Allergy Asthma Immunol Res.  2014 Sep;6(5):376-388. 10.4168/aair.2014.6.5.376.

Small Airways Dysfunction in Asthma: Evaluation and Management to Improve Asthma Control

Affiliations
  • 1Airway Disease Section, National Heart and Lung Institute, Imperial College London & Royal Brompton Hospital, London, UK. o.usmani@imperial.ac.uk

Abstract

The small airways have been neglected for many years, but interest in the topic has been rekindled with recent advances in measurement techniques to assess this region and also the ability to deliver therapeutics to the distal airways. Current levels of disease control in asthmatic patients remain poor and there are several contributory factors including; poor treatment compliance, heterogeneity of asthma phenotypes and associated comorbidities. However, the proposition that we may not be targeting all the inflammation that is present throughout the whole respiratory tree may also be an important factor. Indeed decades ago, pathologists and physiologists clearly identified the importance of small airways dysfunction in asthmatic patients. With improved inhaler technology to deliver drug to target the whole respiratory tree and more sensitive measures to assess the distal airways, we should certainly give greater consideration to treating the small airway region when seeing our asthmatic patients in clinic. The aim of this review is to address the relevance of small airways dysfunction in the daily clinical management of patients with asthma. In particular the role of small particle aerosols in the management of patients with asthma will be explored.

Keyword

Small airways; asthma; physiology; pharmacology; inhalation; aerosols; corticosteroids; long-acting beta agonists

MeSH Terms

Adrenal Cortex Hormones
Aerosols
Asthma*
Comorbidity
Compliance
Humans
Inflammation
Inhalation
Nebulizers and Vaporizers
Pharmacology
Phenotype
Physiology
Population Characteristics
Adrenal Cortex Hormones
Aerosols

Cited by  1 articles

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Seong-Dae Woo, Young-Min Ye, Youngsoo Lee, So-Hee Lee, Yoo Seob Shin, Joo Hun Park, Hyunna Choi, Hyun-Young Lee, Hyun-Jung Shin, Hae-Sim Park
Allergy Asthma Immunol Res. 2020;12(3):454-466.    doi: 10.4168/aair.2020.12.3.454.


Reference

1. Usmani OS, Barnes PJ. Assessing and treating small airways disease in asthma and chronic obstructive pulmonary disease. Ann Med. 2012; 44:146–156.
2. 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; 26:172–179.
3. Contoli M, Bousquet J, Fabbri LM, Magnussen H, Rabe KF, Siafakas NM. The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy. 2010; 65:141–151.
4. Burgel PR, de Blic J, Chanez P, Delacourt C, Devillier P, Didier A, Dubus JC, Frachon I, Garcia G, Humbert M, Laurent F, Louis R, Magnan A, Mahut B, Perez T, Roche N, Tillie-Leblond I, Tunon de Lara M, Dusser D. Update on the roles of distal airways in asthma. Eur Respir Rev. 2009; 18:80–95.
5. Demoly P, Annunziata K, Gubba E, Adamek L. Repeated cross-sectional survey of patient-reported asthma control in Europe in the past 5 years. Eur Respir Rev. 2012; 21:66–74.
6. Lai CK, De Guia TS, Kim YY, Kuo SH, Mukhopadhyay A, Soriano JB, Trung PL, Zhong NS, Zainudin N, Zainudin BM. Asthma Insights and Reality in Asia-Pacific Steering Committee. Asthma control in the Asia-Pacific region: the Asthma Insights and Reality in Asia-Pacific Study. J Allergy Clin Immunol. 2003; 111:263–268.
7. Lavorini F, Usmani OS. Correct inhalation technique is critical in achieving good asthma control. Prim Care Respir J. 2013; 22:385–386.
8. Greening AP, Ind PW, Northfield M, Shaw G. Allen & Hanburys Limited UK Study Group. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Lancet. 1994; 344:219–224.
