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Comparison of Lung Deposition in Two Types of Nebulization^*

Intrapulmonary Percussive Ventilation vs Jet Nebulization

^* From the Departments of Physical Medicine and Rehabilitation (Ms. Cremers), and Pediatry (Mr. Reychler), Nuclear Medicine (Dr. Keyeux), and Pneumology Unit (Mr. Veriter and Drs. Rodenstein and Liistro), Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Correspondence to: Giuseppe Liistro, PhD, Pneumology Unit, Cliniques Universitaires St-Luc (UCL), Avenue Hippocrate 10, 1200 Brussels, Belgium; e-mail: giuseppe.liistro{at}clin.ucl.ac.be

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Background: So-called intrapulmonary percussive ventilation (IPV), frequently coupled with a nebulizer, is increasingly used as a physiotherapy technique; however, its physiologic and clinical values have not been rigorously assessed.

Study objective: To compare in vitro and in vivo characteristics of the nebulizer of the IPV device (Percussionaire; Percussionaire Corporation; Sandpoint, ID) with those of standard jet nebulization (SST) [SideStream; Medic-Aid; West Sussex, UK].

Design: Aerodynamic particle size was studied by an cascade impactor. The deposition of ^99mTc-diethylenetriaminepenta-acetic acid was measured in 10 healthy subjects by tomoscintigraphy during spontaneous breathing with both nebulizers.

Measurements and results: The mass median aerodynamic diameter (0.2 µm vs 1.89 µm for IPV and SST, respectively) and the fine-particle fraction (16.2% vs 67.5%, respectively) were significantly smaller with IPV. In vivo, respiratory frequency (RF) was lower with the IPV device (10.1 ± 3.4 breaths/min vs 14.6 ± 3.4 breaths/min, p = 0.002). Whole-body deposition was significantly higher with IPV (15.63% vs 9.31%), but it was due to a higher extrapulmonary deposition. Although intrapulmonary deposition (IPD) was not different with both devices (4.20% for SST vs 2.49% for IPV), it was much more variable with IPV, compared to SST. The penetration index into the lung was higher with IPV than SST when normalized for RF (0.045 ± 0.018 breaths/min vs 0.026 ± 0.013 breaths/min, p = 0.007).

Conclusion: The two techniques showed comparable lung deposition despite a large difference in particle size. However, IPV IPD was too variable and thus too unpredictable to recommend its use for drug delivery to the lung.

Key Words: intrapulmonary percussive ventilation • lung deposition • nebulization • respiratory therapy • ^99mTc diethylenetriaminepenta-acetic acid

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Nebulizers are widely used in the treatment of pulmonary diseases such as asthma, COPD, and cystic fibrosis. Many patients find nebulizations attractive. However, deposition of nebulized medications may be highly variable. The therapeutic effect depends on the quality of the nebulization,¹ on the drug solution, on the conditions of the nebulization, on the individual patient (pattern of breathing, anatomy, underlying lung pathology), and on the device characteristics. All those variables influence the nebulization.²

Jet nebulization has been studied with different devices in various groups of patients and in different diseases.^{3 4 5 6 7} Lung deposition by jet nebulization was also studied using different drugs.^{3 5 6 7 8 9}

By contrast, intrapulmonary percussive ventilation (IPV) has been poorly studied from this point of view.¹⁰ The device was designed by F.M. Bird in 1979. It consists of a high-frequency percussive ventilation method combined with a nebulizer. It delivers rapid minibursts of air and aerosol solution through a unique sliding Venturi, and it was originally designed, according to the manufacturer, to increase the mucociliary clearance, to improve the gas exchange, to stabilize airway patency, to humidify the airway, and to improve the lung mechanics. Aerosolized antibiotics are used in patients with cystic fibrosis and, combined with albuterol aerosolization, IPV may help to mobilize airway secretions in these subjects.¹¹ However, there is no published study on deposition properties of the IPV. There is therefore a need for validation studies.

The aim of this study was to compare IPV combined with nebulization to a validated jet nebulizer. Comparison of particle deposition with both devices can give important information on their respective efficacy and indications. The aerodynamic particle size analysis was performed, and the lung deposition was investigated by tomoscintigraphy.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Subjects
Ten healthy men, all nonsmokers (mean age, 28 years; range, 23 to 43 years), were investigated. All subjects underwent standard spirometry according to American Thoracic Society guidelines.¹² The Ethics Committee of our institution approved the study, and a written, informed consent was obtained from the volunteers.

