Respiratory

E-cigarette and vaping-associated lung injury (EVALI)

Clinical Overview and When to Suspect EVALI

— Nicotine-only devices have caused cases but THC-containing products dominate (~80%).

— Use of an e-cigarette, vape pen, dab pen, or aerosolized THC/CBD/nicotine product within 90 days (most within 1 week)

— Pulmonary symptoms: dyspnea, cough, pleuritic chest pain, sometimes hemoptysis

— Constitutional: fever, chills, myalgia, fatigue, weight loss

— GI symptoms: nausea, vomiting, diarrhea, abdominal pain — present in >75% and often precede pulmonary symptoms (a major clue)

— Bilateral opacities on chest imaging

— No alternative diagnosis (infection, cardiac, autoimmune) identified

EVALI = E-cigarette or Vaping product use–Associated Lung Injury, a diagnosis of exclusion in patients with recent vaping exposure and acute respiratory, GI, or constitutional symptoms with bilateral pulmonary infiltrates.

Emerged as a national outbreak in mid-2019; CDC peak ~Sept 2019 with >2800 hospitalizations and 68 deaths reported. Continues sporadically — Step 3 vignettes still appear.

Implicated agent: Vitamin E acetate used as a thickening diluent in THC-containing e-cigarette/vape cartridges, especially informal/black-market or "street" products. Confirmed in BAL fluid of affected patients.

Demographics: young, otherwise healthy patients — median age ~24 yrs, male predominance (~2/3), but ranges from adolescents to older adults.

When to suspect EVALI in the ED:

Board pearl: A young vaper presenting with GI symptoms plus bilateral ground-glass opacities and negative respiratory viral/SARS-CoV-2 panel is the prototypical EVALI stem — the GI prodrome distinguishes it from typical CAP or viral pneumonia.

Key distinction: EVALI is clinical and exclusionary — there is no confirmatory test. Always actively rule out infection (influenza, COVID-19, bacterial pneumonia) before anchoring on EVALI, because empiric antibiotics and antivirals are recommended until those are excluded.

Presentation Patterns and Key History

— Respiratory (95%): dyspnea (85%), cough (85%), chest pain (50%), occasionally hemoptysis

— Constitutional (85%): fever, chills, weight loss, fatigue, night sweats

— GI (77%): nausea, vomiting, abdominal pain, diarrhea — often precede or dominate the picture

— Specific products used: e-cigarettes, vape pens, dab pens, wax pens, dank vapes, mods, pod-based devices (e.g., JUUL)

— Substance vaped: nicotine, THC, CBD, "synthetic" cannabinoids, flavoring oils

— Source: licensed dispensary vs. informal/street/online sources (highest risk)

— Frequency, duration, and last use date

— Modifications: refilling cartridges, adding oils, "DIY" liquids

Symptom triad to recognize:

Symptom onset is typically subacute over days to weeks, not hyperacute. Patients often have had prior outpatient visits or urgent care encounters misdiagnosed as gastroenteritis, viral syndrome, or community-acquired pneumonia with failed outpatient antibiotics.

History to elicit — must be deliberate; patients frequently underreport vaping:

Ask in a non-judgmental, confidential manner, especially in adolescents — disclosure improves when parents step out.

Step 3 management: Document a structured vaping history in the chart and report suspected cases to your state health department; EVALI remains a reportable condition in many states under outbreak surveillance.

Risk factors for severe disease: older age, comorbid asthma/COPD, cardiac disease, and heavier THC-vape use.

Board pearl: If the stem describes a college-aged patient with 1–2 weeks of fevers, vomiting, and progressive dyspnea who admits to using a "dab pen" bought from a friend, the answer is EVALI — even if a chest x-ray reads "pneumonia."

Key distinction: Unlike acute eosinophilic pneumonia (which can also follow vape exposure), EVALI typically has neutrophilic — not eosinophilic — BAL and a more subacute course with prominent GI symptoms.

Physical Exam Findings and Hemodynamic Assessment

— Tachypnea (RR >20) — present in ~85%

— Hypoxemia — SpO₂ <95% on room air in ~70%; many require supplemental O₂ at triage

— Tachycardia (HR >100) — common, often >110

— Fever (>38°C) in ~80%

— Blood pressure usually preserved; frank shock suggests alternative diagnosis (sepsis, PE) or progression to ARDS

— Often deceptively normal auscultation despite striking imaging — a recurring exam clue

— When abnormal: bilateral crackles, occasionally rhonchi; wheezing uncommon unless underlying asthma

— No focal consolidation typical of bacterial pneumonia

— Continuous pulse oximetry; consider arterial blood gas if SpO₂ <90% or work of breathing high

— Calculate PaO₂/FiO₂ ratio to grade severity; <300 = ARDS criteria

— Trend respiratory rate and accessory muscle use; rising RR + falling SpO₂ on increasing FiO₂ portends impending intubation

General appearance: ill-appearing young adult, often febrile, tachypneic, and visibly hypoxic — the disconnect between youth/baseline health and acuity is a clue.