9. 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; 172:704–712.
10. Pauwels RA, Löfdahl CG, Postma DS, Tattersfield AE, O'Byrne P, Barnes PJ, Ullman A. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med. 1997; 337:1405–1411.
11. O'Byrne PM, Naya IP, Kallen A, Postma DS, Barnes PJ. Increasing doses of inhaled corticosteroids compared to adding long-acting inhaled beta2-agonists in achieving asthma control. Chest. 2008; 134:1192–1199.
12. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, Pedersen SE. GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004; 170:836–844.
13. Breekveldt-Postma NS, Koerselman J, Erkens JA, van der Molen T, Lammers JW, Herings RM. CAMERA Study GroupMembers listed in the Appendix. Treatment with inhaled corticosteroids in asthma is too often discontinued. Pharmacoepidemiol Drug Saf. 2008; 17:411–422.
14. Wenzel SE. Complex phenotypes in asthma: current definitions. Pulm Pharmacol Ther. 2013; 26:710–715.
15. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, Wardlaw AJ, Green RH. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008; 178:218–224.
16. Wadsworth SJ, Sandford AJ. Personalised medicine and asthma diagnostics/management. Curr Allergy Asthma Rep. 2013; 13:118–129.
17. Usmani OS. Treating the small airways. Respiration. 2012; 84:441–453.
18. Macklem PT, Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J Appl Physiol. 1967; 22:395–401.
19. Green M. How big are the bronchioles? St Thomas Hosp Gaz. 1967; 63:136–139.
20. Weibel ER. Morphometry of the human lung. Berlin: Springer-Verlag;1963.
21. Hamid Q. Pathogenesis of small airways in asthma. Respiration. 2012; 84:4–11.
22. Hamid Q, Song Y, Kotsimbos TC, Minshall E, Bai TR, Hegele RG. Inflammation of small airways in asthma. J Allergy Clin Immunol. 1997; 100:44–51.
23. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004; 350:2645–2653.
24. Yanai M, Sekizawa K, Ohrui T, Sasaki H, Takishima T. Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure. J Appl Physiol (1985). 1992; 72:1016–1023.
25. Mead J. The lung's "quiet zone". N Engl J Med. 1970; 282:1318–1319.
26. Verbanck S. Physiological measurement of the small airways. Respiration. 2012; 84:177–188.
27. Kraft M, Djukanovic R, Wilson S, Holgate ST, Martin RJ. Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med. 1996; 154:1505–1510.
28. Kraft M, Pak J, Martin RJ, Kaminsky D, Irvin CG. Distal lung dysfunction at night in nocturnal asthma. Am J Respir Crit Care Med. 2001; 163:1551–1556.
29. Anderson SD. How does exercise cause asthma attacks? Curr Opin Allergy Clin Immunol. 2006; 6:37–42.
30. Kaminsky DA, Irvin CG, Gurka DA, Feldsien DC, Wagner EM, Liu MC, Wenzel SE. Peripheral airways responsiveness to cool, dry air in normal and asthmatic individuals. Am J Respir Crit Care Med. 1995; 152:1784–1790.
31. Cosio M, Ghezzo H, Hogg JC, Corbin R, Loveland M, Dosman J, Macklem PT. The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med. 1978; 298:1277–1281.
32. in 't Veen JC, Beekman AJ, Bel EH, Sterk PJ. Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes. Am J Respir Crit Care Med. 2000; 161:1902–1906.
33. Verbanck S, Schuermans D, Noppen M, Van Muylem A, Paiva M, Vincken W. Evidence of acinar airway involvement in asthma. Am J Respir Crit Care Med. 1999; 159:1545–1550.
34. Verbanck S, Thompson BR, Schuermans D, Kalsi H, Biddiscombe M, Stuart-Andrews C, Hanon S, Van Muylem A, Paiva M, Vincken W, Usmani O. Ventilation heterogeneity in the acinar and conductive zones of the normal ageing lung. Thorax. 2012; 67:789–795.
