INTRODUCTION E-cigarette or vaping-associated lung injury has been reported extensively throughout the United States without a corresponding number of international cases. Cannabinoid-based products have been implicated in the majority of cases.

OBJECTIVES To collate published reports of E-cigarette or vaping-associated lung injury outside the United States and to identify the reasons behind the discrepancy in reported cases between the United States and the international community.

METHODS PubMed and Healthcare Databases Advanced Search were used to identify published case reports of E-cigarette or vaping-associated lung injury prior to February 2021 using the search terms "e-cigarette", "e-cigarettes", "vaping", "vape" and, "lung injury", "pulmonary", "respiratory". Cases occurring in the United States were excluded. Non-United States case reports were excluded if they did not meet the Centers for Disease Control and Prevention "probable case" criteria. This requires use of a vaping device within 90 days of symptom onset, the presence of pulmonary infiltrates on plain film chest radiography or ground glass opacities on computerised tomography, clinical suspicion that infection was not the underlying cause of lung injury, and the absence of other plausible medical processes to account for the presentation. Patient demographics, nature of exposure, symptomatology and outcome were compared to 125 cases from three regional United States based case series, which were chosen on the basis of having complete data for these comparative factors.

RESULTS Seventeen international cases from 13 countries were identified for analysis. There was a male predominance in both non-United States and United States cohorts (76% vs 58-83%), with a marginally higher median patient age in non-United States cases (31 vs 27, 19, 27 years). Reported use of nicotine/flavoured e-liquids was more common in non-United States cases (100% vs 58-67%), and use of cannabinoid-based products was less common (24% vs 78-92%). The most common symptoms across all cohorts were shortness of breath (76% vs 85-91%), cough (59% vs 78-83%) and fever (47% vs 78-83%). The majority of patients were hypoxic (76% vs 69-86%) and required hospital admission (88% vs 90-94%). Fewer of the non-United States patients required intensive care admission (24% vs 55-67%) though their median length of stay was longer (15 days vs 5, 6, 7 days).

DISCUSSION Uniformity amongst non-United States cases in regards to nicotine based and/or flavoured e-liquid exposure may underestimate the role of these substances in e-cigarette or vaping-associated lung injury. This is consistent with prior United States based research demonstrating increased presentations to emergency departments prior to the recognised "outbreak" of e-cigarette or vaping-associated lung injury at a time of increased nicotine based e-liquid uptake. A longer length of hospital stay, lower rate of intensive care admission and a higher rate of bronchoscopy in the non-United States cohort could be indicative of clinician inexperience internationally. It is unclear why the non-United States cases also had a lower incidence of gastrointestinal symptoms however this may also be explained by poorer diagnostic awareness.

CONCLUSIONS E-cigarette or vaping-associated lung injury is not limited to cannabinoid-based products. Apparent similarities in patient demographics, clinical features, and clinical course between non-United States and United States cases raise concern for underreporting of E-cigarette or vaping- associated lung injury internationally.