Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis

Abstract

Bronchiolitis obliterans syndrome (BOS) represents the leading cause of late mortality after lung transplantation (LTx). Cystic fibrosis (CF) patients frequently show airway colonization with gram-negative bacteria (GNB) both before and after LTx. Graft colonization with GNB and its relevance towards BOS development were investigated in a CF population after LTx. Adult CF patients receiving LTx and surviving at least 6 months were included in this prospective observational study between 1/1/2002 and 30/6/2006 in a single center and followed until 31/3/2007. Pre- and post-LTx respiratory culture samples were compared for the presence of identical GNB. BOS-free survival was compared in colonized and non-colonized patients. Fifty-nine adult CF patients with a median age at LTx of 25.5 (18-49) years were included and had a median follow-up of 966 (128-1889) days. Seven patients (15%) demonstrated immediate eradication of GNB in lower respiratory tract samples. A further 18 patients (34%) demonstrated transient colonization. Thirty-four recipients had further positive samples after LTx. Eighteen patients (31%) developed BOS >or=stage 1, 508 (114-1167) days after LTx. Freedom of graft colonization with pseudomonads was independently associated with less frequent development of BOS (p=0.006). Persistent graft colonization with pseudomonads increases the prevalence of BOS after LTx in CF patients. A significant proportion of post-LTx CF patients demonstrates subsequent GNB eradication during later follow-up and this may have a protective role against development of BOS. Strategies to eradicate airway colonization or reduce bacterial load may prevent BOS in CF patients after LTx.

International practical guidelines on diagnosis, prevention and treatment of bronchiolitis obliterans syndrome

“…Другие факторы риска развития СОБ обсужда ются в дополнительных онлайн материалах и вклю чают наличие антител к антигенам HLA [44][45][46][47][48], ПДТ [49][50][51][52] и наличие ГЭР [53][54][55]. К дополни тельным факторам риска относятся вирусные [29,31,32,[56][57][58][59][60][61][62][63][64], бактериальные [65][66][67][68] и грибковые инфекции [69][70][71].…”

“…R.Vos et al [54] показано, что при персистенции Pseudomonas создается даже больший риск СОБ, чем при "свежей" колонизации. J.Gottlieb et al [55] установлено, что в случае персистирующей колонизации трансплантата Pseudomonas у реципи ентов с муковисцидозом значительно повышается частота СОБ. V.G.Valentine et al [69] обнаружено, что грибковая пневмония или пневмонит являются независимыми факторами, прогнозирующими по следующее развитие СОБ, а S.Weigt et al [70] уста новлено, что колонизация Aspergillus была связана с последующим развитием СОБ независимо от дру гих факторов.…”

Bronchiolitis obliterans syndrome

“…In addition to alloimmune and/ or autoimmune phenomena associated with BOS, many mechanisms that can be perceived as predominantly nonimmune have been implicated as playing a role in BOS pathogenesis. These include injury caused by primary graft dysfunction (PGD) [36,37], gastroesophageal reflux (GER) with microaspiration [38,39], airway ischemia caused by disruption of the bronchial circulation [40•], and infections caused by viruses [41,42], bacteria [43,44], or fungi [45]. These "non-immune" factors may promote tissue inflammation that in turn initiates and may intensify an alloimmune rejection response or autoimmune reaction to lung airway self-antigens.…”

Colonization and Bronchiectasis in Patients with Advanced Chronic Obstructive Pulmonary Disease

“…Previous colonization represents a proven risk factor for increased infection rates as well as chronic allograft dysfunction (rejection) in lung transplant recipients [7].…”