35. Thompson BR, Douglass JA, Ellis MJ, Kelly VJ, O'Hehir RE, King GG, Verbanck S. Peripheral lung function in patients with stable and unstable asthma. J Allergy Clin Immunol. 2013; 131:1322–1328.
36. Global Initiative for Asthma (CA). Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2012 [Internet]. Vancouver: Global Initiative for Asthma;2012. cited 2014 Feb 21. Available from: http://www.ginasthma.org/.
37. Paredi P, Kharitonov SA, Meah S, Barnes PJ, Usmani OS. A novel approach to partition central and peripheral airway nitric oxide. Chest. 2014; 145:113–119.
38. Michils A, Elkrim Y, Haccuria A, Van Muylem A. Adenosine 5'-monophosphate challenge elicits a more peripheral airway response than methacholine challenge. J Appl Physiol (1985). 2011; 110:1241–1247.
39. Van Muylem A, Kerckx Y, Michils A. Axial distribution of nitric oxide airway production in asthma patients. Respir Physiol Neurobiol. 2013; 185:313–318.
40. Scichilone N, Battaglia S, Taormina S, Modica V, Pozzecco E, Bellia V. Alveolar nitric oxide and asthma control in mild untreated asthma. J Allergy Clin Immunol. 2013; 131:1513–1517.
41. Goldman MD, Saadeh C, Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir Physiol Neurobiol. 2005; 148:179–194.
42. Paredi P, Goldman M, Alamen A, Ausin P, Usmani OS, Pride NB, Barnes PJ. Comparison of inspiratory and expiratory resistance and reactance in patients with asthma and chronic obstructive pulmonary disease. Thorax. 2010; 65:263–267.
43. Gonem S, Natarajan S, Desai D, Corkill S, Singapuri A, Bradding P, Gustafsson P, Costanza R, Kajekar R, Parmar H, Brightling CE, Siddiqui S. Clinical significance of small airway obstruction markers in patients with asthma. Clin Exp Allergy. 2014; 44:499–507.
44. Anderson WJ, Zajda E, Lipworth BJ. Are we overlooking persistent small airways dysfunction in community-managed asthma? Ann Allergy Asthma Immunol. 2012; 109:185–189.e2.
45. Perez T, Chanez P, Dusser D, Devillier P. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction. Respir Med. 2013; 107:1667–1674.
46. Sorkness RL, Bleecker ER, Busse WW, Calhoun WJ, Castro M, Chung KF, Curran-Everett D, Erzurum SC, Gaston BM, Israel E, Jarjour NN, Moore WC, Peters SP, Teague WG, Wenzel SE. National Heart, Lung, and Blood Institute Severe Asthma Research Program. Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation. J Appl Physiol (1985). 2008; 104:394–403.
47. Papi A, Paggiaro P, Nicolini G, Vignola AM, Fabbri LM. ICAT SE study group. Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma. Allergy. 2007; 62:1182–1188.
48. Berry M, Hargadon B, Morgan A, Shelley M, Richter J, Shaw D, Green RH, Brightling C, Wardlaw AJ, Pavord ID. Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma. Eur Respir J. 2005; 25:986–991.
49. Zainudin BM, Biddiscombe M, Tolfree SE, Short M, Spiro SG. Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution. Thorax. 1990; 45:469–473.
50. Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003; 56:588–599.
51. 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; 172:1497–1504.
52. Warren S, Taylor G, Smith J, Buck H, Parry-Billings M. Gamma scintigraphic evaluation of a novel budesonide dry powder inhaler using a validated radiolabeling technique. J Aerosol Med. 2002; 15:15–25.
53. Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-eclomethasone metered-dose inhaler compared with CFC-eclomethasone. Eur Respir J. 1998; 12:1346–1353.
54. Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest. 2002; 122:510–516.
