The PARI LC PLUS jet nebulizer powered by the US
DeVilbiss PulmoAide compressor was chosen for delivery
of tobramycin nebuliser solution (TNS) to cystic
fibrosis (CF) patients and was used in US clinical trials
(which subsequently demonstrated the safety and efficacy
of TNS) w1x. The reasons for this choice were that
both the LC PLUS nebulizer and PulmoAide compressor
were (and are) widely available in North America.
Further, the rate of aerosol output and total overall
output were considered ideal for this drug formulation
and patient group. The particle size distribution was
heterodisperse and was thought to contain a high proportion
of particles in a size range (2–5 mm) thought
ideal for targeting aerosol in the central airways w2x,
where TNS is thought to be most effective in the CF
respiratory tract.
The LC PLUS nebulizer has a design commonly
referred to as ‘breath enhanced’, meaning that, although
it continuously produces aerosol (even during patient
exhalation), the aerosol emitted during the inhalation
phase is greater than aerosol output during exhalation.
*Corresponding author. Tel.: q44-1274-234234; fax: q44-1274-
234231.
E-mail address: j.h.dennis@bradford.ac.uk (J.H. Dennis).
During inhalation, make-up air generated by patient
inhalation is entrained through the nebulizer. The nebulizer
is designed to allow this entrained air to ‘pick up’
additional aerosol, thus enhancing the rate of aerosol
output. This design has theoretical and practical advantages
over ‘constant output’ nebulizer designs w3,4x as
it results in less waste, greater aerosol output rates, and
therefore faster delivery times than conventional ‘constant
output’ nebulizer designs.
There is a further little recognized, but critically
important, advantage of breath enhanced nebulizer
design over constant output nebulizer design—the stability
of aerosol size w5x. Nebulized aerosol is made up
of small water droplets, when they are released from the
nebulizer, containing a drug in solution (as with TNS)
or suspension. The size of these droplets, when they are
released from the nebulizer, is only stable as long as
they are enshrouded in air with 100% relative humidity.
Complete humidification of released air is normally the
case within the aerosol emitted from most nebulizers.
However, with conventional nebulizer designs, the ambient
air entrained during patient inhalation mixes with
the released nebulized aerosol in varying proportions
depending on the inhalation flow rate and the rate of
output from the nebulizer. The nebulized aerosol is
mixed into ambient air and evaporates virtually instantaneously w6x until the surrounding air is fully humidified,
whatever the ratio of entrained, partly humidified
air to fully humidified ‘nebulized air’. This evaporative
effect cannot be avoided and can significantly reduce
the size of inhaled aerosol obtained from constant output
nebulizer designs. A schematic illustrating this evaporative
process is shown in Fig. 1.
The extent of the evaporation and consequent reduction
of nebulized aerosol size depends on the capacity
of entrained air to absorb water, which is dependent on
total entrained flow, ambient temperature and ambient
humidity. Thus, the size of nebulized droplets inhaled
from constant output nebulizer designs is inherently
unstable. In contrast, breath-enhanced nebulizer designs
such as the PARI LC PLUS entrain ambient air through
rather than over the nebulizer.