Table 2:

Pathological findings in lung biopsy specimens submitted to the CDC for the evaluation of suspected EVALI

	Specimen type	Lung biopsy site	Weeks from illness onset to biopsy*	Pathological diagnosis in lung tissue	Intra-alveolar macrophages in lung tissue	Other pathological and infectious disease findings†	Findings from initial chest CT or x-ray‡	Age group, years	E-cigarette or vaping product use	Medical comorbidities§ and smoking history	Surveillance case definition classification¶
Case 1	Surgical	Right lower lobe	1 week	Diffuse alveolar damage (exudative and proliferative), multifocal (small samples)‖	Foamy macrophages and non-pigmented macrophages, multifocal	Anthracosis, rare; neutrophilic inflammation, scattered	Innumerable pulmonary nodules with mediastinal lymphadenopathy	≥35	THC, nicotine	Conventional cigarette smoking	Probable
Case 2	Trans-bronchial	Right middle and right lower lobe	1 week	Diffuse alveolar damage (proliferative), diffuse (small samples)‖	Foamy macrophages and non-pigmented macrophages, multifocal	Anthracosis, rare; neutrophilic inflammation, scattered	Multifocal, patchy, and predominantly peripheral ground glass opacities; prominent mediastinal lymph nodes	<35	THC	Chronic pain	Confirmed
Case 3	Surgical	Left upper lobe, lingula	2 weeks	Diffuse alveolar damage (exudative and proliferative), diffuse	Foamy macrophages and non-pigmented macrophages, multifocal	Anthracosis, rare; mild neutrophilic inflammation; mild oedema; mild interstitial lymphocytic infiltrate; Gram stain and GMS: non-contributory; IHC for Streptococcus spp and select Gram-negative bacteria:** negative	Diffuse bilateral ground glass opacities	<35	THC, nicotine, CBD	Not reported	Confirmed
Case 4	Surgical	Left lower lobe	2 weeks	Organising pneumonia with bronchiolitis, airway-centred	Foamy macrophages and non-pigmented macrophages, multifocal, rare; foamy macrophages and non-pigmented macrophages, bronchiolar	Eosinophils within fibroblastic proliferations in the airways; Gram stain and GMS: negative; IHC for Streptococcus spp and select Gram-negative bacteria: negative	Innumerable pulmonary nodules, prominent bilateral hilar lymph nodes	<35	THC, nicotine	Conventional cigarette smoking	Confirmed
Case 5	Surgical	Right middle lobe	3 weeks	Diffuse alveolar damage (proliferative), multifocal, airway-centred	Foamy macrophages and non-pigmented macrophages, multifocal; pigmented macrophages (pigment not otherwise specified), moderate multifocal; pigmented macrophages (haemosiderin-laden), multifocal, rare	Anthracosis, rare; fibrin thrombi, rare; emphysema; neutrophilic inflammation, multifocal; eosinophils, scattered; chronic interstitial inflammation, multifocal; Gram stain: negative; Streptococcus spp IHC: positive; Streptococcus pneumoniae PCR: negative	Extensive ground glass opacities	≥35	THC	Obstructive sleep apnoea	Confirmed
Case 6	Surgical	Left upper lobe, lingula	3 weeks	Diffuse alveolar damage (exudative and proliferative), multifocal	Foamy macrophages, rare; non-pigmented macrophages, moderate	Oedema; neutrophilic infiltrates, moderate; intravascular fibrin thrombi; intravascular leukocytosis, moderate; Gram stain and GMS: non-contributory; Streptococcus spp and select Gram-negative IHC: negative	Diffuse ground glass opacities and airspace opacities	<35	THC, nicotine	Not reported	Confirmed
Case 7	Surgical	Right upper lobe, middle lobe, and lower lobe	3 weeks	Organising pneumonia, diffuse	Foamy macrophages, multifocal; non-pigmented macrophages, extensive; non-pigmented macrophages, bronchiolar; pigmented macrophages (haemosiderin-laden), scattered	Anthracosis, rare; haemorrhage; eosinophils, scattered; fibrosis (severe)	Extensive bilateral infiltrates	<35	THC, nicotine	Chronic respiratory disease; conventional cigarette smoking	Probable
Case 8	Surgical	Right upper lobe	3 weeks	Diffuse alveolar damage (proliferative), diffuse	Foamy macrophages and non-pigmented macrophages, multifocal; pigmented macrophages (haemosiderin-laden and subset of macrophages with pigment not otherwise specified), occasional	Anthracosis, multifocal, rare; intra-alveolar neutrophils, scattered; interstitial lymphocytes, multifocal	Moderate, patchy, diffuse lung consolidation, lower lobe predominant; irregular mass-like process in left lower lobe; mediastinal and hilar borderline lymphadenopathy	≥35	Nicotine	Diabetes; conventional cigarette smoking	Confirmed
Case 9	Surgical	Left lower lobe	4 weeks	Diffuse alveolar damage (proliferative), multifocal and geographic	Foamy macrophages, rare; non-pigmented macrophages, multifocal; pigmented macrophages (haemosiderin-laden), scattered	Anthracosis, multifocal, rare; Gram stain and GMS: negative; Pneumocystis jirovecii, Streptococcus spp, and select Gram-negative IHC: negative	Bilateral abnormality, infiltrates or opacities present, no subpleural sparing	<35	THC, nicotine	Not reported	Probable
Case 10	Surgical	Right middle and right lower lobe	6–8 weeks	Diffuse alveolar damage (proliferative and organising), multifocal (middle lobe) to diffuse (lower lobe)	Foamy macrophages and non-pigmented macrophages, multifocal; pigmented macrophages (haemosiderin-laden), rare, lower lobe	Anthracosis, rare; mild haemorrhage; oedema fluid (subpleural and intra-alveolar); mild chronic interstitial infiltrate; fibrin thrombi	Extensive patchy areas of consolidation and airspace disease in both lungs	<35	THC	Obesity; hypertension; chronic pain	Confirmed

Pathology findings are described as “pathology (characteristic), distribution” unless otherwise specified. CBD=cannabidiol. CDC=Centers for Disease Control and Prevention. EVALI=e-cigarette, or vaping, product use-associated lung injury. GMS=Grocott methenamine silver stain. IHC=immunohistochemistry. THC=tetrahydrocannabinol.

^*Weeks from illness onset to biopsy are defined as 1 week meaning less than 7 days, 2 weeks meaning 7–13 days, etc.

^†Also results from the CDC tissue-based infectious disease testing.

^‡Based on imaging findings reported to the CDC.

^§Includes reported history of one or more of the following: obesity, chronic pain, chronic respiratory disease, obstructive sleep apnoea, diabetes, or hypertension. Seven (70%) of ten individuals had a reported mental health diagnosis; these data are not included at an individual level in this table.

^¶The CDC 2019 lung injury surveillance primary case definition (appendix p 3).²

^‖Assessment limited by small size of the tissue sample.

^**Details to clarify cross-reactivity of the select Gram-negative IHC assay are in the appendix p 2.