A case of bronchiolitis obliterans after living-donor renal transplantation

We herein report the case of a 20 year-old-man who developed bronchiolitis obliterans after living-donor renal transplantation. The patient presented with dyspnea on exertion and wheezing two years after renal transplantation, and spirometry showed an obstructive pattern. Surgical lung biopsy revealed subepithelial fibrosis that constricted and obstructed the intrabronchiolar space. Based on these findings, the patient was diagnosed with bronchiolitis obliterans. He was prescribed bronchodilators and azithromycin, and he achieved stable respiratory function for two years. The differential diagnosis of respiratory symptoms after renal transplantation includes opportunistic infection and drug-induced lung injury; however, bronchiolitis obliterans should also be considered.     

Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis jiroveci infection in orthotopic liver transplantation

Abstract: We report a patient who presented 6 months after orthotopic liver transplantation (OLT) with fever, dyspnea, and pulmonary infiltrates with biopsy‐confirmed Pneumocystis jiroveci infection associated with a process of bronchiolitis obliterans organizing pneumonia (BOOP). We present this second case of BOOP associated with P. carinii pneumonia after OLT to highlight the risk of such disease combination in all transplant patients as well as discuss the protective effect of post‐transplant prednisolone with trimethoprim‐sulfamethoxazole prophylaxis and the possible duration of prophylaxis.     

Constructive (obliterative) bronchiolitis

Constrictive bronchiolitis (CB), also termed in lung transplant patients obliterative bronchiolitis, is inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles with resultant narrowing of their lumens. CB is found in a variety of settings, most often as a complication of lung and heart-lung transplantation (affecting 34% to 39% of patients, usually in the first 2 years after transplantation) and bone marrow transplantation, but also in rheumatoid arthritis, after inhalation of toxic agents such as nitrogen dioxide, after ingestion of certain drugs such as penicillamine and ingestion of the East Asian vegetable Sauropus androgynous, and as a rare complication of adenovirus, influenza type A, measles, and Mycoplasma pneumoniae infections in children. In lung transplants, CB is the single most important factor leading to death thereafter. In one study, the overall mortality rate was 25%. However, at the same time, 87% of patients who were asymptomatic and diagnosed solely by transbronchial biopsy had resolution or stabilization of disease. Decreases in FEV1 from baseline can be used to clinically support CB in transplant patients; the term bronchiolitis obliterans syndrome is used to denote this clinical dysfunction, and a grading system has been established for it that is now widely used in the literature. Significant risk factors for the development of CB in lung transplants include alloantigen-dependent and -independent mechanisms. In the former group are late acute rejection and HLA mismatches at the A loci; in the latter are ischemia/reperfusion injuries to airways that result from the transplantation surgery and cytomegalovirus infection.     

Pulmonary disease caused by Mycobacterium chelonae in a heart-lung transplant recipient with obliterative bronchiolitis

A heart-lung transplant recipient with pulmonary disease caused by the rapidly growing nontuberculous Mycobacterium chelonae and obliterative bronchiolitis is presented. The clinical features, course, and management of the mycobacterial disease and the obliterative bronchiolitis are discussed. The role of transbronchial lung biopsy in determining the significance of rapidly growing mycobacteria in pulmonary specimens and in diagnosing infection and rejection is emphasized.     

Application of selection criteria in sequential double lung transplantation

Since the first sequential double lung transplant was performed in 1986, such procedures have been increasing in number and the criteria used as indications for this type of surgery have broadened. Our aim was to reflect on the application of selection criteria and to describe the anesthetic and surgical techniques and postoperative follow-up of 72 patients who underwent this type of transplant surgery between March 1993 and December 1998. Actuarial survival five years after surgery was 74.4%. Among patients requiring transplantation after septic disease, actuarial survival was 90.8% for cystic fibrosis and 88.2% for bronchiectasis. Of the preoperative risk factors analyzed (prior surgery, pachypleuritis, multiresistant germs, poor nutrition, mechanical ventilation and corticoid therapy), only prior treatment with high doses of corticoids proved significant. Eleven patients have been diagnosed of bronchiolitis obliterans, four have died and only two continue to experience difficulties in daily living. The high survival rate and the restriction-free life after recovery lead us to consider sequential double lung transplantation to be the treatment of choice for all pulmonary diseases.     

