Patrice Poubeau

Increased plasma serotonin in primary pulmonary hypertension

PURPOSE Pulmonary hypertension can occur in patients who have disorders associated with altered platelet serotonin storage, including collagen vascular disease and platelet storage pool disease. We tested the hypothesis that primary pulmonary hypertension (PPH) may be also associated with impaired handling of serotonin by platelets, resulting in increased plasma serotonin levels. PATIENTS AND METHODS We used radioenzymatic assays to measure serotonin in platelets and plasma and serotonin released during in vitro platelet aggregation in 16 patients with PPH, and in 16 normal controls matched for age and sex. Six patients were restudied after heart-lung transplantation to determine whether serotonin abnormalities persisted after pulmonary arterial pressure returned to normal. RESULTS Patients had decreased platelet serotonin concentration (1.8 +/- 0.6 x 10(-18) mol/platelet versus 3.2 +/- 0.2 x 10(-18) mol/platelet in controls; P < 0.01) and increased plasma serotonin concentration (30.1 +/- 9.2 x 10(-9) mol/L versus 0.6 +/- 0.1 x 10(-9) mol/L in controls; P < 0.001). Serotonin released during in vitro platelet aggregation was higher in patients than in controls. After heart-lung transplantation, platelet serotonin concentrations remained decreased and plasma levels remained increased. CONCLUSIONS Abnormal handling of serotonin by platelets leading to an increase in plasma serotonin occurs in PPH. The persistent decrease in platelet storage of serotonin after heart-lung transplantation suggests that this platelet abnormality is not secondary to PPH.

Pulmonary Arterial Hypertension in Patients Treated by Dasatinib

Background— The French pulmonary hypertension (PH) registry allows the survey of epidemiological trends. Isolated cases of precapillary PH have been reported in patients who have chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. Methods and Results— This study was designed to describe incident cases of dasatinib-associated PH reported in the French PH registry. From the approval of dasatinib (November 2006) to September 30, 2010, 9 incident cases treated by dasatinib at the time of PH diagnosis were identified. At diagnosis, patients had moderate to severe precapillary PH with functional and hemodynamic impairment. No other incident PH cases were exposed to other tyrosine kinase inhibitors at the time of PH diagnosis. Clinical, functional, or hemodynamic improvements were observed within 4 months of dasatinib discontinuation in all but 1 patient. Three patients required PH treatment with endothelin receptor antagonist (n=2) or calcium channel blocker (n=1). After a median follow-up of 9 months (min-max 3–36), the majority of patients did not demonstrate complete clinical and hemodynamic recovery, and no patients reached a normal value of mean pulmonary artery pressure (⩽20 mm Hg). Two patients (22%) died at follow-up (1 of unexplained sudden death and 1 of cardiac failure in the context of septicemia, respectively, 8 and 12 months after dasatinib withdrawal). The lowest estimate of incident PH occurring in patients exposed to dasatinib in France was 0.45%. Conclusions— Dasatinib may induce severe precapillary PH fulfilling the criteria of pulmonary arterial hypertension, thus suggesting a direct and specific effect of dasatinib on pulmonary vessels. Improvement is usually observed after withdrawal of dasatinib.

Pulmonary hypertension associated with benfluorex exposure

Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH). The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network. 85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement. The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.

Chikungunya à l’île de la Réunion: chronique d’une épidémie annoncée

Points essentiels Chikungunya est une maladie virale transmise par un moustique du genre Aedes. Actuellement elle sevit sur un mode epidemique a l’ile de la Reunion. Elle se caracterise essentiellement par un syndrome grippal mais associe a des polyarthralgies et une eruption. Le caractere invalidant et chronique des arthralgies est le fait clinique remarquable de l’infection a chikungunya. Il existe des formes graves et inhabituelles qui n’avaient jamais ete decrites dans la litterature. Ces formes doivent etre etudiees afin de pouvoir affirmer une relation directe entre le virus chikungunya et des facteurs de gravite. La therapeutique est uniquement symptomatique, associant antalgiques et/ou anti-inflammatoires. Il n’y a pas de vaccin. L’epidemie n’est pas circonscrite a l’ile de la Reunion car des cas de chikungunya ont ete declares dans les iles voisines (Maurice, Seychelles, Madagascar), un certain nombre de conseils doivent etre donnes aux voyageurs qui desirent venir dans la region.

