Controlled inhalation improves total and peripheral lung deposition in CF

Background: Inhaled therapies are used extensively in the treatment of patients with CF. With progressive impairment of lung function, aerosol deposition of inhaled drug occurs more centrally in the lung. The aim of this study was to determine whether long slow inhalations with a dosimetric nebuliser might improve penetration of drug aerosol into the peripheral lung areas. Methods: A comparison of two inhalation modes was undertaken in 5 subjects with moderately severe CF lung disease (aged 12-18 years; FEV1 63-80%) in a crossover study. The pattern of aerosol distribution was compared using a) long (6 – 8 secs) slow inhalations with the dosimetric AKITA delivery system with Pari LC Sprint nebuliser, and b) tidal breathing with a standard Pari LC Sprint nebuliser and compressor. Distribution and total aerosol dose deposited corrected for attenuation was obtained using gamma scintigraphy. Results: Slow, prolonged inhalation with the AKITA was associated with a higher proportion of the delivered dose depositing in the lungs (74.5%), when compared to tidal breathing (32.1%) with significantly less upper airway deposition with the AKITA. The mean peripheral to central deposition ratios for the 5 subjects were long slow breath 2.16 vs tidal breathing 2.13 (p=0.90). Conclusion: Given that the increased lung dose achieved with long slow inhalation is likely to contain a disproportionate amount of larger droplets that are likely to be deposited centrally, particularly in the presence of significant lung disease, the data supports the suggestion that a greater proportion of the finer droplets reach the lung periphery. Hence total and peripheral lung dose are increased by controlling the inspiratory profile.