Aspergillus Colonization of the Lung Allograft Is a Risk Factor for Bronchiolitis Obliterans Syndrome

Abstract

Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between 1/2000 and 6/2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87 to 520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS.

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

“…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]. Цитомегаловирусной инфекцией поражаются как врожденный, так и адаптивный компоненты иммунитета и стимулируется выработ ка антигенов HLA I и II классов на эпителиальных клетках [72,73], а также стимулируется и усиливает ся аллогенный иммунный ответ и синтез провоспа лительных цитокинов [72,74].…”

“…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.…”

The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation

“…Invasive pulmonary aspergillosis (124) and pulmonary colonization with Aspergillus species have been implicated as potential risk factors for BOS (138). Postoperative pulmonary colonization with Aspergillus spp was reported as a risk factor for the development of BOS after lung transplantation independent of the development of acute rejection (194). Because deposition of Aspergillus conidia in the allograft small airways are required for the development of BOS, only small conidia Aspergillus spp (i.e.…”

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.…”