Abstract
Aerosols are defined as any mixture of solid or liquid particles/droplets that are stable as a suspension in air. Aerosols influence the lives of a large majority of the population. A proportion of particulates exacerbate or induce lung disease. Other aerosols are used in the prevention or control of lung disease or in the investigation of disease. This review covers the mechanisms of deposition of aerosols, the production and sizing of aerosols, factors affecting the variability in output from nebulisers and the use of radionuclides in defining drug deposition from therapeutic nebulisers.
Similar content being viewed by others
References
Morrow PE. Aerosol characterisation and deposition. Am Rev Respir Dis 1974;110: 88–99
Stuart BO. Deposition of inhaled aerosols. Arch Intern Med 1973;131: 60–73
Hatch TF, Gross P. Pulmonary deposition and retention of inhaled aerosols. New York: Academic Press;1964: 13
Tayali NE, Bates CJ. Particle sizing techniques in multiphase flows: a review. Flow Meas Instrum 1990;1: 77–105
Cornillaut J. Particle size analyser. Appl Opt 1972;11: 265–268
Swithenbank J, Beer JM, Taylor DS, Abbot D, McCreath GC. A laser diagnostic for the measurement of droplet and particle size distribution. University of Sheffield Report H1C245. 1977
Ho KKL, Kellaway IW, Tredree R. Particle size analysis of nebulised aerosols using Faunhofer laser diffraction and inertial impaction methods. J Pharm Pharmacol 1986;38: 26
Weibel ER. Morphometry of the human lung. Berlin Heidelberg New York: Springer 1963
Lourenco RV, Loddenkemper R, Carton RW. Patterns of distribution and clearance of aerosols in patients with bronchiectasis. Am Rev Respir Dis 1972;106: 857–866
Chamberlain MJ, Morgan WKC, Vinitski S. Factors influencing the regional deposition of inhaled particles in man. Clin Sci 1983;64: 69–78
Ferron GA, Kreyling WG, Haider B. Inhalation of salt aerosol particles — II. Growth and deposition in the human respiratory tract. J Aerosol Sci 1988;19: 611–631
Morrow PE. Some physical and physiological factors controlling the fate of inhaled substances. I. Health Phys 1960;2: 366–376
Mercer TT. Aerosol technology in hazard evaluation. New York: Academic Press, 1973
Fuchs NA. The mechanics of aerosols. Oxford: Pergamon Press, 1964
Brian J. Aerosol and humidity therapy. Am Rev Respir Dis 1980;122: 17–21
Gerrity TR, Lee PS, Hass FJ, Marinelli A, Werner P, Lourenco RV. Calculated deposition of inhaled particles in the airway generations of normal subjects. J Appl Physiol 1979;47: 867–873
Harris RL Jr, Fraser DA. A model for the deposition of fibres in the human respiratory system. Am Ind Hyg Assoc J 1976;37: 73–76
Morrow PE. Factors determining hygroscopic aerosol deposition in airways. Pysiol Rev 1986;66: 330–336
McFadden ER, Denison DM, Waller IF, Assoufi BI, Peacock A, Sopwith T. Direct recordings of the temperatures in the tracheobronchial tree in man. J Clin Invest 1982;69: 700–705
McFadden ER, Pichurko BMI, Bowman F, Ingenito EP, Burns S, Dowling N, Solway J. Thermal mapping of the airways in humans. J Appl Physiol 1985;58: 564–570
Task Group on Lung Dynamics. Deposition and retention models for internal dosimetry of the human respiratory tract. Health Phys 1966;12: 173–207
Miller RF, O'Doherty MJ. Pulmonary nuclear medicine. Eur J Nucl Med 1992;19: 355–368
Hurford MJ. Production of ferric oxide aerosols with a May spinning top aerosol generator. J Aerosol Sci 1981;12:441–456
May KR. An improved spinning top homogeneous spray apparatus. J Appl Physics 1949;20: 932–938
Wehner AP. Electro aerosol therapy.I. Am J Phys Med 1962;41: 24–40
Wehner AP. Electro aerosol therapy II. Am J Phys Med 1962;41: 68–86
