Heart and lung transplantation in the United States, 1996-2005.

This article examines the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients data on heart and lung transplantation in the United States from 1996 to 2005. The number of heart transplants performed and the size of the heart waiting list continued to drop, reaching 2126 and 1334, respectively, in 2005. Over the decade, post-transplant graft and patient survival improved, as did the chances for survival while on the heart waiting list. The number of deceased donor lung transplants increased by 78% since 1996, reaching 1407 in 2005 (up 22% from 2004). There were 3170 registrants awaiting lung transplantation at the end of 2005, down 18% from 2004. Death rates for both candidates and recipients have been dropping, as has the time spent waiting for a lung transplant. Other lung topics covered are living donation, recent surgical advances and changes in immunosuppression regimens. Heart-lung transplantation has declined to a small (33 procedures in 2005) but important need in the United States.

Development of the new lung allocation system in the United States.

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.

BACKGROUND: We prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population. METHODS: Between January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen. RESULTS: Ten patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques. CONCLUSION: The HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.

Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody.

BACKGROUND: The incidence and the severity of acute lung allograft rejection has been linked to the development of bronchiolitis obliterans syndrome. Therefore, we investigated the effects of daclizumab, a humanized monoclonal antibody directed against the alpha subunit of the interleukin 2 receptor, in reducing acute rejection after transplantation. METHODS: We retrospectively evaluated 27 patients who received daclizumab as induction immunosuppression and compared them with a historical control group of 34 patients. Both groups received similar immunosuppressive regimens involving tacrolimus, prednisone, and either azathioprine or mycophenolate mofetil. All patients received cytomegalovirus and aspergillus prophylaxis. RESULTS: Twenty-one patients in the control group and 22 patients in the daclizumab group were available for analysis at 6 months after lung transplantation. Ten (48%) patients in the control group had at least grade 2 acute rejection compared with four (18%) in the daclizumab group (P<0.04). The incidence of infection was similar in both groups. One patient in each group developed posttransplant lymphoproliferative disease. CONCLUSION: Therapy with daclizumab resulted in a significant decrease in the incidence of grade 2 or greater acute rejection after lung transplantation compared with historical controls. There seems to be no increase in the incidence of adverse effects in the patients treated with daclizumab.

Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation.

BACKGROUND: Currently the most important limitation in lung transplantation is donor availability. Although liberalization of donor criteria may aid in expanding the donor pool, the long-term effects of the use of "marginal" or "extended" donors remains unexplored. METHODS: In this study, we included all patients who underwent lung transplantation from January 1996 to December 1999 at Loyola University Medical Center. We categorized patients as either receiving lungs from an "ideal" donor or an "extended" donor. Extended donors were defined as having any 1 of the following criteria: donor age > 55 years, tobacco history > 20 pack years, presence of infiltrate on chest x-ray, donor ventilator time > 5 days, or donor use of inhaled drugs (cocaine or marijuana). We then compared the 2 groups with regard to short-term (operating room [OR] complications, intensive care unit [ICU] complications) and long-term outcomes (1-year pulmonary function and survival). RESULTS: Sixty-one (54%) patients received lungs from ideal donors and 52 (46%) patients received lungs from extended donors as defined above. We observed no significant differences between the 2 groups in OR complications (cardiopulmonary bypass, bleeding complications, life-threatening arrhythmias) or ICU complications (pneumonia, airway dehiscence, reoperation within 30 days related to transplantation). In addition, the 2 groups had similar median intubation times (21 hours in the ideal donor group and 20 hours in the extended donor group; p = n.s.), hospital length of stay (14+/-12 days in the ideal donor group and 12+/-8 days in the extended donor group; p = n.s.), and hospital survival (80% and 88% in the ideal and extended donor groups, respectively). One-year follow-up revealed similar pulmonary function (forced expiratory volume in 1 sec [FEV(1)] = 2.4 liters and 2.4 liters in the recipients of bilateral ideal and extended donors, respectively, and FEV(1) = 1.9 liters and 1.5 liters in the recipients of single ideal and extended donors) and survival (72% and 79% in the ideal and extended donor groups, respectively; p = n.s.) between the 2 groups. CONCLUSIONS: Liberalization of donor criteria does not affect outcome in the first year after lung transplantation. By liberalizing donor criteria, we can expand the donor pool while assessing other possible mechanisms to increase donor availability.

