The Favorable impact of everolimus on Chronic lung allograft dysfunction in lung transplant recipients.

Standard immunosuppressive therapy for lung transplant recipients combines a calcineurin inhibitor, an antimetabolite, and corticosteroids. In an observational, retrospective, monocentric study, we sought to compare the development of chronic lung allograft dysfunction (CLAD) between 37 patients who received this standard therapy (triple-therapy group) and 59 patients who received the mammalian target of rapamycin (mTOR) inhibitor everolimus in addition to the standard therapy (quadruple-therapy group). In the quadruple-therapy group, the time elapsed from transplantation to everolimus introduction (median [25th-75th percentile]) was 12 [7-25] months. In 46/59 cases, the indication for everolimus introduction was renal function sparing. Median follow-up durations were 36 [20-62] months and 84 [52-123] months in the triple-therapy and quadruple-therapy groups, respectively (p = 0.004). The incidence of CLAD was lower in patients receiving everolimus than in those who did not with an adjusted odds ratio of 0.303 [0.118-0.775]. In addition, the median time from transplantation to CLAD was longer in patients receiving quadruple therapy comprising everolimus than in those who did not (63 [30-92] vs. 29 [12-44] months; p = 0.025). This suggests that the addition of everolimus to a standard triple could result in a lower incidence of CLAD in lung transplant recipients.

Circulating Vesicular-bound HLA-G as Noninvasive Predictive Biomarker of CLAD After Lung Transplantation.

BACKGROUND: Circulating extracellular vesicles (EVs) have shown promising results as noninvasive biomarkers for predicting disease outcomes in solid organ transplantation. Because in situ graft cell expression of the tolerogenic molecule HLA-G is associated with acceptance after lung transplantation (LTx), we hypothesized that plasma EV-bound HLA-G (HLA-GEV) levels could predict chronic lung allograft dysfunction (CLAD) development. METHODS: We analyzed 78 LTx recipients from the Cohort-for-Lung-Transplantation cohort, all in a stable (STA) state within the first year post-LTx. At 3 y, 41 patients remained STA, and 37 had CLAD (bronchiolitis obliterans syndrome, BOS, [n = 32] or restrictive allograft syndrome [n = 5]). HLA-GEV plasma levels were measured at month 6 (M6) and M12 in 78 patients. CLAD occurrence and graft failure at 3 y post-LTx were assessed according to early HLA-GEV plasma levels. RESULTS: In patients with subsequent BOS, (1) HLA-GEV levels at M12 were significantly lower than those in STA patients (P = 0.013) and (2) also significantly lower than their previous levels at M6 (P = 0.04).A lower incidence of CLAD and BOS and higher graft survival at 3 y were observed in patients with high HLA-GEV plasma levels at M12 (high versus low HLA-GEVs patients [cutoff 21.3 ng/mL]: freedom from CLAD, P = 0.002; freedom from BOS, P < 0.001; and graft survival, P = 0.04, [log-rank]). Furthermore, in multivariate analyses, low HLA-GEV levels at M12 were independently associated with a subsequent risk of CLAD, BOS, and graft failure at 3 y (P = 0.015, P = 0.036, and P = 0.026, respectively [Cox models]). CONCLUSIONS: This exploratory study suggests the potential of EV-bound HLA-G plasma levels as a liquid biopsy in predicting CLAD/BOS onset and subsequent graft failure.

Severe asthma care trajectories: the French RAMSES cohort.

Background: The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs). Methods: Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients' characteristics were analysed at inclusion and compared between TRCs and SCCs. Results: 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm-3; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390). Conclusions: Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care.

Several Nocardia abcessus bronchiolitis in a patient treated with inhaled corticosteroids: a case report.

Nocardiosis is a disease that mainly affects immunocompromised patients. Inhaled corticosteroids (ICS) are standard of care for asthma. This treatment can induce respiratory infections but no case of bronchiolitis nocardiosis have been described so far. A 58-year-old man, with history of controlled moderate allergic asthma, develop an increased cought in the last two years associated with dyspnea on exertion. Within two months, although ICS were increased to high doses, symptoms worsened due to a severe obstructive ventilatory disorder as revealed by pulmonary function tests (PFT). Small-scale lesions (< 10%) were found on chest computed tomography (CT). A bronchoalveolar lavage (BAL) found Nocardia abcessus. After six months of Sulfamethoxazole/Trimethoprim, PFT results improved and chest CT became completely normal. We therefore present the case of a bronchiolitis nocardiosis with several bronchial syndrome and the only immunosuppressive factor found were ICS.

