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.

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.

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.

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.

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.

Exercise testing in pediatric lung transplant candidates with cystic fibrosis.

Exercise testing is considered an important prognostic tool for the selection of pediatric lung transplant candidates with end-stage CF lung disease. To better understand the current practice as it pertains to exercise testing, a self-administered questionnaire was distributed to 25 pediatric lung transplant centers within the IPLTC across Australia, Europe, and North America. All centers perform standardized exercise tests. Fifteen centers perform one single-field test (6MWT/12MWT), while seven perform a six-min walk plus an additional test: SWT (N = 1), 3MST (N = 1), and CPET (N = 5). Frequency of testing is markedly different among centers. Two centers conduct exercise testing once, all others at multiple time points. Equipment availability and cost were no limitations, but lack of time (20%) and personnel (16%), and paucity of prognostic evidence (16%) and reference values (12%) were stated. Exercise testing is considered important and extensively used in the evaluation of pediatric lung transplant candidates with CF; methods of exercise test and the frequency of testing vary widely. We propose a prospective multicenter study to evaluate the efficacy of exercise testing and its prognostic value using a standardized protocol.

Persistent photodamage following drug photosensitization in a lung-transplant recipient.

Photosensitivity is a well-known complication of treatment with quinolone antibiotics. Several transient phototoxic drug reactions have been described. We report a case of a persistent phototoxic reaction to ciprofloxacin in a lung-transplant recipient on a long-term immunosuppressive drug regimen.

Evidence for graft colonization with periodontal pathogens in lung transplant recipients. A pilot study.

Bronchiolitis obliterans syndrome (BOS) is a major cause of late graft dysfunction in lung transplant recipients. There is increasing evidence that beside alloimmunologic injury also non-alloimmunologic inflammatory conditions may raise the risk of acute and chronic rejection. The oral cavity represents a possible reservoir for pathogenic bacteria due to its close anatomical proximity. In this pilot study, the presence of pathogenic periodontal bacteria in the oral cavity as well as in the lungs of lung transplant recipients was investigated for the first time. Eight lung transplant recipients underwent broncho-alveolar lavage, transbronchial biopsies, and endobronchial biopsies. In addition to routinely performed examinations, pulmonary as well as plaque samples were assessed for Aggregatibacter actinomycetemcomitans (Aa), Tannerella forsythia (Tf), Porphyromonas gingivalis (Pg), and Treponema denticola (Td) with the aid of a hybridization technique. No or only one periodontal pathogen (solitarily Pg) was found in the gingival plaques of five of the eight patients (group A). In three patients, two or more periodontal pathogens were detetectable in the gingival samples (group B). Whereas group A also had not more than one periodontal pathogen in the lungs, group B had more than one species in the lungs. In group B, all patients suffered from BOS, whereas in group A only one patient was affected. This is the first evidence for the presence of periodontal pathogens in the lungs of lung transplant recipients. Further studies with larger cohorts are required to elucidate potential links between periodontal infection, pulmonary colonization, and rejection.

[Lung transplantation and patient evaluation]. / Lungentransplantation - wann muss in der Praxisdaran gedacht werden?

To date, lung transplantation is an established therapeutic modality for advanced lung disease. Post-transplant survival is excellent, but depends on sophisticated medical follow-up and treatment by a dedicated and experienced multidisciplinary lung transplant team. Transplantation leads to markedly improved quality of life. Medical complications after lung transplantation are frequent, such as infections (viral, bacterial and fungal), gastro-esophageal reflux, osteoporosis and chronic rejection. Prevention of these complications is crucial and lifelong adherence to therapy is warranted. The most important hurdle in transplantation medicine to date is the marked shortage of donor organs making it impossible to transplant all patients in need. Living donation and ex vivo reconditioning of marginal lungs might bring some relief.

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.

