Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.

BACKGROUND: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. METHODS: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. RESULTS: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. CONCLUSION: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.

Blood MMP-9 measured at 2 years after lung transplantation as a prognostic biomarker of chronic lung allograft dysfunction.

BACKGROUND: Long-term outcomes of lung transplantation (LTx) remain hampered by chronic lung allograft dysfunction (CLAD). Matrix metalloproteinase 9 (MMP-9) is a secretory endopeptidase identified as a key mediator in fibrosis processes associated with CLAD. The objective of this study was to investigate whether plasma MMP9 levels may be prognostic of CLAD development. METHODS: Participants were selected from the Cohort in Lung Transplantation (COLT) for which a biocollection was associated. We considered two time points, year 1 (Y1) and year 2 (Y2) post-transplantation, for plasma MMP-9 measurements. We analysed stable recipients at those time points, comparing those who would develop a CLAD within the 2 years following the measurement to those who would remain stable 2 years after. RESULTS: MMP-9 levels at Y1 were not significantly different between the CLAD and stable groups (230 ng/ml vs. 160 ng/ml, p = 0.4). For the Y2 analysis, 129 recipients were included, of whom 50 developed CLAD within 2 years and 79 remained stable within 2 years. MMP-9 plasma median concentrations were higher in recipients who then developed CLAD than in the stable group (230 ng/ml vs. 118 ng/ml, p = 0.003). In the multivariate analysis, the Y2 MMP-9 level was independently associated with CLAD, with an average increase of 150 ng/ml (95% CI [0-253], p = 0.05) compared to that in the stable group. The Y2 ROC curve revealed a discriminating capacity of blood MMP-9 with an area under the curve of 66%. CONCLUSION: Plasmatic MMP-9 levels measured 2 years after lung transplantation have prognostic value for CLAD.

Changes in HCMV immune cell frequency and phenotype are associated with chronic lung allograft dysfunction.

Background: Human cytomegalovirus (HCMV) infection is common and often severe in lung transplant recipients (LTRs), and it is a risk factor associated with chronic lung allograft dysfunction (CLAD). The complex interplay between HCMV and allograft rejection is still unclear. Currently, no treatment is available to reverse CLAD after diagnosis, and the identification of reliable biomarkers that can predict the early development of CLAD is needed. This study investigated the HCMV immunity in LTRs who will develop CLAD. Methods: This study quantified and phenotyped conventional (HLA-A2pp65) and HLA-E-restricted (HLA-EUL40) anti-HCMV CD8+ T (CD8 T) cell responses induced by infection in LTRs developing CLAD or maintaining a stable allograft. The homeostasis of immune subsets (B, CD4T, CD8 T, NK, and γδT cells) post-primary infection associated with CLAD was also investigated. Results: At M18 post-transplantation, HLA-EUL40 CD8 T responses were less frequently found in HCMV+ LTRs (21.7%) developing CLAD (CLAD) than in LTRs (55%) keeping a functional graft (STABLE). In contrast, HLA-A2pp65 CD8 T was equally detected in 45% of STABLE and 47.8% of CLAD LTRs. The frequency of HLA-EUL40 and HLA-A2pp65 CD8 T among blood CD8 T cells shows lower median values in CLAD LTRs. Immunophenotype reveals an altered expression profile for HLA-EUL40 CD8 T in CLAD patients with a decreased expression for CD56 and the acquisition of PD-1. In STABLE LTRs, HCMV primary infection causes a decrease in B cells and inflation of CD8 T, CD57+/NKG2C+ NK, and δ2-γδT cells. In CLAD LTRs, the regulation of B, total CD8 T, and δ2+γδT cells is maintained, but total NK, CD57+/NKG2C+ NK, and δ2-γδT subsets are markedly reduced, while CD57 is overexpressed across T lymphocytes. Conclusions: CLAD is associated with significant changes in anti-HCMV immune cell responses. Our findings propose that the presence of dysfunctional HCMV-specific HLA-E-restricted CD8 T cells together with post-infection changes in the immune cell distribution affecting NK and γδT cells defines an early immune signature for CLAD in HCMV+ LTRs. Such a signature may be of interest for the monitoring of LTRs and may allow an early stratification of LTRs at risk of CLAD.

Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients.