Nebulizers
Both devices were driven by the same pressure: 3.5 bars of compressed air. For standard jet nebulization (SST), we chose a well-studied nebulizer (SideStream; Medic-Aid; West Sussex, UK). Since the collector device is made up of two pieces, we abraded the borders to optimize the sealing of the collector and avoid leaks to the atmosphere. For IPV, an IPV apparatus (Percussionaire; Percussionaire Corporation; Sandpoint, ID) with an operating pressure of 20 cm H₂O for a frequency of 250 cycles per minute was used. The same collector and top of both nebulizers were used throughout all the in vitro and in vivo measurements.

In Vitro Measurements
Particle size was measured by a cascade impactor (1 ACFM Eight Stage NonViable Cascade Impactor; Graseby Andersen; Atlanta, GA) at ambient temperature (23°C). Each stage of the impactor (10 to 0.7 µm) was coated with a hydroxypropylmethylcellulose gel (22.5% weight/volume in water).

The nebulizer and IPV were directly connected to the cascade impactor. For both nebulization devices, 2 mL of sulforhodamine solution were nebulized during 1 min with an inspiratory flow of 28.3 L/min. Fluorescence of the deposited particles was measured by a spectrometer (Luminescence Spectrometer LS50B; Perkin-Elmer; Norwalk, CT) [excitation = 586 nm, emission = 602 nm].

The drug quantities found on each stage were added to determine the emitted dose (ED). The cumulative mass of nebulized solution retained in the successive stages of the cascade impactor was calculated and plotted on a log-probability scale (as percentage of total mass recovered in the impactor) against the effective cutoff diameter. According to Clark and Borgstrom,¹³ the experimental mass median aerodynamic diameter (MMAD) of the particles was defined from this graph as the interpolation of the regression line at 50%. The percentage of particles with a size between 1 µm and 5 µm, defined as the fine-particle fraction (FPF), was calculated.

Output flow of both nebulizers was measured using a spirometer (Expirograph; Godart; Bilthoven, the Netherlands). The nebulizers were connected to the tubing of the spirometer, and the volume of the nebulized solution was measured as a function of time to calculate flow. The measurements were done in triplicate and the mean values are reported.

In Vivo Measurements
For SST, a Hans Rudolf 1410 valve (Hans Rudolf; Kansas City, MO) was inserted between the filter and the mouthpiece to avoid rebreathing (Fig 1 ). We added a filter on the expiratory airway of both systems to avoid atmospheric contamination by radioactive particles. The subjects breathed spontaneously through the same mouthpiece with a nose clip in place. According to manufacturer of the IPV device, 1 mL of solution is nebulized per minute. However, after preliminary testing, we noticed that 4 mL of solution were nebulized in 3 min with IPV. We therefore reduced the nebulization time to 3 min for IPV with continuous percussions. For SST, the duration of nebulization was fixed at 4 min.

View larger version (50K): [in this window] [in a new window] [Download PPT slide]   Figure 1.. Circuit used for the nebulization. 1 = collector; 2 = top of the nebulizer; 3 = mouthpiece; 4 = Hans Rudolf valve; 5 = filter. Arrows show the direction of airflow.

Data Acquisition and Treatment
The collectors of SST (element 1 in Fig 1 ) and IPV were filled with 4 mL of a final solution of ^99mTc-diethylenetriaminepenta-acetic acid aerosol for nebulization, prepared with ethanol according to the recommendations of the provider (Mallinckrodt; Petten, Holland). ^99mTc-diethylenetriaminepenta-acetic acid aerosol is a diagnostic radiopharmaceutical specially designed for administration by inhalation. As determined by chromatography, the labeling efficiency is > 95% and the complex is stable during 6 h in vitro. The absence of modification of the radioactive background in the tissues surrounding the lungs (except the digestive tract) indicated that the radioactive marker was not released during the data acquisition process. Thus, the regional quantification of radioactivity in the lungs is a reliable means for studying aerosol distribution.

