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Biomedical subjects

Gregory I Snell

Publications and source records attributed to Gregory I Snell.

At least 19 recordsLinked to original sources
PubMed2007

Feasibility and utility of a lung donor score: correlation with early post-transplant outcomes.

BACKGROUND: A lung donor score may provide a numerical value of overall donor lung "quality" to allow comparison among different organizations and research protocols. This study aims to develop a simple scoring system and investigate its applicability on predicting donor selection and early post-lung-transplant (LTx) outcomes. METHODS: Data of all donors referred to our institution in 2001 were initially analyzed to create a LTx donor score. Five domains, age, smoking history, chest X-ray, secretions, and arterial blood gas results, were included. A larger cohort of transplant recipients (years 2002 to 2005) was analyzed to validate the score against early post-LTx outcomes. RESULTS: In the initial 2001 cohort, 36 of 87 (41%) donors were used for 41 LTx (used group) and 51 (59%) were declined for medical (lung-exclusion group, n = 31) and general (general-exclusion group, n = 20) reasons. The median donor scores in the used, general-exclusion, and lung-exclusion groups were 2.0, 2.0, and 10.0, respectively (p < 0.0001). In multivariate analysis of the validation cohort, the donor score in bilateral LTx was significantly associated with post-transplant ratio of arterial oxygen tension and inspired oxygen fraction (coefficient = -16.19, p = 0.002), primary graft dysfunction grade (coefficient = 0.21, p < 0.0001), and intubation hours (coefficient = 0.05, p = 0.04); however, a significant association was not seen in single LTx. CONCLUSIONS: A proposed simple donor scoring system, based on five major donor variables available at the time of donor selection, may be useful for data comparison between specific centers, quality control, evaluative research, and clinical decision making in donor selection and management in LTx.

Adult↗
PubMed2006

Preliminary report of the safety and efficacy of hyperbaric oxygen therapy for specific complications of lung transplantation.

BACKGROUND: Lung transplantation (LTx) is a complex therapy requiring immunosuppression and is associated with significant infective morbidity and mortality. Hyperbaric oxygen (HBO) therapy has been used successfully in the treatment of specific serious infections, ischemic injuries and cerebral arterial gas embolism. The purpose of this study was to evaluate the efficacy and safety of HBO therapy after LTx, generally as indicated for refractory infectious complications. METHODS: This investigation was a retrospective study of all lung transplant recipients treated with HBO therapy at the Alfred Hospital between March 1990 and August 2005. RESULTS: In this study we describe 9 patients (1.7%) from a total of 544 overall lung transplants performed over the period. Indications included: sternal osteomyelitis (n = 4); refractory cellulitis (n = 2); refractory septic arthritis (n = 1); ischemic toes (n = 1); and cerebral arterial gas embolism (n = 1). The patients received 1 to 25 HBO treatments at 100% Fio(2) and 100 to 180 kPa for 100 minutes per treatment. The treatment was generally well tolerated, although 2 patients ceased therapy prematurely due to a seizure and ear barotrauma (n = 1 each). Five patients had complete resolution of these life-threatening complications. Long-term survival and graft function were excellent, although graft function temporarily fell. CONCLUSIONS: HBO is a safe therapy for traditional HBO indications after LTx and appears useful, particularly in the management of infectious complications, whereas other therapies have failed or are contraindicated.

Adult↗
PubMed2006

Evaluation of techniques for lung transplantation following donation after cardiac death.