55. Leach CL, Bethke TD, Boudreau RJ, Hasselquist BE, Drollmann A, Davidson P, Wurst W. Two-dimensional and three-dimensional imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers. J Aerosol Med. 2006; 19:117–126.
56. Leach CL, Kuehl PJ, Chand R, Ketai L, Norenberg JP, McDonald JD. Characterization of respiratory deposition of fluticasone-salmeterol hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic patients. Ann Allergy Asthma Immunol. 2012; 108:195–200.
57. Newman S, Salmon A, Nave R, Drollmann A. High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma. Respir Med. 2006; 100:375–384.
58. Nicolini G, Scichilone N, Bizzi A, Papi A, Fabbri LM. Beclomethasone/formoterol fixed combination for the management of asthma: patient considerations. Ther Clin Risk Manag. 2008; 4:855–864.
59. Scichilone N, Spatafora M, Battaglia S, Arrigo R, Benfante A, Bellia V. Lung penetration and patient adherence considerations in the management of asthma: role of extra-fine formulations. J Asthma Allergy. 2013; 6:11–21.
60. De Backer W, Devolder A, Poli G, Acerbi D, Monno R, Herpich C, Sommerer K, Meyer T, Mariotti F. Lung Deposition of BDP/Formoterol HFA pMDI in Healthy Volunteers, Asthmatic, and COPD Patients. J Aerosol Med Pulm Drug Deliv. 2010; 23:137–148.
61. Huchon G, Magnussen H, Chuchalin A, Dymek L, Gonod FB, Bousquet J. Lung function and asthma control with beclomethasone and formoterol in a single inhaler. Respir Med. 2009; 103:41–49.
62. Reddel HK, Gibson PG, Peters MJ, Wark PA, Sand IB, Hoyos CM, Jenkins CR. Down-titration from high-dose combination therapy in asthma: Removal of long-acting beta(2)-agonist. Respir Med. 2010; 104:1110–1120.
63. Godard P, Greillier P, Pigearias B, Nachbaur G, Desfourgeres JL, Attali V. Maintaining asthma control in persistent asthma: comparison of three strategies in a 6-month double-blind randomised study. Respir Med. 2008; 102:1124–1131.
64. Bateman ED, Jacques L, Goldfrad C, Atienza T, Mihaescu T, Duggan M. Asthma control can be maintained when fluticasone propionate/salmeterol in a single inhaler is stepped down. J Allergy Clin Immunol. 2006; 117:563–570.
65. Foresi A, Mastropasqua B, Chetta A, D'Ippolito R, Testi R, Olivieri D, Pelucchi A. Step-down compared to fixed-dose treatment with inhaled fluticasone propionate in asthma. Chest. 2005; 127:117–124.
66. Fardon T, Haggart K, Lee DK, Lipworth BJ. A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma. Respir Med. 2007; 101:1218–1228.
67. Papi A, Nicolini G, Crimi N, Fabbri L, Olivieri D, Rossi A, Paggiaro P. Step-down from high dose fixed combination therapy in asthma patients: a randomized controlled trial. Respir Res. 2012; 13:54.
68. Hoshino M. Comparison of effectiveness in ciclesonide and fluticasone propionate on small airway function in mild asthma. Allergol Int. 2010; 59:59–66.
69. Usmani OS, Biddiscombe MF, Nightingale JA, Underwood SR, Barnes PJ. Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols. J Appl Physiol (1985). 2003; 95:2106–2112.
70. Bateman E, Karpel J, Casale T, Wenzel S, Banerji D. Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma. Chest. 2006; 129:1176–1187.
71. Nelson HS, Bernstein IL, Fink J, Edwards TB, Spector SL, Storms WW, Tashkin DP. Pulmicort Turbuhaler Study Group. Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Chest. 1998; 113:1264–1271.
72. Nelson HS, Busse WW, deBoisblanc BP, Berger WE, Noonan MJ, Webb DR, Wolford JP, Mahajan PS, Hamedani AG, Shah T, Harding SM. Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma. J Allergy Clin Immunol. 1999; 103:267–275.
