Lung diseases such as COPD, asthma and cystic fibrosis are often associated with low vitamin D levels. While oral vitamin D supplements have previously been met with limited success in treating these conditions, a new paper claims that inhaled vitamin D could improve results.
The paper, “Reconsidering Vitamin D Supplementation in Pulmonary Disease: The Case for Targeted Respiratory Delivery,” was published in Chronic Obstructive Pulmonary Diseases: The Journal of the COPD Foundation.
The paper states that randomized controlled trials have failed to demonstrate clinically significant benefits from oral vitamin D supplements and that this course of treatment does not appear to meaningfully improve lung function, reduce flare-ups or exacerbations, or improve quality of life.
“We think the reason is that oral vitamin D gets inactivated by an enzyme in the lung’s blood vessels before it ever reaches airway tissue,” said UNC School of Medicine’s Kevin Schichlein, PhD, in a press release. Dr. Schichlein is first author of the study and a postdoctoral student in the Marsico Lung Institute. “Delivering it directly to the lung through inhalation could bypass the problem entirely.”
The authors wrote that direct delivery of vitamin D to the airway epithelium through topical or inhaled administration may provide a more effective route to treat lung disease. The respiratory epithelium, they explained, already has the complete machinery needed for vitamin D metabolism. This includes expression of cytochrome P450 family 27 subfamily B member 1 (CYP27B1) for local calcitriol synthesis and expression of vitamin D receptors across airway epithelial and immune cells.
“Topical or inhaled delivery of vitamin D is already being explored for upper airway diseases with data from preclinical models and some preliminary clinical trials showing promising results,” said co-author Ilona Jaspers, PhD, a professor in pediatrics and investigator in the Marsico Lung Institute at UNC School of Medicine. “Moving to the lower airways could be a logical extension of those observations.”
M. Bradley Drummond, MD, co-author and professor of medicine in the division of pulmonary diseases and critical care medicine at UNC School of Medicine, said there is a disconnect between the known harms of vitamin D deficiency and the failure of clinical trials using oral vitamin D supplementation to demonstrate a benefit to respiratory health.
“We believe this disconnect may reflect a suboptimal delivery method for vitamin D, rather than its overall ineffectiveness,” Dr. Drummond said. “Direct inhaled delivery of vitamin D could unlock new therapeutic opportunities for COPD and other chronic lung diseases.”
Despite this potential, the authors noted no clinical trials thus far have investigated pulmonary delivery of vitamin D in individuals with chronic lung diseases such as COPD. Future work, they said, should focus on human safety data, dosing and delivery optimization, pharmacokinetics/pharmacodynamics and clinical utility.
“Direct pulmonary delivery of vitamins and nutrients presents an underexplored and promising approach for treating lung disease and warrants further investigation,” they wrote.