Mycophenolate mofetil reduces alveolar inflammation, acute rejection and graft loss due to bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is still the main complication after lung transplantation. Besides other improvements in post-operative management, newer immunosuppressive regimens might decrease the devastating sequelae of this complication. METHODS: We compared the prospectively collected data of lung transplant recipients treated either with azathioprine (AZA; n = 48) or mycophenolate mofetil (MMF; n = 108), who underwent regular monthly surveillance bronchoscopies for at least 6 post-operative months. RESULTS: Patients on MMF had significantly fewer acute (P < 0.001) and recurrent (P < 0.001), as well as less severe rejection episodes (P = 0.01). In addition, MMF significantly reduced the number of alveolar lymphocytes, eosinophils and neutrophils (P < 0.001), and decreased the hemosiderin score reflecting non-specific alveolar-capillary damage (P < 0.001). Although there was no change in the three stages of BOS, there was a trend towards improved survival (P = 0.062) and a significant decrease in graft loss due to BOS (P = 0.049) in patients receiving MMF. CONCLUSIONS: Immunosuppression with MMF significantly decreased the incidence, severity and recurrence of acute rejection episodes in lung transplant recipients. Parameters of alveolar inflammation and alveolar-capillary damage were also decreased. As a potential consequence, MMF significantly reduced graft loss due to BOS and tended to improve overall survival in these patients.

Size-reduced lung transplantation in children--an option worth to consider!

Lung transplantation is an accepted therapy for pediatric end-stage lung disease. However, there is a shortage of suitable donor organs. Therefore, the use of downsized lung allografts seems a valuable option. We report our experience of downsized pediatric lung transplantation in comparison with standard full-size pediatric lung transplantation over one decade. Pediatric recipients undergoing downsized or standard lung transplantation were included (January 1997-December 2006). We compared pretransplant clinical data and surgical and post-operative complications and post-transplant outcome. Ten pediatric lung transplants were performed (median patient age 15.6 yr [12.3-17.8]). Nine of 10 patients had CF. Five patients underwent standard full-size lung transplantation; five had downsized lung transplants. "Downsized" recipients had significantly lower median height and weight Z-scores. Donor/recipient length difference was significantly greater in the "Downsized" Group (p<0.05). All patients had comparable post-transplant functional outcome without additional surgical complications or morbidities in "downsized" recipients. Median post-transplant survival was 65 months (5-77) in the "Standard" Group compared to 86 months (64-121) in the "Downsized" Group (p=0.1). Our data suggest that downsized lung transplantation in pediatric recipients may have post-transplant outcomes comparable to full-size lung transplantation without significant complications.

Not all intravenous immunoglobulin preparations are equally well tolerated.

Intravenous immunoglobulin (IVIG) is used for many indications beyond the original substitution in primary antibody deficiency. Whereas many reports mention adverse reactions, no comparative data exist concerning the incidence of side-effects among the different brands of IVIG. We describe here our experience with the use of different IVIG formulations and their tolerability in a select cohort of 40 patients. The IVIG dose ranged from 0.4 to 3 g/kg/day and was given for 1-2742 days. Fourteen patients (35%) experienced mild to severe adverse reactions during or within 48 h of administration of standard IVIG preparation, which did not recur after switching to an alternative preparation. Adverse reactions included headache, fever, chills, nausea, emesis, hypotension and muscle cramps. One patient experienced a severe adverse reaction; he had a 3-day headache following IVIG infusion. Among the 16 patients who received alternative preparation initially, none experienced adverse reactions. In conclusion, this study shows that IVIG preparations are not all equally well tolerated in patients. The data suggest that, perhaps to a comparable extent to the preparation itself, the infusion rate has a major effect. If a reduction in the infusion rate does not minimize side-effects, one should consider switching the IVIG formulation.

[Subjective experiences following organ transplantation--a qualitative study of 120 heart, lung, liver, and kidney recipients]. / Subjektives Erleben nach einer Organtransplantation--eine qualitative Studie mit 120 Herz-, Lungen-, Leber- und Nierenempfängern.

OBJECTIVES: The communication with patients who have undergoned transplantation is greatly influenced by their subjective experience. This paper deals with this subjective transplant-specific experience six months after surgery. METHODS: Following their heart, lung, liver, or kidney transplantation, 120 patients were questioned concerning their experiences regarding the transplantation, the organ itself, and changes in their personal life. Their statements were investigated by qualitative content analysis. RESULTS: Generally, the statements concerning the transplantation were positive. Interpersonal contact with the medical staff and or family members was perceived as very helpful. Two-thirds of the patients spoke openly about their organ. For the most part, their statements about changes in their personal life were positive, expressed in the sense of personal growth. Fears and insecurities occurred as negative changes. CONCLUSIONS: On the whole, the majority of the patients expressed positive experiences regarding their transplantation. Interpersonal and supportive relationships played a significant role.

