In COPD, vitamin D deficiency is predictive of … nothing (AJRCCM)

For medical researchers, vitamin D deficiency is the new black: it goes with anything. You name the infirmity, someone’s linked vitamin D deficiency to it, and overwrought public health experts have called our supposed collective deficit of the nutrient a “pandemic.” 

Chronic obstructive pulmonary disease (COPD) and asthma are on the long list of conditions in which more severe disease is associated with vitamin D deficiency. However, any C student in epidemiology knows that association doesn’t equal causation; perhaps vitamin D levels fall in people with various chronic illnesses, for unknown reasons and without any problems resulting from the vitamin deficiency itself.

Ken Kunisaki, Dennis Niewoehner, and John Connett throw some cool rain on the vitamin D deficiency “pandemic parade”, reporting in the February Blue Journal that in people with severe COPD, vitamin D levels don’t predict future exacerbations.

What They Did:

Authors followed 973 people with severe COPD for one year, measuring their 25-OH vitamin D levels at baseline and recording their exacerbations. There were the usual high prevalences of vitamin D “insufficiency” (33% with values 20-30 ng/mL); deficiency (32% were <20 ng/mL) and severe deficiency (<10 ng/mL in 8%).

What They Found:

73% of people were labeled as “abnormal” according to relatively arbitrary laboratory value cut-offs for vitamin D levels, with 8% having “severe deficiency.”

However, baseline vitamin D levels had no relationship to COPD exacerbation rates or the time to first acute exacerbation of COPD (AECOPD). There were hundreds of exacerbations, with most patients (63%) experiencing at least one exacerbation, and with an average of ~1.5 AECOPDs per patient during the year.

Speaking more broadly, observational data are conflicting regarding any causal relationship between vitamin D levels and COPD (or most any other condition). The important thing is that most of this research data is cross-sectional; i.e., taken from a population of people at a single point in time. This kind of study is relatively cheap and fast, but bias-prone and any conclusions should be considered hypothesis-generating at best. Answering this type of question requires a prospective longitudinally-followed cohort (as was done here) or a randomized intervention trial. As of this writing, there have been no large randomized trials that suggest vitamin D insufficiency causes or contributes to chronic diseases other than osteoporosis (that said, I’m not one of the 3 people on the planet who can claim to have read the reams of trendy vitamin D research — if you are, please comment for us). A randomized trial testing vitamin D supplementation in COPD is underway in the UK, according to clinicaltrials.gov.

Regarding asthma and vitamin D deficiency, the same story is true: there’s no story, just the possible prelude to one. Low vitamin D levels are associated with worse asthma and more frequent exacerbations, but evidence for causality is lacking. One intervention study in 48 children showed a benefit to supplementation with vitamin D, but the trial was of middling quality and its results confusing (the vitamin-D chomping children had fewer subjectively-defined asthma exacerbations, but no change in asthma symptom scores or objective lung function, for example).

As we all know, research supported by industry is under increasing scrutiny for biases and manipulation. But there’s a more subtle influence afoot when these “hot” areas of investigation catch fire. I can’t prove it, but I bet someone could: the more papers showing positive results, the more hysterical-toned they are, and the more the lay press falls under the spell, the more dollars that will flow to that research area. Of course funding-starved researchers are prone (consciously or not) to fan flames of fear and conjure “pandemics,” spinning wispy stories of causation out of correlation.

Kunisaki KM et al. Vitamin D Levels and Risk of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. A Prospective Cohort Study. Am J Respir Crit Care Med 2012;185:286-290.