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G A Patterson

Publications and source records attributed to G A Patterson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lung transplantation: current status and future prospects.

Lung transplantation recently marked its 35th anniversary. The period has been marked by 20 years of initially slow progress followed by 15 years of explosive growth and success. In 1997 the number of lung and heart-lung transplants exceeded 1000 in the United States and 1400 worldwide. Current 1-year survival exceeds 75% for most diagnoses. Functional results are excellent and durable with first second expired volume (FEV(1)) improving from 15% to 20% of the predicted normal preoperatively to 75% to 80% of the predicted normal postoperatively in most diagnoses. Problems facing lung transplant programs during the next century include the unavailability of graft lung donors, technical limitations of explanted graft lung preservation, and the prevention and treatment of bronchiolitis obliterans syndrome. Current status and future trends for lung transplantation are reviewed.

Cryptogenic Organizing Pneumonia↗
PubMed1999

Gene transfer of heat shock protein 70 protects lung grafts from ischemia-reperfusion injury.

BACKGROUND: We recently demonstrated that heat stress induction of heat shock protein 70 (HSP70) in donor animals before harvest decreases posttransplant ischemia-reperfusion injury in preserved rat lung isografts. The purpose of this study was to investigate the feasibility of HSP70 gene transfection into rat lung isografts using an adenoviral vector, and to study the effects of gene expression on subsequent ischemia-reperfusion injury. METHODS: In preliminary studies to determine the optimal titer, animals were injected with various titers of adenovirus-HSP70 (saline, 5 x 10(9), 1 x 10(10), and 2 x 10(10) plaque forming units [pfu]) and sacrificed 5 days after injection. To determine the optimal exposure time, animals were sacrificed at different times (0, 6, 24, and 72 hours) after intravenous injection of adenovirus-HSP70. In a subsequent series of transplant experiments, donors were allocated to three groups according to transfection strategy. Group 1 (n = 8) donors received 5 x 10(9) pfu adenovirus-HSP70 intravenously, group 2 (n = 7) donors received 5 x 10(9) pfu adenovirus-beta-galactosidase (as a virus control), and group 3 (n = 7) donors received saline and served as a negative control. Twenty-four hours after treatment all grafts were harvested and stored for 18 hours before orthotopic left lung transplantation. Twenty-four hours after implantation animals were sacrificed for assessment. The expression of HSP70 was assessed by Western blot analysis. RESULTS: In preliminary studies, HSP70 was detectable even at low titers (5 x 10(9) pfu) of adenovirus-HSP70, and was detectable at low levels as early as 6 hours after intravenous administration. Heat shock protein 70 expression was maximal at 24 hours. In transplant experiments, Western blot analysis showed that overexpression of HSP70 occurred in the HSP70-transfected lungs. The mean arterial oxygenation 24 hours after reperfusion in group 1 was superior in comparison with other groups (p < 0.05). Wet to dry weight ratio (p < 0.05) and myeloperoxidase activity (p < 0.05) were also significantly less in group 1 grafts compared with the other groups. CONCLUSIONS: This study demonstrates that in vivo, donor adenovirus-mediated gene transfer of HSP70 decreases subsequent ischemia-reperfusion injury in rat lung isografts.

Adenoviridae↗
PubMed1999

Favorable results after sleeve lobectomy or bronchoplasty for bronchial malignancies.

BACKGROUND: Sleeve lobectomy and bronchoplasty are established alternatives to pneumonectomy for bronchial malignancies involving a main bronchus. However, potential bronchial anastomotic complications have deterred the general application of these types of resection. Some reports have contained a mixture of non-small cell lung cancer (NSCLC) and tumors of low-grade malignancy, making it difficult to assess the long-term results of these procedures as an alternative to pneumonectomy for lung cancer. METHODS: We retrospectively reviewed our experience with sleeve lobectomy and bronchoplasty for bronchial malignancies from January 1988 to September 1998 separating NSCLC (n = 58) from tumors of low-grade malignancy (n = 19). We compared the overall results between sleeve lobectomy and pneumonectomy (n = 142) performed for NSCLC over the same time interval. RESULTS: For NSCLC, after sleeve lobectomy, the operative mortality was 5.2% (3 of 58 patients) and the overall 5-year actuarial survival was 37.5%. After pneumonectomy, the operative mortality was 4.9% (7 of 142 patients) and the overall 5-year actuarial survival was 35.8%. For tumors with low-grade malignancy, there was no operative mortality after sleeve lobectomy or bronchoplasty and the 5-year actuarial survival was 100%. Major bronchial anastomotic complications occurred in 3 patients among the 77 patients who underwent sleeve resection. CONCLUSIONS: Sleeve resection can be performed with a low risk of bronchial anastomotic complication. The long-term survival after sleeve resection for NSCLC is similar to pneumonectomy. Excellent results are obtained after sleeve resection for low-grade malignancies.