Litt M, Swift DE. The Babington nebuliser. A new principle for generation of therapeutic aerosols. Am Rev Respir Dis 1972;105:308–310
Muir DC. The production of monodisperse aerosols by a La Mer-Sinclair generator. Ann Occup Hyg 1965;8: 233–238
Newman SP, Pellow PGD, Clarke SW. Flow pressure characteristics of compressors used for inhalation therapy. Eur J Respir Dis 1987;71: 122–126
Davis SS (1978) Physico-chemical studies on aerosol solutions for drug delivery: I. Water-propylene glycol systems. Int J Pharm 1978;1: 71–78
Phipps PR, Gonda I. Droplets produced by medical nebulizers. Some factors affecting their size and solute concentration. Chest 1990;97: 1327–1332
Newman SP, Pellow PGD, Clay MM, Clarke SW. Evaluation of jet nebulisers for use with gentamicin solution. Thorax 1985;40: 671–676
Thomas SHL, O'Doherty MJ, Page CJ, Nunan To. Variability in the measurement of nebulised aerosol deposition in man. Clin Sci 1991;12: 767–775
Thomas SHL, O'Doherty MJ, Page CJ, Nunan TO, Bateman NT. Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulisers. Eur Respir J 1991;4: 616–622
O'Doherty MJ, Thomas SHL, Page CJ, Nunan TO, Treacher DF. Delivery of a nebulised aerosol to a lung model during mechanical ventilation. Effect of ventilator settings and nebuliser type, position and volume of fill. Am Rev Respir Dis 1992;146: 383–388
Clay MM, Pavia D, Newman SP, Lennard-Jones T, Clarke SW. Assessment of jet nebulisers for lung aerosol therapy. Lancet 1983;11: 592–594
Lang RJ. Ultrasonic atomisation of fluids. J Acoust Soc Am 1962;34: 6–9
Pillay M, Akkermans JA, Cox PH. A high efficiency ultrasound nebuliser for radioaerosol studies of the lungs. Eur J Nucl Med. 1987;13: 331–334
Miller RF, Kocjan G, Buckland J. Sputum induction for the diagnosis of pulmonary disease in HIV positive patients. J Infect 1991;23: 5–15
Kohn H, de Jong R, Konig B, Mostbeck A. Aerosol delivery system with high lung deposition efficiency. J Aerosol Med 1988;1: 227
Kohn H, Mostbeck A, Bachmayr S et al. 99mTc-DTPA aerosol for same day post perfusion ventilation imaging: results of a mulitcentre study. Eur J Nucl Med 1993;20: 4–9
Miller RF, Jarritt PH, Lui D, Kilery J, Semple SJG, Ell PJ. The APE nebuliser — a new delivery system for the alveolar targeting of particulate technetium 99m DTPA. Eur J Nucl Med 1991;18: 164–170
Burch WM, Sullivan PJ, Mc Laren CJ. Technegas a new ventilation agent for lung scanning. Nucl Med Commun 1986;7: 865–871
Rojas-Burke J. High hopes for Technegas. J Nucl Med 1991;32(11): 24N-30N
Strong JC, Agnew JE. The particle size distribution of technegas and its influence on regional lung deposition. Nucl Med Commun 1989;10: 425–430
Newman SP, Moren F, Pavia D, Little F, Clarke SW. Deposition of pressurised suspension aerosols inhaled through extension devices. Am Rev Respir Dis 1981;124: 317–320
Newman SP, Millar AB, Lennard-Jones TR, Moren F, Clarke SW. Improvement of pressurised aerosol deposition with Nebuhaler spacer device. Thorax 1984;39: 935–941
Vidgren MT, Paronen TP, Karkkainen A, Karjalainen P. Effect of extension devices on the drug deposition from inhalation aerosols. Int J Pharm 1987;39: 107–112
Newman SP, Weisz AWB, Talaee N, Clarke SW. Improvement of drug delivery with a breath actuated pressurised aerosol for patients with a poor inhaler technique. Thorax 1991;46: 712–716
Davis SS, Hardy JG, Newman SP, Wilding IR. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms. Eur J Nucl Med 1992;19: 971–986
Lippman M, Albert RE. The effect of particle size on the regional deposition of inhaled aerosols in the human respiratory tract. Am Ind Hyg Assoc J 1969;30: 257–275
Asmundsson T, Johnson RF, Kilburn KH, Goodrich JK. Efficiency of nebulisers for depositing saline in human lung. Am Rev Respir Dis 1973;108: 506–512
