Chest
Original ResearchBronchiolitis Obliterans SyndromeReflux-Induced Collagen Type V Sensitization: Potential Mediator of Bronchiolitis Obliterans Syndrome
Section snippets
Trans Vivo Delayed-Type Hypersensitivity Assay
The trans vivo delayed-type hypersensitivity (TV-DTH) assay was used to detect antigen-specific memory responses as previously described.19, 20, 21 Briefly, 7 × 106 to 9 × 106 mononuclear cells derived from peripheral blood were injected along with antigen into the footpads of CB.17 severe combined immunodeficiency mice. Animals were housed and treated in accordance with Association for Assessment and Accreditation of Laboratory Animal Care International and National Institutes of Health
Results
During a 9-year period from May 1998 to May 2007, 107 patients donated blood for measurement of TV-DTH responses to col(V), 54 of whom had already undergone lung transplantation. A second cohort of 53 patients was assayed while on the lung transplant wait-list as a confirmatory cohort. All 54 patients with primary lung transplants were monitored prospectively from the time of transplantation to the onset of BOS. Among these 54 patients, 26 had an objectively documented history of GERD by
Discussion
Long-term survival in lung transplantation recipients continues to be limited despite a substantial increase in the 1-year survival rate.23 BOS, which is characterized by fibrous obliteration of the small airways, is the most common cause of death 6 months after transplantation.2 The syndrome affects 50% to 60% of patients by 5 years posttransplantation. Survival at 5 years posttransplantation is 20% to 40% lower than that in patients who do not develop BOS.24 Once BOS ensues, it continues to
Acknowledgments
Author contributions: Dr Bobadilla: contributed to the experimental design, statistical analysis, critical review, and manuscript review.
Ms Jankowska-Gan: contributed to the experimental design and execution and patient enrollment.
Dr Xu: contributed to the experimental design and execution and patient enrollment.
Ms Haynes: contributed to the experimental design and execution and patient enrollment.
Dr Munoz del Rio: contributed to the statistical analysis.
Dr Meyer: contributed to the
References (37)
- et al.
Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation
Chest
(1984) - et al.
Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation
Ann Thorac Surg
(2006) - et al.
Human leukocyte antigen mismatches predispose to the severity of bronchiolitis obliterans syndrome after lung transplantation
Chest
(2003) - et al.
Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation
J Thorac Cardiovasc Surg
(2003) - et al.
Immunoquantification of type I, III, IV and V collagen in small samples of human lung parenchyma
Int J Biochem Cell Biol
(1995) - et al.
Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants
Am J Transplant
(2006) - et al.
Delayed type hypersensitivity responses
- et al.
The Registry of the International Society for Heart and Lung Transplantation: eighteenth Official Report-2001
J Heart Lung Transplant
(2001) - et al.
Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria
J Heart Lung Transplant
(2002) - et al.
Prevalence of gastroesophageal reflux in end-stage lung disease candidates for lung transplant
Ann Thorac Surg
(2005)
Lung transplantation exacerbates gastroesophageal reflux disease
Chest
Gastroparesis after lung transplantation. Potential role in postoperative respiratory complications
Chest
Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation
J Thorac Cardiovasc Surg
J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease
Ann Thorac Surg
Chronic rejection—an undefined conundrum
Transplantation
Mechanisms of airway obliteration after lung transplantation
Proc Am Thorac Soc
Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation
Am J Respir Crit Care Med
Graft ischemic time and outcome of lung transplantation: a multicenter analysis
Am J Respir Crit Care Med
Cited by (36)
Chronic lung allograft dysfunction is associated with an increased number of non-HLA antibodies
2024, Journal of Heart and Lung TransplantationA potential mechanism by which aspiration of duodenogastric fluid augments the risk for bronchiolitis obliterans syndrome after lung transplantation
2023, Journal of Thoracic and Cardiovascular SurgeryCitation Excerpt :Even in a murine model of syngeneic LTx, Subramanian and colleagues4 determined that in the absence of alloimmunity, antibodies to lung SAgs can lead to airway inflammation and fibrogenesis associated with the accumulation of Kα1T- and Col–V-specific interleukin 17+ T cells. Another theory, particularly related to acid reflux, suggests that autoreactivity against Col-V may be induced by acid-related alteration, which has been implicated in the progression of OB in clinical and basic science investigations.27,28 In the present study, we developed a robust murine model to investigate how transplant status and acute aspiration influence autoimmune responses to lung SAgs (Figure 8 and Video Abstract).
Clinical relevance of lung-restricted antibodies in lung transplantation
2019, Human ImmunologyCitation Excerpt :Clinical studies demonstrated that therapy directed against alloimmunity only reduced the incidence of chronic rejection if autoantibodies were depleted and abrogation of alloimmunity alone was not associated with amelioration of chronic rejection [39,40]. Similarly, gastroesophageal reflux which has been associated with chronic rejection is now known to induce de novo lung-restricted autoimmunity [19,41]. Intriguingly, LRA, especially Col-V, are structural proteins located predominantly in the peri-capillary and peri-bronchiolar tissue where BO lesions are observed [42].
Aspiration Pneumonia and Related Syndromes
2018, Mayo Clinic ProceedingsCitation Excerpt :In fact, assuming that many aspiration events are not related to pill or food matter, such foreign body reactions may not be present at all, making the precise role of lung biopsy as the confirmatory procedure for diagnosing aspiration-related lung disease questionable. Multiple series have reported the increased prevalence of GER among lung transplant recipients,48-50 including the importance of nonacid reflux and esophageal dysmotility related to aspiration and development of bronchiolitis obliterans syndrome.49,51,52 Aspiration in lung transplant recipients has been defined primarily by the detection of pepsin and bile in BALF.
Early fundoplication is associated with slower decline in lung function after lung transplantation in patients with gastroesophageal reflux disease
2018, Journal of Thoracic and Cardiovascular SurgeryDistal airway microbiome is associated with immunoregulatory myeloid cell responses in lung transplant recipients
2018, Journal of Heart and Lung Transplantation
Funding/Support: This study was supported by the National Institutes of Health [Grants R01 AI48624 (Drs Bobadilla and Meyer and Mss Jankowska-Gan and Haynes), R21 A1049900 (Dr Bobadilla and Mss Haynes and Jankowska-Gan), and R01 AR47746 (Dr Greenspan)]. Dr Maloney is supported by a CHEST Foundation award for clinical investigation in lung transplantation.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).