V. David

Neonatal screening of cystic fibrosis: diagnostic problems with CFTR mild mutations

SummaryNewborn screening (NBS) of cystic fibrosis (CF) was implemented throughout the whole of France in 2002, but it had been established earlier in three western French regions. It can reveal atypical CF with one or two known CFTR mild mutations, with an uncertain evolution. The sweat test can be normal or borderline. In Brittany, from 1989 to 2004, 196 CF cases were diagnosed (1/2885 births). The incidence of atypical CF diagnosed by NBS is 9.7% (19 from 196). The outcome of 17 (2 lost of view) has been studied, with 9 other atypical CF cases diagnosed by NBS in two other regions. The follow-up period extends from 0.25 to 19.8 years (NBS implemented in Normandy in 1980) with mean age 4.6 years. The most frequent mild mutation is R117H ISV8−7T (50%). At the time of the last visit, nutritional status is normal. All these CF patients are pancreatic sufficient. Only one patient exhibits respiratory infections, whereas 7 others have them intermittently. Two of them had intermittent Pseudomonas aeruginosa colonization at 2.8 and 6.5 years. Mean Shwachman score is 96.7, mean Brasfield score is 22.8. Eight children have had lung function tests (mean follow-up of 10 years): mean FVC was 99% of predicted, mean FEV1 101%, but one of them has FEV1 of 48%. Predicting the phenotype of these atypical CF patients remains difficult, thus complicating any genetic counselling. A regular clinical evaluation is necessary, if possible by a CF unit, because CF symptoms may appear later.

Psychological Effects of False-Positive Results in Cystic Fibrosis Newborn Screening: A Two-Year Follow-Up

OBJECTIVEnTo evaluate parental stress after a false-positive result at the time of the cystic fibrosis (CF) newborn screening (NBS), attributable to heterozygotism or persistent hypertrypsinemia.nnnSTUDY DESIGNnA prospective study was conducted in 86 French families at 3, 12, and 24 months after NBS. A psychologist conducted interviews with a questionnaire, the Perceived Stress Scale, and the Vulnerable Child Scale.nnnRESULTSnOverall, 96.5% of parents said they had been anxious at the time of the sweat test. However, 86% felt entirely reassured 3 months after the test. The mean Perceived Stress Scale score did not differ from that observed in the French population. Mean Vulnerable Child Scale scores were high, associated with a low Parental Perception of Child Vulnerability. These results did not differ significantly at 1 and 2 years. In total, 86% to 100% of families no longer worried about CF. All parents stated that they would have the test performed again for another child.nnnCONCLUSIONSnCF NBS can lead to false-positive results, causing parental anxiety, which quickly decreases after a sweat test performed soon after the phone call.

Pancreatic enzyme replacement therapy for young cystic fibrosis patients

UNLABELLEDnMaldigestion in cystic fibrosis (CF) affects approximately 90% of patients. As soon as pancreatic insufficiency is identified, enzyme supplementation is prescribed even with breast fed infants. A pancreatic enzyme preparation developed particularly for infants, Creon for children (CfC), contains smaller granules to be administered with a dosing spoon (5000 lipase units per scoop).nnnPATIENTS AND METHODSnIn a prospective, randomised, multi-centre study, 40 infants and toddlers received both CfC and Creon 10000 (C10) for two weeks each in a cross-over design. Dosing of pancreatic enzymes was continued as applied before the study. The primary endpoint was the parents treatment preference. Secondary endpoints included coefficient of fat absorption (CFA), clinical symptoms and safety parameters.nnnRESULTSn20 parents (51%) from the N=39 intent to treat sample preferred CfC, 9 (23%) preferred C10, and 10 (26%) had no preference The applied doses led to a mean CFA with similar results for both treatments (77.8% vs. 78.7%). Gastrointestinal symptoms were reported on a number of study days, and some children had abnormal results for laboratory parameters of malabsorption. Safety and tolerability of the preparations were good and all these parameters were comparable for both treatments.nnnCONCLUSIONnThose parents who had a preference favoured CfC over C10. Both enzyme preparations improved malabsorption to a similar degree, although the applied dosages could have been too low in some children reflected in a suboptimal CFA. These data support the use of CfC for young patients with cystic fibrosis improving the daily care of this cohort detected mainly now through neonatal screening programmes.

Third case of paternal isodisomy for chromosome 7 with cystic fibrosis: A new patient presenting with normal growth†

Many patients with maternal uniparental disomy of chromosome 7 (UPD7) have been described, mainly with intrauterine and postnatal growth retardation or with Silver–Russell syndrome. In contrast, only three cases of paternal UPD7 have been reported, all associated with recessive disorders. Here, we report on the clinical and molecular data of the third patient with paternal UPD7 and cystic fibrosis. Pre‐ and postnatal growth were normal. These findings support the hypothesis that paternal isodisomy for human chromosome 7 may have no phenotypic effect on growth.