Adenocarcinoma↗
PubMed1999

Ex vivo transfection of pulmonary artery segments in lung isografts.

BACKGROUND: Gene transfer to lung grafts may be useful in ameliorating ischemia-reperfusion injury and rejection. Proximal pulmonary artery endothelial transfection may provide beneficial downstream effects on the whole lung graft. We have already demonstrated the feasibility of in vivo and ex vivo transfection in proximal pulmonary artery segments of rat lung grafts. The aim of this study was to determine the optimal conditions for and duration of transfection. METHODS: Orthotopic left lung transplantation was performed in F344 rats after donor lung proximal pulmonary artery segments were isolated and injected with lipid 67/DOPE-chloramphenicol acetyl transferase (CAT) complementary deoxyribonucleic acid construct. Effect of exposure time was studied by exposing donor pulmonary artery segments to the construct for 0, 30, and 60 minutes prior to transplantation. In another series of experiments, pulmonary artery segments were exposed to the construct for 60 minutes prior to transplantation. Onset and duration of gene expression were determined after sacrificing animals at 3, 6, 12, and 24 hours and 3 days as well as 1 week, 2, 4, and 8 weeks after transplantation. Effect of exposure temperature was studied by exposing pulmonary artery segments to the construct for 60 minutes at 4 degrees, 10 degrees, and 23 degrees C. These recipients were sacrificed on postoperative day 3. Effect of exposure pressure was studied by using two volumes of the construct (0.01 and 0.03 mL). These recipients were sacrificed on postoperative day 3. Transgene expression was assessed by chloramphenicol acetyl transferase activity assay. RESULTS: Transgene expression was similar after 30- and 60-minute exposure. Transgene expression was evident within 3 to 6 hours after operation and persisted at 8 weeks after operation. Expression was detected at all temperatures and was equivalent at both exposure pressures. CONCLUSIONS: Gene transfection into graft pulmonary artery segments is possible under a range of conditions applicable to clinical lung transplantation.

Animals↗
PubMed1999

Transfection of pulmonary artery segments in lung isografts during storage.

BACKGROUND: Proximal pulmonary artery segment (PPAS) endothelial transfection of lung grafts may be useful in ameliorating ischemia-reperfusion injury and rejection and may provide beneficial downstream effects on the whole lung graft. Transfection immediately after lung transplantation may be efficacious in ameliorating allograft dysfunction after transplantation. METHODS: In F344 rats, the PPAS was isolated and injected with 0.03 mL of GL-67/DOPE-chloramphenicol acetyl transferase (CAT) plasmid DNA. The PPASs were exposed for 60 minutes at several temperatures. The lung grafts were stored in saline solution (group 1, n = 24) or LPDG solution (group 2, n = 27) for 12 or 24 hours at 4 degrees to 37 degrees C. In group 3 (n = 42), PPASs were stored in endothelial cell culture medium and incubated at 10 degrees or 37 degrees C in a carbon dioxide incubator for 3 to 72 hours. Group 4 (n = 18) served as transplanted controls; after 3 to 24 hours' preservation at 4 degrees C in LPDG solution, lung grafts were transplanted. Transgene expression of PPASs was assessed with two CAT activity assays, thin-layer chromatography enzyme-linked immunosorbent assay and immediately after the preservation period (groups 1 to 3) or 24 hours after transplantation (group 4). RESULTS: In group 1, transgene expression did not appear. In groups 2 and 3, transgene expression was apparent after any storage duration at 37 degrees C. Transgene expression increased successively with longer storage periods. In group 4, transgene expression was detected after any storage duration. The enzyme-linked immunosorbent assay is able to quantify the expression of CAT activity, but thin-layer chromatography is more sensitive. CONCLUSIONS: Transgene expression did not occur during conventional cold storage. Transgene expression in rat PPASs during storage is possible with warm storage (37 degrees C) and appropriate storage solution.

Animals↗
PubMed1999

Endobronchial transfection of naked TGF-beta1 cDNA attenuates acute lung rejection.

