A National Survey Comparing Patients' and Transplant Professionals' Research Priorities in the Swiss Transplant Cohort Study.

We aimed to identify, assess, compare and map research priorities of patients and professionals in the Swiss Transplant Cohort Study. The project followed 3 steps. 1) Focus group interviews identified patients' (n = 22) research priorities. 2) A nationwide survey assessed and compared the priorities in 292 patients and 175 professionals. 3) Priorities were mapped to the 4 levels of Bronfenbrenner's ecological framework. The 13 research priorities (financial pressure, medication taking, continuity of care, emotional well-being, return to work, trustful relationships, person-centredness, organization of care, exercise and physical fitness, graft functioning, pregnancy, peer contact and public knowledge of transplantation), addressed all framework levels: patient (n = 7), micro (n = 3), meso (n = 2), and macro (n = 1). Comparing each group's top 10 priorities revealed that continuity of care received highest importance rating from both (92.2% patients, 92.5% professionals), with 3 more agreements between the groups. Otherwise, perspectives were more diverse than congruent: Patients emphasized patient level priorities (emotional well-being, graft functioning, return to work), professionals those on the meso level (continuity of care, organization of care). Patients' research priorities highlighted a need to expand research to the micro, meso and macro level. Discrepancies should be recognized to avoid understudying topics that are more important to professionals than to patients.

The Actualization of the Transplantation Complex on the Axis of Psychosomatic Totality-Results of a Qualitative Study.

Although transplantation medicine is not new, there is a clinically justified gap in the existing literature with respect to the psychological processing of lung transplants. The present study aims to examine whether lung transplantation leads to an actualization of psychological, e.g., oral-sadistic fantasies. Following a qualitative approach, 38 lung transplant patients were interviewed three times within the first six months after transplantation. Data analysis focused on identifying unconscious and conscious material. The inter-rater reliability for all codes was calculated using Krippendorff's Alpha (c-α-binary = 0.94). Direct and implicit evidence of a so-called transplantation complex was detected e.g., regarding the "incorporation" of the dead donor and his lungs. These processes occur predominantly at an imaginary level and are related to the body. Our findings emphasize that such psychological aspects should be borne in mind in the psychological treatment of lung-transplant patients in order to improve the processing of lung transplants, and that this might have a positive effect on patient adherence.

The experience of transplantation as reflected in dream life: A case study illustrating the mental processing of a lung transplant.

Although it is well known that a lung transplant enhances the recipient's quality of life, our knowledge of how it is processed mentally is limited. In this study, interviews were conducted with a lung-transplant patient two weeks, three months, and six months after surgery so as to investigate the relevant unconscious processing mechanisms. A dream reported in the first interview was analysed in accordance withapplying the Zurich Dream Process Coding System. A 'transplantation complex' was reconstructed on the basis of various sources of information (the dream and the waking narratives). The principal aspects of the transplantation complex that emerged from both the dream and the waking narratives concerned the oral-sadistic phantasy that the donor had been killed and that his lung, or soul, had been violently incorporated in the patient. The main unconscious themes involved in the processing of the transplant were found to have been already laid down in the dream and to have been presented in it in the form of visual analogues. According to our interpretation of the data analysed, powerful cannibalistic phantasies and death wishes played an important part in the processing of the transplant. These archaic phantasies may have been actualized by the transplant.

Transplantation experience as a predictor for quality of life during the first 6 months after lung transplantation.

OBJECTIVE: Quality of life (QoL) is a crucial goal of post-transplant care. This study investigated predictors of QoL within the first 6 months after transplantation. METHODS: Forty patients were assessed 2 weeks (T1), 3 months (T2), and 6 months post-transplant (T3). In the quantitative part, the EuroQol questionnaire (EQ-5D) and visualization methods (Prism) were applied. In the qualitative part, interviews were analyzed. Regression analyses were used to investigate the impact of the pictorial ratings at T1 on QoL at T2 and T3. The pictorial variables were related to the interviews for an in-depth analysis. RESULTS: There was an increase in QoL between T1 and T2 that remained stable from T2 to T3. Smaller distances in the variable Prism_Lung (acceptance of the lung) and larger distances in the variable Prism_Transplantation (distance to the transplantation experience) were related to the increase in QoL between T1 and T2 and to an higher QoL at T2. High-QoL patients were able to create an equilibrium of defense and acceptance. CONCLUSION: Psychological processes early after transplant are of significance for the development of QoL within the 6 months following the surgery. These insights demonstrate that a mixed methodological approach provides a helpful understanding of post-transplant processing.

Idiopathic Pulmonary Fibrosis in Switzerland: Diagnosis and Treatment.

