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Longitudinal Study of Pulmonary Microbial Dynamics in Lung Transplant Recipients with and without Bronchiolitis Obliterans Syndrome
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The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
after HT predicted fatal and non-fatal cardiovascular (CV) events. We additionally analyzed the impact of metabolic risk factors on changes in IVUS measurements. Results: 107 consecutive patients receiving HT between 1999 and 2007 entered the study. During the 11 years of follow-up, incidence of CV death was 8⫾3% and of CV events was 26⫾6%. Between year 1 and 5, MIT and intimal volume increased, lumen volume decreased (Po0.001 for all), while vessel volume was unchanged. By Cox’s model, only MIT increase was associated with subsequent CV death (RR¼4.2 [1.212.1] per mm, P¼0.03) and CV events (RR¼2.6 [1.1-5.6] per mm; P¼0.03). By ROC curves, we found that a MIT change cut-off of 0.35 mm best identified patients at risk for CV death and events (Figure). Among the metabolic parameters, increasing triglycerides and HDL-cholesterol r65mg/dl predicted MIT increase Z 0.35 mm (Pr0.05). Conclusions: This study provides the first suggestive evidence that MIT increase represent a relevant prognostic marker also after the first year after HT. In addition, the finding that clinically relevant MIT is predicted by lipid pattern typical of insulin resistance, provide a strong rationale supporting aggressive therapeutic interventions against metabolic abnormalities mid and long-term after HT.
Purpose: The development of Bronchiolitis Obliterans Syndrome (BOS) has been previously linked to microbial pathogens within the transplanted lung. With advanced molecular technology, we are now able to further define microbial communities within the transplanted lung. We hypothesized that these microbial communities will be distinct in lung transplant recipients who develop BOS compared to those who remain stable. Methods and Materials: Eighteen lung transplant recipients were included in this analysis. Nine patients developed BOS within 2 years. Bronchoscopy with bronchoalveolar lavage (BAL) was performed at 1, 3, 6, and 12 months post transplant. Bacterial 16S rDNA extracted from the BAL fluid was amplified using barcoded primers and PCR products were pooled and sequenced using 454 pyrosequencing. All the sequence reads were denoised and clustered into similar operational taxonomic units. Taxonomy annotation was assigned according to Ribosomal Database Project. Results: The bacterial community of transplanted lungs was taxonomically diversified and consisted of micro-organisms belonging to 14 phyla. Interindividual variation of the microbial community was greater than intraindividual variation for all patients. There was a distinct difference in the microbial community at the phylum and class taxonomic level between BOS and non-BOS patients (po0.05). BOS patients had a greater predominance of the phylum Firmicutes and class Bacilli, while non-BOS patients had a greater predominance of phylum Proteobacteria and class Gammaproteobacteria. In a subset of these patients, the longitudinal patterns of bacterial dynamics were different in BOS and non-BOS patients. Conclusions: The pulmonary microbiota in lung transplant recipients is taxonomically diverse and dynamic over time and is distinct in patients who develop early BOS compared to those who remain stable. Our findings provide novel approaches to address the relationship between microbial communities and BOS development after lung transplantation.
70 Circulating microRNA: Prognostic Biomarker for Pediatric Heart Failure S.D. Miyamoto,1 V. Peterson,2 B. Freed,3 L. Cagle,3 B.L. Stauffer,2 C.C. Sucharov.2 1Pediatrics/Cardiology, University of Colorado Denver, Aurora, CO; 2Medicine/Cardiology, University of Colorado Denver, Aurora, CO; 3Allergy and Immunology, University of Colorado Denver, Aurora, CO. Purpose: MicroRNAs (miRs) are small noncoding 22 nucleotide RNAs capable of modulating the expression of many genes. The purpose of this study was to determine if circulating miRs are useful biomarkers of outcome in children with dilated cardiomyopathy (DCM). Methods and Materials: An array for 386 miRs was performed using the Applied Biosystems technology and the small RNA U6 was used as the endogenous control. Serum from 11 non-failing children (NF) and 34 children with DCM was analyzed. Serum was drawn from all DCM patients when hospitalized and undergoing heart transplant evaluation. The DCM patients (mean age 4.7 yrs, EF 24⫾9%) were categorized based on outcome: 25 required transplant and 4 died (Group 1) and 5 recovered (DCM-R).
69 Longitudinal Study of Pulmonary Microbial Dynamics in Lung Transplant Recipients with and without Bronchiolitis Obliterans Syndrome V. Poroyko,1 E. Semenyuk,2 Z. Xu,1 A. Sperling,1 A. Chong,1 M.-L. Alegre,1 E. Garrity,1 S. Bhorade.1 1Medicine, University of Chicago Medicine, Chicago, IL; 2Microbiology and Immunology, Loyola University Health System, Maywood, IL.
