Cystic Fibrosis Undergoing Lung Transplantation Research Articles

(1404) - Assessing the Relationship Between Pre-Operative Opioid Use and Outcomes of Patients with Cystic Fibrosis Undergoing Lung Transplantation

(1404) - Assessing the Relationship Between Pre-Operative Opioid Use and Outcomes of Patients with Cystic Fibrosis Undergoing Lung Transplantation

737 Psoas muscle area may be a useful measure to predict fracture risk in people with cystic fibrosis undergoing lung transplantation

737 Psoas muscle area may be a useful measure to predict fracture risk in people with cystic fibrosis undergoing lung transplantation

Experiences and perceptions of receiving and prescribing rehabilitation in adults with cystic fibrosis undergoing lung transplantation.

Rehabilitation is prescribed to optimize fitness before lung transplantation (LTx) and facilitate post-transplant recovery. Individuals with cystic fibrosis (CF) may experience unique health issues that impact participation. Patient and healthcare provider semi-structured interviews were administered to explore perceptions and experiences of rehabilitation before and after LTx in adults with CF. Interviews were analyzed via inductive thematic analysis. Eleven participants were interviewed between February and October 2021 (five patients, median 28 (IQR 27-29) years, one awaiting re-LTx, four following first or second LTx) and six healthcare providers. Rehabilitation was delivered both in-person and virtually using a remote monitoring App. Six key themes emerged: (i) structured exercise benefits both physical and mental health, (ii) CF-specific physiological impairments were a large barrier, (iii) supportive in-person or virtual relationships facilitated participation, (iv) CF-specific evidence and resources are needed, (v) tele-rehabilitation experiences during the COVID-19 pandemic resulted in preferences for a hybrid model and (vi) virtual platforms and clinical workflows require further optimization. There was good engagement with remote data entry alongside satisfaction with virtual support. Structured rehabilitation provided multiple benefits and a hybrid model was preferred going forward. Future optimization of tele-rehabilitation processes and increased evidence to support exercise along the continuum of CF care are needed.

Predictors of long-term employment among patients with cystic fibrosis undergoing lung transplantation.

Lung transplantation is an established therapy in selected patients with advanced cystic fibrosis lung disease. Resumption of employment after lung transplantation is generally supported. In Switzerland, there are no data on long-term employment in people with cystic fibrosis undergoing lung transplantation. In a single-centre, cross-sectional study at a Swiss university hospital, clinical data from lung transplant recipients with cystic fibrosis, covering the transplantation period from January 1996 to December 2016, were analysed retrospectively. The potential influence of pre-lung transplantation factors (age, sex, lung function, body mass index, six-minute walk test distance, lung transplantation wait list time, paid employment on the wait list, education, relationship status, housing situation) and post-lung transplantation factors (chronic allograft dysfunction [CLAD], dialysis, cancer diagnosis [except skin cancer]) on paid employment and work percentage after lung transplantation were investigated using mixed logistic and linear regression models. Descriptive analyses of paid employment were performed for various periods after lung transplantation (<1, 1–3, 3–5, 5–10, >10 years). Data are reported as odds ratios (ORs) or coefficients (β) with their 95% confidence intervals (CIs). Eighty-four subjects (46.4% female) with a mean ± SD age of 29.9 ± 8.4 years were included in the study. Mean wait time for lung transplantation was 42.7 ± 40.2 weeks. The number (percentage) of subjects employed <1 year, 1–3 years, 3–5 years, 5–10 years and >10 years after lung transplantation was n = 23 (28%), n = 51 (65%), n = 44 (75%), n = 30 (68%) and n = 21 (75%), respectively. In mixed logistic regression models, pre-lung transplantation paid employment (OR 24.03, 95% CI 6.08 to 164.39, p <0.0001), academic education (OR 7.81, 95% CI 1.66 to 48.66, p = 0.01) and time post lung transplantation (on log scale, OR 5.81, 95% CI 3.15 to 12.78, p <0.0001) were the main factors influencing post-lung transplantation paid employment status. In mixed linear regression models, pre-lung transplantation paid employment (β = 21.40, 95% CI 10.98 to 31.81, p = 0.00014), academic education (β = 12.54, 95% CI 0.48 to 24.55, p = 0.05) and time post lung transplantation (on log scale, β = 8.96, 95% CI 6.17 to 11.82, p <0.0001) were the main factors influencing work percentage post lung transplantation. No evidence for an influence of clinical factors such as CLAD, cancer or dialysis on post-lung transplantation employment and work percentage was found. Pre-transplant employment is the dominant factor influencing lung transplantation employment in people with cystic fibrosis. People with cystic fibrosis undergoing lung transplantation should be encouraged to work for as long as their health status permits. Professional reintegration after successful lung transplantation should be supported by a multi-disciplinary lung transplant team.

