Article information
Resumen
La enfermedad pulmonar obstructiva crónica (EPOC) es una de las afecciones más importantes en el ámbito respiratorio. Se trata de una enfermedad compleja multicomponente, con inflamación crónica, aumento de las resistencias en las vías aéreas y agudizaciones. Actualmente, disponemos de diversos fármacos para su tratamiento que actúan en dianas diferentes. Los broncodilatadores, sobre todo de acción prolongada, son los más potentes, de los cuales hay dos grupos: beta-2 miméticos y anticolinérgicos. Los corticoides inhalados son los principales antiinflamatorios, aunque su eficacia es modesta y se reservan para pacientes graves con exacerbaciones frecuentes y/o rasgos asmáticos. La posibilidad de asociar estos tres fármacos puede contribuir a un control mayor de los síntomas y mejorar la calidad de vida, así como también a una disminución de las agudizaciones. En este artículo se revisan las evidencias que sostienen esta triple combinación, así como los estudios publicados.
Palabras clave:
Triple terapia
Tiotropio
Budesónida-formoterol
Fluticasona-salmeterol
Abstract
Chronic obstructive pulmonary disease (COPD) is one of the most important respiratory diseases, characterized by its multicomponent complexity, with chronic inflammation, increased airway resistance and exacerbations. Several drugs are currently available for its treatment, which act on distinct targets. Bronchodilators, especially prolonged-action bronchodilators, are the most potent and there are two groups: beta-2 mimetics and anticholinergics. Inhaled corticosteroids are the main anti-inflammatory drugs but have modest efficacy and their use is reserved for patients with severe disease and frequent exacerbations and/or asthma traits. Associating these three drugs can improve symptom control, improve quality of life and reduce the number of exacerbations. The present article reviews the evidence supporting this triple combination, as well as published studies.
Keywords:
Triple therapy
Tiotropium
Budesonide-formoterol
Fluticasone-salmeterol
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Bibliografía
[1.]
J.C. Hogg, F. Chu, F. Utokaparch, R. Woods, W.M. Elliot, L. Buzatu, et al.
The nature of small-airway obstruction in chronic obstructive pulmonary disease.
N Engl J Med, 350 (2004), pp. 2645-2653
[2.]
B.R. Celli, C.G. Cote, J.M. Marín, C. Casanova, M. Montes de Oca, R.A. Méndez, et al.
The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease.
N Engl J Med, 350 (2004), pp. 1005-1012
[3.]
A. Ikeda, K. Nishimura, H. Koyama, T. Izumi.
Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone.
Chest, 107 (1995), pp. 401-405
[4.]
P.M. Dorinsky, C. Reisner, G.T. Ferguson, S.S. Menjoge, C.W. Serby, T.J. Witek Jr..
The combination of ipratropium and albuterol optimizes pulmonary function reversibility testing in patients with COPD.
Chest, 115 (1999), pp. 966-971
[5.]
W. Vincken, J.A. Van Noord, A.P. Greefhorst, T.A. Bantje, S. Keste, L. Korducki, et al.
Improved health outcomes in patient with COPD during 1 yr's treatment with tiotropium.
Eur Respir J, 19 (2002), pp. 209-216
[6.]
D.P. Tashkin, B. Celli, M. Decramer, D. Liu, D. Burkhart, C. Cassino, et al.
Bronchodilator responsiveness in patients with COPD.
Eur Respir J, 31 (2008), pp. 742-750
[7.]
S.D. Aaron, K.L. Vandemheen, D. Fergusson, F. Maltais, J. Bourbeau, R. Goldstein, et al.
Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial.
Ann Intern Med, 146 (2007), pp. 545-555
[8.]
S. Suissa.
Methodological controversies in chronic obstructive pulmonary disease therapeutic trials.
Presse Med, 38 (2009), pp. 445-451
[9.]
K.F. Rabe, S. Hurd, A. Anzueto, P.J. Barnes, S.A. Buist, P. Calverley, et al.
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
Am J Respir Crit Care, 176 (2007), pp. 532-555
[10.]
P.M. Calverley, J.A. Anderson, B.R. Celli, G.T. Fergusson, C. Jenkins, P.W. Jones, et al.
Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease.
N Engl J Med, 356 (2007), pp. 775-789
[11.]
D.D. Sin, D. Tashkin, X. Zhang, F. Radner, U. Sjobring, A. Thoren, et al.
Budesonide and the risk of pneumonia: a meta-analysis of individual patient data.
Lancet, 29 (2009), pp. 712-719
[12.]
P. Kardos, M. Wencker, T. Glaab, C. Vogelmeier.
Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 175 (2007), pp. 144-149
[13.]
T. Ohrui, M. Yanai, K. Sekizawa, M. Morikawa, H. Sasaki, T. Takishima.
Effective site of bronchodilation by β-adrenergic and antimuscarinic agents in patients with chronic obstructive pulmonary disease: direct measurement of intrabronchial pressure with a new catheter.
Am Rev Respir Dis, 146 (1992), pp. 88-91
[14.]
G. Celik, O. Kayacan, S. Beder, G. Durmaz.
Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: a crossover, placebo-controlled comparison of onset and duration of action.
Respiration, 66 (1999), pp. 434-439
[15.]
M. Jonhson, S. Rennard.
Alternative mechanisms for long-acting β2-adrenergic agonists in COPD.
Chest, 120 (2001), pp. 258-270
[16.]
S.R. Salpeter, N.S. Buckley, E.E. Salpeter.
