Jean-Christophe Dubus

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (40)113.83 Total impact

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    ABSTRACT: The black Aspergillus group comprises A. niger and 18 other species, which are morphologically indistinguishable. Among this species subset, A. tubingensis, described in less than 30 human cases before 2014, is primarily isolated from ear, nose, and throat samples. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has emerged as a powerful technique to identify microbes in diagnostic settings. We applied this method to identify 1,720 filamentous fungi routinely isolated from clinical samples our laboratory over a two-year study period. Accordingly, we found 85 isolates of A. niger, 58 of A. tubingensis, and six other black Aspergillus (4 A. carbonarius and 2 A. japonicus). A. tubingensis was the fifth most frequent mold isolated in our mycology laboratory, primarily isolated from respiratory samples (40/58 isolates). In this study, we mainly aimed to describe the clinical pattern of Aspergillus tubingensis. We analyzed the clinical features of the patients in whom A. tubingensis had been isolated from 40 respiratory samples. Thirty patients suffered from cystic fibrosis, chronic obstructive pulmonary disease or other types of chronic respiratory failure. Strikingly, 20 patients were experiencing respiratory acute exacerbation at the time the sample was collected. Antifungal susceptibility testing of 36 A. tubingensis isolates showed lower amphotericin B MICs (P < 10−4) and higher itraconazole and voriconazole MICs (P < 10−4 and P = .0331, respectively) compared with 36 A. niger isolates. Further studies are required to better establish the role that this fungus plays in human diseases, especially in the context of cystic fibrosis and chronic pulmonary diseases.
    No preview · Article · Jan 2016 · Medical Mycology
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    ABSTRACT: Pediatric eosinophilic pneumonias (EPs) are characterized by a significant infiltration of the alveolar spaces and lung interstitium by eosinophils, with conservation of the lung structure. In developed countries, EPs constitute exceptional entities in pediatric care. Clinical symptoms may be transient (Löffler syndrome), acute (<1 month and mostly <7 days), or chronic (>1 month). Diagnosis relies on demonstration of alveolar eosinophilia on bronchoalveolar lavage, whether or not associated with blood eosinophilia. EPs are a heterogeneous group of disorders divided into: (i) secondary forms (seen mainly in parasitic infections, allergic bronchopulmonary aspergillosis, and drug reactions); and (ii) primary forms (eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, idiopathic chronic eosinophilic pneumonia, and idiopathic acute eosinophilic pneumonia). Despite their rarity, the etiological approach to EP must be well-defined as some causes can be rapidly life-threatening without initiation of the proper treatment. This approach (i) eliminates secondary forms, with comprehensive history taking and minimal biological assessment, (ii) is oriented in primary forms by the acute or chronic setting, and the existence of extrapulmonary symptoms. Treatment of primary forms has traditionally relied on corticosteroids, usually with a dramatic response. Specific treatments or the adjunction of corticosteroid-sparing treatment or immunosuppressors are currently being evaluated in order to improve the prognosis and the side effects associated with corticosteroid treatment in a pediatric setting. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Dec 2015 · Pediatric Pulmonology
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    ABSTRACT: Background Mycobacterium 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. Methods M. 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. Results M. 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. Conclusions M. 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.
    Preview · Article · Dec 2015 · BMC Pulmonary Medicine

  • No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: The influence of the generalization of cystic fibrosis newborn screening (CFNBS) in France on sweat test (ST) prescription is unknown. In this French retrospective, descriptive, and multicenter study, we studied the indications, number, methods, and results of STs prescribed by a pediatric pulmonologist in children who had a negative CFNBS and an ST for respiratory symptoms in 2012. We included 502 children with 523 STs, performed with four different methods. The main indication was asthma (71.3 %), then chronic cough (52.4 %), atypical lower airway infections (42.2 %), and bronchiectasis (7 %). Four children had a diagnosis of CF (0.8 %), all presenting with chronic productive cough and recurrent respiratory infections. Asthma is the most frequent indication of ST in our cohort. Because of the systematic CFNBS in France, some prescriptions should be avoided, particularly in case of severe or moderate asthma with no other associated symptom. Moreover, methods of STs often do not follow the guidelines and need standardization. What is Known: • Newborn screening (NBS) has become the most frequent circumstance of the diagnosis of cystic fibrosis (CF) in France after its generalization. • The prescription of sweat test (ST) in children with respiratory symptoms who already had a negative NBS has not been studied. What is New: • In children with a negative CF NBS referred to a university hospital for respiratory diseases, despite important variations of ST methods, only 4 children among 502 have been diagnosed as CF. • Despite recommendations, ST prescription should be avoided in children with moderate to severe asthma and no other associated symptom.
