Article information
Resumen
La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad muy prevalente, pero, en contraste, carece de una adecuada definición y existe una gran confusión en cuanto a su tratamiento. Los conocimientos de los que disponemos nos deberían permitir establecer unas normativas de tratamiento más específicas, según las características clínicas de cada paciente. En el presente trabajo se presenta una propuesta de tratamiento dirigido por la clínica. Los broncodilatadores de larga duración, solos o en diversas combinaciones, serán la base del tratamiento, y los corticoides inhalados (CI) se deberán utilizar en un subgrupo de pacientes con características bien definidas. Los últimos estudios indican que los beneficios de los CI son limitados en la EPOC y los riesgos no son despreciables, por lo que su uso debe quedar limitado a pacientes “respondedores” y administrarse siempre asociados a un broncodilatador β2 de larga duración. Se debe conocer más a fondo la patogenia de la enfermedad y clasificar adecuadamente a los pacientes según su gravedad, su frecuencia de agudizaciones, su reversibilidad, comorbilidad y medicación concomitante, para escoger el mejor tratamiento posible.
Palabras clave:
Enfermedad pulmonar obstructiva crónica
Tratamiento
Normativas
Abstract
Chronic obstructive pulmonary disease (COPD) is a highly prevalent but poorly defined disease and there is wide confusion regarding its treatment. The available knowledge should allow guidelines for specific treatment to be established according to each patient's clinical features. The present article describes a proposal for individually-tailored treatment. Long-acting bronchodilators, alone or in various combinations, would be the basis of treatment and inhaled corticosteroids (IC) should be used in a subgroup with well-defined characteristics. The latest studies indicate that the benefits of IC are limited in COPD and that the risks are not inconsiderable. Consequently, these drugs should be limited to “responders” and should always be administered in association with a long-acting β2 bronchodilator. The pathogenesis of this disease should be studied in greater depth and patients should be classified according to their severity, the frequency of acute exacerbations, their reversibility, comorbidity and concomitant medication in order to choose the most appropriate treatment.
Keywords:
Chronic obstructive pulmonary disease
Treatment
Guidelines
Full text is only available in PDF
Bibliografía
[1.]
G. Peces-Barba, J.A. Barberà, A. Agustí, C. Casanova, A. Casas, J.L. Izquierdo, et al.
Guía Clínica SEPAR-ALAT de diagnóstico y tratamiento de la EPOC.
Arch Bronconeumol, 44 (2008), pp. 271-281
[2.]
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 Med, 176 (2007), pp. 532-555
[3.]
M. Miravitlles.
Tratamiento de la enfermedad pulmonar obstructiva crónica. ¿Escalonado o dirigido?.
Med Clin Monogr (Barc), 8 (2007), pp. 54-60
[4.]
J. Morera, M. Miravitlles.
Enfermedad pulmonar obstructiva crónica ¿Enfermedad o síndrome de zugzwang?.
Med Clin (Barc), 130 (2008), pp. 655-656
[6.]
J.G. Scadding.
Meaning of diagnostic terms in bronchopulmonary disease.
BMJ, 2 (1963), pp. 1425-1430
[7.]
G.L. Snider.
Nosology for our day. Its application to chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 167 (2003), pp. 678-683
[8.]
H. Magnussen, B. Bugnas, J. van Noord, P. Schmidt, F. Gerken, S. Kesten.
Improvements with tiotropium in COPD patients with concomitant asthma.
Respir Med, 102 (2008), pp. 50-56
[9.]
H. Iwamoto, A. Yokoyama, N. Shiota, H. Shoda, Y. Haruta, N. Hattori, et al.
Tiotropium bromide is effective for severe asthma with noneosinophilic phenotype.
Eur Respir J, 31 (2008), pp. 1379-1382
[10.]
M. Miravitlles, J. Morera.
It's time for an etiology-based definition of chronic obstructive pulmonary disease.
Respirology, 12 (2007), pp. 317-319
[11.]
A.B. Hill.
The environment and disease: association or causation?.
Proc R Soc Med, 58 (1965), pp. 295-300
[12.]
J.A. Hardie, A.S. Buist, W.M. Vollmer, I. Ellingsen, P.S. Bakke, O. Morkve.
Risk of overdiagnosis of COPD in asymptomatic elderly never-smokers.
Eur Respir J, 20 (2002), pp. 1117-1122
[13.]
S.D. Roberts, M.O. Farber, K.S. Knox, G.S. Phillips, N.Y. Bhatt, J.G. Mastronarde, et al.
