"In early spring, the Minnesota Department of Health was notified of an unexplained death: a middle-aged man who died suddenly at home," said Dr. Victoria Hall, a CDC field officer based in Minnesota. He'd been on long-term opioid therapy for back pain, and his family had worried he might be abusing his medication. The medical examiner assigned to the autopsy tested for and diagnosed both pneumonia and a toxic level of opioids.
"However, on the death certificate, it only listed the pneumonia and made no mention of opioids," Hall said.
The researchers say it may be difficult to track causes of death, such as this one, within surveillance systems that are based solely on autopsy report codes known as International Classification of Diseases, Tenth Edition, or ICD-10.
Over half of the deaths involving opioids in her study had not been captured in the state's total, said Hall.
"While my research cannot speak to what percent we are underestimating, we know we are missing cases," Hall said. "It does seem like it is almost an iceberg of an epidemic."
Hall presented her findings Monday at the annual Epidemic Intelligence Service Conference
, which showcased recent CDC investigations. CDC's "disease detectives' support over 100 field investigations each year in the US and worldwide.
Rural and urban, men and women
Researchers led by Hall examined death records within the Minnesota Department of Health's Unexplained Death surveillance system
, called UNEX, for 2006 through 2015.
The CDC started the system in 1995 in many states, but Minnesota is the only one to maintain it.
The system was developed to "constantly be on the lookout for emerging diseases," especially infectious diseases, explained Hall. It identifies cases in which there's no clear explanation for death so more testing can be performed.
Because research has showed that opioid users are at increased risk of pneumonia, Hall and her colleagues searched for pneumonia as well as other infectious disease deaths among Minnesota residents over the age of 12 to see whether opioids might be involved and found in postmortem toxicology screenings.
Among the 1,676 deaths that fit the researchers' criteria, 59 (or 3.5%) showed evidence of opioid use. Those 59 deaths had not been picked up by the state's opioid surveillance system because they lacked the proper ICD-10 code. And, among these 59 deaths, 22 had involved toxic levels of opioids.
The deceased ranged in age from 16 to 82, with a median age of 43, and 53% were female. Hall said the demographics of cases caught in the UNEX system were very similar to those captured in the state overdose system, with adults of all ages and ethnicities, both rural and urban.
"Opioids don't discriminate," Hall said.
Pneumonia was found in 32 of the 59 deaths. Deaths involving infectious disease like pneumonia can be complicated if you have opioids in your system, explained Hall.
"Opioids at therapeutic or higher than therapeutic levels can impact our immune system," she said. "It actually impacts your macrophages -- so that's one of your main immune cells that's going to help fight off infections -- and it kind of dampens them down. It also dampens down your antibody response."
The sedative action of opioids also affects mechanical aspects of breathing.
"When you take an opioid and it makes you breathe more shallow and breathe slower and less likely to cough, it's a lot more likely things can settle in your lungs," Hall said.
Among the 32 pneumonia cases, nine of the deceased had a history of drug abuse, six had chronic pain, and one was taking methadone.
"Over half the cases that we found that were toxic or lethal were not counted in the system," Hall said.
'Not just a Minnesota problem'
Another complication of the opioid epidemic is that "there's no clear-cut line on what an overdose is," Hall said. Long-term users may be able to take a much higher dose than first-time users, so when national statistics are collected, the CDC must rely on a medical examiner's judgment as to what is an overdose.
More important, there's no "national standardization for how to fill out a death certificate," explained Hall, so when there's a profound infectious disease, such as pneumonia, that's the only thing noted.
"It's quite concerning, because it means that the (opioid) epidemic, which is already quite severe, could potentially be even worse," Hall said. A total of 33,000 opioid-related deaths were reported across the nation in 2015, a historic high, she said.
"While my data doesn't support a percent that we're underestimating, it puts out the question: Is there something we need to look into further?" Hall said. "This is not just a Minnesota problem."