Cathelicidin and Vitamin D: Impact on Populations At-Risk and With COPD

Understanding mechanisms leading to decrements in lung function, the physiologic hallmark of
obstructive lung diseases including chronic obstructive pulmonary disease (COPD), are
necessary to inform interventions to improve lung health. The antimicrobial peptide
cathelicidin, and its primary regulator vitamin D, has been implicated in development and
progression of chronic lung disease. In this study, the investigators will evaluate the
effect of oral vitamin D supplementation on lung cathelicidin levels in humans. Cathelicidin
has bactericidal and inflammatory activities in the lung and is regulated by vitamin D
levels. The investigators hypothesize that oral vitamin D supplementation will raise
cathelicidin levels in the pulmonary compartment, thereby restoring lung cathelicidin
deficiency. To test this hypothesis, the investigators will recruit from two ongoing cohort
studies: 1) At Johns Hopkins, the Subpopulations and Intermediate Outcome Measures in COPD
Study study and 2)at University of North Carolina at Chapel Hill pulmonary and general
medicine clinic. The investigators will measure blood and lung lavage cathelicidin levels in
40 vitamin D insufficient individuals (20 from each cohort) before and after eight weeks of
oral vitamin D supplementation to determine the effect of vitamin D supplementation on
cathelicidin levels.

Inclusion Criteria:

- Men and women age 18-65 who are current or former smokers

- Serum calcium<10.5mg/dl

- 25 OHD<20 ng/ml

- CrCl ≥60 mL/min as estimated by the Cockcroft-Gault equation

- Women of reproductive potential with negative serum or urine pregnancy test and
subjects must refrain from participating in a conception process and subject/partner
must use at least 2 reliable forms of contraceptives for the duration of the study

- For participants with COPD, FEV1 greater than 50% predicted.

- For smokers, current cigarette use (defined as regularly smoking 5 cigarettes per day)

Exclusion Criteria:

- Current use of vitamin D supplements

- Known allergy/sensitivity or any hypersensitivity to components of study drugs or
their formulations

- Pregnancy or currently breast-feeding

- History of nephrolithiasis

- HIV positive serostatus

- Continuous oxygen use >2L/min via nasal cannula

- Any condition that, in the opinion of the site investigator, would compromise the
subject's ability to participate in the study.