Percolation Forces in Lung Inflammation: Determining the Path to Emphysema or Fibrosis

Figures

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  Figure 1. Pulmonary emphysema is characterized by distended and ruptured alveolar walls, whereas interstitial fibrosis is marked by cellular proliferation and fibrosis, resulting in pronounced thickening of alveolar walls.

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  Figure 2. The fragmentation of percolation clusters below a critical threshold corresponds to the rupture of alveolar walls in pulmonary emphysema. This loss of connectivity impairs the distribution of mechanical forces, resulting in air trapping and reduced gas exchange.

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  Figure 3. The increased crosslinking in pulmonary fibrosis corresponds to enhanced percolation connectivity, which increases mechanotransduction-induced fibrogenesis.

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  Figure 4. Flow chart representing the divergence of lung structural changes based on the relationship between crosslink density and the critical probability threshold associated with percolation network connectivity.

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  Figure 5. The release of free desmosine from elastic fibers is exponentially increased as alveolar diameter, as measured by the mean linear intercept method, exceeds 400 µm. This process is associated with the movement of percolation forces below the critical threshold for connectivity. Reprinted with permission [15].

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  Figure 6. Crosslink density in human emphysema shows a sinusoidal change in crosslink density as alveolar diameter increases. However, as airspace size exceeds 400 µm, this process levels off, consistent with a divergence from the continued increase in crosslinking associated with pulmonary fibrosis. Reprinted with permission [15].

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  Figure 7. Flow chart showing the pathways associated with the formation of mature trivalent collagen crosslinks.

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  Figure 8. The formation of the unique desmosine and isodesmosine crosslinks are formed by the condensation of four lysine residues. Reprinted with permission of Creative Commons (https://creativecommons.org/licenses/by-sa/4.0/ (accessed on 10 February 2025)).

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  Figure 9. The loss of elastin crosslinks in pulmonary emphysema is the result of elastase activity combined with mechanical forces.

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  Figure 10. Photomicrograph of CPFE showing cystic airspaces surrounded by interstitial fibrosis.

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  Figure 11. Multiscale mechanisms of injury circumvent therapeutic targeting of a single pathway. Despite molecular blockade by a targeted therapeutic agent, injury propagates through alternative signaling routes and escalates across biological scales. Arrows illustrate bypass routes and upward propagation, emphasizing that single-pathway interventions may be insufficient to halt multiscale injury progression.

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  Figure 12. The application of game theory principles to pulmonary emphysema and interstitial fibrosis suggests that pathological feedback loops become increasingly entrenched, making these diseases more resistant to therapeutic intervention.