FEV1/FVC ratio of 70% misclassifies patients with obstruction at the extremes of age.
Chest, 130 (2006), pp. 200-206
[14.]
D.M. Mannino, A.S. Buist, W.M. Vollmer.
Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function?.
Thorax, 62 (2007), pp. 237-241
[15.]
R. De Marco.
What evidence could validate the definition of COPD?.
Thorax, 63 (2008), pp. 756-757
[16.]
M. Pistolesi.
Beyond airflow limitation: another look at COPD.
Thorax, 64 (2009), pp. 2-3
[17.]
M. Miravitlles, M. Ferrer, A. Pont, J.L. Viejo, J.F. Masa, R. Gabriel, et al.
Characteristics of a population of COPD patients identified from a population-based study. Focus on previous diagnosis and never smokers.
Respir Med, 99 (2005), pp. 985-995
[18.]
S.S. Birring, C.E. Brightling, P. Bradding, J.J. Entwisle, D.D. Vara, J. Grigg, et al.
Clinical, radiologic, and induced sputum features of chronic obstructive pulmonary disease in nonsmokers. A descriptive study.
Am J Respir Crit Care Med, 166 (2002), pp. 1078-1083
[19.]
B.R. Celli, R.J. Halbert, R.J. Nordyke, B. Schau.
Airway obstruction in never smokers: results from the Third National Health and Nutrition Examination Survey.
Am J Med, 118 (2005), pp. 1364-1372
[20.]
J.L. Izquierdo, Y. Anta, P. Resano, C. Almonacid.
Enfermedad pulmonar obstructiva crónica ¿Sólo tabaco?.
Med Clin Monogr (Barc), 8 (2007), pp. 12-16
[21.]
D.E. O’Donnell, S. Aaron, J. Bourbeau, P. Hernandez, D.D. Marciniuk, M. Balter, et al.
Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease – 2007 update.
Can Respir J, 14 (2007), pp. B5-B32
[22.]
M. Miravitlles, C. de la Roza, J. Morera, T. Montemayor, E. Gobartt, J.L. Álvarez-Sala.
Chronic respiratory symptoms, spirometry and knowledge of COPD among general population.
Respir Med, 100 (2006), pp. 1973-1980
[23.]
M. Calle Rubio, J.L. Rodríguez-Hermosa, A. Ortega González, J.L. Álvarez-Sala Walther.
Fenotipos de la enfermedad pulmonar obstructiva crónica.
Med Clin Monogr (Barc), 8 (2007), pp. 22
[24.]
J. Morera.
Historia natural.
Med Clin Monogr (Barc), 8 (2007), pp. 3-11
[25.]
J.B. Soriano, K.J. Davis, B. Coleman, G. Visick, D. Mannino, N.B. Pride.
The proportional Venn diagram of obstructive lung disease.
Chest, 124 (2003), pp. 474-481
[26.]
M.C. Matheson, J. Raven, D.P. Johns, M.J. Abramson, E.H. Walters.
Associations between reduced diffusing capacity and airflow obstruction in community-based subjects.
Respir Med, 101 (2007), pp. 1730-1737
[27.]
J. Reilly.
Using computed tomographic scanning to advance understanding of chronic obstructive pulmonary disease.
Proc Am Thorac Soc, 3 (2006), pp. 450-455
[28.]
S.I. Rennard, J. Vestbo.
The many “small COPDs”: COPD should be an orphan disease.
Chest, 134 (2008), pp. 623-627
[29.]
P. Weiner, M. Weiner, Y. Azgad, D. Zamir.
Inhaled budesonide therapy for patients with stable COPD.
Chest, 108 (1995), pp. 1568-1571
[30.]
M. Miniati, S. Monti, J. Stolk, G. Mirarchi, F. Falaschi, R. Rabinovich, et al.
Value of chest radiography in phenotyping chronic obstructive pulmonary disease.
Eur Respir J, 31 (2008), pp. 509-514
[31.]
R. Leigh, M.M.M. Pizzichini, M.M. Morris, F. Maltais, F.E. Hargreave, E. Pizzichini.
Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment.
Eur Respir J, 27 (2006), pp. 964-971
[32.]
B.R. Celli, C.G. Cote, J.M. Marin, C. Casanova, M. Montes de Oca, R.A. Mendez, et al.
The body-mass index, airflow obstruction, dyspnea, and excercise capacity index in chronic obstructive pulmonary disease.
N Engl J Med, 350 (2004), pp. 1005-1012
[33.]
