Elodie Blanchard

Computed Tomographic Measurement of Airway Remodeling and Emphysema in Advanced Chronic Obstructive Pulmonary Disease. Correlation with Pulmonary Hypertension

RATIONALE Pulmonary hypertension (PH) is an established complication of advanced chronic obstructive pulmonary disease (COPD) associated with increased mortality. The mechanisms coupling PH and bronchial obstruction are unknown; in particular, PH appears to be unrelated to emphysema. We hypothesized that computed tomographic (CT) measurement of airway remodeling instead of emphysema may correlate with PH in COPD. OBJECTIVES We aimed to describe the clinical and CT characteristics of patients with COPD with or without PH and to correlate CT measurements of airway remodeling and emphysema with PH. METHODS Data were retrieved from 60 COPD patients who underwent both right heart catheterization and computed tomography in a period of stability and had no other disease known to cause PH. CT measurement of airway wall thickness (WT-Pi10) was used to assess airway remodeling and low lung area percentage (LAA%) to quantify emphysema extent. MEASUREMENTS AND MAIN RESULTS Thirty-four of the sixty patients with COPD had PH (mean pulmonary arterial pressure [PAPm] ≥ 25 mm Hg). There was no difference between the two groups regarding age, sex, and spirometric results, whereas there was more profound hypoxemia in the PH group. WT-Pi10 was increased in the patients with COPD and PH and correlated with PAPm (ρ = 0.62; P < 0.001). Conversely, there was no difference or correlation between PAPm and LAA% (ρ = 0.12; P = 0.33). In multivariate analysis (R(2) = 0.53), WT-Pi10 was the independent predictor most associated with PAPm elevation, as compared to hypoxia (PaO2) or pulmonary arterial enlargement (diameter ratio between the pulmonary arterial truncus and the ascending aorta). CONCLUSIONS This study demonstrates, for the first time to our knowledge, an association between structural alterations of bronchi and PH in COPD. Unlike quantification of emphysema, CT measurement of airway remodeling correlates with PAPm and could be used to estimate the severity of PH in COPD. Airway remodeling burden is not limited to airflow limitation in the assessment of COPD severity and mortality.

Lung intragraft donor-specific antibodies as a risk factor for graft loss

BACKGROUND The effect of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) on graft survival is recognized in lung transplantation, but not all serum DSAs appear to be harmful. We wondered whether in situ DSA detection from graft biopsy specimens could help in identifying lung transplant recipients (LTRs) at higher risk for graft loss. METHODS Class I and II HLA antibody single-antigen flow bead assays were performed in 53 LTRs to identify immunoglobulin G DSA in biopsy specimen eluates and in sera and to evaluate C1q binding ability of DSA in sera. Intragraft DSAs (gDSAs) were correlated with serum DSAs (sDSAs), clinical and histologic data, and graft survival. RESULTS Twenty-eight (52.8%) LTRs had sDSAs, 12 (22.6%) had C1q-positive sDSAs, and 11 (20.8%) had gDSAs. Fifty sDSAs were found, among which 15 (30%) were C1q-positive and 14 (28%) were found in biopsy specimen eluates. One DSA was detected in the biopsy specimen only. Serum mean fluorescence intensity and biopsy fragment size were higher for sDSAs detected in biopsy specimens (p = 0.003 and p = 0.02, respectively). One-year post-biopsy graft survival was lower for LTRs with gDSAs (p = 0.008 by log-rank test). Presence of gDSA at the time of biopsy constituted a risk factor for graft loss in univariate (odds ratio, 6.67; 95% confidence interval [CI] 1.51-29.47; p = 0.008; hazard risk, 3.44; 95% CI, 1.47-8.01, p = 0.005) and multivariate (odds ratio, 5.85; 95% CI, 1.23-27.68; p = 0.03; hazard risk, 4.51; 95% CI, 1.83-11.13; p = 0001) analyses using logistic regression and a Cox proportional hazard model, respectively. CONCLUSIONS In lung transplantation, gDSA appears to be a valuable biomarker to identify pathogenic DSA and LTRs with a higher risk for graft loss.

Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway

BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial fibrosis. The chronic course of COPD is worsened by recurrent acute exacerbations. OBJECTIVE The aim of the study was to evaluate the recruitment of blood fibrocytes in patients with COPD during exacerbations and, subsequently, to identify potential mechanisms implicated in such recruitment. METHODS Using flow cytometry, we quantified circulating fibrocytes and characterized their chemokine receptor expression in 54 patients with COPD examined during an acute exacerbation (V1) and 2 months afterward (V2) and in 40 control subjects. The role of the chemokines CXCL12 and CCL11 in fibrocyte migration was investigated by using a chemotaxis assay. Patients were followed for up to 3 years after V1. RESULTS We demonstrated a significantly increased number of circulating fibrocytes at V1 compared with control subjects. The number of circulating fibrocytes decreased at V2. A high percentage of circulating fibrocytes during exacerbation was associated with increased risk of death. The percentage of fibrocytes at V2 was negatively correlated with FEV1, forced vital capacity, FEV1/forced vital capacity ratio, transfer lung capacity of carbon monoxide, and Pao2. Fibrocytes highly expressed CXCR4 and CCR3, the chemokine receptors for CXCL12 and CCL11, respectively. Fibrocytes collected from patients with COPD at V1 had increased chemotactic migration in response to CXCL12 but not to CCL11 compared with those from control subjects. Plerixafor, a CXCR4 antagonist, decreased fibrocyte migration to plasma from patients with exacerbating COPD. CONCLUSION Blood fibrocytes are recruited during COPD exacerbations and related to mortality and low lung function. The CXCL12/CXCR4 axis is involved in such fibrocyte recruitment (Firebrob study; ClinicalTrials NCT01196832).

Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolar proteinosis and fibrosis

Over the past few years, genetics has significantly improved the understanding of interstitial lung diseases (ILD). For example, in idiopathic pulmonary fibrosis, telomerase complex mutations have been shown to drive a specific phenotype including haematological, liver and cutaneous abnormalities [1]. Recently, GATA2 deficiency has been associated with a broad phenotype including haematological, vascular, infectious and pulmonary diseases [2–4]. GATA2 is a zinc finger transcription factor essential for differentiation of immature haematopoietic cells. Among many other functions, GATA2 regulates the phagocytosis of alveolar macrophages. Therefore, alveolar macrophage dysfunction is thought to be the pathophysiological basis for the occurrence of pulmonary alveolar proteinosis, the main lung condition in GATA2 deficiency [4]. However, pulmonary alveolar proteinosis associated with GATA2 deficiency does not share the same clinical, biological or radiological features as autoimmune pulmonary alveolar proteinosis. In all cases of GATA2 deficiency-associated pulmonary alveolar proteinosis reported in the literature, granulocyte–macrophage colony-stimulating factor (GM-CSF) antibodies were absent [2, 4]. Moreover, other pulmonary diseases such as fibrosis or pulmonary hypertension (PH) have been reported to occur in GATA2 deficiency [4], suggesting that the precise pathophysiological mechanisms are not fully understood. Pulmonary fibrosis may be more prevalent in adults with GATA2 deficiency due to a longer duration of the disease http://ow.ly/WHnu30aCZ4S

Quel rôle pour la pholcodine dans le traitement de la toux, en 2013 ?

Pholcodine is an opioid that has been widely used worldwide since 1950 for the treatment of non-productive cough in children and adults. The results of early preclinical studies but also those of recent clinical trials have shown the antitussive efficacy of pholcodine to be superior to that of codeine, of longer duration, and with an equivalent or safer toxicity profile. Also, there is no risk of addiction. Concern had been raised over a possible cross-sensitisation with neuromuscular blocking agents. While a recent assessment of the available data by the European Medicines Agency (EMA) has confirmed the favourable risk-benefit ratio of pholcodine, further studies are needed to clear this point.