    No preview · Article · Jun 2015 · European Journal of Pediatrics
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    ABSTRACT: In adults, congenital pulmonary malformations are candidates for surgery due to symptoms. A pre-natal diagnosis is simple and effective, and allows an early thoracoscopic surgical treatment. A retrospective study was performed to assess management in two different populations of adults and children to define the best strategy. Pulmonary malformations followed at the University Hospital from 2000 to 2012 were reviewed. Clinical history, malformation site, duration of hospitalisation, complications and pathology examinations were collected. A total of 52 cases (33 children, 19 adults) were identified. In children, 28 asymptomatic cases were diagnosed pre-natally and 5 during the neonatal period due to infections. Surgery was performed on the children between the ages of 2 and 6 months. Nineteen adults underwent surgery, 16 because of symptoms and 3 adults for anomalies mimicking tumours. The mean age within the adult group was 42.5 years. In children, there was one thoracotomy and 32 thoracoscopies, with 7 conversions for difficult exposure, dissection of vascular pedicles, bleeding or bronchial injury. In the adults, there were 15 thoracotomies and 4 thoracoscopies, with one conversion. Post-operative complications in the adults were twice as frequent than in children. The mean time of the children's hospitalisation was 7.75 days versus 7.16 days for the adults. Pathological examinations showed in the children: 7 sequestrations, 18 congenital cystic pulmonary malformations (CPAM), 8 CPAM associated sequestrations; in adults: 16 sequestrations, 3 intra-pulmonary cysts. Early thoracoscopic surgery allows pulmonary parenchyma conservation with pulmonary development, reduces respiratory and infectious complications, eliminates a false positive cancer diagnosis later in life and decreases risks of thoracic parietal deformation.
    Full-text · Article · Apr 2015 · Journal of Minimal Access Surgery
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    ABSTRACT: Exposure to tobacco smoke has been not evaluated in children with bronchopulmonary dysplasia (BPD). We evaluate the association of in utero smoking (IUS) and environmental tobacco smoke (ETS) with the respiratory events of BPD and non-BPD children. Two hundred sixty-two children born before 35 weeks of gestational age (GA) and regularly followed up in our regional network for preterms were enrolled. They were paired according to their BPD status, their gestational age and birth weight (131 children with BPD and 131 without BPD, 28 mean weeks GA; mean weight 1000 g). Respiratory data were obtained prospectively during their first 2 years of life. A complementary questionnaire was completed by the parents about their child’s respiratory health at the age of 2, their home environment, and tobacco status. IUS concerned 12.6 %; ETS, 48.8 % (67 % in BPD children treated with oxygen at home). No further influence on respiratory outcome could be found by exposure to intrauterine smoke or extrauterine tobacco smoke in this patient sample. Conclusion: IUS and ETS exposures are as high in preterm children as in a general pediatric population. The highest exposure occurs among BPD infants treated with oxygen at home. What is known: • Environmental tobacco smoke (ETS) and in utero smoking (IUS) are responsible for many morphological, functional, and clinical changes in children. • Children with bronchopulmonary dysplasia (BPD) have more respiratory events in their first years of life than preterm children without BPB, maybe triggered by ETS and IUS. What is New: • The exposition to ETS and IUS is high in preterm children with and without BDP, as high as in a general. • Pedaitric population, particularly in children with BPD and treated with oxygen at home. • No further influence on respiratory outcome could be found by exposure to ETS or IUS in our studied population.
    No preview · Article · Jan 2015 · European Journal of Pediatrics

  • No preview · Article · Mar 2014 · The Journal of pediatrics
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    ABSTRACT: Idiopathic eosinophilic pneumonia is extremely rare in children and adults. We present herein the first series describing the specificities of idiopathic chronic (ICEP) and acute (IAEP) eosinophilic pneumonia in children. We retrospectively analyzed all cases of ICEP and IAEP in children that were retrieved from French Reference Centers for rare pediatric lung diseases. Five cases of pediatric ICEP were identified. Corticosteroid or immunosuppressive therapy dramatically improved the outcome in three cases. The remaining two cases had a persistent interstitial pattern with progressive development of cystic airspace lesions. Three cases of IAEP in adolescents were reported, with one requiring four days of extracorporeal membrane oxygenation. ICEP is a rare disease with a polymorphic clinical presentation in children. We identified patients with persistent interstitial patterns progressing to cystic airspace regions, for which the boundaries with idiopathic interstitial pneumonias are difficult to establish. We therefore propose a specific pediatric definition and classification algorithm. IAEP in children remains an inflammatory reaction of the lung to an acute toxic exposure, mainly tobacco, as in adults. International studies are required to comprehensively assess the various clinical forms of the disease as well as the appropriate therapeutic regimens.
