In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 ...by an expanded group of pathologists. The original and revised classifications have served the lung transplant community well, facilitating communication between transplant centers with regard to both patient management and research. In 2006, under the direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme, address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3 (moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1) or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic rejection are described and technical considerations revisited. This consensus revision of the working formulation was approved by the ISHLT board of directors in April 2007.
Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the ...efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS.
This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C2) levels, and corticosteroids. Target C2 levels were lower in the RAD group because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction therapy was not used. Patients were stratified at entry for cystic fibrosis. Confirmation of anastomotic healing was required for randomization. Primary efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis. Secondary efficacy parameters were patient and graft survival and severity of rejection. Treatment failure was defined by graft loss, patient death, drug cessation, or need for other therapy.
The 3-year freedom from BOS Grade 1 was 70% for MPS (n = 80) vs 71% for RAD (n = 84; p = 0.95 by log-rank) in ITT but was lower in the RAD arm of the per-protocol population (p = 0.03). The 3-year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients switched from MPS vs 31 from RAD (p < 0.01). Days on MPS were greater than days on RAD (p < 0.01). Rejection events proven by biopsy specimen were more common on MPS (p = 0.02), as were leucopenia (p < 0.01), diarrhea (p < 0.01), and cytomegalovirus infection (p = 0.04). Venous thromboembolism was more frequent on RAD (p = 0.02). Creatinine at 3 years was 160 ± 112 μmol/1iter in MPS patients vs 152 ± 98 μmol/1iter in RAD patients (p = 0.67).
This 3-year ITT analysis found no significant difference between arms but was underpowered to accept the null hypothesis that RAD and MPS have equivalent efficacy in preventing BOS or death after lung transplantation.
Lung transplantation (LTx) is a therapy for patients with cystic fibrosis (CF) end-stage lung disease. Pseudomonal airway colonization (PAC) is common in CF.
We investigated the influence of ...post-transplant sinus surgery and daily nasal douching on PAC after LTx and the influence of PAC on survival and bronchiolitis obliterans syndrome (BOS).
CF patients transplanted at our centre were included (November 1992 to December 2009). Clinical data, including microbiological data before and after LTx were collected. Survival and BOS following LTx were compared for CF recipients with and without PAC by Kaplan-Meier statistics and Cox regression analysis.
Ninety-four CF patients were transplanted, of whom 82 (87%) underwent sinus surgery after transplantation, and 65% of 66 patients with pre-transplant PAC had persistent PAC after transplantation. Upper and lower PAC is related. Patients without PAC after transplantation had a significantly better survival rate, and BOS was less frequent with a later onset. PAC was the only significant parameter for the development of BOS stage 2 in the multivariate analysis for cytomegalovirus infection, acute rejection and PAC.
Sinus surgery and daily nasal douching reduced PAC in LTx recipients. Absence of post-transplant PAC had a positive impact on post-transplant survival and the development of BOS.
Lung transplantation has been accepted widely as therapy for end-stage pulmonary lymphangioleiomyomatosis (LAM); however, single-center and national experience is limited due to the rarity of LAM.
We ...report the recent European experience of lung transplantation for LAM. A self-administered questionnaire was distributed to 30 European lung transplant centers to evaluate patients who underwent primary lung transplantation for LAM (1997 to 2007).
Seventy percent of centers responded to the questionnaire. A total of 61 lung transplants were undertaken in women only, with mean age at transplant 41.3 years (SD 5.1). Centers performed a median of 2 (0 to 9) transplant operations. Severe pleural adhesions were the most common intra-operative complication. Early deaths (N = 6) were due to primary graft or multiple-organ failure or sepsis. Twelve recipients were diagnosed with bronchiolitis obliterans syndrome at a median of 20 months (range 10 to 86 months) post-transplant. LAM-related complications included renal angiomyolipoma and pneumothorax in the native lung. Recurrence of LAM occurred in 4 recipients. As of December 2007, actuarial Kaplan-Meier survival was 79% at 1 year and 73% at 3 years post-transplant.
Post-transplant outcome for pulmonary LAM in the recent era appears to have improved compared with the previous era. LAM-related complications remain common, but recurrence of LAM in the allograft is rare.
