Drugs & Aging

, Volume 34, Issue 5, pp 321–330 | Cite as

Routine Use of Budesonide/Formoterol Fixed Dose Combination in Elderly Asthmatic Patients: Practical Considerations

  • Nicola ScichiloneEmail author
  • Fulvio Braido
  • Federico Lavorini
  • Mark L. Levy
  • Omar S. Usmani
Therapy in Practice


Asthma has been demonstrated to be as common in the elderly as in younger age groups. Although no specific recommendations exist to manage the disease differently in older individuals, functional features and clinical presentations may be affected by age per se, and by age-related conditions, such as comorbidities and polypharmacy. In this review article, we aimed to explore the efficacy and safety in elderly asthmatic patients of one of the most currently used inhaled treatments for asthma, that is, the fixed-dose combination of budesonide/formoterol. We attempted to address some practical questions that are relevant to the daily practice of clinicians. We focused on the efficacy and real-world effectiveness of inhaled corticosteroids and long-acting β-adrenergic bronchodilators (ICS/LABA) as treatment in the elderly population, since data are extrapolated from younger populations. We investigated whether a maintenance and reliever therapy approach is more effective in the elderly as opposed to maintenance regimens, from both the general practitioner’s and the pulmonologist’s perspective. To address these questions, we scanned electronic databases (PubMed, MEDLINE, Embase, Scopus and Google Scholar) from the date of inception up to October 2016 with a cross-search using the following keywords: ‘asthma’, ‘elderly’, ‘SMART therapy’, ‘MART therapy’, ‘Turbuhaler’, and ‘budesonide/formoterol’. The available literature on the topic confirms that when the age-associated changes are properly managed in clinical practice, asthma in older populations can be optimally controlled with inhaled treatment including ICS/LABA. This also applies for the budesonide/formoterol fixed combination, thus allowing for the maintenance and reliever therapy approach.


Budesonide Fluticasone Propionate Formoterol Mometasone Indacaterol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards

Conflict of interest

Nicola Scichilone has received consulting fees or honoraria from Astra Zeneca, Boehringer Ingelheim, Chiesi, and Mundipharma outside of the submitted work, and support for travel for meetings from Roche. He reports payments for lectures from Astra Zeneca, Chiesi, and Novartis outside of the submitted work. Fulvio Braido has received consulting fees or honoraria from Menarini, Chiesi, Novartis, Astra Zeneca, Boehringer Ingelheim, Malesci/Guidotti, Zambon, Dompè, Biofutura, and GSK outside of the submitted work. Federico Lavorini has received consulting fees or honoraria from Chiesi, Menarini International, Cipla, TEVA, AstraZeneca, and Boehringer Ingelheim, and fees for participating in review activities from Chiesi, Cipla, TEVA, AstraZeneca, Boehringer Ingelheim, and Zentiva. Mark L. Levy has received fees for participating in review activities from DSMB Chiesi Pharmaceuticals, and lecture fees from Astra Zeneca, Chiesi, NAPP, and Teva outside of the submitted work. Omar S. Usmani has received grants from Astra Zeneca, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, and Edmond Pharma. He has also received consulting fees or honoraria from Boehringer Ingelheim, Chiesi, Cipla, Napp, Mundipharma, Sandoz, Takeda, and Zentiva outside of the submitted work. He reports payments for lectures from Aerocrine, Boehringer Ingelheim, Chiesi, Cipla, Mundipharma, Sandoz, and Takeda, outside of the submitted work.


No sources of funding were used to support the writing of this manuscript.


  1. 1.
    Kotaniemi JT, Lundback B, Nieminen MM, Sovijärvi AR, Laitinen LA. Increase of asthma in adults in northern Finland?—a report from the FinEsS study. Allergy. 2001;56:169–74.CrossRefPubMedGoogle Scholar
  2. 2.
    Oraka E, Kim HJ, King ME, Callahan DB. Asthma prevalence among US elderly by age groups: age still matters. J Asthma. 2012;49:593–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Moorman JE, Akinbami LJ, Bailey CM, Zahran HS, King ME, Johnson CA, Liu X. National surveillance of asthma: United States, 2001–2010. Vital Health Stat. 2012;3(35):1–58.Google Scholar
  4. 4.