BACKGROUND: Lung transplantation using "donation after cardiac death" donors is a potential means to alleviate the shortage of suitable donor lungs for transplantation, but the practicality and utility of the various possible techniques need to be clarified. METHODS: Using a dog model, we explored seven variations of standoff (ischemic) time (50 to 240 minutes), topical cooling (60 to 120 minutes), and flush cooling and cold storage (30 to 140 minutes) to mimic different human donor lung retrieval scenarios that can follow donation after cardiac death. The functional status of donation after cardiac death donor lungs was assessed initially with a 250 mL pulmonary arterial blood flush while ventilating with 100% oxygen and then on an ex-vivo perfusion rig for 120 minutes after retrieval. RESULTS: All lungs achieved an excellent pO2/FiO2 ratio ranging from 472 to 586 with stable pulmonary artery pressures and pulmonary vascular resistance and no net weight gain (952 +/- 221 g versus 1,006 +/- 235 g) during the 120-minute evaluation period. Initial blood flush correlated well with measured perfusion rig pO2 at 30 minutes (R2 = 0.63). CONCLUSIONS: This canine study suggests that lungs donated after cardiac death are reproducibly useable for transplantation with ischemic times of as long as 60 minutes. Although more study is needed, a blood flush evaluation is simple and may have a role as a secondary allograft assessment tool. The existing techniques of donor lung evaluation and preservation after donation following cardiac death thus appear both feasible and practical.

Animals↗
PubMed2006

Early outcomes comparing Perfadex, Euro-Collins, and Papworth solutions in lung transplantation.

BACKGROUND: Despite improved surgical techniques and medical management, primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after lung transplantation. Different types of lung preservation solutions have been developed and applied to clinical use; however, the relative clinical efficacy of these solutions to prevent PGD remains controversial. This study aimed to investigate the effect of the three solutions most commonly used (Perfadex [Vitrolife, Göteborg, Sweden], Papworth, and Euro-Collins [Baxter Healthcare, Old Toongabbie NSW, Australia]) on posttransplant outcomes. METHODS: Early outcomes from 157 consecutive lung transplants (113 bilateral and 44 single) performed at The Alfred Hospital were compared across three preservation solutions. RESULTS: Posttransplant oxygenation (p = 0.57), pulmonary vascular resistance (p = 0.34), intubation hours (p = 0.66), intensive care unit days (p = 0.34), severe PGD (grade 3) (p = 0.70), 30-day mortality (p = 0.87), and 3-month % predicted forced expiratory volume in 1 second (p = 0.58) were not statistically different; however, Perfadex trended toward superiority among the three solutions. After adjustment of donor, recipient, and operative factors in multivariate analysis, Perfadex was significantly associated with the prevention of moderate to severe PGD (grade 2 to 3) at 48 hours posttransplant (odds ratio = 0.26 [0.10 to 0.72], p < 0.01) compared with Papworth (odds ratio = 0.75 [0.32 to 1.75], p = 0.51) and Euro-Collins (reference) solutions. CONCLUSIONS: Although any advantageous effects of Perfadex on early posttransplant outcomes were generally subtle and statistically nonsignificant, Perfadex prevented moderate to severe PGD. Switching preservation solution from Euro-Collins (or Papworth) to Perfadex would appear to usefully contribute to a strategy to reduce PGD in lung transplantation.

Adult↗
PubMed2006

Everolimus in pulmonary transplantation: pharmacokinetics and exposure-response relationships.

BACKGROUND: In this study we evaluated exposure, safety and efficacy data from an international trial of everolimus. We sought to identify a tolerated and efficacious range for blood levels of this agent in maintenance lung transplant recipients. METHODS: In a randomized, double-blind, multicenter trial, 213 maintenance lung transplant recipients received either everolimus 1.5 mg twice daily (n = 101) or azathioprine 1 to 3 mg/kg/day (n = 112) with cyclosporine and corticosteroids. At 15 visits over the first 2 years of the trial, we obtained 826 everolimus trough (C0) blood samples. We used median-effect analysis to assess relationships between everolimus C0 vs efficacy and safety responses. RESULTS: Everolimus administration began at 1.5 mg twice daily and was progressively lowered over the first 2 months to an average of 1.2 +/- 0.4 mg twice daily, which was maintained thereafter. This dose yielded median C0 levels of 6.6 ng/ml (10th to 90th percentiles: 2.8 to 11.8 ng/ml). Over this range of everolimus C0, freedom from a decline in pulmonary function with bronchiolitis obliterans syndrome and freedom from biopsy-proven acute rejection were both > or = 88%. The incidence of increased cholesterol (> 6.5 mmol/liter), increased triglycerides (> 2.9 mmol/liter) and transiently decreased platelet count (< 100 x 10(9)/liter) rose significantly with increasing C0. Infections and drug-related adverse events were not significantly related to exposure. CONCLUSIONS: A tolerated and efficacious concentration range for everolimus in maintenance lung transplantation appears to be 3 to 12 ng/ml when used in conjunction with cyclosporine and corticosteroids. This range should be prospectively assessed with possible refinement as more clinical experience is gained.

