When we think of alcohol’s human toll, two causes come to mind: car crashes and cirrhosis. And indeed, twisted metal and scarred livers caused by alcohol consumption kill about 43,000 people in the United States every year. Ten thousand or so absorb their mortal injuries in milliseconds courtesy of booze-complicit auto accidents; the rest sustain their damage over years, via ethanol’s continued erosion of the liver.

These are big numbers, but only part of the story of alcohol’s health impacts. Alcohol is behind about 88,000 U.S. deaths a year, according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA, part of the National Institutes of Health). So what’s killing the other half?

It turns out that heavy alcohol use shares with smoking an ability to harm the body well beyond the narrow bounds of the liver or lungs. In the case of drinking, the cardiovascular system suffers, too (as it does with smoking). But alcohol also hinders the body’s ability to fight infection and even heal broken bones. And new science, led by new University of Colorado School of Medicine researchers, shows that alcohol’s effects on the immune system are more profound – and potentially dangerous – the older you get.
Elizabeth Kovacs, PhD, is new to CU, but her track record studying the impacts of alcohol and health reaches back two decades. She joined the CU Department of Surgery as director of Burn Research from Loyola University Chicago on April 1; her colleague, Brenda Curtis, PhD, came along, too, as did MD-PhD student Devin Boe and postdoctoral researchers Lisbeth Boule, PhD, and Anita Zahs, PhD.

Booze and blood cells

Kovacs and Curtis’s latest study, presented at a national Research Society on Alcoholism meeting in June, considers alcohol’s impact on immune systems already weakened with age. The work combined their two focus areas. Their earlier work had found that drunken macrophages – germ-eating white blood cells – seem to lose their appetites as well as their enthusiasm for signaling to other vital immune cells. They had also studied the elevated inflammatory state among aging immune systems, known as “inflamm-aging.” The new research, which they’re gearing up to publish, shows that mixing alcohol with an old immune system makes people even more susceptible to infection.

“So we’ve got aging that suppresses the immune system and alcohol, and combining them is a double-whammy,” Kovacs said.

The obvious follow-up questions: 1) How old is old? And 2) How much alcohol is too much? It’s a testament to the emerging nature of their research that Kovacs and Curtis can’t answer either one yet – nor can anyone else. Until they and others can, age-adjusted guidelines for safe levels of alcohol consumption remain a pipe dream.

But given the “silver tsunami” of aging baby boomers, the fact that alcohol tolerance in general declines with age, and that aging livers must often deal with an array of medications and supplements in addition to the insults of alcohol, it appears that the impacts of alcohol among older people is an area ripe for research.

Bathroom to research boom

Kovacs happened into her professional specialty in a ladies restroom at Loyola’s Burn and Shock Trauma Institute. It was 1995, and instead of commenting on, say, the sorry play of the Chicago Cubs, she asked a research nurse what sorts of patients were typical in the burn ICU. The nurse said a lot of them consumed alcohol before their injuries, and they didn’t do as well in recovering afterward.

Kovacs brought it up with Richard Gamelli, MD, a renowned Loyola burn surgeon. With $6,000 in seed money, Kovacs launched what would become a multi-million-dollar alcohol research program, one in which about 50 researchers studied alcohol’s impact on the human body “across disciplines and across tissue barriers,” as she put it. They considered alcohol’s impact on the brain, on skin-wound healing, on bone-fracture repair, on gut permeability, on the immune system and lung function, and on other areas.

Alcohol impairs pretty much everything, Kovacs and colleagues have found. For example, with the healing of infected wounds, alcohol suppresses the ability of macrophages and other innate immune cells to migrate to the site of the injury and clear debris. Alcohol also reduces the amount of bacteria-killing antimicrobial peptides in the skin, allowing bacteria to get the upper hand, Kovacs says.

Ellen Burnham, MD, a CU School of Medicine Pulmonary Sciences and Critical Care Medicine associate professor and medical director of the Medical Intensive Care Unit at University of Colorado Hospital, has been a longtime collaborator. Burnham provides clinical insights – that is, how heavy alcohol-using people, as opposed to mice, fare – with respect to pneumonia and lung injury.

“We take the observations in the animal models forward,” Burnham said.

Clinical research performed by Burnham and her group hopes to answer questions as to why heavy drinkers with pneumonia or acute respiratory distress syndrome (ARDS) stay on ventilators and in ICUs longer. Thirty-five percent to 40 percent of patients with ARDS typically die from it; approximately 60 percent of harmful alcohol users die, Burnham says.Marc Moss, MD, now the CU School of Medicine’s associate dean for Clinical Research, was the first to make the connection between alcohol abuse and such poor outcomes, she adds.

In addition to seeing how laboratory findings translate into the reality of an intensive care unit, Burnham is working with other national collaborators to see if blood or lung samples might yield biomarkers that indicate harmful alcohol consumption. Patients and families don’t always know or admit the extent of their loved one’s alcohol use, and it directly impacts care. In a burn ICU, Kovacs says, they’ve found that patients with harmful alcohol use require more fluid resuscitation, more surgeries, more antibiotics, and longer hospital stays. They’re six times likelier to die than someone with the same initial injuries, Kovacs adds.

Collaborations to come

Burnham is one of the big reasons Kovacs and Curtis moved their research program to Colorado, as is Richard Schulick, MD, MBA, the CU Department of Surgery chairman who hired them. But what Kovacs called a “skibattical” in early 2015 left first tracks. She went to seminars and conferences, focusing on learning more about clinical research. She also skied 26 of 92 days. The combination, she said, led her to this thought: “Hey, what if I moved here?”

Having moved here, Kovacs is now collaborating with Department of Surgery colleagues and reaching out to the likes of Robert Schwartz, MD, and Wendy Kohrt, PhD, both of the CU School of Medicine’s highly regarded Geriatric Medicine Division, who have done work  in inflammation among older women; as well as to Cara Wilson, MD, a CU infectious disease specialist who studies intestinal immune function and the microbiomes of the elderly. CU will also soon play host to the NIAAA-funded Alcohol and Immunology Research Interest Group meetings Kovacs has hosted for more than a decade.

And, of course, Kovacs and Curtis will continue their collaborations with Burnham, whose office is now in the same building. Burnham says there’s much work to be done on the impacts of alcohol and the aged in a world in which teenage binge drinking and fetal alcohol syndrome take center stage (and in terms of long-term impacts, rightly so).

“Alcohol is a systemic drug,” she said, and one that impacts everyone from the unborn to centenarians, if in vastly different, still much-too-mysterious ways.