Leczenie astmy wziewnymi glikokortykosteroidami i długo działającymi β2-agonistami – leczenie podtrzymujące i doraźne

• Authors: Iwona Grzelewska-Rzymowska , Paweł Górski

Title variants

EN

Asthma therapy with inhaled corticosteroids and long-acting β2-agonists – MART model

• Languages of publication: PL

Abstracts

PL

Autorzy przedstawiają niektóre problemy dotyczące wziewnego leczenia astmy kombinacją wziewnych glikokortykosteroidów (wGKS) i długo działających β2-agonistów (LAβA), określanego jako leczenie podtrzymujące i doraźne (LPiD). Od 2006 roku międzynarodowe zalecenia dotyczące terapii astmy i jej zapobiegania (GINA – Globalna Inicjatywa dla Astmy) rekomendują małe dawki wGKS jako pierwszą linię leczenia chorych na łagodną, przewlekłą astmę (drugi stopień leczenia) i średnie dawki wGKS lub kombinację wGKS z LAβA jako preferowane leczenie astmy umiarkowanej (trzeci stopień leczenia). Wziewne glikokortykosteroidy stanowią główne leki w astmie, ponieważ są skuteczne w kontrolowaniu objawów choroby i wskaźników spirometrycznych. Salmeterol i formoterol (LAβA) wywierają przede wszystkim działanie rozszerzające oskrzela, które utrzymuje się ponad 12 godzin. Ta grupa leków jest bardzo ważna w leczeniu astmy, pozwala bowiem na zmniejszenie dawki wGKS. Fundamentalną cechą astmy jest zapalenie, które dotyczy dużych i małych dróg oddechowych (o średnicy mniejszej niż 2 mm). Zajęcie małych oskrzeli jest powiązane z ciężkością choroby. W badaniach epidemiologicznych wykazano, że astma nie jest dostatecznie kontrolowana nie tylko w badaniach klinicznych, ale również w real-life. Nowy model terapii astmy, wykorzystujący budezonid oraz formoterol, określony jako leczenie podtrzymujące i doraźne, okazał się skuteczny i dobrze tolerowany. Poprawiał podatność pacjentów na terapię, zmniejszał ryzyko jej przerwania i poprawiał kliniczny przebieg astmy. Technologia Modulate pozwoliła na zmniejszenie cząstek dwupropionianu beklometazonu i formoterolu (BDP/F) w połączeniu, co umożliwiło uzyskanie homogennego rozkładu cząstek leku w całym drzewie oskrzelowym. Ostatnio ta superdrobnocząstkowa formulacja BDP/F była oceniana u chorych na astmę według modelu LPiD. Wykazano, że leczenie kombinacją BPD/F według tego modelu poprawia kliniczny przebieg astmy i zmniejsza liczbę zaostrzeń. Terapia choroby drobnocząstkowym BDP/F była dobrze tolerowana i może być zalecana u pacjentów powyżej 18. roku życia.

EN

The authors of this paper present a few selected problems of inhaled combination therapy of asthma with corticosteroids (ICS) and long-acting β2-agonist (LAβA) in accordance with maintenance and reliever methods, also known as MART model. Since 2006, international guidelines for asthma management and prevention (Global Initiative for Asthma, GINA) have been recommending low dose ICS as the first-line therapy for patients with mild persistent asthma (the second step of therapy) and medium-dose ICS or a combination of ICS therapy with LAβAs as the preferred therapy for moderate asthma (the third step of therapy). ICS are the mainstay of asthma therapy because they are effective in controlling asthma symptoms and ventilatory parameters. LAβAs – salmeterol and formoterol – mainly present bronchodilator action for over 12 hours. This class of drugs is very important in asthma therapy since it allows for the reduction of the ICS dose. The fundamental feature of asthma is inflammation involving both large and small airways, while the term small airways refers to airways <2 mm in diameter. Involvement of small airways determines asthma severity. Epidemiological studies have shown that, overall, asthma is not adequately controlled in patients not only in clinical trials but “real-life” patients as well. The new model of asthma treatment (which refers to budesonide and formoterol) called maintenance and reliever therapy (MART) presents itself as highly effective and well-tolerated. This therapy model has been found to improve patients’ compliance, hence reducing the risk of therapy discontinuation and improving clinical asthma course. The Modulate platform technology allowed tailoring the particle size of formulated inhaled beclomethasone dipropionate and formoterol (BDF/F) fixed combination which provides a homogeneous distribution of the two active drugs throughout the entire bronchial tree. This extrafine formulation BDP/F has recently been assessed in asthmatics following the model maintenance and reliever therapy. The findings of this study show that the BDP/F combination used as maintenance and reliever therapy improved clinical symptoms of asthma and reduced the number of exacerbations. This model of asthma treatment using superfine BDP/F was well tolerated and can be recommended in asthmatics aged over 18 years.

