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SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study

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Abstract

Purpose

To compare in vivo the total and regional pulmonary deposition of aerosol particles generated by a new system combining a vibrating-mesh nebulizer with a specific valved holding chamber and constant-output jet nebulizer connected to a corrugated tube.

Methods

Cross-over study comparing aerosol delivery to the lungs using two nebulizers in 6 healthy male subjects: a vibrating-mesh nebulizer combined with a valved holding chamber (Aerogen Ultra®, Aerogen Ltd., Galway, Ireland) and a jet nebulizer connected to a corrugated tube (Opti-Mist Plus Nebulizer®, ConvaTec, Bridgewater, NJ). Nebulizers were filled with diethylenetriaminepentaacetic acid labelled with technetium-99 m (99mTc-DTPA, 2 mCi/4 mL). Pulmonary deposition of 99mTc-DTPA was measured by single-photon emission computed tomography combined with a low dose CT-scan (SPECT-CT).

Results

Pulmonary aerosol deposition from SPECT-CT analysis was six times increased with the vibrating-mesh nebulizer as compared to the jet nebulizer (34.1 ± 6.0% versus 5.2 ± 1.1%, p < 0.001). However, aerosol penetration expressed as the three-dimensional normalized ratio of the outer and the inner regions of the lungs was similar between both nebulizers.

Conclusions

This study demonstrated the high superiority of the new system combining a vibrating-mesh nebulizer with a valved holding chamber to deliver nebulized particles into the lungs as comparted to a constant-output jet nebulizer with a corrugated tube.

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Abbreviations

99mTc-DTPA:

Diethylenetriaminepentaacetic acid labelled with technetium-99 m

AP:

Anteroposterior planar image

JN:

Jet nebulizer with a corrugated tube

PA:

Posteroanterior planar image

ROI:

Region of interest

SPECT-CT:

Single-photon emission computed tomography combined with a CT scan

VN-C:

Vibrating-mesh nebulizer combined with a specific valved holding chamber

VOI:

Volume of interest

References

  1. Waters V, Smyth A. Cystic fibrosis microbiology: advances in antimicrobial therapy. J Cyst Fibros. 2015;14(5):551–60.

    Article  CAS  PubMed  Google Scholar 

  2. Palmer LB. Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care. 2009;15(5):413–8.

    Article  PubMed  Google Scholar 

  3. Lu Q, Luo R, Bodin L, Yang J, Zahr N, Aubry A, et al. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology. 2012;117(6):1335–47.

    Article  CAS  PubMed  Google Scholar 

  4. Luyt CE, Clavel M, Guntupalli K, Johannigman J, Kennedy JI, Wood C, et al. Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia. Crit Care. 2009;13(6):R200.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Niederman MS, Chastre J, Corkery K, Fink JB, Luyt CE, Garcia MS. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med. 2012;38(2):263–71.

    Article  CAS  PubMed  Google Scholar 

  6. Palmer LB. Ventilator-associated infection: the role for inhaled antibiotics. Curr Opin Pulm Med. 2015;21(3):239–49.

    Article  CAS  PubMed  Google Scholar 

  7. Dolovich MB, Dhand R. Aerosol drug delivery: developments in device design and clinical use. Lancet. 2011;377(9770):1032–45.

    Article  CAS  PubMed  Google Scholar 

  8. Bakker EM, Volpi S, Salonini E, van der Wiel-Kooij EC, Sintnicolaas CJ, Hop WC, et al. Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation. Eur Respir J. 2011;38(6):1328–35.

    Article  CAS  PubMed  Google Scholar 

  9. Devadason SG, Everard ML, Linto JM, Le Souef PN. Comparison of drug delivery from conventional versus “Venturi” nebulizers. Eur Respir J. 1997;10(11):2479–83.

    Article  CAS  PubMed  Google Scholar 

  10. Byrne NM, Keavey PM, Perry JD, Gould FK, Spencer DA. Comparison of lung deposition of colomycin using the HaloLite and the Pari LC Plus nebulisers in patients with cystic fibrosis. Arch Dis Child. 2003;88(8):715–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Coates AL, Green M, Leung K, Chan J, Ribeiro N, Louca E, et al. Rapid pulmonary delivery of inhaled tobramycin for Pseudomonas infection in cystic fibrosis: a pilot project. Pediatr Pulmonol. 2008;43(8):753–9.