Mycobacterial DNA in recurrent sarcoidosis in the transplanted lung--a PCR-based study on four cases.

Sarcoidosis is a systemic granulomatous inflammation, which may be caused by mycobacteria other than M. tuberculosis complex (MOTT) in one-third of cases. A few cases of recurrent sarcoidosis in the transplanted lung have been reported. However, mycobacteria have been excluded by acid-fast stains only. We investigated four cases of recurrent sarcoidosis in lung transplant patients. Using PCR for the insertion sequence 6110 of Mycobacterium tuberculosis complex and a second PCR for the mycobacterial chaperonin (65-kDa antigen coding sequence), we looked for mycobacterial DNA. In three cases sequence analysis was also performed. One patient was negative for mycobacterial DNA in explanted, but positive for M. tuberculosis DNA in transplanted lung, qualifying this case as M. tuberculosis infection in the transplant. Three patients were negative for M. tuberculosis DNA, but were positive for MOTT-DNA in both explanted and transplanted lungs. In these three patients sequence identity of the amplified sequences before and after transplantation was proven, which rules out mycobacteriosis. Recurrent sarcoidosis does occur, but can only be proven by the exclusion of mycobacterial DNA. In cases of recurrent MOTT-DNA-positive sarcoidosis the diagnosis cannot be confirmed except by proof of sequence identity. Probably MOTT-DNA-positive sarcoidosis is more likely to recur in a transplanted lung.

Extracorporeal photopheresis for the treatment of lung allograft rejection.

OBJECTIVES: Acute and chronic rejection continue to limit the survival of lung transplant recipients. Extracorporeal photopheresis has evolved as a possible therapy for patients with acute nd chronic lung allograft rejection. METHODS: We retrospectively reviewed 14 patients diagnosed with BOS who underwent therapy with extracorporeal photopheresis. RESULTS: Three patients were classified as BOS 0'b', five as BOS 1, three as BOS 2, and, three as BOS 3 at the time of diagnosis. Of the patients with BOS 0'b' or BOS 1 seven remain alive and one died of lung cancer. Two have progressed to BOS 2. Of the patients with BOS 2 or 3, four have died of BOS, one died of lung cancer, and one was re-transplanted. In three patients with BOS and concurrent acute rejection, therapy with extracorporeal photopheresis led to the resolution of the acute rejection episode. Two of the 14 patients developed line related sepsis. CONCLUSION: Extracorporeal photopheresis appears to be a promising therapy for patients with early BOS. It may also have a role in the treatment of acute lung allograft rejection.

Refractory post-transplant airway strictures: successful management with wire stents.

OBJECTIVE: Bronchial stenosis, malacia and dehiscence are major airway complications of lung transplantation. Our success in managing this problem evolved from the use of semi-rigid dilators, to balloon dilation and placement of a stent, which were initially silicone, thereafter wire balloon-expandable and finally wire self-expandable. METHODS: From May, 1994 until July 1997, we performed a total of 49 single and 58 bilateral lung transplants. Symptoms of shortness of breath, verified by a drop in the forced expiratory volume in one second (FEV1), led to bronchoscopic inspection of the airway in lung transplant patients. Eighteen patients (16%) suffered a severe form of airway complication (dehiscence or stenosis) in 24 of 151 airways at risk (15.9%). These anastomotic strictures were recalcitrant to conventional therapy. Intervention consisted of rigid bronchoscopy, dilation of the stricture and placement of a stent. Flexible bronchoscopy and fluoroscopy were used for precise placement of the stent. As the initial stent, the Hood silicone stent was placed five times in four patients and the Dumont studded stent five times in four patients. The Palmaz wire stent was used as the initial stent 10 times in seven patients and the Wallstent used eight times in seven patients. Four patients had multiple stents. Balloon inflation moulded the wire stent to the airway. RESULTS: There was no mortality resulting from the airway complication or any intervention. The most serious complication was a perforation of the airway using the semi-rigid dilator that necessitated immediate thoracotomy and re-anastomosis of the bronchus. Other complications necessitated repeat interventions due to restenosis or failure of the stents. The success of the stent placement was measured subjectively by the immediate ease of breathing enjoyed by each patient and objectively by the significant increase of the FEV1 from a pre-operative mean of 1.19 l (SD 0.64 l) to a post-operative mean of 2.06 l (SD 0.70 l) (P < 0001). The mean number of interventions according to the type of wire stent first used was significantly fewer with Wallstent insertion (1.28 (SD 0.48)) than in those patients in whom a Palmaz stent was inserted (5.22 (SD 2.38)) (P < 0008). CONCLUSION: The airway complication of stricture, broncho-malacia or dehiscence following lung transplantation can be managed effectively and easily with the use of balloon catheter dilation followed by precise placement of a self-expandable wire stent. The Wallstent is the superior stent for this application.