Mycobacterial infections in lung transplant recipients

BACKGROUND: Immunosuppression and chronic lung disease are known risk factors for mycobacterial infection and might be expected to develop with an increased frequency in lung transplant recipients. We therefore sought to document the incidence and type of mycobacterial infections in a large lung transplant program. METHODS: A retrospective review of 219 transplant procedures (60 single lung transplants and 159 double lung transplants) in 210 patients was conducted. All patients had scheduled surveillance bronchoscopies at 3, 6, 9, 12, 18, and 24 months, and yearly thereafter. BAL samples were processed routinely for mycobacterium. RESULTS: Eight patients (3.8%) had evidence of infection (5 men, 3 women; age range, 26 to 63 years). The reasons for transplant were obstructive lung disease (six), cystic fibrosis (one), and pulmonary fibrosis (one). Five recipients had infection in their native lungs; two of five cultured mycobacterium from BAL following transplantation. At least four of five patients had nontuberculous mycobacterium (one showed acid fast bacilli and granuloma on a biopsy specimen that was not sent for culture). None of the five developed disease (mean follow-up = 22 months; range, 3 to 30 months). The organisms were Mycobacterium avium complex (three), Mycobacterium xenopi (one), and unidentified (one). Of the three remaining patients who developed infection after transplantation, one grew Mycobacterium chelonae and the others grew Mycobacterium tuberculosis (both received double lung transplants and had no evidence of mycobacterium in their native lungs). The only definite symptomatic disease occurred in the patients with M tuberculosis, one of whom had evidence of dissemination. The patients with M tuberculosis responded to standard treatment. There have been no deaths due to mycobacterium. CONCLUSION: Mycobacterial disease rarely occurs following lung transplantation. Cultures for mycobacterium in surveillance BALs in the absence of symptoms are likely unnecessary.     

A multi-drug regimen for respiratory syncytial virus and parainfluenza virus infections in adult lung and heart–lung transplant recipients

V. Liu, G.S. Dhillon, D. Weill. A multi‐drug regimen for respiratory syncytial virus and parainfluenza virus infections in adult lung and heart–lung transplant recipients.
Transpl Infect Dis 2010: 12: 38–44. All rights reserved Background. Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can cause significant morbidity and mortality in lung and heart–lung transplant recipients. We evaluated the utility of a multi‐drug protocol for the treatment of RSV‐ and PIV‐related infections. Patients and methods. RSV or PIV was identified in 25 patients with a total of 29 infectious episodes between January 2006 and December 2007. The study included 20 women and 5 men, mean age 42 ± 13 years. Fifteen patients had received bilateral lung transplant and the remainder either received single lung or heart–lung transplant. Mean time from transplant to infection was 1192 days. RSV was identified in 23 cases, PIV in 7 cases. Patients underwent treatment with inhaled ribavirin, methylprednisolone, and intravenous immunoglobulin (IVIG). RSV‐positive patients were also treated with palivizumab. We retrospectively evaluated their clinical status and pulmonary function for a 1‐year interval before and after the date of infection. Results. Average baseline forced expiratory volume in 1 s (FEV₁) before infection was 2.14 ± 0.68 L/min. Average decline in FEV₁ was 5.7% at the time of infection. Average FEV₁ during post‐treatment follow‐up was not significantly different than baseline (2.16 ± 0.80 L/min). Among patients with bronchiolitis obliterans syndrome (BOS) stages 1, 2, or 3 at the time of infection, average FEV₁ declined by 14.8% and remained lower at 9.1% during follow‐up when compared with patients with BOS stages 0 or 0p. No complications resulted from treatment. One patient died during follow‐up as a result of pre‐existing liver failure. Conclusions. This study of lung and heart–lung transplant recipients infected with RSV and PIV shows that a multi‐drug regimen including inhaled ribavirin, corticosteroids, and IVIG (with or without palivizumab) is safe and effective. Prompt diagnosis and therapy for patients with RSV or PIV infections are critical for maintaining lung function.     

Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study

Bronchiolitis obliterans syndrome remains the leading cause of morbidity and mortality in the pulmonary transplant population. Previous studies show that macrolide antibiotics may be efficacious in the treatment of panbronchiolitis and cystic fibrosis. In the latter, azithromycin decreases the number of respiratory exacerbations, improves FEV1, and improves quality of life. We hypothesized that oral azithromycin therapy may improve lung function in patients with bronchiolitis obliterans syndrome. To test this hypothesis, we conducted an open-label pilot trial using maintenance azithromycin therapy in six lung transplant recipients (250 mg orally three times per week for a mean of 13.7 weeks). In this study, five of these six individuals demonstrated significant improvement in pulmonary function, as assessed by FEV1, as compared with their baseline values at the start of azithromycin therapy. The mean increase in the percentage of predicted FEV1 values in these individuals was 17.1% (p 相似文献   

Improved Survival Following Lung Transplantation with Long-Term Use Of Bilevel Positive Pressure Ventilation in Cystic Fibrosis

Bilevel positive airway pressure ventilation (BIPAP) has been used in cystic fibrosis (CF) patients as a bridge to transplantation. Our aim was to evaluate the effect of BIPAP use before transplantation on post-transplantation morbidity and mortality. We performed a retrospective study at a tertiary care center. Twelve CF patients (9 males; mean age = 26 years) were assessed. Group 1 consisted of eight patients that did not use BIPAP before lung transplantation. Group 2 comprised four patients who used BIPAP for 3–15 months while awaiting transplantation. Patients were evaluated before and two to ten years after transplantation. All eight patients who did not use BIPAP died two months to ten years after transplantation. All four BIPAP users are alive with no evidence of bronchiolitis obliterans two to eight years after lung transplantation. We demonstrated a significant improvement in acid-base balance (p < 0.01) and body mass index (p < 0.05) and a tendency toward improvement in the work of breathing and number of hospitalizations. We conclude that improvement in nutritional status and respiratory muscle strength before lung transplantation in BIPAP users may prevent post lung transplantation infection and acute rejection rate, which in turn may reduce chronic rejection (bronchiolitis obliterans) and improve long-term survival after lung transplantation.     

Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans.

The majority of patients who develop bronchiolitis obliterans, after lung transplantation, die within 2-3 yrs after onset since treatment with conventional immunosuppression is typically ineffective. A case/control study was conducted in lung transplant recipients with biopsy-documented bronchiolitis obliterans to determine whether aerosol cyclosporin use contributed to increased survival. The cases comprised 39 transplant recipients who received open-label aerosol cyclosporin treatment in addition to conventional immunosuppression. The controls were transplant recipients treated with conventional immunosuppression alone. There were 51 controls from the University of Pittsburgh Medical Center and 100 from a large multicentric database (Novartis Lung Transplant Database). Forced expiratory volume in one second expressed as a percentage of the predicted value was an independent predictor of survival in all patients with bronchiolitis obliterans. Cox proportional-hazards analysis revealed a survival advantage for aerosol cyclosporin cases compared to the Pittsburgh control group. A survival advantage was also seen when comparing study cases to multicentric controls. Aerosol cyclosporin, given with conventional immunosuppression to lung transplant recipients with bronchiolitis obliterans, provides a survival advantage over conventional therapy alone.     

Successful lung transplantation for chronic Mycobacterium abscessus infection in advanced cystic fibrosis,a case series

Pulmonary Mycobacterium abscessus infection in cystic fibrosis (CF) patients is difficult to treat and considered a contra‐indication for lung transplantation in most centers. We present four CF patients with chronic pulmonary M abscessus infection, in whom lung transplantation was performed. Through intensive treatment before transplantation, we achieved control of the infection in all but one patient. After a mean of 16 months of follow up, 3 patients are doing well, without evidence of local or disseminated recurrence. One patient died early post‐transplant due to an unrelated cause. These findings support the possibility of lung transplantation with favorable outcome in CF patients with M abscessus infection.     

Lung transplantation in patients with connective tissue disorders and esophageal dysmotility

SUMMARY. Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24‐h pH monitoring. Twenty‐three patients had esophageal manometry and ambulatory 24‐h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow‐up of 26 months (range 3–45) and one has bronchiolitis obliterans syndrome‐1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow‐up of 25 months (range 19–45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands.     