    Article  PubMed  Google Scholar 

  12. Dahlstrom K, Thorsson L, Larsson P, Nikander K. Systemic availability and lung deposition of budesonide via three different nebulizers in adults. Ann Allergy Asthma Immunol. 2003;90(2):226–32.

    Article  PubMed  Google Scholar 

  13. Hardy JG, Newman SP, Knoch M. Lung deposition from four nebulizers. Respir Med. 1993;87(6):461–5.

    Article  CAS  PubMed  Google Scholar 

  14. Ilowite JS, Gorvoy JD, Smaldone GC. Quantitative deposition of aerosolized gentamicin in cystic fibrosis. Am Rev Respir Dis. 1987;136(6):1445–9.

    Article  CAS  PubMed  Google Scholar 

  15. Newman SP, Pitcairn GR, Hooper G, Knoch M. Efficient drug delivery to the lungs from a continuously operated open-vent nebulizer and low pressure compressor system. Eur Respir J. 1994;7(6):1177–81.

    CAS  PubMed  Google Scholar 

  16. Hess DR. Nebulizers: principles and performance. Respir Care. 2000;45(6):609–22.

    CAS  PubMed  Google Scholar 

  17. Heijerman H, Westerman E, Conway S, Touw D, Doring G. Consensus working g. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: a European consensus. J Cyst Fibros. 2009;8(5):295–315.

    Article  CAS  PubMed  Google Scholar 

  18. Zhou QT, Tang P, Leung SS, Chan JG, Chan HK. Emerging inhalation aerosol devices and strategies: where are we headed? Adv Drug Deliv Rev. 2014;75:3–17.

    Article  CAS  PubMed  Google Scholar 

  19. Ari A, de Andrade AD, Sheard M, AlHamad B, Fink JB. Performance comparisons of Jet and mesh nebulizers using different interfaces in simulated spontaneously breathing adults and children. J Aerosol Med Pulm Drug Deliv. 2015;28(4):281–9.

    Article  CAS  PubMed  Google Scholar 

  20. Fleming J, Bailey DL, Chan HK, Conway J, Kuehl PJ, Laube BL, et al. Standardization of techniques for using single-photon emission computed tomography (SPECT) for aerosol deposition assessment of orally inhaled products. J Aerosol Med Pulm Drug Deliv. 2012;25 Suppl 1:S29–51.

    PubMed  Google Scholar 

  21. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38.

    Article  CAS  PubMed  Google Scholar 

  22. ICRP. Radiation dose to patients from radiopharmaceuticals, publication 53. In: Pergamon press, editor. Annals of ICRP. 18. Oxford, New York 1988. p. 121.

  23. Karsten J, Stueber T, Voigt N, Teschner E, Heinze H. Influence of different electrode belt positions on electrical impedance tomography imaging of regional ventilation: a prospective observational study. Crit Care. 2016;20(1):3.

    Article  PubMed  PubMed Central  Google Scholar 

  24. European Pharmacopoeia. Preparations for inhalation: Aerodynamic assessment of fine particles, section 2.9.18. European Pharmacopoeia. 8th ed. ed. 2008. p. 309–20.

  25. Newman S, Bennett WD, Biddiscombe M, Devadason SG, Dolovich MB, Fleming J, et al. Standardization of techniques for using planar (2D) imaging for aerosol deposition assessment of orally inhaled products. J Aerosol Med Pulm Drug Deliv. 2012;25 Suppl 1:S10–28.

    PubMed  Google Scholar 

  26. De Backer W, Devolder A, Poli G, Acerbi D, Monno R, Herpich C, et al. Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J Aerosol Med Pulm Drug Deliv. 2010;23(3):137–48.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pitcairn GR, Newman S. Tissue attenuation corrections in gamma scintigraphy. J Aerosol Med. 1997;10(3):187–98.

    Article  Google Scholar 

  28. Brand P, Schulte M, Wencker M, Herpich CH, Klein G, Hanna K, et al. Lung deposition of inhaled alpha1-proteinase inhibitor in cystic fibrosis and alpha1-antitrypsin deficiency. Eur Respir J. 2009;34(2):354–60.

    Article  CAS  PubMed  Google Scholar 

  29. Coates AL, Green M, Leung K, Chan J, Ribeiro N, Ratjen F, et al. A comparison of amount and speed of deposition between the PARI LC STAR(R) jet nebulizer and an investigational eFlow(R) nebulizer. J Aerosol Med Pulm Drug Deliv. 2011;24(3):157–63.

