Drug delivery to the lungs is an effective way of targeting inhaled therapeutic aerosols and treating obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In the past 10 years, several new drugs for the management of asthma and COPD have been marketed and more are under development. These new therapeutic respiratory drugs have been furthered by innovations in all categories of pulmonary drug delivery systems to ensure optimal aerosolisation performance, consistency in efficacy and satisfactory patient adherence. In this review, we discuss the technological advances and innovations in recent inhaler devices and the evolving roles of pressurised metered-dose inhalers, dry powder inhalers and nebulisers, as well as their impact on patient adherence to treatment.

1.
Laube BL, Janssens HM, de Jongh FHC, et al: What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-1331.
2.
Dolovich MB, Ahrens Rc, Hess DR, et al: Device selection and outcomes of aerosol therapy: evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest 2005;127:335-371.
3.
Dolovich MB, Dhand R: Aerosol drug delivery: developments in device design and clinical use. Lancet 2011:377:1032-1045.
4.
Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention. http://www.ginaasthma.com (updated December 2012).
5.
Global Initiative for Chronic Obstructive Lung Disease: Global Strategy for Diagnosis, Management, and Prevention of COPD. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2011_Jan21.pdf (2011 update).
6.
Newman S: Improving inhaler technique, adherence to therapy and the precision of dosing: major challenges for pulmonary drug delivery. Expert Opin Drug Deliv 2014;11:365-378.
7.
Heyder J: Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc 2004;1:315-320.
8.
Lavorini F, Corrigan CJ, Barnes PJ, et al: Retail sales of inhalation devices in European countries: so much for a global policy. Respir Med 2011;105:1099-1113.
9.
Doan Q, Shefrin A, Johnson D: Cost-effectiveness of metered-dose inhalers for asthma exacerbations in the pediatric emergency department. Pediatrics 2011;127:1105-1111.
10.
Hendeles L, Colice GL, Meyer RJ: Withdrawal of albuterol inhalers containing chlorofluorocarbon propellants. N Engl J Med 2007;356:1344-1351.
11.
Ross DL, Gabrio BJ: Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system. J Aerosol Med 1999;12:151-160.
12.
Ganderton D, Lewis D, Davies R, et al: Modulite: a means of designing the aerosols generated by pressurized metered dose inhalers. Respir Med 2002;96(suppl D):S3-S8.
13.
Leach CL: The CFC to HFA transition and its impact on pulmonary drug development. Respir Care 2005;50:1201-1208.
14.
Sanchis J, Corrigan C, Levy ML, Viejo JL: Inhaler devices - from theory to practice. Respir Med 2013;107:495-502.
15.
Gabrio BJ, Stein SW, Velasquez DJ: A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers. Int J Pharm 1999;186:3-12.
16.
Acerbi D, Brambilla G, Kottakis I: Advances in asthma and COPD management: delivering CFC-free inhaled therapy using Modulite technology. Pulm Pharmacol Ther 2007;20:290-303.
17.
Dhillon S, Keating GM: Beclometasone dipropionate/formoterol: in an HFA-propelled pressurised metered-dose inhaler. Drugs 2006;66:1475-1483.
18.
Usmani OS, Biddiscombe MF, Barnes PJ: Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med 2005;172:1497-504.
19.
Given J, Taveras H, Iverson H, Lepore M: Prospective, open-label assessment of albuterol sulfate hydrofluoroalkane metered-dose inhaler with new integrated dose counter. Allergy Asthma Proc 2013;34:42-51.
20.
FDA: Guidance for Industry: Integration of Dose-Counting Mechanisms into MDI Drug Products. Rockville, FDA, 2003.
21.
Weinstein C, Staudinger H, Scott I, Amar NJ, LaForce C: Dose counter performance of mometasone furoate/formoterol inhalers in subjects with asthma or COPD. Respir Med 2011;105:979-988.
22.
Conner JB, Buck PO: Improving asthma management: the case for mandatory inclusion of dose counters on all rescue bronchodilators. J Asthma 2013;50:658-563.
23.
Crompton GK, Barnes PJ, Broeder M, et al: The need to improve inhalation technique in Europe: a report from the Aerosol Drug Management Improvement Team. Respir Med 2006;100:1479-1494.
