HYDROFLUOROALKANE (HFA)- VS. CHLOROFLUOROCARBON (CFC)- BECLOMETHASONE DIPROPIONATE
(BDP) DELIVERY USING NEW AEROSOL CHAMBERS FOR NEONATAL INHALED GLUCOCORTICOID DELIVERY
CH Cole, JP Mitchell, MP Foley, MW Nagel, CC Doyle, SL Bates
Tufts University School of Medicine, New England Medical Center
and Trudell Medical International
BACKGROUND
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Inhaled glucocorticoid treatment of neonatal chronic lung
disease
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associated with modest or no pulmonary improvements
variable, limited response may be due to inadequate and
inconsistent aerosol delivery
STUDY DESIGN
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HFA-BDP is of interest from a neonatal perspective because
HFA-BDP solution has a finer aerosol particle size than CFCBDP suspension
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CFC-BDP (Vanceril 50, Schering, 50 µg/dose)
HFA-BDP (Qvar™50, 3M, 50 µg/dose)
Using prototype Aerosol Holding Chambers (Trudell Medical
International, London, Canada) (145 ml)
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*based on aerosol exiting 2.5 mm ETT
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Fine Particle Fraction (<3.1 µm)*:
HFA-BDP 97% vs CFC-BDP 34%
intended for use solely in conjunction with a ventilator
Neonatal Chamber (NC-ETT)
! may be used with manual ventilation of intubated patient
Neonatal Chamber (NC-Mask)
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One cannot extrapolate dose delivery data from adult studies
and apply to neonatal aerosol therapy
TED, µg; (Efficiency,%)
may be used to deliver aerosol by face mask to non-intubated
patients
Neonatal aerosol delivery requires consideration
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Manual Ventilation via NC-ETT
Mechanical Ventilation (40% RH) via NCVS
Mechanical Ventilation (100% RH) via NCVS
Without manual assistance (”spontaneous breathing”)
With manual assistance
Aerosol Delivery in Intubated Patient Simulations:
Aerosol delivery of HFA-BDP is greater in quantity and
efficiency than delivery of CFC-BDP in each of 5 simulations to
ventilated and non-ventilated neonatal models
OBJECTIVE
NC-Mask: No ManV
NC-Mask: ManV
HFA-BDP
(QVAR)
4.1 ± 1.6
(8.2)
26.6 ± 3.1
(53.2)
p<0.001
CFC-BDP
(Vanceril)
2.3 ± 0.7
(4.6)
21.6 ± 4.3
(43.2)
p<0.001
p=0.007
p=0.001
SUMMARY
N = 3 devices/group, 5 replications/device
Manual Ventilation via NC-ETT
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Delivery System
Aerosol Delivery via NC-Mask
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to understand the characteristics and amount of HFAmedications delivered under specific neonatal conditions
HYPOTHESIS
Aerosol Delivery via 2.5 mm ETT
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neonatal patient-related factors
aerosol delivery system-related factors
technique-related factors
New neonatal studies are essential
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5 NEONATAL SIMULATIONS
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Parameters:
Vt = 8 - 10 ml
Rate = 40/min
PEEP = 5 cm H2O
PIP = 20 cm H2O
PIFR = ca. 9 L/min
Table 2: BDP Delivery per actuation via NC-Mask
*based on aerosol exiting 2.5 mm ETT
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BDP Delivery via NC-Mask with
manual assistance
Parameters:
Vt = 8 - 10 ml
Rate = 40/min
PEEP = 5 cm H2O
PIP = 20 cm H2O
Neonatal Chamber-Ventilation System (NCVS)
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MMAD*: HFA-BDP (1.1 µm) < CFC-BDP (ca. 8 µm)
BDP Delivery via NC-Mask during simulation
of spontaneous breathing with no manual
assistance
Compare 2 Inhaled Glucocorticoids
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Aerosol Delivery in Spontaneous Breathing Patient Simulations:
Mechanical Ventilation via NCVS
Parameters:
T = 22°C, 40% RH
T = 36°C, 100% RH
Vt = 11.6 ml
Rate = 40/min
PEEP = 5 cm H2O
PIP = 20 cm H2O
PIFR = ca. 9 L/min
Parameters:
Vt = 8 - 10 ml
Rate = 40/min
PEEP = 5 cm H2O
PIP = 20 cm H2O
PIFR = ca. 9 L/min
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There was significantly greater aerosol delivery of HFA-BDP than
CFC-BDP from each neonatal delivery system (TED, Efficiency)
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Humidification reduced aerosol delivery
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Manual assisted ventilation provided greater dose delivery (TED,
Efficiency) than:
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mechanical ventilation via ETT (Table 1)
spontaneous breathing via NC + face mask (Table 2)
CONCLUSIONS
Table 1: BDP Delivery per actuation via ETT
TED, µg; (Efficiency,%)
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Compare HFA-BDP vs. CFC-BDP in terms of dose delivery from
the holding chamber via endotracheal tube (ETT) or mask
during 5 neonatal in vitro simulations
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Total Emitted Dose (TED, µg)
Efficiency (TED/LCD*,%)
*LCD = label claim dose
Delivery System
ManV + NCETT
MechV + NCVS
(40% RH)
MechV + NCVS
(100% RH)
HFA-BDP
(QVAR)
6.5 ± 0.6
(13.0)
4.4 ± 0.7
(8.8)
1.5 ± 0.2
(3.0)
p<0.001
CFC-BDP
(Vanceril)
1.3 ± 0.5
(2.6)
0.4 ± 0.3
(0.8)
0.02 ± 0.08
(0.04)
p<0.003
p<0.0001
p<0.0001
p<0.0001
Availability of extra-fine HFA-BDP and greater delivery efficiency
offers new opportunities to assess potential clinical benefits, efficacy
and safety of HFA-BDP in the treatment of neonatal chronic lung
disease.
SPR Annual Meeting, 4-7 May 2002, Baltimore, USA