Adult↗
PubMed2006

Definitions of primary graft dysfunction after lung transplantation: differences between bilateral and single lung transplantation.

OBJECTIVE: The primary graft dysfunction definition has been applied to both bilateral lung transplantation and single lung transplantation. However, the differences between bilateral and single lung transplantation in terms of primary graft dysfunction remain unknown. This study aims to investigate the features and utility of the new primary graft dysfunction grading system by comparing early outcomes from bilateral and single lung transplantation. METHODS: The primary graft dysfunction grade of 228 consecutive lung transplants (149 bilateral and 79 single lung transplants) at multiple postoperative time points was analyzed. Subgroup analysis with chronic obstructive pulmonary disease was performed to further validate the difference between bilateral lung transplantation and single lung transplantation. RESULTS: The percentage of grade 3 primary graft dysfunction in bilateral and single lung transplants was 32% and 37% at 0 hours (T0), 9% and 33% at 12 hours (T12), 7% and 26% at 24 hours (T24), and 9% and 18% at 72 hours (T72), respectively. The prevalence of the grade 3 primary graft dysfunction (T24) was significantly different between those undergoing bilateral lung transplantation and those undergoing single lung transplantation (P = .02). The primary graft dysfunction grade (T0) significantly correlated with the duration of intubation in both bilateral (r = 0.35, P < .0001) and single (r = 0.42, P = .001) lung transplantation and length of intensive care unit stay in both bilateral (r = 0.31, P = .0002) and single (r = 0.33, P = .006) lung transplantation. These differences were validated by the subgroup analysis. CONCLUSIONS: The prevalence of primary graft dysfunction grade is different between bilateral and single lung transplantation and varies with time. Although the primary graft dysfunction grade correlated with the early posttransplantation outcomes, for the purposes of description and further studies, primary graft dysfunction in bilateral and single lung transplantation should be considered separately.

Adult↗
PubMed2006

Unilateral radiographic abnormalities after bilateral lung transplantation: exclusion from the definition of primary graft dysfunction?

OBJECTIVES: Unilateral infiltrates on chest x-ray films are occasionally seen after bilateral lung transplantation. In the primary graft dysfunction grading system, the presence or absence of a radiographic abnormality is crucial in determining the incidence and severity of primary graft dysfunction. However, no consideration is given as to whether unilateral infiltrates have the same impact and relevance as bilateral infiltrates. This study aims to describe the incidence, features, and outcomes of posttransplant unilateral infiltrates and their effect on the novel primary graft dysfunction grading system. METHODS: Depending on posttransplant radiographic appearance, 144 patients who underwent bilateral lung transplantation were divided into 3 groups: no infiltrates (clear), unilateral infiltrates (unilateral), or bilateral infiltrates (bilateral). RESULTS: Radiographic abnormalities were seen in 43% of donors and 61% of posttransplant recipients (sensitivity = 76%, specificity = 50%). The percentage of recipients in the unilateral, clear, and bilateral groups was 26%, 39%, and 35%, respectively. Lower posttransplant oxygenation (P < .05), longer intubation hours, and more intensive care unit days (P < .0001) were seen in the bilateral compared with the unilateral and the clear groups. A significant difference in the prevalence of primary graft dysfunction (P < .0001) was seen, depending on whether unilateral infiltrates were included or excluded from the primary graft dysfunction grading. CONCLUSIONS: The incidence of unilateral infiltrates is relatively high after bilateral lung transplantation. The early posttransplant outcome of the unilateral infiltrates is similar to that in the group having a clear chest x-ray film and significantly better than that in those with bilateral infiltrates. In bilateral lung transplantation, only bilateral infiltrates should be used as part of the definition of primary graft dysfunction.