Vital signs (typical at ED presentation):

Pulmonary exam:

Cardiac exam: tachycardia without murmur, no JVD, no peripheral edema — helps distinguish from cardiogenic pulmonary edema.

Abdominal exam: mild diffuse tenderness possible given GI prodrome, but no peritoneal signs; if present, consider alternative.

Skin/extremities: no rash, no joint swelling — presence should prompt evaluation for vasculitis, connective tissue disease, or DRESS.

Hemodynamic assessment in the ED:

CCS pearl: Order pulse oximetry on room air and ambulatory (walking) oximetry — exertional desaturation often unmasks severity in patients whose resting saturation looks acceptable, and it changes disposition from outpatient to admission.

Board pearl: The "hypoxic but quiet chest" young vaper with bilateral infiltrates on CXR is a high-yield Step 3 visual cue for EVALI.

Diagnostic Workup — Initial Labs and Imaging

— Leukocytosis with neutrophilic predominance in ~90%

— Eosinophilia is typically absent — if present, think acute eosinophilic pneumonia or drug reaction instead

— Mild lymphopenia common

— Elevated ESR and CRP (CRP often >50 mg/L)

— Procalcitonin usually low to mildly elevated — useful but not definitive in distinguishing from bacterial pneumonia

— Transaminitis (mild AST/ALT elevation) in ~30%

— Check lipase if abdominal pain prominent — vaping-associated pancreatitis has been reported

— Respiratory viral panel including influenza A/B and SARS-CoV-2 PCR

— Blood cultures × 2 if febrile

— Sputum Gram stain/culture if productive

— Urinary Streptococcus pneumoniae and Legionella antigens

— HIV testing

— Consider mycoplasma, chlamydophila, and in endemic exposure, fungal serologies

— Chest x-ray: bilateral hazy or patchy opacities, often basilar/peripheral predominant; may be normal early (~10%)

— Chest CT (preferred): bilateral ground-glass opacities, often with subpleural sparing, sometimes consolidation, septal thickening, "crazy paving"; pleural effusions uncommon

CBC with differential:

Inflammatory markers:

Chemistry, LFTs, lipase:

Coagulation and D-dimer: D-dimer may be elevated nonspecifically; obtain only if PE is a real consideration to avoid downstream CTA in low-pretest-probability patients.

Infectious workup (mandatory — EVALI is exclusionary):

Imaging:

ECG: sinus tachycardia; obtain to exclude ischemia/myopericarditis if chest pain prominent.

Board pearl: Subpleural sparing on chest CT in a young vaper is a classic EVALI imaging finding and a frequent image-based stem cue.

Step 3 management: Send respiratory viral PCR and urinary antigens before committing to a primary EVALI diagnosis; documenting exclusion of infection is the standard of care and a frequent test point.

Diagnostic Workup — Advanced and Confirmatory Studies

— Diagnosis is uncertain after first-line workup

— Patient fails to improve on empiric therapy

— Immunocompromised host needing broader pathogen evaluation

— Considering alternative diagnoses (DAH, eosinophilic pneumonia, malignancy)

— Neutrophilic predominance (often >25–50%)

— Lipid-laden macrophages on Oil Red O staining — supportive but not specific (also seen in lipoid pneumonia, aspiration)

— Vitamin E acetate detection in BAL fluid (CDC reference lab) — most specific finding; not routinely available clinically

— Negative microbiology

— Confirmed: e-cigarette/vape use within 90 days + pulmonary infiltrate on imaging + infection excluded + no alternative plausible diagnosis

— Probable: same but infection identified yet thought not to fully explain illness

Bronchoscopy with BAL — not required for diagnosis but performed when:

BAL findings in EVALI:

Pulmonary function testing: typically deferred acutely; outpatient PFTs at 2–4 weeks often show restrictive pattern with reduced DLCO.

Echocardiography: consider to exclude cardiogenic pulmonary edema or pulmonary hypertension if exam/BNP suggests cardiac contribution.

Surgical lung biopsy: rarely needed; histology shows patterns of organizing pneumonia, diffuse alveolar damage, or acute fibrinous pneumonitis — non-specific.

Autoimmune serologies (ANA, ANCA, anti-GBM): obtain only if vasculitis or DAH suspected (hemoptysis, hematuria, sinusitis).

CDC case definition for surveillance (must know for Step 3):

Key distinction: Lipid-laden macrophages do not confirm EVALI — they are a sensitive but non-specific marker. Vitamin E acetate in BAL is the most specific biomarker but is a research/public-health test, not a clinical decision tool.

Board pearl: Bronchoscopy is reserved for diagnostic uncertainty or treatment failure — it is not required to start empiric corticosteroids when EVALI is clinically obvious and infection has been reasonably excluded.

Risk Stratification and First-Line Management Logic

— Outpatient management considered only if all of: SpO₂ ≥95% on RA, no respiratory distress, no comorbidities, reliable follow-up within 24–48 hours, social support, and access to return precautions.

— Admit if: SpO₂ <95% on RA, respiratory distress, comorbidities (cardiopulmonary, immunocompromise), inability to follow up, or concerning trajectory.

