Beclomethasone revisited: the modern view of a classic inhaled corticosteroid
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Editorial Board Pneumon
Petros Bakakos   

1st Depattment of Respiratory Medicine, Medical School of National and Kapodistrian University of Athens, "Sotiria" Hospial of Chest Diseases, Athens, Greece, 11 Konons Str., 116 34 Αthens, Greece
Pneumon 2014;27(2):125–130
Asthma is a worldwide problem affecting more than 300 million people of all ages with a relevant impact on quality of life and healthcare resources. International guidelines recommend the combination of a long acting beta-2-agonist and an inhaled corticosteroid when asthma is not fully controlled by low-dose ICS alone. The beclomethasone/formoterol combination is formulated as a hydrofluoroalkane-134a-containing pressurised metereddose inhaler, using the Modulite solution formulation technology. Comparative studies of this combination have shown similar efficacy versus budesonide/formoterol and fluticasone/salmeterol in patients with moderate-to-severe asthma. Several studies have indicated that inflammatory and structural changes occur in the small airways of asthmatic subjects. Beclomethasone/formoterol extra-fine formulation results in drug delivery to both central and peripheral airways, so that airway inflammation can be treated uniformly throughout the lower respiratory tract. The improved delivery of beclomethasone/formoterol extra-fine formulation translates into significant clinical benefits compared to traditional large particle inhaled medications. Despite the fixed combination of beclomethasone/formoterol delivering more drug to the lungs, it results in a lower systemic exposure. The beclomethasone/formoterol extra-fine formulation is an advantageous and safe treatment choice for patients with asthma and/or COPD.
Masoli M et al. The global burden of asthma: executive summary of the GINA dissemination committee report. Allergy 2004; 59: 469-478.
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. revised 2009. Available from: http://www.ginasthma.org/.
Barnes PJ. Scientific rationale for using a single inhaler for asthma control. Eur Respir J 2007; 29:587-595.
Lewis DA, Ganderton D, Meakin BJ, Brambilla G. Modulite: a simple solution to a difficult problem. Respiration 2005; 72(Suppl. 1):3-5.
Dhillon S, Keating GM. Beclometasone dipropionate/formoterol: in an HFA-propelled pressurised metered-dose inhaler. Drugs 2006; 66:1475-1483.
Papi A, et al. Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma. Allergy 2007;62:1182–1188.
Papi A, et al. Beclomethasone/formoterol versus budesonide/ formoterol combination therapy in asthma. Eur Respir J 2007; 29:682–689.
Weibel ER. Principles and methods for the morphometric study of the lung and other organs. Lab Invest 1963;12:131-155.
Ranga V, Kleinerman J. Structure and function of small airways in health and disease. Arch Pathol Lab Med 1978;102:609-617.
Hamid Q, Song Y, Kotsimbos TC, et al. Inflammation of small airways in asthma. J Allergy Clin Immunol 1997;100:44-51.
Martin RJ. Therapeutic significance of distal airway inflammation in asthma. J Allergy Clin Immunol 2002;109:S447-S460.
Shaw RJ, Djukanovic R, Tashkin DP, Millar AB, du Bois RM, Orr PA. The role of small airways in lung disease. Respir Med 2002;96:67-80.
Carroll N, Cooke C, James A. The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics. Eur Respir J 1997;10:292-300.
Carroll N, Carello S, Cooke C, James A. Airway structure and inflammatory cells in fatal attacks of asthma. Eur Respir J 1996;9:709-715.
Hamid QA. Peripheral inflammation is more important than central inflammation. Respir Med 1997;91(Suppl A):11-12.
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004; 350:2645–2653.
Macklem PT, Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J Appl Physiol 1967;22:395-401.
Brown R, Woolcock AJ, Vincent NJ, Macklem PT. Physiological effects of experimental airway obstruction with beads. J Appl Physiol 1969;27:328-335.
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.
Leach CL, Davidson PJ, Hasselquist BE, et al. 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.
Thongngarm T, Silkoff PE, Kossack WS, Nelson HS. Hydrofluoroalkane-134A beclomethasone or chlorofluorocarbon fluticasone: effect on small airways in poorly controlled asthma. J Asthma 2005;42:257-263.
Goldin JG, Tashkin DP, Kleerup EC, et al. 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:S258-67.
Rigamonti E, Kottakis I, Pelc M, Grzelewska-Rzymowska I, Feschencko Y. Comparison of a new extra-fine beclomethasone dipropionate HFA134a-formulated pMDI with a standard BDP CFC pMDI in adults with moderate persistent asthma. Eur Respir J 2006; 28(Suppl. 50):206s.