73. Zeidler MR, Kleerup EC, Goldin JG, Kim HJ, Truong DA, Simmons MD, Sayre JW, Liu W, Elashoff R, Tashkin DP. Montelukast improves regional air-trapping due to small airways obstruction in asthma. Eur Respir J. 2006; 27:307–315.
74. Goldin JG, Tashkin DP, Kleerup EC, Greaser LE, Haywood UM, Sayre JW, Simmons MD, Suttorp M, Colice GL, Vanden Burgt JA, Aberle DR. Comparative effects of hydrofluoroalkane and chlorofluorocarbon beclomethasone dipropionate inhalation on small airways: assessment with functional helical thin-section computed tomography. J Allergy Clin Immunol. 1999; 104:S258–S267.
75. King GG. Tomographic Imaging of Small Airways. Respiration. 2012; 84:265–274.
76. Fritscher LG, Rodrigues MT, Zamel N, Chapman KR. The effect of montelukast on exhaled nitric oxide of alveolar and bronchial origin in inhaled corticosteroid-treated asthma. Respir Med. 2009; 103:296–300.
77. Gelb AF, Taylor CF, Simmons M, Shinar C. Role of add-on zileuton on total exhaled, large airway, and small airway/alveolar nitric oxide in moderate-severe persistent adult asthmatics on fluticasone 250 microg/Salmeterol 50 microg. Pulm Pharmacol Ther. 2009; 22:516–521.
78. Nieto A, Pamies R, Oliver F, Medina A, Caballero L, Mazon A. Montelukast improves pulmonary function measured by impulse oscillometry in children with asthma (Mio study). Respir Med. 2006; 100:1180–1185.
79. Berger P, Scotto-Gomez E, Molimard M, Marthan R, Le Gros V, Tunon-de-Lara JM. Omalizumab decreases nonspecific airway hyperresponsiveness in vitro. Allergy. 2007; 62:154–161.
80. Hanania NA, Wenzel S, Rosén K, Hsieh HJ, Mosesova S, Choy DF, Lal P, Arron JR, Harris JM, Busse W. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013; 187:804–811.
81. Matsuno O, Komori C, Hang Y, Matsumoto T, Minamoto S. Effectiveness of omalizumab in a patient with severe asthma, low serum IgE level, and lack of sensitized allergens induced by oral steroid therapy: the usefulness of impulse oscillation for assessment of omalizumab therapy. J Asthma. 2012; 49:839–842.
82. Price D, Thomas M. Breaking new ground: challenging existing asthma guidelines. BMC Pulm Med. 2006; 6:Suppl 1. S6.
83. Roche N, Reddel HK, Agusti A, Bateman ED, Krishnan JA, Martin RJ, Papi A, Postma D, Thomas M, Brusselle G, Israel E, Rand C, Chisholm A, Price D. Respiratory Effectiveness Group. Integrating real-life studies in the global therapeutic research framework. Lancet Respir Med. 2013; 1:e29–e30.
84. Price D, Martin RJ, Barnes N, Dorinsky P, Israel E, Roche N, Chisholm A, Hillyer EV, Kemp L, Lee AJ, von Ziegenweidt J, Colice G. Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: a real-world observational study. J Allergy Clin Immunol. 2010; 126:511–518.e1-10.
85. Barnes N, Price D, Colice G, Chisholm A, Dorinsky P, Hillyer EV, Burden A, Lee AJ, Martin RJ, Roche N, von Ziegenweidt J, Israel E. Asthma control with extrafine-particle hydrofluoroalkane-beclometasone vs. large-particle chlorofluorocarbon-beclometasone: a real-world observational study. Clin Exp Allergy. 2011; 41:1521–1532.