Endoscopic narrow-band imaging-quantitative assessment of airway vascularity after lung transplantation.

In lung transplant recipients, the submucosal vascular plexus of the airway wall potentially represents one of the key structures of graft injury. Narrow band imaging is a novel endoscope technique that allows visual enhancement of the mucosa vasculature. It was our aim to investigate the ability of narrow-band imaging in combination with computerized image analysis to quantitatively assess airway vascularity in lung transplant recipients. In consecutive lung transplant recipients, in addition to the routine procedures, optical analysis of the main carina (autologous tissue) and the upper lobe carina (allogeneic tissue) were performed. From every site, three representative pictures were chosen. A total of 63 bronchoscopies were analyzed. The intraclass correlation coefficient (measure for test-retest reliability) of the three measurements were 0.69 and 0.74 for the main carina and the upper lobe carina, respectively. A mixed linear regression revealed increased vascularity in autologous tissue of patients with cystic fibrosis (p=0.06) and decreased vascularity in allogeneic tissue with time after transplantation (p=0.09). Endoscopic narrow-band imaging (NBI) in combination with computerized image analysis allows consistent assessment of airway vascularity in vivo. In lung transplant recipients, there might be differences in airway vascularity in both autologous and allogeneic large airways.

Extracorporeal photopheresis in a rat model of pulmonary fibrosis.

Extracorporeal photopheresis has anti-inflammatory properties. The development of pulmonary fibrosis includes inflammatory episodes. This study evaluates effects of extracorporeal photopheresis in experimental pulmonary fibrosis. The bleomycin model of pulmonary fibrosis was used. Two groups of 4 rats received intratracheal bleomycin to induce fibrosis. The treatment group received infusions of photochemically treated leukocytes harvested from syngeneic animals. All animals were sacrificed at day 21 after fibrosis induction and analyzed with respect to lung histology and hydroxyproline content, cellular composition of bronchoalveolar lavages, serum and lavage concentrations of transforming growth factor-beta, interferon-gamma, and interleukin-10, and expression of selected genes in the lung. Interleukin-10 and transforming growth factor-beta protein concentrations increased in the plasma of treated animals, whereas the interferon-gamma protein concentration was higher in bronchoalveolar lavages. Interferon-gamma gene expression was up-regulated in the lung tissue of treated animals. No significant differences between treated and untreated animals were found with respect to hydroxyproline, histology, and lavage cell count. To conclude, extracorporeal photopheresis has positive molecular effects but does not attenuate experimental lung fibrosis with respect to histology, hydroxyproline, and lavage cell count in the applied treatment regimen. Further investigations of extracorporeal photopheresis in experimental pulmonary fibrosis are justified.

Extended nitric oxide measurements in exhaled air of cystic fibrosis and healthy adults.

In cystic fibrosis (CF) lung disease, exhaled nitric oxide (FeNO) is not raised, but rather is normal or even decreased when measured at a single expiratory flow. FeNO measurements at several flow rates allow differentiation between alveolar and bronchial nitric oxide (NO) production. Extended FeNO measurements therefore should be useful to localize the FeNO deficit in CF airways. FeNO was measured in stable CF adults with moderate lung disease and in healthy controls. Bronchial NO fluxes (J(NO,Br)) and alveolar NO concentrations (C(Alv)) were calculated from FeNO measurements at flow rates of 100, 150 and 200 ml/s using a method previously described. Thirty-two adults were included in the study, 12 of whom had CF. CF adults had significantly lower FeNO values at all flow rates. The median J(NO,Br) was significantly lower in CF adults than in healthy controls [0.31 nl/s (range = 0.11-0.63) vs. 0.70 nl/s (0.27-3.52); P < 0.001], while the median C(Alv) was similar in both groups [1.7 ppb (0.3-3.9) vs. 1.2 (0.1-5.2)]. Pulmonary NO exchange did not differ significantly between subgroups of CF patients with and without chronic Pseudomonas aeruginosa infection. No significant correlation was detectable between FEV(1)/VC and J(NO,Br) and C(Alv), respectively. Extended FeNO measurements can separate alveolar and bronchial NO outputs in CF adults. The lower FeNO in adults with moderate to severe CF lung disease is likely to be the result of lower bronchial NO output.