Dominique Grenet - Academia.edu (original) (raw)

Papers by Dominique Grenet

Research paper thumbnail of Near Fatal Lung Injury with Rapid-Onset Bronchiectasis Caused by Traditional Fumigation Therapy on the French Island of Mayotte

Annals of the American Thoracic Society, 2017

Research paper thumbnail of Liste des collaborateurs

Pathologies maternelles et grossesse, 2014

Research paper thumbnail of Blood and alveolar lymphocyte subsets in pulmonary cytomegalovirus infection after lung transplantation

Background: Cytomegalovirus (CMV) pneumonitis has been shown to be associated with lymphocytic al... more Background: Cytomegalovirus (CMV) pneumonitis has been shown to be associated with lymphocytic alveolitis after lung transplantation. In the present study, we investigated a series of bronchoalveolar (BAL) and blood samples, collected in the absence of rejection or acute infectious episodes. in order -1: to evaluate intra-alveolar cell population changes concomitant with CMV replication and -2: to reappraise the value of cell population analysis in the management of patients after lung transplantation.

Research paper thumbnail of Predictive Value of Cytomegalovirus Dna Detection by Polymerase Chain Reaction in Blood and Bronchoalveolar Lavage in Lung Transplant PATIENTS1

Transplantation, 1997

Despite promising results, the efficacy of polymerase chain reaction (PCR) for clinical managemen... more Despite promising results, the efficacy of polymerase chain reaction (PCR) for clinical management of cytomegalovirus (CMV) infection in transplanted patients is still controversial. A prospective study of CMV detection, with concurrent shell vial cultures and PCR in blood and bronchoalveolar lavage (BAL), was conducted in 13 lung transplant recipients, monitored for 15 months (range: 1-42 months). CMV DNA was detected by PCR amplification of a 406-bp fragment in the Us region and a 290-bp fragment in the immediate early region of the viral genome. When comparing PCR to viral culture, the sensitivity and specificity of CMV DNA detection were 100% and 65.7% in blood (n=122) and 100% and 75% in BAL (n=104). The positive and negative predictive values of PCR for a forthcoming diagnosis of CMV infection were 50% and 97% in blood, and 67% and 85% in BAL. Seventeen CMV infections were evaluated at the end of treatment: when PCR was still positive either in blood or BAL, CMV infection relapsed within 35+/-5 days; when PCR was negative, CMV infection relapsed after 142+/-57 days (P=0.01). Negative CMV detection by PCR strongly advocates against a forthcoming CMV infection. PCR assay seems to be a good predictor for early recurrence of CMV infection, and would be useful for monitoring the response to antiviral therapy.

Research paper thumbnail of Lessons from a French collaborative case–control study in cystic fibrosis patients during the 2009 A/H1N1 influenza pandemy

BMC Infectious Diseases, 2015

Viral infections such as influenza are thought to impact respiratory parameters and to promote in... more 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. 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. 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. Our results do not demonstrate any change in sputum colonization nor significant lung disease progression after pandemic A/H1N1 influenza. Clinical Trials.gov registration number: NCT01499914.

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

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 18, 2015

Little data exist on causes of death in cystic fibrosis (CF) patients in the era of lung transpla... more Little data exist on causes of death in cystic fibrosis (CF) patients in the era of lung transplantation. 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. 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. These data suggest that improvement in transplantation referral strategies may result in transplantation-related survival benefits.

Research paper thumbnail of Expression of Calcineurin Activity after Lung Transplantation: A 2-Year Follow-Up

PLoS ONE

The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineu... more 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 the...

Research paper thumbnail of High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post transplant mortality

Transplant International, 2015

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of gr... more Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1(st) July 2007 to 31(th) May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g.perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, p=0.0005). No significant difference was observed between HELT and non HELT patients in mechanical ventilation duration (15.5d vs. 11d, p=0.27), intensive care unit length of stay (15d. vs. 10d, p=0.22) or survival rate at 12 (81% vs. 80%) and 24 months post LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Combined Lung And Kidney Transplantation For Cystic Fibrosis With Renal Amyloïdosis And Nephrotic Syndrome

D44. COUGH, PFT AND INTERESTING CASE REPORTS IN AIRWAY DISEASE, 2010

Research paper thumbnail of Expression of Calcineurin Activity after Lung Transplantation: A 2-Year Follow-Up

PLoS ONE, 2013

The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineu... more 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.