Adult↗
PubMed2005

High donor age, low donor oxygenation, and high recipient inotrope requirements predict early graft dysfunction in lung transplant recipients.

BACKGROUND: Early dysfunction in lung transplants is characterized by poor oxygenation, which may then lead to prolonged mechanical ventilation. This may be due to a combination of donor, recipient, and management factors. Our aim was to determine the incidence and severity of hypoxia and graft dysfunction and which factors were directly associated with poor oxygenation within the first 24 hours after lung transplantation. METHODS: A retrospective study of all 128 lung transplants between 1999 and 2002 was undertaken. Multiple linear regression analysis was performed to determine which donor, recipient, operative, and intensive care unit (ICU) parameters were associated with the worst recorded arterial blood gas partial pressure of oxygen (PAO2)/fraction of inspired oxygen (FIO2) ratio in the initial 24 hours after operation. RESULTS: Eighty-three percent of the patients (104 of 128) had a PAO2/FIO2 ratio below 300 within the first 24 hours post-transplantation, and 60% (77 of 128) had a PAO2/FIO2 ratio below 200. A high donor age (p = 0.004), low donor PAO2 (p = 0.007), and high post-operative inotrope requirements (p = 0.02) were correlated with a low PAO2/FIO2 ratio. Recipient diagnosis, ischemic time, use of cardiopulmonary bypass, fluid balance in the ICU, and cardiac index were not related. There was no difference in the long-term outcomes of patients with high or low PAO2/FIO2 ratios. CONCLUSIONS: A low PAO2/FIO2 ratio is a common finding in the first 24 hours after lung transplantation. Donor factors such as age and PAO2, and the need for increasing inotrope requirements in ICU predict early graft dysfunction and hypoxia.

APACHE↗
PubMed2005

Longitudinal comparisons of lymphocytes and subtypes between airway wall and bronchoalveolar lavage after human lung transplantation.

BACKGROUND: T lymphocytes are crucial in lung allorejection. The contribution of lymphocyte subtypes to the pathogenesis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) remains unclear. METHODS: Twenty-nine initially healthy lung transplant recipients underwent 136 bronchoscopic assessments, including bronchoalveolar lavage (BAL) (with flow cytometry) and endobronchial biopsies (EBB) (with immunohistochemistry) over 3 years of follow-up. RESULTS: Of the 29 patients studied over 3 years, 23 developed BOS category 0 p and 17 went on to BOS 1. Compared with controls, the BAL percentage of CD4 cells was lower and the percentage of CD8 cells was increased significantly early posttransplant. Subsequent BAL lymphocyte subtype changes with time, or with the development of BOS, were minimal. By contrast, the early posttransplant EBB lymphocyte numbers were normal (P>0.05 vs. controls); subsequently, CD3 and CD8 (but not CD4) cells were increased with time in patients who did not develop BOS (P<0.05) and, more strikingly, in patients who eventually developed BOS (P<0.01). Multivariate analyses suggested an association between BAL lymphocytes (percentage) and azathioprine dose, female gender, rejection grade A on transbronchial biopsies, and pre-BOS status, whereas EBB CD8 cell counts were associated with time posttransplant, pretransplant diagnosis, and rejection grade B on TBB. CONCLUSIONS: There is an early, persistent low percentage of BAL CD4 T cells, high BAL CD8 T cells, and progressively increasing airway wall CD3 and CD8 T cells with time posttransplant in healthy patients (but more predominantly in BOS patients) after transplantation. These immunopathologic changes may suggest that CD8 T cells could escape current immunosuppression and participate in chronic lung rejection.

