Innate immune modulation in COPD: moving closer towards vitamin D therapy
J. of Pharmacology and Experimental Theraputics March 9, 2015 jpet.115.223032
Nele Heulens, Hannelie Korf, and Wim Janssens wim.janssens@uzleuven.be
Katholieke Universiteit Leuven, Belgium
Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases and a major cause of morbidity and mortality worldwide. Disturbed innate immune processes characterize the pathogenesis of COPD. Vitamin D deficiency is very common in COPD patients and has been associated with disease severity. Interestingly, a number of mechanistic evidence from animal and in vitro studies has demonstrated important innate immunomodulatory functions of vitamin D, including anti-inflammatory, anti-oxidative and antimicrobial functions. In this review, we will discuss in detail how these innate immunomodulatory functions of vitamin D could provide therapeutic potential in COPD patients. Finally, the remaining challenges associated with vitamin D therapy in COPD patients will be discussed.
Clipped from Conclusions
The airways and lung parenchyma of COPD patients are characterized by exaggerated inflammation, increased oxidative stress, impaired host defense and lung remodeling. As vitamin D could positively affect each of these processes, vitamin D therapy may have great therapeutic potential in COPD patients, who often present with vitamin D deficiency. Appropriate antimicrobial treatment is essential in the treatment of acute exacerbations of COPD. However, repetitive and long-term treatment with antibiotics should still be avoided as they contribute to the multi-resistance of colonizing strains. Therefore, vitamin D could be a potential alternative due to its dual antimicrobial and anti-inflammatory properties in the (pulmonary) immune system. Moreover, as vitamin D has been shown to improve responsiveness to GCs, co-administration of inhaled GCs and vitamin D may enhance the anti-inflammatory effects of existing GC therapies in COPD patients. A subsequent lower but still efficacious dose of inhaled GCs may be beneficial by reducing the risk for pneumonia associated with high doses (Calverley, et al., 2007;Dransfield, et al., 2013;Ernst, et al., 2007;Wedzicha, et al., 2008).
Although an abundance of epidemiological and mechanistic studies support the potential benefit of vitamin D therapy in COPD patients, more well-designed trials are necessary to unravel the potential efficacy of vitamin D therapy in COPD patients. Here, the administration dose, form of vitamin D and route of administration should be taken into consideration. Additionally, it must be noted that vitamin D therapy may only be effective in COPD patients with defined vitamin D deficiency, as demonstrated in two intervention trials with high-dose vitamin D supplementation in COPD patients (Lehouck, et al., 2012;Martineau, et al., 2014). Taken together, despite the clear potential of vitamin D in reversing a disturbed innate immune defense in COPD, many unknowns remain. Further research is needed to implicate the therapeutic potential of local upregulation of vitamin D signaling in the lungs of patients with COPD.
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See also VitaminDWiki
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- COPD becoming suddenly worse is 30X more likely if low vitamin D – Dec 2014
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- Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014
- COPD reduced by vitamin D taken once every 60 days – RCT Dec 2014
- COPD 2X as likely if low vitamin D – review of 3 studies – March 2014
- COPD fought by Vitamin D - many studies
Dr. Spock died of COPD a few days ago. Wish he had been taking vitamin D