— ICU if: respiratory failure requiring high-flow O₂/NIPPV/intubation, hemodynamic instability, or rapid clinical deterioration.

— Establish IV access, place on telemetry and pulse ox

— Supplemental O₂ to maintain SpO₂ ≥92% (≥88% if comorbid COPD)

— Send infectious workup (above)

— Start empiric antibiotics for CAP (ceftriaxone + azithromycin, or respiratory fluoroquinolone) — continue until bacterial etiology excluded

— Start empiric oseltamivir during influenza season until influenza PCR returns negative

— Initiate corticosteroids in admitted patients with hypoxemia or progressive disease once infection is reasonably excluded (typically methylprednisolone 1 mg/kg/day or equivalent)

— Mild: >300

— Moderate: 200–300

— Severe/ARDS: <200 → ICU, lung-protective ventilation strategy

CDC/ATS-endorsed disposition framework — memorize for Step 3:

Empiric ED workup-to-treatment pathway:

Severity grading by PaO₂/FiO₂:

CCS pearl: On the CCS interface, when EVALI is suspected — order CXR, CBC, CMP, CRP, respiratory viral PCR including influenza and SARS-CoV-2, urinary antigens, blood cultures, oxygen therapy, IV access, telemetry, and advance the clock; once infection is reasonably ruled out and hypoxemia persists, add methylprednisolone and pulmonology consult.

Board pearl: Even mild-appearing EVALI patients deserve admission if discharge follow-up cannot be guaranteed within 48 hours — relapse and rapid deterioration after ED discharge is a documented pattern.

Pharmacotherapy — First-Line Drug Regimen

— Methylprednisolone 1 mg/kg IV daily (typical 40–60 mg IV q12–24h) in hospitalized hypoxemic patients

— Or prednisone 40–60 mg PO daily in less severe inpatients tolerating oral intake

— Begin after infection has been reasonably excluded (negative viral PCR, low procalcitonin, improving cultures)

— Most patients show clinical improvement within 24–48 hours of initiation

— Typical course 2–6 weeks with gradual taper guided by clinical and radiographic response

— Rapid tapers (<2 weeks) associated with rebound/relapse — a tested point

— Outpatient taper coordinated with pulmonology follow-up

— CAP coverage: ceftriaxone 1–2 g IV daily + azithromycin 500 mg IV/PO daily, or levofloxacin 750 mg IV/PO daily

— Influenza coverage (in season): oseltamivir 75 mg PO BID × 5 days until PCR negative

— Add MRSA (vancomycin) or anti-pseudomonal coverage only if risk factors present

— Antiemetics (ondansetron) for GI symptoms

— Antipyretics (acetaminophen) — avoid NSAIDs if acute kidney injury

— Bronchodilators (albuterol) if wheezing or underlying obstructive disease

— DVT prophylaxis (enoxaparin 40 mg SC daily) in admitted patients

— Stress-ulcer prophylaxis if on high-dose steroids and critically ill

Systemic corticosteroids are the cornerstone of EVALI treatment:

Steroid taper:

Empiric antimicrobials (continue until infection excluded):

Supportive pharmacotherapy:

Step 3 management: When starting steroids, also start PCP prophylaxis (TMP-SMX) for patients expected to receive ≥20 mg prednisone equivalent for ≥4 weeks, monitor glucose (steroid-induced hyperglycemia), and counsel on infection precautions.

Board pearl: Corticosteroid initiation produces rapid radiographic and clinical improvement — failure to improve within 48–72 hours should prompt reconsideration of the diagnosis (infection, organizing pneumonia from another cause, vasculitis) and bronchoscopy.

Procedures and Advanced Respiratory Management

— Nasal cannula 1–6 L/min → target SpO₂ ≥92%

— Venturi mask or simple face mask 6–10 L/min

— High-flow nasal cannula (HFNC) — preferred next step in moderate-severe hypoxemia, allows titration of FiO₂ and flow

— Non-invasive positive pressure ventilation (BiPAP/CPAP) — selected patients without altered mental status

— Endotracheal intubation and mechanical ventilation — ~30% of admitted EVALI patients in original cohorts required intubation

— Tidal volume 6 mL/kg ideal body weight

— Plateau pressure <30 cm H₂O

— Driving pressure <15 cm H₂O

— PEEP titrated per ARDSnet table

— Permissive hypercapnia, target SpO₂ 88–95%

— Consider prone positioning for P/F <150

— Empiric broad antibiotics indefinitely — discontinue once infection excluded to limit C. difficile risk

— Diuresis — EVALI is not cardiogenic edema; aggressive diuresis can worsen hypoperfusion without benefit

Most EVALI patients do not require procedures, but respiratory support escalates predictably:

Oxygen escalation ladder:

Mechanical ventilation strategy (ARDS-style lung protection):

ECMO — venovenous ECMO has been used successfully in refractory EVALI with severe ARDS; consult early in young patients with reversible lung injury.

Bronchoscopy with BAL — therapeutic role limited; primarily diagnostic when diagnosis uncertain or treatment failing.