Adult↗
PubMed2005

Chlamydia pneumoniae serology in donors and recipients and the risk of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a common late complication in lung transplant recipients (LTR). Chlamydia pneumoniae (C. pneumoniae) is a common but difficult to diagnose respiratory pathogen with a propensity to latency. METHODS: We studied the impact of C. pneumoniae on BOS development using donor-recipient serology obtained before transplantation in a cohort of 76 LTR. RESULTS: BOS was present in 29.9% patients (mean follow-up 866 days). High donor C. pneumoniae immunoglobulin (Ig)G titers were associated with BOS in the recipient (area under the curve [AUC] 0.71, 95% confidence interval [CI] 0.52-0.91, P=0.027), whereas high recipient titers were inversely associated with BOS (AUC 0.27, 95% CI 0.11-0.44, P=0.018). The risk of developing BOS was 75.0% in the case of a primary seromismatch for C. pneumoniae (D+/R-), whereas a reverse mismatch had a risk of 4.6% (likelihood ratio 9.8, P=0.02). In a multivariate model that included human leukocyte antigen matching, acute rejection and cytomegalovirus pneumonitis, C. pneumoniae IgG donor 32 or greater and C. pneumoniae IgG recipient 32 or greater remained positive and negative independent risk factors, respectively, for BOS in LTR. In the freedom from BOS analysis, BOS occurred more frequently and earlier in C. pneumoniae seropositive donors, and the reverse was true in seronegative recipients. CONCLUSION: C. pneumoniae serology in donor and recipient is associated with the development of BOS in LTR.

Adult↗
PubMed2005

Occlusion of a broncho-cutaneous fistula with endobronchial one-way valves.

Bronchopleural and broncho-cutaneous fistulas can be problematic after lobectomy for tumors or aspergillomas. Closure of the air leak and treatment of infection are essential to allow the fistula to heal. The initial treatment can usually proceed along standard lines, but if the fistula persists, then treatment can be problematic. This report is the first description of the use of multiple Emphasys Medical endobronchial valve prostheses (Emphasys Medical, Inc, CA) to control a previously intractable broncho-cutaneous fistula. The valves have been specifically designed for airway placement as part of a therapeutic approach to severe emphysema. The advantages of using valves in this situation are discussed.

Bronchial Fistula↗
PubMed2005

Airway vascular changes after lung transplant: potential contribution to the pathophysiology of bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains the primary factor limiting successful lung transplantation. In asthma and lung transplantation BOS-increased sub-mucosal vascularity has been shown to contribute to airflow limitation. Vascularity has 2 components: sprouting angiogenesis (more vessels) and microvascular enlargement (larger vessels). We hypothesized that the lack of a reanastomosed bronchial arterial blood supply at the time of transplant might stimulate angiogenesis and be a risk factor for subsequent BOS. METHODS: Twenty-seven initially stable lung transplant recipients (BOS 0) were recruited at 148 +/- 80 days post-transplant and underwent clinical and bronchoscopic longitudinal follow-up for at least 3 years. Eight remained stable and BOS developed in 19. Nine normal controls were also recruited. Airway vasculature was examined immunohistochemically in endobronchial biopsy (EBB) specimens with collagen IV antibody, quantified by computer image analysis, and expressed as average vessel size, vessel number, and overall vascularity. The effects of demographic, clinical, bronchoalveolar lavage (BAL), and EBB variables on airway vasculature were analyzed in a multivariate model. RESULTS: No significant differences in airway vascularity were found between stable and BOS lung transplant recipients cross-sectionally or longitudinally. However, both lung transplant groups at baseline showed significantly greater airway vascularity compared with normal controls (p < .05). Multivariate analysis suggested that the percentage of BAL CD3+ cells and acute rejection are the most influential variables on airway vasculature. CONCLUSIONS: This study suggests early and persistent airway vasculature changes occur in lung transplant recipients, mainly manifested as microvascular enlargement. Potentially this baseline change contributes to airway obstruction and also puts all lung transplant recipients at risk for further exponential loss of airway caliber with any subsequent airway inflammatory insult.

Adult↗
PubMed2005

Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation.

