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Vol. 38. Issue 4.
Pages 172-176 (April 2002)
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Vol. 38. Issue 4.
Pages 172-176 (April 2002)
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Inflamación sistémica durante las agudizaciones de la enfermedad pulmonar obstructiva crónica
Systemic inflammation during exacerbations of chronic obstructive pulmonary disease
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A. Noguera, O. Malo, J. Sauleda, X. Busquets, C. Miralles, A.G.N. Agustí
Corresponding author
aagusti@hsd.es

Correspondencia: Servei Pneumologia. Hospital Universitari Son Dureta. Andrea Doria, 55. 07014 Palma Mallorca
Servei de Pneumologia, Analisis Cliniques y Unidad de Investigación. Hospital Universitari Son Dureta. Palma de Mallorca
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Objetivo

La concentración de varias citocinas inflamato-rias y proteínas de fase aguda está incrementada en la circu-lación sistémica de pacientes con enfermedad pulmonar obs-tructiva crónica (EPOC) en fase estable. Sin embargo, no se ha investigado hasta ahora si estos marcadores de inflama-ción aumentan durante la agudización de la enfermedad, o se modifican con el tratamiento esteroide

Por este motivo, los objetivos de este estudio son: 1) des-cribir la evolución de varios marcadores inflamatorios en la circulación sistémica durante la agudización de la EPOC, y 2) valorar los potenciales efectos del tratamiento esteroide durante esta agudización

Método

Los valores en suero del factor de necrosis tumo-ral a (TNF- α), interleucina 6 (IL-6), interleucina 8 (IL-8) y proteína Creactiva (PCR) se determinaron en 10 pacientes (65 ± 2 años) con EPOC grave (FEV 1 35 ± 4% referencia), hos-pitalizados debido a un fracaso respiratorio agudo (PaO2 57 ± 2mmHg; PaCO2 48 ± 3mmHg). Las muestras de sangre fue-ron obtenidas en la sala de urgencias (antes de comenzar el tratamiento con esteroides i.v.), en las primeras 24 h de hospi-talización, en el momento del alta médica y 2 meses más tarde. Paralelamente se estudiaron 8 sujetos sanos no fumadores de edad similar (54 ± 3 años) que se utilizaron como casos control

Resultados

En comparación con los casos control, los pa-cientes de EPOC evidenciaron en la sala de urgencias con-centraciones más elevadas de IL-6 (5,1 ± 1,6 frente a 1,8 ± 0,5pg/ml; p<0,05) y PCR (2,2 ± 0,4 frente a 0,6± 0,2mg/dl; p<0,005), pero concentraciones similares de IL-8 (29 ± 11,3 frente a 34,7 ± 10,3pg/ml; p = ns). Durante su recuperación, y a pesar del uso de esteroides i.v., ninguno de estos valores se modificó de manera estadísticamente significativa. Dos meses después del alta hospitalaria tampoco se observaron cambios en los valores de los marcadores estudiados

El ensayo ELISA utilizado no fue capaz de detectar TNF-α ni en los pacientes ni en los casos control en ninguna de las muestras obtenidas

Conclusiones

Estos resultados indican que: a) existe evi-dencia de inflamación sistémica durante una agudización del EPOC, y b) esta inflamación sistémica no parece estar influenciada de manera significativa por el tratamiento con esteroides por vía intravenosa

Palabras clave:
Bronquitis crónica
Enfisema
Inflamación
Tratamiento antiinflamatorio
Objective

The circulating blood levels of several inflam-matory cytokines and acute phase proteins are higher in patients with stable chronic obstructive pulmonary disease (COPD). However, whether or not these inflammatory markers increase during COPD exacerbation or are modi-fied by corticosteroid treatment has not been investigated

The objective of this study was therefore 1 ) to describe changes in several inflammatory markers in systemic cir-culation during COPD exacerbation, and 2) to assess the potential effects of corticosteroid treatment during exacer-bation