24.
Newman SP, Weisz A, Talaee N, Clarke S: Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. Thorax 1991;46:712-716.
25.
Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ: Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler. J Aerosol Med 2005;18:379-385.
26.
Price DB, Pearce L, Powell SR, Shirley J, Sayers MK: Handling and acceptability of the Easi-Breathe device compared with a conventional metered dose inhaler by patients and practice nurses. Int J Clin Pract 1999;53:31-36.
27.
Hampson NB, Mueller MP: Reduction in patient timing errors using a breath-activated metered dose inhaler. Chest 1994;106:462-465.
28.
Lenny J, Innes J, Crompton GK: Inappropriate inhaler use: assessment of use and patient preference of seven inhalation devices. Respir Med 2000;94:496-500.
29.
Hoppentocht M, Hagedoorn P, Frijlink HW, de Boer AH: Technological and practical challenges of dry powder inhalers and formulations. Adv Drug Deliv Rev 2014 DOI: 10.1016/j.addr.2014.04.004.
30.
Azouz W, Chrystyn H: Clarifying the dilemmas about inhalation techniques for dry powder inhalers: integrating science with clinical practice. Prim Care Respir J 2012;21:208-213.
31.
Geller DE, Weers J, Heuerding S: Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere™ technology. J Aerosol Med Pulm Drug Deliv 2011;24:175-182.
32.
Newman SP, Busse WW: Evolution of dry powder inhaler design, formulation, and performance. Respir Med 2002;96:293-304.
33.
Islam N, Gladki E: Dry powder inhalers (DPIs) - a review of device reliability and innovation. Int J Pharm 2008;360:1-11.
34.
Atkins PJ: Dry powder inhalers: an overview. Respir Care 2005;50:1304-1312.
35.
Smith IJ, Bell J, Bowman N, Everard M, Stein S, Weers JG: Inhaler devices: what remains to be done? J Aerosol Med Pulm Drug Deliv 2010;23(suppl 2):S25-S37.
36.
Voshaar T, Spinola M, Linnane P, Campanini A, Lock D, Lafratta A, Scuri M, Ronca B, Melani AS: Comparing usability of NEXThaler with other inhaled corticosteroid/long-acting β2-agonist fixed combination dry powder inhalers in asthma patients. J Aerosol Med Pulm Drug Deliv 2013, Epub ahead of print.
37.
Svedsater H, Dale P, Garrill K, Walker R, Woepse MW: Qualitative assessment of attributes and ease of use of the ELLIPTA™ dry powder inhaler for delivery of maintenance therapy for asthma and COPD. BMC Pulm Med 2013;13:72.
38.
Chrystyn H, Niederlaender C: The Genuair inhaler: a novel, multidose dry powder inhaler. Int J Clin Pract 2012;66:309-317.
39.
Newman SP, Sutton DJ, Segarra R, Lamarca R, de Miquel G: Lung deposition of aclidinium bromide from Genuair, a multidose dry powder inhaler. Respiration 2009;78:322-328.
40.
Magnussen H, Watz H, Zimmermann I, et al: Peak inspiratory flow through the Genuair inhaler in patients with moderate or severe COPD. Respir Med 2009;103:1832-1837.
41.
Islam N, Cleary MJ: Developing an efficient and reliable dry powder inhaler for pulmonary drug delivery - a review for multidisciplinary researchers. Med Eng Phys 2012;34:409-427.
42.
O'Callaghan C, Barry PW: The science of nebulised drug delivery. Thorax 1997;52(suppl 2):S31-S44.
43.
Hess DR: Nebulizers: principles and performance. Respir Care 2000:45:609-622.
44.
Boe J, Dennis JH, O'Driscoll BR, et al: European Respiratory Society Guidelines on the use of nebulizers. Eur Respir J 2001;18:228-242.
45.
Hess DR, Fisher D, Williams P, Pooler S, Kacmarek RM: Medication nebulizer performance. Effects of diluent volume, nebulizer flow, and nebulizer brand. Chest 1996;110:498-505.
46.
Skaria S, Smaldone GC: Omron NE U22: comparison between vibrating mesh and jet nebulizer. J Aerosol Med Pulm Drug Deliv 2010;23:173-180.