Clinical Outcomes after Pediatric Lung Transplantation at Cystic Fibrosis Care Centers

Clinical outcomes remain extremely poor for children with cystic fibrosis undergoing lung transplantation. Since 1961, the Cystic Fibrosis Foundation has maintained a network of accredited Cystic Fibrosis Care Centers (CFCC) designated to deliver specialized, multidisciplinary care for people with cystic fibrosis (CF). While this integrated clinical approach is thought to be beneficial in patients undergoing transplantation, it remains unknown whether lung transplantation at a CFCC is associated with improved long-term outcomes among children with CF. We used the Scientific Registry of Transplant Recipients to identify all children (age <18 years) with CF who underwent first-time lung transplantation between 2005-2018. Clinical, demographic, and donor characteristics were compared between groups. We used multivariable Cox proportional hazards modeling to compare graft survival (defined as freedom from death, graft failure, or retransplantation) in children treated at CFCCs and non-CFCC centers. We included 336 children with CF who underwent lung transplantation during the study period. Of these patients, 229 (68%) were transplanted at CFCCs. During a median follow-up time of 2.5 person-years, 35 (10%) children experienced graft failure or underwent retransplantation, and 7 (2%) children were lost to follow-up. In our multivariable Cox proportional hazards model, there was no significant difference in graft survival (HR 1.13, 95% CI 0.82-1.56) or overall survival (HR 1.10, 95% CI 0.77-1.57). In children with CF, lung transplantation at a designated CFCC was not associated with a significant improvement in overall or graft survival. While treatment at a CFCC may not be associated with improved survival after pediatric lung transplantation, specialized care at a CFCC may result in improvements in other aspects of care which could not be assessed in this analysis.

Bone Mineral Density and Fat-Soluble Vitamin Status in Adults with Cystic Fibrosis Undergoing Lung Transplantation: A Pilot Study.

Patients with cystic fibrosis (CF) often experience low bone mineral density (BMD) pre- and post-lung transplantation (LTX). The study purpose was to describe BMD and micronutrient status in adults with CF pre- and post-LTX. Twelve patients with CF (29 ± 8 years) were recruited from the CF clinic at the University of Alberta Lung Transplant Program. BMD and vitamins A, D, E, K status, and parathyroid hormone were measured pre- and post-LTX. No significant differences pre- and post-LTX were observed at the different bone sites measured (lumber-spine, femoral-neck (FN), hip, and femoral-trochlea) (P > 0.05). BMD T-scores (<-2) was present in lumbar-spine, FN, hip, and femoral-trochlea in 33%, 17%, 17%, and 25% of individuals pre-LTX and 58%, 33%, 58%, and 33% of individuals post-LTX, respectively. More than 50% of patients had suboptimal vitamin K levels (PIVKA-II values >3 ng/mL) pre- and post-LTX. Adults with CF pre- and post-LTX had reduced BMD and suboptimal vitamin K status.

Impact of pulmonary hypertension on survival in patients with cystic fibrosis undergoing lung transplantation: An analysis of the UNOS registry

BackgroundPulmonary hypertension (PH) is a comorbidity reported in patients with cystic fibrosis (CF) with research limited to single-center studies. MethodsTo assess the impact of PH in patients with CF who received a lung transplant (LTx), the United Network for Organ Sharing was queried from 1987 to 2012, restricting analysis to transplant patients 6–55years old between 1/1/2005 and 7/6/2011. ResultsOf 23,951 lung transplants, 1177 met inclusion criteria with 831 having mean pulmonary artery pressure (mPAP) data available. For the entire cohort, mean age was 30.3 (SD=9.2, range 12–55), and mean mPAP was 26.5 (SD=7.8, range 5–66) mmHg. A total of 470 (57%) had PH defined as mPAP≥25mmHg. Comparing PH to non-PH groups, mean forced expiratory volume in one second (FEV1) was 24.4 (SD=13.8) vs. 26 (SD=13.9) % of predicted, mean supplemental oxygen requirement at rest was 4.5 (SD=4.1) vs. 3.7 (SD=3.0) liters per minute, and mean lung allocation score was 49 (SD=16) vs. 43 (SD=12), respectively. For the PH group, median survival was 84.4months compared to 67.1months for the non-PH group (log-rank p-value=0.326). The adjusted hazard ratio for PH vs. non-PH was 0.862 (95% CI: 0.653–1.138; p=0.293), thus indicating no statistically significant effect of PH on survival. ConclusionsA high prevalence of PH was found in CF patients prior to LTx. Based on our models despite PH being prevalent, there is no strong evidence suggesting that it significantly alters the risk of death in CF patients after LTx.

285* The impact of BMI on survival of patients with cystic fibrosis undergoing lung transplantation: a single centre experience

285* The impact of BMI on survival of patients with cystic fibrosis undergoing lung transplantation: a single centre experience

Outcomes of patients with cystic fibrosis undergoing lung transplantation with and without cystic fibrosis-associated liver cirrhosis*

People with severe cystic fibrosis (CF) lung disease with co-existent CF-associated liver disease (CFLD) are often excluded from consideration of sole lung transplantation, largely because of the concerns that they will subsequently develop hepatic decompensation. This retrospective cohort study aimed at determining whether patients with severe cirrhosis caused by CFLD have any differences in perioperative and relevant post-transplant outcomes compared to CF patients without CFLD when undergoing sole lung transplantation. Six patients with CFLD were matched with 18 CF patients without CFLD undergoing sole lung transplant at the same institution. There were no differences in total operative time or intra-operative requirements for cardiopulmonary bypass or blood products. Over a period of five yr post-transplant, no differences were observed between the two groups in body mass index, six-min walk, lung function, and survival. None of the CFLD subjects developed variceal bleeding; however, one developed hepatocellular and renal failure at four yr post-transplant and is being assessed for liver-kidney transplant. One additional patient with CFLD required repeat lung transplantation for bronchiolitis obliterans syndrome. This study provides evidence that CF patients with liver cirrhosis caused by CFLD can safely be considered for sole lung transplantation provided there is no evidence of significant hepatocellular dysfunction with decompensated cirrhosis or hepatic synthetic failure.

