Unravelling a Clinical Paradox - Why Does Bronchial Thermoplasty Work in Asthma?

Rationale Bronchial thermoplasty is a relatively new but effective treatment in asthmatic subjects who do not respond to conventional therapy. While the favoured mechanism is ablation of the airway smooth muscle layer, because bronchial thermoplasty treats only a small number of central airways, there is ongoing debate regarding its precise method of action. Objectives Elucidate the underlying method of action behind bronchial thermoplasty. Methods We employ a combination of extensive human lung specimens and novel computational methods. Whole left lungs were acquired from the Prairie Provinces Fatal Asthma Study. Subjects were classified as control (N=31), non-fatal asthma (N=32), or fatal asthma (N=25). Simulated lungs for each group were constructed stochastically, and flow distributions and functional indicators were quantified both before and after a 70% reduction in airway smooth muscle in the thermoplasty-treated airways. Main Results Bronchial thermoplasty triggers global redistribution of clustered flow patterns, wherein structural changes to the treated central airways lead to a re-opening cascade in the small airways and significant improvement in lung function via reduced spatial heterogeneity of flow patterns. This mechanism accounts for progressively greater efficacy of thermoplasty with both severity of asthma and degree of muscle activation, consistent with existing empirical results. Conclusions We report a probable mechanism of action for bronchial thermoplasty: alteration of lung-wide flow patterns in response to structural alteration of the treated central airways. This insight could lead to improved therapy via patient-specific, tailored versions of the treatment -- as well as implications for more conventional asthma therapies.