Keywords

EN

asthma; astma; długo działający β2-agoniści; inhaled corticosteroids; leczenie podtrzymujące i doraźne; long-acting β2-agonists; maintenance and reliever therapy; wziewne glikokortykosteroidy

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Pediatria i Medycyna Rodzinna
• Year: 2014
• Volume: 10
• Issue: 1
• Pages: 15-24

Contributors

author

Iwona Grzelewska-Rzymowska

• Klinika Pneumonologii i Alergologii, I Katedra Chorób Wewnętrznych, Uniwersytet Medyczny w Łodzi. Kierownik Kliniki: prof. dr hab. n. med. Paweł Górski

author

Paweł Górski

• Klinika Pneumonologii i Alergologii, I Katedra Chorób Wewnętrznych, Uniwersytet Medyczny w Łodzi. Kierownik Kliniki: prof. dr hab. n. med. Paweł Górski

References

• 1. Politiek M.J., Boorsma M., Aalbers R.: Comparison of formoterol, salbutamol and salmeterol methacholine-induced severe bronchoconstriction. Eur. Respir. J. 1999; 13: 988–992.
• 2. Greening A.P., Ind P.W., Northfield M., Shaw G.: Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group. Lancet 1994; 344: 219–224.
• 3. Woolcock A., Lundback B., Ringdal N., Jacques L.A.: Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am. J. Respir. Crit. Care Med. 1996; 153: 1481–1488.
• 4. Pearlman D.S., Stricker W., Weinstein S. i wsp.: Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma. Ann. Allergy Asthma Immunol. 1999; 82: 257–265.
• 5. Pauwels R.A., Löfdahl C.G., Postma D.S. i wsp.: 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: 1405–1411.
• 6. Tattersfield A.E., Postma D.S., Barnes P.J. i wsp.: Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group. Am. J. Respir. Crit. Care Med. 1999; 160: 594–599.
• 7. O’Byrne P.M., Barnes P.J., Rodriguez-Roisin R. i wsp.: Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am. J. Respir. Crit. Care Med. 2001; 164: 1392–1397.
• 8. Ind P.W., Villasante C., Shiner R.J. i wsp.: Safety of formoterol by Turbuhaler as reliever medication compared with terbutaline in moderate asthma. Eur. Respir. J. 2002; 20: 859–866.
• 9. Global Initiative for Asthma. NHLB/WHO Workshop Report: Global Strategy for Asthma Management and Prevention 2002.
• 10. Global Initiative for Asthma. NHLB/WHO Workshop Report: Global Strategy for Asthma Management and Prevention 2006.
• 11. Global Initiative for Asthma. NHLB/WHO Workshop Report: Global Strategy for Asthma Management and Prevention 2009. Adres: www.ginasthma.com.
• 12. Rabe K.F., Vermeire P.A., Soriano J.B., Maier W.C.: Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study. Eur. Respir. J. 2000; 16: 802–807.
• 13. Kowalski M.L., Jędrzejczak M., Cirlić M.: Efektywność leczenia astmy oskrzelowej w Polsce w ocenie pacjentów – wyniki badania AIRCEE. Alergia Astma Immunol. 2004; 9: 187–195.
• 14. Partridge M.R., van der Molen T., Myrseth S.E., Busse W.W.: Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm. Med. 2006; 6: 13.
• 15. Zetterström O., Buhl R., Mellem H. i wsp.: Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone. Eur. Respir. J. 2001; 18: 262–268.
• 16. FitzGerald J.M., Boulet L.P., Follows R.M.: The CONCEPT trial: a 1-year, multicenter, randomized, double-blind, double-dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/budesonide in adults with persistent asthma. Clin. Ther. 2005; 27: 393–406.