    Onder G, Petrovic M, Tangiisuran B, Meinardi MC, Markito-Notenboom WP, Somers A, Rajkumar C, Bernabei R, van der Cammen TJ. Development and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older: the GerontoNet ADR risk score. Arch Intern Med. 2010;170(13):1142–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Lavorini F, Mannini C, Chellini E, Fontana GA. Optimising inhaled pharmacotherapy for elderly patients with chronic obstructive pulmonary disease: the importance of delivery devices. Drugs Aging. 2016;33(7):461–73.CrossRefPubMedGoogle Scholar
  6. 6.
    Bellia M, Benfante A, Menozzi M, Augugliaro G, Scichilone N, Cannizzaro F, Midiri M, Bellia V. Validation of lung densitometry threshold at CT for the distinction between senile lung and emphysema in elderly subjects. Monaldi Arch Chest Dis. 2011;75(3):162–6.PubMedGoogle Scholar
  7. 7.
    Verbeken EK, Cauberghs M, Mertens I, Clement J, Lauweryns JM, Van de Woestijne KP. The senile lung. Comparison with normal and emphysematous lungs. 2. Functional aspects. Chest. 1992;101(3):800–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Verbeken EK, Cauberghs M, Mertens I, Clement J, Lauweryns JM, Van de Woestijne KP. The senile lung. Comparison with normal and emphysematous lungs. 1. Structural aspects. Chest. 1992;101(3):793–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated with ageing. Eur Respir J. 1999;13(1):197–205.CrossRefPubMedGoogle Scholar
  10. 10.
    Beasley R, Coleman ED, Hermon Y, Holst PE, O’Donnell TV, Tobias M. Viral respiratory tract infection and exacerbations of asthma in adult patients. Thorax. 1988;43(9):679–83.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Scichilone N, Callari A, Augugliaro G, Marchese M, Togias A, Bellia V. The impact of age on prevalence of positive skin prick tests and specific IgE tests. Respir Med. 2011;105(5):651–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Bozek A, Filipowski M, Fischer A, Jarzab J. Characteristics of atopic bronchial asthma in seniors over 80 years of age. Biomed Res Int. 2013;2013:689782.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    van den Akker M, Buntinx F, Metsemakers JF, Roos S, Knottnerus JA. Multimorbidity in general practice: prevalence, incidence, and determinants of co-occurring chronic and recurrent diseases. J Clin Epidemiol. 1998;51(5):367–75.CrossRefPubMedGoogle Scholar
  14. 14.
    Wardzynska A, Kubsik B, Kowalski ML. Comorbidities in elderly patients with asthma: Association with control of the disease and concomitant treatment. Geriatr Gerontol Int. 2015;15(7):902–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Cousens NE, Goeman DP, Douglass JA, Jenkins CR. The needs of older people with asthma. Aust Fam Physician. 2007;36(9):729–31.PubMedGoogle Scholar
  16. 16.
    Chan WL, Yang KP, Chao TF, Huang CC, Huang PH, Chen YC, Chen TJ, Lin SJ, Chen JW, Leu HB. The association of asthma and atrial fibrillation–a nationwide population-based nested case-control study. Int J Cardiol. 2014;176(2):464–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Global Strategy for Asthma Management and Prevention (GINA). 2016. Accessed Oct 2016.
  18. 18.
    Braman SS. Growing old with asthma: what are the changes and challenges? Expert Rev Respir Med. 2010;4(2):239–48.CrossRefPubMedGoogle Scholar
  19. 19.
    Morales DR, Dreischulte T, Lipworth BJ, Donnan PT, Jackson C, Guthrie B. Respiratory effect of beta-blocker eye drops in asthma: population-based study and meta-analysis of clinical trials. Br J Clin Pharmacol. 2016;82(3):814–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Battaglia S, Basile M, Spatafora M, Scichilone N. Are asthmatics enrolled in randomized trials representative of real-life outpatients? Respiration. 2015;89(5):383–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Wooten JM. Pharmacotherapy considerations in elderly adults. South Med J. 2012;105(8):437–45.CrossRefPubMedGoogle Scholar
  22. 22.