Tumor shape pulmonary mucormycosis associated with sinonasal aspergillosis in a diabetic patient

Mucormycosis is a rare and life-threatening fungal infection of the Mucorales order occurring mainly in immunosuppressed patients. The most common forms are rhinocerebral but pulmonary or disseminated forms may occur. We report the case of a 61-year-old patient in whom pulmonary mucormycosis was diagnosed during his first-ever episode of diabetic ketoacidosis. While receiving liposomal amphotericin B, a sinusal aspergillosis due to Aspergillus fumigatus occurred. Evolution was slowly favorable under antifungal tritherapy by liposomal amphotericin B, posaconazole and caspofungin.

Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis

Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment. We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension. Clinical, radiological, microbiological features and treatment response of patients with invasive aspergillosis that occurred despite posaconazole prophylaxis were analyzed. Diagnostic accuracy of serum galactomannan assay according to posaconazole plasma concentrations has been performed. A total of 288 patients with acute myeloid leukemia, treated by induction chemotherapy, who received posaconazole prophylaxis for more than five days were included in the present study. The incidence of invasive aspergillosis was 8% with 12 (4.2%), 8 (2.8%) and 3 (1%), possible, probable and proven invasive aspergillosis, respectively. Posaconazole plasma concentration was available for 258 patients. Median duration of posaconazole treatment was 17 days, and median posaconazole plasma concentration was 0.5 mg/L. None of patients with invasive aspergillosis and posaconazole concentration ≥ 0.5 mg/L had a serum galactomannan positive test. Sensitivity of serum galactomannan assay to detect probable and proven invasive aspergillosis was 81.8%. Decreasing the cut-off value for serum galactomannan optical density index from 0.5 to 0.3 increased sensitivity to 90.9%. In a homogenous cohort of acute myeloid leukemia patients during induction chemotherapy, increasing the posaconazole concentration decreases the sensitivity of serum galactomannan assay.

3D ultrashort echo time MRI of the lung using stack-of-spirals and spherical k-Space coverages: Evaluation in healthy volunteers and parenchymal diseases: Lung MRI With 3D UTE Spiral VIBE Sequence

Ultrashort echo time (UTE) has been shown to improve lung MRI quality in three dimensions. The evaluation of 3D‐UTE stack‐of‐spirals VIBE (3D‐USV) sequence for parenchymal diseases and a comparison of performance with that of a spherical mode of acquisition is needed.

Incidence, outcomes and risk factors for neoplasms in explanted lungs

The detection of a cancer in a potential recipient is an absolute contraindication for lung transplantation. However, there is a small proportion of unexpected neoplasms in lung explants. It seems that risk factors for neoplasms in explant could be a long period between computed tomographic scan and transplantation, COPD, idiopathic pulmonary fibrosis (IPF), and tobacco exposure. The aims of our study were to review our institution9s incidence and outcomes of malignancies found in lung explants and to identify risk factors for neoplasms in explants. 132 consecutive lung transplants files were collected from Bordeaux University9s transplant center, from 2008 to 2015. Intergroup comparisons were performed using the Mann-Whitney U test for continuous variables and the Fisher exact test for categorical variables. 5 neoplasms (adenocarcinomas) were found among the 132 lung explants, representing a 3.8% incidence. 4 of 5 were detected at an early stage (stage IA) of which 2 in the setting of emphysema and 2 in the setting of fibrosis interstitial disease (1 IPF and 1 systemic sclerosis): no recurrence was found. 1 of 5 neoplasms was detected at an advanced stage (stage IV) in the setting of IPF and recurrence occurred 6 months after transplantation. Incidence of unexpected cancer was higher (p Fibrosis lung diseases, particularly IPF seem to be risk factors for undetected neoplasms in lung explants. Efforts to improve screening in these populations seem needed.