Busse WW, Brazinsky S, Jacobson K, et al. Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol 1999; 104:1215-22.
Barnes N, Price D, Colice G, et al. Asthma control with extrafineparticle hydrofluoroalkane-beclometasone vs. large-particle chlorofluorocarbon-beclometasone: a real-world observational study. Clin Exp Allergy 2011.
Juniper E, Price DB, Stampone PA, Creemers JPHM, Mol SJM, Fireman P. Clinically important improvements in asthmaspecific Quality of Life, but no difference in conventional clinical indexes in patients changed from conventional beclomethasone dipropionate approximately half the dose of extrafine beclomethasone dipropionate. Chest 2002; 121:1824-32.
Bousquet J, Poli G, Acerbi D, Monno R, Ramael S, Nollevaux F. Systemic exposure and implications for lung deposition with an extra-fineHFA beclometasone dipropionate-formoterol fixed combination. Clinical Pharmacokinet. 2009; 48:347–358.
De Backer W, Devolder A, Poli G, et al. Lung Deposition of BDP=Formoterol HFA pMDI in Healthy Volunteers, Asthmatic, and COPD Patients. Journal of Aerosol Medicine and Pulmonary Drug Delivery 2010; 23:1-12.
Scichilone N, Battaglia S, Sorino C, et al. Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy 2010;65:897-902.
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.
Haughney J, Price D, Kaplan A, et al. Achieving asthma control in practice: understanding the reasons for poor control. Respir Med 2008; 102:1681-1693.
Thomson NC, Chaudhuri R. Asthma in smokers: challenges and opportunities. Curr Opin Pulm Med Jan 2009; 15:39-45.
Invernizzi G, Ruprecht A, De Marco C, Mazza R, Nicolini G, Boffi R. Inhaled steroid/tobacco smoke particle interactions: a new light on steroid resistance. Respir Res Jun 11 2009; 10:48.
Allegra L, Cremonesi G, Girbino G, et al. Real-life prospective study on asthma control in Italy: Cross-sectional phase results. Respir Med 2012; 106:205-214.
Brusselle G, Peche R, Van de Brande P, Verhulst A, Hollanders W, Bruhwyler J. Real-life effectiveness of extrafine beclomethasone diporpionate/formoterol in adults with persistent asthma according to smoking status. Respir Med 2012.
Chawes BLK, Piccinno A, Kreiner-Møller E, et al. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children. Br J Clin Pharmacol 2012; 75:1081-1088.
Calverley PMA, Kuna P, Monso E, et al. Beclomethasone/formoterol in the management of COPD: A randomised controlled trial. Respir Med 2010; 104:1858-1868.
Vos W, De Backer J, Poli G, et al. Novel Functional Imaging of Changes in Small Airways of Patients Treated with Extrafine Beclomethasone/Formoterol. Respiration 2013;.
Singh D, Corradi M, Bindi E, Baronio R, Petruzzelli S, Paggiaro P. Relief of methacholine-induced bronchospasm with extrafine beclomethasone dipropionate/formoterol in comparison with salbutamol in asthma. Pulm Pharmacology and Therapeutics 2012; 25:392-398.
Papi A, Corradi M, Pigeon-Francisco C, et al. Beclometasone– formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir Med 2013; 1:23-31.
Contoli M, Bousquet J, Fabbri LM, et al. The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy 2010; 65:141-151.
Scichilone N, Battaglia S, Olivieri D, Bellia V. The role of small airways in monitoring the response to asthma treatment: what is beyond FEV1? Allergy 2009; 64:1563-1569.
Popov TA, Petrova D, Kralimarkova TZ, et al. Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics. Pulmonary Pharmacology & Therapeutics 2013;.
Dempsey OJ, Wilson AM, Coutie WJR, Lipworth BJ. Evaluation of the effect of a large volume spacer on the systemic bioactivity of fluticasone propionate metered-dose inhaler. Chest 1999; 116:935–940.
Singh D, Collarini S, Poli G, Acerbi D, Amadasi A, Rusca A. Effect of AeroChamber Plus™ on the lung and systemic bioavailability of beclometasone dipropionate/formoterol pMDI. Br J Clin Pharmacol 2011; 72:932-939.
Corradi M, Chrystyn H, Cosio BG, et al. NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma. Expert Opin Drug Deliv 2014; 12:1-10. [Epub ahead of print].