OBJECTIVE: Immunocompromised patients have an increased risk of a severe form of COVID-19. The clinical efficacy of the tixagevimab/cilgavimab monoclonal antibody combination as pre-exposure prophylaxis against BA.1 and BA.2 SARS-CoV-2 Omicron sublineages is unknown. We aimed to describe the incidence and outcomes of COVID-19 among immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis during the Omicron wave in France. METHODS: This was an observational multicentre cohort study of immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis between December 28, 2021 and March 31, 2022. Patients received tixagevimab/cilgavimab 150/150 mg intramuscularly if they had impaired vaccine response and a high risk of severe form of COVID-19. RESULTS: Tixagevimab/cilgavimab was administered to 1112 immunocompromised patients. After a median (range) follow-up of 63 (49-73) days, COVID-19 was confirmed in 49/1112 (4.4%) ≥5 days after treatment. During the study period, mean weekly incidence rate was 1669 in 100 000 inhabitants in Ile-de-France and 530 in 100 000 among patients who received tixagevimab/cilgavimab prophylaxis. Among infected patients, 43/49 (88%) had a mild-to-moderate form and 6/49 (12%) had a moderate-to-severe form of COVID-19. Patients with moderate-to-severe illnesses were less likely to have received early therapies than patients with mild forms (53.5% vs. 16.7% respectively) and 2/49 (4%) patients died from COVID-19. DISCUSSION: Our study reported a low rate of infections and severe illnesses among immunocompromised patients treated with tixagevimab/cilgavimab. A global preventive strategy including vaccines, preexposure prophylaxis with monoclonal antibodies, and early therapies might be effective to prevent severe forms of COVID-19 among severely immunocompromised patients.

Chronic Lung Allograft Dysfunction Post Lung Transplantation: A Review of Computed Tomography Quantitative Methods for Detection and Follow-Up.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of morbidity and mortality after lung transplantation. The term encompasses both obstructive and restrictive phenotypes, as well as mixed and undefined phenotypes. Imaging, in addition to pulmonary function tests, plays a major role in identifying the CLAD phenotype and is essential for follow-up after lung transplantation. Quantitative imaging allows for the performing of reader-independent precise evaluation of CT examinations. In this review article, we will discuss the role of quantitative imaging methods for evaluating the airways and the lung parenchyma on computed tomography (CT) images, for an early identification of CLAD and for prognostic estimation. We will also discuss their limits and the need for novel approaches to predict, understand, and identify CLAD in its early stages.

COVID-19 in Lung Transplant Recipients.

BACKGROUND: A concern about the susceptibility of immunocompromised patients to the worldwide pandemic of coronavirus disease 2019 (COVID-19) has been raised. We aimed at describing COVID-19 infections in the French cohort of lung transplant (LT) patients. METHODS: Multicenter nationwide cohort study of all LT recipients with COVID-19 diagnosed from March 1 to May 19, 2020. Recipient main characteristics and their management were retrieved. Hospitalization characteristics, occurrence of complications and survival were analyzed. RESULTS: Thirty-five LT patients with a COVID-19 infection were included. Median age was 50.4 (40.6-62.9) years, 16 (45.7%) were female, and 80% were double-LT recipients. Infection was community-acquired in 25 (71.4%). Thirty-one (88.6%) required hospitalization, including 13 (41.9%) in the intensive care unit. The main symptoms of COVID-19 were fever, cough, and diarrhea, present in 71.4%, 54.3%, and 31.4% of cases, respectively. Extension of pneumonia on chest CT was moderate to severe in 51.4% of cases. Among the 13 critically ill patients, 7 (53.9%) received invasive mechanical ventilation. Thrombotic events occurred in 4 patients. Overall survival rate was 85.7% after a median follow-up of 50 days (41.0-56.5). Four of 5 nonsurvivors had had bronchial complications or intensification of immunosuppression in the previous weeks. On univariate analysis, overweight was significantly associated with risk of death (odds ratio, 16.0; 95% confidence interval, 1.5-170.6; P = 0.02). CONCLUSIONS: For the 35 LT recipients with COVID-19, the presentation was severe, requiring hospitalization in most cases, with a survival rate of 85.7%.

Pneumocystis pneumonia after lung transplantation: A retrospective multicenter study.

