J.-C. Dubus

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (151)131.39 Total impact

  • Revue des Maladies Respiratoires. 09/2014; 31(7):649.
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    Archives de Pédiatrie. 08/2014; 21(8):905.
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    ABSTRACT: Ceftazidime is particularly efficient against P. aeruginosa in cystic fibrosis patients. Thus, the spontaneous production of pyridine, which is a toxic product, raises some concern. Our aim was to examine the kinetics of degradation of ceftazidime in portable infusion pumps either at 4, 22, or 33 °C and to propose some recommendations in order to reduce the pyridine exposure. Two administration models were studied in vitro. In Model 1, we administered 12 g/23 hours of ceftazidime (once daily infusion) vs. 2 × 6 g/23 hours in Model 2 (twice daily regimen). Samples were collected at H0, and then every 4 and 2 hours after the shaping of portable infusion pumps in Models 1 and 2, respectively. Both ceftazidime and pyridine were analyzed using a HPLC-UV. Production of pyridine is highly depending on the temperature. The in situ production of pyridine per day of treatment, decreases at a ratio close to 1/6 and 1/3 between 33 and 4 °C, in Models 1 and 2, respectively. Regardless of the conditions, the production of pyridine is significantly lower in Model 2, whereas the total delivery amount of ceftazidime are significantly higher at 4 and 33 °C vs. Model 1. According to a the precautionary principle, these findings lead to three major recommendations: a) exposing a solution of ceftazidime to over 22 °C should be strictly avoided; b) a divided dose of 6 g/12 hours instead of a once daily administration is preferred, and c) infusion should be administered immediately after reconstitution.
    Antimicrobial Agents and Chemotherapy 03/2014; · 4.57 Impact Factor
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    ABSTRACT: In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined.
    Revue des Maladies Respiratoires. 01/2014;
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    ABSTRACT: Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP2A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP2A website.
    Archives de Pédiatrie. 01/2014;
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    ABSTRACT: Recurrent tracheoesophageal fistula (TEF) is possible after repair of congenital esophageal atresia. The frequency of recurrent TEF is observed in about 10% of the cases. Within a cohort of 67 children with type III esophageal atresia repaired between 1998 and 2009, we aimed to identify the number of children with recurrent TEF, the risk factors for this condition, and the treatment proposed. The sex ratio was 1.7. Surgery was performed between 4 and 36 hours of life. Five children (7.5%) had a recurrent TEF, usually during the first 3 months, revealed by respiratory symptoms related to feeding in some cases. We noted that recurrent TEF was more frequent with anastomotic leakage (P = 0.09) or postsurgical pneumothorax (P < 0.01). The diagnosis was made in four cases out of five by a methylene blue test performed during a tracheobronchial endoscopy. Surgical treatment was noted in four children, with three postsurgical secondary effects. One child was treated by endoscopy and an esophageal clip. With a median follow-up of 52 months, no recurrence was noted. The recurrence of TEF may be linked to postsurgical events. Diagnosis is not easy and treatment is not clearly codified. Endoscopic treatment may be an advantageous option to surgery, likely with less morbidity.
    Archives de Pédiatrie. 01/2014;
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    ABSTRACT: Acute epiglottitis has become an exceptional observation in pediatrics. The introduction of Haemophilus influenzae type B vaccine changed the morbidity, mortality, and microbiology of this disease. We report the case of an 11-month-old infant with acute epiglottitis due to group A β-hemolytic streptococcus.
    Archives de Pédiatrie. 01/2014;
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    ABSTRACT: Nicolau syndrome is a rare, potentially severe complication that may occur after any drug injection, particularly after intramuscular injection. It is characterized by the acute onset of cutaneous and soft-tissue aseptic necrosis. Here, we report the case of a 14-year-old boy diagnosed with Nicolau syndrome on the right lower limb, after a benzathine-penicillin intramuscular injection for suspected rheumatic fever. The short-term progression was marked by uncomplicated rhabdomyolysis and the constitution of homolateral testicular torsion. The cutaneous-muscular disorders evolved favorably under symptomatic treatment. We discuss this insufficiently known complication of intramuscular injection, which may motivate reduced use of this route of drug administration in children and strict adherence to the procedure. Furthermore, it is important to note that Nicolau syndrome may evolve to homolateral testicular torsion, as, to the best of our knowledge, is reported for the first time in this case.