Pulmonary scedosporium infection following lung transplantation

Abstract: Infectious complications are frequent following lung transplantation. Tracheobronchial aspergillosis is the predominant fungal infection in these patients. Infections with Scedosporium apiospermium ( Pseudoallescheria boydii ) and Scedosporium prolificans ( Scedosporium inflatum ) have mainly been described in bone marrow transplant recipients and only occasionally in solid organ transplant recipients. We analysed risk factors, the clinical course and outcome of seven lung transplant recipients who developed pulmonary scedosporium infection. Scedosporium apiospermium was documented in bronchoalveolar lavage (BAL) of all seven and Scedosporium prolificans in the BAL of four of these patients. Scedosporium was detected 9–58 months after transplantation. Five of the seven patients had been treated for several months with itraconazole because of previous detection of aspergillus in BAL. All seven patients with scedosporium infection showed airway problems, including early ischemic airway stenosis in one and bronchiolitis obliterans syndrome in the other six patients. Combined treatment with itraconazole and fluconazole was not able to eradicate scedosporium. Four of the seven patients died with advanced bronchiolitis obliterans 3–35 months after the diagnosis of pulmonary scedosporium infection. Three patients are currently alive 3, 6 and 7 years after transplantation, showing persistent scedosporium infection. In conclusion, pulmonary scedosporium infection was seen in lung transplant recipients with structurally abnormal airways and under long-term therapy with itraconazole. Eradication of scedosporium proved difficult, but under combined treatment with itraconazole and fluconazole this opportunistic infection did not disseminate.     

HIV/AIDS合并非结核分枝杆菌肺病97例临床分析

目的 探讨HIV/AIDS合并非结核分枝杆菌(nontuberculosis mycobacteria, NTM)肺病的临床特点,以提高诊疗水平. 方法 对我院2009—2012年97例HIV/AIDS合并NTM肺病患者进行回顾性分析. 结果 97 例中咳嗽 93 例(95.88%),咳痰88例(90.72%),气喘71例(73.20%),发热70例(72.16%),消瘦69例(71.13%),乏力58例(59.79%),胸痛 47 例(48 . 45%),腹泻36例(37.11%). HIV感染途径为性乱史64例(65.98%),静脉吸毒史26例(26.80%),输血史2例(2.06%),不详5例(5.15%). 胸部影像学表现以双肺中下叶多见,多为左下肺受累,形态多种多样,并容易形成空洞及支气管扩张样改变,可见胸膜病变. 结论 HIV/AIDS合并NTM肺病的临床症状、胸部影像学表现、痰涂片、PPD试验和结核抗体检查酷似肺结核,在痰培养结果未回报前,临床上二者鉴别诊断非常困难.患者通常合并多处浅表淋巴结肿大,反复痰涂片抗酸杆菌阳性. 痰培养药物敏感性试验提示对一线抗结核药物耐药率高,应引起临床足够重视.     

High-dose corticosteroid therapy for bronchiolitis obliterans after bone marrow transplantation in children

Bronchiolitis obliterans (BO) is a rare but serious complication of paediatric allogenic bone marrow transplantation (BMT). Currently, there is no clear evidence that therapeutic interventions have a positive impact on the course of the disease. We here report our experience with high-dose pulse methylprednisolone therapy in children after BMT. Nine patients fulfilling clinical and radiologic signs of BO were included in this analysis. The total amount of treatment cycles with pulse methylprednisolone therapy ranged from 1 to 6 cycles (median four cycles). Oxygen saturation increased significantly with normalization of oxygen saturation at the end of therapy in all individuals. Normal oxygen saturation was maintained in all but one patient during follow-up (mean follow-up period 42 {plus/minus} 20 months, range 19-67 months). Forced expiratory volume in 1 s (FEV1) was within the normal range prior BMT and significantly diminished at the time of BO diagnosis. Treatment led to stabilization of lung function, with a significant improvement of FEV1 after 2 months. In all, 7/9 patients remained in clinically stable condition without further deterioration of lung function during follow-up. These data would suggest that anti-inflammatory therapy may be a valuable treatment option in paediatric patients with bronchiolitis obliterans after BMT.     

In sickness and in health: Living HIV positive kidney donation from a wife to her husband,with 7 years' post‐transplant follow‐up

Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for kidney transplantation. After the introduction of ART, several studies have demonstrated comparable patient and graft outcomes between HIV‐negative and HIV‐positive kidney recipients. The US Congress passed the HIV Organ Policy Equity (HOPE) Act in 2013, which permits research in the area of HIV‐positive to HIV‐positive transplantation. HIV‐infected living donation is also permitted under the HOPE Act. However, there is a concern regarding the safety of kidney donation in an HIV‐infected person, given the risk of renal disease associated with HIV infection. We report here the case of successful kidney transplantation from HIV‐positive living donor to HIV‐positive recipient performed in our center on July 2012. To the best of our knowledge, this is the earliest case done in this medical context to be reported in the literature, therefore, potentially carrying several important messages to the transplantation community. In the present case, the living‐donor kidney transplant was performed between a married couple infected with same strain of HIV‐1, both on effective ART with efficiently suppressed viral replication and satisfactory pre‐transplantation immune status.     