J. Stolk, M.I.M. Versteegh, L.J. Montenij, M.E. Bakker, E. Grebski, M. Tutic, et al.
Densitometry for assessment of effect of lung volume reduction surgery for emphysema.
Eur Respir J, 29 (2007), pp. 1138-1143
[34.]
J. De Miguel Díez, M. Calle Rubio, J.L. Rodríguez Hermosa, J.L. Álvarez-Sala.
Guidelines for the treatment of COPD.
Hot Topics in Respiratory Medicine, 5 (2007), pp. 7-14
[35.]
D.P. Tashkin, C.B. Cooper.
The role of long-acting bronchodilators in the management of stable COPD.
Chest, 125 (2004), pp. 249-259
[36.]
P.W. Jones, T.K. Bosh.
Quality of life changes in COPD patients treated with salmeterol.
Am J Respir Crit Care Med, 155 (1997), pp. 1283-1289
[37.]
R. Dahl, L.A.P.M. Greefhorts, D. Nowak, V. Nonikov, A.M. Byrne, M.H. Thompson, et al.
Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 164 (2001), pp. 778-784
[38.]
D.E. O’Donnell, N. Voduc, M. Fitzpatrick, K.A. Webb.
Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease.
Eur Respir J, 24 (2004), pp. 86-94
[39.]
W.D.C. Man, N. Mustfa, D. Nikoletou, S. Kaul, N. Hart, G.F. Rafferty, et al.
Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD.
Thorax, 59 (2004), pp. 471-476
[40.]
M.R. Littner, J.S. Ilowite, D.P. Tashkin, M. Friedman, C.W. Serby, S.S. Menjoge, et al.
Longacting bronchodilation with once-daily dosing of tiotropium (Spiriva) in stable chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 161 (2000), pp. 1136-1142
[41.]
J.A. Van Noord, T.A. Bantje, L. Korducki, P.J.G. Cornelissen, On behalf of the Dutch Tiotropium Study Group.
A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease.
Thorax, 55 (2000), pp. 289-294
[42.]
J.A. Van Noord, J.J. Smeets, F.L. Custers, L. Korducki, P.J.G. Cornelissen.
Pharmacodynamic steady state of tiotropium in patients with chronic obstructive pulmonary disease.
Eur Respir J, 19 (2002), pp. 639-644
[43.]
V. Brusasco, R. Hodder, M. Miravitlles, L. Korducki, L. Towse, S. Kesten.
Health outcomes following six months treatment with once daily tiotropium compared to twice daily salmeterol in patients with COPD.
Thorax, 58 (2003), pp. 399-404
[44.]
D. Tashkin, S. Kesten.
Long-term treatment benefits with tiotropium in COPD patients with and without short-term bronchodilator responses.
Chest, 123 (2003), pp. 1441-1449
[45.]
A. Richter, S.F. Anton, P. Koch, S.L. Dennett.
The impact of reducing dose frequency on health outcomes.
Clin Ther, 25 (2003), pp. 2307-2335
[46.]
J.I. Jaén Díaz, C. de Castro Mesa, B. Cordero García, M.J. Gontán García-Salamanca, S. Callejas Pérez, F. López de Castro.
Efectividad del tratamiento con bromuro de tiotropio en pacientes con enfermedad pulmonar obstructiva crónica.
Med Clin (Barc), 124 (2005), pp. 1-3
[47.]
D.P. Tashkin, B. Celli, S. Senn, D. Burkhart, S. Kesten, S. Menjoge, et al.
A 4-year trial of tiotropium in chronic obstructive pulmonary disease.
N Engl J Med, 359 (2008), pp. 1543-1554
[48.]
M. Miravitlles, A. Anzueto.
Insights into interventions in managing COPD patients: lessons from the TORCH and UPLIFT studies.
Int J Chron Obstruct Pulmon Dis, 4 (2009), pp. 185-201
[50.]
S.V. Culpitt, C. de Matos, R.E. Russell, L.E. Donnelly, D.F. Rogers, P.J. Barnes.
Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 165 (2002), pp. 1371-1376
[51.]
P.K. Jeffery.
Structural and inflammatory changes in COPD: a comparison with asthma.
Thorax, 53 (1998), pp. 129-136
[52.]
P.S. Burge, P.M.A. Calverley, P.W. Jones, S. Spencer, J.A. Anderson, T.K. Maslen.
Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.
BMJ, 320 (2000), pp. 1297-1303
[53.]