    Archives de Pédiatrie. 01/2014;
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    ABSTRACT: Background Asthma is the most common chronic disease in childhood. With its high economic burden, it is considered a disease of major public health importance by the World Health Organization. The link between respiratory tract infections and acute exacerbation has been recognized for a long time. The aim of this retrospective study in routine care was to evaluate our practices concerning microbiological prescriptions in children hospitalized for asthma exacerbation. Study design All children aged from 2 to 15 years hospitalized for asthma exacerbation between January 2010 and December 2011 in our unit were included in the study. Microbiological prescriptions, their indications, their results, and their cost were studied. Results One hundred ninety-seven children were included in the study. A potential causative agent was sought in 79.7% of the children (n = 157) by immunofluorescence assay (IFA) and/or polymerase chain reaction (PCR). The main indications were upper airway infections, hypoxemia, and pneumonia. Viruses were detected in 23.8% of them (30/126). Mycoplasma pneumoniae was detected by PCR in only 3.2% of these patients (4/125). No other bacterial agent was identified. There was no correlation between the severity of asthma exacerbation and the microbiological diagnosis of infection. The results did not influence the therapy given. These prescriptions represented a substantial cost for each child. Conclusion These analyses do not seem to have a real advantage for the patient except for epidemiology. It would be important to conduct a new study analyzing the role of rhinovirus, and of other viruses such as coronavirus, bocavirus, and enterovirus, not routinely investigated in our hospital, and to question the value of these costly microbiological tests.
    Archives de Pédiatrie. 01/2014;
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    ABSTRACT: Background: Ceftazidime (CAZ) remains one of the main anti-infective agents against P. aeruginosa in cystic fibrosis patients. However, a spontaneous production of pyridine (P) raises some concern in cases of continuous IV infusions. Our aim was to study the kinetics of spontaneous degradation of CAZ shaped in Portable Infusion Pumps (PIPs) and the potential risk of exposure to P. Material and Methods: 18 PIPs LV10 Baxter® were filled by 12g of CAZ diluted in 230mL of saline solution (52.17 mg/mL). Devices were stored either at 4, 22, or 33°C. Samples were collected immediately before and then every 4 hrs after the shaping of PIPs until the 24th h. Both CAZ and P were analysed by HPLC. Model-independent kinetic parameters were determined for both CAZ and P (Table 1). Data are expressed as mean ± SD. Results: Table 1 Storage temperature of PIPs. The flow controller of the devices was maintained at 33°C. 4°C (n=6) 22°C (n=6) 33°C (n=6) Compound CAZ Pyridine CAZ Pyridine CAZ Pyridine Final concentration: C24 (mg/mL) 51.7±2.3 0.133±0,066 46.1±1.0 0.425±0.015 43.0±2.0 0.790±0.007 Terminal half-life: t1/2 (h) 312.4±66.3 -21.6±8.0 88.6±17.2 -10±0.3 76.8±8.8 -6.7±0.1 Total Delivered Amount (g) 7.5±0.1 - 11.6±0.3 - 10.8±0.5 - Total Delivered Amount (mg) - 15.6±0.7 - 55.7±0.1 - 91.5±0.1 Remaining Volume after 24 hrs into the PIPs (mL) 80.5±7.1 <1.0 <1.0 Conclusions: Taking into account the unavoidable presence of P in the medium, it is an ethical question to ensure a better monitoring of the treatment. We suggest: a) to avoid exposing a solution of CAZ to over 22°C, especially in cases of prolonged infusion, b) to replace the once daily administration schedule by a twice daily infusion (6 g/12 hrs leads to a theoretical production of ~36mg (vs.~56mg) of P per day of treatment at 22°C). Other options to be tested are a decrease of the daily dose of CAZ and maintaining PIPs at 4°C.
    36th European Cystic Fibrosis Conference, Lisbon, Portugal; 06/2013
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    ABSTRACT: We report the case of late vitamin K deficiency bleeding (VLDB), with appropriate but insufficient prophylaxis, secondary to extrahepatic cholestasis. Late VKDB is rare today but serious, with a risk of intracranial hemorrhage in more than half of the cases. The diagnosis, causes and prevention of this disease are discussed.
    Archives de Pédiatrie. 05/2013; 20(5):503–506.
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    ABSTRACT: Omalizumab was shown to reduce exacerbation rate in moderate to severe allergic asthma.To evaluate omalizumab efficacy and safety in a real life setting in severe asthmatic children.104 children (6-18 y), followed-up in paediatric pulmonary tertiary care centres were included at omalizumab onset. Asthma control levels, exacerbations, inhaled corticosteroids (ICS) dose, lung function and adverse events (AEs) were evaluated over one year.Children were characterized by allergic sensitisation to ≥3 allergens (66%), high IgE levels (mean: 1125 kU·l(-1)), high rate of exacerbations (4.4/year) and health care use during the previous year, high ICS dose (mean: 703 μg equivalent fluticasone/day). Asthma control levels defined as good, partial or poor, improved from 0%, 18%, and 82% at entry to 53%, 30% and 17% at week 20, and to 67%, 25% and 8% at week 52, respectively (p<0.0001). Exacerbation and hospitalisation rates dropped by 72 and 88.5%. At 12 months, FEV1 improved by 4.9% (p=0.023), and ICS dose decreased by 30% (p<0.001). Six patients stopped omalizumab for related significantAEs.Omalizumab improved asthma control in children with severe allergic asthma and was generally well tolerated. The observed benefit was greater than that reported in clinical trials.
