Dr Fernando Holguin Describes How Metabolic Syndrome Impacts Risk of Pulmonary Disease

Fernando Holguin, MD, explains the mechanisms that account for increased risk of pulmonary disease among individuals with metabolic syndrome.

There are likely to be multiple mechanisms accounting for the relationship between these 2 conditions, said Fernando Holguin, MD, a pulmonologist and critical care doctor at the University of Colorado Anschutz Medical Campus. Holguin discussed these topics at this year's American Thoracic Society (ATS) meeting.


What aspects of metabolic syndrome can affect risk for pulmonary disease? What is the mechanism behind this association?

I think now for over at least 2 decades or more, it's been widely recognized through a number of studies that obesity impairs asthma control, diminishes response to therapy, and increases the chances you can have an asthma exacerbation. There are multiple mechanisms. I don't think that we really know for certain which one drives, and maybe the fact that multiple mechanisms complicate maybe even the same patients or different patients in different ways. But what became really interesting is obese subjects are more likely to have metabolic syndrome. Metabolic syndrome, for you to remember, is just really more of having a number of risk factors together, which typically are lipid disorders or dyslipidemia, issues with glycemic control or diabetes, hypertension, and increased abdominal girth. So actually obesity is not one of them, abdominal girth is, which is different for men and females.

People have done different epidemiological studies. Both longitudinal and cross-sectional studies have shown that having metabolic syndrome—whether it's because you have 3 or more of these risk factors, or actually some of these risk factors independently—have been associated with increased incidence of asthma. And in those with asthma, it has been associated with increased risk of having worse symptoms and worse control. In many cases, not in every study, but in some of the studies, some of these associations remain even after adjusting for body mass index, suggesting that there is indeed an independent risk factor that relates between what happens in the airway and some of these metabolic factors at play.

Now, the mechanisms, I think there are likely to be multiple mechanisms. For one, for example, increased insulin and hyperinsulinemia have been associated with hypercontractility in animal models. If you remember, a long time ago there was this drug called Exubera, I think it was. It was an inhaled insulin for patients with asthma. One of the things that got it sort of knocked out of the market is because it induced pulmonary changes. There's something about insulin in the airways that higher levels of insulin don't sit very well with the lungs. Changes in lipids, Deepa Rastogi, MD, MS, at National Children's Hospital has done a lot of really wonderful work showing that changes in lipids, like low HDL [high-density lipoproteins] and high HDL can really affect the degree of activation and subpopulation of peripheral blood monocytes, and those, in turn, can actually amplify immune responses in the lung.

Other things that may happen is with increased adiposity. Work by Anne Dixon, MD, has shown that there's a lot of crosstalk between the adipose tissue—in particular, in the more metabolically active in the abdominal region of the lung—by way of training or changing the profiling of different macrophages and leading to inflammasome activation, as well as generating adipokines like leptin, for example, in great concentrations may potentially influence the lung. That's been shown, I think, more nicely in animal studies than in humans, but there's this idea that some adipokine imbalance can—more leptin, less adiponectin—potentially influence lung function and increase bronchial hyperactivity as well. So as you can see, there's just a number of factors that can lead to metabolic syndrome affecting asthma.

Are there any pulmonology diseases for which metabolic syndrome poses a greater risk than others?

Certainly, the epidemiological data show that people with metabolic syndrome have increased risk of having both restrictive and obstructive lung diseases, but clearly where I think we know the most is people in relation to obstructive lung disease, particularly asthma.