Efficacy of three COVID-19 vaccine doses in lung transplant recipients: a multicentre cohort study.

QUESTION ADDRESSED BY THE STUDY: Do three coronavirus disease 2019 (COVID-19) vaccine doses induce a serological response in lung transplant recipients? METHODS: We retrospectively included 1071 adults (551 (52%) males) at nine transplant centres in France. Each had received three COVID-19 vaccine doses in 2021, after lung transplantation. An anti-spike protein IgG response, defined as a titre >264 BAU·mL-1 after the third dose (median (interquartile range (IQR)) 3.0 (1.7-4.1) months), was the primary outcome and adverse events were the secondary outcomes. Median (IQR) age at the first vaccine dose was 54 (40-63) years and median (IQR) time from transplantation to the first dose was 64 (30-110) months. RESULTS: Median (IQR) follow-up after the first dose was 8.3 (6.7-9.3) months. A vaccine response developed in 173 (16%) patients. Factors independently associated with a response were younger age at vaccination, longer time from transplantation to vaccination and absence of corticosteroid or mycophenolate therapy. After vaccination, 51 (5%) patients (47 non-responders (47/898 (5%)) and four (4/173 (2%)) responders) experienced COVID-19, at a median (IQR) of 6.6 (5.1-7.3) months after the third dose. No responders had severe COVID-19 compared with 15 non-responders, including six who died of the disease. CONCLUSIONS: Few lung transplant recipients achieved a serological response to three COVID-19 vaccine doses, indicating a need for other protective measures. Older age and use of mycophenolate or corticosteroids were associated with absence of a response. The low incidence of COVID-19 might reflect vaccine protection via cellular immunity and/or good adherence to shielding measures.

SARS-CoV-2 anti-spike antibodies after a fourth dose of COVID-19 vaccine in adult solid-organ transplant recipients.

BACKGROUND: A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known. METHODS: We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT. RESULTS: 825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9-69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (>260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p < 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p < 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4. CONCLUSION: A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.

Chronic lung allograft dysfunction is associated with an early increase of circulating cytotoxic CD4+CD57+ILT2+ T cells, selectively inhibited by the immune check-point HLA-G.

BACKGROUND: Survival after lung transplantation (LTx) still remains limited by chronic lung allograft dysfunction (CLAD), thought to represent a form of chronic rejection. We investigated whether the immune checkpoint HLA-G/ILT2 expressed by peripheral T-cell subpopulations could predict CLAD. METHODS: We used data for 150 LTx recipients from COLT (Cohort-For-Lung-Transplantation) cohort with ≥1 available blood sample at 1-, 6-, or 12-months post-Tx. Analysis of T cells by flow cytometry focused on the ILT2 receptor of HLA-G and other markers (CD57, CD25, CD127). T-cell subset analyses compared stable patients and those with CLAD at 3 years post-LTx. RESULTS: With data for 78 stable and 72 CLAD patients, among 21 T-cell subsets expressing ILT2, only CD4+CD57+ILT2+ T cells were associated with outcome. At 1-month post-Tx, low proportion of CD4+CD57+ILT2+ T cells was associated with reduced 3-year incidence of CLAD (CD4+CD57+ILT2+ T cells ≤ first IQR [25%] vs > first IQR, log-rank test, p = 0.028). Furthermore, the incidence of CLAD was higher with >2.6- vs ≤2.6-fold increased proportion of CD4+CD57+ILT2+ T cells over the first year post-LTx (3-year freedom frequencies: 27% [95%CI: 8-50] vs 64% [95%CI: 48-77] (log-rank test, p = 0.014). On multivariable analysis, increased proportion of CD4+CD57+ILT2+ T cells over the first year predicted CLAD (hazard ratio 1.25; 95%CI: 1.09-1.44; p = 0.001). Focusing on CD4+CD57+ILT2+ T cells, we demonstrated ex vivo that they are cytotoxic CD4+ T cells, selectively inhibited by HLA-G. CONCLUSIONS: Our data suggest that an early increase of CD4+CD57+ILT2+ T cells after LTx may be associated with CLAD onset.

Impact of Interface Type on Noninvasive Ventilation Efficacy in Patients With Neuromuscular Disease: A Randomized Cross-Over Trial.