    Full-text · Article · Feb 2014 · Orphanet Journal of Rare Diseases
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    ABSTRACT: Clinical isolates of Pseudomonas aeruginosa exhibiting high-level resistance to carbapenems were recovered from a French patient with cystic fibrosis (CF) who had not received carbapenem therapy. This study was conducted to investigate the molecular mechanism conferring the carbapenem-resistant phenotype in clinical isolates of P. aeruginosa recovered from the same CF patient chronically colonised since 2005. Investigation of imipenem resistance of P. aeruginosa strain_02 isolated in May 2011 showed no carbapenemase activity. However, amplification and sequencing of the oprD porin gene revealed disruption of this gene by an insertion sequence (IS) element of 1337bp that contained a novel transposase of 1227bp (ISPa46) bordered by two terminal imperfect inverted repeats of 28bp, which was associated with carbapenem resistance. Retrospective analysis of five additional strains of P. aeruginosa isolated before May 2011 from the same patient revealed that all isolates were likely to be the same clone by multilocus sequence typing analysis (ST540/551), but one of the five isolates was imipenem-susceptible. Although it was possible to demonstrate the presence of ISPa46 in all strains by PCR, this IS was transposed in the oprD gene only for imipenem-resistant isolates. Therefore, this study reports a novel IS element (ISPa46) in P. aeruginosa clinical isolates of a CF patient in Marseille, France, that was associated with carbapenem resistance and was selected in the absence of carbapenem treatment.
    No preview · Article · Jul 2013 · International journal of antimicrobial agents
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    ABSTRACT: Background: The use of valved holding chambers (VHCs) with pressurized metered dose inhalers (pMDIs) is reported to reduce the oral deposition of inhaled drugs and to facilitate the handling of these devices by patients, especially children. Although the number of commercially available VHCs is increasing, the correct choice of VHC in clinical practice is important, because VHCs are not equally effective regarding medication delivery. Hence, we aimed to evaluate the use of three small-volume VHCs-Vortex(®), AeroChamber(®) Plus (ACP), and Able Spacer™ (AS)-along with a commercial pMDI containing a combination of beclomethasone and formoterol (Innovair(®)) frequently used by asthma patients. Methods: Evaluation of the delivered dose of both drugs and analysis of particle size distribution of aerosols emitted for the inhaler were performed using the Next Generation Impactor with and without the tested VHCs. Results: The VHCs retained significant quantities of both drugs and dramatically reduced the quantity of drugs deposited in the throat of the impactor, indicating that particles with large size were preferably retained in the VHCs. Interestingly, although the delivered dose of both drugs was reduced by the use of VHCs, the use of the Vortex and the ACP resulted in comparable fine particle doses (FPDs) to that obtained when the pMDI was used alone, whereas the AS VHC significantly reduced the FPDs of both drugs. This may be due to the fact that, unlike the AS VHC, the Vortex and the ACP VHCs are made of antistatic materials that minimize the electrostatic interaction with emitted aerosols, enhancing medication delivery. Conclusion: The Vortex and the ACP VHCs present interesting advantages over the AS VHC to be used with Innovair pMDI. However, these results are based on an in vitro evaluation and need to be validated in an in vivo study in order to clinically assess the performance of these VHCs.
    No preview · Article · Oct 2012 · Journal of Aerosol Medicine and Pulmonary Drug Delivery
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    ABSTRACT: The emergence of multidrug-resistant Gram-negative bacteria that cause nosocomial infections is a growing problem worldwide. Colistin was first introduced in 1952 and was used until the early 1980s for the treatment of infections caused by Gram-negative bacilli. In vitro, colistin has demonstrated excellent activity against various Gram-negative rod-shaped bacteria, including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Recent clinical findings regarding colistin activity, pharmacokinetic properties, clinical uses, emerging resistance, toxicities and combination therapy have been reviewed. Recent approaches to the use of colistin in combination with other antibiotics hold promise for increased antibacterial efficacy. It is probable that colistin will be the 'last-line' therapeutic drug against multidrug-resistant Gram-negative pathogens in the 21st century.
