Transplant-related bronchiolitis obliterans (BOS) demonstrates unique cytokine profiles compared to toxicant-induced BOS

Svetlecic, Jennifer A.; Molteni, Agostino; Chen, Yayan; Alhamed, M.; Quinn, Tim; Herndon, Betty

doi:10.1016/j.yexmp.2005.08.008

Cited by 8 publications

(1 citation statement)

References 22 publications

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“…The chronic gastric fluid aspiration‐induced upregulation of proinflammatory cytokines that we observed could play a major role in propagating the process or processes responsible for tissue damage and eventual airway fibrosis and obliteration (24). In particular, the proinflammatory cytokine IL‐1α significantly increased in both the BAL fluid and the serum of allograft recipients receiving chronic gastric fluid‐aspiration could be a mitigator.…”

Section: Discussionmentioning

confidence: 90%

Chronic Aspiration of Gastric Fluid Induces the Development of Obliterative Bronchiolitis in Rat Lung Transplants

Li¹,

Hartwig²,

Appel³

et al. 2008

American Journal of Transplantation

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Long-term survival of a pulmonary allograft is currently hampered by obliterative bronchiolitis (OB), a form of chronic rejection that is unique to lung transplantation. While tracheobronchial aspiration from gastroesophageal reflux disease (GERD) has clinically been associated with OB, no experimental model exists to investigate this problem. Using a WKY-to-F344 rat orthotopic left lung transplant model, the effects of chronic aspiration on pulmonary allograft were evaluated. Recipients received cyclosporine with or without 8 weekly aspirations of gastric fluid into the allograft. Six (66.7%) of 9 allografts with aspiration demonstrated bronchioles with surrounding monocytic infiltrates, fibrosis and loss of normal lumen anatomy, consistent with the development of OB. In contrast, none of the allografts without aspiration (n = 10) demonstrated these findings (p = 0.002). Of the grafts examined grossly, 83% of the allografts with chronic aspiration but only 20% without aspiration appeared consolidated (p = 0.013). Aspiration was associated with increased levels of IL-1a , IL-1b , IL-6, IL-10, TNF-a and TGF-b in BAL and of IL-1a , IL-4 and GM-CSF in serum. This study provides experimental evidence linking chronic aspiration to the development of OB and suggests that strategies aimed at preventing aspiration-related injuries might improve outcomes in clinical lung transplantation.

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Section: Discussionmentioning

confidence: 90%

Chronic Aspiration of Gastric Fluid Induces the Development of Obliterative Bronchiolitis in Rat Lung Transplants

Li¹,

Hartwig²,

Appel³

et al. 2008

American Journal of Transplantation

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Metabolic and Biochemical Responses of the Healthy Human Lung to Nonthoracic Surgery

Herndon

Yagan

Reisz

et al. 2007

Lung

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The objective of this study was to evaluate and assign numbers to biochemical or cellular entities in lung-healthy patients that change immediately postsurgery compared with the same parameters immediately presurgery, with the hypothesis that biochemical markers with significant change could be the basis of tests to predict postoperative respiratory complications. Thirty lung-healthy adults who were to undergo elective surgical procedures requiring general anesthesia participated. The population included sequential persons that met inclusion criteria and gave consent. At intubation and before surgery, a bonchoalveolar lavage (BAL) was performed. Before extubation but after completion of surgical procedures, a second 100-ml BAL was performed in the contralateral lung. Serum from both time periods was also collected. Total cell counts were elevated postsurgery in smokers and subjects claiming childhood but not current asthma, who also showed increased postsurgical BAL IL-1 but not increased TNFalpha. LDH and its isoenzymes, measured in both BAL and serum, showed no correlation with time on surgical ventilation, average FiO2, or average peak pressure during surgical ventilation. BAL LDH isoenzyme 4 showed a significant elevation pattern pre-to-post surgery when the entire subject population was considered irrespective of surgery type or time on ventilation. Presurgery versus postsurgery variation was best measured in BAL rather than in serum. The pulmonary, biochemical, and cellular parameters measured in the pre- and postsurgical BALs of lung-healthy subjects undergoing nonthoracic surgery show subtle modulations of pulmonary defense markers, defined by significantly increased proinflammatory cytokines and cell counts postsurgery compared to the same patient presurgery.

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Bronchiolitis Obliterans

Lee¹,

White²

2008

Pediatric Respiratory Medicine

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Transplant-related bronchiolitis obliterans (BOS) demonstrates unique cytokine profiles compared to toxicant-induced BOS

Cited by 8 publications

References 22 publications

Chronic Aspiration of Gastric Fluid Induces the Development of Obliterative Bronchiolitis in Rat Lung Transplants

Chronic Aspiration of Gastric Fluid Induces the Development of Obliterative Bronchiolitis in Rat Lung Transplants

Metabolic and Biochemical Responses of the Healthy Human Lung to Nonthoracic Surgery

Bronchiolitis Obliterans

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