BACKGROUND AND OBJECTIVE: Around 25% of patients with neuro-muscular diseases (NMD) are treated by home noninvasive ventilation (NIV) through an oronasal mask. However, there is growing evidence that nasal masks require lower NIV pressures and result in fewer residual obstructive events. We hypothesized that nasal masks would improve efficacy and reduce side effects compared to oronasal masks in this population. METHODS: open label, cross-over, randomized, study in 2 tertiary care hospitals. Patients with NMD treated by home NIV were randomized for one-week periods to nasal and oronasal interfaces respectively (cross-over). At the end of each period, nocturnal polygraphy (monitoring mouth opening) under NIV, synchronized with transcutaneous partial pressure in CO2 (tcCO2) was performed. Data were collected from the NIV built-in software and NIV side-effects were collected. Intention-to-treat and per protocol analyses were performed. The primary outcome was mean nocturnal SpO2. The secondary outcomes were: percentage of sleep with SpO2<90%, oxygen desaturation index (ODI), mean tcCO2, mean duration of mouth opening during sleep, level of non-intentional leaks and side-effects. RESULTS: Thirty patients with NMD were included. There were no between-group differences for either the primary or secondary outcomes. Post hoc comparisons showed that changing between interfaces reduced NIV efficacy: mean nocturnal SpO2 (p=0.04), ODI (p=0.01), mean tcCO2 (p=0.048), side-effects (p=0.008). CONCLUSION: Nasal masks did not improve NIV efficacy or reduce side effects compared to oronasal masks in patients with NMD treated by home NIV. The efficacy of NIV is reduced during the transition to another interface, requiring close monitoring. Registration number: NCT03458507.

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%.

Direct Molecular Diagnosis of Aspergillosis and CYP51A Profiling from Respiratory Samples of French Patients.

BACKGROUND: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. METHODS: A total of 97 respiratory samples including bronchoalveolar lavages (BAL), bronchial aspirates (BA), tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive aspergillosis (n = 12), chronic pulmonary aspergillosis (n = 3), allergic bronchopulmonary aspergillosis (n = 7), or colonization (n = 11) and 28 controls. Each specimen was evaluated by culture, pan-Aspergillus qPCR, and CYP51A PCR and sequencing. RESULTS: One A. flavus and 19 A. fumigatus with one multiazole resistant strain (5.3%) were cultured from 20 samples. Culture positivity was 62.5, 75, 42.9, and 15.8% in ABPA, CPA, IA, and colonized patients, respectively. Aspergillus detection rate was significantly higher by pan-Aspergillus qPCR than by culture in IA (90.5 vs. 42.9%; P < 0.05) and colonization group (73.7 vs. 15.8%; P < 0.05). The CYP51A PCR found one TR34/L98H along with 5 novel cyp51A mutations (4 non-synonymous and 1 promoter mutations), yet no association can be established currently between these novel mutations and azole resistance. The analysis of 11 matched pairs of BA and BAL samples found that 9/11 BA carried greater fungal load than BAL and CYP51A detection was more sensitive in BA than in BAL. CONCLUSION: Direct molecular detection of Aspergillus spp. and azole resistance markers are useful adjunct tools for comprehensive aspergillosis diagnosis. The observed superior diagnostic value of BAs to BAL fluids warrants more in-depth study.

[Therapeutic Drug Management for Transplanted Women with a Planned Pregnancy: About Two Cases of Lung and Heart-lung Transplantation]. / Traitement médicamenteux chez la femme transplantée avec un projet de grossesse : à propos de deux cas de transplantation pulmonaire et cardio-pulmonaire.

Advances in lung transplantation allow the women of childbearing age to consider becoming mothers. When planning to become pregnant, a therapeutic drug management of immunosuppressive drugs and associated therapies is required. It must take into account teratogenic and fetotoxic drugs, as well as pharmacokinetic changes encountered during pregnancy. Increasingly data are currently available on the management of immunosuppressive drugs and associated therapies during pregnancy. We report the case management of drug therapy before and during pregnancy in two patients after a lung or heart-lung transplantation. To prevent the emergence of complications for mother and child, a literature review has been necessary to manage drug therapies of each patient.

Nonspecific immunoglobulin replacement in lung transplantation recipients with hypogammaglobulinemia: a cohort study taking into account propensity score and immortal time bias.