Newman SP, Woodman G, Clarke SW. Deposition of carbenicillin aerosols in cystic fibrosis: effects of nebuliser system and breathing pattern. Thorax 1988;43: 318–322
Ruffin RE, Dolovich MB, Wolff RK, Newhouse MT. The effects of preferential deposition of histamine in the human airway. Am Rev Respir Dis 1978;117: 485–491
Macey DJ, Marshall R. Absolute quantitation of radiotracer uptake in the lungs using a gamma camera. J Nucl Med 1982;23: 731–735
Fleming JS. A technique for the absolute measurement of activity using a gamma camera and computer. Phys Med Biol 1979;24: 176–180
Wu RK, Siegel JA. Absolute quantitation of radioactivity using the buildup factor. Med Phys 1984;11: 189–192
Siegel JA, Wu RK, Maurer AH. The buildup factor: effect of scatter on absolute volume determination. J Nucl Med 1985;26: 390–394
Siegel JA. The effect of source size on the buildup factor calculation of absolute volume. J Nucl Med 1985;26: 1319–1322
Fleming JS. Technique for the use of standard outlines for attenuation correction and quantification in SPECT. Nucl Med Commun 1990;11: 685–696
Perring S, Summers Q, Fleming JS, Holgate S. The quantitative assessment of pulmonary penetration for aerosol administered by metered dose inhaler using aligned CT and SPECT data sets [abstract]. Nucl Med Commun 1990;11: 893
Phipps PR, Gonda I, Bailey DL, Borham P, Bautovich G, Anderson SD. Comparison of planar and tomographic gamma scintigraphy to measure the penetration index of inhalation aerosols. Am Rev Respir Dis 1989;139: 1516–1523
Forge NI, Mountford PJ, O'Doherty MJ. A comparison of quantification techniques in planar radionuclide lung imaging. Eur J Nucl Med 1993;20: 10–15
Chan TL, Lippmann M. Experimental measurements and empirical modelling of the regional deposition of inhaled particles in humans. Am Ind Hyg Assoc J 1980;41: 399–409
Stahlhofen W, Gebhart J, Heyder J. Biological variability of regional deposition of aerosol particles in the human respiratory tract. Am Ind Hyg Assoc J 1981;42: 348–352
Horsfield K, Cumming G. Angles of branching and diameters of branches in the human bronchial tree. Bull Math Biophys 1967;29: 245–249
Horsfield K, Dart G, Olson DE, Filley GF, Cumming G. Models of the human bronchial tree. J Appl Physiol 1971;31: 207–217
Koblinger L, Hofmann W. Analysis of human lung morphometric data for stochastic aerosol deposition calculations. Phys Med Biol 1985;30: 541–556
Foster WM, Langenback EG, Smaldone GC, Bergofsky EH, Bohning DE. Flow limitations on expiration induces central particle deposition and disrupts effective flow of airway mucus. Ann Occup Hyg 1988;Suppl 6: 101–105
Foster WM. Editorial: is 24 hour lung retention an index of alveolar deposition? J Aerosol Med 1988;1: 1
Smaldone GC, Perry RJ, Bennet WD, Messina MS, Zwang J, Ilowite J. Interpretation of “24 hour lung retention” in studies of mucociliary clearance. J Aerosol Med 1988;1: 11–16
Camner P. Clearance of particles from the human tracheobronchial tree. Clin Sci 1980;59: 79–85
Pavia D, Bateman JRM, Clarke SW. Deposition and clearance of inhaled particles. Bull Eur Physiopathol Respir 1980;16: 335–366
Stahlhofen W, Gebhart J, Rudolf G, Scheuch G. Measurement of lung clearance with pulses of radioactively labelled aerosols. J Aerosol Sci 1986;17: 333–337
Pavia D, Thomson ML, Clarke SW, Shannon HS. Effect of lung function and mode of inhalation on penetration of aerosol into the human lung. Thorax 1977;32: 194–197
Muir DCF, Davies CN. The deposition of 0.5 μm diameter aerosols in the lungs of man. Ann Occup Hyg 1967;10: 161–174
Dennis WL. The effect of breathing rate on the deposition of particles in the human respiratory system. In: Walton WH, ed. Inhaled particles III.: Unwin Brothers; Old Woking Surrey 1971: 91–102
