Individual Patient Data Meta-Analysis of Histopathological Patterns and Vaping-Associated Lung Injury: Different Pathophysiology of Nicotine and Marijuana-Based Vaping

Background:
E-cigarette or vaping-associated lung injury (EVALI) presents with heterogeneous histopathological findings, yet systematic analyses remain limited. Although case reports have documented patterns such as diffuse alveolar damage (DAD) and organizing pneumonia, no prior meta-analysis has examined these findings at the individual patient level or explored how injury patterns differ by vaping substance.

Methods:

This individual patient data (IPD) meta-analysis systematically evaluated histopathological features in e-cigarette or vaping product use-associated lung injury (EVALI), synthesizing evidence from 10 studies comprising 38 cases. Following PRISMA-IPD guidelines, we searched MEDLINE, Embase, PubMed, Scopus, and conference proceedings without restrictions. Eligible studies reported lung biopsy/autopsy findings in CDC-defined EVALI cases. Composite variables were created for inflammation severity (none/mild/moderate-severe), macrophage/lipid abnormalities (present/absent), and dominant pathological patterns (e.g., diffuse alveolar damage [DAD], organizing pneumonia).

Results:
Acute fibrinous pneumonitis (31.6%), organizing pneumonia (23.7%), and diffuse alveolar damage (13.2%) were the most common histopathological patterns. Lipid-laden macrophages were detected in 21.1% of cases. Vape type significantly predicted macrophage/lipid abnormalities (χ²(3)=14.97, p=.002), with the highest prevalence among nicotine-only users (62.5%). In contrast, THC-only users showed a markedly lower prevalence (7.1%). No significant associations were observed between macrophage abnormalities and age, sex, smoking history, vaping duration, or immune cell profiles in bronchoalveolar lavage fluid (p > .05).

Conclusion:
This IPD meta-analysis highlights acute fibrinous pneumonitis as the predominant pattern in EVALI and suggests that nicotine-based products may be more strongly associated with lipid-related macrophage abnormalities than THC products. These findings support the hypothesis of substance-specific lung injury mechanisms and underscore the need for tailored diagnostic criteria and regulatory oversight.