Study objectives: To develop a model that quantified
the nebulizer output that was inhaled by subjects with cystic fibrosis
(CF) in order to predict the amount of drug likely to enter the upper
airway contained in particles small enough to be deposited in the lower
respiratory tract of individual patients.
Forty-three patients (age, 6 to 18 years) with CF, with
FEV1 of 26 to 124% of predicted, breathed through a
nebulizer circuit with a pneumotachograph in place at the distal end.
Algorithms were developed from the measured flows through the
pneumotachograph, allowing partitioning of inspiration into undiluted
aerosol and fresh gas. In order to validate the algorithms, argon was
added to the nebulizing gas flow and then its concentration was
analyzed at the mouth by mass spectrometry.
Predictions of the concentration of argon at the mouth were concordant
with that measured by mass spectrometry, thus validating the model.
Combining data from the model with in vitro nebulizer
performance data, predictions for estimates for lung deposition for
individuals were possible. Total estimate was independent of patient
size or FEV1. The respiratory duty cycle was 0.44 ± 0.05
(mean ± SD) and correlated (r = 0.91, p < 0.001)
with estimated deposition and minute ventilation
(r = 0.60, p < 0.01). However, when expressed in
milligrams per kilogram of body weight, the estimated deposition in
smaller children was fourfold higher than in larger children.
Conclusions: If the effect of patient size and pattern of
breathing on estimated drug deposition are not considered when
prescribing drugs given by nebulization, the result may be overdosing
younger children, underdosing older children, or