    Pfeifer MA, Weinberg CR, Cook D, Best JD, Reenan A, Halter JB. Differential changes of autonomic nervous system function with age in man. Am J Med. 1983;75(2):249–58.CrossRefPubMedGoogle Scholar
  23. 23.
    Gupta P, O’Mahony MS. Potential adverse effects of bronchodilators in the treatment of airways obstruction in older people: recommendations for prescribing. Drugs Aging. 2008;25(5):415–43.CrossRefPubMedGoogle Scholar
  24. 24.
    Greening AP, Ind PW, Northfield M, Shaw G. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen and Hanburys Limited UK Study Group. Lancet. 1994;344(8917):219–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Juniper EF, Svensson K, O’Byrne PM, Barnes PJ, Bauer CA, Löfdahl CG, Postma DS, Pauwels RA, Tattersfield AE, Ullman A. Asthma quality of life during 1 year of treatment with budesonide with or without formoterol. Eur Respir J. 1999;14(5):1038–43.CrossRefPubMedGoogle Scholar
  26. 26.
    Matz J, Emmett A, Rickard K, Kalberg C. Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an analysis of asthma exacerbations. J Allergy Clin Immunol. 2001;107(5):783–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Pauwels RA, Löfdahl CG, Postma DS, Tattersfield AE, O’Byrne P, Barnes PJ, Ullman A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997;337(20):1405–11.CrossRefPubMedGoogle Scholar
  28. 28.
    Woolcock A, Lundback B, Ringdal N, Jacques LA. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med. 1996;153(5):1481–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Shrewsbury S, Pyke S, Britton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ. 2000;320(7246):1368–73.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Adcock IM, Maneechotesuwan K, Usmani O. Molecular interactions between glucocorticoids and long-acting beta2-agonists. J Allergy Clin Immunol. 2002;110(6 Suppl):S261–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Usmani OS, Ito K, Maneechotesuwan K, Ito M, Johnson M, Barnes PJ, Adcock IM. Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy. Am J Respir Crit Care Med. 2005;172(6):704–12.CrossRefPubMedGoogle Scholar
  32. 32.
    Chapman KR, Ringdal N, Backer V, Palmqvist M, Saarelainen S, Briggs M. Salmeterol and fluticasone propionate (50/250 microg) administered via combination Diskus inhaler: as effective as when given via separate Diskus inhalers. Can Respir J. 1999;6(1):45–51.CrossRefPubMedGoogle Scholar
  33. 33.
    Rosenhall L, Elvstrand A, Tilling B, Vinge I, Jemsby P, Ståhl E, Jerre F, Bergqvist PB. One-year safety and efficacy of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler) for the treatment of asthma. Respir Med. 2003;97(6):702–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Drazen JM, O’Byrne PM. Risks of long-acting beta-agonists in achieving asthma control. N Engl J Med. 2009;360(16):1671–2.CrossRefPubMedGoogle Scholar
  35. 35.
    Szefler SJ, Busse WW. The long-acting beta-adrenergic agonist controversy in asthma: troublesome times! J Allergy Clin Immunol. 2012;130(6):1256–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Stempel DA, Raphiou IH, Kral KM, Yeakey AM, Emmett AH, Prazma CM, Buaron KS. Pascoe SJ; AUSTRI Investigators. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. N Engl J Med. 2016;374(19):1822–30.CrossRefPubMedGoogle Scholar
  37. 37.
    Horne R. Compliance, adherence, and concordance: implications for asthma treatment. Chest. 2006;130(1 Suppl):65S–72S.CrossRefPubMedGoogle Scholar
  38. 38.
    Lasmar L, Camargos P, Champs NS, Fonseca MT, Fontes MJ, Ibiapina C, Alvim C, Moura JA. Adherence rate to inhaled corticosteroids and their impact on asthma control. Allergy. 2009;64(5):784–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Haughney J, Price D, Kaplan A, Chrystyn H, Horne R, May N, Moffat M, Versnel J, Shanahan ER, Hillyer EV, Tunsäter A, Bjermer L. Achieving asthma control in practice: understanding the reasons for poor control. Respir Med. 2008;102(12):1681–93.CrossRefPubMedGoogle Scholar
  40. 40.