BACKGROUND: We investigated endobronchial transfection of CAT and TGF-beta1 cDNA selectively delivered to the lung graft with or without liposomes. METHODS: Phase I: F344 rats received 130 microg of naked plasmid pCF1-CAT or complexed to liposome GL67 via left main bronchus instillation. Rats were awakened (pCF1-CAT, n = 4; GL67:pCF1-CAT, n = 4) or served as donors in an isogenic transplant (pCF1-CAT, n = 5; GL67:pCF1-CAT, n = 5). ELISA was performed on lungs, hearts, and livers on POD 2. Phase II: BN lungs received TGF-beta1 sense (n = 6); antisense (n = 5); GL67:TGF-beta1 sense (n = 10); or saline solution (n = 10). F344 recipients were sacrificed on POD 5. The arterial pO2 and rejection were assessed. RT-PCR for murine TGF-beta1 was performed. RESULTS: Phase I: CAT expression was 519+/-287 pg and 63+/-68 with pCF1-CAT and 104+/-67 and 37+/-45 with GL67:pCF1-CAT, respectively, in the non-transplant and in the transplant setting. No protein was detected in the hearts, livers, and in the native lung of the recipients. Phase II: RT-PCR confirmed murine TGF-beta1 transfection. pO2 was 362.7+/-110.2 (mean mm Hg +/- SD) for sense TGF-beta1; 146.88+/-85.5 for antisense; 241.5+/-181.5 for GL67-TGF-beta1 sense; and 88.4+/-38.7 for saline. TGF-beta1 sense versus all other groups, p<0.05, GL67-TGF-beta1 sense versus saline, p = 0.01. Rejection was significantly lower for TGF-beta1 sense versus saline, p = 0.04. CONCLUSIONS: Endobronchial administration of naked plasmid achieves selective transfection of lung grafts. Using this strategy, TGF-beta1 reduces early lung allograft rejection.

Acute Disease↗
PubMed1999

The current role of mediastinoscopy in the evaluation of thoracic disease.

OBJECTIVE: Mediastinoscopy is a common procedure used for the diagnosis of thoracic disease and the staging of lung cancer. We sought to determine the current role of mediastinoscopy in the evaluation of thoracic disease. METHODS: We conducted a retrospective review of all mediastinoscopies performed by members of our service between January 1988 and September 1998. RESULTS: We performed mediastinoscopies on 2137 patients. A total of 1745 patients underwent mediastinoscopy for known or suspected lung cancer. In 422 of these procedures, N2 or N3 disease was identified; only 28 of these patients underwent resection. The remaining 1323 had no evidence of metastatic disease. In these patients 947 had lung cancer. Only 76 of the patients with lung cancer were found to have N2 disease at exploration. Among the 1323 patients with a negative mediastinoscopy result, 52 underwent resection of a nonbronchogenic malignancy, and 217 had resection of a benign lesion. A total of 392 patients underwent mediastinoscopy for the evaluation of mediastinal adenopathy in the absence of any identifiable pulmonary lesion. Of these, 161 had a nonbronchogenic malignancy, 209 had benign disease, and 25 had no diagnosis established; mediastinoscopy established a definitive diagnosis in 93.6% of patients. In the entire group of 2137 patients, there were 4 perioperative deaths and 12 complications. Only one death was directly attributed to mediastinoscopy. No deaths or complications occurred in patients undergoing mediastinoscopy for benign disease. CONCLUSIONS: Mediastinoscopy is a highly effective and safe procedure. We believe that mediastinoscopy should currently be used routinely in the diagnosis and staging of thoracic diseases.

Aged↗
PubMed1999

Ex vivo transfection of transforming growth factor-beta1 gene to pulmonary artery segments in lung grafts.