The first autochthonous case of human melioidosis in Reunion Island

G. Borgherini a,∗, G. Camuset a, A. Foucher a, J.C. Maiza b, F.M. Thibault c, S. Picot d, P. Poubeau a a Service de maladies infectieuses, centre hospitalier universitaire de Saint-Pierre, BP 350, 97448 Saint-Pierre, Reunion b Endocrinologie, centre hospitalier universitaire de Saint-Pierre, 97448 Saint-Pierre, Reunion c Institut de recherche biomédicale des Armées, 91220 Brétigny-sur-Orge, France d Microbiologie, centre hospitalier universitaire de Saint-Pierre, 97448 Saint-Pierre, Reunion

Pulmonary manifestations of leptospirosis

BACKGROUND Pulmonary manifestations in leptospirosis are considered a major complication and are related to a poor prognosis. We present a large series of patients with pulmonary involvement using a practical approach based on the presence of acute respiratory failure (ARF). METHODS A retrospective study of patients with confirmed leptospirosis. RESULTS One hundred and sixty-nine patients with a laboratory-confirmed diagnosis of leptospirosis were investigated. One hundred and thirty-four patients (36.7±14 years of age) had pulmonary involvement. Severe pulmonary involvement was defined by evidence of ARF. Univariate analysis found the following factors related to severe pulmonary leptospirosis: dyspnoea (OR=10.14, p<0.0001), pulmonary crepitations (OR=4.8, p<0.0004), abnormal chest X-ray (OR=9.88, p<0.007) with alveolar shadowing (OR=8.12, p<0.0001), oliguria/anuria (OR=5.48, p<0.0001), hepatomegaly (OR=7.11, p< 0.0001), shock (OR=8.38, p< 0.0001), ICU admission (OR=60.08, p< 0.0001), dialysis (OR=4.87, p< 0.001), mechanical ventilation (OR=216, p< 0.0001) and development of nosocomial infection (OR=21.5, p< 0.0001). The mortality rate was significantly different between severe (40%) and non-severe (5.3%) pulmonary forms (OR=11.87, p< 0.0001). Multivariate analysis found two independent factors related to severe pulmonary involvement: dyspnoea (OR=10.18, p< 0.0001) and oliguria/anuria (OR=4.87, p< 0.0009). We performed a multivariate analysis to assess independent factors related to mortality and found: mechanical ventilation requirement (OR=27.85, p< 0.0001) and AST greater than 150 IU/L (OR=4.57, p< 0.02). Haemoptysis was associated with survival (OR=0.2, p< 0.02). CONCLUSIONS Severe pulmonary involvement in leptospirosis is associated with extensive disease involving other organs. The association of multiple factors is associated with severe forms of the disease and a high mortality rate.

Manifestations pulmonaires de la leptospirose

Resume Introduction L’atteinte pulmonaire de la leptospirose est consideree comme une complication majeure. Nous presentons une serie de patients atteints de formes pulmonaires avec une approche pragmatique basee sur la presence d’une insuffisance respiratoire aigue (IRA). Methodes Analyse retrospective chez des patients avec un diagnostic formel de leptospirose. Resultats 169 patients ont ete investigues, 134 (36,7 ± 14 ans) avec atteinte pulmonaire ont ete analyses. Une atteinte pulmonaire severe etait definie par la presence d’une IRA. L’analyse univariee a retrouve comme facteur de severite : dyspnee (OR 10,14), crepitants (OR 4,8), radiographie thoracique anormale (OR 9,88), atteinte alveolaire (OR 8,12), oligo-anurie (OR 5,48), hepatomegalie (OR 7,11), choc (OR 8,38), admission en reanimation (OR 60,08), dialyse (OR 4,87), ventilation mecanique (OR 216), l’infection nosocomiale (OR 21.5). La mortalite etait differente entre les formes severes (40%) et non severes (5,3%) (OR 11,87). L’analyse multivariee retrouvait 2 facteurs independants lies aux formes pulmonaires severes : dyspnee et oligo-anurie. Une analyse multivariee a trouve les facteurs independants de mortalite : ventilation mecanique (OR 27,85), ASAT > 150 (OR 4,57). La presence d’hemoptysie etait protectrice (OR 0,2). Conclusions L’atteinte pulmonaire severe est associee a une maladie diffuse multi-organes. Les complications et le taux eleve de mortalite sont lies a de multiples facteurs.