47.
Dhand R: Nebulisers that use a vibrating mesh or plate with multiple apertures to generate aerosol. Respir Care 2002;47:1406-1416.
48.
Coates AL, Green M, Leung K, et al: A comparison of amount and speed of deposition between the PARI LC STAR® jet nebulizer and an investigational eFlow® nebulizer. J Aerosol Med Pulm Drug Deliv 2011;24:157-163.
49.
Nikander K: Adaptive aerosol delivery: the principles. Eur Respir Rev 1999;7:385-387.
50.
Denyer J: Adaptive aerosol delivery in practice. Eur Respir Rev 1997;7:388-389.
51.
Van Dyke RE, Nikander K: Delivery of iloprost inhalation solution with the HaloLite, Prodose, and I-neb adaptive aerosol delivery systems: an in vitro study. Respir Care 2007;52:184-190.
52.
Rubin BK: Pediatric aerosol therapy: new devices and new drugs. Respir Care 2011;56:1411-1421.
53.
Brand P, Schulte M, Wencker M, et al: Lung deposition of inhaled alpha1-proteinase inhibitor in cystic fibrosis and alpha1-antitrypsin deficiency. Eur Respir J 2009;34:354-360.
54.
Brand P, Beckmann H, Maas Enriquez M, et al: Peripheral deposition of alpha-1 protease inhibitor using commercial inhalation devices. Eur Respir J 2003;22:262-267.
55.
Mainz JG, Canisius S, Scheuch G, Mullinger B, Nocker K, Hofmann T: An open-label randomized pilot trial to evaluate tolerability, safety and applicability of budesonide inhalation suspension (BIS) delivered via AKITA JET in children aged 3-11 years with mild to moderate asthma (abstract). Chapel Hill, Congress of the International Society for Aerosols in Medicine, 2013.
56.
Hofmann T: Optimized steroid delivery in severe and pediatric asthma: improved compliance and efficacy (abstract). Chapel Hill, Congress of the International Society for Aerosols in Medicine, 2013.
57.
Janssens HM, Overweel J: Specific targeting of inhaled steroids to small airways in children with problematic severe asthma using the AKITA: a case series (abstract). Chapel Hill, Congress of the International Society for Aerosols in Medicine, 2013.
58.
Dalby R, Spallek M, Voshaar T: A review of the development of Respimat soft mist inhaler. Int J Pharm 2004;283:1-9.
59.
Kassner F, Hodder R, Bateman ED: A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via Respimat soft mist inhaler in patients with asthma and chronic obstructive pulmonary disease. Drugs 2004;64:1671-1682.
60.
Lavorini F, Magnan A, Dubus JC, et al: Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD. Respir Med 2008;102:593-604.
61.
Press VG, Pincavage AT, Pappalardo AA: The Chicago Breathe Project: a regional approach to improving education on asthma inhalers for resident physicians and minority patients. J Natl Med Assoc 2010;102:548-555.
62.
Giraud V, Roche N: Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. Eur Respir J 2002;19:246-251.
63.
Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, Serra M, Scichilone N, Sestini P, Aliani M, Neri M: Gruppo Educazionale Associazione Italiana Pneumologi Ospedalieri. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med 2011;105:930-938.
64.
Levy ML, Hardwell A, McKnight E, Holmes J: Asthma patients' inability to use a pressurised metered-dose inhaler (pMDI) correctly correlates with poor asthma control as defined by the Global Initiative for Asthma (GINA) strategy: a retrospective analysis. Prim Care Respir J 2013;22:406-411.
65.
Lavorini F, Levy ML, Corrigan C, Crompton G; ADMIT Working Group: The ADMIT series - issues in inhalation therapy. 6) Training tools for inhalation devices. Prim Care Respir J 2010;19:335-341.
66.
Price D, Bosnic-Anticevich S, Briggs A, et al: Inhaler competence in asthma: common errors, barriers to use and recommended solutions. Respir Med 2013;107:37-46.
67.
Fink JB, Rubin BK: Problems with inhaler use: a call for improved clinician and patient education. Respir Care 2005;50:1360-1374.
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