OBJECTIVE: Proximal pulmonary artery segment transfection may provide beneficial downstream effects on the whole-lung graft. In this study, transforming growth factor-beta1 was transfected to proximal pulmonary artery segments, and the efficacy of transforming growth factor-beta1 transfection was examined in ischemia-reperfusion injury and acute rejection models of rat lung transplantation. METHODS: In the ischemia-reperfusion injury model, orthotopic left lung transplantation was performed in F344 rats. In group I, the PPAS was isolated and injected with saline solution. In 2 other groups, lipid67:DOPE:sense (group II) or antisense transforming growth factor-beta1pDNA construct (group III) was injected instead of saline solution. After cold preservation at 4 degrees C for 18 hours, lung grafts were implanted. Graft function was assessed 24 hours later. In the acute rejection model, donor lung grafts were harvested. Proximal pulmonary artery segments were injected with saline solution (group I) or sense (group II) or antisense lipid gene construct (group III) and then implanted. Graft function was assessed on postoperative day 5. RESULTS: In the ischemia-reperfusion injury study, there were no significant differences in oxygenation, wet-to-dry weight ratios, graft myeloperoxidase activity, or transforming growth factor-beta1 levels in platelet-poor serum or proximal pulmonary artery segment homogenates. In the acute rejection study, oxygenation was significantly improved in group II receiving transforming growth factor-beta1 (group II vs I and III, 136.0 +/- 32.5 vs 54.0 +/- 9.6 mm Hg and 53.8 +/- 14.8 mm Hg; P =.016 and.016). There were no significant pathologic differences. Transforming growth factor-beta1 concentrations from proximal pulmonary artery segment homogenates in group II were significantly higher compared with controls. CONCLUSIONS: Ex vivo transfection of transforming growth factor-beta1 to proximal pulmonary artery segments did not affect reperfusion injury of lung isografts. In acute rejection, however, ex vivo transfection of transforming growth factor-beta 1 to proximal pulmonary artery segments improved allograft function. This suggests that transfection to proximal pulmonary artery segments exerts beneficial downstream effects on the whole-lung allograft.

Acute Disease↗
PubMed1999

Cytotoxic T lymphocytes directed against donor HLA class I antigens on airway epithelial cells are present in bronchoalveolar lavage fluid from lung transplant recipients during acute rejection.

BACKGROUND: The lung epithelium is among the first donor tissues encountered by the lung allograft recipient's immune system. The purpose of this study was to determine whether lung epithelium was recognized by T lymphocytes that are isolated from bronchoalveolar lavage fluid of lung allograft recipients during periods of acute rejection. METHODS: Lymphocytes isolated from 45 bronchoalveolar lavage samples (from 41 lung transplant recipients) served as effector cells in standard cell-mediated cytolytic assays with several cell lines as targets: BEAS-2B (an immortalized airway epithelial cell line); B-lymphoblastoid cell lines; and K562 (a natural killer-sensitive cell line). Cytotoxic T-lymphocyte activity of bronchoalveolar lavage lymphocytes was correlated with pathologic status. RESULTS: During acute rejection alone (ie, without concomitant cytomegalovirus infection), mean lysis of the airway epithelial target was significantly greater, compared with during no rejection, when these targets expressed donor-specific HLA class I antigens (P =.007). Lysis of donor class I-matched B-lymphoblastoid cell line targets during rejection was not significantly different from lysis during no-rejection periods (P =.18). Mean lysis of K562, a natural killer cell target, did not differ between acute rejection (without concomitant cytomegalovirus infection) and no rejection (P =.30). During cytomegalovirus infection (without concomitant acute rejection), there was no difference in mean lysis of airway epithelial cells, B-lymphoblastoid cell lines, or K562 targets compared with during no cytomegalovirus infection, whereas during acute rejection, compared with cytomegalovirus infection without rejection, there was a significant increase in mean lysis of the airway epithelial target when it expressed donor-specific HLA antigens (P =.01). CONCLUSIONS: Donor HLA class I-specific cytotoxic T-lymphocyte activity directed at airway epithelial cells was demonstrated in bronchoalveolar lavage lymphocytes from lung transplant recipients. Lysis of these targets was significantly higher during episodes of acute rejection.

Acute Disease↗
PubMed1999

Bilateral sequential lung transplantation without sternal division eliminates posttransplantation sternal complications.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of an alternative surgical incision for bilateral sequential lung transplantation. The vast majority of these operations worldwide have been performed through an anterolateral thoracosternotomy known as the "clamshell" incision. Recently, we have undertaken most of these operations through bilateral anterolateral thoracotomies without sternal division. METHODS: Our medical center performed 262 bilateral sequential single lung transplantations from 1989 to April 1998. Between July 1996 and April 1998 we performed 69 bilateral sequential single lung transplantations on 68 recipients with 52 transplantations being conducted without initial sternal division. We retrospectively reviewed the results of these operations to assess the safety of the altered exposure and the efficacy in avoiding sternal wound complications such as malunion, dehiscence, osteomyelitis, and migrating hardware. Comparison was made to a historical control group composed of the last 50 patients in whom the full clamshell incision was used. RESULTS: Of the 68 patients who underwent transplantations, 52 patients underwent the initial exploratory procedure without sternal division. Two patients required emergency sternal division for institution of cardiopulmonary bypass to control life-threatening bleeding. Eleven of 68 patients were placed on bypass electively to permit transplantation, and the lack of a sternotomy in 8 patients did not present an obstacle to ascending aortic and right atrial cannulation. There were no wound healing complications in the 50 patients for whom the sternum was left intact. In a historical control group of 50 patients who underwent transplantation with sternal division, 34% experienced morbidity or mild disability as a direct result of poor sternal healing. CONCLUSIONS: We conclude that bilateral anterolateral thoracotomy without sternal division is a safe approach that allows adequate exposure without the risk of commonly observed problems with sternal healing.

