Chest
Volume 118, Issue 4, October 2000, Pages 1069-1076
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Clinical Investigations
CYSTIC FIBROSIS
Targeting Aerosol Deposition in Patients With Cystic Fibrosis: Effects of Alterations in Particle Size and Inspiratory Flow Rate

https://doi.org/10.1378/chest.118.4.1069Get rights and content

Study objective:

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

Setting:

Outpatient research laboratory.

Patients:

Nine adult patients with CF.

Interventions:

Patients inhaled an aerosol comprised of3.68 ± 0.04 μm saline solution droplets (two visits) or1.01 ± 0.2 μm saline solution droplets (two visits) for 30 s, starting from functional residual capacity and breathing at a slow orfaster inspiratory flow rate. On all visits, the saline solution wasadmixed with the radioisotope 99mTc. Immediately afterinhalation, a gamma camera recorded the deposition pattern of theradioaerosol in the lungs. Deposition images were analyzed in terms of the inner:outer zone (I: O) ratio, a measure of deposition in an innerzone (large, central airways) vs an outer zone (small airways andalveoli).

Measurements and results:

For the 3.68-μmaerosol, I: O ratios averaged 2.29 ± 1.45 and 2.54 ± 1.48(p > 0.05), indicating that aerosol distribution within the lungswas unchanged while breathing at 12 ± 2 L/min vs 31 ± 5 L/min, respectively. For the 1.01-μm aerosol, I: O ratios averaged2.09 ± 0.96 and 3.19 ± 1.95 (p < 0.05), indicating thatdeposition was predominantly in the smaller airways while breathing at18 ± 5 L/min and in the larger airways while breathing at 38 ± 8L/min, respectively.

Conclusions:

These resultssuggest that the targeted delivery of an aerosol to the smaller, peripheral airways or the larger, central airways of adult CF patientsmay be achieved by generating an aerosol comprised of approximately1.0-μm particles and inspiring from functional residual capacity atapproximately 18 L/min and ∼ 38 L/min, respectively.

Section snippets

Patient Characteristics

Nine patients (six men; three women), who had a documented sweatchloride value > 60 mEq/L by quantitative pilocarpine ionophoresisand one finding consistent with the clinical diagnosis of CF, participated in the study. Patients ranged in age from 21 to 47 years(mean ± SD age, 30 ± 8 years). FEV1, as apercent of predicted values, ranged between 25% and 124% for the ninepatients. Patients were receiving stable therapies for antibiotics, bronchodilators, recombinant human deoxyribonuclease,

Baseline FEV1 Values

Baseline FEV1 values, as a percent of predicted, for all nine patients on each of the four study days are shown in Table 1. Baseline FEV1 values on allfour study days were similar, averaging 65 ± 27%, 66 ± 28%,64 ± 28%, and 65 ± 27% for study days 1 through 4,respectively.

Aerosol Particle Size Characteristics

The average MMAD for the Pari nebulizer (n = 3) was3.68 ± 0.04 μm. Mean geometric SD averaged 3.01 ± 0.07. ThisMMAD was significantly larger than that of the Medicator nebulizer(n = 4), which averaged 1.01 ± 0.2 μm (p =

Discussion

To achieve a full therapeutic effect with any aerosolizedmedication, an adequate dose of drug must be deposited beyond theoropharynx. The distribution of drug within the lungs may also play arole in optimizing the effect of therapy. Aerosol particle size andinspiratory flow rate are two major determinants of deposition fractionand distribution of aerosol within the lungs. By varying these factors, it may be possible to develop methods for targeting the delivery of aerosolized medications to

ACKNOWLEDGMENT

The authors wish to thank Ta-Chun Lin, PhD, for histechnical assistance in performing these experiments, and LoisBrass-Ernst, RN, for her expertise in recruiting patients for thesestudies.

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This work was supported in part by the CF Foundation's CF Gene TherapyCenter Pilot Projects Grant S879 and by the CF Foundation's CFTherapeutics Development Network Grant CFTDN ZEITLI98Y0.

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