• 17. Dahl R., Chuchalin A., Gor D. i wsp.: EXCEL: A randomized trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma. Respir. Med. 2006; 100: 1152–1162.
• 18. Bateman E.D., Boushey H.A., Bousquet J. i wsp.; GOAL Investigators Group: Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am. Respir. Crit. Care Med. 2004; 170: 836–844.
• 19. Boushey H.A., Holtzman M.J., Sheller J.R., Nadel J.A.: Bronchial hyperreactivity. Am. Rev. Respir. Dis. 1980; 121: 389–413.
• 20. Anderson G.P.: Formoterol: pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective beta 2-adrenoceptor agonist bronchodilator. Life Sci. 1993; 52: 2145–2160.
• 21. Tulic M.K., Christodoulopoulos P., Hamid Q.: Small airway inflammation in asthma. Respir. Res. 2001; 2: 333–339.
• 22. McDonough J.E., Yuan R., Suzuki M. i wsp.: Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N. Engl. J. Med. 2011; 365: 1567–1575.
• 23. Hamid Q., Song Y., Kotsimbos T.C. i wsp.: Inflammation of small airways in asthma. J. Allergy Clin. Immunol. 1997; 100: 44–51.
• 24. Contoli M., Bousquet J., Fabbri L.M. i wsp.: The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy 2010; 65: 141–151.
• 25. Nakano Y., Wong J.C., de Jong P.A. i wsp.: The prediction of small airway dimensions using computed tomography. Am. J. Respir. Crit. Care Med. 2005; 171: 142–146.
• 26. Wagner E.M., Bleecker E.R., Permutt S., Liu M.C.: Direct assessment of small airways reactivity in human subjects. Am. J. Respir. Crit. Care Med. 1998; 157: 447–452.
• 27. Kaminsky D.A., Irvin C.G., Lundblad L. i wsp.: Oscillation mechanics of the human lung periphery in asthma. J. Appl. Physiol. 2004; 97: 1849–1858.
• 28. Verbanck S., Schuermans D., Meysman M. i wsp.: Noninvasive assessment of airway alterations in smokers: the small airways revisited. Am. J. Respir. Crit Care Med. 2004; 170: 414–419.
• 29. Cazzola M., Matera M.G., Lötvall J.: Ultra long-acting β2-agonists in development for asthma and chronic obstructive pulmonary disease. Expert Opin. Investig. Drugs 2005; 14: 775–783.
• 30. Tattersfield A.E., Löfdahl C.G., Postma D.S. i wsp.: Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. Lancet 2001; 357: 257–261.
• 31. Villa J., Kuna P., Enger J., Brander R.: Safety of formoterol reliever therapy compared with terbutaline in asthmatic children taking anti-inflammatory therapy. Eur. Respir. J. 2002; 38: 431s.
• 32. Pauwels R.A., Sears M.R., Campbell M. i wsp.; RELIEF Study Investigators: Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial. Eur. Respir. J. 2003; 22: 787–794.
• 33. Tötterman K.J., Huhti L., Sutinen E. i wsp.: Tolerability to high doses of formoterol and terbutaline via Turbuhaler for 3 days in stable asthmatic patients. Eur. Respir. J. 1998; 12: 573–579.
• 34. Malolepszy J., Böszörményi Nagy G., Selroos O. i wsp.: Safety of formoterol Turbuhaler® at cumulative dose of 90 μg in patients with acute bronchial obstruction. Eur. Respir. J. 2001; 18: 928–934.
• 35. Nelson H.S., Weiss S.T., Bleecker E.R. i wsp.: The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006; 129: 15–26.
• 36. Salpeter S.R., Buckley N.S., Ormiston T.M., Salpeter E.E.: Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann. Intern. Med. 2006; 144: 904–912.
• 37. Jaeschke R., O’Byrne P.M., Mejza F. i wsp.: The safety of longacting beta-agonists among patients with asthma using inhaled corticosteroids: systematic review and metaanalysis. Am. J. Respir. Crit. Care Med. 2008; 178: 1009–1016.