    European Respiratory Journal 03/2013; · 6.36 Impact Factor
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    ABSTRACT: The working group on aerosol therapy (GAT) of the Société de pneumologie de langue française (SPLF) organized its third “Aerosolstorming” in 2012. During the course of one day, different aspects of inhaled therapy were discussed, and these will be treated separately in two articles, this one being the first. Inhaled products represent a large volume of prescriptions both in the community and in hospital settings and they involve various specialties particularly ENT and respiratory care. Technical aspects of the development of these products, their mode of administration and compliance with their indications are key elements for the effective therapeutic use of inhaled treatments. In this first article, we will review issues concerning generic inhaled products, the existence of inhaled antidotes, new anti-infective agents and indications for inhaled pentamidine.
    Revue des Maladies Respiratoires. 01/2013;
  • A. Sapet, M. Oudyi, J.-C. Dubus
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    ABSTRACT: Three different devices are available for inhaled medications in children: the pressurized metered dose inhalers (pMDIs, breath-actuator synchronized pMDI, and valved holding spacers), the dry powder inhalers, and the nebulizers. To choose the better device for a particular patient, a perfect knowledge of the available devices, of their mode of use, of their advantages and inconvenient is required. The use of a pMDI coupled to a valved holding spacer is the first mode of delivery to propose in children aged less than 6 years. After 6 years old, the DPIs may be proposed depending on the child's competences. At last, the nebulizations are indicated in some particular and severe indications, but new indications are appearing because of recent progresses.
    Revue de Pneumologie Clinique 01/2013; 69(4):198–206. · 0.20 Impact Factor
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    ABSTRACT: Objective To describe the chest radiographs of infants hospitalized for acute bronchiolitis and to assess whether patient management changed after radiography. Study design All infants hospitalized in our pediatric unit with a first episode of acute bronchiolitis from October 2010 to March 2012 were included in the study. Infants with chronic disease or transferred from a pediatric intensive care unit were excluded. The following data were collected: sex, age, neonatal history, atopy, tobacco exposure, admission criteria, treatment, laboratory parameters, ultrasonography and its outcome, results of chest radiography on admittance, the reason for a second chest radiograph, change in management as a result of the radiograph. Results The study comprised 232 infants (median age 2.2 months, boys 56%, positive respiratory syncytial virus 73.4%). Among them, 227 children had a routine chest radiograph revealing distension and/or bronchial wall thickening (n = 141, 62.4%), focal opacity (19.9%), or atelectasis (17.7%). This radiograph led to the prescription of antibiotics in six patients (2.6%) and allowed the diagnosis of vascular abnormality to be made in one case (0.4%). Thirty-five patients (15.4%) had a second chest radiograph during their hospitalization owing to oxygen dependency (n = 21), respiratory distress (n = 11), persistent fever (n = 2), or no reason specified (n = 1). Pneumonia (n = 7) and/or atelectasis (n = 15) were then found in 62.9%. Patient management (antibiotics, postural maneuvers) was modified in six patients (17.1%). Conclusions Routine chest radiographs contribute only partially to the treatment of infants hospitalized for acute bronchiolitis. However, radiography is useful when the hospitalized child does not improve at the expected rate or if the disease is severe. The indication of chest radiography in infants hospitalized for acute bronchiolitis should be discussed on a case by a case basis.
    Archives de Pédiatrie. 12/2012; 19(12):1308–1315.
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    ABSTRACT: Airplanes are widely used by families and their children and pediatricians are increasingly asked to answer questions on this subject. The main purpose of this study was to evaluate the knowledge of pediatricians in this field except for medical transportation. Pediatricians belonging to the AFPA, the SFP, the SNPEH, or the SP2A were emailed a questionnaire on the physiological particularities of airborne transportation, contraindications to flight related to diseases (infections, diabetes, sickle-cell anemia, respiratory diseases, etc.) and the possible medication intake on board. Among the 232 responders, 82.3% had an exclusive hospital practice and 65% were specialized in more than one area of medicine. Regarding contraindications to flying, the rate of correct answers varied from 14 to 84% with divided opinions regarding respiratory and hematological pathologies. However, contraindications related to infections were well known. Items related to oxygen therapy raised questions as 35–68% of pediatricians stated that they could not answer. On the whole, this work demonstrated very fragmented knowledge on this topic.
    Archives de Pédiatrie. 11/2012; 19(11):1148–1156.