Idiopathic pulmonary fibrosis (IPF) is a severe progressive and irreversible lung disease. Novel antifibrotic drugs that slow disease progression are now available. However, many issues regarding patient management remain unanswered, such as the choice between available drugs, their use in particular subgroups and clinical situations, time of treatment onset, termination, combination or switch, or nonpharmacologic management. To guide Swiss respiratory physicians in this evolving field still characterized by numerous areas of uncertainty, the Swiss Working Group for interstitial and rare lung diseases of the Swiss Respiratory Society provides a position paper on the diagnosis and treatment of IPF.

Patients' Early Post-Operative Experiences with Lung Transplantation: A Longitudinal Qualitative Study.

BACKGROUND AND OBJECTIVES: Lung transplantation is a complex medical treatment, and for patients with end-stage lung diseases it is often the last therapeutic option available for survival. However, lung transplantation poses not only a physical but also a psychological challenge for patients. The aim of this study was to gain a deeper understanding of patients' individual concerns related to their lung transplantation within the first 6 months post-transplant. METHODS: Forty lung transplant patients were interviewed at three different measurement timepoints post-transplant (T1: 2 weeks; T2: 3 months; and T3: 6 months) using semi-structured interviews to address their thoughts, feelings, and attitudes with respect to the transplantation process, their new lungs, and their medication. Interviews were analyzed by means of qualitative content analysis. RESULTS: "Physical complaints", "fear of organ rejection", "side effects of medication", and "restrictions in everyday life" were the most frequently named concerns within the first 6 months post-transplant. Most themes remained unchanged over time, whereas mentions of restrictions in everyday life increased significantly over the three assessments. CONCLUSIONS: Although the majority of the patients experienced considerable improvements in physical health after transplantation, they simultaneously reported that they were suffering from physical complaints, fear of organ rejection and infections, medication adverse effects, and restrictions in everyday life. For patients, lung transplantation therefore often means replacing one disease with another. Healthcare providers are challenged to support patients in dealing with this unresolvable dilemma.

Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Intra-operative extracorporeal membrane oxygenation use in pediatric lung transplantation--the Zurich experience.

There is a lack of data regarding use of ECMO in children undergoing lung transplantation. We evaluated our experience of ECMO in pediatric lung transplant recipients. All patients (<18 yr) who underwent lung transplants between 1997 and 2011 were included (17 children; nine males; median age 16 yr), and the use of intra-operative ECMO evaluated. Transplant procedures were carried out with intra-operative ECMO in seven children (all bilateral lung transplants). Demographics of ECMO and non-ECMO patients were comparable. One child was already on ECMO pre-operative. Lung graft size reduction was undertaken in five ECMO and four non-ECMO cases, respectively. Five patients were taken off ECMO intra-operatively; the other patients were weaned off ECMO within 48 h post-operatively. Three-months survival was 100%. By 12 months post-transplantation, one patient each died in the ECMO and in the non-ECMO group. At the end of the study, six of seven ECMO cases were still alive (median survival 48.5 months); one patient required a retransplant at 53 months. Our small case series suggests that lung transplant procedures can be safely carried out in selected children on intra-operative ECMO support; however, our pediatric experience regarding this scenario is very limited but probably almost unique.

A new heterotopic transplant animal model of intestinal fibrosis.

BACKGROUND: Severe mucosal tissue damage requiring efficient wound healing is a main feature of inflammatory bowel disease but excessive tissue repair promotes fibrosis. The clinical investigation of fibrosis is confined to the limited amount of biological material available from patients. This makes the establishment of a new animal model, a highly desirable goal. We investigated whether intestinal fibrosis occurs after heterotopic transplantation of small bowel resections in rats. METHODS: Donor (Brown Norway or Lewis rats) small bowel resections were transplanted subcutaneously into the neck of recipients (Lewis rats). Grafts were explanted 2, 7, 14, and 21 days after transplantation. RESULTS: Heterotopic intestinal transplants remained viable for 21 days. Rapid loss of crypt structures at day 2 after intestinal transplantation was followed by lymphocyte infiltration and obliteration of the intestinal lumen by fibrous tissue at day 21. Loss of the intestinal epithelium was confirmed by the lack of cytokeratin staining in immunohistochemistry. Collagen expression was increased with time after transplantation as confirmed by real-time PCRs, Elastica van Gieson, and Sirius Red staining. Lumen obliteration was connected with increased expression of potent mediators of fibrosis such as α5ß6 integrin, interleukin (IL)-13, and transforming growth factor ß. Myofibroblast phenotype was demonstrated by the presence of both α-smooth muscle actin and vimentin in the obliterated lumen. CONCLUSIONS: We established a method for heterotopic transplantation of small bowel resections. A variety of histologic and molecular features of fibrosis were observed in the heterotopic intestinal grafts which suggests, that this new in vivo model will be instrumental in studying pathogenesis and treatment of intestinal fibrosis.