Cardiopulmonary Bypass↗
PubMed1999

Liposome-mediated gene transfer in rat lung transplantation: A comparison between the in vivo and ex vivo approaches.

OBJECTIVE: We compared the efficacy of in vivo and ex vivo liposome transfection in rat lung transplantation. METHODS: (1) Chloramphenicol acetyltransferase group: Fischer rats underwent isogeneic transplantation (n = 4 per group). Recipients were put to death on postoperative day 2 for chloramphenicol acetyltransferase activity. Ex vivo setting: Grafts received cDNA complexed or not with liposomes and were transplanted after 1.5 or 10 hours at 10 degreesC. In vivo setting: Donors were intravenously injected with cDNA complexed or not with liposomes. Lungs were harvested after 1.5 or 10 hours, preserved at 10 degreesC, and transplanted. (2) Transforming growth factor-beta1 group: Brown-Norway rats served as donors and Fischer rats as recipients. All grafts were preserved for 3 hours at 10 degreesC. On postoperative day 5, arterial oxygenation and histologic rejection scores were assessed. Ex vivo setting: Grafts received transforming growth factor-beta1 sense (n = 8) or antisense (n = 7) complexed with liposomes or cDNA alone (n = 5). In vivo setting: Donors were intravenously injected with liposome:transforming growth factor-beta1 sense cDNA (n = 7). Exposure time was 3 hours. RESULTS: (1) Chloramphenicol acetyltransferase-transfection was superior in the ex vivo group but was not statistically different for longer exposure times. (2) Transforming growth factor-beta1-arterial oxygenation was superior in the ex vivo liposome:sense group. cDNA alone was inefficient. Rejection scores were not statistically different between ex vivo and in vivo liposome:sense groups but were better when the ex vivo liposome:sense group was compared with the cDNA alone or the antisense groups. CONCLUSIONS: (1) With current liposome technology, the ex vivo route is superior to the in vivo approach; (2) cDNA alone does not provide transgene expression at levels to produce a functional effect.

Animals↗
PubMed1999

Lung transplantation: a decade of experience.

OBJECTIVE: To review the 10-year clinical experience of a single institution's adult lung transplant program. METHODS: Since July 1988, 450 lung transplants have been performed in 443 patients. Recipient diagnoses included emphysema in 229 patients, cystic fibrosis in 70 patients, pulmonary fibrosis in 48 patients, pulmonary hypertension in 49 patients, and miscellaneous end-stage lung diseases in 47 patients. Single-lung transplant was performed in 157 cases, bilateral sequential lung transplant in 283 cases, en bloc double-lung transplant in 8 cases, and heart-lung transplant in 2 cases. Graft lungs were obtained from local donors in 24% of cases and from distant donors in 76% of cases. Ideal donors were used in 74% of cases; in 26%, the donor was classified as marginal based on objective criteria. RESULTS: Four hundred six (91.6%) lung transplant recipients survived to hospital discharge. There were 37 hospital deaths from cardiac events (n = 8), primary graft failure (n = 8), sepsis (n = 6), anastomotic dehiscence (n = 6), and other causes (n = 9). A diagnosis of chronic rejection (bronchiolitis obliterans syndrome [BOS]) was made in 191 patients (42.5%). BOS has not been improved by any specific therapy. Rates of freedom from BOS at 1, 3, and 5 years after the transplant are 82%, 42%, and 25%. One-, 3-, and 5-year actuarial survival rate for the entire group are 83%, 70%, and 54%. There is no statistical difference in survival according to diagnosis or type of lung transplant. Recipient waiting time was 116 days in the first 90 patients and 634 days in the most recent 90 patients. CONCLUSIONS: Lung transplantation offers patients with end-stage lung disease acceptable prospects for 5-year survival. Chronic rejection and long waiting lists for donor lungs continue to be major problems facing lung transplant programs. The use of marginal and distant donors is a successful strategy in improving donor availability.

Adult↗
PubMed1999

Results of transcervical thymectomy for myasthenia gravis in 100 consecutive patients.

