Amplification of Inflammation in Emphysema and Its Association with Latent Adenoviral Infection

Abstract

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m(2) surface area by R(2) values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.

Functional single nucleotide polymorphisms of the CCL5 gene and nonemphysematous phenotype in COPD patients

“…An increased prevalence of viral infections, as well as the persistence of cells expressing viral proteins in patients with asthma [4,5] or COPD [6][7][8], has been reported, suggesting that viral infections, such as human rhinovirus and respiratory syncytial virus (RSV), may play a critical role in the pathogenesis of airway inflammation and the subsequent deterioration in lung function in patients with asthma and COPD. Studies of respiratory secretions from individuals with Data are presented as mean¡SD or median (range) unless otherwise indicated.…”

“…Rather, infections, including respiratory viruses, may be more likely to be involved in the pathophysiology of late-onset asthma through host response mechanisms [3]. Viral infections are associated with most exacerbations of asthma and chronic obstructive pulmonary disease (COPD) [4][5][6][7][8], and the most prominent aspect of the epithelial immune response towards viral respiratory infections consists of the production and release of CCL5 [9][10][11][12]. Indeed, exacerbation of mild COPD is associated with the upregulation of CCL5 in both the inflammatory and epithelial cells of the bronchial mucosa [11,13].…”

Oligoclonal CD4+T Cells in the Lungs of Patients with Severe Emphysema

“…This continued inflammation despite smoking cessation may result from latent infections because several pathogens have been identified in the lungs of patients with severe emphysema (6,30,31). Alternatively, other authors have proposed an autoimmune mechanism as the cause of these T-cell accumulations (32)(33)(34).…”

Células inflamatórias e seus mediadores na patogênese da DPOC

“…No entanto, os linfócitos T CD4 também estão aumentados no parênquima de pacientes com DPOC, especialmente naqueles com doença mais grave 26 . Embora o papel destas células ainda esteja obscuro, é possível que elas tenham importância na manutenção da memória imunológica que perpetuaria o processo mesmo após a suspensão do tabagismo 1 .…”