Effects of lung transplantation on inpatient end of life care in cystic fibrosis

BACKGROUND: The impact of lung transplantation on end of life care in cystic fibrosis (CF) has not been widely investigated. METHODS: Information about end of life care was collected from records of all patients who died in our hospital from complications of CF between 1995 and 2005. Transplant and non-transplant patients were compared. RESULTS: Of 38 patients who died, 20 (53%) had received or were awaiting lung transplantation ("transplant" group), and 18 (47%) were not referred, declined transplant, or were removed from the waiting list ("non-transplant"). Transplant patients were more likely than non-transplant patients to die in the intensive care unit (17 (85%) versus 9 (50%); P=0.04). 16 (80%) transplant patients remained intubated at or shortly before death, versus 7 (39%) non-transplant patients (P=0.02). Do-not-resuscitate orders were written later for transplant patients; 12 (60%) on the day of death versus 5 (28%) in non-transplant patients (P=0.02). Transplant patients were less likely to participate in this decision. Alternatives to hospital death were rarely discussed. CONCLUSIONS: Receiving or awaiting lung transplantation affords more aggressive inpatient end of life care. Despite the chronic nature of CF and knowledge of a shortened life span, discussions about terminal care are often delayed until patients themselves are unable to participate.     

Defining palliative care in cystic fibrosis: A Delphi study

Background

The goal of palliative care is to improve quality of life for people with serious illness. We aimed to create a cystic fibrosis (CF)-specific definition of palliative care.

Cumulative radiation dose after lung transplantation in patients with cystic fibrosis

Purpose

The purpose of this study was first to evaluate the imaging-related cumulative post-transplantation radiation dose in cystic fibrosis (CF) lung transplantation (LT) recipients and second, to identify the occurrence and type of malignancies observed after LT.

Introducing the need for lung transplantation in children with cystic fibrosis: Parental experiences

Lung transplantation (LTx) is the only treatment available for adult and pediatric end-stage lung disease secondary to cystic fibrosis (CF). The timing of introducing LTx has significant medical and psychological implications for the child and the family. This study explored the views and recommendations of parents of children with CF, who had been asked to consider LTx and referred to a national transplant centre. Parents participated in a telephone-based, semi-structured interview. Responses were analysed using Content Analysis. Parental recommendations and the emergent protocol are discussed, together with implications for clinical practice.     

Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation

Background

Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies.

Long-term outcome of lung transplantation for cystic fibrosis — Danish results

Objective: Over the last decades improvements in medical therapies have delayed the progression of lung disease in cystic fibrosis (CF). However, lung disease is still the most common cause of premature death, and lung transplantation today is the only treatment for end-stage lung disease in patients with CF. We present a retrospective review of the outcome of CF patients transplanted in Denmark since start of the national lung transplantation programme in 1992. Methods: In a 10-year period, 47 patients with CF were listed for lung transplantation; 29 patients underwent transplantation and 18 patients died while waiting for donor organs. Eleven patients received en block double lung transplantation with direct bronchial artery revascularization and 18 patients received bilateral sequential lung transplantation. Median age at transplantation was 29 years (range 11–50). Results: The perioperative mortality (≤30 days) was 3.5% (1/29 patients). Actuarial survival of transplanted patients at 1, 3, 5 and 8 years was 89, 80, 80 and 70%, respectively. Actuarial survival of non-transplanted patients on the waiting list at 1 and 2 years was 28 and 11% (P<0.0001). Causes of death of transplanted patients were: respiratory failure on day 7 (n=1), bronchiolitis obliterans syndrome (n=2), infection (Cytomegalovirus, Aspergillus fumigatus) (n=2), bronchial anastomosis dehiscence (n=1). Pulmonary function (FEV₁% predicted) improved from median 20% (range 13–31) pre-transplant to 71% (range 19–118) after 5 years (P<0.0001). Renal function (⁵¹Cr-EDTA clearance) decreased from median 97 ml/min (range 45–190) pre-transplant to 32 ml/min (range 8–84) 6 months after transplantation (P<0.001). Three patients (11%) received dialysis post-transplant of whom two underwent kidney transplantation. Immunosuppressive induction therapy with rabbit-antithymocyte-globulin compared to daclizumab resulted in fewer treatments for acute rejection within the first 3 months post-transplant (P=0.05 at 5–8 weeks). Burkholderia multivorans was present in three patients pre-transplant with satisfying long-term outcome in one patient. Conclusions: Lung transplantation is a well-established life-extending treatment for patients with CF and end-stage lung disease. The operative mortality is low and CF patients have a significant early survival benefit after lung transplantation. Satisfying long-term results can be achieved in this young and severely ill group of patients.     

