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Jason D Christie

Publications and source records attributed to Jason D Christie.

At least 19 recordsLinked to original sources
PubMed2026

Idiopathic pulmonary fibrosis risk loci in East Asian populations mirror those of European populations.

RATIONALE: Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations. OBJECTIVES: To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations. METHODS: We included 1026 patients with IPF and compared them to 1723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject. MEASUREMENTS AND MAIN RESULTS: We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations. CONCLUSIONS: We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

Aged↗
PubMed2024

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

Humans↗
PubMed2006

Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction.

BACKGROUND: Acute lung injury is characterized by hypercoagulability and impaired fibrinolysis. We hypothesized that lower protein C and higher type 1 plasminogen activator inhibitor (PAI-1) levels in plasma would be associated with primary graft dysfunction (PGD) after lung transplantation. DESIGN: Prospective, multicenter cohort study. METHODS: We measured plasma levels of protein C and PAI-1 before lung transplantation and 6, 24, 48, and 72 h after allograft reperfusion in 128 lung transplant recipients at six centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) 72 h after transplantation. Biomarker profiles were evaluated using logistic regression and generalized estimating equations. RESULTS: Patients who developed PGD had lower protein C levels 24 h posttransplantation than did patients without PGD (mean +/- SD [relative to control]: 64 +/- 27 vs. 92 +/- 41%, respectively; p = 0.002). Patients with PGD also had PAI-1 levels that were almost double those of patients without PGD at 24 h (213 +/- 144 vs. 117 +/- 89 ng/ml, respectively; p < 0.001). Throughout the 72-h postoperative period, protein C levels were significantly lower (p = 0.007) and PAI-1 levels were higher (p = 0.026) in subjects with PGD than in others. These differences persisted despite adjustment for potential confounders in multivariate analyses. Higher recipient pulmonary artery pressures, measured immediately pretransplantation, were associated with higher PAI-1 levels and increased risk of PGD. CONCLUSION: Lower postoperative protein C and higher PAI-1 plasma levels are associated with PGD after lung transplantation. Impaired fibrinolysis and enhanced coagulation may be important in PGD pathogenesis.

Biomarkers↗
PubMed2006

Multiple variables affecting blood usage in lung transplantation.

BACKGROUND: A few publications have reported on the role of variables affecting blood component usage during lung transplantation. METHODS: Transfusion records for lung transplantation patients at the Hospital of the University of Pennsylvania (November 1991 to July 2004) were reviewed. Bivariate analyses and regression models were used to correlate usage of packed red blood cells (RBC), fresh-frozen plasma (FFP) and platelets (PLT) with variables such as disease, number of pulmonary lobes (1 or 2), cardiopulmonary bypass (CPB) status and time on bypass. RESULTS: Among 376 patients examined during the study period, blood product usage (in units) was significantly higher in double- than in single-lung recipients (RBC, 5.76 vs 1.21; FFP, 5.55 vs 1.10; PLT, 1.15 vs 0.16; p < 0.001). Patients on CPB also used significantly more units (RBC, 8.28 vs 1.45; FFP, 9.70 vs 0.73; PLT, 1.86 vs 0.14; p < 0.001), correlating with time on bypass. Patients transplanted for Eisenmenger syndrome (ES) and cystic fibrosis (CF) received significantly more blood products than those transplanted for other diseases (RBC, ES = 17.91 vs CF = 7.31 vs all others <2.00; FFP, ES = 19.18 vs CF = 5.72 vs others <2.00; PLT, ES = 4.73 vs CF = 1.22 vs others <0.40; p < 0.001). A regression model identified variables predictive of blood product usage, including the number of lungs transplanted, CPB status, disease and patient age. CONCLUSIONS: Patients receiving double-lung transplantations, on CPB, or transplanted for ES and CF exhibited a very highly statistically significant demand (p < 0.001) for more blood products. Additional selected variables differentially predicted usage. These data will help transplant surgeons and transfusion medicine specialists better anticipate and prepare blood products for use in lung transplantation.

Adult↗
PubMed2006

Formation and validation of a telephone battery to assess cognitive function in acute respiratory distress syndrome survivors.