86. Colice G, Martin RJ, Israel E, Roche N, Barnes N, Burden A, Polos P, Dorinsky P, Hillyer EV, Lee AJ, Chisholm A, von Ziegenweidt J, Barion F, Price D. Asthma outcomes and costs of therapy with extrafine beclomethasone and fluticasone. J Allergy Clin Immunol. 2013; 132:45–54.
87. Allegra L, Cremonesi G, Girbino G, Ingrassia E, Marsico S, Nicolini G, Terzano C. PRISMA (PRospectIve Study on asthMA control) Study Group. Real-life prospective study on asthma control in Italy: cross-sectional phase results. Respir Med. 2012; 106:205–214.
88. Terzano C, Cremonesi G, Girbino G, Ingrassia E, Marsico S, Nicolini G, Allegra L. PRISMA (PRospectIve Study on asthMA control) Study Group. 1-year prospective real life monitoring of asthma control and quality of life in Italy. Respir Res. 2012; 13:112.
89. Müller V, Gálffy G, Eszes N, Losonczy G, Bizzi A, Nicolini G, Chrystyn H, Tamási L. Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation. BMC Pulm Med. 2011; 11:40.
90. Popov TA, Petrova D, Kralimarkova TZ, Ivanov Y, Popova T, Peneva M, Odzhakova T, Ilieva Y, Yakovliev P, Lazarova T, Georgiev O, Hodzhev V, Hodzheva E, Staevska MT, Dimitrov VD. Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics. Pulm Pharmacol Ther. 2013; 26:624–629.
91. Brusselle G, Peché R, Van den Brande P, Verhulst A, Hollanders W, Bruhwyler J. Real-life effectiveness of extrafine beclometasone dipropionate/formoterol in adults with persistent asthma according to smoking status. Respir Med. 2012; 106:811–819.
92. Price D, Small I, Haughney J, Ryan D, Gruffydd-Jones K, Lavorini F, Harris T, Burden A, Brockman J, King C, Papi A. Clinical and cost effectiveness of switching asthma patients from fluticasone-salmeterol to extra-fine particle beclometasone-formoterol: a retrospective matched observational study of real-world patients. Prim Care Respir J. 2013; 22:439–448.
93. Compalati E, Ridolo E, Passalacqua G, Braido F, Villa E, Canonica GW. The link between allergic rhinitis and asthma: the united airways disease. Expert Rev Clin Immunol. 2010; 6:413–423.
94. Corren J, Manning BE, Thompson SF, Hennessy S, Strom BL. Rhinitis therapy and the prevention of hospital care for asthma: a case-control study. J Allergy Clin Immunol. 2004; 113:415–419.
95. Hargreave FE. Induced sputum for the investigation of airway inflammation: Evidence for its clinical application. Can Respir J. 1999; 6:169–174.
96. Papi A, Paggiaro PL, Nicolini G, Vignola AM, Fabbri LM. Inhaled Combination Asthma Treatment versus SYmbicort (ICAT SY) Study Group. Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma. Eur Respir J. 2007; 29:682–689.
97. Barnes N, van Noord JA, Brindicci C, Lindemann L, Varoli G, Perpiña M, Guastalla D, Casula D, Patel S, Chanez P. FACTO (Foster® As Complete Treatment Option) Study Group. Stepping-across controlled asthmatic patients to extrafine beclometasone/formoterol combination. Pulm Pharmacol Ther. 2013; 26:555–561.
98. Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paternò A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy. 2010; 65:897–902.
99. Corda L, Gardenghi GG, Modina D, Montemurro LT, Novali M, Tantucci C. Effects on small airway obstruction of long-term treatments with beclomethasone/formoterol hydrofluoroalkane (metered-dose inhaler) versus fluticasone/salmeterol (dry-powder inhaler) in asthma: a preliminary study. Allergy Asthma Proc. 2011; 32:29–34.
100. Dahl R, Engelstätter R, Trebas-Pietraś E, Kuna P. A 24-week comparison of low-dose ciclesonide and fluticasone propionate in mild to moderate asthma. Respir Med. 2010; 104:1121–1130.