BACKGROUND: After lung transplantation (LT), immunoglobulin (Ig) G plasma concentrations<6 g/L are common and correlate with an increased risk of chronic lung allograft dysfunction (CLAD) and a poorer survival. METHODS: We conducted an open substitution intervention with nonspecific intravenous Ig (IVIg), in all patients with IgG plasma less than 6 g/L post-LT in 54 of 84 consecutive recipients since 1998 who survived more than 3 months. Pre-LT and post-LT events were retrospectively analyzed. RESULTS: Both substituted and nonsubstituted groups demonstrated similar donor or recipient characteristics and events over a median follow-up of 2.8 years (Q1-Q3, 1.4-5.7], except for initial diagnosis with more chronic obstructive pulmonary disease patients and less cases of pulmonary arterial hypertension in NS group. Intravenous Ig substitution started 3.5 months (0.5-9.4) after transplantation and lasted 4.5 months after (1.0-17.7), mean cumulative dose was 52.8±47.7 g. In multivariate Cox regression model, hypogammaglobulinemic patients who were substituted with IVIg had actually a 5-year survival (hazard ratio, 0.63; 95% confidence interval, 0.26-1.49; P=0.29) and CLAD-free 5-year survival (hazard ratio, 0.51; 95% confidence interval, 0.15-1.67; P=0.27) really close to nonhypogammaglobulinemic and nonsubstituted patients. Complementary analysis using propensity score and time-dependent analysis showed that survival and CLAD-free survival were not different in both groups. CONCLUSION: Intravenous Ig post-LT achieved similar survival and CLAD-free survival in recipients with hypogammaglobulinemia as compared to those with normal IgG plasmatic rate. A randomized control trial is required to confirm benefic effects of IVIg and disentangle mechanisms, including protection from infections, acute cellular and humoral rejections in patients with hypogammaglobulinemia after LT.

Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry.

INTRODUCTION: Our objective was to investigate characteristics risk factors and outcomes of patients with chronic pulmonary aspergillosis (CPA). METHODS: The Aspergillosis Committee prospectively collected Aspergillus notifications from January 2000 to December 2011. A retrospective analysis of data was performed. RESULTS: Among 1614 notifications registered, 44 cases of CPA in non-immunocompromised patients were identified. The median age was 65 years (Q1-Q3: 54-75), the median body mass index (BMI) was 20 kg/m(2) (Q1-Q3: 16-22) and 15 had chronic obstructive pulmonary disease. All patients had a positive specific serum precipitin antibody titer. Radiological presentations were: cavitations [single n = 31 (70%); multiple n = 12 (27%)] containing mycetomas [n = 18 (41%)], consolidations [n = 19 (43%)], emphysema [n = 15 (34%)] and sequelae of mycobacterial infection [n = 10 (23%)]. The median duration of follow-up was 30 months (Q1-Q3: 14-55). The median duration of antifungal treatment was 6 months (Q1-Q3: 3-12). Outcomes were unfavorable in 14 patients, and 12 (27%) died. Analysis by multivariate Cox regression model with bootstrapping showed that a higher BMI and a lower Charlson index score were predictive of favorable evolution, hazard ratio (95% confidence interval): BMI (+1) = 0.83 (0.71-0.97), Charlson (+1) = 1.37 (1.01-1.85). When analyses were restricted to chronic CPA and chronic necrotizing pulmonary aspergillosis, the multivariate Cox regression model showed that both BMI and Charlson index score were not statistically significant. CONCLUSION: Our results provide data on clinical characteristics and outcomes of CPA emphasizing the role of preexisting chronic respiratory conditions and protective effect of preserved BMI and lower Charlson index score.

Influence of intention to adhere, beliefs and satisfaction about medicines on adherence in solid organ transplant recipients.

INTRODUCTION: Nonadherence to immunosuppressive (IS) therapy is associated with poor outcomes. Identifying factors predicting poor adherence is therefore essential. The primary objective of this study was to test whether parameters of a model adapted from the theory of planned behavior, and more specifically attitudes that are influenced by beliefs and satisfaction with medication, could predict adherence in solid organ transplant patients. METHODS: Adherence was assessed with a self-reported medication adherence scale and IS blood trough concentrations over 6 months, in four transplant units. Satisfaction and beliefs were assessed using the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) and Beliefs about Medicines Questionnaire (BMQ), respectively. Theory of planned behavior was assessed with a specific questionnaire exploring intentions, subjective norms, attitudes and perceived behavioral control. Treatment characteristics and socioeconomic data were also collected. RESULTS: One hundred and fifty-three solid organ transplant patients were enrolled, including lung (n=33), heart (n=43), liver (n=42), and kidney (n=44) patients. Satisfaction and positive beliefs about medication were higher in adherent than those in nonadherent patients. Factors independently associated with an increased risk of nonadherence were negative general beliefs about medications (odds ratio [OR]=0.89 [0.83-0.97]), living alone (OR=2.78 [1.09-7.09]), heart transplantation (OR=3.49 [1.34-9.09]), and being on everolimus (OR=5.02 [1.21-20.8]). CONCLUSION: Negative beliefs toward medications were shown to be an independent risk factor of poor adherence. Therefore, the BMQ could be an effective, easy to implement tool, for use in everyday practice, to identify patients needing interventions to improve adherence to IS.