BACKGROUND: The significance of gastroesophageal reflux (GER) and aspiration are unclear in cystic fibrosis (CF) and may contribute to declining lung function before and after lung transplantation (LTx). METHODS: We sought to establish whether GER occurs in patients with CF on the LTx waiting list and after LTx. We then investigated whether GER correlates with patients' symptoms. Adults with CF on the waiting list and after LTx were prospectively recruited. Completion of a valid, structured symptom questionnaire was followed by ambulatory, dual-probe, 24-hour esophageal pH monitoring. RESULTS: Twenty-four patients were studied, including 11 (6 males) in the pre-LTx group and 13 (9 males) in the post-LTx group. The pre-LTx group was 29.3 +/- 8.2 years of age, and the post-LTx group was 32.7 +/- 8.2 years of age. DeMeester score (normal value <14.7) was 36.6 +/- 22.3 for the pre-LTx group and 40.0 +/- 37.3 for the post-LTx group. Proximal esophageal acid exposure was significantly higher in both CF groups compared with normal. Symptom scores (normal <4, range -2 to 18) were: pre-LTx group, 5.8 +/- 6.5; post-LTx group, 7.7 +/- 5.4. Percent forced expiratory volume in 1 second (FEV1%) predicted was: pre-LTx group, 31.3 +/- 7.8; post-LTx group, 65.2 +/- 29.3. In the pre-LTx group, 10 of 11 (90.9%) patients had significant GER on monitoring, including 4 (40%) with symptomatic GER and 6 (60%) with silent GER. In the post-LTx group, 11 of 13 (84.6%) had significant GER on monitoring, including 9 (82%) with symptomatic GER and 2 (18%) with silent GER. CONCLUSIONS: GER, symptomatic and silent, is a significant problem in CF. This condition should be aggressively treated and surgery should be considered if GER persists on re-testing.

Adolescent↗
PubMed2005

Early changes in basement membrane thickness in airway walls post-lung transplantation.

BACKGROUND: Identification of early histopathologic markers of future bronchiolitis obliterans syndrome (BOS) may enable preemptive targeted intervention, delaying and perhaps preventing the onset of BOS. This study aimed to determine if early changes in airway epithelial basement membrane thickness predisposes transplant recipients to the subsequent development of BOS. METHODS: Basement membrane thickness was measured in serial endobronchial biopsies taken from 29 initially stable lung transplant recipients (sLTR) recruited 148 +/- 80 days post-transplant and followed for 3 years. A further 2 years of clinical follow-up was undertaken without biopsies to follow lung function and define ultimate BOS status. Nine healthy subjects (non-atopic, non-asthmatic) were recruited as controls. Sections of paraffinized endobronchial biopsies were stained for collagen type I immunohistochemically, and basement membrane thickness was assessed by computer image analysis. RESULTS: BOS developed in 21 of 29 patients in the 5 years of follow-up, 16 of which had endobronchial biopsies available for analysis before BOS developed (ever-BOS). The first endobronchial biopsies showed increased BMT in the combined sLTR and ever-BOS patients compared with the controls. This initial increase in basement membrane thickness resolved to normal levels within 300 days post-transplant, with a strong negative correlation (r2 = 0.424, p < 0.0001) of basement membrane thickness vs time. Paradoxically, the sLTR tended to have the greatest basement membrane thickness at baseline. CONCLUSION: An initial increase in basement membrane thickness is seen in the airway walls of all lung transplant recipients. This is transient and does not appear to be a risk factor for the subsequent development of BOS in lung allograft recipients.

Adolescent↗
PubMed2005

Evaluation of the oxygenation ratio in the definition of early graft dysfunction after lung transplantation.