101. Pedersen S, Engelstätter R, Weber HJ, Hirsch S, Barkai L, Emeryk A, Weber H, Vermeulen J. Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma. Pulm Pharmacol Ther. 2009; 22:214–220.
102. Bateman ED, Linnhof AE, Homik L, Freudensprung U, Smau L, Engelstätter R. Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma. Pulm Pharmacol Ther. 2008; 21:264–275.
103. Knox A, Langan J, Martinot JB, Gruss C, Häfner D. Comparison of a step-down dose of once-daily ciclesonide with a continued dose of twice-daily fluticasone propionate in maintaining control of asthma. Curr Med Res Opin. 2007; 23:2387–2394.
104. Magnussen H, Hofman J, Staneta P, Lawo JP, Hellwig M, Engelstätter R. Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in patients with persistent asthma. J Asthma. 2007; 44:555–563.
105. von Berg A, Engelstätter R, Minic P, Sréckovic M, Garcia Garcia ML, Latoś T, Vermeulen JH, Leichtl S, Hellbardt S, Bethke TD. Comparison of the efficacy and safety of ciclesonide 160 microg once daily vs. budesonide 400 microg once daily in children with asthma. Pediatr Allergy Immunol. 2007; 18:391–400.
106. Adachi M, Ishihara K, Inoue H, Kudo K, Takahashi K, Morita Y, Masuda K, Sakai T, Kato R, Miyamoto T. Efficacy and safety of inhaled ciclesonide compared with chlorofluorocarbon beclomethasone dipropionate in adults with moderate to severe persistent asthma. Respirology. 2007; 12:573–580.
107. Boulet LP, Bateman ED, Voves R, Müller T, Wolf S, Engelstätter R. A randomized study comparing ciclesonide and fluticasone propionate in patients with moderate persistent asthma. Respir Med. 2007; 101:1677–1686.
108. Ukena D, Biberger C, Steinijans V, von Behran V, Malek R, Weber HH, Beck E, Linnhoff A. Ciclesonide is more effective than budesonide in the treatment of persistent asthma. Pulm Pharmacol Ther. 2007; 20:562–570.
109. Pedersen S, Garcia Garcia ML, Manjra A, Theron I, Engelstätter R. A comparative study of inhaled ciclesonide 160 µg/day and fluticasone propionate 176 µg/day in children with asthma. Pediatr Pulmonol. 2006; 41:954–961.
110. Hansel TT, Benezet O, Kafé H, Hans-Hermann P, Cheung D, Engelstätter R, Barnes PJ. A multinational, 12-week, randomized study comparing the efficacy and tolerability of ciclesonide and budesonide in patients with asthma. Clin Ther. 2006; 28:906–920.
111. Buhl R, Vinkler I, Magyar P, Györi Z, Rybacki C, Middle MV, Escher A, Engelstätter R. Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma. Pulm Pharmacol Ther. 2006; 19:404–412.
112. Zietkowski Z, Bozenta-Lukasyk A, Tomasiak MM, Szymanski W, Skiepko R. Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with mild allergic asthma. Respir Med. 2006; 100:1651–1656.
113. Boulet LP, Drollmann A, Magyar P, Timar M, Knight A, Engelstätter R, Fabbri L. Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma. Respir Med. 2006; 100:785–794.
114. Niphadkar P, Jagannath K, Joshi JM, Awad N, Boss H, Hellbardt S, Gadgil DA. Comparison of the efficacy of ciclesonide 160 µg QD and budesonide 200 µg BID in adults with persistent asthma: a phase III, randomized, double-dummy, open-label study. Clin Ther. 2005; 27:1752–1763.
115. Lee DK, Fardon TC, Bates CE, Haggart K, McFarlane LC, Lipworth BJ. Airway and systemic effects of hydrofluoroalkane formulations of high dose ciclesonide and fluticasone in moderate persistent asthma. Chest. 2005; 127:851–860.
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