A study published in Nature Communications has found that fatal asthma is associated with immune abnormalities extending well beyond the lungs, with notable changes detected in lymph nodes linked to both pulmonary and gastrointestinal tissue. The findings suggest that the immune conditions contributing to a fatal asthma attack may be organised across multiple organ systems rather than confined to the airways.
Researchers at Columbia University analysed immune cells collected from the lungs, blood, spleen, jejunum, lung-associated and mesenteric lymph nodes, and bone marrow of 695 organ donors sampled between 2012 and 2025. Of these, 41 had died during an asthma attack, 78 had asthma but died from unrelated causes, and 576 had no documented asthma history.
All fatal asthma donors with available data showed elevated immunoglobulin E (IgE) levels, indicating a pronounced type 2 inflammatory pattern. Their lung tissue contained higher proportions of type 2 helper T cells, type 2 innate lymphoid cells, and mast cells, all of which can amplify airway inflammation and mucus production. Lung-associated lymph nodes showed markedly reduced regulatory T cell populations in both asthma groups, suggesting this deficit is associated with the condition itself rather than solely with fatal exacerbation.
A notable finding was that immune populations in the lungs of fatal asthma donors showed stronger associations with responses in gut-associated lymph nodes than those observed in donors without asthma. Memory T and B cells also accumulated at younger ages in mucosal-associated lymph nodes of fatal asthma donors, implying earlier immune changes of a kind typically associated with ageing.
The authors emphasise that the study identifies associations rather than causal relationships, and that the relatively small size of the fatal asthma group and absence of data on corticosteroid use limit interpretation.
Source: Lee Y et al. Fatal asthma and systemic immune abnormalities. Nature Communications (2026).