Research paper thumbnail of Central venous thrombosis and thrombophilia in cystic fibrosis: A prospective study

Journal of Cystic Fibrosis, 2015

Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thro... more Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thrombophilic tendency was described in cystic fibrosis (CF), the significance of which remains unclear. The aims of this study were to (1) document the frequency of catheter venous thrombosis detected by colour-Doppler-ultrasound (Doppler-US), (2) assess genetic and acquired thrombophilia risk factors for catheter venous thrombosis and hypercoagulability status and (3) provide recommendations on laboratory screening when considering insertion of a totally implantable vascular access device (TIVAD) in CF patients. We designed a multicentre prospective study in patients selected at the time of catheter insertion. Doppler-US was scheduled at 1 and 6months after insertion and before insertion in case of a previous central line. Blood samplings were drawn at insertion and at 1 and 6months later. One-hundred patients received a TIVAD and 90 completed the 6-month study. Prevalence of thrombophilia abnormalities and hypercoagulability was found in 50% of the cohorts. Conversely, catheter venous thrombosis frequency was low (6.6%). Our data do not support biological screening at the time of a TIVAD insertion. We emphasise the contribution of a medical history of venous thromboembolism and prospective Doppler-US for identifying asymptomatic catheter venous thrombosis to select patients who may benefit from biological screening and possible anticoagulant therapy.

Research paper thumbnail of Impact of Osteopathic Treatment on Pain in Adult Patients with Cystic Fibrosis – A Pilot Randomized Controlled Study

PLoS ONE, 2014

Background: Pain is a common complication in patients with cystic fibrosis (CF) and is associated... more Background: Pain is a common complication in patients with cystic fibrosis (CF) and is associated with shorter survival. We evaluated the impact of osteopathic manipulative treatment (OMT) on pain in adults with CF.

Research paper thumbnail of Cystic fibrosis and AA amyloidosis: a survey in the French cystic fibrosis network

Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2014

To define the characteristics of CF patients developing AA amyloidosis. A 30-year retrospective s... more To define the characteristics of CF patients developing AA amyloidosis. A 30-year retrospective survey conducted within the national French CF network to identify cases of CF associated with AA amyloidosis. Nine cases of AA amyloidosis were identified (CF prevalence in France is approximately 6000 patients) and sufficient data were collected in six. The clinical presentation was renal disease in four cases, a compressive goiter in one case, and epigastric pain in one case. Organ involvement included kidney disease in all cases (proteinuria, with a median age at onset of 24 years, 4 cases with nephrotic syndrome, 5 with renal failure); gastrointestinal (4 cases with duodenal ulcer); thyroid (2 cases); and hepatobiliary system (3 cases). The median age at diagnosis of CF was 6.5 years. Five patients had pancreatic insufficiency. All patients had chronic respiratory infections requiring intravenous antibiotics several times a year. Five patients have died, at a median age of 29 years a...

Research paper thumbnail of Increased ENDOTHELIN-1 Associated with Bacterial Infection in Lung Transplant RECIPIENTS1

Transplantation, 2001

Background. Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role i... more Background. Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role in pulmonary fibrosis and certain inflammatory airway diseases is now well known. Its production is, in part, triggered by infectious processes. Episodes of infection are suspected to be involved in the development of bronchiolitis obliterans syndrome (BOS), which is the main feature of chronic lung rejection and the major factor limiting the long-term survival of transplanted patients. We postulated that ET-1 is upregulated during infectious complications arising from the graft and that this could partly explain the remodeling of airway structures observed in BOS. We, therefore, set up this study to assess ET-1 expression in relation to complications of the graft in human lung transplant recipients.