Analysis of risk factors for the development of bronchiolitis obliterans syndrome.

Chronic rejection after lung transplantation, manifesting as bronchiolitis obliterans syndrome (BOS), has become the dominant challenge to long-term patient and graft survival. In order to elucidate risk factors for development of BOS we utilized the 1995 revision of the working formulation for the classification of lung allograft rejection (), and devised a quantitative method to retrospectively study lung transplant biopsies from all patients who survived at least 90 d. All transbronchial biopsies were regraded 0 to 4 for acute perivascular rejection and lymphocytic bronchitis/bronchiolitis (LBB), and the grades were totaled over a period of time to give two scores, respectively, for each patient. Also examined were timing of acute rejection and LBB episodes and decreased immunosuppression defined as two or more cyclosporine A levels < 200 ng/ml. Sixty-six patients with BOS and 68 with no BOS (NBOS) satisfied our criteria for inclusion in the study. Demographics including age, sex, and primary diagnoses were similar. The mean perivascular score for BOS was 6.2 over a mean follow-up of 822 d (range, 113 to 2,146) compared with 3.2 for NBOS over 550 d (range, 97 to 1,734) mean follow-up. Airway scores were 5.3 and 1.7, respectively, for the same follow-up periods. There was no correlation between length of follow-up and rejection or LBB scores, although mean length of follow-up for the two groups was significantly different. Late acute rejection and LBB were significantly associated with BOS as was decreased immunosuppression. In addition to perivascular rejection, LBB, late acute rejection, and decreased immunosuppression are significant risk factors for the development of BOS. Analysis of the current data leads us to believe that LBB, in the absence of infection, is in fact a manifestation of acute rejection, with similar implications for graft function as acute perivascular rejection.

Lung transplantation at Loyola University Medical Center.

The Loyola Lung Transplant Program shows a long record of offering transplants to suitable recipients, with good clinical results. The overall one-year survival rate was 84% for 53 lung transplant recipients in 1998-99. Our local perception on donor management appears to be successful at increasing donor organ availability. In addition, continuous evolution in posttransplant care and willingness to utilize newer immunosuppressive agents has reduced our incidence of acute rejection episodes to 23% during the past 2 years. Time will tell if there is also a measurable reduction in bronchiolitis obliterans syndrome. Finally, longitudinal research on QOL after lung transplantation continues to buoy our spirits based on patient acceptance and satisfaction with results. We continue to be strong advocates for transplantation and organ donation.

Partitioning of lung and chest-wall mechanics before and after lung-volume-reduction surgery.

