Lipid-laden macrophages as biomarkers of vaping-associated lung injury

Since April, 2019, more than 2600 cases of electronic cigarette, or vaping, product use associated lung injury (EVALI) have been reported across the USA, associated with 60 deaths, according to data from the US Centers for Disease Control and Prevention. These numbers are expected to continue to rise. Yet no tests or markers for the diagnosis or risk assessment of EVALI currently exist, and diagnosis is based on the exclusion of other causes of acute lung injury in patients who vape. Patients with EVALI consistently present with lipid-laden macrophages (foam cells) in the lungs or in bronchoalveolar lavages.^1,2 However, the use of foam cells as a biomarker for vaping-associated lung injury has been questioned,² because EVALI is associated not only with lipoid pneumonia, but also with manifestations as diverse as acute eosinophilic pneumonia, organising pneumonia, diffuse alveolar damage and acute respiratory distress, hyper-sensitivity pneumonitis, and rare giant-cell interstitial pneumonitis.^1–4 In addition, the cause of lipoid pneumonia (ie, whether exogenous or endogenous) has also been a point of discussion, in view of the morphology of lipid-laden macrophages in the injured lungs.⁴

These lines of reasoning imply that foam cells form only in response to the uptake of lipids, which is not the case. Foam cells can form in the context of sustained inflammation in diverse pathologies, including in metabolic diseases with or without hyperlipidaemia, some infectious diseases (eg, tuberculosis), and some cancers (eg, papillary renal cell carcinoma).⁵ Foam cells can be induced by excess lipoproteins in atherosclerosis, pathogen-recognising patterns, and proinflammatory cytokine receptors in tuberculosis, and possibly by many other unknown signals. Furthermore, the lipids that accumulate in foam cells are pathology-dependent. For example, atherogenic foam cells are cholesterol-rich, whereas foam cells within the necrotic granulomas associated with advanced tuberculosis are enriched in triglycerides.⁵ Although foam cells might form via different biogenetic pathways, a unifying element exists across all disease contexts: foam cells exhibit impaired macrophage immune functions, actively worsen inflammation, and contribute to disease manifestation or progression. Thus, the consistent presence of foam cells in severe, acute lung injury observed in EVALI is not surprising.

In conclusion, although the value of foam cells as an EVALI diagnostic marker or susceptibility trait undoubtedly requires further study, research needs to move away from misconceptions of foam cell biogenesis that could preclude their careful evaluation.