Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

Verleden, Stijn E.; Scheers, Hans; Nawrot, Tim S.; Vos, Robin; Fierens, Frans; Geenens, Rachel; Yserbyt, Jonas; Wauters, Shana; Verbeken, E.K.; Nemery, Benoît; Dupont, Lieven; Raemdonck, Dirk Van; Verleden, Geert M.; Vanaudenaerde, Bart M.

doi:10.1111/j.1600-6143.2012.04134.x

Cited by 44 publications

(43 citation statements)

References 28 publications

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“…It has been shown that azithromycin has a protective effect on lymphocytic bronchiolitis in the posttransplant setting for lung recipients (36). Generally, our program initiates azithromycin therapy at physician discretion in response to drops in lung function.…”

Section: Discussionmentioning

confidence: 99%

Air Pollution and the Development of Posttransplant Chronic Lung Allograft Dysfunction

Bhinder

Chen

Sato

et al. 2014

American Journal of Transplantation

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Chronic lung allograft dysfunction (CLAD) is the leading cause of mortality following lung transplantation. We conducted a retrospective cohort study including 397 bilateral lung recipients transplanted in from 1996 to 2009 to determine the association between ambient air pollution, CLAD and mortality. Pollution exposure was assessed using satellite‐based estimates of nitrogen dioxide, distance to major roadway and total length of roadways around a patient's home. Cumulative exposures to ozone and particulate matter were estimated from concentrations measured at fixed‐site stations near patients' homes using inverse distance weighted interpolation. Cox proportional hazards models were used to estimate the associations of CLAD with air pollution exposure, adjusting for various individual and neighborhood characteristics. During the follow‐up, 185 patients developed CLAD (47%) and 101 patients died (25%). Fifty‐four deaths (53%) were due to CLAD. We observed an association between CLAD development and road density within 200 m of a patient's home (HR 1.30 [95% CI 1.07–1.58]). Although based on a subgroup of 14 patients, living within 100 m of a highway was associated with a high risk for developing CLAD (HR 4.91 [95% CI 2.22, 10.87]). These data suggest that exposure to traffic‐related air pollution is associated with development of CLAD among lung transplant recipients.

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Section: Discussionmentioning

confidence: 99%

Air Pollution and the Development of Posttransplant Chronic Lung Allograft Dysfunction

Bhinder

Chen

Sato

et al. 2014

American Journal of Transplantation

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“…The pathogenesis of AR however, is fundamentally different than the other injury patterns. While many cases of DAD, OP and LB are initiated by exposure related insults (e.g., aspiration, infection, pollution (13, 33, 60)), AR represents an allo-immune response. Transplant recipients with early AR may have had the early presence of circulating allo-responsive memory T-cells.…”

Section: Discussionmentioning

confidence: 99%

“…Since there are no effective treatments available for CLAD, the identification of risk factors is a key step towards both understanding CLAD pathogenesis and improving post-transplant outcomes. There are numerous “non-alloimmune” (e.g., respiratory infections (2-9), gastroesophageal reflux (10, 11), air pollution (12, 13), autoimmune reactivity (14, 15)) and “alloimmune” insults (e.g. acute cellular rejection (16-18)) which challenge the lung allograft.…”

Section: Introductionmentioning

confidence: 99%

Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation

Shino

Weigt

et al. 2017

American Journal of Transplantation

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The impact of allograft injury time-of-onset on the risk of chronic lung allograft dysfunction (CLAD) remains unknown. We hypothesized that episodes of late-onset (≥6 months) allograft injury would produce an augmented CXCR3/ligand immune response, leading to increased CLAD. In a retrospective single-center study, 1894 transbronchial biopsies from 441 lung transplant recipients were reviewed for the presence of acute rejection (AR), lymphocytic bronchiolitis (LB), diffuse alveolar damage (DAD) and organizing pneumonia (OP). The association between the time-of-onset of each injury pattern and CLAD was assessed using multivariable Cox models with time-dependent covariates. BAL CXCR3 ligand concentrations were compared between early and late-onset injury patterns using linear mixed-effects models. Late-onset DAD and OP were strongly associated with CLAD: adjusted HRs 2.8 95%CI 1.5-5.3 and 2.0 95%CI 1.1-3.4, respectively. The early-onset form of these injury patterns did not increase CLAD risk. Late-onset LB and AR predicted CLAD in univariable models, but lost significance after multivariable adjustment for late DAD and OP. AR was the only early-onset injury pattern associated with CLAD development. Elevated BAL CXCR3 ligand concentrations during late-onset allograft injury parallel the increase in CLAD risk and support our hypothesis that late allograft injuries result in a more profound CXCR3/ligand immune response.

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“…Therefore, it follows that thoughtful, informationweighted and value-driven decision making will always be required to manage the intrinsic risk trade-off between alloreactivity and infection/toxicity that will never be able to be completely resolved with the use of these more specific but nevertheless still ''blunt'' immunosuppressant agents. These trade-offs are particularly relevant in the LTR who routinely receives a non-HLA matched donor organ which is necessarily fully exposed to aero-environmental irritants, allergens and infections [155,156] and will, therefore, require a vigilant and indefinite review of immunosuppression strategy.…”

Section: Individual Patient Management Issuesmentioning

confidence: 99%

Update on lung transplantation: programmes, patients and prospects

Kotsimbos¹,

Williams²,

Anderson³

2012

European Respiratory Review

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Lymphocytic Bronchiolitis After Lung Transplantation Is Associated With Daily Changes in Air Pollution

Cited by 44 publications

References 28 publications

Air Pollution and the Development of Posttransplant Chronic Lung Allograft Dysfunction

Air Pollution and the Development of Posttransplant Chronic Lung Allograft Dysfunction

Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation

Update on lung transplantation: programmes, patients and prospects

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