In the study reported here, we partitioned the mechanics of the respiratory system into lung and chest-wall components, using the rapid occlusion technique in seven patients with severe emphysema before lung-volume-reduction surgery and 3 mo later. Patients showed improvements in 6-min walk (p < 0.01) and dyspnea (p < 0.05). The resistances of the respiratory system and chest wall were not altered by surgery. Ohmic airway resistance did not change, but the component of lung resistance (DeltaRL) due to viscoelastic behavior (stress relaxation) and time-constant inhomogeneities (pendelluft) decreased in six patients (p < 0.03). Dynamic elastance of the lung (Edyn,L) decreased after surgery (p < 0.02), whereas dynamic elastance of the chest wall did not change. The ratio of dynamic intrinsic positive end-expiratory pressure (PEEPi) to static PEEPi, which also reflects viscoelastic properties and time-constant inhomogeneities, increased after surgery (p < 0.05). The decrease in dyspnea was related to the decrease in Edyn,L (r = 0.81, p = 0.03), and tended to be related to the decrease in DeltaRL (r = 0.71, p = 0. 07). In conclusion, lung-volume-reduction surgery decreased dynamic pressure dissipations caused by stress relaxation and time-constant inhomogeneities within lung tissue, and it had no effect on the static mechanical properties of the chest wall.

Lung transplantation for fibrotic lung diseases.

The underlying disease of a candidate for lung transplantation, especially advanced pulmonary fibrosis, can cause particular and dramatic difficulties. Pulmonary fibrosis is the end-result of a variety of pathological diseases and their associated processes. This article summarizes the diagnosis and management of some of the more common causes of fibrosis, outlines their natural histories and treatment outcomes, and describes the trade-off of pulmonary fibrosis for lung transplantation. Four main categories of end-stage fibrosis are discussed: idiopathic pulmonary fibrosis, sarcoidosis, pulmonary fibrosis from systemic diseases or drugs, and occupational- or environmental-related pulmonary fibrosis. Each group will be covered systematically and the options and indications for lung transplantation will be addressed.

Effect of lung volume reduction surgery on neuromechanical coupling of the diaphragm.

The mechanisms for symptomatic improvement following lung volume reduction surgery for emphysema are poorly understood. We hypothesized that enhanced neuromechanical coupling of the diaphragm is an important factor in this improvement. We studied seven patients with diffuse emphysema before and 3 mo after surgery. Patients showed improvements in 6-min walking distance (p = 0.002) and dyspnea (p = 0.04). The pressure output of the respiratory muscles, quantified as pressure-time product per minute (PTP/min), decreased after surgery (p = 0.03), as did PaCO2 (p = 0.02). Maximal transdiaphragmatic pressures (Pdi(max)) increased from 80.3 +/- 9.5 (SE) to 110.8 +/- 9.3 cm H2O after surgery (p = 0.03), and the twitch transdiaphragmatic pressure response to phrenic nerve stimulation (Pdi(tw)) increased from 17.2 +/- 2.4 to 25.9 +/- 3.0 cm H2O (p = 0.02); these increases were greater than could be accounted for by a decrease in lung volume. The contribution of the diaphragm to tidal breathing, assessed by relative changes in gastric and transdiaphragmatic pressures, increased after surgery (p = 0.008). Net diaphragmatic neuromechanical coupling, quantified as the quotient of tidal volume (normalized to total lung capacity) to tidal change in Pdi (normalized to Pdi(max)), improved after surgery (p = 0.03) and was related to the increase in 6-min walking distance (r = 0.86, p = 0.03) and decrease in dyspnea (r = 0.76, p = 0.08). In conclusion, lung volume reduction surgery effects an improvement in diaphragmatic function, greater than can be accounted for by a decrease in operating lung volume, and enhances diaphragmatic neuromechanical coupling.

Perioperative management in lung transplantation.

Despite the multitude of potential complications that may be encountered during the early post-transplant period, the majority of transplant recipients experience a smooth transition from postoperative intensive care, to step-down unit, to the regular medical floor, and, ultimately, to their home within 10 to 14 days without any significant unexpected events. The likelihood of serious complications can be greatly reduced through careful recipient selection, impeccable donor management, and the cooperative efforts of surgeons, pulmonologists, nurse specialists, and the numerous experienced consultants required for a successful transplant program. Although many unique facets contribute to the complexity of lung transplant patient care, attention to the details of high-quality general postsurgical care will yield excellent results.