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Vol. 8. Issue 6.
Pages 547-580 (November - December 2002)
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Vol. 8. Issue 6.
Pages 547-580 (November - December 2002)
PRÉMIO THOMÉ VILLAR/BOEHRINGER INGELHEIM 2001 (SECÇÃO A)/THOMÉ VILLAR/BOEHRINGER INGELHEIM AWARD 2001 (SECTION A)
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Associação entre a reversibilidade brônquica e a inflamação das vias aéreas em doentes com doença pulmonar obstrutiva crónica
Association between bronchial reversibility and airway inflammation in patients with Chronic Obstructive Pulmonary Disease
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António Bugalho*, Nuno Neuparth**
* Interno do Internato Complementar de Pneumologia do Hospital de Pulido Valente
** Professor Auxiliar de Fisiopatologia da Faculdade de Ciências Médicas, Universidade Nova de Lisboa
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RESUMO

A Doença Pulmonar Obstrutiva Crónica (DPOC) é uma das principais causas de morbilidade e mortalidade a nível mundial. É caracterizada por obstrução das vias aéreas e inflamação pulmonar crónica, factores que variam significativamente entre doentes. Este estudo tem como objectivo avaliar os mecanismos fisiopatológicos e de inflamação num grupo de doentes com reversibilidade brônquica comparativamente a um grupo sem variabilidade do FEV1. Para tal, foram seleccionados 24 doentes com DPOC estável, moderada a grave, ex-fumadores, 12 com reversibilidade e 12 sem reversibilidade ao broncodilatador. Todos efectuaram provas de função respiratória, determinação de óxido nítrico (NO) no ar expirado e estudo de células e mediadores solúveis (interleucina-8, 5 e proteína catiónica do eosinófilo) na expectoração induzida e no sangue periférico.

O estudo confirmou a existência de uma inflamação crónica persistente nas vias aéreas em doentes com DPOC, que se traduziu pela presença aumentada de neutrófilos e de factores quimiotáticos, como a IL-8, na expectoração. O subgrupo de doentes com reversibilidade à medicação broncodilatadora apresentou características significativamente diferentes da restante população, verificandose uma elevação dos valores de NO no ar expirado, e aumento dos eosinófilos e de ECP na expectoração, não explicados pela libertação de IL-5, por uma população de linfócitos T citotóxicos. Estes dados sugerem a existência de um mecanismo inflamatório, diferente da asma, na génese da reversibilidade. O NO no ar expirado e a expectoração induzida permitem, de forma não invasiva, determinar quais os doentes com DPOC com inflamação eosinofílica das vias aéreas. Podem constituir um factor importante na avaliação inicial da doença e mesmo prever e monitorizar a resposta ao tratamento com corticosteróides, nestes doentes. A diminuição do índice de massa corporal associada ao aumento de mediadores inflamatórios, nomeadamente de IL-8, confirma a presença de um componente inflamatório sistémico na DPOC.

REV PORT PNEUMOL VIII (6): 547-580

Palavras-chave:
DPOC
inflamação
reversibilidade brônquica óxido nítrico
expectoração induzida
eosinófilos
ECP
IL-5
IL-8
ABSTRACT

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide. It is characterized by airflow limitation and chronic inflammation of the lungs that varies significantly among patients. The aim of this study was to evaluate the pathophysiologic and inflammatory mechanisms in a group of patients with and without FEV1, reversibility. We selected 24 moderate to severe, stable COPD patients, all ex-smokers, 12 with no reversibility and 12 with reversibility of airflow limitation to bronchodilator therapy. Lung function tests, exhaled nitric oxide (NO) concentrations, induced sputum and peripheral blood samples to determine cells and soluble mediators (interleukin-8, 5 and eosinophil cationic protein), were obtained from all subjects.

This study confirmed the presence of chronic and persistent inflammation of the airways of COPD patients, with an increased number of neutrophils and IL-8 concentrations in sputum. Exhaled NO levels, sputum eosinophils and ECP were higher in COPD patients with bronchodilator reversibility, and this data could not explained by a production of IL-5 by a subpopulation of T cytotoxic cells. An inflammatory mechanism, different from asthma, seems to be responsible for the airflow reversibility. Exhaled NO and induced sputum are noninvasive methods that can identify COPD patients with eosinophilic airway inflammation. These methods can be useful in the early assessment of the disease and to predict and monitor the response to glucocorticosteroid treatment. Low body mass index was related to an increase in inflammatory mediators, namely IL-8, confirming the presence of systemic inflammation in COPD.

REV PORT PNEUMOL VIII (6): 547-580

Key-words:
COPD
inflammation
bronchial reversibility
nitric oxide
induced sputum
eosinophils
ECP
IL-5
IL-8
RÉSUMÉ

La Bronchopneumopathie Chronique Obstructive (BPCO) est une cause majeur de morbidité et mortalité mondial. Elle est caractérisée par une obstruction des voies aériennes et une inflammation chronique pulmonaire qui varie significativement entre malades. L'objectif de cette étude est d'évaluer les mécanismes physiopathologiques et de l'inflammation dans un groupe de malades avec et sans réversibilité du volume expiratoire maximal dans la première, seconde (FEV1) aux bronchodilatateurs. Nous avons choisi 24 malades porteurs de BPCO stabilisée, modérée et sévère, ex-fumeurs, 12 sans réversibilité et 12 avec réversibilité des voies aériennes. Tous les malades ont subit des études fonctionnelles respiratoires, des concentrations exhalées de l'oxyde nitrique (NO) et des déterminations de cellules et de médiateurs solubles (interleulkine-8, 5 et protéine cationique dérivée des éosinophiles) dans la expectoration induite et le sang périphérique.

Cette étude a confirmé la présence d'inflammation chronique et persistante des voies aériennes de malades avec BPOC, traduit par une augmentation de neutrophiles et IL-8 dans la expectoration. Le groupe de malades avec réversibilité présentait des niveaux élevés de NO, et des éosinophiles et de l'ECP dans la expectoration qui ne peut être expliqués par une production de IL-5, par une population de cellules T cytotoxiques. Un mécanisme inflammatoire, différent de l'asthme, semble être responsable par la réversibilité des voies aériennes. Ces méthodes peuvent être utiles dans la première évaluation de la maladie et prédire et contrôler la réponse au traitement avec corticostéroïdes. La baisse de 1'index de masse corporel associée à l'augmentation de médiateurs d'inflammation, principalement IL-8, confirme la présence d'inflammation systémique dans la BPOC.

REV PORT PNEUMOL VIII (6): 547-580

Mots-clé:
BPCO
inflammation
réversibilité des vois aériennes
oxide nitrique
expectoration induite
éosinophiles
ECP
IL-5
IL-8
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