Research paper thumbnail of Failure of Ganciclovir Treatment Associated with Selection of a Ganciclovir-Resistant Cytomegalovirus Strain in a Lung Transplant Recipient

Transplantation, 1997

We report the case of a lung transplant recipient with progressive cytomegalovirus (CMV) disease ... more We report the case of a lung transplant recipient with progressive cytomegalovirus (CMV) disease due to a resistant CMV strain emerging under ganciclovir (GCV) therapy. A discriminative polymerase chain reaction (PCR) assay, designed to detect the resistance-related V460 mutation within the viral enzyme UL97, revealed the presence of a mutated strain in a heterogeneous isolate 51 days after transplantation. The conventional antiviral susceptibility assay had failed to demonstrate resistance to GCV. Under prolonged GCV therapy, the mutated strain dominated the wild-type strain, as shown by the PCR assay. This domination led to laboratory resistance, associated with recurrent fever and progressively severe retinitis. As this discriminative PCR assay was shown to be effective in detecting mutated strains that constitute a minority in the virus load, it should allow better management of patients with CMV disease.

Research paper thumbnail of Management of Takotsubo Cardiomyopathy in a Lung Transplant Recipient

Research paper thumbnail of Small-cell Lung Carcinoma of Recipient Origin After Bilateral Lung Transplantation For Cystic Fibrosis

The Journal of Heart and Lung Transplantation, 2006

Bronchial carcinoma, usually of the non-small-cell type, is uncommon after lung transplantation a... more Bronchial carcinoma, usually of the non-small-cell type, is uncommon after lung transplantation and occurs predominantly in single-lung transplant ex-smoker recipients on their native lung. Bronchial carcinoma of donor origin is much rarer. We report the case of a small-cell lung carcinoma of recipient origin that occurred 12 months after a bilateral lung transplantation for cystic fibrosis in a 25-year-old woman who was a non-smoker. The tumor was of recipient origin, due to a gender mismatch between donor and recipient. This unusual observation corroborates the hypothesis of chimerism of the bronchial epithelium after lung transplantation. J Heart Lung Transplant 2006;25:981-4.

Research paper thumbnail of Occurrence of CFTR de novo mutations is not so rare

Journal of Cystic Fibrosis, 2008

Research paper thumbnail of Microbiological and Epidemiological Features of Clinical Respiratory Isolates of Burkholderia gladioli

Journal of Clinical Microbiology, 2009

Burkholderia gladioli, primarily known as a plant pathogen, is involved in human infections, espe... more Burkholderia gladioli, primarily known as a plant pathogen, is involved in human infections, especially in patients with cystic fibrosis (CF). In the present study, the first respiratory isolates recovered from 14 French patients with CF and 4 French patients without CF, identified by 16S rRNA gene analysis, were tested for growth on B. cepacia selective media, for identification by commercial systems, and for their antimicrobial susceptibilities, and were compared by pulsed-field gel electrophoresis (PFGE). Patients' data were collected. All 18 isolates grew on oxidation-fermentation-polymyxin B-bacitracin-lactose medium and Pseudomonas cepacia agar, but only 13 grew on Burkholderia cepacia selective agar. API 20NE strips did not differentiate B. gladioli from B. cepacia, whereas Vitek 2 GN cards correctly identified 15 isolates. All isolates were susceptible to piperacillin, imipenem, aminoglycosides, and ciprofloxacin and were far less resistant to ticarcillin than B. cepacia complex organisms. Fifteen PFGE types were observed among the 18 isolates, but shared types were not identified among epidemiologically related patients. The microbiological follow-up of CF patients showed that colonization was persistent in 3 of 13 documented cases; B. gladioli was isolated from posttransplantation cultures of blood from 1 patient. Among the patients without CF, B. gladioli was associated with intubation (three cases) or bronchiectasis (one case). In summary, the inclusion of B. gladioli in the databases of commercial identification systems should improve the diagnostic capabilities of those systems. In CF patients, this organism is more frequently involved in transient infections than in chronic infections, but it may be responsible for complications posttransplantation; patient-to-patient transmission has not been demonstrated to date. Lastly, B. gladioli appears to be naturally susceptible to aminoglycosides and ciprofloxacin, although resistant isolates may emerge in the course of chronic infections.

