in which they would either receive monthly oral dose of 100,000 IU Vitamin D or a placebo  (those on low dose Vitamin D at starting point were divided evenly among groups)

7. Methods: Procedures  Patients screened during hospitalization for an exacerbation of COPD  Randomization occurred 5-6 weeks after screening  Baseline characteristics  BMI  Airflow obstruction  Shortness of breath  Exercise Capacity Index  Charlson Comorbidity Index

8. Methods: Procedures  Primary endpoint: time to first exacerbation  Secondary endpoints: exacerbation rate, time to 1 st hospitalization, time to 2 nd exacerbation, FEV 1, QOL, death

9. Methods: Procedures  Follow-up visits every 4 months  Patients asked to keep diary every 2 weeks of:  Respiratory tract symptoms  Hospitalizations  Visits to healthcare providers  Changes in meds

10. Methods: Statistical Analysis  Study designed to demonstrate at least 25% delay in time to 1 st flare-up  20% receiving low dose Vitamin D at baseline for osteoporosis  Of 182 participants, at least 120 needed who were not receiving any Vitamin D treatment at baseline  P values <0.05 statistically significant

11. Results  419 patients screened-> 340 eligible-> 182 included  150 participants completed the study, 15 died, 17 dropped out  Overall, collected info on flare-ups for 175 participants, information on survival for all 182

12. Results  Total of 468 exacerbations  229 in Vitamin D group  239 in placebo group

13. Results  No significant difference in median time to 1 st or 2 nd exacerbation, exacerbations per year, or median time to hospitalization for flare-up  No significant difference in survival  30 participants were Vitamin D deficient at baseline- 15 randomly chosen to receive Vitamin D supplement  Significant increase in serum 25-(OH)D levels

14. Discussion  Main finding: monthly dose of 100,000 IU Vitamin D in addition to regular therapy does not reduce time to 1 st exacerbation or amount of exacerbations in patients with moderate to severe COPD

15. Discussion: Advantages  Study sample prone to exacerbations  Most participants chosen during hospitalization were admitted for acute exacerbation

16. Discussion: Disadvantages  Small sample size  Most were already receiving treatment to control/decrease exacerbations  Difficult to obtain additional information on effect of Vitamin D alone

17. Discussion  Lack of overall Vitamin D effect could be explained by local insensitivity due to smoking or chronic inflammation  Supports idea that Vitamin D deficiency in COPD patients could increase risk of flare-ups  More studies needed to explore need and safety for recommending higher doses of Vitamin D to see beneficial effects in areas other than bone health