    Full-text · Article · Aug 2012 · Expert Review of Anti-infective Therapy
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    ABSTRACT: Interstitial lung diseases (ILDs) in children represent a heterogeneous group of rare respiratory disorders that affect the lung parenchyma. After the launch of the French Reference Centre for Rare Lung Diseases (RespiRare®), we created a national network and a web-linked database to collect data on pediatric ILD. Since 2008, the database has been set up in all RespiRare® centres. After patient's parents' oral consent is obtained, physicians enter the data of children with ILD: identity, social data and environmental data; specific aetiological diagnosis of the ILD if known, genetics, patient visits to the centre, and all medical examinations and tests done for the diagnosis and/or during follow up. Each participating centre has a free access to his own patients' data only, and cross-centre studies require mutual agreement. Physicians may use the system as a daily aid for patient care through a web-linked medical file, backed on this database. Data was collected for 205 cases of ILD. The M/F sex ratio was 0.9. Median age at diagnosis was 1.5 years old [0-16.9]. A specific aetiology was identified in 149 (72.7%) patients while 56 (27.3%) cases remain undiagnosed. Surfactant deficiencies and alveolar proteinosis, haemosiderosis, and sarcoidosis represent almost half of the diagnoses. Median length of follow-up is 2.9 years [0-17.2]. We introduce here the French network and the largest national database in pediatric ILDs. The diagnosis spectrum and the estimated incidence are consistent with other European databases. An important challenge will be to reduce the proportion of unclassified ILDs by a standardized diagnosis work-up. This database is a great opportunity to improve patient care and disease pathogenesis knowledge. A European network including physicians and European foundations is now emerging with the initial aim of devising a simplified European database/register as a first step to larger European studies.
    Full-text · Article · Jun 2012 · Orphanet Journal of Rare Diseases
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    ABSTRACT: Spacer devices are used to optimize airway aerosol deposition from pressurized metered-dose inhalers (pMDI). The in vitro performance of the combination fluticasone/salmeterol pMDI alone and con- nected to 3 different valved holding chambers (VHC) was compared by measuring impactor entry port (“throat”) deposition and fine particle dose (FPD) of each medication. Salmeterol (SX) and Fluticasone (FP) throat deposition was reduced over 90 % by all VHC compared to pMDI alone (p < 0,001). The FPD obtained from pMDI alone and connected to VHCs Vortex®, AeroChamber Plus® and Able Spacer® for Salmeterol (25 μg nominal dose) were 12.2 ± 0.7, 12.5 ± 0.5, 11.6 ± 0.8, and 7.9 ± 0.9 μg, respectively. For Fluticasone (125 μg nominal dose) the FPD were 42.5 ± 2.6, 36.3 ± 3.1, 39.8 ± 2.4, and 22.8 ± 3.5 μg, respec- tively. There were no statistical differences in FPD between devices, except for AbleSpacer® that delivered a lower FPD for both drugs (p < 0.001).
    Full-text · Article · Jun 2012 · LATIN AMERICAN JOURNAL OF PHARMACY
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    ABSTRACT: We report the case of a 6-year-old boy who had Kawasaki disease resistant to intravenous immunoglobulin and systemic steroids. Because of an uncontrolled disease course, with significant lesions of the coronary arteries, anti-CD20 treatment was used. Rapid clinical, biological, and cardiac improvement was observed. The patient tolerated the treatment well.
    No preview · Article · Feb 2012 · The Journal of pediatrics
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    ABSTRACT: Mycobacterium chimaera is a recently described species within the Mycobacterium avium complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection. An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a Mycobacterium avium complex organism further identified as M. chimaera. Using sequencing-based methods of identification, we observed that M. chimaera organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with M. avium subsp. hominissuis isolates. We believe that M. chimaera should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.
