Influence of lung transplantation on the essential fatty acid profile in cystic fibrosis.

Lung transplantation is assumed to normalize essential fatty acid (EFA) profile in the plasma, described as abnormal in patients with cystic fibrosis (CF). This study sought to evaluate the EFA profile in both the plasma and erythrocyte membrane according to lung status by comparing CF patients with or without a lung transplant. A total of 50 homozygous F508del patients (33 CF patients [CF group] and 17 CF patients with a lung transplant [TX CF group]) were included. In comparison with the CF group, in the plasma, the levels of total n-3, α-linolenic, eicosapentaenoic, and docosahexaenoic acids were higher and the n-6/n-3 ratio was lower in the TX CF group. Yet, these differences were not observed in the erythrocyte membrane. This study supports that lung transplantation improves the EFA profile in the plasma but not in the erythrocyte membrane by means of the different mechanisms suggested in this article.

[Impact of the transition period from childhood to adulthood in cystic fibrosis]. / Impact de la période de transition de l'enfance à l'âge adulte dans la mucoviscidose.

INTRODUCTION: The aim of this study was to evaluate the impact of the transition period from childhood to adulthood in patients with cystic fibrosis (CF) being followed up in our reference center. METHODS: The clinical, functional, inflammatory and microbiological parameters of all transition patients were compared two years before (T-2) and two years after the transfer (T+2) from paediatric to adult centers and further analysed according to whether the transition conditions were optimal or suboptimal. RESULTS: Twenty-eight patients were included. The mean age at the transfer visit was 19.5 years (±3.5). There were no deaths during the study period. Consultations were more numerous at T-2 [14.5 (±5.9) vs. 12.0 (±5.1), P<0.004]. Chronic colonization with Pseudomonas aeruginosa was more frequent at T+2 (46.4% vs. 17.9%, P=0.021). A progressive decrease in FEV1 and FVC was observed between T-2 and T+2. The number of pulmonary exacerbations was lower in the optimal transition group. CONCLUSION: The period of transition from childhood to adulthood in patients with CF appears to be associated with functional and microbiological changes.

Emergence of livestock-associated MRSA isolated from cystic fibrosis patients: Result of a Belgian national survey.

BACKGROUND: This study aims to determine the prevalence and characteristics of Staphylococcus aureus in Belgian cystic fibrosis (CF) patients. METHODS: Non-duplicate respiratory samples from 510 CF-patients (2012-2013) were examined. One isolate per patient was analysed unless different phenotypes were recovered. Isolates were investigated for mecA/mecC, toxins presence, spa-typing, MLST and SCCmec-typing. Potential livestock-associated (LA) isolates were examined for their immune-evasion-cluster (IEC) genes. RESULTS: S. aureus (n = 380), including 41 small-colony variants (SCVs), were isolated from 66.7% patients. The prevalence of methicillin-resistant S. aureus (MRSA) colonization was 4.9%. Two MRSA isolates carried toxic shock syndrome toxin 1 (TSST-1). Most MRSA (65%) belonged to two nosocomial epidemic clones (CC5, CC8) widespread in Belgium. Methicillin susceptible S. aureus (MSSA) showed great genetic diversity. Five of 33 isolates belonging to potential LA-lineages were IEC negative, including three methicillin-resistant isolates, suggesting an animal origin. CONCLUSIONS: The MRSA-prevalence in Belgian CF-patients remained constant (2001-2013), but SCV-prevalence increased. Most MRSA belonged to health-care-associated clones. Three patients carrying LA-MRSA were found, requiring further investigation to determine the risk factors for LA-MRSA acquisition.

Culture-Based Methods and Molecular Tools for Azole-Resistant Aspergillus fumigatus Detection in a Belgian University Hospital.