Methods

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) were determined for 10 patients (65 ± 2 years old) with severe COPD (FEV1 35 ± 4% refe-rence) who were hospitalized for acute respiratory failure (PaO2 57 ± 2mm Hg; PaCO2 48 ± 3mm Hg). Blood sam-ples were obtained in the emergency room (before starting intravenous corticosteroid treatment), during the first 24 hours of admission, upon discharge and two months later. Eight healthy non-smokers of a similar age (54 ± 3 years) were also studied as control subjects

Results

The COPD patients had higher concentrations of IL-6 (5.1 ± 1.6 vs. 1.8 ± 0.5pg/mL, p<0.05) and CRP (2.2 ± 0.4 vs. 0.6 ± 0.2mg/dL, p<0.005) than did controls, but the concentrations of IL-8 were similar (29 ± 11.3 vs. 34.7 ± 10.3pg/mL, p = ns). No statistically significant changes were seen either during recovery, in spite of intravenous corticos-teroid treatment, or two months after discharge

The ELISA test used was unable to detect TNF-alpha in any of the samples obtained from either patients or controls

Conclusions

The results show that 1) there is evidence of systemic inflammation during exacerbation of COPD, and 2) such systemic inflammation does not appear to be in-fluenced significantly by intravenous corticosteroid treat-ment