BACKGROUND: Lung transplantation (LT) is an identified risk factor for Pneumocystis pneumonia (PCP). However, PCP management and outcomes remain poorly described in LT recipients and PCP incidence is rarely documented in this population. METHODS: PCP episodes that occurred in 9 French LT centers between January 2010 and October 2017 were included in this analysis. PCP was defined as compatible clinical and radiologic findings associated with fungal identification. RESULTS: Forty-seven PCP were included. The annual incidence rate of PCP was 2.7/1000 patients/year. Patients had a mean age of 53 ± 14 years. Median time from LT was 2.4 ± 3.0 years. Sixty-five percent of patients were not on prophylaxis at the time of PCP while all patients were receiving steroids at the time of PCP. Diagnosis was obtained by bronchoalveolar lavage in 91% (direct examination: 47%, PCR: 62%). The majority of patients were treated with trimethoprim-sulfamethoxazole (78%). Fifty-five percent of patients were hospitalized in ICU for organ failure (for which non-invasive ventilation was used for 21% and mechanical ventilation for 23%). Mortality rate was 15% at day 28 and reached 23% at day 90. Mortality was associated with decreased FEV1, everolimus treatment, Pseudomonas aeruginosa coinfection, fungal coinfection (especially Aspergillus sp.), mechanical ventilation and vasopressors. PCP primary prophylaxis, steroid modification during PCP and the number of immunosuppressive molecules were not associated with mortality. CONCLUSION: PCP is associated with a high mortality in LT. Our data suggest the need for a lifetime PCP prophylaxis in LT recipients. The benefit of adjuvant steroids remains unclear.

Pregnancy after lung and heart-lung transplantation: a French multicentre retrospective study of 39 pregnancies.

Pregnancy after lung and heart-lung transplantation remains rare. This French study deals with change in lung function after a pregnancy and the maternal and newborn outcomes. We retrospectively included 39 pregnancies in 35 women aged >20 years. Data on patients, course of pregnancies and newborns were collected from nine transplantation centres. Mean age at time of pregnancy was 28 years. Cystic fibrosis affected 71% of patients. Mean±sd time between transplantation and pregnancy was 63±44 months. 26 births occurred (67%) with a mean term of 36 weeks of amenorrhoea and a mean birthweight of 2409 g. Prematurity was observed in 11 cases (43%). Forced expiratory volume in 1 s was 83.9% of predicted before pregnancy and 77.3% of predicted 1 year after the end of pregnancy (p=0.04). 10 patients developed chronic lung allograft dysfunction after delivery. Nine patients died at a mean±sd time after transplantation of 8.2±7 years and a mean±sd time after pregnancy of 4.6±6.5 years. These data show that pregnancy remains feasible in lung and heart-lung transplant recipients, with more frequent maternal and newborn complications than in the general population. Survival in this cohort appears to be similar to the global survival observed in lung transplant recipients. Planned pregnancy and multidisciplinary follow-up are crucial.

Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis.

Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations (C0) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL) C0 measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively (P = 0.001* [asterisk means that statistical test is significant]), and the PSZ C0 exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively (P < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL C0/dose ratio (C0/D) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution (P = 0.034*). The ERL C0/D was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; P = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients.

Clinical outcome of cystic fibrosis patients colonized by Scedosporium species following lung transplantation: A single-center 15-year experience.

BACKGROUND: Fungi of the genus Scedosporium are emerging pathogens responsible for severe infections in lung transplant recipients. These infections are associated with poor prognosis and some centers consider now Scedosporium species colonization as a contraindication to lung transplantation (LT) even though no published evidence demonstrates that Scedosporium species colonization is associated with higher morbidity or mortality after LT. METHODS: Here, we aim to describe characteristics and outcome of cystic fibrosis (CF) lung transplant recipients colonized with Scedosporium species in a single center over a 15-year period. RESULTS: During the study period, 14 patients had scedosporial colonization reported. Only one patient, colonized before transplantation by Lomentospora prolificans, developed scedosporial disease. Among the eight patients colonized before transplantation by Scedosporium apiospermum complex, the median survival was 1.92 year (range 0.21-12.5). All these patients except one became free of fungal colonization after transplantation with antifungal prophylaxis including voriconazole or posaconazole. For the five patients colonized after LT, including two with L. prolificans, the median survival was 1.75 years (range 0.1-13); three of them are still alive. CONCLUSIONS: It appears to us that scedosporial colonization may not be a contraindication for LT in CF patients, as long as S. apiospermum complex is involved and a life-long azole prophylaxis prescribed.

Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study.

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO2), particulate matter with an aerodynamic cut-off diameter of x µm (PMx) and ozone (O3)) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m-3 of PM10; -0.75%, 95% CI -1.38--0.12 for 2 µg·m-3 of PM2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m-3 of NO2). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM10 was associated with lower FEV1Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides.