Azole-resistant Aspergillus fumigatus is an increasing worldwide problem with major clinical implications. Surveillance is warranted to guide clinicians to provide optimal treatment to patients. To investigate azole resistance in clinical Aspergillus isolates in our institution, a Belgian university hospital, we conducted a laboratory-based surveillance between June 2015 and October 2016. Two different approaches were used: a prospective culture-based surveillance using VIPcheck on unselected A. fumigatus (n = 109 patients, including 19 patients with proven or probable invasive aspergillosis [IA]), followed by molecular detection of mutations conferring azole resistance, and a retrospective detection of azole-resistant A. fumigatus in bronchoalveolar lavage fluid using the commercially available AsperGenius PCR (n = 100 patients, including 29 patients with proven or probable IA). By VIPcheck, 25 azole-resistant A. fumigatus specimens were isolated from 14 patients (12.8%). Of these 14 patients, only 2 had proven or probable IA (10.5%). Mutations at the cyp51A gene were observed in 23 of the 25 A. fumigatus isolates; TR34/L98H was the most prevalent mutation (46.7%), followed by TR46/Y121F/T289A (26.7%). Twenty-seven (27%) patients were positive for the presence of Aspergillus species by AsperGenius PCR. A. fumigatus was detected by AsperGenius in 20 patients, and 3 of these patients carried cyp51A mutations. Two patients had proven or probable IA and cyp51A mutation (11.7%). Our study has shown that the detection of azole-resistant A. fumigatus in clinical isolates was a frequent finding in our institution. Hence, a rapid method for resistance detection may be useful to improve patient management. Centers that care for immunocompromised patients should perform routine surveillance to determine their local epidemiology.

Difference in release kinetics of unwashed and washed platelet-released supernatants from bone substitute materials: the impact of platelet preparation modalities.

BACKGROUND AND OBJECTIVE: In regenerative dentistry, platelet preparations are applied to stimulate bone healing and periodontal regeneration. Here, we pursue a strategy where bone substitutes are used as carriers for platelet-released supernatants. The mitogenic capacity and release kinetics of loaded bone substitutes were assessed. MATERIAL AND METHODS: Platelet-released supernatants of washed platelets (washed PRS) and platelet-released supernatants of unwashed platelets (unwashed PRS) were lyophilized onto the bone substitutes deproteinized bovine bone mineral, hydroxyapatite and ß-tricalcium phosphate. Scanning electron microscopy images were taken. Supernatants of bone substitutes were collected at hours 1, 3, 6, 24, and 48 and medium was replaced. We evaluated the protein content with the bicinchoninic acid assay and the effect on proliferation using bioassays with human periodontal fibroblasts. Release of growth factors from the loaded bone substitutes was measured based on the platelet-derived growth factor isoform (PDGF-BB) and thrombin immunoassays. Furthermore, we assessed DNA and RNA content of washed PRS and unwashed PRS. RESULTS: Unwashed PRS showed higher total protein concentrations than washed PRS, while the concentration of PDGF-BB, thrombin, DNA, RNA and their mitogenic effect was not significantly different. The bone substitute materials adsorbed protein over time but no significant changes in overall appearance was found. Supernatants collected from unwashed PRS-loaded bone substitute after 1 h induced a potent mitogenic response in periodontal fibroblasts. This pro-mitogenic capacity of the supernatants decreased over the observation period. Supernatants of washed PRS-loaded bone substitutes did not induce a substantial mitogenic effect. Levels of PDGF-BB, thrombin and protein were higher in supernatants of unwashed PRS-loaded bone substitutes than of washed PRS-loaded bone substitutes. CONCLUSION: Bone substitutes loaded with unwashed PRS, but not bone substitutes loaded with washed PRS show continuously declining release kinetics. These data suggest that plasma components in platelet preparations can modify the release kinetics profile.

T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction.

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-ß. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-ß-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD.

The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients - A pilot study.

Effectiveness of omega-3 supplementation in cystic fibrosis (CF) remains controversial. This study sought to evaluate clinical status, exercise tolerance, inflammatory parameters, and erythrocyte fatty acid profile after 1 year of oral omega-3 supplementation in CF patients. Fifteen ΔF508-homozygous patients undergoing chronic azithromycin were randomized to receive omega-3 fish oil supplementation at a dose of 60mg/Kg/day or placebo. In comparison with the previous year, in the supplemented group, the number of pulmonary exacerbations decreased at 12 months (1.7 vs. 3.0, p<0.01), as did the duration of antibiotic therapy (26.5 days vs. 60.0 days, p<0.025). Supplementation significantly increased the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as early as <3 months of administration, with concomitant decreases in arachidonic acid (AA) levels. This pilot study suggests that long-term omega-3 supplementation offers several clinical benefits as to the number of exacerbations and duration of antibiotic therapy in CF patients.

[Small airway diseases and immune deficiency]. / Atteinte des voies aériennes distales et immunodépression.