Thoracentesis — rarely needed; pleural effusions uncommon and small when present.

Procedures to avoid or use cautiously:

CCS pearl: In a CCS case progressing to respiratory failure, escalate to HFNC, then intubation with lung-protective settings, transfer to ICU, consult pulmonology/critical care, and consider ECMO referral if P/F remains <100 despite optimized ventilation and prone positioning.

Board pearl: Young EVALI patients with refractory ARDS are excellent ECMO candidates — early referral improves survival, and the question often tests recognition of this.

Special Populations — Elderly and Organ Impairment

— Less common but disproportionately severe — higher rates of ICU admission, intubation, and death (CDC data show all fatal cases skewed older with comorbidities)

— Higher prevalence of cardiopulmonary comorbidities (COPD, CHF, CAD) complicates differential and worsens prognosis

— More likely to be on polypharmacy → review for drug-induced pneumonitis (amiodarone, methotrexate, nitrofurantoin)

— Lower threshold for admission and ICU

— Adjust antimicrobials: levofloxacin, cefepime, vancomycin require renal dosing

— Corticosteroids do not require renal adjustment but monitor for fluid retention and hypertension in CKD

— Avoid NSAIDs; cautious contrast use for CT (consider non-contrast CT chest, which is sufficient for EVALI)

— Monitor for AKI from hypoxemia, sepsis mimicry, or contrast

— Mild transaminitis is common in EVALI itself; baseline LFTs important

— Adjust acetaminophen dosing (≤2 g/day in cirrhosis)

— Steroids may worsen ascites/edema; monitor closely

— Avoid hepatotoxic antibiotics where possible

— Broader differential mandatory — PCP, CMV, invasive fungal, mycobacterial

— Lower threshold for bronchoscopy/BAL

— Coordinate with infectious disease and transplant teams before high-dose steroids

— Often present with more severe baseline symptoms and slower recovery

— Optimize controller therapy on discharge

Older adults (≥50 years):

Renal impairment:

Hepatic impairment:

Immunocompromised hosts (HIV, transplant, chemotherapy, chronic steroids):

Patients with underlying lung disease (asthma, COPD, ILD):

Step 3 management: In elderly or comorbid EVALI patients, anticipate longer steroid courses, closer outpatient follow-up (within 48 hours), and aggressive optimization of underlying cardiopulmonary disease (statins, ACEi, inhalers) at discharge to reduce readmission.

Board pearl: Mortality in EVALI clusters in patients with older age, cardiac disease, COPD, and diabetes — the stem describing a 60-year-old vape user with HFrEF should raise concern for fulminant course.

Special Populations — Pregnancy, Pediatrics, and Adolescents

— ~15% of cases <18 years; ~40% aged 18–24

— Frequently underreport vaping; interview separately from parents with confidentiality assurances (within state minor consent laws)

— High rates of THC vaping, often from informal sources

— Co-use of nicotine vapes plus combustible tobacco and cannabis common

— Weight-based corticosteroid dosing: methylprednisolone 1–2 mg/kg/day (max 60 mg)

— Same diagnostic exclusion of infection applies; add consideration of pertussis and viral bronchiolitis

— Mental health screening — vaping correlates with depression, anxiety, and substance use disorders

— Engage adolescent medicine, pulmonology, and behavioral health

— Vaping during pregnancy is rising and associated with low birth weight, preterm delivery, and developmental concerns

— EVALI in pregnancy is rare but management priorities: maintain maternal SpO₂ ≥95% to protect fetal oxygenation, avoid teratogenic medications

— Corticosteroids: prednisone/methylprednisolone are preferred (extensively metabolized by placenta) over dexamethasone/betamethasone (which cross placenta — used only when fetal lung maturity desired)

— Antibiotics: ceftriaxone and azithromycin are pregnancy-compatible; avoid fluoroquinolones, tetracyclines

— Continuous fetal monitoring in viable pregnancies; coordinate with MFM

— Complete cessation of all vaping/e-cigarette products is the discharge expectation

— Discuss FDA reporting of suspect products

— Address co-occurring nicotine and cannabis use with appropriate cessation support

Adolescents and young adults are the dominant EVALI demographic:

Pediatric management considerations:

Pregnancy:

Counseling for all younger patients:

Key distinction: In pediatric/adolescent EVALI, confidentiality and honest history-taking trump speed of disposition — a missed THC vape disclosure leads to misdiagnosis.

Board pearl: In a teenager with bilateral GGOs and GI prodrome, interview the patient alone — this is both the right clinical move and a frequent ethics/communication question on Step 3.