Murine Typhus, Reunion, France, 2011–2013

Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011–January 2013 in Reunion. Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin.

Invasive Group B Streptococcal Disease in Non-pregnant Adults, Réunion Island, 2011

OBJECTIVES While the prevalence of Group B streptococcus (GBS) colonization is important, little is known about invasive GBS (iGBS) disease in tropical areas. Our objective was to assess the burden of iGBS disease among non-pregnant adults. METHODS A prospective hospital-based study of all non-pregnant adult patients with iGBS disease was conducted between January and December 2011 in Saint Pierre, Réunion Island, to assess its cumulative incidence rate (CIR). Capsular serotyping and multilocus sequence typing were performed to characterize GBS isolates. Case-control study was done to identify risk factors. RESULTS The overall CIR of iGBS disease was 10.1 per 100,000. The CIR in elderly patients (≥ 65 yrs) was estimated at 40.6 per 100.000, and that of adults (15-64 years) at 6.7 per 100.000. Aboriginal origin in the Indian Ocean and overweight were both associated with iGBS disease. The most prominent clinical forms were osteo-articular and skin/soft tissue infections, as a consequence of diabetic foot. The serotypes were classic, type-Ia being the most prevalent. The hyper virulent ST-17 (CC17) was associated with type-III. CONCLUSIONS The incidence of iGBS disease found in Réunion island is twofold that usually reported. This burden is linked to overweight in aboriginal people from the Indian Ocean.

Acute chikungunya virus infection and asthma

To the Editors: From March 2005 to June 2006, Reunion Island, a French overseas territory in the Indian Ocean, faced an explosive chikungunya outbreak (a mosquito-borne disease caused by an alphavirus of the Togaviridae family). It was estimated that about 300,000 people were affected by the disease 1. Many patients experienced related chikungunya disease symptoms (fever, polyarthralgia, skin rashes, diarrhoea, vomiting). To date, there are no studies describing a respiratory tract involvement due to chikungunya infection. During this period, many patients complained of respiratory symptoms such as de novo dyspnoea or a worsening of various respiratory symptoms in patients with asthma. We hypothesised that acute chikungunya infection (ACI) may induce airway hyperresponsiveness (AHR) and therefore increases symptoms of asthma. The study was prospectively conducted from December 2005 to May 2006. All patients had ACI defined as symptoms (fever, polyarthralgia) that occurred in the 10 days preceding the evaluation, with a laboratory-confirmed diagnosis of acute chikungunya: positive RT-PCR, positive immunoglobulin (Ig)M serological test. All asthmatic patients had a history of significant reversibility of airflow obstruction. Pulmonary function testing (PFT) was performed with a phletysmograph (Medisoft®, Dinant, Belgium) at baseline and after inhaling 400 μg of salbutamol. Results (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), maximum mid-expiratory flow at 25–75% of FVC) were compared with former data recorded with the same phletysmograph. Patients were asked to fill a validated asthma 15-question questionnaire to assess quality of life (mini-Asthma Quality of Life Questionnaire (AQLQ)). The questionnaire generated an overall score and a four-domain score: symptoms, five questions; activities, four questions; emotion, three questions; environmental exposure, three questions. Each ranged 1–7, with higher scores indicating better quality of life in the last 2 weeks. Treatment for asthma was carefully recorded. Nonasthmatics subjects had no history of asthma or any respiratory disease. …