Bacterial colonization of the donor lower airways is a predictor of poor outcome in lung transplantation☆

Avlonitis, Vassilios S.; Krause, Anna; Luzzi, Luca; Powell, H.; Phillips, Julie A.; Corris, Paul A.; Gould, F.K.; Dark, John H.

doi:10.1016/s1010-7940(03)00454-8

Cited by 85 publications

(56 citation statements)

References 15 publications

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“…Other studies have demonstrated that donor colonization impairs LTx outcomes [30], with the impact of donor-to-host transmission being previously described [31]. In our study, airway colonization was evident in the bronchoalveolar lavage fluid of 50% of EVLR patients after LTx, much higher than would be expected or indeed observed among non-ELVR patients.…”

Section: Discussionsupporting

confidence: 61%

Lung Transplantation after Endoscopic Lung Volume Reduction

Fuehner¹,

Clajus²,

Fuge³

et al. 2015

Respiration

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Background: Endoscopic lung volume reduction (ELVR) has become an established treatment option in selected patients with end-stage lung emphysema. ELVR, however, does not always prevent disease progression, and patients may inevitably be considered for lung transplantation. Objectives: Currently, limited data exist regarding the impact of preceding ELVR on lung transplantation outcomes. Methods: A retrospective, single-center analysis of lung transplantation (LTx) waiting list candidates, who had previously undergone ELVR for emphysema between 2010 and 2014, was performed. Outcomes were compared to matched (1:2) controls who underwent LTx for emphysema without previous ELVR. The 12-month survival after LTx represented the primary end point. Results: In total 23/693 (3%) patients listed for LTx between January 2010 and May 2014 had undergone ELVR, of whom 20/23 (87%) proceeded to LTx (ELVR group). Forty matched non-ELVR emphysema patients acted as controls. Bronchiectasis on CT prior to LTx was more evident in ELVR patients [11/20 (55%) vs. 12/40 (30%); p = 0.04] as well as airway colonization after LTx [10/20 (50%) vs. 6/40 (15%); p = 0.004]. Among ELVR patients, the most prevalent colonizing organism was Stenotrophomonas maltophilia (4/10 patients, 40%). No significant differences were observed in LTx waiting list time, duration of LTx procedure, ventilatory support, ICU stay after LTx or time to hospital discharge. One ELVR patient (5%) died 189 days after LTx from pneumonia, compared to 1 non-ELVR patient (3%) who died after 269 days (p = 0.61). Conclusions: Previous ELVR treatment was not associated with differing outcomes following LTx. Increased bacterial colonization rates were evident and warrant further investigation.

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Section: Discussionsupporting

confidence: 61%

Lung Transplantation after Endoscopic Lung Volume Reduction

Fuehner¹,

Clajus²,

Fuge³

et al. 2015

Respiration

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“…Although dendritic cells are the most potent APCs, the lung is rich in monocytes/macrophages and depletion of these cells in the donor lung before transplantation was associated with decreased local induction of proinflammatory cytokines, such as TNF-a (44). The donor lung is frequently colonized with microbial pathogens that are a rich source of TLR ligands (45), and lung transplantation itself results in exposure of antigenic col(V) (10). We hypothesize that the combination of donor lung monocyte/macrophage-induced alloimmunity that is enhanced by TLR ligands may result in high local levels of proinflammatory cytokines, such as IL-1 and IL-6, which may potentiate PGD in col(V)-presensitized patients, while promoting de novo development of Th-17 cells reactive to col(V) in patients not previously col(V) reactive, thus predisposing to BOS (14).…”

Section: Discussionmentioning

confidence: 99%

Th-17, Monokines, Collagen Type V, and Primary Graft Dysfunction in Lung Transplantation

