Bruno Philippe

Detection of Aspergillus Galactomannan Antigenemia To Determine Biological and Clinical Implications of Beta-Lactam Treatments

ABSTRACT Detection of Aspergillus galactomannan (GM) in serum with the Platelia Aspergillus enzyme immunoassay (EIA) is useful for diagnosing invasive aspergillosis. From May 2003 to November 2004, 65 patients who did not develop aspergillosis had at least two positive sera while receiving a beta-lactam treatment (GM index [GMI], ≥0.5). Of the 69 treatment episodes scored, 41 consisted of a beta-lactam other than piperacillin-tazobactam (n = 29), namely, amoxicillin-clavulanate (n = 25), amoxicillin (n = 10), ampicillin (n = 3), or phenoxymethylpenicillin (n = 2). In all cases, antigenemia became negative 24 h to 120 h upon stopping the antibiotic. Monitoring of 35 patients, including 26 with hematological malignancies, revealed three antigenemia kinetic patterns: each was observed with any drug regimen and consisted of a persistent GMI of >2.0 (65.7%), >0.5, and ≤1.5 (25.7%) or a variable GMI (14.3%) from the onset of antibiotic therapy. All available drug batches given to 26 patients cross-reacted with the EIA. Galactomannan titration in batches failed to predict the GM titers in the five patients studied at cumulative doses of ampicillin or amoxicillin-clavulanate, regardless of the time lapse between serum sampling and infusion period. Our results show that beta-lactams other than piperacillin-tazobactam may lead to false presumption of aspergillosis. The resulting kinetic patterns of GM antigenemia are variable, and sampling serum prior to the next beta-lactam dose may not decrease GMI below the threshold. Consequently, testing of suspected antibiotic batches remains the only indicator of possible false EIA positivity.

Diagnosis and management of idiopathic pulmonary fibrosis: French practical guidelines.

Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.

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.

Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment

Chronic pulmonary aspergillosis (CPA) affects individuals with non-systemic or mildly systemic immunodepression or altered pulmonary integrity due to underlying disease. It has been reported with a variety of clinical and radiological patterns. The condition should be distinguished from simple aspergilloma and allergic bronchopulmonary aspergillosis as well as invasive aspergillosis in severely immunocompromised patients. CPA generally requires long-term antifungal treatment and surgery may be considered. Life-threatening haemoptysis may be prevented by bronchial arteriography with embolisation. However, currently there are no documented treatment recommendations for CPA. This review provides an up-to-date practical overview of this condition, including a comprehensive update on diagnosis and management.

Telemetric monitoring of pulmonary function after allogeneic hematopoietic stem cell transplantation.

Background. Late-onset noninfectious pulmonary complications (LONIPC) are both frequent and severe after allogeneic hematopoietic stem cell transplantation (HSCT). The high mortality rate (40–80%) may be related to delayed diagnosis. We assessed the use of telemetric home surveillance of pulmonary function for early diagnosis of LONIPC in transplant recipients. Methods. This prospective study monitored pulmonary function in 37 allogeneic HSCT recipients. About 3 months after HSCT, they received a portable spirometer that measured forced vital capacity, forced expiratory volume per second, and midexpiratory flow 25–75 (MEF25–75). Data were transmitted twice weekly by telephone. Conventional plethysmography confirmed any significant deterioration (>20%). Results. Thirteen episodes of spirometric deterioration were detected by telemetry in 11 patients during a median 17-month (4–41) follow-up period after transplantation. In these cases, examinations including spirometry, high-resolution thoracic computed tomography and bronchoalveolar lavage diagnosed LONIPC in eight episodes in seven patients (cumulative incidence 23.4%, SE 0.08, at month 24 after transplant): bronchiolitis obliterans (BO, n=3), interstitial pneumonia (IP, n=4), or both BO and IP (n=1). Five episodes improved and three were stabilized with increased immunosuppressive therapy. At the last follow-up, of the seven patients with LONIPC, one successfully stopped immunosuppressive therapy, two were receiving low-dose mycophenolate mofetil, and four were receiving low-dose corticosteroid therapy. There were no cases of respiratory failure and no patient died from LONIPC. Conclusion. Telemetric home monitoring of pulmonary function is a useful procedure for early diagnosis of LONIPC before clinical pulmonary symptoms and may improve outcome after allogeneic HSCT.

Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.

Phenotyping chronic pulmonary aspergillosis by cluster analysis.

Chronic pulmonary aspergillosis (CPA) is a complex disorder involving various underlying conditions and risk factors, clinical and radiological features, and natural histories or responses to treatment [1]. Untreated, patients with CPA have ≥50% 5-year mortality [2, 3]. Recently, it was proposed that CPA includes simple aspergilloma, chronic cavitary pulmonary aspergillosis (CCPA) and chronic necrotising pulmonary aspergillosis (CNPA) [1]. Cluster analysis based on clinical and radiological settings does not distinguish any specific phenotype of CPA http://ow.ly/QZq7V

Pleural ultrasonography, new standard for para pneumonic effusion? French multicentric prospective study. Preliminary report

Introduction: Parapneumonic pleuritis are frequently associated with high morbidity and severe sequelae. Management of this complication include early pleural evacuation. Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pleural effusion. Chest x-ray (CXR) is the simplest diagnostic tool of Community Acquired Pneumonia (CAP), but it has some limitation. Therefore, the aim of this study is evaluate pleural sequelae with early use of LUS in detection Methods: In this multicentric prospective study, a consecutive sample of suspected patients with CAP was underwent daily LUS. Each patient received a chest x-ray and ultrasound on admission every day. The analysis of the pleural fluid was left to the discretion of the physician . The patients were monitored only 4 days if they had no para pneumonic pleurisy and benefited from an appropriate management if not. Complete respiratory explorations were carried out at 3 and 6 months. Results: In this preliminary reports , 65 patients with CAP were enroled : 48,3% females , mean age 64,4 years Sensitivity of LUS and CXR in detection of parapneumonic effusion were 91% and 40% respectively. Specificity of CXR was 40% while the LUS specificity was 92%. The evolution of pleurisy was unpredictable over the observation period with a significant diagnostic delay of the CXR. No pleurisy occurred after the 4-day period, the failure was 4.6% Compared with nearly 20% of the literature. Conclusion: Findings of the present study demonstrated high incidence of parapneumonic effusion and the higher diagnostic accuracy of LUS versus CXR. A daily echography is necessary and sufficient to detect the effusion and take care of it.