PURPOSE: Describe initial development and validation of a test battery composed of established instruments designed to detect, via telephone interview, cognitive abnormalities in survivors of acute respiratory distress syndrome. METHODS: Two cross-sectional studies were performed, including the following phases: (1) initial battery construction, (2) feasibility, (3) item reduction, (4) convergent and divergent validity, and (5) telephone administration compared with in-face interviews in a separate population. RESULTS: There was a broad range of cognitive function detected in the derivation population, and all subjects completed the interview. There was convergence of cognitive impairment with moderate/severe anxiety (P = .008), the Sickness Impact Profile Psychosocial Summary Score (mean difference, 15.3; 95% CI, 7.74-22.9; P = .0001), and the mental health domains of the Short Form 36. Subjects with cognitive impairment had no detectable difference in the physical function domains of the Short Form 36. When administered to the validation population, telephone tests of memory, attention, reasoning, and executive functions had good intraclass correlation with the in-face interviews (P < .01). CONCLUSIONS: Detection of cognitive abnormalities in acute respiratory distress syndrome survivors using a telephone-administered test battery derived from standard cognitive tests is feasible and has evidence of construct validity. This battery may be useful as a research tool when in-face interviews are not feasible.

Adult↗
PubMed2006

Evaluation of a new method for measurement of minute ventilation recovery time.

PURPOSE: To determine if the measurement of minute ventilation recovery time (V (E)RT), a recently proposed predictor of extubation outcome, can be reproduced using a more practical, simpler method. METHODS: A case series with convenience sampling was performed in the surgical intensive care unit of a tertiary-care hospital. Nineteen patients were enrolled during weaning from mechanical ventilation, prior to the initial extubation attempt. Within-subject comparisons of V (E)RT were performed, using 2 alternative methods for measuring baseline V (E) and one alternative method for determining the threshold for recovery of V (E) during the final spontaneous breathing trial prior to extubation. Comparison methods for baseline V (E) included an 8-hour average and the last V (E) measurement prior to the spontaneous breathing trial. The alternative threshold for defining recovery of V (E) was 100% of the baseline value (vs 110% in the original method). RESULTS: The study subjects were primarily cardiac surgery patients (63%) and were ventilated for a median of 5 days prior to extubation. V (E)RT calculated using the 8-hour average or the last V (E) measurement prior to the spontaneous breathing trial as baseline, and a threshold of 100% of baseline V (E) to define recovery most closely approximated V (E)RT obtained by the original method and similarly classified patients at high risk for reintubation (kappa statistic = 0.78 +/- 0.2). CONCLUSIONS: V (E)RT can be determined using a simpler method for measuring both baseline V (E) and the recovery threshold. These methodological modifications may increase the feasibility of measuring V (E)RT, while reproducing the results obtained by the original method.

Adult↗
PubMed2006

Change in forced expiratory time and spirometric performance during a single pulmonary function testing session.

BACKGROUND: Among patients with obstructive lung disease, the correlation between clinical improvement and bronchodilator response is poor. Forced expiratory time (FET) may explain some discrepancy, but FET has received little attention. METHODS: We analyzed change in FET during the 3 initial satisfactory flow-volume loops in 102 consecutive patients, 37 with normal spirometry and 65 with airflow obstruction referred to a Veterans Administration pulmonary function testing (PFT) laboratory over 5 months. Patients included both PFT-naïve and PFT-experienced individuals. We also evaluated the relationship between FET and spirometric performance (sum of forced expiratory volume in the first second and forced vital capacity) and the effect of inhaled bronchodilator on FET among patients with airflow obstruction. RESULTS: Normals and patients with airflow obstruction showed significant increments in FET and in spirometric performance during the 3 initial successive pre-bronchodilator attempts (p < 0.001 for both groups). This was true for PFT-naïve and PFT-experienced individuals. There were significant associations between increments in FET and improvements in spirometric performance in all subgroups. After inhaled bronchodilator there was a further FET increment among patients with airflow obstruction (p = 0.009), but there was no significant difference between bronchodilator responders and nonresponders. CONCLUSIONS: Patients with normal pulmonary function and those with obstruction develop longer FET during the initial phases of spirometric testing, regardless of previous PFT experience. Longer FET is associated with better spirometric performance. Bronchodilator administration is associated with modest prolongation of FET, but change in FET did not help identify bronchodilator responders.

Adult↗
PubMed2005

The effect of primary graft dysfunction on survival after lung transplantation.