Zurich University Hospital lung transplantation programme: update 2012.

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.

Chronic infection with Pseudomonas aeruginosa in cystic fibrosis: a risk factor for nasal polyposis after lung transplantation.

BACKGROUND: Nasal polyposis (NP) is common in cystic fibrosis (CF) patients. The prevalence of the CF phenotype with NP after lung transplantation (LTx) is unknown. Risk factors for the development of NP after LTx are not well described. METHODS: CF patients with LTx at our center between November 1992 and December 2009 were included. They were regularly investigated with nasal endoscopy and aspiration of sinus secretions with microbiological evaluation. Patients with and without development of NP were compared along the following parameters: gender, age, dF508, diabetes, acute rejection, NP at LTx, and microbiology of the sinuses before and after LTx. A multivariate Cox regression analysis was performed. RESULTS: The study included 94 patients; 21 were excluded because of incomplete data. Thirty-five (48%) of the remaining 73 patients developed NP. Mean time to diagnosis of NP was 4.2 (2.9-5.6) years after LTx. Prevalence of NP was 11% after the first year and 18%, 33%, and 44% after the first 2, 5, and 10 years, respectively. Patients with posttransplantation NP were younger, had NP before LTx, and were chronically infected with Pseudomonas aeruginosa (PA) in the nose. Multivariate analysis demonstrated that chronic infection with PA was the only significant risk factor for the development of nasal polyps after LTx (hazards ratio, 7.2; 95% confidence interval, 2.1-24.2; P=0.001). CONCLUSIONS: In contrast to pretransplantation patients, NP is more common after LTx. Development of NP occurs throughout the whole observation time. Chronic sinonasal PA infection seems to be the only significant risk factor for NP after LTx.

Nasal polyposis in lung transplant recipients with cystic fibrosis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis is common in patients with cystic fibrosis (CF). There are still many open questions regarding factors related to this condition. Furthermore, the prevalence of nasal polyposis and its implications for the outcomes in lung transplant recipients with cystic fibrosis are unknown. METHODS: All CF patients who underwent lung transplantation at our centre between November 1992 and December 2009 were included. Nasal polyp status was determined endoscopically at time sinus surgery and its relationships to gender, age at lung transplantation, Liou raw score, body mass index, FEV1%predicted, diabetes mellitus, pre-transplant pseudomonas colonisation of the sinuses and the lungs, pre-transplant corticosteroid use and type of mutation of the CFTR gene were analysed. The post-transplant survival times and the incidence of bronchiolitis obliterans syndrome in patients with or without nasal polyposis were compared. RESULTS: Nasal polyps were found in 19% (17 patients) of the 89 lung transplant recipients, whose data was available for statistical analysis. None of the factors analysed was related to the nasal polyp status. The post-transplant survival times and the incidence of bronchiolitis obliterans syndrome did not significantly differ between patients with or without nasal polyposis. CONCLUSIONS: CF-related nasal polyposis occurs in a relevant fraction of lung transplant recipients. A specific effect of nasal polyposis on post-transplant outcome could not be confirmed. Nevertheless, there was a trend to NP recurrence in patients with post-transplant sinonasal pseudomonas colonisation and is a tendency of less chronic rejection in CF patients with nasal polyps.

Impact of sinus surgery on pseudomonal airway colonization, bronchiolitis obliterans syndrome and survival in cystic fibrosis lung transplant recipients.

BACKGROUND: Lung transplantation (LTx) is a therapy for patients with cystic fibrosis (CF) end-stage lung disease. Pseudomonal airway colonization (PAC) is common in CF. OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Posttransplant sinus surgery in lung transplant recipients with cystic fibrosis: a single institutional experience.

Chronic rhinosinusitis is hypothesised to play a major role in lung transplant recipients with cystic fibrosis. Paranasal sinuses are considered to accumulate a significant bacterial load, potentially leading to lung allograft infection with ensuing complications such as bronchiolitis obliterans syndrome, i.e. allograft rejection. We therefore would like to present our combined medical and surgical treatment plan, which consists of an endoscopic fronto-spheno-ethmoidectomy as well as a meticulous daily nasal care program. The microbiological results show that our combined concept is effective, whereas especially daily nasal care with isotonic saline solution is the cornerstone in preventing significant colonisation of the sinuses and spreading bacteria to the lower respiratory tract causing lung allograft infection. Regarding the surgical part of our treatment, it should be emphasised that all sinuses and ethmoidal air cells should be widely opened. Edges such as bony overhangs should be smoothened to avoid mucus retention and consecutive bacterial recolonisation requiring subsequent revision surgery.

Long-term outcomes of bilateral lobar lung transplantation.