    Article  CAS  PubMed  Google Scholar 

  30. Haussermann S, Winnips C, Edelman J, Kappeler D, Herpich C, Ehlich H, et al. Lung deposition of Alpha1-proteinase inhibitor (human) (A1-PI[H]) inhalation solution using Two inhalation modes of the I-neb adaptive aerosol delivery (AAD) system in healthy subjects and subjects with cystic fibrosis. J Aerosol Med Pulm Drug Deliv. 2016;29(3):242–50.

    Article  PubMed  Google Scholar 

  31. Rau JL, Ari A, Restrepo RD. Performance comparison of nebulizer designs: constant-output, breath-enhanced, and dosimetric. Respir Care. 2004;49(2):174–9.

    PubMed  Google Scholar 

  32. Coates AL, Leung K, Chan J, Ribeiro N, Charron M, Schuh S. Respiratory system deposition with a novel aerosol delivery system in spontaneously breathing healthy adults. Respir Care. 2013;58(12):2087–92.

    Article  PubMed  Google Scholar 

  33. Harvey CJ, O’Doherty MJ, Page CJ, Thomas SH, Nunan TO, Treacher DF. Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation. Thorax. 1995;50(1):50–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nikander K, Nicholls C, Denyer J, Pritchard J. The evolution of spacers and valved holding chambers. J Aerosol Med Pulm Drug Deliv. 2014;27 Suppl 1:S4–23.

    Article  PubMed  Google Scholar 

  35. Coates AL, Green M, Leung K, Louca E, Tservistas M, Chan J, et al. The challenges of quantitative measurement of lung deposition using 99mTc-DTPA from delivery systems with very different delivery times. J Aerosol Med. 2007;20(3):320–30.

    Article  CAS  PubMed  Google Scholar 

  36. Duarte AG. Inhaled bronchodilator administration during mechanical ventilation. Respir Care. 2004;49(6):623–34.

    PubMed  Google Scholar 

  37. Coates AL, Denk O, Leung K, Ribeiro N, Chan J, Green M, et al. Higher tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis. Pediatr Pulmonol. 2011;46(4):401–8.

    Article  PubMed  Google Scholar 

  38. Dubus JC, Vecellio L, De Monte M, Fink JB, Grimbert D, Montharu J, et al. Aerosol deposition in neonatal ventilation. Pediatr Res. 2005;58(1):10–4.

    Article  PubMed  Google Scholar 

  39. Sagalla RB, Smaldone GC. Capturing the efficiency of vibrating mesh nebulizers: minimizing upper airway deposition. J Aerosol Med Pulm Drug Deliv. 2014;27(5):341–8.

    Article  PubMed  Google Scholar 

  40. Boukhettala N, Poree T, Diot P, Vecellio L. In vitro performance of spacers for aerosol delivery during adult mechanical ventilation. J Aerosol Med Pulm Drug Deliv. 2015;28(2):130–6.

    Article  CAS  PubMed  Google Scholar 

  41. Fleming J, Conway J, Majoral C, Tossici-Bolt L, Katz I, Caillibotte G, et al. The use of combined single photon emission computed tomography and X-ray computed tomography to assess the fate of inhaled aerosol. J Aerosol Med Pulm Drug Deliv. 2011;24(1):49–60.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Majoral C, Fleming J, Conway J, Katz I, Tossici-Bolt L, Pichelin M, et al. Controlled, parametric, individualized, 2D and 3D imaging measurements of aerosol deposition in the respiratory tract of healthy human volunteers: in vivo data analysis. J Aerosol Med Pulm Drug Deliv. 2014;27(5):349–62.

    Article  PubMed  Google Scholar 

  43. Lenney W, Edenborough F, Kho P, Kovarik JM. Lung deposition of inhaled tobramycin with eFlow rapid/LC Plus jet nebuliser in healthy and cystic fibrosis subjects. J Cyst Fibros. 2011;10(1):9–14.

    Article  CAS  PubMed  Google Scholar 

  44. Carvalho TC, Peters JI, Williams 3rd RO. Influence of particle size on regional lung deposition--what evidence is there? Int J Pharm. 2011;406(1–2):1–10.

