Medications delivered through oral inhalation represent the cornerstone of pharmacotherapy for asthma and chronic obstructive pulmonary diseases. Several options exist as methods of delivering aerosols to the lung, including metered-dose inhalers, metered-dose inhalers attached to spacers or valved holding chambers, dry powder inhalers, and nebulizers. Delivery of aerosols to the lung is affected by numerous factors including characteristics of aerosol particles, patients’ ventilatory patterns, and physical condition of the lung. It has become increasingly clear that the device used to deliver the medication is an important factor in the extent of deposition and the ultimate therapeutic effect. Further, the same therapeutic agent may exhibit differing effects depending on which delivery device is used. Each inhalation device has specific instructions for use, and the techniques for use vary significantly among the available products. In each case, patients should be instructed and observed to ensure that they have the proper technique of use to achieve an optimal effect.
NHLBI, National Asthma Education and Prevention Program, Expert Panel Report II. Guidelines for the diagnosis and management of asthma. Publication No. 97-4051A. Bethesda, MD: US Department of Health and Human Services, 1997.
6.
Bisgaard H.Delivery of inhaled medication to children. J Asthma. 1997; 34(6):443-467.
7.
Thiringer, Svedmyr N.Comparison of infused and inhaled terbutaline in patients with asthma. Scand J Respir Dis. 1976; 57:17-24.
8.
Toogood JH, Baskerville J, Jennings B, et al. Bioequivalent doses of budesonide and prednisolone in moderate and severe asthma. J Allergy Clin Immunol. 1989; 83:688-700.
9.
Toogood JH, Frankish CW, Jennings BH, et al. A study of the mechanisms of the antiasthmatic action of inhaled budesonide. J Allergy Clin Immunol. 1990; 85:872-880.
10.
Pongracic JA. Asthma medications and how to use them. Curr Opin Pulm Med. 2000; 6:55-58.
Dolovich MA. Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung. Respir Care. 2000; 45:597-608.
13.
Hickey AJ. Characteristics influencing the effective administration of drugs as inhalation aerosols. Chest. 1993; 103:657-658.
14.
Johnson CE. Principles of nebulizer-delivered drug therapy for asthma. Am J Hosp Pharm. 1989; 46:1845-1855.
15.
Whelan AM, Hahn NW. Optimizing drug delivery from metered-dose inhalers. Ann Pharmacotherapy. 1991; 25:638-645.
16.
AARC Clinical Practice Guidelines: selection of aerosol delivery device. Respir Care. 1992; 37:891-897.
17.
Brain JD, Valberg PA. Deposition of aerosol in the respiratory tract. Am Rev Respir Dis. 1979; 120:1325-1373.
18.
Morrow PE. Aerosol characterization and deposition. Am Rev Respir Dis. 1974; 110:88-99.
19.
Newhouse MT, Ruffin RE. Deposition and fate of aerosolized drugs. Chest. 1973; (suppl. 6): 936S-942S.
20.
Dolovich M, Ruffin RE, Roberts R, et al. Optimal delivery of aerosols from metered-dose inhalers. Chest. 1981; 80:S911-S915
Epstein SW, Manning CPR, Ashley MJ, et al. Survey of the clinical use of pressurized aerosol inhalers. CMAJ.1979; 120:813-816.
29.
DeBlaquiere P, Christensen DB, Carter WB, et al. Use and misuse of metered-dose inhalers by patients with chronic lung disease. Am Rev Respir Dis. 1989; 140:910-916.
30.
Goodman DE, Israel E, Rosenberg M, et al. The influence of age, diagnosis, and gender on proper use of metered-dose inhalers. Am J Respir Crit Care Med. 1994; 150:1256-1261.
31.
Thompson J, Irvine T, Grathwohl K, et al. Misuse metered-dose inhalers in hospitalized patients. Chest. 1994; 105:715-717.
32.
Farr SJ, Rowe AM, Rubsamen R, et al. Aerosol deposition in the human lung following administration from a microprocessor controlled pressurized metered-dose inhaler. Thorax. 1995; 50:639-644.
33.
Larsen JS, Hahn M, Ekholm B, et al. Evaluation of conventional press and breathe metered-dose inhaler technique in 501 patients. J Asthma. 1994; 31(3):193-199.
34.
Guidry GG, Brown WD, Stogner SW, et al. Incorrect use of metered-dose inhalers by medical personnel. Chest. 1992; 101(1):31-33.
35.
Chhabra SK. A comparison of “closed” and “open” mouth techniques of inhalation of a salbutamol metered-dose inhaler. J Asthma. 1994; 31:123-125.