Lessons from a French collaborative case-control study in cystic fibrosis patients during the 2009 A/H1N1 influenza pandemy.

BACKGROUND: Viral infections such as influenza are thought to impact respiratory parameters and to promote infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF). However, the real morbidity of the influenza virus in CF needs to be further investigated because previous studies were only observational. METHODS: CF patients were included in a case-control study (n = 44 cases and n = 371 controls) during the 2009 pandemic A/H1N1 influenza. Cases were patients with polymerase reaction chain-confirmed influenza A/H1N1 infection. Controls did not report any influenza symptoms during the same period. Sputum colonization and lung function were monitored during 1 year after inclusion. RESULTS: Cases were significantly younger than controls (mean(SD) 14.9 years(11) versus 20.1 years (13.2) and significantly less frequently colonized with P. aeruginosa (34 % versus 53 %). During influenza infection, 74 % of cases had pulmonary exacerbation, 92 % had antibiotics adapted to their usual sputum colonization and 82 % were treated with oseltamivir. Two cases required lung transplantation after A/H1N1 infection (one had not received oseltamivir and the other one had been treated late). The cases received a mean number of antibiotic treatments significantly higher during the year after the influenza infection (mean(SD) 2.8 (2.4) for cases versus 1.8(2.1) for controls; p = 0.002). An age-matched comparison did not demonstrate any significant modification of bronchopulmonary bacterial colonization during the year after influenza infection nor any significant change in FEV1 at months 1, 3 and 12 after A/H1N1 infection. CONCLUSIONS: Our results do not demonstrate any change in sputum colonization nor significant lung disease progression after pandemic A/H1N1 influenza. TRIAL REGISTRATION: Clinical Trials.gov registration number: NCT01499914.

Causes of death in French cystic fibrosis patients: The need for improvement in transplantation referral strategies!

BACKGROUND: Little data exist on causes of death in cystic fibrosis (CF) patients in the era of lung transplantation. METHODS: Deaths in CF patients in France (2007-2010) were identified using the French CF Registry and causes of deaths were determined based on medical files by a mortality adjudication committee. RESULTS: Of 256 deaths, half occurred after lung transplantation and were related to early or late complications of transplantation, whereas half occurred in patients who did not receive lung transplantation and were primarily related to respiratory failure or massive hemoptysis. Among patients who did not receive lung transplantation, only 19% died while waiting on a lung transplantation list. Lack of listing for lung transplantation was primarily related to late, or to lack of transplantation referral, rather than to contraindication to transplantation. CONCLUSIONS: These data suggest that improvement in transplantation referral strategies may result in transplantation-related survival benefits.

Lung transplantation in childhood and adolescence: unicentric 14-year experience with sex matching as the main prognosticator.

OBJECTIVES: Lung transplantation (LTx) is an accepted therapy for selected infants, children and adolescents with end-stage lung and pulmonary vascular disease. It remains a challenge for a selected group of patients. In 2011, the number of paediatric lung transplantations (PLTxs) worldwide was 107. In France, a total of 131 PLTxs have been performed since 2000 (data from ABM: Agence de biomédecine), 65 of which were conducted at our institution. METHODS: All patients under 18 (4.8-17.11) years of age matching inclusion and exclusion criteria, who underwent LTx at our institution were included in this study (n = 58). We analysed the outcomes of these patients in terms of survival rates, controlling for indications for transplantations and surgical procedures. Secondary outcomes were analysis of surgical and medical complications and identification of prognostic factors in the field of LTx in these categories of ages. RESULTS: The 30-day mortality rate was 10%. Kaplan-Meier survival rates at 1 month, 1, 3, 5 and 10 years were 90, 81, 66, 60 and 57%, respectively; the median survival was 91 months. Reduced-size transplantation was performed in 33% of double-lung transplantation (DLTx) patients without negatively impacting survival. In our series, female sex, the presence of a sex mismatching and, in particular, the occurrence of a male donor to a female recipient (F/M group) have been poor prognostic factors after PLTx. CONCLUSIONS: The overall survival after PLTx was encouraging (57% at 10 years). A PLTx should be offered to the small number of patients with end-stage pulmonary disease. The limited number of paediatric donor organs can be overcome by using reduced-size organs without a survival disadvantage to the patients. In our series, male sex and sex matching seemed to be positive predictive prognostic factors after PLTx but further studies are required to confirm these results and to also clarify the role of age of donor, time of cold ischaemia and body mass index in PLTx.

