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Targeting Aerosol Deposition in Patients With Cystic Fibrosis^*

Effects of Alterations in Particle Size and Inspiratory Flow Rate

^* From the Johns Hopkins Medical Institutions (Drs. Laube and Zeitlin), and the University of Maryland (Drs. Jashnani and Dalby), Baltimore, MD.

Correspondence to: Beth L. Laube, PhD, Johns Hopkins Hospital, Park 316, 600 North Wolfe St, Baltimore, MD 21287-2533; e-mail: blaube{at}welchlink.welch.jhu.edu

Study objective: To determine if aerosolized medications can be targeted to deposit in the smaller, peripheral airways or the larger, central airways of adult cystic fibrosis (CF) patients by varying particle size and inspiratory flow rate.

Design: Randomized clinical trial.

Setting: Outpatient research laboratory.

Patients: Nine adult patients with CF.

Interventions: Patients inhaled an aerosol comprised of 3.68 ± 0.04 µm saline solution droplets (two visits) or 1.01 ± 0.2 µm saline solution droplets (two visits) for 30 s, starting from functional residual capacity and breathing at a slow or faster inspiratory flow rate. On all visits, the saline solution was admixed with the radioisotope ^99mTc. Immediately after inhalation, a gamma camera recorded the deposition pattern of the radioaerosol in the lungs. Deposition images were analyzed in terms of the inner:outer zone (I:O) ratio, a measure of deposition in an inner zone (large, central airways) vs an outer zone (small airways and alveoli).

Measurements and results: For the 3.68-µm aerosol, I:O ratios averaged 2.29 ± 1.45 and 2.54 ± 1.48 (p > 0.05), indicating that aerosol distribution within the lungs was unchanged while breathing at 12 ± 2 L/min vs 31 ± 5 L/min, respectively. For the 1.01-µm aerosol, I:O ratios averaged 2.09 ± 0.96 and 3.19 ± 1.95 (p < 0.05), indicating that deposition was predominantly in the smaller airways while breathing at 18 ± 5 L/min and in the larger airways while breathing at 38 ± 8 L/min, respectively.

Conclusions: These results suggest that the targeted delivery of an aerosol to the smaller, peripheral airways or the larger, central airways of adult CF patients may be achieved by generating an aerosol comprised of approximately 1.0-µm particles and inspiring from functional residual capacity at approximately 18 L/min and 38 L/min, respectively.

Key Words: aerosols • cystic fibrosis • gene therapy • inspiratory flow rate • particle size

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