Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome: Do Specific Risk Factors Differ?

Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community-acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction.

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“…The role of lung allograft colonization by P aeruginosa as a risk factor for the development of BOS has not been fully determined (11,165).…”

Section: Bacterial Respiratory Tract Infectionmentioning

confidence: 99%

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

Martín-Gandul

Mueller

Pascual

et al. 2015

American Journal of Transplantation

131

105

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“…Alloimmune and nonalloimmune factors (3)(4)(5)(6)(7)(8), such as primary graft dysfunction (9), gastroesophageal reflux (10), and viral respiratory and chronic low-grade bacterial and fungal respiratory infections (11)(12)(13)(14), contribute to chronic inflammation and development of obliterative bronchiolitis (OB), the pathognomonic feature of BOS (15). Lymphoid neogenesis, the de novo formation of ectopic germinal centers observed in chronic inflammation associated with autoimmune disorders and chronic infections (16), has been described by us as associated with CLAD (17,18), likely by perpetuating the inflammatory processes initiated by alloimmune and nonalloimmune stimuli.…”

Section: Introductionmentioning

confidence: 99%

Spleen Tyrosine Kinase Modulates Fibrous Airway Obliteration and Associated Lymphoid Neogenesis After Transplantation

Matsuda

Wang

Oishi

et al. 2016

American Journal of Transplantation

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Chronic lung allograft dysfunction, the major cause of death following lung transplantation, usually manifests as irreversible airflow obstruction associated with obliterative bronchiolitis (OB), a lesion characterized by chronic inflammation, lymphoid neogenesis, fibroproliferation and small airway obliteration. Spleen tyrosine kinase (Syk), a tyrosine kinase that regulates B cell function and innate immunity, has been implicated in the pathogenesis of chronic inflammation and tissue repair. This study evaluated the role of Syk in development of OB, using an intrapulmonary tracheal transplant model of OB with the conditional Syk-knockout Syk flox/flox // rosa26-CreER T2 mice and a Syk-selective inhibitor, GSK2230413. BALB/c trachea allografts were transplanted into Syk-knockout (Syk del/del ) mice or wild-type C57BL/6 recipients treated with GSK2230413. At day 28, histological analysis revealed that in the Syk del/del and GSK2230413-treated C57BL/6 recipients, the graft lumen remained open compared with allografts transplanted into Syk-expressing (Syk flox/flox ) and placebo controltreated C57BL/6 recipients. Immunofluorescence showed lymphoid neogenesis with distinct B and T cell zones in control mice. In contrast, lymphoid neogenesis was absent and few B or T cells were found in Syk del/del and GSK2230413-treated mice. These observations suggest that inhibition of Syk may be a potential therapeutic strategy for the management of OB following lung transplantation.Abbreviations: BOS, bronchiolitis obliterans syndrome; CLAD, chronic lung allograft dysfunction; IPTT, intrapulmonary tracheal transplant; MC, methylcellulose; OB, obliterative bronchiolitis; PBS, phosphate-buffered saline; PNAd, peripheral node addressin; Syk, spleen tyrosine kinase

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“…Acute cellular and small airways rejection have been shown to be associated with chronic airways rejection and bronchiolitis obliterans syndrome (BOS), major complications and limiting factors for lung allograft survival. [1][2][3] Obliterative (constrictive) bronchiolitis, the histopathologic substrate of BOS, is rarely identified on conventional biopsies, at least in part owing to the relative paucity of small airways and sampling bias.…”

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confidence: 99%

Transbronchial Cryobiopsies in the Evaluation of Lung Allografts: Do the Benefits Outweigh the Risks?

Roden¹,

Kern

Aubry³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Transbronchial cryobiopsy technique yields larger biopsies with enhanced quality. The benefits and safety of cryobiopsies have not been thoroughly studied in lung allografts.Objective.-To compare size, quality, reproducibility of interpretation of rejection and complications of cryobiopsies with those of conventional biopsies from lung allografts.Design.-All cryobiopsies (March 2014-January 2015) of lung allografts performed at Mayo Clinic, Rochester, and medical records were reviewed. For comparison, conventional biopsies from the same patient or, if unavailable, from a random patient, were selected. Two pathologists blinded to outcome reviewed all biopsies. Specimen volume, number of alveoli, small airways, and pulmonary vessels were counted and statistically compared.Results.-Fifty-four biopsies (27 cryobiopsies) from 18 patients (11 men) were reviewed. A median of 3 (range, 2-5) and 10 (range, 6-12) specimens were obtained with cryobiopsies and conventional biopsies, respectively. Cryobiopsies were larger and contained more alveoli (P , .001, both) and small airways (P ¼ .04). Conventional biopsies showed more fresh alveolar hemorrhage (procedural) and crush artifact/atelectasis (P , .001, both). Cryobiopsies contained more pulmonary veins and venules (P , .001). There was no significant difference between the types of biopsies with respect to the reviewers' agreement on grades of rejection. Complications were more frequent in the cryobiopsy group, though the difference was not statistically significant.Conclusions.-Cryobiopsies of lung allografts are larger and have less artifact. However, complications occur and should be considered. Three cryobiopsy specimens appear sufficient for histopathologic evaluation of lung allografts.

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Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome: Do Specific Risk Factors Differ?

Cited by 43 publications

References 0 publications

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

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

Spleen Tyrosine Kinase Modulates Fibrous Airway Obliteration and Associated Lymphoid Neogenesis After Transplantation

Transbronchial Cryobiopsies in the Evaluation of Lung Allografts: Do the Benefits Outweigh the Risks?

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