Carine Gomez

The integrated place of tracheobronchial stents in the multidisciplinary management of large post-pneumonectomy fistulas: our experience using a novel customised conical self-expandable metallic stent

BACKGROUND Stump dehiscence after pneumonectomy is a cause of morbidity and mortality in patients treated for non-small-cell lung carcinoma. Surgical repair remains the treatment of choice but can be postponed or contraindicated. Bronchoscopic techniques may be an option with curative intent or as a bridge towards definitive surgery. The aim of the study is to evaluate the efficacy and the outcome of a new customised covered conical self-expandable metallic stent in the management of large bronchopleural fistulas complicating pneumonectomies. METHODS A case series using chart review of non-operable patients presenting with large bronchopleural fistulas (>6mm) post-pneumonectomies as a definitive treatment with curative intent for non-small-cell lung carcinomas and requiring the use of a dedicated conical shaped stent in two tertiary referral centres. RESULTS Seven patients presenting large post-pneumonectomy fistulas (between 6 and 12 mm) were included. Cessation of the air leak and clinical improvement was achieved in all the patients after stent placement. Stent-related complications (two migrations and one stent rupture) were successfully managed using bronchoscopic techniques in two patients and surgery in one. Mortality, mainly related to overwhelming sepsis, was 57%. Delayed definitive surgery was achieved successfully in three patients (43%). CONCLUSIONS This case series assesses the short-term clinical efficacy of a new customised covered conical self-expandable metallic stent in the multidisciplinary management of large bronchopleural fistulas complicating pneumonectomies in patients deemed non-operable. Long-term benefits are jeopardised by infectious complications.

Parvovirus 4 in French in-patients: a study of hemodialysis and lung transplant cohorts.

The epidemiology and the clinical implication of human parvovirus 4 (PARV4) in human populations is still under evaluation. The distribution of PARV4 DNA was determined in cohorts of French hemodialysis and lung transplant patients. Plasma samples (n = 289) were tested for PARV4 by real‐time PCR assay (ORF2), and amplification products selected at random were sequenced. Analysis of available serological and biological markers was also undertaken. Fifty‐seven samples out of 185 (30.8%) were positive for PARV4 DNA in the cohort of hemodialysis patients. A higher prevalence of the virus was identified in patients with markers of HBV infection. PARV4 was also identified in 14 out of 104 samples (13.5%) from lung transplant recipients, with no clear‐cut association with available clinical markers. Point mutations located on the zone of real‐time detection were identified for some amplification products. This study describes the detection of PARV4 in the blood of hemodialysis and lung transplanted patients with significant difference in prevalence in these two cohorts. Further studies will be needed in order to understand better both the potential implication in host health and the natural history of this virus. J. Med. Virol. 83:717–720, 2011.

HLA-G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end‐stage lung disease. Soluble HLA‐G (sHLA‐G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA‐G haplotypes named UTRs, defined by SNPs from both the 5′URR and 3′UTR, have been reported to reliably predict sHLA‐G level. The aim of this retrospective study was to determine the impact of HLA‐G alleles and UTR polymorphism from LTx recipients on anti‐HLA allo‐immunization risk, overall survival and chronic rejection (CLAD). HLA‐G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA‐G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA‐G*01:06∼UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long‐term survival post‐LTx. HLA‐G*01:04∼UTR3 haplotype was associated with lower levels of sHLA‐G at D0 and M3 (p = 0.03), impaired long‐term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor‐specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA‐G alleles and UTRs in LTx.

Systematic Analysis of Blood Cell Transcriptome in End-Stage Chronic Respiratory Diseases