Radioactivity of the collector was measured before (initial dose [ID]) and after nebulization with a radioisotope calibrator (Capintec CRC-12; Capintec; Ramsey, NJ). By subtraction of both measurements, the nebulized dose was calculated and expressed in megabecquerels. The collector was weighed (Mettler H10W Mettler Instrumente AG; Greifensee, Switzerland) empty, before, and then after the nebulization. By subtracting these weights, we obtained the residual weight (RW) of the doses. The emitted weight was obtained by subtracting the weight of the collector after nebulization from the weight of the filled collector.

Respiratory frequency (RF), tidal volume (VT), minute ventilation, and inspiratory time (TI) were measured by inductance plethysmography (Respitrace; Ambulatory Monitoring; Ardsley, NY) after calibration with a spirometer (Expirograph) to determine the pattern of breathing during nebulization. Calibration of the inductance plethysmograph was done using the isovolume maneuver.¹⁴

As soon as nebulization was completed, the subjects were driven in a wheelchair to the gamma camera. The subjects were then placed in supine position on the moving bed of a three-head gamma camera (Triad XLT20; Trionix; Twinsburg, OH) fitted with low-energy ultra-high resolution collimators. A 60°-angle emission tomography of the entire thorax was acquired in a 64 x 64 matrix for a total duration of 10 min. With the subjects remaining in the same position, emission tomography was immediately followed by a transmission tomography using the displacement of a linear ¹⁵³Gd source over the thorax for each of the 30 angles of a 180° rotation of the camera with a total duration of 30 min.

At the end of the study, the radioactivity of the inhalation material (elements 2, 3, 4, 5 in Fig 1 ) was measured by use of a head of the camera as detector. Activity in cycles per minute was expressed in megabecquerels after calibration of the detector by a source of technetium.

One-pixel (8.96 mm)-thick transverse planes were reconstructed by convolution back projection and a first-order Chang attenuation correction¹⁵ using a constant coefficient as derived from the transmission data. For each subject, reconstructed transmission tomography images were used to define right lung boundaries in coronal views. Three consecutive (one pixel) coronal slices centered on the hilum of the right lung were summed together. On this 26.88-mm thick slice, a peripheral strip and central square areas were drawn in order to delineate a peripheral region of interest (ROI) and a central pulmonary ROI according to the criteria proposed by Phipps et al.¹⁶

Radioactivity Deposition Parameters
Comparison of both ROIs allowed the calculation of the penetration index (PI) as follows: PI = peripheral ROI (counts per second per pixel)/central ROI (counts per second per pixel). Activity distributed to both lungs was obtained by summing the activities of all the coronal slices taking care to avoid the activities of the trachea and of the digestive tract. Global lung activity (intrapulmonary deposition [IPD]) was expressed in percentage of the initial dose.

Activity distributed to the whole body (whole-body dose [WBD]) was obtained by subtracting the residual activities of the nebulization accessories from the ID and expressing the result as a percentage. The IPD/WBD ratio was calculated as follows: WBD = ID - residual activity (in the collector, the filter, and the instrumental dead space).

During the first test, the expired gas was collected in a neoprene balloon connected to the filter to check its efficacy. Since no significant level of radioactivity was recorded in the balloon at the end of the test, this precaution was no longer taken.

Statistical Methods
The RW and radioactivity of both collectors were compared using an unpaired Student t test. A Student paired t test was used with a level of significance of p < 0.05 for the comparisons of ventilatory and scintigraphic parameters. We compared respiratory parameters and deposition results between the two methods. Each subject was his own control. We also compared the IPV-first group with the SST-first group to assess an eventual training effect. A standard linear regression analysis was used to examine the relationship between ventilatory and scintigraphic variables, as well as between gravimetric parameters. The coefficient of variation was used to evaluate the variability (SD/mean x 100).

	Results

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Lung Function Tests
Table 1 presents average anthropometric and lung function data of the subjects. All volunteers had spirometric values in the normal range.

Pattern of Breathing During Nebulization
Table 2 summarizes the data of ventilation. Average RF was significantly lower with IPV than with SST. Average VT was higher with IPV, though not significantly. There was no significant difference between the two groups for the TI (p = 0.396), while the duration of nebulization was shorter in the IPV group. The ratio of TI to total time did not show any significant difference (p = 0.261).