• 38. Bousquet J., Bourdin A., Demoly P.: Safety of β2-agonists: a 50-year debate closed? Eur. Respir. J. 2014; 43: 6–9.
• 39. Singh D., Piccinno A., Borrill Z. i wsp.: Tolerability of high cumulative doses of the HFA modulate beclomethasone dipropionate/formoterol combination inhaler in asthmatic patients. Pulm. Pharmacol. Ther. 2008; 21: 551–557.
• 40. Emeryk A. (red.): Aerozoloterapia w praktyce. α-medica press, Bielsko-Biała 2008.
• 41. Scichilone N., Battaglia S., Sorino C. i wsp.: Effects of extrafine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy 2010; 65: 897–902.
• 42. Barnes P.J.: Scientific rationale for using a single inhaler for asthma control. Eur. Respir. J. 2007; 29: 587–595.
• 43. O’Byrne P.M., Bisgaard H., Godard P.P. i wsp.: Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am. J. Respir. Crit. Care Med. 2005; 171: 129–136.
• 44. Rabe K.F., Atienza T., Magyar P. i wsp.: Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet 2006; 368: 744–753.
• 45. Rabe K.F., Pizzichini E., Ställberg B. i wsp.: Budesonide/formoterol is a single inhaler for maintenance and relief in mild-to-moderate asthma. A randomized, double-blind trial. Chest 2006; 129: 246–256.
• 46. De Backer W., Devolder A., Poli G. i wsp.: Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J. Aerosol Med. Pulm. Drug Deliv. 2010; 23: 137–148.
• 47. Fabbri L.M., Nicolini G., Olivieri D., Papi A.: Inhaled beclomethasone dipropionate/formoterol extra-fine fixed combination in the treatment of asthma: evidence and future perspectives. Expert Opin. Pharmacother. 2008; 9: 479–490.
• 48. Huchon G., Magnussen H., Chuchalin A. i wsp.: Lung function and asthma control with beclomethasone and formoterol in a single inhaler. Respir. Med. 2009; 103: 41–49.
• 49. van den Berge M., ten Hacken N.H., Cohen J. i wsp.: Small airway disease in asthma and COPD: clinical implications. Chest 2011; 139: 412–423.
• 50. Papi A., Paggiaro P.L., Nicolini G. i wsp.: Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma. Eur. Respir. J. 2007; 29: 682–689.
• 51. Papi A., Paggiaro P.L., Nicolini G. i wsp.: Beclomethasone/formoterol versus fluticasone/salmeterol inhaled combination in moderate to severe asthma. Allergy 2007; 62: 1182–1188.
• 52. Barnes N., Price D., Colice G. i wsp.: Asthma control with extrafine-particle hydrofluoroalkane–beclometasone vs. large-particle chlorofluorocarbon–beclometasone: a real-world observational study. Clin. Exp. Allergy 2011; 41: 1521–1532.
• 53. Allegra L., Cremonesi G., Girbino G. i wsp.: Real-life prospective study on asthma control in Italy: cross-sectional phase results. Respir. Med. 2012; 106: 205–214.
• 54. Müller V., Gálffy G., Eszes N. i wsp.: 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.
• 55. Terzano C., Cremonesi G., Girbino G. i wsp.; 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: 112–122.
• 56. Ståhl E.: Respiratory Patients Opinions Survey (RESPONSE): market research for asthma patients in Europe. Am. J. Respir. Crit. Care Med. 2002; 165: A109.
• 57. Papi A., Corradi M., Pigeon-Francisco C. i wsp.: Beclometasone–formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir. Med. 2013; 1: 23–31.

• Document Type: article