    Lindmark B. Differences in the pharmacodynamics of budesonide/formoterol and salmeterol/fluticasone reflect differences in their therapeutic usefulness in asthma. Ther Adv Respir Dis. 2008;2(5):279–99.CrossRefPubMedGoogle Scholar
  41. 41.
    Welsh EJ, Cates CJ. Formoterol versus short-acting beta-agonists as relief medication for adults and children with asthma. Cochrane Database Syst Rev 2010(9):CD008418.Google Scholar
  42. 42.
    Bousquet J, Boulet LP, Peters MJ, Magnussen H, Quiralte J, Martinez-Aguilar NE, Carlsheimer A. Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone. Respir Med. 2007;101(12):2437–46.CrossRefPubMedGoogle Scholar
  43. 43.
    O’Byrne PM, Bisgaard H, Godard PP, Pistolesi M, Palmqvist M, Zhu Y, Ekström T, Bateman ED. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med. 2005;171(2):129–36.CrossRefPubMedGoogle Scholar
  44. 44.
    Scicchitano R, Aalbers R, Ukena D, Manjra A, Fouquert L, Centanni S, Boulet LP, Naya IP, Hultquist C. Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma. Curr Med Res Opin. 2004;20(9):1403–18.CrossRefPubMedGoogle Scholar
  45. 45.
    Sears MR, Boulet LP, Laviolette M, Fitzgerald JM, Bai TR, Kaplan A, Smiljanic-Georgijev N, Lee JS. Budesonide/formoterol maintenance and reliever therapy: impact on airway inflammation in asthma. Eur Respir J. 2008;31(5):982–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Vogelmeier C, D’Urzo A, Pauwels R, Merino JM, Jaspal M, Boutet S, Naya I, Price D. Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option? Eur Respir J. 2005;26(5):819–28.CrossRefPubMedGoogle Scholar
  47. 47.
    Kuna P, Peters MJ, Manjra AI, Jorup C, Naya IP, Martínez-Jimenez NE, Buhl R. Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. Int J Clin Pract. 2007;61(5):725–36.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Bisgaard H, Le Roux P, Bjåmer D, Dymek A, Vermeulen JH, Hultquist C. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest. 2006;130(6):1733–43.CrossRefPubMedGoogle Scholar
  49. 49.
    Patel M, Pilcher J, Pritchard A, Perrin K, Travers J, Shaw D, Holt S, Harwood M, Black P, Weatherall M. Beasley R; SMART Study Group. Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial. Lancet. Respir Med. 2013;1(1):32–42.Google Scholar
  50. 50.
    Papi A, Corradi M, Pigeon-Francisco C, Baronio R, Siergiejko Z, Petruzzelli S, Fabbri LM, Rabe KF. Beclometasone-formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir Med. 2013;1(1):23–31.CrossRefPubMedGoogle Scholar
  51. 51.
    Cates CJ, Lasserson TJ. Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2009; (2):CD007313.Google Scholar
  52. 52.
    Cates CJ, Lasserson TJ. Combination formoterol and inhaled steroid versus beta2-agonist as relief medication for chronic asthma in adults and children. Cochrane Database Syst Rev 2009; (1):CD007085.Google Scholar
  53. 53.
    Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2013; (12):CD009019.Google Scholar
  54. 54.
    Sovani MP, Whale CI, Oborne J, Cooper S, Mortimer K, Ekström T, Tattersfield AE, Harrison TW. Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help? Br J Gen Pract. 2008;58(546):37–43.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Molimard M, Raherison C, Lignot S, Depont F, Abouelfath A, Moore N. Assessment of handling of inhaler devices in real life: an observational study in 3811 patients in primary care. J Aerosol Med. 2003;16(3):249–54.CrossRefPubMedGoogle Scholar
  56. 56.
    Allen SC. Competence thresholds for the use of inhalers in people with dementia. Age Ageing. 1997;26(2):83–6.CrossRefPubMedGoogle Scholar
  57. 57.
    Bellia V, Battaglia S, Matera MG, Cazzola M. The use of bronchodilators in the treatment of airway obstruction in elderly patients. Pulm Pharmacol Ther. 2006;19(5):311–9.CrossRefPubMedGoogle Scholar
  58. 58.
    Ziegler MG, Lake CR, Kopin IJ. Plasma noradrenaline increases with age. Nature. 1976;261(5558):333–5.CrossRefPubMedGoogle Scholar
  59. 59.