OBJECTIVE: Despite the clinical importance of early graft dysfunction, no standardized definition is available. We hypothesized that the arterial blood gas oxygen tension/fraction of inspired oxygen ratio (PaO2 /FIO2) would prove to be a useful marker for predicting subsequent outcomes of early graft dysfunction. The aims of this study were to define the prevalence of various ranges of PaO2 /FIO2 over the first 48 hours after lung transplantation and to evaluate which measurement using the PaO2 /FIO2 best correlates with the duration of intubation, the length of stay in the intensive care unit, and 30-day mortality, which are important alternative indicators of early graft performance. METHODS: A retrospective study was performed that included all 68 bilateral single-lung transplantations at The Alfred Hospital from January 2000 to December 2002. RESULTS: PaO2 /FIO2 at 6 and 12 hours after admission to the intensive care unit was significantly associated with the duration of intubation ( r = -0.44; P < .001 and r = -0.48; P < .001, respectively), and PaO2 /FIO2 at 6 and 24 hours was also significantly associated with the length of intensive care unit stay ( r = -0.38; P = .002 and r = -0.44; P = .001, respectively). Thirty-day mortality was significantly associated with a lower PaO2 /FIO2 at 6 hours (219 +/- 93 vs 306 +/- 101; P = .03). CONCLUSIONS: PaO2 /FIO2 taken between 6 and 12 hours after transplantation is a useful marker associated with lung transplantation outcomes. There is the potential for therapeutic interventions during this time that may be able to enhance PaO2 /FIO2 by 12 hours and improve subsequent outcomes.

Adult↗
PubMed2005

Unexpected donor pulmonary embolism affects early outcomes after lung transplantation: a major mechanism of primary graft failure?

OBJECTIVE: Primary graft failure remains a significant cause of morbidity and mortality after lung transplantation, and its mechanism is not understood. Previously 2 case reports described fatal primary graft failure due to donor-related unexpected pulmonary embolism. This study investigated the incidence, early outcome, and risk factors of unexpected pulmonary embolism in lung transplantation. METHODS: An exploratory retrograde donor lung flush before implantation to diagnose pulmonary embolism (emboli group) or no pulmonary embolism (no-emboli group) was performed in 74 of 122 consecutive lung transplantations. RESULTS: The incidence of macroscopic unexpected pulmonary embolism was 38% (28% clot and 9% fat). In the emboli group, significantly decreased oxygenation (P < .05), increased pulmonary vascular resistance (P < .001), an increased proportion of opacity on chest radiograph (P = .03), prolonged intubation (P < .001) and intensive care unit stay (P < .01), and decreased 1-year survival (P = .03) were seen after transplantation. In multivariate analysis, pulmonary embolism was an independent risk factor for prolonged intubation (hazard ratio, 2.42; P < .01). In logistic regression, death due to trauma with fracture and a smoking history of more than 20 pack-years were significant donor risk factors for pulmonary embolism (adjusted odds ratio, 8.77 and 5.64; P = .02 and .04, respectively). No deleterious effects of the exploratory flush were seen. CONCLUSIONS: Unexpected pulmonary embolism is relatively common, is potentially predicted by donor history (but not by arterial blood gas analysis or chest radiograph), and is associated with primary graft failure. Donor lungs with risk factors of pulmonary embolism should undergo an exploratory flush. When pulmonary embolism is diagnosed, further therapeutic strategies must be considered.

Adult↗
PubMed2005

Everolimus alters the bronchoalveolar lavage and endobronchial biopsy immunologic profile post-human lung transplantation.

Everolimus has recently shown promise in terms of short- and long-term clinical lung transplant outcomes. This study aims to determine the altered lung allograft cellular and cytokine mileau when everolimus is substituted for azathioprine (AZA). Twenty-three stable lung transplantation (LTx) recipients were randomized in a double-blinded study to receive everolimus (13) or AZA (10) plus standard cyclosporine/prednisolone. Bronchoalveolar lavage (BAL) and endobronchial biopsies (EBB) were performed on three occasions (T(0)-T(2)) to elucidate cellular and cytokine profiles via immunocytochemistry, immunohistology and enzyme-linked immunosorbent assay (ELISA) techniques. There were no group differences for demographics or clinical events throughout the study nor baseline cellular/cytokine differences. BAL lymphocyte percentage fell in the AZA group by T(2) (p = 0.05). BAL and EBB CD4 measures significantly declined in the everolimus group by T(2) (p < 0.05). EBB neutrophils rose significantly in the AZA group, with a fall in the everolimus group resulting in a significant difference at T(2) (p = 0.01). In conclusion, everolimus has contributed to potentially important differences in BAL and EBB cellular profiles.

Anti-Inflammatory Agents↗