Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Basic Science Investigations Respiration 2011;82:177–184 DOI: 10.1159/000326897 Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease Tatiana Lanças   a David Itiro Kasahara   a Jefferson Luiz Gross   b Ruy Camargo Pires-Neto   a Daniel Deheinzelin   b Thais Mauad   a Elnara Márcia Negri   a, b Marisa Dolhnikoff   a a  Experimental Air Pollution Laboratory (LIM 05), Department of Pathology, São Paulo University Medical School, and b  Department of Thoracic Surgery, A.C. Camargo Hospital, São Paulo, Brazil 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 correla- tion between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = –0.451, p ! 0.05). Conclu- sions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflam- mation and to the degree of airway obstruction on the pul- monary function test. Copyright © 2011 S. Karger AG, Basel Introduction Airway hyperresponsiveness (AHR), defined as an ex- aggerated response of the airway to nonspecific stimuli, is considered to be a characteristic feature of asthma [1]. However, the prevalence of AHR is also high in patients with chronic obstructive pulmonary disease (COPD), varying from 25 to 87% [2–4]. Key Words Chronic obstructive pulmonary disease  Bronchial hyperreactivity  Lung strips Abstract Background: Up to 60% of chronic obstructive pulmonary disease (COPD) patients can present airway hyperrespon- siveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to non- smoking 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 neu- trophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of -smooth muscle actin- positive cells and elastic and collagen fibers. We further in- vestigated whether changes in in vitro parenchymal me- chanics correlated to structural and inflammatory parame- ters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in Received: October 1, 2010 Accepted after revision: February 16, 2011 Published online: May 11, 2011 Tatiana Lanças, RT, PhD Department of Pathology, São Paulo University Medical School Room 1155, Av. Dr. Arnaldo, 455 São Paulo, SP 01246-903 (Brazil) Tel. +55 11 3061 8521, E-Mail tatilancas  @  usp.br © 2011 S. Karger AG, Basel 0025–7931/11/0882–0177$38.00/0 Accessible online at: www.karger.com/res