    Connolly MJ, Crowley JJ, Charan NB, Nielson CP, Vestal RE. Impaired bronchodilator response to albuterol in healthy elderly men and women. Chest. 1995;108(2):401–6.CrossRefPubMedGoogle Scholar
  60. 60.
    Abrass IB, Scarpace PJ. Human lymphocyte beta-adrenergic receptors are unaltered with age. J Gerontol. 1981;36(3):298–301.CrossRefPubMedGoogle Scholar
  61. 61.
    Duncan PG, Brink C, Douglas JS. β-Receptors during aging in respiratory tissues. Eur J Pharmacol. 1982;78(1):45–52.CrossRefPubMedGoogle Scholar
  62. 62.
    Sitar DS, Aoki FY, Warren CP, Knight A, Grossman RF, Alexander M, Soliman S. A placebo-controlled dose-finding study with bambuterol in elderly patients with asthma. Chest. 1993;103(3):771–6.CrossRefPubMedGoogle Scholar
  63. 63.
    Haalboom JR, Deenstra M, Struyvenberg A. Hypokalaemia induced by inhalation of fenoterol. Lancet. 1985;1(8438):1125–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Santus P, et al. Why use long acting bronchodilators in chronic obstructive lung diseases? An extensive review on formoterol and salmeterol. Eur J Intern Med. 2015;26(6):379–84.CrossRefPubMedGoogle Scholar
  65. 65.
    Scichilone N, Contoli M, Paleari D, Pirina P, Rossi A, Sanguinetti CM, Santus P, Sofia M, Sverzellati N. Assessing and accessing the small airways; implications for asthma management. Pulm Pharmacol Ther. 2013;26(2):172–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Piatti G, Ambrosetti U, Santus P, Allegra L. Effects of salmeterol on cilia and mucus in COPD and pneumonia patients. Pharmacol Res. 2005;51(2):165–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Edsbacker S, Wollmer P, Selroos O, Borgström L, Olsson B, Ingelf J. Do airway clearance mechanisms influence the local and systemic effects of inhaled corticosteroids? Pulm Pharmacol Ther. 2008;21(2):247–58.CrossRefPubMedGoogle Scholar
  68. 68.
    Pang L, Knox AJ. Synergistic inhibition by β2-agonists and corticosteroids on tumor necrosis factor-α-induced interleukin-8 release from cultured human airway smooth-muscle cells. Am J Respir Cell Mol Biol. 2000;23(1):79–85.CrossRefPubMedGoogle Scholar
  69. 69.
    Skevaki CL, Christodoulou I, Spyridaki IS, Tiniakou I, Georgiou V, Xepapadaki P, Kafetzis DA, Papadopoulos NG. Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus. Clin Exp Allergy. 2009;39(11):1700–10.CrossRefPubMedGoogle Scholar
  70. 70.
    Dalby C, Polanowski T, Larsson T, Borgström L, Edsbäcker S, Harrison TW. The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir Res. 2009;10:104.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Lasserson T.J, Cates CJ, Ferrara G, Casali L. Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children. Cochrane Database Syst Rev 2008; (3):CD004106.Google Scholar
  72. 72.
    Latorre M, Novelli F, Vagaggini B, Braido F, Papi A, Sanduzzi A, Santus P, Scichilone N, Paggiaro P. Differences in the efficacy and safety among inhaled corticosteroids (ICS)/long-acting beta2-agonists (LABA) combinations in the treatment of chronic obstructive pulmonary disease (COPD): Role of ICS. Pulm Pharmacol Ther. 2015;30:44–50.CrossRefPubMedGoogle Scholar
  73. 73.
    Lavorini F, Corrigan CJ, Barnes PJ, Dekhuijzen PR, Levy ML, Pedersen S, Roche N, Vincken W, Crompton GK. Retail sales of inhalation devices in European countries: so much for a global policy. Respir Med. 2011;105(7):1099–103.CrossRefPubMedGoogle Scholar
  74. 74.