RATIONALE: Primary graft dysfunction is a severe acute lung injury syndrome after lung transplantation. Long-term outcomes of subjects with primary graft dysfunction have not been studied. OBJECTIVES: We sought to test the relationship of primary graft dysfunction with both short- and long-term mortality using a large registry. METHODS: We used data collected on 5,262 patients in the United Network for Organ Sharing/International Society of Heart and Lung Transplantation registry between 1994 and 2000. We assessed outcomes in all subjects; to assess potential bias from the effects of early mortality, we also evaluated subjects who survived at least 1 year, using Cox proportional hazards models with time-varying covariates. MAIN RESULTS: The overall incidence of primary graft dysfunction was 10.2% (95% confidence intervals [CI], 9.2, 10.9). The incidence did not vary by year over the period of observation (p = 0.22). All-cause mortality at 30 days was 42.1% for primary graft dysfunction versus 6.1% in patients without graft dysfunction (relative risk = 6.95; 95% CI, 5.98, 8.08; p < 0.001); among subjects who died by 30 days, 43.6% had primary graft dysfunction. Among patients surviving at least 1 year, those who had primary graft dysfunction had significantly worse survival over ensuing years (hazard ratio, 1.35; 95% CI, 1.07, 1.70; p = 0.011). Adjustment for clinical variables including bronchiolitis obliterans syndrome did not change this relationship. CONCLUSION: Primary graft dysfunction contributes to nearly half of the short-term mortality after lung transplantation. Survivors of primary graft dysfunction have increased risk of death extending beyond the first post-transplant year.

Cause of Death↗
PubMed2005

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.

Administration, Inhalation↗
PubMed2005

Microarrays.

Explore the source record for details and available documents.

Critical Illness↗
PubMed2005

Impact of primary graft failure on outcomes following lung transplantation.

STUDY OBJECTIVES: Primary graft failure (PGF) is a severe acute lung injury syndrome that occurs following lung transplantation. We compared the clinical outcomes of patients who developed PGF with those who did not. METHODS: We conducted a retrospective cohort study including 255 consecutive lung transplant procedures. PGF was defined as (1) diffuse alveolar opacities developing within 72 h of transplantation, (2) an arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio of < 200 beyond 48 h postoperatively, and (3) no other secondary cause of graft dysfunction. PGF was tested for acceptance with 30-day and all-cause hospital mortality rates, overall survival, hospital length of stay (HLOS), duration of mechanical ventilation, and best 6-min walk test (6MWT) distance achieved within 12 months. SETTING: Academic medical center. RESULTS: The overall incidence of PGF was 11.8% (95% confidence interval [CI], 7.9 to 15.9%). The all-cause mortality rate at 30 days was 63.3% in patients with PGF and 8.8% in patients without PGF (relative risk [RR], 7.15; 95% CI, 4.34 to 11.80%; p < 0.001). A total of 73.3% of patients with PGF died during hospitalization vs 14.2% of patients without PGF (RR, 5.18%; 95% CI, 3.51 to 7.63; p < 0.001). The median HLOS in 30-day survivors was 47 days in patients with PGF vs 15 days in those without PGF (p < 0.001), and the mean duration of mechanical ventilation was 15 days in patients with PGF vs 1 day in those without PGF (p < 0.001). By 12 months, a total of 28.5% of survivors with PGF achieved a normal age-appropriate 6MWT distance vs 71.4% of survivors without PGF at 12 months (p = 0.014). The median best 6MWT distance achieved within the first 12 months was 1,196 feet in patients with PGF vs 1,546 feet in those without PGF (p = 0.009). CONCLUSIONS: PGF has a significant impact on mortality, HLOS, and duration of mechanical ventilation following lung transplantation. Survivors of PGF have a protracted recovery with impaired physical function up to 1 year following transplantation.

Exercise Test↗
PubMed2005

Relationship of environmental exposures to the clinical phenotype of sarcoidosis.

STUDY OBJECTIVES: Sarcoidosis is a granulomatous disorder with heterogeneous clinical manifestations, which are potentially reflective of a syndrome with different etiologies leading to similar histologic findings. We examined the relationship between environmental and occupational exposures, and the clinical phenotype of sarcoidosis. DESIGN: We performed a cross-sectional study of incident sarcoidosis cases that had been identified by A Case Control Etiologic Study of Sarcoidosis. Subjects were categorized into the following two groups: (1) pulmonary-only disease; and (2) systemic disease (with or without pulmonary involvement). Logistic regression was used to examine the associations of candidate exposures with clinical phenotype. SETTING: Ten academic medical centers across the United States. PATIENTS: The current study included 718 subjects in whom sarcoidosis had been diagnosed within 6 months of study enrollment. Patients met the following criteria prior to enrollment: (1) tissue confirmation of noncaseating granulomas on tissue biopsy on one or more organs within 6 months of study enrollment with negative stains for acid-fast bacilli and fungus; (2) clinical signs or symptoms that were consistent with sarcoidosis; (3) no other obvious explanation for the granulomatous disease; and (4) age > 18 years. MEASUREMENTS AND RESULTS: Several exposures were associated with significantly less likelihood of having extrapulmonary disease in multivariate analysis, including agricultural organic dusts and wood burning. The effects of many of these exposures were significantly different in patients of different self-defined race. CONCLUSIONS: The differentiation of sarcoidosis subjects on the basis of clinical phenotypes suggests that these subgroups may have unique environmental exposure associations. Self-defined race may play a role in the determination of the effect of certain exposures on disease phenotypes.