View larger version (15K): [in this window] [in a new window] [Download PPT slide]   Figure 2.. Individual data of IPD obtained with SST and IPV showing the difference of interindividual variability.

The pattern of breathing during nebulization (Table 2) was not influenced by the system used except for RF, which was 45% higher with SST than with IPV. VT was also increased with IPV, albeit not significantly because of a large variability.

There was no significant relationship between RF and IPD for both devices. By contrast, we found a significant correlation between RF and PI for SST (r = -0.65, p < 0.05) but not for IPV (Fig 3 ). There was no significant training effect between the subjects starting with the SST or the IPV in terms of WBD, IPD, or PI.

View larger version (13K): [in this window] [in a new window] [Download PPT slide]   Figure 3.. Relationship between PI and RF for both devices.

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion References

 
We have found that nebulization combined with IPV resulted in a higher WBD than SST. This was due to a higher extrapulmonary deposition with the IPV. This device delivered intrapulmonary aerosols irregularly in a group of naive healthy subjects.

Although in vitro testings present some limitations and may give an overestimation of the lung deposition measured in vivo,¹⁷ it remains nevertheless an acceptable way to compare two methods in a standardized protocol. FPF was small, and particle size distribution was theoretically less favorable for IPD with IPV than with SST. The aerodynamic data of the SideStream device reported here are consistent with the literature (FPF, 67.5% vs 71.95%; MMAD, 1.89 µm vs 2.1 µm).^{18 19} Then we postulated the validity of the comparison of the aerodynamic characteristics (FPF, ED, and MMAD) of the two devices.

The design of the dead space of IPV might have explained part of the differences in aerodynamic properties, because the larger particles could have remained in the instrumental dead space before reaching the impactor. However, the residual radioactivity measured in the devices, including their dead space, was significantly less with IPV than with SST, ruling out this hypothesis.

Classicaly, using a jet nebulizer, < 10% of a nebulized drug deposits in the lung.⁴ Lung deposition depends on particle size distribution, which is under the influence of air flow, filling volume, drug solution, and ambient temperature.^{1 2 6 20} In this study, those parameters were kept constant to avoid variability. We used a fixed driving pressure of compressed air for both nebulizers that corresponded to the minimal pressure recommended by the IPV manufacturer (3.5 bars).

The pattern of breathing is also important, as lung deposition depends principally on inspiration.²¹ In our study, the TI was comparable in the two groups, and thus the potential influence of the inspiration on deposition was minimized.

As shown by previous reports,^{22 23} the mouthpiece may influence the results. We therefore used an identical mouthpiece with the two devices. The same nebulizers were reused during all measurements. Because each subject was his own control, we avoided the effect of anatomical and mechanical variability as confounding factors. The disease can modify the pattern of breathing,⁴ but the subjects were all healthy volunteers.

We did not calculate the dose retained in the body from the difference between the weight of the ID and the RW. Indeed, we had to take into account the dead space of the devices, which were different (36 mL with SST and 76 mL with IPV), and the loss of solvent during nebulization by the concomitant process of evaporation.²⁴ Scintigraphy of the dead space and the collector enabled us to measure the nebulized solution retained in the devices. That was the reason why all the components of the ID (residual, retained in the filter, in the dead space) except WBD were measured by their radioactivity.

IPD was higher with SST in seven subjects, without reaching statistical significance. However, one of the more striking results was the variability of IPD with IPV. The IPD varied 33-fold with the IPV (Fig 2 ). All other parameters being constant, the causes of this variability may be related to the changes in pattern of breathing of the subjects or to the device itself. As shown on Table 2 , only VT was more markedly affected by interindividual variation, but there was no relationship between VT and IPD with the IPV. We have also found that RF was significantly lower during IPV nebulization. As stated before, a low RF would increase lung deposition, but this was not the case. Another explanation is the fact that the subjects reported frequent swallowing during IPV nebulization. Indeed, the IPD/WBD ratio showed that more drug was dispersed in the body and less deposited in the lung with IPV than with SST. This characteristic may explain the variability of IPD and the lower IPD/WBD ratio we observed, the aerosolized particles being swallowed by the subjects, or impacted in the upper extrathoracic airways. Calculated WBD did not give an indication on the exact localization of extrathoracic deposition. A total body deposition imaging would be necessary to evaluate this precisely, but inspection of the scintigraphic images showed systematically an intense spot at the gastric level with IPV. Because some drugs have side effects linked to the extrathoracic deposition (eg, inhaled corticosteroids), this could be a disadvantage for the IPV.