Mycobacterial infection after renal transplantation in a Western population

Abstract:  Mycobacterial infection is a serious opportunistic infection in renal transplant recipients. The incidence is higher in developing than in developed Western countries. This study is a single-centre retrospective review of the records of 2502 renal transplant recipients in Belgium. Fourteen cases of mycobacterial infection (9 Mycobacterium tuberculosis and 5 atypical mycobacterial infection) were diagnosed. The time interval between transplantation and diagnosis was 64 ± 80 months (mean ± SD, range 5–188) for M. tuberculosis and 92 ± 75 months (range 14–209) for atypical mycobacterial infection. The localisation of M. tuberculosis was pulmonary/pleural in 67% and extrapulmonary in 33%. The atypical mycobacterial infections were located in skin, tendons, and joints. Eight patients received IV prednisolone pulse therapy for acute rejection long before the time of mycobacterial infection. The initial antimycobacterial therapy consisted of a combination of isoniazid, rifampicin, and ethambutol in all patients. In patients with M. tuberculosis infection, a good response to antimycobacterial therapy was obtained. In patients with atypical mycobacterial infection, initial treatment was successful in 3 out of 5 patients, in 1 patient recurrence was diagnosed and in another patient, who is still under treatment at present, the initial treatment was adjusted after identification of the atypical mycobacterium and its antibiogram.
The incidence of mycobacterial infection after renal transplantation did not increase with newer immunosuppressive therapy. The major risk factor is the total dose of corticosteroids. All patients responded well without major reductions in immunosuppressive therapy. Chemoprophylaxis for high-risk patients still is recommended.     

High prevalence of gastroesophageal reflux in children after lung transplantation

Bronchiolitis obliterans and its clinical correlate bronchiolitis obliterans syndrome (BOS) are a major cause of morbidity and mortality following lung transplantation. Gastroesophageal reflux disease (GERD) may be a contributing factor for the development of BOS. Since 2002, all recipients of lung and heart-lung transplantation at our institution have been routinely investigated for GERD. In this observational study, we report on the prevalence of GERD in this population, including all pediatric patients undergoing single (SLTx) or double (DLTx) lung transplantation or heart-lung (HLTx) transplantation from January 2003-May 2004. GERD was assessed 3-6 months after transplantation by 24-hr pH testing. The fraction time (Ft) with a pH < 4 within a 24-hr period was recorded. Spirometry data, episodes of confirmed acute rejection, and demographic data were also collected. Ten transplant operations were performed: 4 DLTx, 1 SLTx, and 5 HLTx. Nine patients had cystic fibrosis. One patient had end-stage pulmonary disease secondary to chronic aspiration pneumonia and postadenovirus lung damage. Of 10 patients tested, 2 had severe GERD (Ft > 20%), 5 had moderate GERD (Ft 10-20%), 2 had mild GERD (Ft 5-10%), and 1 had no GERD. The only patient in this group with no GERD had a Nissen fundoplication pretransplant. All study patients were asymptomatic for GERD. All patients with episodes of rejection had moderate to severe GERD posttransplant. There was no association between severity of GERD and peak spirometry results posttransplant. Moderate to severe GERD is common following lung transplantation in children.     

Indications for liver transplantation for chronic viral hepatitis,and therapies for controlling hepatitis B virus infection before and after transplantation

The general indications for liver transplantation in hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and the issues surrounding treatment for HBV infection in the pre‐ and post‐transplant periods, are discussed. In general, transplantation is reserved for patients with end‐stage liver failure secondary to cirrhosis and a small population with acute liver failure. It is proposed that certain guidelines can be developed and that these should include any one of the following: a Child‐Pugh score ≥ 9, diuretic resistant ascites, recurrent portal hypertensive bleeding, recurrent encephalopathy, spontaneous bacterial peritonitis and the development of a small hepatocellular cancer (≤ 5 cm in diameter). Treatment for HBV infection now includes lamivudine therapy pre and post transplantation together with hepatitis B immunoglobulin. Such an approach has virtually abolished recurrence of HBV infection following liver transplantation.