Exploring a Novel Approach to Asthma Management: Targeting Upstream Live Cell Extrusion
Asthma, affecting over 300 million individuals globally, remains a significant health concern with a high mortality
rate. Despite advancements in treatment, many patients still struggle with symptom control and recurrent attacks.
While inflammation has been the focal point of asthma research, a recent study sheds light on a mechanical aspect
that could refine our understanding and treatment of the condition.
Asthma exacerbations are characterized by bronchoconstriction, leading to breathing difficulties, wheezing, and
increased mucus production. This mechanical response serves as the hallmark diagnostic feature of asthma.
However, its role extends beyond mere symptom manifestation; it initiates a cascade of events that perpetuate
airway inflammation and exacerbate the condition.
Airway epithelia form a crucial protective barrier in the lungs, contributing to innate immunity. Maintaining an
optimal density of epithelial cells is vital for barrier function. A interesting discovery in this regard is the process of
cell extrusion, which regulates cell turnover and preserves epithelial integrity. Physiological crowding triggers
controlled cell extrusion, ensuring homeostasis. However, pathological crowding induced by bronchoconstriction
disrupts this delicate balance.
A recent study by Bagley et al. (2024) elucidates how bronchoconstriction-induced crowding leads to excessive cell
extrusion, damaging the airway epithelial barrier (Figure 1). This disruption not only triggers inflammation but also
increases susceptibility to infections, perpetuating the asthma cycle. Importantly, conventional treatments like
albuterol fail to prevent epithelial damage and inflammation, highlighting the need for alternative therapeutic
strategies.
By inhibiting the extrusion pathway, researchers were able to mitigate airway damage and inflammation post-
bronchoconstriction. Gadolinium (Gd3+), an extrusion inhibitor, showed promising results in preserving epithelial
integrity and dampening the inflammatory response. This approach offers a novel avenue for asthma management,
potentially disrupting the vicious cycle of inflammation and recurrent attacks.
Understanding the mechanical underpinnings of asthma opens new possibilities for therapeutic intervention. By
targeting extrusion upstream in the pathway, it may be possible to prevent not only immediate symptoms but also
long-term complications such as airway remodeling and hypersensitivity to triggers. Moreover, insights from this
research may extend to other inflammatory conditions characterized by smooth muscle constriction, offering hope
for novel treatment modalities.
The study by Bagley et al. (2024) reveals a crucial aspect of asthma pathogenesis, emphasizing the mechanical
damage caused by bronchoconstriction-induced cell extrusion. By targeting this pathway, researchers pave the way
for innovative therapeutic strategies that could revolutionize asthma management. Addressing the mechanical
aspects of asthma offers a promising avenue for improving patient outcomes and reducing the global burden of this
debilitating condition.
Reference
Bronchoconstriction damages airway epithelia by crowding-induced excess cell extrusion. (2024). Bagley, D.C., et
al. Science, Vol 387, Issue 6691, DOI: 10.1126/science.adk2758
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