INTRODUCTION: Innate or acquired immune deficiency may show respiratory manifestations, often characterized by small airway involvement. The purpose of this article is to provide an overview of small airway disease across the major causes of immune deficiency. BACKGROUND: In patients with common variable immune deficiency, recurrent lower airway infections may lead to bronchiolitis and bronchiectasis. Follicular and/or granulomatous bronchiolitis of unknown origin may also occur. Bronchiolitis obliterans is the leading cause of death after the first year in patients with lung transplantation. Bronchiolitis obliterans also occurs in patients with allogeneic haematopoietic stem cell transplantation, especially in the context of systemic graft-versus-host disease. VIEWPOINT AND CONCLUSION: Small airway diseases have different clinical expression and pathophysiology across various causes of immune deficiency. A better understanding of small airways disease pathogenesis in these settings may lead to the development of novel targeted therapies.

Erratum to "Practical guidelines: lung transplantation in patients with cystic fibrosis".

[This corrects the article DOI: 10.1155/2014/621342.].

Practical guidelines: lung transplantation in patients with cystic fibrosis.

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.

Percutaneous endoscopic jejunostomy in patients with gastroparesis following lung transplantation: feasibility and clinical outcome.

The aim of the present study was to describe success rates, complications, and outcome in patients who underwent percutaneous endoscopic jejunostomy (PEJ) because of gastroparesis due to previous lung transplantation. Between October 2008 and May 2011, 14 attempts at PEJ placement were made in 12 patients in our center. Of the 14 attempts, 11 were successful, giving a technical success rate of 78.6 %. Median duration of followup was8.5 months (2­15 months). No immediate complications were reported. Two severe complications occurred during follow up (one volvulus and one jejunocolic fistula). Jejunal nutrition was well tolerated in most of patients (9 /10). PEJ insertion is a feasible technique, which could help to provide nutritional support for patients with gastroparesis and previous lung transplantation.

[Complications of lung transplantation]. / Complications de la transplantation pulmonaire: complications médicales.

In 2009 lung transplantation is a valuable therapeutic option for a number of patients suffering from end-stage pulmonary diseases. Lung transplantation frequently offers a major improvement in quality of life; however, long-term survival is often limited by the development of the bronchiolitis obliterans syndrome, which is the equivalent of a chronic pulmonary graft rejection. As the bronchiolitis obliterans syndrome is the commonest cause of death in the medium- and long-terms, all patients receive intense immunosuppressive treatment in order to prevent or stabilize this complication. This treatment induces a number of potentially severe complications including metabolic complications, infections and malignancies. The most frequent metabolic complications are arterial hypertension, chronic renal insufficiency, hyperlipidaemia, diabetes and osteoporosis. Bacterial, viral and fungal infections are the second commonest cause of mortality. They are to be considered as medical emergencies and require urgent assessment and targeted therapy after microbiological specimens have been obtained. They should not under any circumstances be treated empirically and it should also be kept in mind that the lung transplant recipient may present several concomitant infections. The most frequent malignancies are post-transplant lymphoproliferative disorders, cutaneous neoplasias, Kaposi's sarcoma, some peculiar types of head and neck neoplasia, bronchogenic carcinomas and cancers of the digestive tract. The respiratory physician should recognize the symptoms and signs of specific complications induced by the immunosuppressive regimen and the goal of this report is to give a general overview of the most frequently encountered complications. Their assessment and treatment, though, will most often require the input of other specialists and a multidisciplinary approach.

[Medical complications of lung transplantation]. / Complications non chirurgicales de la transplantation pulmonaire.

In 2010, lung transplantation is a valuable therapeutic option for a number of patients suffering from of end-stage non-neoplastic pulmonary diseases. The patients frequently regain a very good quality of life, however, long-term survival is often hampered by the development of complications such as the bronchiolitis obliterans syndrome, metabolic and infectious complications. As the bronchiolitis obliterans syndrome is the first cause of death in the medium and long term, an intense immunosuppressive treatment is maintained for life in order to prevent or stabilize this complication. The immunosuppression on the other hand induces a number of potentially severe complications including metabolic complications, infections and malignancies. The most frequent metabolic complications are arterial hypertension, chronic renal insufficiency, diabetes, hyperlipidemia and osteoporosis. Bacterial, viral and fungal infections are the second cause of mortality. They are to be considered as medical emergencies and require urgent assessment and targeted therapy after microbiologic specimens have been obtained. They should not, under any circumstances, be treated empirically and it has also to be kept in mind that the lung transplant recipient may present several concomitant infections. The most frequent malignancies are skin cancers, the post-transplant lymphoproliferative disorders, Kaposi's sarcoma and some types of bronchogenic carcinomas, head/neck and digestive cancers. Lung transplantation is no longer an exceptional procedure; thus, the pulmonologist will be confronted with such patients and should be able to recognize the symptoms and signs of the principal non-surgical complications. The goal of this review is to give a general overview of the most frequently encountered complications. Their assessment and treatment, though, will most often require the input of other specialists and a multidisciplinary and transversal approach.

