Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping)

A Report of Eight Cases

Sanjay Mukhopadhyay, MD; Mitra Mehrad, MD; Pedro Dammert, MD; Andrea V. Arrossi, MD; Rakesh Sarda, MD; David S. Brenner, MD; Fabien Maldonado, MD; Humberto Choi, MD; Michael Ghobrial, MD


Am J Clin Pathol. 2019;153(1):30-39. 

In This Article


Clinical Findings

The clinical findings are summarized in Table 1. All eight patients were men (age range, 19–61 years; mean, 29 years) who developed respiratory symptoms following e-cigarette use (vaping). All patients reported vaping THC; two were also vaping nicotine. One individual had a history of dabbing. The most common presenting symptoms were fever (n = 7/8 patients), cough (n = 6/8), and dyspnea (n = 5/8). Most patients had no significant prior medical illness. One patient had a history of inflammatory bowel disease (case 5). Another had a history of chronic pain (on medical marijuana, tramadol, baclofen, and pregabalin), degenerative disc disease, cervical radiculopathy, peripheral neuropathy, and neurogenic bladder (case 3). Four patients were hypoxic at presentation. Empiric broad-spectrum antibiotics were administered in seven. Bilateral crackles were audible in the lungs on auscultation in two individuals and bilateral coarse rhonchi in one. Notable laboratory findings included leukocytosis (n = 6/8) with neutrophil predominance and elevations in erythrocyte sedimentation rate and C-reactive protein in a few individuals. Workup for infection was negative in seven of eight cases. The tests performed were different for each patient but generally included respiratory viral panels, serologic studies for fungi, testing for Legionella and HIV, and microbiologic cultures of sputum, blood, BAL fluid, and biopsied lung tissue. In case 4, there was a weakly positive Legionella immunoglobulin G, but immunoglobulin M testing and urine antigen were negative. Bronchoscopy with transbronchial lung biopsies were performed in seven patients and surgical lung biopsy in one. There was no clinical or laboratory evidence for other plausible etiologies in any patient; autoimmune serologies were negative in all patients tested. Chest CT showed bilateral ground-glass opacities in all patients Image 1. In addition, bilateral consolidation was noted in some. Seven individuals were treated with corticosteroids and one with antibiotics. Most recovered with corticosteroid therapy and were discharged home within a few days. One patient (61-year-old man, case 3) developed severe acute respiratory distress syndrome. His condition continued to deteriorate, with worsening hypoxia and fever, and his course was complicated by methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia on day 21 of admission. Despite receiving appropriate antibiotic therapy and mechanical ventilation, his condition worsened and he died on day 31 of admission.

Image 1.

Chest computed tomography findings in severe pulmonary disease associated with e-cigarette use (vaping). A, Case 1: diffuse bilateral ground-glass opacities with peripheral prominence, mimicking eosinophilic pneumonia. B, Case 2: diffuse bilateral ground-glass opacities with areas of consolidation. C, Case 4: bilateral basilar dependent consolidations with diffuse ground-glass opacities and mild smooth septal thickening. D, Case 6: bilateral ground-glass opacities in a somewhat patchy distribution.

Lung Biopsy Findings

The pathologic findings are summarized in Table 2 and illustrated in Image 2, Image 3, and Image 4. All eight biopsy specimens showed acute lung injury, manifesting as organizing pneumonia, diffuse alveolar damage (DAD), unclassifiable organizing acute lung injury, or a combination of these patterns. Four biopsy specimens featured variably prominent areas of organizing pneumonia, characterized by the presence of serpiginous or polypoid fibroblast plugs (Masson bodies) within airspaces (Image 2). This was accompanied by mild interstitial chronic inflammation in three cases and focal acute inflammation within the airspaces in case 8. Two biopsy specimens showed DAD (Image 2). In case 3, the only surgical lung biopsy specimen in this series, areas of DAD were admixed with areas of organizing pneumonia (mixed acute lung injury pattern). Both biopsy specimens with DAD featured hyaline membranes (acute stage of DAD) as well as alveolar septal expansion by fibroblasts (organizing stage of DAD). Two biopsy specimens showed organizing acute lung injury that could not be further classified.

Image 2.

Lung biopsy findings in vaping-associated pulmonary illness. A, Organizing pneumonia (case 3). A polypoid fibroblast plug fills an airspace (H&E, ×200). B, Organizing pneumonia, case 2 (H&E, ×200). C, Diffuse alveolar damage, case 3. Note hyaline membranes and interstitial thickening (H&E, ×200). D, Diffuse alveolar damage, case 1. Hyaline membranes are beginning to detach into airspaces (H&E, ×200).

Image 3.

Fibrinous exudates and interstitial inflammation in vaping-related lung injury. A, B, Fibrinous exudates within airspaces (A, case 1, H&E, ×200; B, case 3, H&E, ×200). C, Interstitial inflammation, case 1 (H&E, ×200). D, Interstitial inflammatory infiltrate at high magnification, showing lymphocytes and a rare eosinophil (case 2, H&E, ×400).

Image 4.

Macrophages in vaping-related lung injury. A, Foamy macrophages within airspaces, case 3 (H&E, ×400). B, Few intra-alveolar macrophages without distinctive features, case 2 (H&E, ×400). C, Macrophages in bronchoalveolar lavage fluid do not show prominent intracytoplasmic vacuoles (Papanicolaou stain, ×400). D, Oil red O–positive macrophages, case 4, courtesy of Margaret Compton, MD (oil red O, ×400).

Fibrinous exudates with varying degrees of organization were noted within airspaces in six of eight biopsy specimens (Image 3). In most cases, they were a focal finding. Overall, interstitial chronic inflammation composed mainly of lymphocytes was noted in six of eight cases. In cases 1 and 8, immunohistochemical stains showed that the lymphocytic infiltrate was composed mainly of CD3-positive T cells and very few CD20-positive B cells.

Variable numbers of macrophages were present within airspaces in all cases (Image 4). However, they were not a prominent finding in any biopsy specimen. A CD68 stain (performed in cases 1 and 8) confirmed the presence of several CD68-positive macrophages, mainly within airspaces. The macrophages contained foamy cytoplasm in three cases, but the coarsely vacuolated cytoplasm characteristic of exogenous lipoid pneumonia was not noted in any of the biopsy specimens. Similarly, interstitial lipid deposits surrounded by multinucleated giant cells—as seen in exogenous lipoid pneumonia—were absent in all cases. BAL fluid was macrophage predominant in six cases, without a foamy appearance or coarse vacuoles. Oil red O staining, performed in cases 4, 5, and 6, was positive in all three cases. The lipid index was 12 in case 4 and 6 in cases 5 and 6.

In all biopsy specimens in which special stains for mycobacteria and fungi (Ziehl-Neelsen and/or Grocott methenamine silver) were performed, they were negative. No granulomas or malignant cells were identified, and there were no histologic findings suggesting a plausible alternative etiology.