Background End-stage chronic respiratory diseases (CRD) have systemic consequences, such as weight loss and susceptibility to infection. However the mechanisms of such dysfunctions are as yet poorly explained. We hypothesized that the genes putatively involved in these mechanisms would emerge from a systematic analysis of blood mRNA profiles from pre-transplant patients with cystic fibrosis (CF), pulmonary hypertension (PAH), and chronic obstructive pulmonary disease (COPD). Methods Whole blood was first collected from 13 patients with PAH, 23 patients with CF, and 28 Healthy Controls (HC). Microarray results were validated by quantitative PCR on a second and independent group (7PAH, 9CF, and 11HC). Twelve pre-transplant COPD patients were added to validate the common signature shared by patients with CRD for all causes. To further clarify a role for hypoxia in the candidate gene dysregulation, peripheral blood mononuclear cells from HC were analysed for their mRNA profile under hypoxia. Results Unsupervised hierarchical clustering allowed the identification of 3 gene signatures related to CRD. One was common to CF and PAH, another specific to CF, and the final one was specific to PAH. With the common signature, we validated T-Cell Factor 7 (TCF-7) and Interleukin 7 Receptor (IL-7R), two genes related to T lymphocyte activation, as being under-expressed. We showed a strong impact of the hypoxia on modulation of TCF-7 and IL-7R expression in PBMCs from HC under hypoxia or PBMCs from CRD. In addition, we identified and validated genes upregulated in PAH or CF, including Lectin Galactoside-binding Soluble 3 and Toll Like Receptor 4, respectively. Conclusions Systematic analysis of blood cell transcriptome in CRD patients identified common and specific signatures relevant to the systemic pathologies. TCF-7 and IL-7R were downregulated whatever the cause of CRD and this could play a role in the higher susceptibility to infection of these patients.

Haemophilus pittmaniae respiratory infection in a patient with siderosis: a case report

IntroductionHaemophilus pittmaniae was described in 2005 as a new species distantly related to Haemophilus parainfluenzae. This member of the human saliva microbiota has also been further isolated from various body fluids without formal description of the patients.Case presentationWe report the case of H. pittmaniae isolate made from a sputum specimen collected from a 58-year-old Caucasian man with a massive fibrotic form of siderosis who was awaiting lung transplantation. Identification of the isolate was ascertained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene sequencing. H. pittmaniae was considered to be responsible for the worsening of the patient’s chronic respiratory failure and was successfully treated with oral amoxicillin.ConclusionH. pittmaniae should be regarded as a new pathogen responsible for respiratory tract infection in patients with chronic lung diseases.

Development of a multivariate prediction model for early-onset bronchiolitis obliterans syndrome and restrictive allograft syndrome in lung transplantation

BACKGROUND Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. METHODS LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. RESULTS Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. CONCLUSION Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

The lung microbiome: the perfect culprit for COPD exacerbations?

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of diseases which affects more and more patients in Europe and represents an important challenge for the respiratory community. These airway diseases present different faces from a clinical, functional and pathophysiological point. So, we should better understand the underlying mechanisms contributing to the various phenotypes, which are probably the consequences of interactions between genes and environmental factors. Our current treatments are mainly symptom-driven and do not interfere with the natural history of the disease. The accelerated decline in lung function and the recurrence of severe exacerbations are important features representing most of the patient burden. Exacerbations are clearly defined at least from a clinical perspective, now, but still represent a challenging goal to be fully deciphered. A better understanding of the pathophysiological mechanisms of these acute events is required to optimise their management and their prevention. Interaction between lung microbiota and inflammation is closely related to the pathogenesis of COPD exacerbation http://ow.ly/Z1B7o

Prevalence of Mycobacterium lentiflavum in cystic fibrosis patients, France

BackgroundMycobacterium lentiflavum is rarely isolated in respiratory tract samples from cystic fibrosis patients. We herein describe an unusually high prevalence of M. lentiflavum in such patients.MethodsM. lentiflavum, isolated from the respiratory tract of cystic fibrosis patients, was identified using both rpoB partial sequencing and detected directly in the sputum by using real-time PCR targeting the smpB gene.ResultsM. lentiflavum emerged as the third most prevalent nontuberculous mycobacterial species isolated in cystic fibrosis patients in Marseille, France. Six such patients were all male, and two of them may have fulfilled the American Thoracic Society clinical and microbiological criteria for M. lentiflavum potential lung infection.ConclusionsM. lentiflavum was the third most common mycobacteria isolated in cystic fibrosis patients, particularly in six male patients. M. lentiflavum outbreaks are emerging particularly in cystic fibrosis patients.

Coxiella burnetii: A Hidden Pathogen in Interstitial Lung Disease?

We report 7 patients with interstitial lung disease seen at computed tomographic scan review. Coxiella burnetii infection was diagnosed in situ in 1 lung biopsy specimen. Q fever may be a cofactor of interstitial lung disease, especially in endemic areas.

HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.