Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older

Several inhaled drugs for use by cystic fibrosis (CF) patients are formulated for nebulizer use only. This therapy is time consuming and includes the risk of contamination of the nebulizers. Dry powder inhalers (DPI) can be an attractive alternative for CF drugs. Inhaled flow rate and volume, and the device resistance are important determinants for optimal dispersion of drug from a DPI. It is important to understand how these variables interact in the CF population in order to properly design a new DPI formulation targeted for these patients. The objective of this study was to assess the inspiratory variables of a representative population of CF subjects 6 years and older with varying degrees of lung disease while inhaling through resistances that simulate DPI devices. Ninety-six stable CF patients were enrolled, ages 6-54 years, FEV 1 19-126% predicted. Subjects inhaled forcefully through four different resistances (0.019, 0.024, 0.038, and 0.048 kP0.5/LPM, respectively), while inspiratory time (ITDPI), peak inspiratory flow (PIFDPI), and volumes (VDPI) were measured. For any resistance, inspired VDPI increased with the older age groups; PIFDPI was similar between adults and adolescents but lower in the children. Subjects with lower FEV1 had lower VDPI and PIFDPI. As resistance increased, PIFDPI decreased, IT DPI increased, with no significant change in VDPI. At the lowest resistance mean PIFDPI was 105 LPM (range 45-163) for all patients; 112 LPM (range 75-163) in adults; and 89 LPM (45-126) in children. Mean inspired VDPI was 1.75 L for all patients; 2.2 L (0.8-3.7) in adults; and 1.2 L (0.5-1.8) in children. At the lowest resistance a minimal flow rate of 30, 45, and 60 LPM was attained in 100%, 99%, and 96% of all patients. Volumes of 1.0, 1.5, and 2.0 L were attained by 85%, 57%, and 30% of the patients. At the highest resistance mean PIFDPI was 52 LPM (range 26-70) for all patients; 55 LPM (40-70) in adults; and 47 LPM (26-62) in children. Mean inspired VDPI was 1.5 L in all patients; 1.9 L (0.9-3.5) in adults and 1.1 L (0.5-2.3) in children. At the highest resistance, a minimal flow rate of 30, 45, and 60 LPM was attained in 99%, 80%, and 22% of all patients. Volumes of 1, 1.5, and 2 L were attained in 84%, 45%, and 23% of the patients. We defined ranges for inspiratory variables in a diverse CF population for a range of device resistances that bracket those of current DPIs. The recorded inspiratory patterns can be used on the bench to design and test new dry powder formulations and devices to target the largest proportion of the CF population.

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