Woodman PS, Courts CT, Mole DR, Dendy PP, Higenbottam TW. Sites of deposition of aqueous aerosols: a study of efficiency of delivery systems for lung ventilation imaging in man. Nucl Med Commun 1989;10: 171–180
Goldberg IS, Lourenco RV. Deposition of aerosols in pulmonary disease. Arch Intern Med 1973;131: 88–91
Dolovich M, Ryan G, Newhous MT. Aerosol penetration into the lung: influence on airway responses. Chest 1981;80 (Suppl): 834–836
Newman SP, Pavia D, Clarke SW. How should a pressurised beta-adrenergic bronchodilator be inhaled. Eur J Respir Dis 1981;62: 3–21
Pavia D, Thompson ML. The fractional deposition of inhaled 2 and 5 micron particles in the alveolar and tracheobronchial regions of the healthy human lung. Ann Occup Hyg 1976;19: 109–114
Ilowite JS, Gorvoy JD, Smaldone GC. Quantitative deposition of aerosolised gentamicin in cystic fibrosis. Am Rev Respir Dis 1987;136:1445–1449
Sanchis J, Dolovich M, Chalmers R, Newhouse M. Quantitation of regional aerosol clearance in the normal lung. J Appl Physiol 1972;33: 757–762
O'Doherty MJ, Thomas SHL, Page CJ, Bradbeer C, Nunan TO, Bateman NT. Does inhalation of pentamidine in the supine position increase deposition in the upper part of the lung? Chest 1988;97: 1343–1348
Bennett WD, Smaldone GC. Human variation in the peripheral air-space deposition of inhaled particles. J Appl Physiol 1987;62: 1603–1610
Dickenson G, Smaldone GC. Particle deposition and failure of prophylaxis using aerosolized pentamidine [abstract]. Am Rev Respir Dis 1990;131: A150
O'Doherty MJ, Thomas SHL, Page CJ, Blower PJ, Bateman NT, Nunan TO. Lung deposition of aerosolised pentamidine using a direct radiolabel 123I iodo-pentamidine. Nucl Med Commun 1993;14:8–11
O'Doherty M, Thomas S, Page C, Bradbeer CS, Nunan T, Bateman N. Pulmonary deposition of nebulised pentamidine. The effect of nebuliser type, dose and volume of fill. Thorax 1990;45: 460–464
O'Doherty MJ, Thomas S, Page C, Bradbeer C, Barlow D, Nunan TO, Bateman NT. Differences in the relative efficiency of nebulisers for pentamidine administration. Lancet 1988;II: 1283–1286
Clay MM, Clarke SW. Effect of nebulised aerosol size on lung deposition in patients with mild asthma. Thorax 1987;42: 190–194
Clay MM, Pavia D, Clarke SW. Effect of aerosol particle size on bronchodilation with nebulised terbutaline in asthmatic subjects. Thorax 1986;41: 364–368
Newman Sp, Pellow PG, Clarke SW. Choice of nebulisers and compressors for delivery of carbenicillin aerosol. Eur J Respir Dis 1986;69: 160–168
O'Callahan C, Clarke AR, Milner AD. Inaccurate calculation of drug output from nebulisers. Eur J Pediatr 1989;148: 473–474
Newman SP, Pellow PG, Clarke SW. Droplet size distributions of nebulized aerosols for inhalation therapy. Clin Phys Physiol Meas 1986;7: 139–146
Tsanakas JN, Wilson AJ, Boon AW Evaluation of nebulisers for bronchial challenge tests. Arch Dis Child 1987;62: 506–508
Wanner A, Brodnan JM, Perez J, Henke KG, Kim CS. Variability of airway responsiveness to histamine aerosol in normal subjects. Role of deposition. Am Rev Respir Dis 1985;131:3–7
O'Riordan TG, Greco MJ, Perry RJ, Smaldone GC. Nebulizer function during mechanical ventilation. Am Rev Respir Dis 1992;145: 1117–1122
Fuller HD, Dolovich MB, Posmituck G, Wong Pack W, Newhouse MT. Pressurised aerosol versus jet aerosol delivery to mechanically ventilated patients. Comparison of dose to the lungs. Am Rev Respir Dis 1990;141: 440–444
MacIntyre NR, Silver RM, Miller CW, Schuler F, Coleman RE. Aerosol delivery in intubated, mechanically ventilated patients. Crit Care Med 1985;13: 81–84
