Comparison of Breath-Enhanced to Breath-Actuated Nebulizers for Rate, Consistency, and Efficiency

doi:10.1378/chest.126.5.1619

Chest

Volume 126, Issue 5, November 2004, Pages 1619-1627

https://doi.org/10.1378/chest.126.5.1619 Get rights and content

Objectives:

To evaluate differences between three new-generation nebulizers—Pari LC Star (Pari Respiratory Equipment; Mississauga, ON, Canada), AeroEclipse (Trudell Medical International, London, ON, Canada), and Halolite (Medic-Aid Limited, West Sussex, UK)—in terms of rate and amount of expected deposition as well as the consistency of the doses delivered.

Methods:

The in vitro performance characteristics were determined and then coupled to the respiratory pattern of seven patients with cystic fibrosis (age range, 4 to 18 years) in order to calculate expected deposition. The Pari LC Star and AeroEclipse were characterized while being driven by the Pari ProNeb Ultra compressor (Pari Respiratory Equipment) for home use, and by a 50-psi medical air hospital source. The Halolite has its own self-contained compressor. Algorithms for the rate of output for the inspiratory flow were developed for each device. Patient flow patterns were divided into 5-ms epochs, and the expected deposition for each epoch was calculated from the algorithms. Summed over a breath, this allowed the calculation of the estimated deposition for each patient’s particular pattern of breathing.

Results:

The rate of deposition was highest for the Pari LC Star and lowest for the Halolite. Rate of deposition was independent of respiratory pattern for the Pari LC Star and AeroEclipse, but proportional to respiratory rate for the Halolite. The differences between the Pari LC Star and AeroEclipse were less when driven by the 50-psi source. The AeroEclipse had the least amount of drug wastage. As designed, the Halolite delivered a predetermined amount of drug very accurately, whereas expected deposition when run to dryness of the other two devices had significant variations.

Conclusions:

To minimize treatment time, the Pari LC Star would be best. To minimize drug wastage, the AeroEclipse would be best. To accurately deliver a specific drug dose, the Halolite would be best.

Section snippets

Device Operation

The nebulizers and compressors used in this study were the Pari LC Star nebulizer driven by the Pari Proneb Ultra compressor (Pari Respiratory Equipment); the AeroEclipse nebulizer, which was also driven by the Pari compressor, as no specific compressor was recommended; and the Halolite nebulizer with a built-in compressor. The Halolite is a microprocessor-controlled device that activates the compressor on each inspiration. Three examples of both the Pari LC Star and the AeroEclipse were

Results

The steady-state in vitro assessment of both the total rate of output and that in the RF for the Pari LC Star and AeroEclipse is shown in Figure 4. With increasing entrained flow, the Pari LC Star increases both the Ot and that in the RF. The AeroEclipse begins producing aerosol when the entrained flow reaches 8 L/min (patient inspiratory flow is 13 L/min when the compressor driving flow is taken into consideration), and there is a slight fall off in Ot with increasing entrained flow, but there

Discussion

This study demonstrates that three of the new generation of nebulizers each has particular strengths and weaknesses. In terms of rapid drug delivery, a factor that may shorten treatment time and improve adherence with recommended therapy in a disease like CF,^16,¹⁷ the Pari LC Star appears to be the superior device when using a compressor. If the nebulizers are driven at 8 L/min from a compressed air source, as would be likely in a hospital setting, the rate of output for the Pari LC Star

Appendix

$V_{R} = Weightpost - Weightdry$

$OT = DI - (V_{R} \times CI) (Osmpost / Osmpre)$

$ORF = OT \times RF$

$Rate of output = OT / time for nebulization$

$I n v i v o efficiency = ORF inspiration / (OT inspiration + OT expiration)$ where Ot = total drug output (in milligrams), Di = initial dose of drug put into nebulizer (in milligrams); Ci = initial concentration of drug solution (milligrams per milliliter); OsmPOST = osmolality of drug solution after nebulization (millimoles per kilogram); OsmPRE = osmolality of drug solution before nebulization (millimiles

References (24)