Bobadilla¹,

Love²,

Jankowska‐Gan³

et al. 2008

Am J Respir Crit Care Med

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Rationale: The pathogenesis of primary graft dysfunction (PGD), a serious complication of lung transplantation, is poorly understood. Human studies and rodent models have shown that collagen type V (col [V]), stimulates IL-17-dependent cellular immunity after lung transplantation. Objectives: To determine whether patients with end-stage lung disease develop pretransplant col(V)-specific cellular immunity, and if so, the impact of this response on PGD. Methods: Trans-vivo delayed-type hypersensitivity (TV-DTH) assays were used to evaluate memory T-cell responses to col(V) in 55 patients awaiting lung transplantation. Pa O 2 /FI O 2 index data were used to assess PGD. Univariate risk factor analysis was performed to identify variables associated with PGD. Rats immunized with col(V) or irrelevant antigen underwent lung isografting to determine if prior anti-col(V) immunity triggers PGD in the absence of alloreactivity. Measurements and Main Results: We found that 58.8% (10/17) of patients with idiopathic pulmonary fibrosis, and 15.8% (6/38) of patients without idiopathic pulmonary fibrosis tested while on the wait list for a lung transplant were col(V) DTH positive. Col(V) reactivity was CD4 + T-cell and monocyte mediated, and dependent on IL-17, IL-1b, and tumor necrosis factor (TNF)-a. Pa O 2 /FI O 2 indices were impaired significantly 6-72 hours after transplantation in col(V)-reactive versus nonreactive patients. Univariate risk factor analysis identified only preoperative TV-DTH to col(V) and ischemic time as predictors of PGD. Finally, in a rat lung isograft model, col(V) sensitization resulted in significantly lower Pa O 2 /FI O 2 , increased local TNF-a and IL-1b production, and a moderate-to-severe bronchiolitis/ vasculitis when compared with control isografts. Conclusions: The data suggest that activation of innate immunity by col(V)-specific Th-17 memory cells represents a novel pathway to PGD after lung transplantation.Keywords: lung transplantation; primary graft dysfunction; collagen type V; autoimmunity; memory T cellThe historic paradigm of allograft failure due primarily to humoral and cell-mediated immune responses to foreign major histocompatability complex (MHC) antigens has recently been challenged by additional hypotheses (1-3). Although it is clear that immunity to donor human leukocyte antigen (HLA) serves a significant role in mediating allograft rejection, recent evidence suggests that self-antigens exposed during ischemiareperfusion injury may, under some circumstances, present an equal, if not greater, barrier to graft acceptance (4-6). In lung transplantation, one such cryptic self-antigen is collagen type-V (col[V]) (2). Col(V) is classified as a minor fibrillar collagen and, in the human lung, the ratio of matrix collagens is 86:28:8:1.6 (for collagens I, III, IV, and V, respectively) (7). Under normal physiologic conditions, col(V) coassembles into heterotypic fibrils with the major fibrillar collagen type I (8, 9). In fact, the majority of the col(V) monomer is normally partitioned ...

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“…Several studies demonstrated that 46-89% of donor lungs had positive bronchoalveolar lavage (BAL) bacterial cultures and that frequent donor-to-recipient transmission of infection put the recipients at higher risk for subsequent lung infection and poor posttransplant outcome (3)(4)(5). Bacteria cause most cases of VAP, and many infections are polymicrobial.…”

Section: Introductionmentioning

confidence: 99%

Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs

Nakajima

Cypel

Bonato

et al. 2016

American Journal of Transplantation

128

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Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high‐dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic‐treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad‐spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL‐1β and macrophage inflammatory proteins 1α and 1β at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad‐spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function.

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Bacterial colonization of the donor lower airways is a predictor of poor outcome in lung transplantation☆

Abstract: Donor lungs with lower airways colonized with bacteria result in inferior recipient outcome. Bacterial colonization of the donor lower airways could therefore be used as a marker of donor lung injury, but evidence from a prospective study is necessary.

Cited by 85 publications

References 15 publications

Lung Transplantation after Endoscopic Lung Volume Reduction

Lung Transplantation after Endoscopic Lung Volume Reduction

Th-17, Monokines, Collagen Type V, and Primary Graft Dysfunction in Lung Transplantation

Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs

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