    Price D, Chrystyn H, Kaplan A, Haughney J, Román-Rodríguez M, Burden A, Chisholm A, Hillyer EV, von Ziegenweidt J, Ali M, van der Molen T. Effectiveness of same versus mixed asthma inhaler devices: a retrospective observational study in primary care. Allergy Asthma Immunol Res. 2012;4(4):184–91.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Frijlink HW, De Boer AH. Dry powder inhalers for pulmonary drug delivery. Expert Opin Drug Deliv. 2004;1(1):67–86.CrossRefPubMedGoogle Scholar
  76. 76.
    Borgstrom L, Bondesson E, Morén F, Trofast E, Newman SP. Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects. Eur Respir J. 1994;7(1):69–73.CrossRefPubMedGoogle Scholar
  77. 77.
    Borgstrom L, Derom E, Ståhl E, Wåhlin-Boll E, Pauwels R. The inhalation device influences lung deposition and bronchodilating effect of terbutaline. Am J Respir Crit Care Med. 1996;153(5):1636–40.CrossRefPubMedGoogle Scholar
  78. 78.
    Newman SP, Weisz AW, Talaee N, Clarke SW. Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. Thorax. 1991;46(10):712–6.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Thorsson L, Edsbacker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J. 1994;7(10):1839–44.CrossRefPubMedGoogle Scholar
  80. 80.
    Borgstrom L, Bengtsson T, Derom E, Pauwels R. Variability in lung deposition of inhaled drug, within and between asthmatic patients, with a pMDI and a dry powder inhaler. Turbuhaler. Int J Pharm. 2000;193(2):227–30.CrossRefPubMedGoogle Scholar
  81. 81.
    Wieshammer S, Dreyhaupt J. Dry powder inhalers: which factors determine the frequency of handling errors? Respiration. 2008;75(1):18–25.CrossRefPubMedGoogle Scholar
  82. 82.
    Barrons R, Pegram A, Borries A. Inhaler device selection: special considerations in elderly patients with chronic obstructive pulmonary disease. Am J Health Syst Pharm. 2011;68(13):1221–32.CrossRefPubMedGoogle Scholar
  83. 83.
    Chrystyn H, Price DB, Molimard M, Haughney J, Bosnic-Anticevich S, Lavorini F, Efthimiou J, Shan D, Sims E, Burden A, Hutton C, Roche N. Comparison of serious inhaler technique errors made by device-naive patients using three different dry powder inhalers: a randomised, crossover, open-label study. BMC Pulm Med. 2016;16:12.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Voshaar T, Spinola M, Linnane P, Campanini A, Lock D, Lafratta A, Scuri M, Ronca B, Melani AS. Comparing usability of NEXThaler((R)) with other inhaled corticosteroid/long-acting beta2-agonist fixed combination dry powder inhalers in asthma patients. J Aerosol Med Pulm Drug Deliv. 2014;27(5):363–70.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    van der Palen J, Klein JJ, Kerkhoff AH, van Herwaarden CL. Evaluation of the effectiveness of four different inhalers in patients with chronic obstructive pulmonary disease. Thorax. 1995;50(11):1183–7.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Jones V, Fernandez C, Diggory P. A comparison of large volume spacer, breath-activated and dry powder inhalers in older people. Age Ageing. 1999;28(5):481–4.CrossRefPubMedGoogle Scholar
  87. 87.
    Canonica GW, Arp J, Keegstra JR, Chrystyn H. Spiromax, a new dry powder inhaler: dose consistency under simulated real-world conditions. J Aerosol Med Pulm Drug Deliv. 2015;28(5):309–19.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Malmberg LP, Everard ML, Haikarainen J, Lähelmä S. Evaluation of in vitro and in vivo flow rate dependency of budesonide/formoterol Easyhaler®. J Aerosol Med Pulm Drug Deliv. 2014;27(5):329–40.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of Biomedicine and Internal and Specialist Medicine, DIBIMISUniversity of PalermoPalermoItaly
  2. 2.Allergy and Respiratory Diseases Department, DIMI, IRCCS AOU San Martino-ISTUniversity of GenoaGenoaItaly
  3. 3.Department of Experimental and Clinical MedicineCareggi University HospitalFlorenceItaly
  4. 4.Kenton Bridge Medical CentreLondonUK
  5. 5.Airway Disease Section, National Heart and Lung Institute (Royal Brompton Campus)Imperial College LondonLondonUK

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