Complications and Adverse Outcomes

— Acute respiratory failure requiring intubation in ~30% of hospitalized cases

— ARDS with prolonged mechanical ventilation

— Pneumothorax/pneumomediastinum — particularly in patients with intense coughing or barotrauma on PPV; spontaneous cases also reported

— Persistent radiographic abnormalities at 2 months in many patients

— Reduced DLCO and restrictive PFTs lasting months

— Sinus tachycardia, occasional myocarditis/myopericarditis

— Increased risk of arrhythmia in severe hypoxemia

— Long-term vaping associated with increased MI and stroke risk (independent of EVALI)

— Dehydration, electrolyte derangements from vomiting/diarrhea

— Rare reports of vaping-associated pancreatitis and hepatitis

— Steroid-induced hyperglycemia — anticipate and manage with sliding scale insulin

— Steroid-induced hypertension, mood changes, insomnia

— Opportunistic infection risk with prolonged high-dose steroids

— C. difficile colitis from empiric broad-spectrum antibiotics

— VTE from immobility and acute inflammation

— Overall ~2–3%; higher in older patients with comorbidities

— Death typically from refractory ARDS, sepsis from secondary infection, or multi-organ failure

— Documented after rapid steroid tapers or resumption of vaping

— Some patients re-present with worsening symptoms within days of ED discharge — a critical Step 3 disposition pitfall

— Substance use disorder, depression, anxiety frequently co-exist and worsen outcomes

Respiratory complications:

Cardiovascular:

Gastrointestinal:

Metabolic/iatrogenic:

Mortality:

Relapse:

Psychosocial:

Step 3 management: At discharge, screen and manage steroid-induced hyperglycemia with fingerstick checks, prescribe calcium/vitamin D for prolonged courses, and arrange follow-up PFTs in 4–6 weeks to detect persistent lung function decline.

Board pearl: Pneumomediastinum on imaging in a young vaper is a classic presentation, especially with subcutaneous emphysema after intense coughing.

When to Escalate Care — ICU, Consultation, and Triage

— SpO₂ <88% on supplemental O₂ or rising O₂ requirement

— Respiratory rate >30 or accessory muscle use despite HFNC

— P/F ratio <300 (definite if <200)

— Hemodynamic instability (hypotension, lactate elevation)

— Altered mental status

— Need for mechanical ventilation or NIPPV

— Pneumothorax, pneumomediastinum with hemodynamic compromise

— Mild-moderate hypoxemia responsive to low-flow O₂

— Stable vital signs without escalating respiratory support

— Reliable monitoring with continuous pulse oximetry

— Pulmonology — essentially all hospitalized cases for diagnostic confirmation, bronchoscopy decisions, and outpatient follow-up

— Critical care — for ICU-level care and ventilator management

— Infectious disease — when atypical pathogens, immunocompromised host, or diagnostic uncertainty persists

— Toxicology/Poison Control — for guidance on product identification, reporting suspect cartridges

— Adolescent medicine/behavioral health — for pediatric patients and substance use co-management

— Social work — for housing instability, follow-up logistics, cessation resources

— Cardiology — if myocarditis, arrhythmia, or significant cardiac comorbidity

— Refractory ARDS → transfer to ECMO-capable tertiary center

— Lack of pulmonology/ICU coverage at receiving facility

— Report to state/local health department per ongoing CDC surveillance

— Report defective/illicit products to FDA Safety Reporting Portal

ICU admission criteria:

Step-down/floor admission:

Consultations to obtain:

Transfer criteria:

Reporting obligations:

CCS pearl: On CCS, when patient deteriorates on the floor, transfer to ICU, intubate with lung-protective settings, place arterial line and central line, start vasopressors if needed, and consult pulmonology and critical care — sequencing these orders before the simulation clock advances earns disposition points.

Board pearl: Discharging a marginally hypoxic EVALI patient without 48-hour follow-up is the wrong answer; readmission and death after ED discharge are documented patterns.

Key Differentials — Same-Category (Pulmonary) Causes

— Bacterial: focal consolidation, productive cough, elevated procalcitonin, positive urinary antigens or culture

— Viral (influenza, COVID-19, RSV): bilateral infiltrates can mimic EVALI; PCR distinguishes

— Key distinction: CAP rarely has prominent GI prodrome; EVALI has nausea/vomiting in >75% with patchy bilateral GGOs and subpleural sparing

— Also linked to vaping/new smoking

— BAL shows >25% eosinophils; peripheral eosinophilia may be absent acutely

— Responds dramatically to steroids

— Key distinction: EVALI = neutrophilic BAL; AEP = eosinophilic BAL

— Hemoptysis (only ~1/3), dropping hemoglobin, progressively bloodier BAL aliquots, hemosiderin-laden macrophages

— Associated with vasculitis (ANCA), anti-GBM, lupus

— Antigen exposure history (birds, molds, hot tubs); centrilobular nodules and mosaic attenuation

— Migratory peripheral consolidations; responsive to steroids; often subacute

— Immunocompromised host; bilateral perihilar GGOs; elevated LDH; positive PCR or stain

— Rapidly progressive DAD without identified cause; diagnosis of exclusion

— Aspiration of oils (mineral oil, oil-based products); lipid-laden macrophages; chronic course typically

— Can co-exist or mimic; D-dimer and CTA when pretest probability raised

Community-acquired pneumonia (CAP):

Acute eosinophilic pneumonia (AEP):

Diffuse alveolar hemorrhage (DAH):

Hypersensitivity pneumonitis:

Organizing pneumonia (cryptogenic or secondary):

PJP (Pneumocystis jirovecii) pneumonia:

Acute interstitial pneumonia (Hamman-Rich):

Lipoid pneumonia:

Pulmonary embolism:

Board pearl: When BAL eosinophilia is the punchline, the answer is acute eosinophilic pneumonia — not EVALI — even if the patient vapes. Both improve with steroids but the labels (and prognosis) differ.