E Kerem et al.
Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma
J Pediatr
(1993)
AL Coates et al.
A comparison of the availability of tobramycin for inhalation from vented versus unvented nebulizers
Chest
(1998)
SL Katz et al.
Nebulizer choice for treatment of cystic fibrosis patients with inhaled colistin
Chest
(2001)
AL Coates et al.
The choice of jet nebulizer, nebulizing flow and the addition of Ventolin Respiratory Solution affects tobramycin aerosols used in cystic fibrosis
Chest
(1997)
AR Clark
The use of laser diffraction for the evaluation of the aerosol clouds generated by medical nebulizers
Int J Pharm
(1995)
AL Coates et al.
Effect of size and disease on expected deposition of drugs given by jet nebulization to children with cystic fibrosis
Chest
(2001)
JH Wildhaber et al.
Inhalation therapy in asthma: nebulizer or pressurized metered-dose inhaler with holding chamber?In vivocomparison of lung deposition in children
J Pediatr
(1999)
DE Geller et al.
Efficiency of pulmonary administration of tobramycin solution for inhalation in cystic fibrosis using an improved drug delivery device
Chest
(2003)
JA Kastelik et al.
A widely available method for the assessment of aerosol delivery in cystic fibrosis
Pulm Pharmacol Ther
(2002)
BW Ramsey et al.
Intermittent administration of inhaled tobramycin in patients with cystic fibrosis
N Engl J Med
(1999)

BW Ramsey et al.

Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis

Am Rev Respir Dis

(1993)

BW Ramsey et al.

Consensus conference: practical implications of Pulmozyme

Pediatr Pulmonol

(1994)

Cited by (59)

Nebulised delivery of RNA formulations to the lungs: From aerosol to cytosol
2024, Journal of Controlled Release
In the past decade RNA-based therapies such as small interfering RNA (siRNA) and messenger RNA (mRNA) have emerged as new and ground-breaking therapeutic agents for the treatment and prevention of many conditions from viral infection to cancer. Most clinically approved RNA therapies are parenterally administered which impacts patient compliance and adds to healthcare costs. Pulmonary administration via inhalation is a non-invasive means to deliver RNA and offers an attractive alternative to injection. Nebulisation is a particularly appealing method due to the capacity to deliver large RNA doses during tidal breathing. In this review, we discuss the unique physiological barriers presented by the lung to efficient nebulised RNA delivery and approaches adopted to circumvent this problem. Additionally, the different types of nebulisers are evaluated from the perspective of their suitability for RNA delivery. Furthermore, we discuss recent preclinical studies involving nebulisation of RNA and analysis in in vitro and in vivo settings. Several studies have also demonstrated the importance of an effective delivery vector in RNA nebulisation therefore we assess the variety of lipid, polymeric and hybrid-based delivery systems utilised to date. We also consider the outlook for nebulised RNA medicinal products and the hurdles which must be overcome for successful clinical translation. In summary, nebulised RNA delivery has demonstrated promising potential for the treatment of several lung-related conditions such as asthma, COPD and cystic fibrosis, to which the mode of delivery is of crucial importance for clinical success.
Aerosol pulmonary immune engineering
2023, Advanced Drug Delivery Reviews
Aerosolization of immunotherapies poses incredible potential for manipulating the local mucosal-specific microenvironment, engaging specialized pulmonary cellular defenders, and accessing mucosal associated lymphoid tissue to redirect systemic adaptive and memory responses. In this review, we breakdown key inhalable immunoengineering strategies for chronic, genetic, and infection-based inflammatory pulmonary disorders, encompassing the historic use of immunomodulatory agents, the transition to biological inspired or derived treatments, and novel approaches of complexing these materials into drug delivery vehicles for enhanced release outcomes. Alongside a brief description of key immune targets, fundamentals of aerosol drug delivery, and preclinical pulmonary models for immune response, we survey recent advances of inhaled immunotherapy platforms, ranging from small molecules and biologics to particulates and cell therapies, as well as prophylactic vaccines. In each section, we address the formulation design constraints for aerosol delivery as well as advantages for each platform in driving desirable immune modifications. Finally, prospects of clinical translation and outlook for inhaled immune engineering are discussed.
Effect of nebuliser and patient interface type on fugitive medical aerosol emissions in adult and paediatric patients
2023, European Journal of Pharmaceutical Sciences
Open circuit aerosol therapy is associated with the potential for fugitive emissions of medical aerosol. Various nebulisers and interfaces are used in respiratory treatments, including the recent consideration of filtered interfaces. This study aims to quantify fugitive medical aerosols from various nebuliser types, in conjunction with different filtered and non-filtered interfaces.