R.A. Pauwels, C.-G. Löfdahl, L.A. Laitinen, J.P. Schouten, D.S. Postma, N.B. Pride, et al.
Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking.
N Engl J Med, 340 (1999), pp. 1948-1953
[54.]
A. Alsaeedi, D.D. Sin, F.A. McAlister.
The effect of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review of randomized placebo-controlled trials.
Am J Med, 113 (2002), pp. 59-65
[55.]
P.W. Jones, L.R. Willits, P.S. Burge, P.M.A. Calverley.
Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations.
Eur Respir J, 21 (2003), pp. 68-73
[56.]
N.J. Roland, R.K. Bhalla, J. Earis.
The local side effects of inhaled corticosteroids.
Chest, 126 (2004), pp. 213-219
[57.]
S. Singh, A.V. Amin, Y.K. Loke.
Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease. A meta-analysis.
Arch Intern Med, 169 (2009), pp. 219-229
[58.]
P. Ernst, A.V. Gonzalez, P. Brassard, S. Suissa.
Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia.
Am J Respir Crit Care Med, 176 (2007), pp. 162-166
[59.]
R.B. Hubbard, C.J.P. Smith, L. Smeeth, T.W. Harrison, A.E. Tattersfield.
Inhaled corticosteroids and hip fracture. A population-based case-control study.
Am J Respir Crit Care Med, 166 (2002), pp. 1563-1566
[60.]
J.D. Leuppi, R. Tandjung, S.D. Anderson, D. Stolz, M.H. Brutsche, R. Bingisser, et al.
Prediction of treatment-response to inhaled corticosteroids by mannitol-challenge test in COPD. A proof of concept.
Pulm Pharmacol Ther, 18 (2005), pp. 83-88
[61.]
H.A.M. Kerstjens, S.E. Overbeek, J.P. Schouten, P.L.P. Brand, D.S. Postma.
Airways hyperresponsiveness, bronchodilator response, allergy and smoking predict improvement in FEV1 during long-term inhaled conticosteroid treatment.
Eur Respir J, 6 (1993), pp. 868-876
[62.]
W. Szafranski, A. Cukier, A. Ramirez, G. Menga, R. Sansores, S. Nahabedian, et al.
Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.
Eur Respir J, 21 (2003), pp. 74-81
[63.]
P.M. Calverley, W. Boonsawat, Z. Cseke, N. Zhong, S. Peterson, H. Olsson.
Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease.
Eur Respir J, 22 (2003), pp. 912-919
[64.]
P. Calverley, R. Pawels, J. Vestbo, P. Jones, N. Pride, A. Gulsvik, et al.
Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial.
Lancet, 361 (2003), pp. 449-456
[65.]
M. Cazzola, R. Dahl.
Inhalde combination therapy with long-acting beta2-agonists and corticosteroids in satble COPD.
Chest, 126 (2004), pp. 220-237
[66.]
M. Cazzola, P. Santus, F. Di Marco, B. Boveri, F. Castagna, P. Carlucci, et al.
Bronchodilator effect of an inhlade combination therapy with salmeterol + fluticasone and formoterol + budesonide in patients with COPD.
Respir Med, 97 (2003), pp. 453-457
[67.]
P.M.A. Calverley, J.A. Anderson, B. Celli, G.T. Ferguson, 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
[68.]
B.R. Celli, N.E. Thomas, J.A. Anderson, G.T. Ferguson, C. Jenkins, P.W. Jones, et al.
Effect of pharmacotherapy on rate of decline of lung function in COPD: results from the TORCH study.
Am J Respir Crit Care Med, 178 (2008), pp. 332-338
[69.]
D.A. Mahler, P. Wire, D. Horstman, C.N. Chang, J. Yates, T. Fischer, et al.
Effectiveness of fluticasone propionate and salmeterol combination delivered via the diskus device in the treatment of chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 166 (2002), pp. 1084-1091
[70.]
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
[71.]
E.R. Bleecker, A. Emmett, G. Crater, K. Knobil, C. Kalberg.
Lung function and symptom improvement with fluticasone propionate/salmeterol and ipratropium bromide/albuterol in COPD: response by beta-agonist reversibility.
Pulm Pharmacol Ther, 21 (2008), pp. 682-688
[72.]
G.T. Ferguson, A. Anzueto, R. Fei, A. Emmett, K. Knobil, C. Kalberg.
Effect of fluticasone propionate/salmeterol (250/50 ?g) or salmeterol (50 ?g) on COPD exacerbations.
