Acute bronchodilation increases ventilatory complexity during resting breathing in stable COPD: Toward mathematical biomarkers of ventilatory function?

Human tidal breathing features mathematical complexity and breath-by-breath variability. Fluctuations in these descriptors from one state to another are related to the load imposed on the respiratory system. We hypothetized that bronchodilators would increase ventilatory complexity and variability in patients suffering from chronic obstructive pulmonary disease (COPD). Eleven patients with stable COPD (9 men; age 48–79; FEV1 42–80%; FRC above 120%) were studied before and after 400 μg salbutamol. Breath-by-breath variability (coefficient of variation of tidal volume and breathing frequency – f) and ventilatory complexity (noise limit – NL, a quantifier of nonlinearity and complexity; largest Lyapunov exponent – LLE, an indicator of the sensitivity of the system to initial conditions) were described. Acute bronchodilation revealed or increased nonlinearity (NL 31% [20–38] to 43% [35–58], P = 0.0051). Little changes in variability were observed (increased coefficient of variation of f). These observations might open new avenues toward resting breathing pulmonary function testing and novel respiratory biomarkers suitable for home-based lung disease monitoring.

► Human tidal breathing features mathematical complexity and breath-by-breath variability.
► These characteristics are related to respiratory neuromechanical coupling.
► In patients with COPD, unloading the respiratory system with bronchodilators increases ventilatory complexity.
► This could provide novel diagnostic and follow-up respiratory biomarkers.