Is lung transplantation survival better in infants? Analysis of over 80 infants

Khan, Muhammad S.; Heinle, Jeffrey S.; Samayoa, Andres X.; Adachi, Iki; Schecter, M.G.; Mallory, George B.; Morales, David L.S.

doi:10.1016/j.healun.2012.09.027

Cited by 39 publications

(48 citation statements)

References 17 publications

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“…Lung transplantation is an option for infants and children with end-stage lung disease (203)(204)(205)(206)(207). There are several reports of the successful transplantation in infants with chILD syndrome (144,145,208), although the number of patients reported is small.…”

Section: Lung Transplantationmentioning

confidence: 99%

An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy

Kurland¹,

Deterding²,

Hagood³

et al. 2013

Am J Respir Crit Care Med

396

499

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Section: Lung Transplantationmentioning

confidence: 99%

An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy

Kurland¹,

Deterding²,

Hagood³

et al. 2013

Am J Respir Crit Care Med

396

499

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“…Patient and graft survival estimates were calculated using the Kaplan-Meier product limit method. As previously reported by others (15), a conditional survival analysis was performed that excluded cases of graft failure or patient death during the first year after transplantation to minimize the effects of recipient status at the time of surgery on and changes in perioperative care over time which might impact on long-term graft and patient survival. Time series were created to study: trends in the types of transplants over time; liver donor or deceased donor transplants; patient status at the time of transplantation; 1-and 5-year actuarial survival; and 1-year conditional survival.…”

Section: Descriptive and Survival Statisticsmentioning

confidence: 99%

Intestinal Transplant Registry Report: Global Activity and Trends

Grant

Abu‐Elmagd

Mazariegos

et al. 2015

American Journal of Transplantation

400

288

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“…broadinstitute.org) [accessed January 2016]). However, fewer than 10 infants per year undergo lung transplantation for ABCA3 deficiency (15), suggesting that prediction programs may overestimate frequency of disruptive mutations, some infants may be unrecognized, additional phenotypes may exist, or other genetic or environmental factors may modify disease presentation. With the increased availability of ABCA3 sequencing for symptomatic infants and children, the variable prognosis for individuals with missense, splice site, and in-frame insertion/deletions, and the limited functional prediction data, methods to distinguish pathogenic mutations from benign variants are needed to inform clinical decision making, predict disease trajectory, and assess recurrence risk (16 …”

mentioning

confidence: 99%

Functional Characterization of ATP-Binding Cassette Transporter A3 Mutations from Infants with Respiratory Distress Syndrome

Wambach

Yang

Wegner

et al. 2016

Am J Respir Cell Mol Biol

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Mutations in the ATP-binding cassette transporter A3 gene (ABCA3) result in severe neonatal respiratory distress syndrome and childhood interstitial lung disease. As most ABCA3 mutations are rare or private, determination of mutation pathogenicity is often based on results from in silico prediction tools, identification in unrelated diseased individuals, statistical association studies, or expert opinion. Functional biologic studies of ABCA3 mutations are needed to confirm mutation pathogenicity and inform clinical decision making. Our objective was to functionally characterize two ABCA3 mutations (p.R288K and p.R1474W) identified among term and latepreterm infants with respiratory distress syndrome with unclear pathogenicity in a genetically versatile model system. We performed transient transfection of HEK293T cells with wild-type or mutant ABCA3 alleles to assess protein processing with immunoblotting. We used transduction of A549 cells with adenoviral vectors, which concurrently silenced endogenous ABCA3 and expressed either wildtype or mutant ABCA3 alleles (p.R288K and p.R1474W) to assess immunofluorescent localization, ATPase activity, and organelle ultrastructure. Both ABCA3 mutations (p.R288K and p.R1474W) encoded proteins with reduced ATPase activity but with normal intracellular localization and protein processing. Ultrastructural phenotypes of lamellar body-like vesicles in A549 cells transduced with mutant alleles were similar to wild type. Mutant proteins encoded by ABCA3 mutations p.R288K and p.R1474W had reduced ATPase activity, a biologically plausible explanation for disruption of surfactant metabolism by impaired phospholipid transport into the lamellar body. These results also demonstrate the usefulness of a genetically versatile, human model system for functional characterization of ABCA3 mutations with unclear pathogenicity.Keywords: surfactant; childhood interstitial lung disease; neonatal respiratory distress; respiratory distress syndrome ATP-binding cassette transporter A3 (ABCA3), a member of a large family of proteins that hydrolyze ATP to transport substances across biologic membranes, is encoded by an 80-kb gene (ABCA3; NM_001089.2, Gene ID 21) and consists of 1,704 amino acids with two membranespanning domains and two nucleotide binding domains. ABCA3 is expressed in alveolar type II cells, localizes to the membranes of lamellar bodies, and transports phospholipids into the lamellar body, where surfactant, a complex protein-phospholipid mixture that reduces surface tension and prevents alveolar collapse at end expiration, is assembled and stored (1-3). ABCA3 is also required for lamellar body biogenesis (4).Biallelic loss-of-function (nonsense, frameshift) mutations in ABCA3 result in severe, progressive neonatal respiratory distress syndrome (RDS) that is lethal by 1 year of age without lung transplantation (5). However, for individuals with missense, T.C., F.V.W., A.H., B.P.H., and F.S.C.; drafting and revising the manuscript for important intellectual content-J.A.W., P.Y....

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Is lung transplantation survival better in infants? Analysis of over 80 infants

Cited by 39 publications

References 17 publications

An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy

An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy

Intestinal Transplant Registry Report: Global Activity and Trends

Functional Characterization of ATP-Binding Cassette Transporter A3 Mutations from Infants with Respiratory Distress Syndrome

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