Key Differentials — Other-Category Causes

— Orthopnea, PND, JVD, S3, lower extremity edema; CXR with cephalization, Kerley B lines, effusions

— Elevated BNP/NT-proBNP; echo with reduced EF or diastolic dysfunction

— Key distinction: EVALI patients are young, with preserved cardiac function and absent volume overload signs

— Identify source (urinary, intra-abdominal, skin); positive cultures; lactate elevation; shock physiology

— Chest pain, troponin elevation, ECG changes (diffuse ST elevation or PR depression), reduced LVEF; can co-occur with vaping

— Amiodarone, methotrexate, nitrofurantoin, bleomycin, immune checkpoint inhibitors — medication reconciliation essential

— Witnessed aspiration, altered mental status, alcohol/drug use; right-lower-lobe predominant

— Sudden-onset dyspnea, pleuritic pain, tachycardia; risk factors (OCPs, immobility, malignancy); D-dimer and CTA

— RA, SLE, scleroderma — joint, skin, renal findings; positive serologies

— Sinopulmonary-renal syndrome, hematuria, ANCA-positive, palpable purpura

— Hemoptysis + AKI; anti-GBM antibodies

— Rash, eosinophilia, organ involvement; recent culprit drug exposure (4–8 weeks)

Cardiogenic pulmonary edema / HF exacerbation:

Sepsis / septic shock from non-pulmonary source:

Acute myocarditis:

Drug-induced lung injury:

Aspiration pneumonitis:

Pulmonary embolism:

Connective tissue disease–associated ILD or flare:

Vasculitis (GPA, EGPA, MPA):

Goodpasture syndrome:

Acute interstitial lung diseases or malignancy (lymphangitic carcinomatosis, leukemic infiltrates): typically subacute with weight loss; tissue diagnosis

DRESS or other systemic drug hypersensitivity:

Step 3 management: A young dyspneic vaper with hematuria and elevated creatinine is not EVALI — pursue pulmonary-renal syndrome workup (ANCA, anti-GBM, ANA, urinalysis with microscopy) urgently; missing this is high-yield.

Board pearl: Always reconcile the timeline of exposure; EVALI symptoms occur within 90 days (usually days) of vaping, while drug-induced ILD often appears over weeks-months.

Secondary Prevention, Discharge Medications, and Long-Term Plan

— Complete abstinence from all e-cigarette, vape, and aerosolized nicotine/THC products — frame as non-negotiable

— Avoid informal/black-market THC cartridges in particular

— Provide written cessation plan and pharmacotherapy

— Varenicline (most effective) 0.5 mg titrated to 1 mg BID × 12 weeks

— Bupropion SR 150 mg daily × 3 days then BID × 7–12 weeks

— Nicotine replacement therapy — combination patch (long-acting) + lozenge/gum (short-acting); often the preferred initial choice in adolescents and patients avoiding systemic medications

— Counseling and behavioral support (1-800-QUIT-NOW, state quitlines, text-based programs like SmokefreeTXT)

— Oral corticosteroid taper (e.g., prednisone starting 40–60 mg, taper over 2–6 weeks per response)

— PPI if on prolonged high-dose steroids with GI symptoms

— Calcium 1200 mg + vitamin D 800 IU daily for steroid-related bone loss

— Consider PCP prophylaxis (TMP-SMX) if cumulative steroid exposure expected ≥20 mg prednisone for ≥4 weeks

— Optimize underlying conditions: inhalers for asthma/COPD, statin/antihypertensive adherence

— Influenza (annually), COVID-19 booster per current CDC, PPSV23/PCV20 if indicated by age/comorbidities, Tdap

Cessation is the cornerstone of secondary prevention:

Nicotine cessation pharmacotherapy (offer to all nicotine users):

THC/cannabis cessation: behavioral therapy, motivational interviewing; refer to addiction medicine if dependence

Discharge medications:

Vaccinations to update before discharge:

Step 3 management: Document and prescribe at least one evidence-based cessation pharmacotherapy plus behavioral support at discharge for every EVALI patient who used nicotine — pharmacotherapy doubles quit rates and is a quality measure.

Board pearl: Counseling alone is insufficient; the correct discharge plan combines pharmacotherapy + behavioral counseling + scheduled follow-up for tobacco/nicotine dependence.