Loss of Cystic Fibrosis Transmembrane Conductance Regulator Function Enhances Activation of p38 and ERK MAPKs, Increasing Interleukin-6 Synthesis in Airway Epithelial Cells Exposed to Pseudomonas aeruginosa

In cystic fibrosis (CF), the absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) translates into chronic bacterial infection, excessive inflammation, tissue damage, impaired lung function and eventual death. Understanding the mechanisms underlying this vicious circle of inflammation is important to design better therapies for CF. We found in CF lung biopsies increased immunoreactivity for p38 MAPK activity markers. Moreover, when compared with their non-CF counterpart, airway epithelial cells expressing the most common mutation in CF (CFTRDeltaF508) were more potent at inducing neutrophil chemotaxis through increased interleukin (IL)-6 synthesis when challenged with Pseudomonas aeruginosa diffusible material. We then discovered that in CFTRDeltaF508 cells, the p38 and ERK MAPKs are hyperactivated in response to P. aeruginosa diffusible material, leading to increased IL-6 mRNA expression and stability. Moreover, although TLR5 contributes to p38 MAPK activation upon P. aeruginosa challenge, it only played a weak role in IL-6 synthesis. Instead, we found that the production of reactive oxygen species is essential for IL-6 synthesis in response to P. aeruginosa diffusible material. Finally, we uncovered that in CFTRDeltaF508 cells, the extracellular glutathione levels are decreased, leading to a greater sensitivity to reactive oxygen species, providing an explanation for the hyperactivation of the p38 and ERK MAPKs and increased IL-6 synthesis. Taken together, our study has characterized a mechanism whereby the CFTRDeltaF508 mutation in airway epithelial cells contributes to increase inflammation of the airways.

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients

Special Considerations for Patients With Cystic Fibrosis Undergoing Lung Transplantation

This article reviews lung transplantation in patients with cystic fibrosis (CF). Lung transplantation is commonly utilized for patients with end-stage CF. There are several characteristics of CF that present unique challenges before and after lung transplantation. There is new information available that can be utilized to predict outcomes in patients with end-stage CF, and therefore can help in decisions of referral and listing for lung transplantation. The new lung allocation score, which allocates organs to patients who are on the lung transplant waiting list in the United States, presents new challenges and opportunities for patients with end-stage CF. In addition, the effect of the presence of microbiological flora prior to lung transplantation has been better linked to outcomes after lung transplantation. It is now known that, other than those patients harboring Burkholderia cepacia in their lungs before transplantation, most CF patients can undergo transplantation successfully. Nutrition remains an important issue among CF patients, and diabetes is a common problem after lung transplantation. In contrast, liver disease does not usually present major problems but, if it is severe, can necessitate liver and lung transplantation. Mechanical ventilation prior to transplantation might not be an absolute contraindication for CF patients. CF lung transplant recipients have good outcomes after lung transplantation compared with those of other lung transplant recipients. Quality of life is dramatically improved. However, they are still prone to common complications that all lung transplant recipients are prone to, including primary graft dysfunction, acute and chronic rejection, a variety of infections and malignancies, and renal failure.

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.

Burkholderia cepacia infection and lung transplantation.

Burkholderia cepacia has emerged as an important pathogen in patients with cystic fibrosis (CF) undergoing lung transplantation. Taxonomic analyses have divided B. cepacia into 7 closely related species called genomovars. The prevalence of B. cepacia infection ranges from 2% to 13% in CF patients with genomovar III being most prevalent. Risk factors for the acquisition of B. cepacia include greater severity of underlying CF, increasing age, having a sibling colonized with B. cepacia, and previous hospitalizations. One-year survival in patients with CF undergoing lung transplantation usually have been reported to be less than 70%. The antimicrobial resistance pattern of B. cepacia has correlated with inconsistent effect on survival. Presence of genomovar III also has been linked with survival of B. cepacia-infected patients; the survival rates were inferior for genomovar III as compared with non-genomovar III patients. Standard infection control techniques including isolation of both colonized and noncolonized individuals with frequent sputum culture have been recommended to prevent CF patients from acquiring B. cepacia infection. B. cepacia is inherently resistant to antipseudomonal antibiotics, colistin, and polymyxin. The combination of 2 or more antibiotics usually is recommended for the treatment of B. cepacia infections. Studies delineating the epidemiology and influence of B. cepacia infection on lung transplantation are warranted. This is a US government work. There are no restrictions on its use.