    Article  CAS  PubMed  Google Scholar 

  45. Thomas SH, O’Doherty MJ, Page CJ, Nunan TO. Variability in the measurement of nebulized aerosol deposition in man. Clin Sci (Lond). 1991;81(6):767–75.

    Article  CAS  Google Scholar 

  46. Brand P, Beckmann H, Maas Enriquez M, Meyer T, Mullinger B, Sommerer K, et al. Peripheral deposition of alpha1-protease inhibitor using commercial inhalation devices. Eur Respir J. 2003;22(2):263–7.

    Article  CAS  PubMed  Google Scholar 

  47. Nikander K, Prince I, Coughlin S, Warren S, Taylor G. Mode of breathing-tidal or slow and deep-through the I-neb adaptive aerosol delivery (AAD) system affects lung deposition of (99 m)Tc-DTPA. J Aerosol Med Pulm Drug Deliv. 2010;23 Suppl 1:S37–43.

    CAS  PubMed  Google Scholar 

  48. Reychler G, Aubriot AS, Depoortere V, Jamar F, Liistro G. Effect of drug targeting nebulization on lung deposition: a randomized crossover scintigraphic comparison between central and peripheral delivery. Respir Care. 2014;59(10):1501–7.

    Article  PubMed  Google Scholar 

  49. Hubert D, Leroy S, Nove-Josserand R, Murris-Espin M, Mely L, Dominique S, et al. Pharmacokinetics and safety of tobramycin administered by the PARI eFlow rapid nebulizer in cystic fibrosis. J Cyst Fibros. 2009;8(5):332–7.

    Article  CAS  PubMed  Google Scholar 

  50. Ehrmann S, Mercier E, Vecellio L, Ternant D, Paintaud G, Dequin PF. Pharmacokinetics of high-dose nebulized amikacin in mechanically ventilated healthy subjects. Intensive Care Med. 2008;34(4):755–62.

    Article  CAS  PubMed  Google Scholar 

  51. Brown JS, Zeman KL, Bennett WD. Regional deposition of coarse particles and ventilation distribution in healthy subjects and patients with cystic fibrosis. J Aerosol Med. 2001;14(4):443–54.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGEMENTS AND DISCLOSURE

This study was funded by an unrestricted grand by Aerogen Ltd. (Galway, Ireland)

Author information

Authors and Affiliations

  1. Institut de Recherche Expérimentale et Clinique (IREC), Pneumologie, ORL & Dermatologie, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Jonathan Dugernier & Gregory Reychler

  2. Soins Intensifs, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Jonathan Dugernier, Jean Roeseler & Pierre-François Laterre

  3. Médecine Physique, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Jonathan Dugernier & Gregory Reychler

  4. Médecine Nucléaire, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Michel Hesse, Virginie Depoortere & François Jamar

  5. Louvain Drug Research Institute (LDRI), Université Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Rita Vanbever

  6. Haute Ecole de Santé Vaud, Filière physiothérapie, University of Applied Sciences and Arts Western Switzerland, Avenue de Beaumont 21, 1011, Lausanne, Switzerland

    Jean-Bernard Michotte

  7. Pneumologie, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Gregory Reychler

Authors
  1. Jonathan Dugernier
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  2. Michel Hesse
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  7. Pierre-François Laterre
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  8. François Jamar
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  9. Gregory Reychler
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Corresponding author

Correspondence to Jonathan Dugernier.

Additional information

ClinicalTrial registration

NCT02298101

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Figure S1

Bland Altman plot illustrating the agreement between the two imaging techniques (SPECT-CT vs Planar) used to assess the lung deposition fraction obtained with the vibrating-mesh nebulizer combined with a specific valved holding chamber (orange) and the jet nebulizer (blue). Although the differences of lung deposition between both techniques increased with lung deposition measurements (higher differences with the vibrating-mesh nebulizer combined with a specific inhalation chamber than with the jet nebulizer), most but two values of lung deposition remain in both limits of agreement from −3.79 to 2.89 (dotted lines) with a mean bias of −0.45 (solid line). (GIF 183 kb)

High resolution image (TIF 104 kb)

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Dugernier, J., Hesse, M., Vanbever, R. et al. SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study. Pharm Res 34, 290–300 (2017). https://doi.org/10.1007/s11095-016-2061-7

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  • DOI: https://doi.org/10.1007/s11095-016-2061-7

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