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.

Seven-year surveillance of nosocomial invasive aspergillosis in a French University Hospital.

OBJECTIVES: This study aims at describing the evolution of the epidemiology of invasive aspergillosis (IA) in a French University Hospital focussing on nosocomial cases, in order to assess the efficiency of the environmental preventive measures which were implemented. METHODS: From 2003 to 2009, IA cases were reviewed monthly and classified according to the EORTC/MSG criteria and the origin of contamination. RESULTS: Five proven and 65 probable IA cases were diagnosed. Most of the cases (74.3%) occurred in patients with haematological malignancies. Incidences of IA and nosocomial IA (NIA) were 0.106 and 0.032 cases per 1000 admissions, respectively. All the 21 NIA cases occurred in the absence of air treatment (laminar air flow facilities or Plasmair decontamination units) and/or during construction works. The 3-month and 1-year overall survival rates were 50.6% [38.2-61.7] and 31.1% [20-42.9] respectively, and did not differ according to the origin of contamination. CONCLUSION: Nosocomial IA still accounted for a third of all IA cases diagnosed from 2003 to 2009 and mainly occurred in the absence of environmental protective measures, which were confirmed to be effective when applied. Our results show that extension and/or reinforcement of these measures is needed, especially in the haematology unit and during construction works.

Development of a pharmacist collaborative care program for pulmonary arterial hypertension.

Patients with Pulmonary Arterial Hypertension (PAH) require multidisciplinary care. Involving pharmacists in PAH multidisciplinary care teams may enhance patient education and improve medication use. We describe the implementation of a Pharmacist Collaborative Care Program (PCCP) in a PAH referral centre in Grenoble, France. Initiated in 2007, the PCCP program includes a pharmacist intervention whose goals are educational, psychosocial, and technical. During patient interviews, pharmacists make an 'educational diagnosis' and provide a patient-specific education session. Patient skills are evaluated at the end of the session. Pharmacists provide feedback to nurses and physicians through a standardized report form and discussion during medical rounds and PAH group meetings. Pharmacists re-evaluate patients' skills every 3-6 months during multidisciplinary clinical evaluations. The PCCP program for PAH is an established practice in Grenoble and may inform future patient education programs involving pharmacists in France, where legislation has recently been passed to standardize patient education.

Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

BACKGROUND: Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. METHODS: In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. RESULTS: Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. CONCLUSIONS: We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

Sphincter pharyngoplasty as a treatment of velopharyngeal incompetence in young people: a prospective evaluation of effects on sleep structure and sleep respiratory disturbances.

BACKGROUND: Sphincter pharyngoplasty (SP) appears to be the more "physiologic" surgical technique to treat velopharyngeal incompetence (VPI). This procedure creates a dynamic sphincter of variable diameter and keeps the flexibility of the soft palate. SP also induces velopharyngeal size reduction, mainly in the transverse diameter, which may cause upper airway (UA) occlusions during sleep. AIM: To prospectively evaluate the effects of SP by a modified Orticochea procedure on sleep structure and sleep respiratory disturbances. METHODS: Polysomnographic studies before and after surgery in 17 consecutive patients treated by a modified Orticochea procedure SP for VPI. RESULTS: For the whole group, SP did not induce significant impairment of apnea-hypopnea index or nocturnal oxygen saturation. Slow-wave sleep (SWS) was significantly reduced after surgery (25 +/- 9% of total sleep time [TST] vs 28 +/- 9% of TST before SP [p = 0.04]). Following surgery, there was a trend for an increase in the microarousal index) (p = 0.09) and more specifically in respiratory-related microarousals. CONCLUSION: SP, although creating a clinically obvious reduction of velopharyngeal diameter, generally did not lead to the occurrence of an obstructive sleep apnea syndrome. However, we found a significant reduction of SWS quantity and a trend toward an increase in the number of cortical microarousals. These findings suggest that the reduction of UA diameter associated with the surgical technique leads to increases in respiratory effort sufficient to induce sleep fragmentation and SWS reduction, even in the absence of apneas or hypopneas.