Cardiac, respiratory, and mental health conditions should be on clinicians’ radar

As the Covid-19 pandemic keeps the world on alert, it seems like a lifetime ago that serious lung injuries and deaths related to e-cigarette, or vaping product use-associated lung injury (EVALI) were rising to epidemic proportions in the U.S.; however, as recently as last September, EVALI was peaking, with the curve flattening in early 2020.

As of February 2020, there were 2,807 hospitalized cases and 68 deaths.

Researchers writing in the New England Journal of Medicine took a look back to compare the clinical characteristics of those who died with those who survived the illness with the intent of being able to help clinicians better ascertain who is at risk of complications from the serious lung injury. They found that more people who died had cardiac disease, asthma, or chronic obstructive pulmonary disease, and, interestingly, 65% of those who died had known mental health conditions.

“More than half the patients with fatal cases (63%) received a diagnosis of acute respiratory distress syndrome, which can lead to life-threatening acute hypoxemic respiratory failure,” Angela K. Werner, MD, and colleagues from the CDC’s Lung Injury Response Mortality Working Group wrote. “Patients with EVALI who have multiple chronic conditions may be at higher risk for acute respiratory distress syndrome and its complications. Because traditional mechanical ventilation can worsen lung injury in patients with acute lung injury or acute respiratory distress syndrome, which would then increase the risk of nonpulmonary organ or system failure, clinicians should consider evidence-based principles regarding the management of acute respiratory distress syndrome when treating patients with severe cases of EVALI.”

To date, the evidence points to vaping products that are obtained from informal sources, such as online, on the street, or from friends, and that contain THC and vitamin E acetate, as the main source of EVALI. Matthew B. Stanbrook, MD, PhD, from the University of Toronto, and Jeffrey M. Drazen, MD, from the New England Journal of Medicine, writing in an accompanying editorial, pointed out that the first report of an EVALI-like illness was reported in 2012.

“These reports reveal a wide variety of pulmonary pathologic conditions, ranging from organizing pneumonia and diffuse alveolar damage to interstitial lung disease. It seems unlikely that a single toxin would account for such heterogeneous disease patterns,” Stanbrook and Drazen wrote. “Indeed, e-cigarette vapor can contain a diverse mixture of different chemicals, some with known toxic or carcinogenic potential, but many others for which the effects of inhalation are unknown… This evidence suggests that we are witnessing more than one syndrome of vaping-induced lung disease: an acute, severe syndrome that affects a large number of e-cigarette users and another, more subtle syndrome that either affects a much smaller proportion of users or requires a longer time to manifest itself in most users. We will only learn whether the latter is the case going forward, but we must address this possibility proactively with much more attention and concern.”

Werner and colleagues reviewed all the fatal and nonfatal cases reported to the CDC as of Jan. 7, 2020 — 2,558 nonfatal hospitalizations and 60 fatalities. For those patients for whom data were available, the researchers looked at demographics, e-cigarette or vaping product use, and clinical characteristics.

Specifically, they found:

  • Most of the patients in both the fatal and nonfatal cases were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively).
  • Non-Hispanic whites made up most of the fatal and nonfatal cases (39 of 49 [80%] and 1104 of 1818 [61%], respectively).
  • The median age of those who died was 51 (range 15-75)
  • The median age of the non-fatal cases was 25 (ranges)13-85)
  • 73% of those who died were 35 or older (44 of 60)
  • 22% of non-fatal cases (555 of 2,514) occurred in those 35 or older.

As for clinical characteristics, Werner and colleagues noted that “patients with fatal cases were more likely than those with nonfatal cases to have a history of any respiratory disease (25 of 57 [44%] versus 371 of 1429 [26%]), cardiac disease (26 of 55 [47%] versus 115 of 1169 [10%]), and any mental health condition (32 of 49 [65%] versus 575 of 1398 [41%]).” They also reported that 52% of those who died had obesity.

The incidence of mental health conditions was higher than that of the U.S. general population (19%). “Patients, particularly former smokers, with mental health conditions are more likely to report lifetime and current e-cigarette, or vaping, product use,” Werner and colleagues wrote. “The prevalence of mental health conditions is higher among persons reporting concurrent use of cannabis and conventional cigarettes.”

Nearly half (46%) of the patients who died initially presented in an outpatient setting, such as a primary care office, urgent care center, or emergency department, and were not admitted for EVALI-related symptoms.

Werner and colleagues noted that glucocorticoid use varied widely among those who died and was frequently administered with antibiotics. They noted that glucocorticoid administration has been associated with rapid clinical improvement in EVALI patients and noted that, for those that died, the steroid treatment may have come too late in the clinical course.

“Among the hospitalized patients with fatal cases, 40 of 55 (73%) had hypoxia, 25 of 54 (46%) had tachycardia, and 26 of 52 (50%) had tachypnea at the time of admission to the hospital,” the researchers wrote. “The laboratory values at the initial admission showed that 37 of 52 patients (71%) with fatal cases had leukocytosis (white cell counts >11,000 per cubic millimeter) and 29 of 45 (64%) had neutrophil predominance (white cell count with >80% neutrophils). Most of the patients with fatal cases (93%) died in the hospital.

Most of the patients who died from EVALI had used THC-containing products, nearly a third of them only used nicotine products, and about 25% reported using both THC-containing-products and nicotine products, “which suggests that other causal mechanisms may need to be considered,” Werner and colleagues wrote. “The median age was higher among the patients with fatal cases than among those with nonfatal cases, and the proportion of patients who had chronic medical conditions or were current or former combustible tobacco smokers was higher among those with fatal cases.”

Another finding that Werner and colleagues said should be on clinicians’ radar is the presence of gastrointestinal symptoms (diarrhea and nausea), which were present in both fatal and non-fatal cases, but more so in those who survived the illness.

Limitations of the study include that the researchers counted all EVALI patients who died as a fatal EVALI case, but pre-existing conditions may have contributed to the death, and likewise such conditions may have led to hospitalizations. If there were deaths after hospitalizations, they may have been missed. Also, the researchers noted that they were able to collect more data on those who died versus the nonfatal cases.

  1. Patients with EVALI are at a higher risk of dying from the illness if they have underlying cardiac, respiratory, or mental health condition.

  2. Be aware that the researchers also found an association between death from EVALI and obesity.

Candace Hoffmann, Managing Editor, BreakingMED™

Werner had nothing to disclose.

Drazen is the editor of NEJM Group.

Stanbrook had nothing to disclose.

Cat ID: 195

Topic ID: 89,195,730,102,914,138,139,142,143,192,150,151,195,489,925