36.
Newman SP, Weisz AWB, Talaee N, et al. Improvement of drug delivery with a breath actuated pressurized aerosol for patients with poor inhaler technique. Thorax. 1991; 46:712-716.
37.
Asmus MJ, Teresi ME, Milavetz G, et al. How will the Freon ban affect MDIs?J Respir Dis. 1996; 17:34-37.
38.
Oenbrink RJ. Unexpected adverse effects of Freon 11 and Freon 12 as medication propellants. J Amer Osteo Assoc. 1993; 93:714-718.
39.
Pierson DJ. Toward international consensus on clinical aerosol administration. Chest. 1991; 100:1100-1101.
Partridge MR, Woodcock AA, Sheffer AL, et al. Chlorofluorocarbon-free inhalers: are we ready for the change?Eur Respir J. 1998; 11:1006-1008.
42.
June D.A new generation of inhaler technology. Br J Clin Prac. 1995; (suppl 79):18-21.
43.
Barry PW, O’Callaghan C. In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices. Eur Respir J. 1997; 10:1345-1348.
44.
Tinkelman DG, Bleecker ER, Ramsdell J, et al. HFA albuterol has a similar safety profile as CFC albuterol during regular use in asthmatics. Chest. 1998; 113:290-296.
45.
Bleeker ER, Tinkelman DG, Ramsdell J, et al. HFA albuterol provides comparable bronchodilation as CFC albuterol over 12 weeks of regular use in asthmatics. Chest. 1998; 113:283-289.
46.
Ramsdell JW, Klinger NM, Ekholm BP, et al. Safety of long-term treatment with HFA albuterol. Chest. 1999; 115:945-951.
47.
Bronsky E, Ekholm BP, Klinger NM, et al. Switching patients with asthma from CFC albuterol to HFA albuterol. J Asthma. 1999; 36:107-114.
48.
Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J. 1998; 12:1346-1353.
49.
Davies RJ, Stampone P, O’Connor BJ. Hydrofluoroalkane—134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose. Respir Med. 1998; 92(suppl A):23-31.
50.
Gross G, Thompson PJ, Chervinsky P, et al. Hydrofluoroalkane-134a beclomethasone dipropionate 400 mcg is as effective as chlorofluorocarbon beclomethasone dipropionate 800 mcg for the treatment of moderate asthma. Chest. 1999; 115:343-351.
51.
Tashkin DP. Extra-fine corticosteroid aerosols from hydrofluoroalkane-134a metered-dose inhalers: potential advantages and disadvantages. Chest. 1999; 115:316-318.
52.
Dalby RN, Somaraju S, Chavan VS, et al. Evaluation of aerosol drug output from the OptiChamber and AeroChamber spacers in a model system. J Asthma. 1998; 35:173-177.
53.
Ahrens R, Lux C, Bahl T, et al. Choosing the metered-dose inhaler, spacer or holding chamber that matches the patient’s need: evidence that the specific drug being delivered is an important consideration. J Allergy Clin Immunol. 1995; 96:288-294.
54.
Barry PW, O’Callaghan C.Inhalational drug delivery from seven different spacer devices. Thorax. 1996; 51:835-840.
55.
Clark DJ, Lipworth BJ. Effect of multiple actuations, delayed inhalation and antistatic treatment on the bioavailability of salbutamol via a spacer device. Thorax. 1996; 51:981-984.
56.
O’Callaghan C, Cant M, Robertson C.Delivery of beclomethasone dipropionate from a spacer device: what dose is available for inhalation?Thorax. 1994; 49:961-964.
57.
Wildhaber JH, Devadason SG, Hayden MJ, et al. Electrostatic charges on plastic spacer devices influences the delivery of salbutamol. Eur Respir J. 1996; 9:1943-1946.
58.
Rau J, Zhu Y.Reservoir design and dose availability with long-term metered-dose inhaler corticosteroid use. J Aerosol Med. 1998; 11(1):15-26.
59.
O’Callaghan C, Lynch J, Cant M, et al. Improvement in sodium cromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drugs. Thorax. 1993; 48:603-606.
Bisgaard H.A metal aerosol holding chamber devised for young children with asthma. Eur Respir J. 1995; 8:855-860.
62.
Lee H, Evans HE. Evaluation of inhalation aids of metered-dose inhalers in asthmatic children. Chest. 1987; 91:366-369.
63.