Follow-Up, Monitoring Parameters, and Rehabilitation

— Primary care or pulmonology visit within 48 hours of discharge — non-negotiable per CDC guidance because of documented relapse risk

— Pulmonology follow-up at 2 weeks with repeat clinical assessment

— Repeat chest imaging at 2–4 weeks to confirm radiographic improvement

— PFTs with DLCO at 4–6 weeks to assess residual restriction/diffusion impairment

— Continue follow-up every 1–3 months until clinical and PFT recovery

— Symptoms: dyspnea, cough, fevers — any worsening prompts urgent re-evaluation

— Blood glucose monitoring, especially in diabetics or pre-diabetics

— Blood pressure

— Mood, sleep, infection signs

— Refer patients with persistent dyspnea, reduced exercise tolerance, or significant PFT decline

— Structured exercise improves recovery and quality of life

— Address substance use disorder (nicotine, THC, polysubstance) with specialty referral

— Screen and treat depression/anxiety (PHQ-9, GAD-7)

— Adolescents → adolescent medicine, school-based supports

— Persistent reduced DLCO, exercise intolerance, increased airway hyperreactivity

— Possible increased long-term cardiovascular risk from vaping (independent of EVALI)

— Document in problem list and address at annual visits

— Use mMRC dyspnea scale or CAT score for longitudinal tracking

Post-discharge follow-up cadence:

Monitoring during steroid taper:

Pulmonary rehabilitation:

Behavioral health follow-up:

Repeat cessation counseling at every visit — relapse to vaping precipitates EVALI recurrence

Long-term concerns:

Patient-reported outcomes:

Step 3 management: When transitioning EVALI patients from ED/hospital to outpatient, ensure the 48-hour follow-up is scheduled before discharge (not just recommended) — transitions-of-care gaps are a Step 3 patient safety theme and the leading cause of EVALI readmission.

Board pearl: Persistent reduced DLCO at 6 weeks despite resolved imaging is a common finding and warrants ongoing pulmonology follow-up rather than reassurance.

Ethical, Legal, and Patient Safety Considerations

— EVALI is reportable to state and local health departments under CDC outbreak surveillance

— Suspected defective or contaminated products report to FDA Safety Reporting Portal

— Required regardless of patient consent, similar to other communicable/public health threats

— Many states permit minors to consent to substance use treatment and reproductive health independently

— Interview adolescents alone with parents stepping out; explain limits of confidentiality (mandatory reporting for harm to self/others, abuse)

— Be explicit that substance use disclosure typically remains confidential unless safety concerns arise — this directly improves diagnostic accuracy

— Empiric corticosteroids carry significant short- and long-term risks (hyperglycemia, infection, bone loss, mood); discuss in plain language

— Bronchoscopy: discuss risk-benefit, especially with hypoxemia

— Mechanical ventilation/ECMO: surrogate decision-making frameworks for incapacitated patients

— Documented readmission and death after ED discharge of marginally stable EVALI patients

— 48-hour follow-up appointment must be scheduled, not just recommended

— Medication reconciliation including steroid taper, cessation pharmacotherapy, vaccines

— Written instructions in patient's language; teach-back to confirm understanding

— Return precautions: worsening dyspnea, chest pain, fever, hemoptysis

— Informal THC markets disproportionately affect lower-income and minority youth

— Cessation resources should be culturally and linguistically appropriate

— Suspected sales of vape products to minors → state tobacco enforcement

— Suspected illicit THC product manufacturing → varies by jurisdiction

— Avoid premature discharge — track 30-day readmission as a quality marker

— Document tobacco cessation counseling (meaningful use measure)

Mandatory public health reporting:

Adolescent confidentiality:

Informed consent edge cases:

Transition-of-care safety:

Health equity:

Mandatory reporting nuances:

Patient safety / quality measures:

Step 3 management: When a 16-year-old presents with EVALI and refuses to disclose vaping in front of a parent, the correct action is to request parental privacy, reaffirm confidentiality within legal limits, and obtain an honest history — then loop in parents for treatment planning with the patient's permission where possible.

High-Yield Associations and Rapid-Fire Clinical Facts

Causative agent: Vitamin E acetate in THC-containing cartridges (CDC/BAL evidence).

Demographics: young (median ~24 yrs), male predominance (~2/3), often THC vape users from informal sources.

Symptom triad: respiratory + constitutional + prominent GI (nausea/vomiting in >75%).

Labs: neutrophilic leukocytosis, elevated ESR/CRP, eosinophilia absent, mild transaminitis.

Imaging: bilateral ground-glass opacities with subpleural sparing on CT chest; CXR may be normal in 10%.

BAL: neutrophilic predominance, lipid-laden macrophages (supportive, not specific).

Diagnosis: clinical, exclusionary — must rule out infection (viral PCR including influenza/COVID, urinary antigens, blood cultures).

Treatment: systemic corticosteroids (methylprednisolone 1 mg/kg/day) after infection reasonably excluded; empiric antibiotics and oseltamivir until cultures/PCR return.

Disposition: admit if SpO₂ <95% on RA, comorbidities, or unreliable 48-hr follow-up.

ICU rates: ~30% intubated; mortality ~2–3%, higher in elderly/comorbid.

Cessation pharmacotherapy: varenicline > bupropion ≈ NRT combination; behavioral counseling pairs with all.

Reportable: state health department; FDA for product issues.

Mimics to know: acute eosinophilic pneumonia (BAL eos), DAH (hemoptysis, anemia), CAP (focal consolidation, productive cough), HF (BNP, JVD, S3), PJP (immunocompromised, LDH).

