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Doctoral Thesis
DOI
10.11606/T.5.2009.tde-08032010-155914
Document
Author
Full name
Tatiana Lanças
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Dolhnikoff, Marisa (President)
Deheinzelin, Daniel
Fernandes, Ana Luisa Godoy
Garcia, Maria Lucia Bueno
Martins, Milton de Arruda
Title in Portuguese
Responsividade do tecido pulmonar periférico de pacientes com doença pulmonar obstrutiva crônica
Keywords in Portuguese
Alvéolos pulmonares
Bronquite crônica
Doença pulmonar obstrutiva crônica
Enfisema pulmonar
Hiper-reatividade brônquica
Mecânica
Pulmão/fisiopatologia
Abstract in Portuguese
Mais de 60% dos pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC) podem apresentar hiper-responsividade brônquica. Entretanto, não se sabe se, além das vias aéreas, o tecido pulmonar periférico também apresenta uma resposta exagerada a um agonista na DPOC. No presente estudo foi investigado o comportamento mecânico in vitro e as alterações estruturais e inflamatórias do tecido pulmonar periférico de 10 pacientes com DPOC comparados com 10 controles não fumantes. Foram realizadas medidas de resistência (R) e elastância (E) de fatias pulmonares em situação basal e após desafio com Acetilcolina. Também foram analisados no tecido alveolar as densidades de neutrófilos, eosinófilos, macrófagos, mastócitos e linfócitos CD8+ e CD4+, além do conteúdo de células positivas para -actina de músculo liso, fibras elásticas e colágenas. Os valores de R após o tratamento com Acetilcolina (RACh) e a porcentagem de aumento de resistência (%R) foram significativamente maiores no grupo DPOC comparado ao grupo controle (p0,03). O grupo DPOC também apresentou densidade de macrófagos (p=0,04) e linfócitos CD8+ (p=0,017) significativamente maior e conteúdo de fibras elásticas significativamente menor (p=0,003) comparado ao grupo controle. Foi observada uma correlação positiva significativa entre a %R e a densidade de eosinófilos e linfócitos CD8+ (r=0,608, p=0,002; e r=0,581, p=0,001, respectivamente), e também uma correlação negativa significativa entre a %R e a relação VEF1/ CVF (r=-0,451, p<0,05). Concluímos que a resposta colinérgica de fatias de parênquima pulmonar está aumentada em pacientes com doença pulmonar obstrutiva crônica e parece estar relacionada tanto à densidade de eosinófilos e de linfócitos CD8+ no tecido alveolar quanto ao grau de obstrução determinado pela prova de função pulmonar.
Title in English
Hyperresponsiveness of peripheral lung parenchyma in chronic obstructive pulmonary disease
Keywords in English
Bronchial hyperreactivity
Chronic bronchitis
Chronic obstructive pulmonary disease
Lung/physiopathology
Mechanics
Pulmonary alveoli
Pulmonary emphysema
Abstract in English
Up to 60% of COPD patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also presents an exaggerated response to agonists in COPD. In this study we investigated the in vitro mechanical behavior and structural and inflammatory changes of peripheral lung tissue of 10 COPD patients and compared to 10 non-smoking controls. We measured resistance (R) and elastance (E) of lung strips at baseline and after acetylcholine (ACh) challenge. We further assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, and the content of -smooth muscle actin+ cells, elastic fibers and collagen fibers. Values of R after ACh treatment (RACh) and percent increase of tissue resistance (%R) were significantly higher in COPD group compared to controls (p0.03). There was a significantly higher density of macrophages (p=0.04) and CD8+ cells (p=0.017) and a lower elastic fiber content (p=0.003) in COPD group compared to controls. We observed a significant positive correlation between %R and eosinophil and CD8+ cells density (r=0.608, p=0.002; and r=0.581, p=0.001, respectively), and also a negative correlation between %R and FEV1/FVC (r=-0.451, p<0.05). We conclude that the cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and also to the degree of airway obstruction at pulmonary function test.
 
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Publishing Date
2010-03-16
 
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