La fibroscopie bronchique chez l’enfant: Expertise des centres français de pneumologie pédiatrique

INTRODUCTIONnFibreoptic bronchoscopy (FB) is an important diagnostic examination in paediatric pulmonology. In 2002 the Paediatric Pulmonology and Allergy Club undertook a retrospective study to establish the current status of fibreoptic bronchoscopy among its members.nnnMETHODSnIn 2001 sixty five paediatric pulmonologists carried out an average of 116 examinations (+/- 111) in 35 paediatric centres. FB was performed either in an operating theatre (15 centres), a dedicated bronchoscopy suite (6 centres) or an endoscopy suite shared with gastro-enterologists (7 centres). Other examinations were performed in areas dedicated to, or associated with intensive care. General anaesthesia was routinely used in 18 centres. The others used sedation including an equimolar mixture of oxygen and nitrous oxide in 14 centres. Ten centres performed less than 50 examinations, 12 between 51 and 100, 4 between 101 and 200 and 8 centres more than 200 in the year. Seventy two per cent of the children were less than 6 years old. The washing and disinfection procedures were manual in 20 centres and automatic in 15.nnnRESULTSnThree principal indications were reported: persistent wheezing, suspicion of a foreign body and ventilatory difficulties. Cough, desaturation and fever were the most frequently reported side effects.nnnCONCLUSIONSnThis is the first survey in paediatric pulmonology in France. It shows a wide variation in the practice of fibreoptic bronchoscopy in children.Resume Introduction La fibroscopie bronchique est un examen complementaire cle dans la demarche diagnostique en pneumologie pediatrique. Le Club Pediatrique de Pneumologie et d’Allergologie a realise en 2002 une enquete retrospective permettant d’etablir un etat des lieux de la pratique par les pneumopediatres de la fibroscopie bronchique. Methodes Soixante cinq pneumopediatres ont effectues en moyenne 116 examens (± 111) dans 35 centres pediatriques en 2001. Les fibroscopies ont ete realisees soit dans un bloc operatoire (15 centres), soit un bloc dedie a la fibroscopie (6 centres), soit un site partage avec les gastroenterologues (7 centres). Les autres examens ont ete pratiques dans des locaux pediatriques (salle dediee et/ou unite de soins intensifs). L’anesthesie generale a ete systematique dans 18 centres. Les autres centres ont pratique une sedation consciente, avec utilisation de melange gazeux equimolaire oxygene protoxyde d’azote dans 14 centres. Dix centres ont realise moins de 50 examens, 12 entre 51 et 100, 4 entre 101 et 200 et 8 centres plus de 200 fibroscopies dans l’annee. Soixante douze pour cent des enfants avaient moins de 6 ans. Les procedures de lavage desinfection ont ete « manuelles » dans 20 centres et automatisees dans 15 centres. Resultats Trois indications principales ont ete rapportees : respiration sifflante persistante, suspicion de corps etranger et troubles de ventilation. Parmi les effets indesirables, la toux, la desaturation en oxygene et la fievre ont ete le plus souvent rapportees. Conclusion Cette enquete est une premiere en pneumologie pediatrique en France. Elle montre l’heterogeneite des pratiques en matiere de fibroscopie bronchique chez l’enfant.

Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study

n n Objectiven To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs).n n n Study designn A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15xa0years of age with acute viral infections between 2006 andxa02009.n n n Resultsn Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72xa0hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1xa0day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, Pxa0=xa0.004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, Pxa0=xa0.04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs.n n n Conclusionsn NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children.n n

Retrospective observational study of French patients with cystic fibrosis and a Gly551Asp-CFTR mutation after 1 and 2 years of treatment with ivacaftor in a real-world setting

BACKGROUNDnIvacaftor has been shown to improve lung function and body weight in patients with CF and a gating mutation. Real-world evaluation is warranted to examine its safety and effectiveness over the long term.nnnMETHODSnA retrospective observational multicentre study collected clinical data in the year before and the 2years after ivacaftor initiation in patients with CF and a Gly551Asp-CFTR mutation.nnnRESULTSnFifty-seven patients were included. Mean absolute change in FEV1% predicted improved from baseline to Year 1 (8.4%; p<0.001) and Year 2 (7.2%; p=0.006). Statistically significant benefits were observed with increased body mass index, fewer Pseudomonas aeruginosa and Staphylococcus aureus positive cultures, and decreased IV antibiotics and maintenance treatment prescriptions (including azithromycin, Dornase alpha and nutritional supplements). No significant adverse events were reported.nnnCONCLUSIONnThe clinical benefits of ivacaftor reported in previous clinical trials were confirmed in a real-world setting two years post-initiation, also reducing treatment burden.