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    ABSTRACT: BACKGROUND: The bacterial contamination of nebulizers represents a major problem for cystic fibrosis (CF) patients that can lead to reduced nebulizer performance and increase the risk of patient reinfection by the contaminating bacteria. OBJECTIVE: We investigated the potential use of squalamine, a broad-spectrum antimicrobial compound, as a nebulizer disinfectant. METHODS: Pari LC nebulizers were artificially contaminated with a suspension of bacteria (Staphylococcus aureus and Pseudomonas aeruginosa; 10(8)CFU/mL) and fungi (Candidida albicans and Aspergilus niger; 10(7)CFU/mL) and then disinfected by immersion in squalamine solution for 20min. Glutaraldehyde and Korsolex peracetic acid were used as disinfectant controls. RESULT: We found that 0.5g/L squalamine reduced the levels of viable S. aureus and P. aeruginosa by 5 log(10) and the level of viable C. albicans by 4 log(10) after 20min. A concentration of 2g/L was needed to reduce the level of A. niger cells by 4 log(10) in 6hours. Finally, a formulation of squalamine in the form of a soluble disinfecting tablet containing 2.5% (w/w) squalamine was developed and successfully applied for nebulizer disinfection. CONCLUSION: Our results suggest that aminosterol derivatives may be used by CF patients for rapid and easy home nebulizer disinfection and that soluble tablets may be developed for this purpose.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 06/2012; · 3.19 Impact Factor
  • Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society, Dublin, Ireland; 06/2012
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    ABSTRACT: Acute viral bronchiolitis affects infants, is frequent, and can be severe. Its treatment is only based on symptoms. Hypertonic saline (HS) may act favorably in this situation by fighting virus-induced dehydration of the airway liquid surface. Because of an osmotic action, HS attracts the water from the epithelial cells and improves mucociliary clearance. Five double-blind placebo-controlled studies concerning hospitalized infants with acute viral bronchiolitis showed that repeated nebulizations of 3% HS induce a 20% improvement in the clinical severity score and reduced the hospital length of stay by 24 h. Tolerance is excellent. On the other hand, a few questions remain unresolved: what is the optimal salt concentration? What is the recommended nebulizer? What is the best frequency for nebulizer use? Can nebulized HS be used at home? What are the results with systematic physiotherapy when HS is used?
    Archives de Pédiatrie. 06/2012; 19(6):635–641.
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    ABSTRACT: No aerosol system on the market is perfectly suited for aerosol therapy in infants. The RESPIRE project aims to answer this need by developing an innovative piezoelectric microperforated vibrating membrane nebulizer, the Baby Nimbus™; efficient, fast, portable and silent. Consisting of three complementary partners, the project was divided into three phases: technology development by the company Télémaq (Sophia Antipolis), in vitro and in vivo test performed on baboons by Inserm U618 (Tours), clinical trials in infants led by AP–HM (Marseille). Studies conducted by Inserm U618 and AP–HM focused on the influence of particle size on lung deposition in baboons and the clinical score in infants. Three devices of different droplet sizes were compared in the in vivo study, the Pari LC Sprint SP® (Pari, Germany, MMAD 4.5μm – flow 0.18 mL/min), the E-Flow Rapid® (Pari, Germany, MMAD 4.8μm – flow 0.35 mL/min) and Baby Nimbus™ (Télémaq, France). Four versions of Baby Nimbus™ were needed to achieve the MMAD of 2.4 μm and flowrate of 0.4 mL/min (Spraytec®, Malvern, England). Preliminary in vivo results show that the amount of the initial charge deposited in the lungs is 0.9% for the Pari LC Sprint SP®, 1.2% for E-Flow Rapid® and 2.2% for the Baby Nimbus™. Additional in vivo tests and clinical trials are under way to rule definitively on the efficiency provided by the Baby Nimbus™.
    IRBM. 04/2012; 33(2):61–66.

Publication Stats

317 Citations
131.39 Total Impact Points

Institutions

  • 2008–2010
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • University of Tours
      Tours, Centre, France
  • 2007–2008
    • Cliniques Universitaires Saint-Luc
      Bruxelles, Brussels Capital Region, Belgium
  • 2005
    • Centre Hospitalier Saint-nazaire
      Saint-Nazaire, Pays de la Loire, France
  • 2004
    • CHU de Lyon - Hôpital Gériatrique des Charpennes
      Lyons, Rhône-Alpes, France
  • 2000–2003
    • Assistance Publique Hôpitaux de Marseille
      • Service de médecine infantile
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2002
    • CHU de Lyon - Hôpital Femme-Mère-Enfant
      Lyons, Rhône-Alpes, France
  • 1999
    • Aix-Marseille Université
      Marsiglia, Provence-Alpes-Côte d'Azur, France