For both simulated adult and paediatric breathing, four nebuliser types were assessed including; a small volume jet nebuliser (SVN), a breath enhanced jet nebuliser (BEN), a breath actuated jet nebuliser (BAN) and a vibrating mesh nebuliser (VMN). A combination of different interfaces were used including filtered and unfiltered mouthpieces, as well as open, valved and filtered facemasks. Aerosol mass concentrations were measured using an Aerodynamic Particle Sizer at 0.8 m and 2.0 m. Additionally, inhaled dose was assessed.
Highest mass concentrations recorded were 214 (177, 262) µg m⁻³ at 0.8 m over 45-minute run. The highest and lowest fugitive emissions were observed for the adult SVN facemask combination, and the adult BAN filtered mouthpiece combination respectively. Fugitive emissions decreased when using breath-actuated (BA) mode compared to continuous (CN) mode on the BAN for the adult and paediatric mouthpiece combination. Lower fugitive emissions were observed when a filtered facemask or mouthpiece was used, compared to unfiltered scenarios. For the simulated adult, highest and lowest inhaled dose were 45.1 (42.6, 45.6)% and 11.0 (10.1,11.9)% for the VMN and SVN respectively. For the simulated paediatric, highest and lowest inhaled dose were 44.0 (42.4, 44.8)% and 6.1 (5.9, 7.0)% for the VMN and BAN CN respectively. Potential inhalation exposure of albuterol was calculated to be up to 0.11 µg and 0.12 µg for a bystander and healthcare worker respectively.
This work demonstrates the need for filtered interfaces in clinical and homecare settings to minimise fugitive emissions and to reduce the risk of secondary exposure to care givers.
Inhaler Devices
2021, Encyclopedia of Respiratory Medicine, Second Edition
Inhalation is the cornerstone in the management of airway disease. By targeting drug directly to the lungs, inhalation compared to systemic therapy has key advantages that translate into therapeutic benefit for patients. There are four main classes of inhaler device used in everyday clinical practice available with a variety of drugs for the treatment of patients with asthma and COPD. Global directives now emphasize the assessment of inhaler technique, adherence and adjustment of the inhaler device as part of their core management cycles. Healthcare professionals therefore must have clear knowledge of inhaler devices and be proficient in their use, in order to select the right device for the right patient. Errors in the inhaler technique by the patient lead to significantly poor disease outcomes and significantly greater health-economic burden. Respiratory prescribing is unique in that it is the only branch of medicine where treatment efficacy depends not only the medication class but also the inhaler device. The inhaler device is as important as the pharmacological drug.
Devices and formulations: General introduction and wet aerosol delivery systems
2021, Inhaled Medicines: Optimizing Development through Integration of In Silico, In Vitro and In Vivo Approaches
Since steam and compressed air driven sprayers became popular for pulmonary administration of thermal waters and spas in the 19th century, a variety of different devices has become available for the aerosolization of aqueous based drug formulations. Currently, jet and ultrasonic nebulizers are most widely used for the administration of mainly antimicrobial drugs against various lung infections, chemotherapeutics for the treatment of lung cancer and provocative agents in bronchial challenge tests, but they are not very efficient and burdensome in use for the patient. New aerosolization technologies, like vibrating mesh, impinging jets and Rayleigh break-up have been introduced in the past 50 years and breath adaptive delivery has been developed for these principles to increase the efficiency of lung deposition. This opens the way for the administration of new and expensive biopharmaceuticals, but the drug stability and patient burden remain a limitation of this class of administration devices.
Insight into pulmonary drug delivery: Mechanism of drug deposition to device characterization and regulatory requirements
2019, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
The baffle present in the aerosol stream generates small particles from larger particles, draining rest of the large particles into the reservoir for re-nebulization. Practically, jet nebulizers of this type are not efficient in achieving high rates of lung deposition which is a major drawback leading to the further development of modern and effective devices [68]. Jet nebulizers are classified into four types.

View all citing articles on Scopus

The nebulizers studied were provided through the generosity of PARI Respiratory Equipment Inc., Trudell Medical International Inc., and Medic-Aid Limited.

Supported from a grant from the Hospital for Sick Children’s Foundation, made possible by a generous donation from Arnold and Lynn Irwin for cystic fibrosis research.

View full text

Chest

Laboratory and Animal InvestigationsComparison of Breath-Enhanced to Breath-Actuated Nebulizers for Rate, Consistency, and Efficiency

Objectives:

Methods:

Results:

Conclusions:

Section snippets

Device Operation

Results

Discussion

Appendix

J Pediatr

Chest

Chest

Chest

Int J Pharm

Chest

J Pediatr

Chest

Pulm Pharmacol Ther

Intermittent administration of inhaled tobramycin in patients with cystic fibrosis

N Engl J Med

Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis

Am Rev Respir Dis

Consensus conference: practical implications of Pulmozyme

Pediatr Pulmonol

Laboratory and Animal Investigations
Comparison of Breath-Enhanced to Breath-Actuated Nebulizers for Rate, Consistency, and Efficiency