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
after HT predicted fatal and non-fatal cardiovascular (CV) events. We additionally analyzed the impact of metabolic risk factors on changes in IVUS measurements. Results: 107 consecutive patients receiving HT between 1999 and 2007 entered the study. During the 11 years of follow-up, incidence of CV death was 8⫾3% and of CV events was 26⫾6%. Between year 1 and 5, MIT and intimal volume increased, lumen volume decreased (Po0.001 for all), while vessel volume was unchanged. By Cox’s model, only MIT increase was associated with subsequent CV death (RR¼4.2 [1.212.1] per mm, P¼0.03) and CV events (RR¼2.6 [1.1-5.6] per mm; P¼0.03). By ROC curves, we found that a MIT change cut-off of 0.35 mm best identified patients at risk for CV death and events (Figure). Among the metabolic parameters, increasing triglycerides and HDL-cholesterol r65mg/dl predicted MIT increase Z 0.35 mm (Pr0.05). Conclusions: This study provides the first suggestive evidence that MIT increase represent a relevant prognostic marker also after the first year after HT. In addition, the finding that clinically relevant MIT is predicted by lipid pattern typical of insulin resistance, provide a strong rationale supporting aggressive therapeutic interventions against metabolic abnormalities mid and long-term after HT.
Purpose: The development of Bronchiolitis Obliterans Syndrome (BOS) has been previously linked to microbial pathogens within the transplanted lung. With advanced molecular technology, we are now able to further define microbial communities within the transplanted lung. We hypothesized that these microbial communities will be distinct in lung transplant recipients who develop BOS compared to those who remain stable. Methods and Materials: Eighteen lung transplant recipients were included in this analysis. Nine patients developed BOS within 2 years. Bronchoscopy with bronchoalveolar lavage (BAL) was performed at 1, 3, 6, and 12 months post transplant. Bacterial 16S rDNA extracted from the BAL fluid was amplified using barcoded primers and PCR products were pooled and sequenced using 454 pyrosequencing. All the sequence reads were denoised and clustered into similar operational taxonomic units. Taxonomy annotation was assigned according to Ribosomal Database Project. Results: The bacterial community of transplanted lungs was taxonomically diversified and consisted of micro-organisms belonging to 14 phyla. Interindividual variation of the microbial community was greater than intraindividual variation for all patients. There was a distinct difference in the microbial community at the phylum and class taxonomic level between BOS and non-BOS patients (po0.05). BOS patients had a greater predominance of the phylum Firmicutes and class Bacilli, while non-BOS patients had a greater predominance of phylum Proteobacteria and class Gammaproteobacteria. In a subset of these patients, the longitudinal patterns of bacterial dynamics were different in BOS and non-BOS patients. Conclusions: The pulmonary microbiota in lung transplant recipients is taxonomically diverse and dynamic over time and is distinct in patients who develop early BOS compared to those who remain stable. Our findings provide novel approaches to address the relationship between microbial communities and BOS development after lung transplantation.
70 Circulating microRNA: Prognostic Biomarker for Pediatric Heart Failure S.D. Miyamoto,1 V. Peterson,2 B. Freed,3 L. Cagle,3 B.L. Stauffer,2 C.C. Sucharov.2 1Pediatrics/Cardiology, University of Colorado Denver, Aurora, CO; 2Medicine/Cardiology, University of Colorado Denver, Aurora, CO; 3Allergy and Immunology, University of Colorado Denver, Aurora, CO. Purpose: MicroRNAs (miRs) are small noncoding 22 nucleotide RNAs capable of modulating the expression of many genes. The purpose of this study was to determine if circulating miRs are useful biomarkers of outcome in children with dilated cardiomyopathy (DCM). Methods and Materials: An array for 386 miRs was performed using the Applied Biosystems technology and the small RNA U6 was used as the endogenous control. Serum from 11 non-failing children (NF) and 34 children with DCM was analyzed. Serum was drawn from all DCM patients when hospitalized and undergoing heart transplant evaluation. The DCM patients (mean age 4.7 yrs, EF 24⫾9%) were categorized based on outcome: 25 required transplant and 4 died (Group 1) and 5 recovered (DCM-R).
69 Longitudinal Study of Pulmonary Microbial Dynamics in Lung Transplant Recipients with and without Bronchiolitis Obliterans Syndrome V. Poroyko,1 E. Semenyuk,2 Z. Xu,1 A. Sperling,1 A. Chong,1 M.-L. Alegre,1 E. Garrity,1 S. Bhorade.1 1Medicine, University of Chicago Medicine, Chicago, IL; 2Microbiology and Immunology, Loyola University Health System, Maywood, IL.