Thomas SHL, O'Doherty MJ, Fidler H, Page CJ, Nunan TO, Treacher DF. Aerosol deposition during mechanical ventilation. Thorax 1993;48: 154–159
Smaldone GC, Perry RJ, Deutsch DG. Characteristics of nebulisers used in the treatment of AIDS related Pneumocystis carinii pneumonia. J Aerosol Med 1988;1: 113–126
O'Doherty MJ, Thomas SHL, Page C, Clarke AR, Mitchell D, Heduan E, Nunan TO, Bateman NT. Does 99mTc human serum albumin alter the characteristics of nebulised pentamidine isethionate? Nucl Med Commun 1989;10: 523–529
Perry RJ, O'Riordan TG, Smaldone GC. Inaccuracies in measurements of nebulised drug delivery. Am Rev Respir Dis 1991;143: A708
Nolop KB, Braude S, Royston D, Maxwell DL, Hughes JMB. Positive end expiratory pressure increases pulmonary clearance of inhaled 99m-Tc DTPA in nonsmokers but not in healthy smokers. Bull Eur Physiopathol Respir 1987;23: 57–60
Barrowcliffe MP, Zanelli GD, Jones JG. Pulmonary clearance of radiotracers after positive end expiratory pressure or acute lung injury. J Appl Physiol 1989;66: 288–294
Clarke SW. Inhaler therapy. Q J Med 1988;67: 355–368
Fraser I, DaVall A, Dolovich M, Newhouse MT. Therapeutic aerosol delivery in ventilator systems. Am Rev Respir Dis 1981;123:107
Lawford P, Jones BJM, Milledge JS. Comparison of intravenous and nebulised salbutamol in initial treatment of severe asthma. Br Med J 1978;I: 84
Gay PC, Rodarte JR, Tayyab M, Hubmayr RD. Evaluation of bronchodilator responsiveness in mechanically ventilated patients. Am Rev Respir Dis 1987;136: 880–885
Wegener T, Wretman S, Sandhagen B, Nystrom SO. Effect of ipratropium bromide aerosol on respiratory function in patients under ventilator treatment. Acta Anaesthesiol Scand 1987;31: 652–654
Legare M, Petrof B, Simkovitz P, Goldberg P, Gottfried S. Aerosolised ipratopium bromide in mechanically ventilated COPD patients [abstract]. Am Rev Respir Dis 1988;137: 60
Ahrens RC, Ries RA, Popendorf W, Wiese JA. The delivery of therapeutic aerosols through endotracheal tubes. Pediatr Pulmonol 1986;2: 19–26
Flavin M, MacDonald M, Dolovich M, Coates G, O'Brodovich H. Aerosol delivery to the rabbit lung with an infant ventilator. Pediatr Pulmonol 1986;2: 35–39
Alderson PO, Secher-Walker RH, Stominger DB, Markham BS, Hill RL. Pulmonary deposition of aerosols in children with cystic fibrosis. J Pediatr 1974;84: 479–484
O'Doherty MJ, Thomas SHL, Gibb D et al. Deposition of aerosolized pentamidine in children. Thorax 1993;48:220–226
Collis GG, Cole CH, Le Souef PN. Dilution of nebulised aerosols by air entrainment in children. Lancet 1990;336: 341–343
Le Souef PN. Validity of methods used to test airway responsiveness in children. Lancet 1992;339: 1282–1284
Wolfsdorf J, Swift DL, Avery ME. Mist therapy reconsidered; an evaluation of the respiratory deposition of labelled water aerosols produced by jet and ultrasonic nebulizers. Pediatrics 1969;43: 799–808
Cook G, Clarke SEM. An evaluation of Technegas as a ventilation agent compared with krypton-81m in the scintigraphic diagnosis of pulmonary embolism. Eur J Nucl Med 1992;19: 770–774
Hilson AJW, Pavia D, Diamond PD, Agnew JE. An ultrafine 99m-Tc aerosol (Technegas) for lung ventilation scintigraphy — a comparison with Kr-81m. J Nucl Med 1989;30: 744
Vezina W, Chamberlain M, Vinitski S, King M, Nicholson R, Morgan WK. Radioaerosol ventilation imaging in ventilator-dependent patients. Technical considerations. Clin Nucl Med 10: 759–766
Author information
Authors and Affiliations
Additional information
Correspondence to: M.J. O'Doherty
Rights and permissions
About this article
Cite this article
O'Doherty, M.J., Miller, R.F. Aerosols for therapy and diagnosis. Eur J Nucl Med 20, 1201–1213 (1993). https://doi.org/10.1007/BF00171019
Issue Date:
DOI: https://doi.org/10.1007/BF00171019