Inhalation et nébulisation chez l'enfant

La voie inhalee est la voie dadministration preferentielle des medicaments a visee respiratoire. La quantite de produit deposee au niveau pulmonaire depend principalement du systeme dinhalation et de la technique utilisee. Levaluation de cette deposition est d ifficile, en particulier chez lenfant, les etudes portant surtout sur les caracteristiques des medicaments et des systemes de delivrance et peu sur le depot pulmonaire lui-meme ; en effet, celui-ci necessite des etudes scintigraphiques dont lirradiation limite les indications chez lenfant. Les systemes dinhalation disponibles sont varies : nebuliseurs, aerosol-doseurs avec ou sans chambres dinhalation, inhalateurs de poudre. Quel que soit le systeme utilise, un bon controle de lasthme ne sera obtenu quen controlant regulierement la technique dinhalation de lenfant.

Éducation thérapeutique et mucoviscidose : l’expérience d’un CRCM pédiatrique

La mucoviscidose est une maladie chronique grave dont l’espérance de vie s’est considérablement allongée depuis ces dernières années (Observatoire National de la Mucoviscidose 2002) ; les différents aspects de la prise en charge requièrent une coopération active du patient et de sa famille. La contrainte de soins devient de plus en plus importante au fur et à mesure de l’évolution et nécessite une gestion de la vie AVEC la maladie : l’éducation thérapeutique trouve ici sa place. Elle a été définie en 1998 par l’OMS : « c’est former le malade pour qu’il puisse acquérir un savoir-faire adéquat, afin d’arriver à un équilibre entre sa vie et le contrôle optimal de sa maladie. C’est un processus continu qui fait partie intégrante des soins médicaux. Il comprend la sensibilisation, l’information, l’apprentissage du traitement, le support psychosocial, tous liés à la maladie et au traitement. La formation doit aussi permettre au malade et à sa famille de mieux collaborer avec les soignants. » (OMS 1998).

La fibroscopie bronchique chez l’enfant

INTRODUCTIONnFibreoptic bronchoscopy (FB) is an important diagnostic examination in paediatric pulmonology. In 2002 the Paediatric Pulmonology and Allergy Club undertook a retrospective study to establish the current status of fibreoptic bronchoscopy among its members.nnnMETHODSnIn 2001 sixty five paediatric pulmonologists carried out an average of 116 examinations (+/- 111) in 35 paediatric centres. FB was performed either in an operating theatre (15 centres), a dedicated bronchoscopy suite (6 centres) or an endoscopy suite shared with gastro-enterologists (7 centres). Other examinations were performed in areas dedicated to, or associated with intensive care. General anaesthesia was routinely used in 18 centres. The others used sedation including an equimolar mixture of oxygen and nitrous oxide in 14 centres. Ten centres performed less than 50 examinations, 12 between 51 and 100, 4 between 101 and 200 and 8 centres more than 200 in the year. Seventy two per cent of the children were less than 6 years old. The washing and disinfection procedures were manual in 20 centres and automatic in 15.nnnRESULTSnThree principal indications were reported: persistent wheezing, suspicion of a foreign body and ventilatory difficulties. Cough, desaturation and fever were the most frequently reported side effects.nnnCONCLUSIONSnThis is the first survey in paediatric pulmonology in France. It shows a wide variation in the practice of fibreoptic bronchoscopy in children.Resume Introduction La fibroscopie bronchique est un examen complementaire cle dans la demarche diagnostique en pneumologie pediatrique. Le Club Pediatrique de Pneumologie et d’Allergologie a realise en 2002 une enquete retrospective permettant d’etablir un etat des lieux de la pratique par les pneumopediatres de la fibroscopie bronchique. Methodes Soixante cinq pneumopediatres ont effectues en moyenne 116 examens (± 111) dans 35 centres pediatriques en 2001. Les fibroscopies ont ete realisees soit dans un bloc operatoire (15 centres), soit un bloc dedie a la fibroscopie (6 centres), soit un site partage avec les gastroenterologues (7 centres). Les autres examens ont ete pratiques dans des locaux pediatriques (salle dediee et/ou unite de soins intensifs). L’anesthesie generale a ete systematique dans 18 centres. Les autres centres ont pratique une sedation consciente, avec utilisation de melange gazeux equimolaire oxygene protoxyde d’azote dans 14 centres. Dix centres ont realise moins de 50 examens, 12 entre 51 et 100, 4 entre 101 et 200 et 8 centres plus de 200 fibroscopies dans l’annee. Soixante douze pour cent des enfants avaient moins de 6 ans. Les procedures de lavage desinfection ont ete « manuelles » dans 20 centres et automatisees dans 15 centres. Resultats Trois indications principales ont ete rapportees : respiration sifflante persistante, suspicion de corps etranger et troubles de ventilation. Parmi les effets indesirables, la toux, la desaturation en oxygene et la fievre ont ete le plus souvent rapportees. Conclusion Cette enquete est une premiere en pneumologie pediatrique en France. Elle montre l’heterogeneite des pratiques en matiere de fibroscopie bronchique chez l’enfant.