Influence of breathing pattern on pulmonary aerosol deposition in patients with cystic fibrosis (CF): A pharmacokinetic approach

The therapeutic effect of inhaled antibiotics on lung infection in CF patients is dependent on the aerosol deposition achieved in the lungs. Objectives: To evaluate the influence of two breathing patterns on pulmonary aerosol deposition using pharmacokinetic parameters as surrogate for deposition. Methods: In a randomized, open-label, crossover study pulmonary deposition in 18 adult CF patients is evaluated following inhalation of tobramycin aerosol using the I-neb nebulizer with TBM (Tidal Breathing Mode) and TIM (Target Inhalation Mode) breathing patterns. Breathing in TIM forced the patient to inhale in a slow and deep manner. According to their lung function, patients were categorized in subgroup 1, 2 or 3 corresponding to FEV1 predicted ≤59%, 60-79% or ≥80%. Blood samples were collected in order to model tobramycin pharmacokinetics. Results: Mean Cmax and AUC0-24hr were significantly increased for TIM compared to TBM. Inhalation in TIM also resulted in higher mean Cmax and AUC0-24hr for each subgroup. Mean bioavailability of TIM relative to TBM breathing pattern (Frel) was 1.53±0.41 and mean Frel in each subgroup was also significantly higher than 1. Subgroup category did not affect the results. Conclusion: Slow and deep inhalation of aerosolized tobramycin with the I-neb nebulizer resulted in an estimated 53% higher lung deposition compared to tidal breathing. This result was independent from lung function category, which suggests that regardless the disease state, slow and deep inhalation always results in higher pulmonary aerosol deposition compared to tidal breathing