Research paper thumbnail of Advances in lung transplantation for cystic fibrosis that may improve outcome

European Journal of Cardio-Thoracic Surgery, 2010

Objective: To study the advances in the management of lung-transplanted patients for cystic fibro... more Objective: To study the advances in the management of lung-transplanted patients for cystic fibrosis in our centre and their impact on the outcome. Methods: A retrospective study has included 100 patients who underwent lung transplantation for cystic fibrosis between 1 January 1990 and 15 January 2007. There were 78 sequential double-lung transplantations and 22 lobar transplantations. This series has been equally divided in two groups according to the date of transplantation: group I, before September 2003 and, group II, after September 2003. Results: Recipient characteristics were similar in both groups. In group II, donors were older (40 vs 33 years, respectively, P = 0.013), with lower partial pressure of oxygen in arterial blood (PaO 2 )/fractional inspired oxygen (FiO 2 ) ratios (372 vs 427 mm Hg, P = 0.022). In group II, recipients received, more often, thoracic epidural analgesia (n = 35 vs n = 13, P < 0.001), the surgical approach was mostly a sternum-sparing bilateral anterior thoracotomy (n = 42 vs n = 9, P < 0.001), and lobar transplantations were performed more frequently (n = 15 vs n = 7, P = 0.30). Early tracheal extubation was more frequent in group II (P = 0.005). The overall median survival time was 52 months. In the first group, 1-, 2-and 3-year survival rates were 75%, 65% and 55%, respectively, whereas in the second group, these survival rates were 88%, 78% and 69%, respectively (P = 0.09). Conclusions: The acceptance of marginal donors and the frequent practice of lobar transplantations allowed an increasing number of lung transplantations for cystic fibrosis over time. Concomitantly, the extensive use of thoracic epidural analgesia has increased the rate of early extubation and contributed to a trend towards a survival improvement. #

Research paper thumbnail of Near Fatal Lung Injury with Rapid-Onset Bronchiectasis Caused by Traditional Fumigation Therapy on the French Island of Mayotte

Annals of the American Thoracic Society, 2017

Research paper thumbnail of Liste des collaborateurs

Pathologies maternelles et grossesse, 2014

Research paper thumbnail of Blood and alveolar lymphocyte subsets in pulmonary cytomegalovirus infection after lung transplantation

Background: Cytomegalovirus (CMV) pneumonitis has been shown to be associated with lymphocytic al... more Background: Cytomegalovirus (CMV) pneumonitis has been shown to be associated with lymphocytic alveolitis after lung transplantation. In the present study, we investigated a series of bronchoalveolar (BAL) and blood samples, collected in the absence of rejection or acute infectious episodes. in order -1: to evaluate intra-alveolar cell population changes concomitant with CMV replication and -2: to reappraise the value of cell population analysis in the management of patients after lung transplantation.

Research paper thumbnail of Predictive Value of Cytomegalovirus Dna Detection by Polymerase Chain Reaction in Blood and Bronchoalveolar Lavage in Lung Transplant PATIENTS1

Transplantation, 1997

Despite promising results, the efficacy of polymerase chain reaction (PCR) for clinical managemen... more Despite promising results, the efficacy of polymerase chain reaction (PCR) for clinical management of cytomegalovirus (CMV) infection in transplanted patients is still controversial. A prospective study of CMV detection, with concurrent shell vial cultures and PCR in blood and bronchoalveolar lavage (BAL), was conducted in 13 lung transplant recipients, monitored for 15 months (range: 1-42 months). CMV DNA was detected by PCR amplification of a 406-bp fragment in the Us region and a 290-bp fragment in the immediate early region of the viral genome. When comparing PCR to viral culture, the sensitivity and specificity of CMV DNA detection were 100% and 65.7% in blood (n=122) and 100% and 75% in BAL (n=104). The positive and negative predictive values of PCR for a forthcoming diagnosis of CMV infection were 50% and 97% in blood, and 67% and 85% in BAL. Seventeen CMV infections were evaluated at the end of treatment: when PCR was still positive either in blood or BAL, CMV infection relapsed within 35+/-5 days; when PCR was negative, CMV infection relapsed after 142+/-57 days (P=0.01). Negative CMV detection by PCR strongly advocates against a forthcoming CMV infection. PCR assay seems to be a good predictor for early recurrence of CMV infection, and would be useful for monitoring the response to antiviral therapy.