Pediatric pearl: interview adolescent alone.

Pregnancy pearl: prednisone/methylprednisolone preferred over dexamethasone for maternal EVALI treatment.

Imaging pearl: subpleural sparing is high-yield.

Follow-up pearl: 48-hour outpatient follow-up; PFTs at 4–6 weeks.

Complication pearl: pneumomediastinum in young coughing vaper.

CCS pearl: start steroids only after sending viral PCR and urinary antigens.

Surveillance pearl: CDC case definition requires vape use within 90 days + infiltrates + infection excluded.

Vitamin E acetate pearl: the diluent — not the THC itself — is the inflammatory trigger.

Board pearl: The "vaping + GI prodrome + bilateral GGOs + neutrophilic BAL" gestalt is the canonical Step 3 EVALI vignette.

Board Question Stem Patterns

— 22-year-old with 1 week of fever, vomiting, dyspnea; uses "dab pen" from a friend; SpO₂ 89% RA; bilateral GGOs with subpleural sparing on CT; negative viral PCR.

— Answer: start methylprednisolone + admit; cessation counseling at discharge.

— Same patient; question asks "next best step before steroids?"

— Answer: send respiratory viral PCR, blood cultures, urinary Strep/Legionella antigens, start empiric antibiotics + oseltamivir.

— Mildly symptomatic vaper, SpO₂ 96% RA, no comorbidities, lives alone with no transportation.

— Answer: admit (cannot ensure 48-hour follow-up); do not discharge.

— 16-year-old with EVALI; declines to disclose vaping in front of mother.

— Answer: ask parent to step out, reaffirm confidentiality within legal limits, obtain history.

— Young vaper with same imaging but BAL >30% eosinophils.

— Answer: acute eosinophilic pneumonia, not EVALI.

— Vaper with hemoptysis, hematuria, AKI, anemia.

— Answer: pulmonary-renal syndrome workup (ANCA, anti-GBM, urinalysis) — not EVALI.

— EVALI patient on steroids × 72 hours, no improvement.

— Answer: bronchoscopy with BAL; reconsider diagnosis.

— Patient improves, tapered over 7 days, returns worse.

— Answer: restart steroids, extend taper to 4–6 weeks.

— Discharge plan for nicotine vape user.

— Answer: combine pharmacotherapy (varenicline/bupropion/NRT) + behavioral counseling + quitline.

— Confirmed EVALI case; question asks next step in public health.

— Answer: report to state health department; report suspect product to FDA.

Pattern 1 — The classic young vaper:

Pattern 2 — Exclusion misstep:

Pattern 3 — Disposition decision:

Pattern 4 — Confidentiality with minor:

Pattern 5 — Mimic distinction:

Pattern 6 — Pulmonary-renal red flag:

Pattern 7 — Failure to improve:

Pattern 8 — Steroid taper relapse:

Pattern 9 — Cessation pharmacotherapy:

Pattern 10 — Reporting:

Board pearl: When the stem emphasizes subpleural sparing, GI prodrome, or vape pen + informal source, anchor on EVALI and move directly to exclusion-of-infection + steroid logic.

One-Line Recap

— Suspect in any vaper with bilateral infiltrates + GI symptoms; exclude influenza, COVID-19, bacterial pneumonia, PJP, eosinophilic pneumonia, DAH, vasculitis, and HF before anchoring.

— Treat with methylprednisolone 1 mg/kg/day after infection is reasonably excluded; continue empiric ceftriaxone + azithromycin and oseltamivir until cultures/PCR return; admit if SpO₂ <95% or unreliable follow-up; escalate to HFNC → intubation with lung-protective ventilation → prone positioning → ECMO referral for refractory ARDS.

— Discharge with a 2–6 week steroid taper, combination cessation pharmacotherapy + behavioral counseling for nicotine users, vaccines updated, calcium/vitamin D, and a 48-hour follow-up appointment scheduled (not just recommended); arrange PFTs at 4–6 weeks and pulmonology continuity.

— Remember the Step 3 layer: report to the state health department, report suspect products to the FDA, interview adolescents alone within confidentiality limits, anticipate steroid-induced hyperglycemia and rebound disease on rapid tapers, and treat transitions-of-care as the highest-risk safety moment in the disease course.

One-liner: EVALI is a clinical, exclusionary diagnosis in a young patient with recent (≤90 days) e-cigarette/vape use — especially THC products containing vitamin E acetate — presenting with respiratory symptoms, constitutional findings, and a prominent GI prodrome, bilateral ground-glass opacities with subpleural sparing, neutrophilic BAL, and managed with infection exclusion, empiric antibiotics/antivirals, and systemic corticosteroids, followed by mandatory cessation and 48-hour outpatient follow-up.

Recap bullets:

Final Board pearl: Vitamin E acetate + THC vape + GI prodrome + subpleural sparing + neutrophilic BAL = EVALI; the right answer almost always involves excluding infection, starting corticosteroids, and locking in close follow-up with cessation pharmacotherapy.