Transient Airway Colonization Is Associated with Airway Inflammation After Lung Transplantation

Abstract

Lower airway tract colonization may trigger neutrophil-mediated airway inflammation. We investigated whether transient airway colonization influences airway inflammation and pulmonary function after lung transplantation (LTx). In this retrospective study, stable LTx patients with consecutive broncho-alveolar lavages (BAL), the first colonized and the second noncolonized, were included to create a Pooled group (P, n = 32) and a Gram Negative (GN, n = 14), Gram Positive (GP, n = 9) and Fungi (F, n = 9) subgroup. Similarly, LTx patients with consecutive, noncolonized BAL samples were included as Control group (C, n = 19). BAL analysis (cell counts, IL6, IL8) and forced expiratory volume (FEV 1 ) were compared between groups. In the P group and the GN subgroup, colonized BAL samples showed a significant increase in total cells, neutrophilia and IL8-concentration and a significant decrease in FEV 1 , even when compared with the matched samples of the C group. A significant increase in neutrophilia was observed in the GP subgroup, but no other significant difference was found either in the GP and F subgroup or the C group. IL6 levels were not significantly different between groups. Transient airway colonization, especially with Pseudomonas-like GN bacteria, in stable LTx patients may be associated with IL8-dependent neutrophilic airway inflammation and a, albeit subtle, decrease in FEV 1 .

Pseudomonas aeruginosaaccentuates epithelial-to-mesenchymal transition in the airway

“…Our group has previously shown that TNF-a and IL-1b can cause dysregulated wound repair of injured epithelium by accentuating TGF-b1-driven EMT, demonstrating the link between acute inflammation and epithelial remodelling [5]. Previous data from VOS et al [27] suggest that even transient infection with P. aeruginosa in lung transplant recipients is associated with a significant increase in inflammation. We therefore hypothesised that acquisition of P. aeruginosa in the transplanted lung might produce sufficient inflammatory stimulus to accentuate dysregulated repair via EMT in the airway epithelium.…”

The Role of Intrapulmonary De Novo Lymphoid Tissue in Obliterative Bronchiolitis after Lung Transplantation

“…2), indicating that lymphoid neogenesis is initiated before the development of OB. Moreover, considering alloantigen-independent inflammatory stimuli such as ischemia-reperfusion injury at the time of transplantation (40), bacterial colonization in airways (41,42), and bile/acid aspiration (43,44) that contribute to OB/BOS, these Ag-independent factors might be enough to activate resident cells such as endothelial cells in airways to initiate lymphoid neogenesis. An interesting question to be answered in the future is how soon such phenotypical changes in the resident cells (e.g., endothelial cells) leading to lymphoid neogenesis start after lung transplantation.…”

Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after lung transplantation?

“…In the present retrospective study, approved by the Ethical Review Board of the University Hospital Gasthuisberg (Leuven, Belgium), freedom of BOS was investigated in colonised and noncolonised double (SS)LTx recipients, transplanted between January 2000 and December 2005, who underwent routine longitudinal follow-up at the outpatient clinic, as previously described [17].…”

“…Colonisation with mucoid or multiple-antibiotic resistant P. aeruginosa or B. cepacia is associated with a worse prognosis, particularly in cystic fibrosis (CF) patients [10][11][12]. It has been extensively shown that colonisation triggers expression of diverse cytokines by structural airway cells, inducing neutrophil recruitment and thereby perpetuating a cycle of airway inflammation and destruction [13][14][15][16][17][18]. However, whether pseudomonal airway colonisation after LTx occurs secondary to the airway remodelling in bronchiolitis obliterans syndrome (BOS), the major cause of late graft failure and death in long-term survivors after LTx [19], or similarly plays a primordial role in its aetiology and progression remains elusive [7,[20][21][22].…”