Keywords:
Chronic bronchitis
Emphisema
Inflamation
Anti-inflamatory treatment
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Bibliografía
[1.]
P.K. Jeffery.
Bronchial biopsies and airway inflammation.
Eur Respir J, 9 (1996), pp. 1583-1587
[2.]
M. Saetta, A. Di Stefano, P. Maestrelli, A. Ferraresso, R. Drigo, A. Potena, et al.
Activated T-Lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis.
Am Rev Respir Dis, 147 (1993), pp. 301-306
[3.]
I. Rahman, D. Morrison, K. Donaldson, W. MacNee.
Systemic oxidative stress in asthma, COPD, and smokers.
Am J Respir Crit Care Med, 154 (1996), pp. 1055-1060
[4.]
A. Noguera, X. Busquets, J. Sauleda, J.M. Villaverde, W. MacNee, A. Agusti.
Expression of adhesion molecules and G proteins in circulatig neutrophils in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 158 (1998), pp. 1664-1668
[5.]
N. Yasuda, K. Gotoh, S. Minatoguchi, K. Asano, K. Nishigaki, M. Nomura, et al.
An increase of soluble Fas, an inhibitor of apoptosis, associated with progression of COPD.
Respir Med, 92 (1998), pp. 993-999
[6.]
A.M.W.J. Schols, W.A. Buurman, A.J. Staal-van den Brekel, M.A. Dentener, E.F.M. Wouters.
Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease.
Thorax, 51 (1996), pp. 819-824
[7.]
B. Celli, G. Snider, J. Heffner, B. Tied, I. Ziment, B. Make, et al.
Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Official statement of the American Thoracic Society.
Am J Respir Crit Care Med, 152 (1995), pp. S77-S120
[8.]
N.M. Siafakas, P. Vermeire, N.B. Pride, P. Paoletti, J. Gibson, P. Howard, et al.
Optimal assessment and management of chronic obstructive pulmonary disease (COPD). European Respiratory Society consensus statement.
Eur Respir J, 8 (1995), pp. 1398-1420
[9.]
The COPD Guidlines group.
BTS Guidelines for the management of chronic obstructive pulmonary disease.
Thorax, 52 (1997), pp. S1-S28
[10.]
American Thoracic Society Official Statement.
Standardization of Spirometry. 1994 Update.
Am J Respir Crit Care Med, 152 (1995), pp. 1107-1136
[11.]
J. Roca, J. Sanchis, A. Agusti-Vidal, F. Segarra, D. Navajas, P. Rodriguez- Roisin, et al.
Spirometric reference values for a mediterranean population.
Bull Eur Physiopathol Respir, 22 (1986), pp. 217-224
[12.]
H.O. Peltola.
C-reactive protein for rapid monitoring of infections of the central nervous system.
Lancet, 1 (1982), pp. 980-983
[13.]
E.M. Salonen, A. Vaheri.
C-reactive protein in acute viral infections.
J Med Virol, 8 (1981), pp. 161-167
[14.]
J.J. Morley, I. Kushner.
Serum C-reactive protein levels in disease.
Ann NY Acad Sci, 389 (1982), pp. 406-418
[15.]
M. Turner, M. Feldman.
Comparison of patterns of expression of tumor necrosis factor, lymphotoxin and interleukin-6 mRNA.
Bichem Biophys Res Commun, 153 (1988), pp. 1144-1151
[16.]
M. Sironi, F. Breviario, P. Prozerpio.
IL-1 stimulates IL-6 production in endothelial cells.
J Immunol, 142 (1989), pp. 549-553
[17.]
M. Nijsten, E.R. De Groot, H.J. Ten Duis, H.J. Klasen, C.E. Hack, L.A. Aarden.
Serum levels of interleukin-6 and acute phase responses.
Lancet, 2 (1987), pp. 921
[18.]
J.T. Whitcher, S.W. Evans.
Cytokines in disease.
Clin Chem, 36 (1990), pp. 1269-1281
[19.]
J.V. Castell, T. Andus, D. Kunz, P.C. Heinrich.
Interleukin-6 the major regulator of acute phase protein sybthesis in man and rat.
Ann NY Acad Sci, 557 (1989), pp. 87-101
[20.]
V.M. Keatings, A. Jatakanon, Y.M. Worsdell, P.J. Barnes.
Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD.
Am J Respir Crit Care Med, 155 (1997), pp. 542-548
[21.]
A.G.N. Agusti, J.M. Villaverde, B. Togores.
Serial measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease.
Eur Respir J, 15 (2000), pp. 177-180
[22.]
D.E. Niewoehner, M.L. Erbland, R.H. Deupree, D. Collins, N.F. Gross, R.W. Light, et al.
Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease.
N Engl J Med, 340 (1999), pp. 1941-1947
[23.]
S.A. Kharitonov, D. Yates, R.A. Robbins, R. Logan-Sinclair, E.A. Shinebourne, P.J. Barnes.
Increased nitric oxide in exhaled air of asthmatic patients.
Lancet, 343 (1994), pp. 133-135
[24.]
I. Engelberts, A. Moller, G. Schoen, C.J. Van der Linden, W.A. Buurman.
Evaluation of measurement of human TNF by ELISA.
Lymphokine Cytokine Res, 10 (1991), pp. 69-76
[25.]
V.M. Keatings, P.D. Collins, D.M. Scott, P.J. Barnes.
Differences in interleukin-8 and tumor necrosis factor-a in induced sputum from patients with chronic obstructive pulmonary disease or asthma.
Am J Respir Crit Care Med, 153 (1996), pp. 530-534
[26.]
M. Di Francia, D. Barbier, J.L. Mege, J. Orehek.
Tumor necrosis factor- alpha levels and weight loss in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 150 (1994), pp. 1453-1455
[27.]
I. De Godoy, M. Donahoe, W.J. Calhoun, J. Mancino, R.M. Rogers.
Elevated TNF-α Production by peripheral blood monocytes of weight-losing COPD Patients.
Am J Respir Crit Care Med, 153 (1996), pp. 633-637
[28.]
H. Loetscher, Y. Pan, H.W. Lanhm, M. Brockaus, H. Tabuchi, W. Lesslauer.
Molecular cloning and expression of the human 55kD tumor necrosis factor receptor.
Cell, 61 (1990), pp. 351-359
[29.]
C.A. Smith, T. Davis, D. Anderson, L. Solam, M.P. Beckmann, R. Jerzy, et al.
A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins.
Science, 248 (1990), pp. 1019-1023
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Archivos de Bronconeumología
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