Barry PW, O’Callaghan C.The effect of delay, multiple actuations, and spacer static charge on the in vitro delivery of budesonide from the Nebuhaler. Br J Clin Pharmacol. 1995; 40(1):76-78.
64.
Amirav I, Newhouse MT. Metered-dose inhaler accessory devices in acute asthma. Efficacy and comparison with nebulizers; a literature review. Arch Pediatr Adolesc Med. 1997; 151:876-882.
65.
Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction: a meta-analysis. Arch Intern Med. 1997;157:1736-1744.
66.
Rodrigo C, Rodrigo G.Salbutamol treatment of acute severe asthma in the ED: MDI versus handheld nebulizer. Am J Emerg Med. 1998; 16:637-642.
67.
Closa RM, Ceballos JM, Gomez-Papi A, et al. Efficacy of bronchodilators administered by nebulizers versus spacer devices in infants with acute wheezing. Pediatr Pulmonol. 1998; 26(5):344-348.
68.
Ganderton D.The generation of respirable clouds from coarse powder aggregates. J Biopharm Sci. 1992; 3:101-105.
69.
Edwards AM, Chambers A.Comparison of a lactose-free formulation of sodium cromoglycate and sodium cromoglycate plus lactose in the treatment of asthma. Curr Med Res Opin. 1989; 11:283-292.
70.
Pover GM, Langdon CG, Jones SR, et al. Evaluation of a breath operated inhaler. J Int Med Res. 1988; 16:201-203.
71.
Zainuddin BMZ, Biddiscombe M, Tolfree SEJ, et al. Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurized metered-dose inhaler, as a dry powder and as nebulized solution. Thorax. 1990; 45:469-473.
72.
Thorsson L, Dahlstrom K, Edsbacker S, et al. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol. 1997; 43:155-161.
73.
Thorsson L, Edsbacke S, Conradson TB. Lung deposition from Turbuhaler is twice that from a pressurized metered-dose inhaler (pMDI). Eur Respir J. 1994; 7:1839-1914.
74.
Schlaeppi M, Edwards K, Fuller RW, et al. Patients’ perception of the Diskus inhaler: a comparison with the Turbuhaler inhaler. Br J Clin Pract. 1996; 50:14-19.
75.
Engel T, Heinig JH, Madsen F, et al. Peak inspiratory flow rate and inspiratory vital capacity of patients with asthma measured with and without a new dry powder inhaler device (Turbuhaler). Eur Respir J. 1990; 3:1037-1041.
76.
Rajkumari NJ, Byron PR, Dalby RN. Testing of dry powder aerosol formulations in different environmental conditions. Int J Pharmac. 1995; 113:123-130.
77.
Kesten S, Alias M, Cartier A, et al. Patient handling of a multidose dry powder inhalation device for albuterol. Chest. 1994; 105:1077-1081.
78.
van der Palen J, Klein JJ, Kerhoff AHM, et al. Evaluation of the long-term effectiveness of three instruction modes for inhaling medicines. Pat Educ and Counseling. 1997; 32:887-895.
79.
Hess DR. Nebulizers: principles and performance. Respir Care. 2000; 45:609-622.
80.
Smith EC, Denyer J, Kendrick AH. Comparison of twenty three nebulizer/compressor combinations for domiciliary use. Eur Respir J. 1995; 8:1214-1221.
81.
Clay MM, Pavia D, Newman SP, et al. Assessment of jet-nebulizers for lung aerosol therapy. Lancet. 1983; 2:592-594.
82.
Newman SP, Pellow PGD, Clay MM, et al. Evaluation of jet nebulizers for use with gentamicin solution. Thorax. 1985; 40:671-676.
83.
Phipps PR, Gonda I.Droplets produced by medical nebulizers. Chest. 1990; 97:1327-1332.
84.
Blake KV, Hoppe M, Harman E, et al. Relative amount of albuterol delivered to lung receptors from a metered-dose inhaler and nebulizer solution. Chest. 1992; 101:309-315.
85.
Thomas SHL, O‘Doherty MJ, Page CJ, et al. Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulizers. Eur Respir J. 1991; 4:616-622.
86.
Lewis RA, Fleming JS. Fractional deposition from a jet nebulizer: How it differs from a metered-dose inhaler. Br J Dis Chest. 1985; 79:361-367.
87.
Hartley-Sharpe CJ, Booth H, Johns DP, et al. Differences in aerosol output and airways responsiveness between the DeVilbiss 40 and 45 handheld nebulizers. Thorax. 1995; 50(6):635-638.
88.