    Preview · Article · Sep 2011 · Journal of Medical Case Reports
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    ABSTRACT: Most hospital admissions for asthma exacerbation are avoidable with adequate disease management. The objective of this study was to describe the characteristics of children hospitalized with an asthma exacerbation to identify modifiable factors leading to hospitalization. The study was conducted in 14 pediatric units and included children 3-17 years of age who were hospitalized for an asthma exacerbation. The present analysis covers 498 children with known asthma. Staff physicians used a standardized questionnaire to collect data. Asthma history came from a parental interview and included usual asthma care, frequency of symptoms and quick-relief medication use in the previous month, frequency of exacerbations and number of unscheduled healthcare visits during the past year, and prior asthma-related hospitalizations. More than half the children had previously been hospitalized for an exacerbation, 42% used continuous inhaled corticosteroids, and 57% had a regular follow-up for asthma. Asthma had been well controlled over the past year for 11%, 12% had experienced exacerbations during the past year but that had been optimally controlled during the previous month, and 11% had recently become poorly controlled (infrequent exacerbations in the previous year and non-optimal control in the previous month). The remaining 327 children (66%) were consistently poorly controlled (non-optimal asthma control in the previous month and frequent exacerbations over the previous year). Among this group, 69% had at least one of the following preventable risk factors for hospitalization: no regular controller therapy (49%), no asthma action plan (40%), or no follow-up for asthma (35%). Two-thirds of the children with asthma hospitalized for an exacerbation had been consistently poorly controlled during the previous year. They were frequently undertreated and insufficiently educated about asthma. Further efforts are needed to improve asthma treatment and education in France.
    No preview · Article · May 2011 · Journal of Asthma
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    ABSTRACT: Jet nebulizers are commonly used to administer aerosolized tobramycin to CF patients. The aim of this study was to assess the performance of disposable jet nebulizers as an alternative to reusable nebulizers such as the Pari LC Plus. From a survey conducted in 49 CF centers in France, 18 disposable jet nebulizer systems were selected. An in vitro study was performed with 20 jet nebulizer/air source combinations (18 disposable and 2 reusable) to determine their performance with tobramycin solution (300 mg/5 mL). A scintigraphic deposition study in baboons was performed to validate the in vitro data. In vitro and in vivo results correlated. There was no overall relationship between the compressed air source and nebulizer performance, but the nebulizer interface was responsible for significantly different results. None of the disposable nebulizers tested in this study can be recommended as an alternative to the Pari LC Plus nebulizer for tobramycin.
    No preview · Article · Nov 2010 · Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society
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    ABSTRACT: Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. Nocardia are rarely implicated in these infections and few reports of the involvement of this species are found in the literature. We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant Nocardia farcinica in a patient with cystic fibrosis. The chronic colonization of this uncommon bacterium in patients with cystic fibrosis was proved using a newly developed real-time polymerase chain reaction assay, which indicates that this bacterium, despite treatment, is difficult to eradicate. Our case report confirms that this organism can be recovered in persons with cystic fibrosis. Its eradication is necessary especially if the patient is to undergo lung transplantation.
    Full-text · Article · Mar 2010 · Journal of Medical Case Reports
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    ABSTRACT: Systematic flexible bronchoscopy is advocated in the initial management of childhood pulmonary tuberculosis. Our aim was to describe and to compare the systematic flexible bronchoscopy findings of 53 children (6.5 + or - 4.4 years; 52.8% boys) with active pulmonary tuberculosis to their initial clinical and radiological (chest x-ray, n=53; CT, n=45) features in an 11-year retrospective study. Flexible bronchoscopy was normal in 51% of cases. A severe tracheobronchial involvement (extrinsic compression >50% or obstructive endoluminal mass >25% of the lumen) was found in 10 patients. Flexible bronchoscopy guided therapy in 13 cases (steroids n=12, bronchoscopic extraction of a granuloma n=1) and permitted isolation of Mycobacterium tuberculosis in three patients (5.7%). No useful information was obtained by flexible bronchoscopy in 73.5% of cases. No correlation was found between flexible bronchoscopy findings and clinical features or x-ray findings. Conversely, a strong correlation was found between severe bronchoscopic involvement and tracheobronchial luminal narrowing on CT. The CT negative predictive value was 100% (95% CI 91% to 100%). Based on CT results, flexible bronchoscopy could have been avoided in about 60% of our patients. Flexible bronchoscopy remains a very relevant tool in the diagnostic and therapeutic management of childhood pulmonary tuberculosis but resulted in treatment modification or microbiological proof in a minority of our patients. We propose that flexible bronchoscopy in children with pulmonary tuberculosis be limited to those who show tracheobronchial luminal narrowing on an initial CT scan.
    No preview · Article · Feb 2010 · Archives of Disease in Childhood

Publication Stats

568 Citations
113.83 Total Impact Points

Institutions

  • 2012-2015
    • Aix-Marseille Université
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2012-2014
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2008
    • Hôpital Européen, Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2007
    • University of Tours
      • INSERM U 1100 Centre d'étude des pathologies respiratoires
      Tours, Centre, France
  • 2005
    • Unité Inserm U1077
      Caen, Lower Normandy, France