Respir Med, 102 (2008), pp. 1099-1108
[73.]
M. Miravitlles, C. Murio, G. Tirado-Conde, G. Levy, H. Muellerova, J.B. Soriano, et al.
Geographic differences in clinical characteristics and management of COPD: the EPOCA study.
Int J Chron Obstruct Pulmon Dis, 3 (2008), pp. 803-814
[74.]
P.J. Poole, P.N. Black.
Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: a systematic review.
BMJ, 322 (2001), pp. 1271-1274
[75.]
M. Decramer, M. Rutten-van Mölken, P.N.R. Dekhuijzen, T. Troosters, C. van Herwaarden, R. Pellegrino, et al.
Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomised on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial.
Lancet, 365 (2005), pp. 1552-1560
[76.]
J.P. Zheng, J. Kang, S.G. Huang, P. Chen, W.Z. Yao, L. Yang, et al.
Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE study): a randomised placebo-controlled study.
Lancet, 371 (2008), pp. 2013-2018
[77.]
C. Steurer-Stey, L.M. Bachmann, J. Steurer, M.R. Tramèr.
Oral purified bacterial extracts in chronic bronchitis and COPD.
Chest, 126 (2004), pp. 1645-1655
[78.]
A. Prieto, E. Reyes, E.D. Bernstein, B. Martínez, J. Montserrat, J.L. Izquierdo, et al.
Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (Inmunoferon).
Am J Respir Crit Care Med, 163 (2001), pp. 1578-1583
[79.]
M. Álvarez-Mon, M. Miravitlles, J. Morera, L. Callol, J.L. Álvarez-Sala.
Treatment with the immunomodulator AM3 (Inmunoferon) improves the health-related quality of life of patients with chronic obstructive pulmonary disease.
Chest, 127 (2005), pp. 1212-1218
[80.]
M. Miravitlles, C. Murio, J. Morera, L. Callol, J.L. Álvarez-Sala, M. Álvarez-Mon.
Efecto de AM3 en la calidad de vida de pacientes con enfermedad pulmonar obstructiva crónica en subgrupos de riesgo.
Med Clin (Barc), 130 (2008), pp. 688-692
[81.]
M. Miravitlles.
Tratamiento de la enfermedad pulmonar obstructiva crónica.
Med Clin (Barc), 125 (2005), pp. 65-74
[82.]
P.W. Jones, K. Wilson, S. Sondhi.
Cost-effectiveness of salmeterol in patients with chronic obstructive pulmonary disease: an economic evaluation.
Respir Med, 97 (2003), pp. 20-26
[83.]
M. Rutten-van Mölken, J.B. Oostenbrink, M. Miravitlles, B.U. Monz.
Modelling the 5-year cost-effectiveness of tiotropium, salmeterol and ipratropium for the treatment of COPD in Spain.
Eur J Health Econ, 8 (2007), pp. 123-135
[84.]
J.A. Van Noord, J.-L. Aumann, E. Janssens, J.J. Smeets, 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
[85.]
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
[86.]
R.L. ZuWallack, D.A. Mahler, D. Reilly, N. Church, A. Emmett, K. Rickard, et al.
Salmeterol plus theophylline combination therapy in the treatment of COPD.
Chest, 119 (2001), pp. 1661-1670
[87.]
M. Miravitlles, J.L. Álvarez-Sala, R. Lamarca, M. Ferrer, F. Masa, H. Verea, et al.
Treatment and quality of life in patients with chronic obstructive pulmonary disease.
Qual Life Res, 11 (2002), pp. 329-338
[88.]
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.
Ann Intern Med, 146 (2007), pp. 545-555
[89.]
M. Najafzadeh, C.A. Marra, M. Sadatsafavi, S.D. Aaron, S.D. Sullivan, K.L. Vandemheen, et al.
Cost effectiveness of therapy with combinations of long-acting bronchodilators and inhaled steroids for treatment of COPD.
Thorax, 63 (2008), pp. 962-967
[90.]
M. Miravitlles, M. Brosa, M. Velasco, C. Crespo, E. Gobartt, N. González-Rojas.
An economic analysis of pharmacological treatment of COPD in Spain.
Respir Med, 103 (2009), pp. 714-721
[91.]
R. Siva, R.H. Green, C.E. Brightling, M. Shelley, B. Hargadon, McKenna, et al.
Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial.
Eur Respir J, 29 (2007), pp. 906-913
Copyright © 2009. Sociedad Española de Neumología y Cirugía Torácica
