title: Cholinergic hyperresponsiveness of peripheral lung parenchyma in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Up to 60% of chronic obstructive pulmonary disease (COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD.
  
  
  OBJECTIVE
  To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls.
  
  
  METHODS
  We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of α-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function.
  
  
  RESULTS
  Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p ≤ 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = -0.451, p < 0.05).
  
  
  CONCLUSIONS
  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 to the degree of airway obstruction on the pulmonary function test.
authors.affiliation: Experimental Air Pollution Laboratory (LIM 05), Department of Pathology, São Paulo University Medical School, São Paulo, Brazil. tatilancas@usp.br
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lanças
authors.forename: David Itiro
authors.initials: DI
authors.lastname: Kasahara
authors.forename: Jefferson Luiz
authors.initials: JL
authors.lastname: Gross
authors.forename: Ruy Camargo
authors.initials: RC
authors.lastname: Pires-Neto
authors.forename: Daniel
authors.initials: D
authors.lastname: Deheinzelin
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.forename: Elnara Márcia
authors.initials: EM
authors.lastname: Negri
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolhnikoff
mesh_terms: D000328:Adult; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*