[Complications of lung transplantation: perioperative complications, acute and chronic rejection]. / Complications de la transplantation pulmonaire: complications péri-opératoires, rejet aigu et chronique.

In 2009 lung transplantation is a valuable therapeutic option for a spectrum of end-stage pulmonary diseases. To many patients who are dying, lung transplantation offers a new and normal life for several years. However, lung transplantation is a major surgical intervention associated with a significant early mortality. Moreover, matching according to the major human histocompatibilty antigens is impossible, exposing the recipient to an increased risk of acute and chronic rejection. Chronic rejection and its clinical corollary the bronchiolitis obliterans syndrome, is the main cause of death medium and long term. The immunosuppressive treatment administered in order to prevent or stabilize this complication induces a number of potentially severe complications including infection, malignancies, and cardio-vascular, metabolic and renal complications which not only limit autonomy and quality of life, but also cause death in a number of long term survivors. A better understanding of the precise mechanisms underlying the development of the bronchiolitis obliterans syndrome and the development of specific preventive or therapeutic strategies will be key elements for the improvement of long term survival. The control of this main cause of death will allow individual tailoring of the immunosuppressive therapy and decrease the incidence of infectious and metabolic complications.

Clostridium difficile colitis in cystic fibrosis patients with and without lung transplantation.

BACKGROUND: Despite a large carriage rate of Clostridium difficile among cystic fibrosis (CF) patients, C. difficile-associated disease (CDAD) is rather rare. In case of lung transplantation, the incidence and clinical aspects of CDAD in this patient population are not well known. METHODS: We reviewed the medical files of all CF patients who presented with symptomatic C. difficile infection from January 1998 to December 2004 and compared the incidence, clinical aspects, severity of disease, and clinical outcome between non-transplanted and transplanted CF patients. RESULTS: Between 1998 and 2004, 106 adult CF patients were followed at our clinic. Forty-nine patients underwent lung transplantation; 15 before 1998 and 34 after 1998. The incidence density of CDAD was higher in transplanted CF patients as compared with non-transplanted CF patients (24.2 vs. 9.5 episodes/100,000 patient-days; risk ratio: 2.93 [1.41-6.08]; P=0.0044). Diarrhea was a very frequent feature, but was notably absent in 20% of the cases. Rates of moderate and severe colitis were similar in both groups. However, only transplanted patients developed complicated colitis. CT scan and endoscopy were performed more frequently in the transplant group. Two transplant recipients died because of CDAD. CONCLUSION: CF patients who undergo lung transplantation are at a higher risk of developing CDAD and seem to present more often atypical and/or complicated disease. CDAD should be part of the differential diagnosis in case of digestive symptoms, even in the absence of diarrhea, and requires early treatment.

Guidelines for the management of pregnancy in women with cystic fibrosis.

Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF.

Paradoxical worsening of tuberculosis in a heart-lung transplant recipient.

UNLABELLED: We report on a heart-lung transplant recipient who presented with pulmonary tuberculosis (TB) 2.5 months after transplantation and then developed a paradoxical reaction after 4 months of adequate anti-TB treatment. She eventually recovered with anti-TB and high-dose steroid treatments. METHODS: Using sequential bronchoalveolar lavages, we assessed the inflammatory response in the lung and investigated the alveolar immune response against a Mycobacterium tuberculosis antigen. RESULTS: The paradoxical reaction was characterized by a massive infiltration of the alveolar space by M. tuberculosis antigen-specific CD4(+) T cells and by the presence of a CD4(-)CD8(-) T lymphocyte subpopulation bearing phenotypic markers (CD16(+)/56(+)) classically associated with NK cells. CONCLUSION: This case report illustrates that even solid organ transplant recipients receiving intense triple-drug immune suppression may be able to develop a paradoxical reaction during TB treatment. Transplant physicians should be aware of this phenomenon in order to differentiate it from treatment failure.