This proposal will evaluate a potential mechanism of increased risk of lung function impairment, cathelicidin levels, as well as determine if vitamin D replacement can alter this pathway. This study will improve the understanding of factors which can lead to chronic lung disease. If effective, this application would also provide the justification to study vitamin D as a therapy to improve lung health.

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-Hydroxy Vitamin D (OHD)<20 ng/mL
• Creatinine Clearance ≥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, Forced Expiratory Volume in 1 second (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 >2 liters/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.

Individual participant data will not be made publicly available

Adverse event data were collected from the time of informed consent until final bronchoscopy procedure, an approximate total of 8 weeks.

Study enrollment did not achieve targeted sample size enrollment during the time frame of the funding award.