The PI, the ratio of PD to CD of aerosolized particles in the lung, is another important characteristic of a aerosol. Both average CD and PD were comparable between the two aerosols, but we observed a trend for a higher PI with IPV, though not significant (Table 3) .

At variance with previous data from the literature,²⁵ we did not observe a relationship between RF and IPD with either device. This may be due to interindividual anthropometric variability and to the small number of volunteers studied. But the significant correlation between RF and PI for SST shows that the PD is improved with a decrease in RF (Fig 3 ). To our knowledge, this influence of RF on the PI has not been previously reported. In the IPV group, the changes in RF were not related to PI.

We therefore normalized scintigraphic variables with respect to RF. As shown in Table 4 , the normalized PI was significantly higher with the IPV, together with normalized WBD, but IPD was unchanged.

Besides the different aerodynamic properties and the pattern of breathing, percussions could also explain the observed lung deposition. They could slow down inhaled small particles in the respiratory tract and could have the same effect as a postinspiratory pause. The superimposed percussions of IPV could also enhance turbulence in the carrier gas stream. These turbulences could increase the coalescence of aerosolized particles, increasing their size and promoting their impaction in the upper airway.

Our subjects were not trained before the study. Contrary to a classic nebulizer, the IPV could be rather surprising for a naive subject, and could influence the breathing pattern. But we did not find any difference between the SST-first group and the IPV-first group. However, to verify this hypothesis, a similar study with a previous training or with a fixed RF could be useful.

In conclusion, we have found large differences in the aerodynamic properties of IPV and SST nebulizers. The Percussionaire IPV device presents a potential interesting property in terms of a higher PI when normalized for RF, but our study demonstrates that IPV cannot replace a standard nebulizer if a pharmacologic agent must be delivered to the lung. However, our results cannot be extrapolated to patients with COPD or cystic fibrosis. These diseases are characterized by totally different respiratory mechanics and respiratory muscle functions. Because of the high cost of IPV and the large interindividual variability of its IPD, we cannot recommend this device as a first choice for inhaled drug therapy.

	Acknowledgements

 
The authors thank R. Vanbever and C. Bosquillon for help in collecting and interpreting in vitro data.

	Footnotes

 
Abbreviations: CD = central deposition; ED = emitted dose; FPF = fine-particle fraction; ID = initial dose; IPD = intrapulmonary deposition; IPV = intrapulmonary percussive ventilation; MMAD = mean median aerodynamic diameter; PD = peripheral deposition; PI = penetration index; RF = respiratory frequency; ROI = region of interest; RW = residual weight; SST = standard jet nebulization; TI = inspiratory time; VT = tidal volume; WBD = whole-body dose

Partly supported by the Belgian "Fonds National de la Recherche Scientifique" grant No. 3.4536.98.

Received for publication April 14, 2003. Accepted for publication July 17, 2003.

	References

TOP Abstract Introduction Materials and Methods Results Discussion References

 