Meta-analysis: anticholinergic, but not β-agonists reduce severe exacerbations and mortality in COPD.
J Gen Intern Med, 21 (2006), pp. 1011-1021
[17.]
G.J. Rodrigo, R.J. Nannini, R. Rodriguez-Roisin.
Safety of long-acting β-agonists in stable COPD: a systematic review.
Chest, 133 (2008), pp. 1079-1087
[18.]
A. Kliber, L.D. Lynd, D.D. Sin.
The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease.
Respir Res, 11 (2010), pp. 56
[19.]
A. Rossi, S. Khirani, M. Cazzola.
Long-acting β2-agonists in chronic obstructive pulmonary disease: efficacy and safety.
Int J Chron Obstruct Pulm Dis, 3 (2008), pp. 521-529
[20.]
M. Cazzola, F. Imperatore, A. Salzillo, F. Di Perna, F. Calderaro, A. Imperatore, et al.
Cardiac effects of formoterol and salmeterol in patients suffering from COPD with preexisting cardiac arrhytmias and hypoxemia.
Chest, 144 (1998), pp. 411-415
[21.]
J.F. Donohue, J.A. Van Noord, E.D. Bateman, S.J. Langley, A. Lee, T.J. Witek Jr., et al.
A 6 month placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol.
Chest, 122 (2002), pp. 47-55
[22.]
D.P. Tashkin, B. Celli, S. Senn, D. Bukhart, S. Kesten, S. Mejoge, et al.
A 4-year trial of tiotropium in chronic obstructive pulmonary disease.
N Engl J Med, 359 (2008), pp. 1543-1554
[23.]
J.A. Wedzicha, P.M. Calverley, T.A. Seemungal, G. Hagan, Z. Ansari, R.A. Stockley.
The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide.
Am J Respir Crit Care Med, 177 (2008), pp. 19-26
[24.]
S. Singh, Y.K. Loke, C.D. Furberg.
Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review an meta-analysis.
JAMA, 300 (2008), pp. 1439-1450
[25.]
B. Celli, M. Decramer, I. Leimer, U. Vogel, S. Kesten, D.P. Tashkin.
Cardiovascular safety of tiotropium in patients with COPD.
Chest, 137 (2010), pp. 20-30
[26.]
M.G. Cosío, M. Saetta, A. Agustí.
Immunologic aspects of chronic obstructive pulmonary disease.
N Engl J Med, 360 (2009), pp. 2445-2454
[27.]
P. Barnes.
Corticosteroids effects on cell signaling.
Eur Respir J, 27 (2006), pp. 413-426
[28.]
P.J. Barnes, I.M. Adcock.
Glucocorticoid resistance in inflammatory diseases.
Lancet, 373 (2009), pp. 1905-1917
[29.]
D.D. Sin, L. Wu, J.A. Anderson, N.R. Anthonisen, A.S. Buist, P.S. Burge, et al.
Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease.
Thorax, 60 (2005), pp. 992-997
[30.]
J.B. Soriano, D.D. Sin, X. Zhang, P.G. Camp, J.A. Anderson, N.R. Anthonisen, et al.
A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticoids or placebo.
Chest, 131 (2007), pp. 682-689
[31.]
A. Langhammer, S. Forsmo, U. Syversen.
Long-term therapy in COPD: any evidence of adverse effect on bone?.
Int J Chron Obstruct Pulmon Dis, 4 (2009), pp. 365-380
[32.]
S.F. Man, D.D. Sin.
Effects of corticosteroids on systemic inflammation in chronic obstructive pulmonary disease.
Proc Am Thorac Soc, 2 (2005), pp. 78-82
[33.]
J.CW. Mak, M. Nishikawa, H. Shirasaki, K. Miyayasu, P.J. Barnes.
Protective effects of a glucocorticoid on downregulation of pulmonary β2-adrenergic receptors in vivo.
J Clin Invest, 96 (1995), pp. 99-106
[34.]
M. Roth, P.R. Johnson, J.J. Rudiger, G.G. King, Q. Ge, J.K. Burgess, et al.
Interaction between glucocorticoids and beta2 agonists on bronchial airway smooth muscle cells through synchronized cellular signaling.
Lancet, 360 (2002), pp. 1293-1299
[36.]
M. Cazzola, F. Andò, P. Santus, P. Ruggeri, F. Di Marco, A. Sanduzzi, et al.
A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD.
Pulm Pharmacol, 20 (2007), pp. 556-561
[37.]
D. Singh, J. Brooks, G. Hagan, A. Cahn, B.J. O’Connor.
Superiority of “triple” therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD.
Thorax, 63 (2008), pp. 592-598
[38.]
F. Pasqua, G. Biscione, G. Crigna, L. Auciello, M. Cazzola.
Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.
Respir Med, 104 (2010), pp. 412-417
[39.]
J.A. Van Noord, L. Aumann J-, E. Janssens, J.J. Smeets, J.J. Verhaert, B. Disse, et al.
Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD.
Eur Respir J, 26 (2005), pp. 214-222
[40.]
K.F. Rabe, W. Timmer, A. Sagkriotis, K. Viel.
Comparison of a combination of Tiotropium plus Formoterol to Salmeterol plus Fluticasone in moderate COPD.
Chest, 134 (2008), pp. 255-262
[41.]
T. Welte, M. Miravitlles, P. Hernández, G. Eriksson, S. Peterson, T. Polanowski, et al.
Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 180 (2009), pp. 741-750
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