Club cell secretory protein and lung function in children with cystic fibrosis

BackgroundClub cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF).MethodsWe used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEV₁ levels in adolescence (LLF and HLF groups, respectively; N = 130-per-group). Single nucleotide variants (SNVs) in the SCGB1A1, EHF-APIP loci were tested for association with circulating CC16 and with decline of FEV₁ and FEV₁/FVC% predicted levels between ages 7–16 using mixed models.ResultsCompared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p = 0.0002) and higher levels of the normalized inflammatory score (-0.21 vs 0.21, p = 0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p<0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEV₁/FVC and, marginally, FEV₁ (p = 0.003 and 0.025, respectively; N = 611 participants, 20,801 lung function observations).ConclusionsSerum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240 A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.     

Combined heart-lung-liver, double lung-liver, and isolated liver transplantation for cystic fibrosis in children

Abstract Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF) who were accepted either for combined transplantation or isolated liver transplantation died while waiting for a graft; 11 underwent transplantation and 5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group 1) underwent one of the following procedures: heart-lung-liver ( n = 4), sequential double lung-liver ( n = 2), or bilateral lobar lung from a split left lung and reduced liver ( n = 1). During the same period, the four other children (group 2) underwent isolated liver transplantation (three full-size livers, one partial liver). There was one perioperative death in each group. Pulmonary infection was the most common cause of morbidity in group 1. Other complications in group 1 included tracheobronchial stenosis ( n = 2), biliary stricture ( n = 2), and severe ascites ( n = 2). All were successfully treated. Oblit-erative bronchiolitis developed in three patients. This was treated with FK 506. In group 2, pulmonary function tests improved or remained stable after liver transplantation. Surgical complications in group 2 included severe ascites ( n = 1), biliary stricture ( n = 1), and abscess of the liver ( n = 1). Actuarial survival was 85.7 %% 2 % in group 1 at 1 year; it remained unchanged at 3 years and was 64.2 % at 5 years.     

双肺移植治疗儿童囊性纤维化的多学科综合诊疗

目的  通过多学科综合诊疗（MDT）模式提高双肺移植治疗儿童囊性纤维化的外科疗效。方法  对1例国内罕见的终末期囊性纤维化10岁患儿进行肺移植术前MDT讨论,制定对应治疗方案。结果  患儿确诊囊性纤维化5年,肺移植指征明确,经过MDT讨论决定行Clam-shell切口下双肺移植术,术中维持生命体征稳定,术后给予呼吸机辅助通气、抗感染、免疫抑制、抑酸和预防应激性溃疡等治疗,并根据患儿特点给予个体化治疗方案,术后恢复良好。结论  通过肺移植术前MDT讨论,肺移植治疗儿童囊性纤维化的手术效果满意,减少了术后并发症的发生风险,值得临床推广。     

Combined heart-lung-liver,double lung-liver,and isolated liver transplantation for cystic fibrosis in children

Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF) who were accepted either for combined transplantation or isolated liver transplantation died while waiting for a graft; 11 underwent transplantation and 5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group 1) underwent one of the following procedures: heartlung-liver (n = 4), sequential double lung-liver (n = 2), or bilateral lobar lung from a split left lung and reduced liver (n = 1). During the same period, the four other children (group 2) underwent isolated liver transplantation (three full-size livers, one partial liver). There was one perioperative death in each group. Pulmonary infection was the most common cause of morbidity in group 1. Other complications in group 1 included tracheobronchial stenosis (n = 2), biliary stricture (n = 2), and severe ascites (n = 2). All were successfully treated. Obliterative bronchiolitis developed in three patients. This was treated with FK 506. In group 2, pulmonary function tests improved or remained stable after liver transplantation. Surgical complications in group 2 included severe ascites (n =1), biliary stricture (n = 1), and abscess of the liver (n = 1). Actuarial survival was 85.7 % ± 2 % in group 1 at 1 year; it remained unchanged at 3 years and was 64.2 % at 5 years.     

Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.     

Pulmonary exacerbations and acute declines in lung function in patients with cystic fibrosis

Background

Patients with cystic fibrosis (CF) who experience acute declines in percent predicted FEV₁ (ppFEV₁ decreased ≥10% relative to baseline) are often not treated with antibiotics for pulmonary exacerbations (PEx), whereas other patients are treated even when they have not experienced a decline in lung function.