1. Dolovich, M, Ryan, G, Newhouse, MT (1981) Aerosol penetration into the lung; influence on airway responses. Chest 80(6 Suppl),834-836
2. Suarez, S, Hickey, AJ Drug properties affecting aerosol behavior. Respir Care 2000;45,652-666[Medline]
3. Asmus, MJ, Milavetz, G, Tice, AL, et al In vitro characteristics of tobramycin aerosol from ultrasonic and jet nebulizers. Pharmacotherapy 2001;21,534-539[Medline]
4. Coates, AL, Allen, PD, MacNeish, CF, et al Effect of size and disease on estimated deposition of drugs administered using jet nebulization in children with cystic fibrosis. Chest 2001;119,1123-1130[Abstract/Free Full Text]
5. Faurisson, F, Dessanges, JF, Grimfeld, A, et al Etude comparative sur les performances et l’ergonomie de nebuliseurs dans la mucoviscidose. [Comparative study of the performance and ergonomics of nebulizers in cystic fibrosis]. Rev Mal Respir 1996;13,155-162[Medline]
6. Newman, SP Lung deposition from nebulizers. Eur Respir Rev 2000;10,224-227
7. Thomas, SH, O’Doherty, MJ, Graham, A, et al Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers. Thorax 1991;46,717-721[Abstract]
8. Khatri, L, Taylor, KM, Craig, DQ, et al An assessment of jet and ultrasonic nebulisers for the delivery of lactate dehydrogenase solutions. Int J Pharm 2001;227,121-131[Medline]
9. Terzano, C, Guerra, S, Allegra, L Effectiveness of beclomethasone dipropionate aerosolized through different nebulizers to asthmatic patients. Eur Rev Med Pharmacol Sci 2001;5,43-51[Medline]
10. Homnick, DN, White, F, de Castro, C Comparison of effects of an intrapulmonary percussive ventilator to standard aerosol and chest physiotherapy in treatment of cystic fibrosis. Pediatr Pulmonol 1995;20,50-55[ISI][Medline]
11. Natale, JE, Pfeifle, J, Homnick, DN Comparison of intrapulmonary percussive ventilation and chest physiotherapy: a pilot study in patients with cystic fibrosis. Chest 1994;105,1789-1793[Abstract/Free Full Text]
12. American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995;152,1107-1136[ISI][Medline]
13. Clark, A, Borgstrom, L In vitro testing of pharmaceutical aerosol and predicting lung deposition from in vitro measurements. Bisgaard, H O’Callaghan, C Smaldone, GC eds. Drug delivery to the lung 2002,105-142 Marcel Dekker. New York, NY:
14. Konno, K, Mead, J Measurement of the separate volume changes of rib cage and abdomen during breathing. J Appl Physiol 1967;22,407-422[Free Full Text]
15. Chang, LT A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978;NS-25,638-643
16. Phipps, PR, Gonda, I, Bailey, DL, et al Comparisons of planar and tomographic gamma scintigraphy to measure the penetration index of inhaled aerosols. Am Rev Respir Dis 1989;139,1516-1523[ISI][Medline]
17. Snell, NJ, Ganderton, D Assessing lung deposition of inhaled medications: consensus statement from a workshop of the British Association for Lung Research, held at the Institute of Biology, London, UK, on 17 April 1998. Respir Med 1999;93,123-133[Medline]
18. Geller, DE, Eigen, H, Fiel, SB, et al Effect of smaller droplet size of dornase alfa on lung function in mild cystic fibrosis: Dornase Alfa Nebulizer Group. Pediatr Pulmonol 1998;25,83-87[Medline]
19. Loffert, DT, Ikle, D, Nelson, HS A comparison of commercial jet nebulizers. Chest 1994;106,1788-1792[Abstract/Free Full Text]
20. Clay, MM, Pavia, D, Newman, SP, et al Factors influencing the size distribution of aerosols from jet nebulisers. Thorax 1983;38,755-759[Abstract]
21. Knoch, M, Sommer, E Jet nebulizer design and function. Eur Respir Rev 2000;10,183-186
22. Everard, ML, Hardy, JG, Milner, AD Comparison of nebulised aerosol deposition in the lungs of healthy adults following oral and nasal inhalation. Thorax 1993;48,1045-1046[Abstract]
23. Lin, TC, Breysse, PN, Laube, BL, et al Mouthpiece diameter affects deposition efficiency in cast models of the human oral airways. J Aerosol Med 2001;14,335-341[Medline]
24. Dennis, JH, Stenton, SC, Beach, JR, et al Jet and ultrasonic nebuliser output: use of a new method for direct measurement of aerosol output. Thorax 1990;45,728-732[Abstract]
25. Hakkinen, AM, Uusi-Heikkila, H, Jarvinen, M, et al The effect of breathing frequency on deposition of drug aerosol using an inhalation-synchronized dosimeter in healthy adults. Clin Physiol 1999;19,269-274[CrossRef][ISI][Medline]

This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Reychler, G. Articles by Liistro, G. Search for Related Content PubMed PubMed Citation Articles by Reychler, G. Articles by Liistro, G.