Browsing by Subject "Lung transplant"

Now showing 1 - 3 of 3
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    Exploring the Developmental Impact of Cystic Fibrosis on Lung Transplant Candidacy: Considerations for Adulthood
    (Springer, 2021-01-29) Powell, Anna-Leigh; Teh, Lisa; Patel, Anahli; Chernak, Yelena
    The average life expectancy for cystic fibrosis (CF) has increased over the past four decades resulting in a higher rate of adult CF patients. Adults seeking lung transplant to address CF-related advanced lung disease (ALD) represent a small, yet growing, subset of lung transplant recipients. Psychosocial factors such as adherence to medical recommendations, self-management of medical care, and caregiver support have been identified as positive prognostic factors in lung transplant outcomes. These factors are also implicated in the pediatric chronic illness literature and are crucial as patients begin to transition to a more autonomous and independent role in their own health management. Adults with CF facing ALD must navigate through another transitional phase as lung transplant requires additional supports and new expectations. A case series is used to highlight specific psychosocial considerations in this population and to explore the seemingly dichotomous relationship between independent self-management and caregiver support.
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    Obesity-related IL-18 Impairs T-Regulatory Cell Function and Promotes Lung Ischemia–Reperfusion Injury
    (American Thoracic Society, 2021) Akimova, Tatiana; Zhang, Tianyi; Christensen, Lanette M.; Wang, Zhonglin; Han, Rongxiang; Negorev, Dmitry; Samanta, Arabinda; Sasson, Isaac E.; Gaddapara, Trivikram; Jiao, Jing; Wang, Liqing; Bhatti, Tricia R.; Levine, Matthew H.; Diamond, Joshua M.; Beier, Ulf H.; Simmons, Rebecca A.; Cantu, Edward; Wilkes, David S.; Lederer, David J.; Anderson, Michaela; Christie, Jason D.; Hancock, Wayne W.; Medicine, School of Medicine
    Rationale: Primary graft dysfunction (PGD) is a severe form of acute lung injury, leading to increased early morbidity and mortality after lung transplant. Obesity is a major health problem, and recipient obesity is one of the most significant risk factors for developing PGD. Objectives: We hypothesized that T-regulatory cells (Tregs) are able to dampen early ischemia–reperfusion events and thereby decrease the risk of PGD, whereas that action is impaired in obese recipients. Methods: We evaluated Tregs, T cells, and inflammatory markers, plus clinical data, in 79 lung transplant recipients and 41 liver or kidney transplant recipients and studied two groups of mice on a high-fat diet (HFD), which did (“inflammatory” HFD) or did not (“healthy” HFD) develop low-grade inflammation with decreased Treg function. Measurements and Main Results: We identified increased levels of IL-18 as a previously unrecognized mechanism that impairs Tregs’ suppressive function in obese individuals. IL-18 decreases levels of FOXP3, the key Treg transcription factor, decreases FOXP3 di- and oligomerization, and increases the ubiquitination and proteasomal degradation of FOXP3. IL-18–treated Tregs or Tregs from obese mice fail to control PGD, whereas IL-18 inhibition ameliorates lung inflammation. The IL-18–driven impairment in Tregs’ suppressive function before transplant was associated with an increased risk and severity of PGD in clinical lung transplant recipients. Conclusions: Obesity-related IL-18 induces Treg dysfunction that may contribute to the pathogenesis of PGD. Evaluation of Tregs’ suppressive function together with evaluation of IL-18 levels may serve as a screening tool to identify obese individuals with an increased risk of PGD before transplant.
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    Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant
    (American Thoracic Society, 2018-01-15) Cantu, Edward; Diamond, Joshua M.; Suzuki, Yoshikazu; Lasky, Jared; Schaufler, Christian; Lim, Brian; Shah, Rupal; Porteous, Mary; Lederer, David J.; Kawut, Steven M.; Palmer, Scott M.; Snyder, Laurie D.; Hartwig, Matthew G.; Lama, Vibha N.; Bhorade, Sangeeta; Bermudez, Christian; Crespo, Maria; McDyer, John; Wille, Keith; Orens, Jonathan; Shah, Pali D.; Weinacker, Ann; Weill, David; Wilkes, David; Roe, David; Hage, Chadi; Ware, Lorraine B.; Bellamy, Scarlett L.; Christie, Jason D.; Medicine, School of Medicine
    RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.