Adult↗
PubMed2005

Measurement of a baseline minute ventilation for the calculation of minute ventilation recovery time: is a subjective method reliable?

BACKGROUND: Minute ventilation recovery time is a new predictor of extubation outcome that uses a subjective method for the determination of baseline minute ventilation (V(E)) during its measurement. The purpose of the current study is to evaluate the inter-rater reliability of this subjective method for determining baseline V(E). METHODS: Three critical-care physicians served as independent readers. Each was trained with 5 practice V(E) trends, using the published method for determining baseline V(E), defined as the lowest, stable nadir lasting 15-30 min prior to the final weaning trial before extubation. Readers then determined baseline V(E) prospectively from an 8-hour V(E) trend for 19 patients who were weaning from mechanical ventilation in the surgical intensive care unit of a tertiary care hospital. Each V(E) trend was an objective recording of V(E) every 15 min for 8 hours, immediately prior to the final weaning trial before extubation. RESULTS: There was excellent inter-rater reliability between trained readers for determination of a subjective V(E) baseline. Baseline V(E) was within 1 L/min for 15/19 patients (79%). Intra-class correlation across the 3 readers was 0.92 (p < 0.01). Tukey's test revealed no significant variability between readers (p > 0.5), and Spearman correlations between all reader pairs were significant (p < 0.01). CONCLUSION: After minimal training, readers can reliably determine a subjective baseline V(E). This study validates the original methodology for determining baseline V(E), an essential step in the measurement of minute ventilation recovery time.

Aged↗
PubMed2004

Genetic epidemiology of acute lung injury: choosing the right candidate genes is the first step.

In an innovative scientific review in this issue, Grigoryev and colleagues report a method for choosing candidate genes for acute lung injury (ALI) based on gene expression data derived from multiple animal models of mechanical ventilation and shear stress. The authors conclude there are five key biologic processes that warrant further investigation: inflammatory and immune responses, cell proliferation, chemotaxis, and blood coagulation. This review represents an important first step toward studying the genetic epidemiology of ventilator-induced lung injury and ALI. The application of these findings to future human studies of the genetic influence on ALI risks and outcomes is discussed here.

Animals↗
PubMed2004

The outcome of extubation failure in a community hospital intensive care unit: a cohort study.

INTRODUCTION: Extubation failure has been associated with poor intensive care unit (ICU) and hospital outcomes in tertiary care medical centers. Given the large proportion of critical care delivered in the community setting, our purpose was to determine the impact of extubation failure on patient outcomes in a community hospital ICU. METHODS: A retrospective cohort study was performed using data gathered in a 16-bed medical/surgical ICU in a community hospital. During 30 months, all patients with acute respiratory failure admitted to the ICU were included in the source population if they were mechanically ventilated by endotracheal tube for more than 12 hours. Extubation failure was defined as reinstitution of mechanical ventilation within 72 hours (n = 60), and the control cohort included patients who were successfully extubated at 72 hours (n = 93). RESULTS: The primary outcome was total ICU length of stay after the initial extubation. Secondary outcomes were total hospital length of stay after the initial extubation, ICU mortality, hospital mortality, and total hospital cost. Patient groups were similar in terms of age, sex, and severity of illness, as assessed using admission Acute Physiology and Chronic Health Evaluation II score (P > 0.05). Both ICU (1.0 versus 10 days; P < 0.01) and hospital length of stay (6.0 versus 17 days; P < 0.01) after initial extubation were significantly longer in reintubated patients. ICU mortality was significantly higher in patients who failed extubation (odds ratio = 12.2, 95% confidence interval [CI] = 1.5-101; P < 0.05), but there was no significant difference in hospital mortality (odds ratio = 2.1, 95% CI = 0.8-5.4; P < 0.15). Total hospital costs (estimated from direct and indirect charges) were significantly increased by a mean of 33,926 US dollars (95% CI = 22,573 US dollars - 45,280 US dollars; P < 0.01). CONCLUSION: Extubation failure in a community hospital is univariately associated with prolonged inpatient care and significantly increased cost. Corroborating data from tertiary care centers, these adverse outcomes highlight the importance of accurate predictors of extubation outcome.

APACHE↗