OBJECTIVES: Lobar lung transplantation is an option that provides the possibility of transplanting an urgent listed recipient of small size with a size-mismatched donor lung by surgically reducing the size of the donor lung. We report our short- and long-term results with bilateral lobar lung transplantation (BLLT) and compare it with the long-term outcomes of our cohort. METHODS: Retrospective analyses of 75 lung transplant recipients who received downsized lungs with a special focus on 23 recipients with BLLT performed since January 2000. Postoperative surgical complications, lung function tests, late complications and survival were analyzed. The decision to perform lobar transplantation was considered during allocation and finally decided prior to implantation. RESULTS: Cystic fibrosis was the most common indication (43.5%) followed by pulmonary fibrosis (35%). Median age at transplantation was 41 (range 13-66) years. Fifteen were females. Nineteen of the transplantations (83%) were done with extracorporeal membrane oxygenation (ECMO) support; 3 of them were already on ECMO prior to transplantation. There was no 30-day or in-hospital mortality. No bronchial complications occurred. The most common early complication was haematothorax (39%), which required surgical intervention. The rate of postoperative atrial arrhythmias was 30%. Forced expiratory volumes in 1 s (% predicted) at 1 and 2 years were 76 ± 23 and 76 ± 22, respectively (mean ± standard deviation). By 2-year follow-up, bronchiolitis obliterans syndrome was documented in 3 patients with a median follow-up of 1457 days. Overall survivals at 1 and 5 years were 82 ± 8 and 64 ± 11%, respectively and were comparable with those of 219 other recipients who received bilateral lung transplantation during the same period (log rank test, P = 0.56). CONCLUSIONS: This study demonstrates that BLLT has short- and long-term outcomes comparable with those of standard bilateral lung transplantation. The limitation of lung transplantation due to size-mismatch, particularly in smaller recipients, could be overcome by utilizing lobar lung transplantation.

Body mass index and its effect on outcome in children after lung transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Practical approach to emergencies in lung transplant recipients: how we do it.

Lung transplant recipients (LTRs) are prone to medical complications and emergencies due to the transplanted organ being in constant direct contact with the environment and the need for life-long profound immunosuppression (IS). As a result of these specific circumstances, the medical and surgical management of LTRs frequently differs from usual standard care. Therefore, we outline here some of the principles we take into account when dealing with the most frequent medical emergencies encountered in our lung transplant cohort in Zurich. The main topics dealt with are: diagnostics and treatment of infections, gastrointestinal emergencies, IS and other medication issues as well as work-up of unclear inflammatory signs and peri-operative precautions in LTRs. Early post-operative transplant complications, rare medical emergencies and surgical problems are not covered. Our report is intended to help internists and pulmonologists new to the field to obtain a better understanding of the peculiarities of LTRs and their management.

Crystal precipitation and granulomatous inflammation in multiple organs after foscarnet therapy in a lung transplant recipient.

We present the case of a lung transplant recipient with disseminated crystal precipitation, and granulomatous and fibrinous inflammation after therapy with foscarnet (Foscavir; AstraZeneca, Zug, Switzerland) for recurring ganciclovir-resistant cytomegalovirus (CMV) reactivation. This is the first description of systemic crystal precipitation and granulomatous inflammation associated with foscarnet therapy with predominant involvement of the heart, kidneys and lungs.

Attitudes towards transplantation and medication among 121 heart, lung, liver and kidney recipients and their spouses.

QUESTIONS UNDER STUDY: A transplant represents a decisive event for patients and their caregivers. This article deals with the attitudes patients and their spouses have towards the transplantation. METHODS: In a cross-sectional study, 121 patients and their spouses were surveyed by questionnaire after a heart, lung, liver or kidney transplant. Attitudes were assessed by means of semantic differentials. Based on the results, an 'Attitudes towards Transplantation' Scale was developed. Sense of coherence (SOC-13), quality of life (Sf-36), quality of the relationship (RAS), burnout (BM) and the patient's emotional response to the transplant (TxEQ-D) were additional psychosocial variables measured in order to assess the association between the attitudes and psychosocial characteristics of transplant patients and their spouses. RESULTS: The majority of patients and their spouses reported positive attitudes towards the transplant, including the attitudes towards medication, their perceived self and fate of being a transplant patient or spouse. Patients and spouses, however, had a negative attitude towards the transplantation in terms of stress and anxiety. Patients reported greater emotional stress from the transplant and rated their post-transplant perceived fate more negatively than their spouses. Attitudes towards the transplant were significantly associated with the sense of coherence and the quality of relationship. CONCLUSION: The attitudes of patients and spouses to different aspects of the transplant itself and to being a transplant patient or spouse should be deliberately reconsidered and facilitated in the psychosocial counselling with regard to the comprehensibility, manageability and meaningfulness of the transplant experience as well as to potential conflicts in the partnership.