Research paper thumbnail of Lessons from a French collaborative case–control study in cystic fibrosis patients during the 2009 A/H1N1 influenza pandemy

BMC Infectious Diseases, 2015

Viral infections such as influenza are thought to impact respiratory parameters and to promote in... more 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. 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. 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. Our results do not demonstrate any change in sputum colonization nor significant lung disease progression after pandemic A/H1N1 influenza. Clinical Trials.gov registration number: NCT01499914.

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

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 18, 2015

Little data exist on causes of death in cystic fibrosis (CF) patients in the era of lung transpla... more Little data exist on causes of death in cystic fibrosis (CF) patients in the era of lung transplantation. 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. 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. These data suggest that improvement in transplantation referral strategies may result in transplantation-related survival benefits.

Research paper thumbnail of Expression of Calcineurin Activity after Lung Transplantation: A 2-Year Follow-Up

PLoS ONE

The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineu... more 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 the...

Research paper thumbnail of High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post transplant mortality

Transplant International, 2015

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of gr... more Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;High Emergency Lung Transplantation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1(st) July 2007 to 31(th) May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g.perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, p=0.0005). No significant difference was observed between HELT and non HELT patients in mechanical ventilation duration (15.5d vs. 11d, p=0.27), intensive care unit length of stay (15d. vs. 10d, p=0.22) or survival rate at 12 (81% vs. 80%) and 24 months post LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Combined Lung And Kidney Transplantation For Cystic Fibrosis With Renal Amyloïdosis And Nephrotic Syndrome

D44. COUGH, PFT AND INTERESTING CASE REPORTS IN AIRWAY DISEASE, 2010

Research paper thumbnail of Expression of Calcineurin Activity after Lung Transplantation: A 2-Year Follow-Up

PLoS ONE, 2013

The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineu... more 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.

Research paper thumbnail of Central venous thrombosis and thrombophilia in cystic fibrosis: A prospective study

Journal of Cystic Fibrosis, 2015

Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thro... more Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thrombophilic tendency was described in cystic fibrosis (CF), the significance of which remains unclear. The aims of this study were to (1) document the frequency of catheter venous thrombosis detected by colour-Doppler-ultrasound (Doppler-US), (2) assess genetic and acquired thrombophilia risk factors for catheter venous thrombosis and hypercoagulability status and (3) provide recommendations on laboratory screening when considering insertion of a totally implantable vascular access device (TIVAD) in CF patients. We designed a multicentre prospective study in patients selected at the time of catheter insertion. Doppler-US was scheduled at 1 and 6months after insertion and before insertion in case of a previous central line. Blood samplings were drawn at insertion and at 1 and 6months later. One-hundred patients received a TIVAD and 90 completed the 6-month study. Prevalence of thrombophilia abnormalities and hypercoagulability was found in 50% of the cohorts. Conversely, catheter venous thrombosis frequency was low (6.6%). Our data do not support biological screening at the time of a TIVAD insertion. We emphasise the contribution of a medical history of venous thromboembolism and prospective Doppler-US for identifying asymptomatic catheter venous thrombosis to select patients who may benefit from biological screening and possible anticoagulant therapy.

Research paper thumbnail of Impact of Osteopathic Treatment on Pain in Adult Patients with Cystic Fibrosis – A Pilot Randomized Controlled Study

PLoS ONE, 2014

Background: Pain is a common complication in patients with cystic fibrosis (CF) and is associated... more Background: Pain is a common complication in patients with cystic fibrosis (CF) and is associated with shorter survival. We evaluated the impact of osteopathic manipulative treatment (OMT) on pain in adults with CF.