MacNeish CF, Meisner D, Thibert R, et al. A comparison of pulmonary availability between Ventolin (albuterol) nebules and Ventolin (albuterol) Respirator Solution. Chest. 1997; 111(1):204-208.
89.
Coates AL, MacNeish CF, Meisner D, et al. The choice of jet nebulizer, nebulizing flow, and addition of albuterol affects the output of tobramycin aerosols. Chest. 1997; 111(5):1206-1212.
90.
Hardy JG, Newman SP, Knoch M.Lung deposition from four nebulizers. Respir Med. 1993; 87(6):461-465.
91.
Johnson MA, Newman SP, Blood R, et al. Delivery of albuterol and ipratropium bromide from two nebulizer systems in chronic stable asthma: efficacy and pulmonary deposition. Chest. 1989; 96(1):6-10.
92.
Vassal S, Taamma R, Marty N, et al. Microbiologic contamination study of nebulizers after aerosol therapy in patients with cystic fibrosis. Am J Infect Control. 2000; 28:347-351.
93.
Martonen T, Yang Y.Deposition mechanics of pharmaceutical particles in human airways. In: Hickey AJ, editor. Inhalation Aerosols: physical and biological basis for therapy. New York: Marcel Dekker; 1996:3-27.
94.
Cole CH. Special problems in aerosol delivery: neonatal and pediatric considerations. Respir Care. 2000; 45:646-651.
95.
Hendricks HJE, Overberg PC, Brackel HJL, et al. Handling of a spacer (Babyhaler) for inhalation therapy in 0- to 3-year old children. J Asthma. 1998; 35(3):297-304.
96.
Agertoft L, Pedersen S.Importance of training for correct Turbuhaler use in preschool children. Acta Paediatr. 1998; 87:842-847.
97.
DeBoeck K, Alifier M, Warnier G.Is the correct use of a dry powder inhaler (Turbuhaler) age dependent?J Allergy Clin Immunol. 1999; 103:763-767.
98.
Arthur V, Pushkin S, Emery P.Inhaler use in patients with arthritic hands. Clin Trials Meta Analy. 1992; 28:23-28.
99.
Thwaites JH. Practical aspects of drug treatment in elderly patients with mobility problems. Drugs Aging. 1999; 14(2):105-114.
100.
Trescoli C, Ward MJ. Systemic activity of inhaled and swallowed beclomethasone dipropionate and the effect of different inhaler devices. Postgrad Med J. 1998; 877:675-677.
101.
Kamada AK, Szefler SJ, Martin RJ, et al. Issues in the use of inhaled glucocorticoids. Am J Respir Crit Care Med. 1996; 153:1739-1748.
102.
Wales D, Makker H, Kane J, et al. Systemic bioavailability and potency of high-dose inhaled corticosteroids: A comparison of four inhaler devices and three drugs in healthy adult volunteers. Chest. 1999; 115:1278-1284.
103.
Borgstrom L, Derom E, Stahl E, et al. The inhalation device influences lung deposition and bronchodilating effect of terbutaline. Am J Respir Crit Care Med. 1996; 153:1636-1640.
104.
Cates CJ. Holding chambers versus nebulizers for beta agonist treatment of acute asthma (Cochrane Review). In: The Cochrane Library, Issue 3, 1999. Oxford: Update Software.
105.
Camargo CA, Kenney PA. Assessing costs of aerosol therapy. Respir Care. 2000; 45:756-763.
106.
Anderson PJ. Assessment end points for inhaled drug delivery. Respir Care. 2000; 45:737-755.
107.
Erickson SR, Horton A, Kirking DM. Assessing metered-dose inhaler technique: Comparison of observation vs. patient self-report. J Asthma. 1998; 35(7):575-583.
108.
Beerendonk I, Mesters I, Mudde AN, et al. Assessment of the inhalation technique in outpatients with asthma or chronic obstructive pulmonary disease using a metered-dose inhaler or dry powder inhaler device. J Asthma. 1998, 35(3):273-279.
109.
Ernst P.Inhaled drug delivery: A practical guide to prescribing inhaler devices. Can Respir J. 1998; 5(3):180-183.
110.
Dayan SH, Portugal LG, Walner DL, et al. Laryngeal obstruction after inhalation of a penny from a metered-dose inhaler. Otol Head Neck Surg. 1999; 120(4):548-551.
111.
Laube BL, Benedict GW, Dobs AS. The lung as an alternative route of delivery for insulin in controlling postprandial glucose levels in patients with diabetes. Chest. 1998; 114:1734-1739.