OBJECTIVE: To review the results of the authors' most recent 100 consecutive cases of transcervical thymectomy for myasthenia gravis (MG) in terms of complications and outcome in comparison with other reported techniques. SUMMARY BACKGROUND DATA: Myasthenia gravis is believed to be an autoimmune disorder characterized by increasing fatigue with exertion. The role of thymectomy in the management of the disease remains unproven, but there is widespread acceptance of the notion that complete thymectomy improves the course of the disease. Complete excision of the thymus is the goal in all cases; however, the best technique to achieve complete thymectomy remains controversial. The authors favor a transcervical approach through a small collar incision aided by a specially designed sternal retractor. Others prefer a transsternal, a combined transcervical and transsternal ("maximal"), or a video-assisted thoracoscopic surgical approach. METHODS: A retrospective review of the authors' most recent 100 consecutive transcervical thymectomies for nonthymoma-associated MG was performed using medical records and telephone interviews. Patients' symptoms were graded before surgery and at the most recent (within the last 6 months) postoperative time point, using the modified Osserman classification: 0 = asymptomatic, 1 = ocular signs and symptoms, 2 = mild generalized weakness, 3 = moderate generalized weakness, bulbar dysfunction, or both, and 4 = severe generalized weakness, respiratory dysfunction, or both. RESULTS: There were 61 female patients and 39 male patients with a mean age of 38 years (range, 14 to 84). The median hospital stay was 1 day. There were no deaths and no significant complications. Seventy-eight patients who had undergone surgery >12 months ago were available for analysis. In these patients, with a mean follow-up time of 5 years (median 5.3; range, 12 months to 10 years), the median preoperative Osserman grade improved from 3.0 (mean 2.73) before surgery to 1.0 after surgery (mean 0.94). CONCLUSIONS: The transcervical approach for thymectomy for the treatment of MG produces results similar to those of other surgical approaches, with the added benefits of shortened hospital stay, decreased complications, reduced cost, and broader physician and patient acceptance of surgical treatment.

Adolescent↗
PubMed1999

Physiologic consequences of pneumonectomy. Consequences on the esophageal function.

Esophageal and upper gastrointestinal dysmotility occur after both pneumonectomy without pulmonary replacement and recipient pneumonectomy for thoracic organ transplantation. After pneumonectomy without pulmonary replacement, there is a shift of the esophagus to the side of pneumonectomy and disturbance of esophageal peristalis. After recipient pneumonectomy for thoracic organ transplantation, esophageal dysmotility and delayed gastric emptying are common. Injury of the vagal nerves, local ischemia, postoperative scarring of the esophagus and mediastinum, and disturbance of the autonomic nervous systems are the major causes of the abnormality. To reduce the incidence of esophageal dysmotility after pneumonectomy, every effort should be made during surgery to prevent direct injury of the esophagus or the vagal nerves.

Esophageal Motility Disorders↗
PubMed1998

HLA-A locus mismatches and development of antibodies to HLA after lung transplantation correlate with the development of bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the most common cause of morbidity and mortality after lung transplantation (LT). A retrospective analysis of clinical and immunologic variables were done to identify those that might predict the development of BOS. METHODS: Of 112 LT performed over a 42-month interval, 94 survived at least 3 months and form the basis of this analysis. There was a minimum of 21 months follow-up. BOS was defined on the basis of declining spirometry (FEV1 <80% of baseline) and/or the presence of histologic obliterative bronchiolitis. All variables analyzed were subjected first to a univariate analysis; those variables appearing to carry significance were then subjected to a multivariate logistic regression analysis. RESULTS: Univariate analysis revealed the following to be predictors of the development of BOS: age (the probability of developing BOS declined with advancing age); donor/recipient HLA-A locus mismatch, with actuarial freedom from BOS being significantly greater with no A-locus mismatches versus cases with one or two mismatches (P=0.031); and development of anti-HLA antibodies after transplantation (P=0.006 vs. recipients without detectable antibodies). In multivariate analysis, only HLA locus mismatch and development of anti-HLA antibodies were significant independent predictors of the development of BOS. The remaining clinical variables (gender, type of LT, indication for LT, graft ischemic time, use of cardiopulmonary bypass, cytomegalovirus) and immunologic variables (crossmatch, frequent early acute rejection) did not correlate with the development of BOS. CONCLUSIONS: These data suggest that BOS is the result of an immune process, that differences at the HLA-A locus may play an important role in this process, and antibody-mediated injury may play a role in BOS.

Adult↗