肺移植治疗囊性纤维化1例并文献复习

目的 探讨肺移植治疗囊性纤维化（CF）的疗效和预后。 方法 回顾性分析行同种异体双肺移植术治疗1例终末期CF受者的临床资料,对CF受者的临床特点、诊断方法及治疗策略进行总结。 结果 本例受者幼年发病,反复咳嗽、咳浓痰30年,肺部反复感染合并急性加重、慢性鼻窦炎及极重度营养不良,肺移植术前因呼吸肌无力难以脱离有创呼吸机,长期入住重症监护室（ICU）。影像学检查提示双肺多发囊柱状支气管扩张伴感染,经汗液测试和基因检测进一步确诊为CF。该受者2017年8月17日接受双肺移植术后经过康复治疗,肺功能逐渐恢复正常,康复后至投稿日已2年余,享有与同龄健康人同等的生活质量。 结论 肺移植术作为终末期CF的有效治疗手段,不仅能挽救患者生命,而且还能显著提高患者的生活质量。     

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease

Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1 s [ppFEV₁] < 40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV₁: 34 [31–36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV₁ from baseline at 2-hours (median [IQR] relative change: ? 19 [? 21 to ? 11]%, p < 0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV₁ < 40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease.     

Variability of lung clearance index in clinically stable cystic fibrosis lung disease in school age children

Background

Data on long term variability of Lung Clearance Index (LCI) in Cystic Fibrosis (CF) is urgently needed to guide test result interpretation. Our aim was to evaluate LCI variability in clinically stable CF lung disease in school age children.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF.Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases.We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.     

Transplant center volume and outcomes in lung transplantation for cystic fibrosis

Transplant volume represents lung transplant (LTx) expertise and predicts outcomes, so we sought to determine outcomes related to center volumes in cystic fibrosis (CF). United Network for Organ Sharing data were queried for patients with CF in the United States (US) receiving bilateral LTx from 2005 to 2015. Multivariable Cox regression was used to model survival to 1 year and long‐term (>1 year) survival, conditional on surviving at least 1 year. A total of 2025 patients and 67 centers were included in the analysis. The median annual LTx volumes were three in CF [interquartile range (IQR): 2, 6] and 17 in non‐CF (IQR: 8, 33). Multivariable Cox regression in cases with complete data and surviving at least 1 year (n = 1510) demonstrated that greater annual CF LTx volume (HR per 10 LTx = 0.66; 95% CI: 0.49, 0.89; P = 0.006) but not greater non‐CF LTx volume (HR = 1.00; 95% CI: 0.96, 1.05; P = 0.844) was associated with improved long‐term survival in LTx recipients with CF. A Wald interaction test confirmed that CF LTx volume was more strongly associated with long‐term outcomes than non‐CF LTx volume (P = 0.012). In a US cohort, center volume was not associated with 1‐year survival. CF‐specific expertise predicted improved long‐term outcomes of LTx for CF, whereas general LTx expertise was unassociated with CF patients’ survival.     

Incidence and prevalence of diabetes mellitus in patients with cystic fibrosis undergoing lung transplantation before and after lung transplantation

Cystic fibrosis (CF) related diabetes mellitus (DM) occurs in 15% of adult pancreatic insufficient CF patients. Lung transplantation is a treatment option for end-stage CF. We hypothesized that the prevalence of DM increases after lung transplantation. The study population included adult patients undergoing lung transplantation from March 1988 to March 2002 for end-stage CF at the University of Toronto. Demographic data, exocrine pancreatic function, presence of DM before and after transplant, as well as timing of its development after transplant were collected. Eighty-six patients met the study criteria; 77 of 86 (89.5%) of patients were pancreatic insufficient and were further analyzed. Median follow-up post-transplant was 3.3 yr (interquartile range: 1.2-7.2). Their mean age was 29.7 +/- 8.1 yr and 46 of 77 (59.7%) were male. The prevalence of DM increased from 22 of 77 (28.6%) before transplant to 38 of 77 (49.4%) after transplant (p = 0.008). The median time of DM development after transplant was 80 d (range: 13-4352). Sixteen of 55 (29.1%) of pancreatic insufficient patients who were non-diabetic prior to transplant, developed DM after transplant. DM is common in CF patients undergoing lung transplantation and the prevalence increases after transplant.