Research paper thumbnail of Cystic fibrosis and AA amyloidosis: a survey in the French cystic fibrosis network

Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2014

To define the characteristics of CF patients developing AA amyloidosis. A 30-year retrospective s... more To define the characteristics of CF patients developing AA amyloidosis. A 30-year retrospective survey conducted within the national French CF network to identify cases of CF associated with AA amyloidosis. Nine cases of AA amyloidosis were identified (CF prevalence in France is approximately 6000 patients) and sufficient data were collected in six. The clinical presentation was renal disease in four cases, a compressive goiter in one case, and epigastric pain in one case. Organ involvement included kidney disease in all cases (proteinuria, with a median age at onset of 24 years, 4 cases with nephrotic syndrome, 5 with renal failure); gastrointestinal (4 cases with duodenal ulcer); thyroid (2 cases); and hepatobiliary system (3 cases). The median age at diagnosis of CF was 6.5 years. Five patients had pancreatic insufficiency. All patients had chronic respiratory infections requiring intravenous antibiotics several times a year. Five patients have died, at a median age of 29 years a...

Research paper thumbnail of Increased ENDOTHELIN-1 Associated with Bacterial Infection in Lung Transplant RECIPIENTS1

Transplantation, 2001

Background. Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role i... more Background. Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role in pulmonary fibrosis and certain inflammatory airway diseases is now well known. Its production is, in part, triggered by infectious processes. Episodes of infection are suspected to be involved in the development of bronchiolitis obliterans syndrome (BOS), which is the main feature of chronic lung rejection and the major factor limiting the long-term survival of transplanted patients. We postulated that ET-1 is upregulated during infectious complications arising from the graft and that this could partly explain the remodeling of airway structures observed in BOS. We, therefore, set up this study to assess ET-1 expression in relation to complications of the graft in human lung transplant recipients.

Research paper thumbnail of Failure of Ganciclovir Treatment Associated with Selection of a Ganciclovir-Resistant Cytomegalovirus Strain in a Lung Transplant Recipient

Transplantation, 1997

We report the case of a lung transplant recipient with progressive cytomegalovirus (CMV) disease ... more We report the case of a lung transplant recipient with progressive cytomegalovirus (CMV) disease due to a resistant CMV strain emerging under ganciclovir (GCV) therapy. A discriminative polymerase chain reaction (PCR) assay, designed to detect the resistance-related V460 mutation within the viral enzyme UL97, revealed the presence of a mutated strain in a heterogeneous isolate 51 days after transplantation. The conventional antiviral susceptibility assay had failed to demonstrate resistance to GCV. Under prolonged GCV therapy, the mutated strain dominated the wild-type strain, as shown by the PCR assay. This domination led to laboratory resistance, associated with recurrent fever and progressively severe retinitis. As this discriminative PCR assay was shown to be effective in detecting mutated strains that constitute a minority in the virus load, it should allow better management of patients with CMV disease.

Research paper thumbnail of Management of Takotsubo Cardiomyopathy in a Lung Transplant Recipient

Research paper thumbnail of Small-cell Lung Carcinoma of Recipient Origin After Bilateral Lung Transplantation For Cystic Fibrosis

The Journal of Heart and Lung Transplantation, 2006

Bronchial carcinoma, usually of the non-small-cell type, is uncommon after lung transplantation a... more Bronchial carcinoma, usually of the non-small-cell type, is uncommon after lung transplantation and occurs predominantly in single-lung transplant ex-smoker recipients on their native lung. Bronchial carcinoma of donor origin is much rarer. We report the case of a small-cell lung carcinoma of recipient origin that occurred 12 months after a bilateral lung transplantation for cystic fibrosis in a 25-year-old woman who was a non-smoker. The tumor was of recipient origin, due to a gender mismatch between donor and recipient. This unusual observation corroborates the hypothesis of chimerism of the bronchial epithelium after lung transplantation. J Heart Lung Transplant 2006;25:981-4.