A new endoscopic standardized grading system for macroscopic central airway complications following lung transplantation: the MDS classification.

OBJECTIVES: After lung transplant, between 9 and 13% of bronchial anastomoses develop complications severe enough to warrant therapeutic intervention. These complications include stenosis, dehiscence, granulation tissue, bronchomalacia and fistula. Most of these have already been included in a classification or another, but none of these have been universally accepted. Moreover, no grading system has integrated all of these complications. The Groupe Transplantation (GT) (Transplant Group), from the Société de Pneumologie de Langue Française (SPLF) [French Language Pulmonology Society], maintains a prospective national registry of lung transplants performed in France. The GT has mandated the Groupe d'Endoscopie de Langue Française (GELF), also from the SPLF, to develop an endoscopic classification, in order to describe the macroscopic aspect of the bronchial anastomoses, and downhill airways, using a standardized and exhaustive grading system. METHODS: An endoscopic classification that would take into account the three major aspects of the description of bronchial anastomoses was elaborated. The first parameter is the macroscopic aspect (M), the second, the diameter (D) of the anastomosis and the third, the sutures (S) of the anastomosis. This classification was then submitted to expert bronchoscopists from nine centres, responsible for lung transplants in France, for their opinion, using a five-item questionnaire, according to the Delphi methodology. RESULTS: After the first round of consultation, all experts (100%) agreed on Questions 1 and 4. Answers were positive for Questions 2 (59%), 3 (56.25%) and 5 (70%). A modified classification, incorporating propositions from the first round, was then submitted. This second round allowed a consensus to be reached between all experts: the MDS classification. Each parameter (M, D and S) can be classified from 0 to 3. For M and D, it is possible to determine the extent of abnormalities downhill from the anastomosis into four subgroups (a, b, c or d). For S, the localization of abnormalities can be divided between two subgroups (e and f). CONCLUSION: The MDS classification, established by a consensus of French experts in bronchoscopy, could represent a standardized, universally acceptable system to describe central airway complications after lung transplant.

Expression of calcineurin activity after lung transplantation: a 2-year follow-up.

The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineurin during the first 2 years after lung transplantation. From March 2004 to October 2008, 107 patients were prospectively enrolled and their follow-up was performed until 2009. Calcineurin activity was measured in peripheral blood mononuclear cells. We report that calcineurin activity was linked to both acute and chronic rejection. An optimal activity for calcineurin with two thresholds was defined, and we found that the risk of rejection was higher when the enzyme activity was above the upper threshold of 102 pmol/mg/min or below the lower threshold of 12 pmol/mg/min. In addition, we report that the occurrence of malignancies and viral infections was significantly higher in patients displaying very low levels of calcineurin activity. Taken together, these findings suggest that the measurement of calcineurin activity may provide useful information for the management of the prevention therapy of patients receiving lung transplantation.

One-year experience with high-emergency lung transplantation in France.

BACKGROUND: The continuing significant number of patients who die while on a waiting list for lung transplantation (LTx) has led several countries to modify their lung allocation rules in recent years. France has implemented high-emergency allocation rules to allow patients at imminent risk of death to undergo priority transplantation within several days. The aim of this study was to report on the early (2-year) experience of high-emergency LTx (HELTx) in France. METHODS: From July 1, 2007, to June 30, 2008, 186 patients underwent LTx in France in nine centers. Among them, 32 patients (17.2%) underwent HELTx (19 with cystic fibrosis, 7 pulmonary fibrosis, and 6 other diagnoses). The reasons for HELTx were risk of invasive mechanical ventilation (n=20), invasive mechanical ventilation (n=8), and extracorporeal membrane oxygenation (n=4). RESULTS: The median time between being placed on the HELTx waiting list and LTx was 3 days (interquartile range: 1-8 days). Survival rates in the HELTx group were 90.5%, 71%, 64.5%, 55%, and 51.5% at 1, 3, 6, 12, and 24 months, respectively, which were significantly lower than for 154 patients who underwent regular, nonurgent LTx during the study period (88.5%, 83%, 79%, 77%, and 71%, respectively). CONCLUSIONS: Our data demonstrate that the new LTx allocation rules implemented in France since 2007 allow for rapid organ procurement for patients at imminent high risk of death. HELTx is feasible but yields poorer survival than elective LTx. Further studies are needed to assess implications of this organ allocation policy on the long run.