Alveolar macrophages from EVALI patients and e-cigarette users: a story of shifting phenotype.

Exposure to e-cigarette vapors alters important biologic processes including phagocytosis, lipid metabolism, and cytokine activity in the airways and alveolar spaces. Little is known about the biologic mechanisms underpinning the conversion to e-cigarette, or vaping, product use-associated lung injury (EVALI) from normal e-cigarette use in otherwise healthy individuals. We compared cell populations and inflammatory immune populations from bronchoalveolar lavage fluid in individuals with EVALI to e-cigarette users without respiratory disease and healthy controls and found that e-cigarette users with EVALI demonstrate a neutrophilic inflammation with alveolar macrophages skewed towards inflammatory (M1) phenotype and cytokine profile. Comparatively, e-cigarette users without EVALI demonstrate lower inflammatory cytokine production and express features associated with a reparative (M2) phenotype. These data indicate macrophage-specific changes are occurring in e-cigarette users who develop EVALI.

Diagnosis of EVALI: General Approach and the Role of Bronchoscopy.

A 23-year-old man arrives at the ED with a 3-week history of dyspnea, dry cough, fevers, and night sweats. Two weeks previously, he was evaluated in an outpatient clinic and given a course of azithromycin for presumed infectious pneumonia. His symptoms did not improve, and he was seen 1 week later in an urgent care center and given a prescription for doxycycline, which he has been taking without improvement. He states that he feels miserable, has severe nausea and vomiting, and has not eaten in several days. His only medical history is childhood asthma. He reports no surgeries and takes no medications. He has no risk factors for HIV, does not smoke combustible cigarettes or use IV drugs, and has not recently traveled. Examination shows a room air saturation of 89%, a temperature of 38.3°C, and a respiratory rate of 22 breaths/min. Results of his examination are normal, and there are no rales or wheezing heard in the lungs. Chest radiograph shows bilateral, consolidative opacities. WBC count is 14,000, with left shift. Results of biochemistries are normal. Erythrocyte sedimentation rate is 104, and procalcitonin is 0.08. Urine toxicology screen is positive for tetrahydrocannabinol (THC). Asked specifically about vaping and e-cigarette use, he reports that he recently began using THC "carts" that his friend gets from an unknown supplier. What is the diagnosis and what additional steps are necessary to confirm it? Is bronchoscopy indicated?

Clinical, Bronchoscopic, and Imaging Findings of e-Cigarette, or Vaping, Product Use-Associated Lung Injury Among Patients Treated at an Academic Medical Center.

Importance: e-Cigarette, or vaping, product use-associated lung injury (EVALI) has caused more than 2800 illnesses and 68 deaths in the United States. Better characterization of this novel illness is needed to inform diagnosis and management. Objective: To describe the clinical features, bronchoscopic findings, imaging patterns, and outcomes of EVALI. Design, Setting, and Participants: This case series of 31 adult patients diagnosed with EVALI between June 24 and December 10, 2019, took place at an academic medical center in Salt Lake City, Utah. Exposures: e-Cigarette use, also known as vaping. Main Outcomes and Measures: Symptoms, laboratory findings, bronchoscopic results, imaging patterns, and clinical outcomes. Results: Data from 31 patients (median [interquartile range] age, 24 [21-31] years) were included in the study. Patients were primarily men (24 [77%]) and White individuals (27 [87%]) who used e-cigarette products containing tetrahydrocannabinol (THC) (29 [94%]). Patients presented with respiratory (30 [97%]), constitutional (28 [90%]), and gastrointestinal (28 [90%]) symptoms. Serum inflammatory markers were elevated in all patients. Bronchoscopy was performed in 23 of 28 inpatients (82%) and bronchoalveolar lavage (BAL) revealed the presence of lipid-laden macrophages (LLMs) in 22 of 24 cases (91%). BAL samples tested positive for Pneumocystis jirovecii (3 patients [13%]), rhinovirus (2 patients [8%]), human metapneumovirus and Aspergillus (1 patient each [4%]); all except human metapneumovirus were determined to be false-positives or clinically inconsequential. The exclusive or dominant computed tomography (CT) pattern was organizing pneumonia in 23 of 26 cases (89%). Patients received antibiotics (26 [84%]) and corticosteroids (24 [77%]), and all survived; 20 patients (65%) seen in follow-up showed marked improvement, but residual symptoms (13 [65%]), radiographic opacities (8 [40%]), and abnormal pulmonary function tests (8 of 18 [44%]) were common. Conclusions and Relevance: In this case series, patients with EVALI characteristically presented with a flu-like illness with elevated inflammatory markers, LLMs on BAL samples, and an organizing pneumonia pattern on CT imaging. Bronchoscopic testing for infection had a high incidence of false-positive results. Patients had substantial residual abnormal results at early follow-up. These data suggest a limited role for bronchoscopy in typical presentations of EVALI without risk factors for alternative diagnoses and the need for careful longitudinal follow-up.