E‐cigarette, or Vaping, Associated Lung and Hepatic Injury

Abstract

E-cigarette usage is an increasing mode of nicotine consumption in the United States since it became commercially available in 2006. The National Youth Tobacco Survey revealed a 3-fold increase in e-cigarette usage between 2011 and 2013 in adolescents without a previous history of smoking (1). As of November 2019, reports from the CDC verified 1479 cases of severe lung illnesses associated with e-cigarettes from 49 states (2). Patients presented with complaints of cough, shortness of breath, fever, chest pain, nausea, and diarrhea. Chest radiographs demonstrated bilateral opacities, whereas computerized tomography (CT) showed diffuse ground-glass opacities. Among the most reported cases, nearly all patients were negative for infectious causes with minimal extrapulmonary involvement, such as, gastrointestinal involvement. Recent studies have shown an association of e-cigarette use and liver damage. Hasan, et al, reported that E-cigarette smoke exposure in mice was associated with increased oxidative stress and hepatocyte apoptosis, and rats exposed to e-cigarette extract had elevated liver enzyme levels (3). We report a teenage boy with e-cigarette-related disease presenting with abdominal pain and elevated liver enzymes. It is our hope that abdominal pain and liver injury, in the context of a history of e-cigarette use, will better support a diagnosis of e-cigarette-induced injury, and minimize delay in treatment. CASE REPORT A 17-year-old boy with no significant past medical history was transferred from an outside hospital for intractable vomiting, fever, jaundice, and diarrhea. The patient presented to his pediatrician for a febrile episode, who diagnosed him with acute hepatitis and sent him to the outside hospital for an abdominal ultrasound. The patient was suspected of probable infectious hepatitis and was referred to our facility for further evaluation. On admission, the patient presented with anorexia, abdominal pain, diarrhea, nausea, vomiting, and myalgias. Physical examination only revealed mild jaundice. The patient denied any recent sexual activities but admitted to frequent THC vaping 2 to 3 times per week for the past 6 months. Initial evaluation, including hepatitis labs, was negative. Abdominal and pelvic CT was unremarkable for hepatic or biliary duct obstruction or inflammation. Labs were significant for lymphocytosis with neutrophilia, thrombocytosis, elevated total and direct bilirubin, increased fibrinogen, and decreased albumin (Table 1). A drug screen was positive for tetrahydrocann abinol (THCO) and negative for acetaminophen. Infectious disease evaluation was unremarkable including negative CMV IgG. Antismooth-muscle and liver-kidney-microsomal antibodies. While hospitalized, the patient had 12 febrile spikes every 12.8 hours on average, accompanied by tachycardia. Infectious disease consultant suspected zoonotic infections, such as tularemia, leptospirosis, and bartonellosis, and initiated doxycycline. Serology and febrile panels were negative for Bartonella spp., tularemia, Ehrlichia spp., and brucellosis. Karius tests were also negative. Other diagnoses, such as endocarditis, respiratory infection, and autoimmune disorders were also considered. A brief episode of cough with clear secretions prompted a pulmonology consultation. Spirometry testing demonstrated mild obstructive disease, mildly reactive to bronchodilators; high-resolution CT lung scan revealed bilateral diffuse alveolar infiltrates and right paratracheal lymphadenopathies (Fig. 1). The patient was treated with indomethacin and remained afebrile for 48 hours. After 10 days of hospitalization, the patient was diagnosed with e-cigarette vaping-associated lung injury (EVALI) and discharged. A 1-week follow-up revealed marked clinical and laboratory improvement (Fig. 2).TABLE 1: Hematologic and metabolic laboratoryFIGURE 1: High-resolution computerized tomography. HRCT lung scan shows bilateral diffuse alveolar infiltrates. HRCT = high-resolution computerized tomography.FIGURE 2: Aspartate transaminase, alanine transaminase, total and direct bilirubin levels after admission. Indomethacin, was initiated on day 7 of hospitalization.DISCUSSION Although most current e-cigarette case reports describe patients with acute inflammatory lung disease, our case with EVALI presented with anorexia, abdominal pain, diarrhea, nausea, vomiting, and myalgias, suggesting that vaping-related disease can present without apparent thoracic injury (4). Our patient also presented with liver enzyme abnormalities, most consistent with hepatocellular pattern (Table 1). This pattern is mostly consistent with viral and toxic hepatitis, as well as end-stage cirrhosis from any cause. Viral hepatitis, including hepatitis E virus, could present similarly. Our patient, however, denied any recent travel to endemic areas or associated consumption of potentially contaminated food. Additionally, our patient had evidence of acute lung injury on imaging and spirometry making viral hepatitis infection less likely (Fig. 2). Preliminary reports have shown that gastrointestinal and constitutional symptoms are reported in 81% and 100%, respectively, of all patients who are ultimately diagnosed with EVALI. Nausea is present in 70% of patients, followed by vomiting in 66%, and diarrhea and abdominal pain in 43% each. Additionally, 2% of patients present without respiratory symptoms, and 38% present with oxygen saturation between 89% and 94% (5). Clinical reports of e-cigarette-induced abdominal symptoms are lacking. Some researchers, however, have demonstrated potential mechanisms of vaping-related hepatic disease. Alexander et al (6) demonstrated that chronic inhalation of e-cigarette vapor in mice bronchial epithelial cells can induce systemic inflammation and organ damage. Investigators showed that chronic inhalation of propylene glycol (PG), glycerine (Gly), and nicotine (24 mg/ml) induced a 1.9-fold higher deposition of collagen compared with controls. In addition, PG, Gly, and nicotine inhalation stimulated bronchial epithelial secretion of multiple inflammatory proteins, including dipeptidyl peptidase-4 (DPP4), a known fibrosis-associated enzyme (6). Golli et al (7) showed that mice exposed to e-cigarette refill liquid causes hepatic oxidative stress in vivo. PG, Gly, and nicotine (18 mg/ml) injection into rat peritoneum was associated with elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, lactate dehydrogenase, and reduced antioxidant enzyme activity. Additionally, histopathological changes revealed moderate leukocyte infiltration, apoptosis, mild lipid deposits, and vascular congestion (7). Our patient had increased AST, ALT, and direct and total bilirubin levels that returned to normal values post indomethacin treatment and abstinence from e-cigarette use. The patient was cleared for discharge and advised to avoid further e-cigarette usage. Follow-up was scheduled with pulmonology, infectious disease, and gastroenterology specialists as an outpatient. From our experience, we suggest keeping e-cigarette-related injury in the differential diagnosis of any patient presenting with abdominal complaints and a history of e-cigarette usage, even with minimal pulmonary symptoms. Additionally, ordering liver enzyme tests could further expedite the diagnosis of vaping-related injury in future cases.