Lung transplantation is the ultimate therapy for end-stage cystic fibrosis (CF) lung disease; however, the debate continues as to whether lung transplantation improves survival. We report ...post-transplant outcome in CF at our institution by comparing 5-year post-transplant survival with a calculated 5-year survival without lung transplantation, using a predictive 5-year survivorship model, and describe pre-transplant parameters influencing transplant outcome.
CF patients undergoing lung transplantation at our center were included (1992 to 2007). Survival rates were calculated and compared, and univariate and multivariate Cox regression analyses were used for statistical assessment.
Eighty transplants were performed in CF patients, 11 (13.8%) of whom were children. Mean age at transplant was 26.2 years (95% confidence interval: 24.4 to 28.0). The Liou raw score at transplant was -20 (95% confidence interval: -16 to -24), resulting in an estimated 5-year survival without transplantation of 33 +/- 14%, compared with a 5-year post-transplant survival of 68.2 +/- 5.6%. Further improvement was noted in the recent transplant era (since 2000), with a 5-year survival of 72.7 +/- 7.3%. Univariate analysis revealed that later year of transplant and diagnosis of diabetes influenced survival positively. Pediatric age had no negative impact. In the multivariate analysis, only diabetes influenced survival, in a positive manner.
Lung transplantation performed at centers having experience with the procedure can offer a true survival benefit to patients with end-stage CF lung disease.
Lung transplantation is an established therapeutic option for end-stage lung disease in selected patients. During the last 30 years more than 34,000 transplantations have been performed worldwide. ...Emphysema, pulmonary fibrosis, cystic fibrosis and primary pulmonary hypertension are the most common indications. This type of surgical treatment is increasingly successful, with better early and late survival rates. However, lung transplantation is still hampered by persisting problems such as donor organ shortage, primary graft dysfunction, late graft dysfunction and morbidity related to long-term immunosuppression. The first lung transplantation in Switzerland was performed the 10th November 1992 at Zurich University Hospital. Since then the lung transplant programme has progressively increased its yearly transplant volume. Since the beginning of our lung transplantation programme, overall patient survival has increased steadily and has been at benchmark levels since the year 2000. The most important factors influencing this result are presumably good teamwork among all involved specialists, improved surgical techniques, and close and long-term patient follow-up by the transplant pulmonologists. In this paper we present our programme structure, managing strategies for some specific problems and outcome after lung transplantation. The results presented here are from recipients who underwent lung transplantation up to the end of 2011.
Malnutrition is common in children undergoing lung transplantation, particularly among those with cystic fibrosis (CF). However, the effect of body habitus on outcome after pediatric lung ...transplantation is unknown. We studied body mass index (BMI) and its effect on outcome in pediatric lung transplantation.
The International Society for Heart and Lung Transplantation Registry on Pediatric Lung Transplantation was queried for primary pediatric lung transplant recipients (aged<18 years) between 1990 and 2008. BMI cohorts were defined according to International Obesity Task Force cutoffs: thinness grade 3, BMI<16 kg/m(2); thinness grade 2, 16 to<17 kg/m(2); thinness grade 1, 17 to<18.5 kg/m(2); normal, 18.5 to<25 kg/m(2); overweight, 25 to<30 kg/m(2); and obese, ≥ 30 kg/m(2). Survival was compared among BMI cohorts within CF and non-CF recipient groups.
Included were 897 recipients. The median age at transplantation was 14 years (interquartile, 11, 16 years) and 63% had CF. The incidence of thinness was 59% in CF vs 39% in non-CF patients (p<0.001). A significant proportion of CF patients were underweight, whereas more non-CF patients were obese. Cox regression showed neither underweight nor overweight CF recipients differed in survival compared with recipients of normal-weight recipients. Grade of thinness was not related to outcome after transplantation. For non-CF recipients, being overweight/obese increased risk of death compared with normal-weight recipients (hazard ratio, 2.05; 95% confidence interval, 1.28-3.26; p = 0.002).
The incidence of underweight status amongst pediatric lung transplant recipients with CF is high. However, we did not find a significant negative effect of underweight body habitus on survival in CF children after lung transplantation. Overweight pediatric recipients appear to have poorer survival after transplant.
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