Research paper thumbnail of Occurrence of CFTR de novo mutations is not so rare

Journal of Cystic Fibrosis, 2008

Research paper thumbnail of Microbiological and Epidemiological Features of Clinical Respiratory Isolates of Burkholderia gladioli

Journal of Clinical Microbiology, 2009

Burkholderia gladioli, primarily known as a plant pathogen, is involved in human infections, espe... more Burkholderia gladioli, primarily known as a plant pathogen, is involved in human infections, especially in patients with cystic fibrosis (CF). In the present study, the first respiratory isolates recovered from 14 French patients with CF and 4 French patients without CF, identified by 16S rRNA gene analysis, were tested for growth on B. cepacia selective media, for identification by commercial systems, and for their antimicrobial susceptibilities, and were compared by pulsed-field gel electrophoresis (PFGE). Patients' data were collected. All 18 isolates grew on oxidation-fermentation-polymyxin B-bacitracin-lactose medium and Pseudomonas cepacia agar, but only 13 grew on Burkholderia cepacia selective agar. API 20NE strips did not differentiate B. gladioli from B. cepacia, whereas Vitek 2 GN cards correctly identified 15 isolates. All isolates were susceptible to piperacillin, imipenem, aminoglycosides, and ciprofloxacin and were far less resistant to ticarcillin than B. cepacia complex organisms. Fifteen PFGE types were observed among the 18 isolates, but shared types were not identified among epidemiologically related patients. The microbiological follow-up of CF patients showed that colonization was persistent in 3 of 13 documented cases; B. gladioli was isolated from posttransplantation cultures of blood from 1 patient. Among the patients without CF, B. gladioli was associated with intubation (three cases) or bronchiectasis (one case). In summary, the inclusion of B. gladioli in the databases of commercial identification systems should improve the diagnostic capabilities of those systems. In CF patients, this organism is more frequently involved in transient infections than in chronic infections, but it may be responsible for complications posttransplantation; patient-to-patient transmission has not been demonstrated to date. Lastly, B. gladioli appears to be naturally susceptible to aminoglycosides and ciprofloxacin, although resistant isolates may emerge in the course of chronic infections.

Research paper thumbnail of Advances in lung transplantation for cystic fibrosis that may improve outcome

European Journal of Cardio-Thoracic Surgery, 2010

Objective: To study the advances in the management of lung-transplanted patients for cystic fibro... more Objective: To study the advances in the management of lung-transplanted patients for cystic fibrosis in our centre and their impact on the outcome. Methods: A retrospective study has included 100 patients who underwent lung transplantation for cystic fibrosis between 1 January 1990 and 15 January 2007. There were 78 sequential double-lung transplantations and 22 lobar transplantations. This series has been equally divided in two groups according to the date of transplantation: group I, before September 2003 and, group II, after September 2003. Results: Recipient characteristics were similar in both groups. In group II, donors were older (40 vs 33 years, respectively, P = 0.013), with lower partial pressure of oxygen in arterial blood (PaO 2 )/fractional inspired oxygen (FiO 2 ) ratios (372 vs 427 mm Hg, P = 0.022). In group II, recipients received, more often, thoracic epidural analgesia (n = 35 vs n = 13, P < 0.001), the surgical approach was mostly a sternum-sparing bilateral anterior thoracotomy (n = 42 vs n = 9, P < 0.001), and lobar transplantations were performed more frequently (n = 15 vs n = 7, P = 0.30). Early tracheal extubation was more frequent in group II (P = 0.005). The overall median survival time was 52 months. In the first group, 1-, 2-and 3-year survival rates were 75%, 65% and 55%, respectively, whereas in the second group, these survival rates were 88%, 78% and 69%, respectively (P = 0.09). Conclusions: The acceptance of marginal donors and the frequent practice of lobar transplantations allowed an increasing number of lung transplantations for cystic fibrosis over time. Concomitantly, the extensive use of thoracic epidural analgesia has increased the rate of early extubation and contributed to a trend towards a survival improvement. #