Lung disease in ataxia-telangiectasia.

UNLABELLED: Ataxia-telangiectasia (AT) is a multi-systemic disease caused by mutational inactivation of the ATM gene. We report a retrospective study of lung disease in 15 patients. PATIENTS AND METHODS: A diagnosis of AT was made if the patient met the following criteria: neurological features and at least one the following: oculo-cutaneous telangiectasia, elevated serum alpha-feto-protein level. RESULTS: Recurrent sino-pulmonary infections were usually present in 11 of the cases and occurred during the first 2 years of life. Other lung injuries noted were bronchiectasis, obstruction and restriction of the airways, fibrosis, pneumothorax and haemoptysis. Eleven children had immunodeficiencies. DISCUSSION: Recurrent sino-pulmonary manifestations precede neurological complications, but the severity of neuro-degeneration and pulmonary disease were not correlated. Pulmonary status was a prognosis factor. Immunodeficiency was the main, but not the only, aetiology for lung disease in AT. CONCLUSION: There is little dispute over the role of ATM in lung and respiratory epithelium. To reduce the morbidity associated with AT, there needs to be greater awareness of respiratory complications. Early management and monitoring lung function is necessary to minimize lung damage.

[Fatal evolution of a dilated cardiomyopathy during a primary Epstein-Barr virus infection]. / Myocardiopathie dilatée d'évolution fatale au cours d'une primo-infection par le virus Epstein-Barr.

We report the observation of a 2-year-old child who developed an acute heart failure during a primary EBV infection. The viral serological diagnosis showed CMV and EBV IgM positivity. The detection of EBV genome by PCR and the characteristic evolution of EBV serological response confirmed a primary EBV infection.

Parental knowledge and use of epinephrine auto-injector for children with food allergy.

Epinephrine should be prescribed for patients at risk of anaphylaxis. Our purpose was to determine the use of Anapen prescribed for food-allergic children, to assess parental knowledge regarding Anapen, and to evaluate the arrangements for emergency kits and personalized care projects in everyday life. A prospective study was performed with a questionnaire sent to families with a food-allergic child previously prescribed Anapen. One hundred and fifty two families were contacted and finally 111 children included (median age 6.5 yrs). Main food allergens were peanuts (n = 89), egg (n = 39) and cow's milk (n = 10). The use of Anapen had been demonstrated to 90% of parents (by prescribing physician, 69%; pharmacist, 25%; general practitioner, 5%; nurse 1%), with a training device (76%) and/or written instructions (49%). When asked to list symptoms requiring injection, 48% of parents cited more than one response: breathing difficulties only (23%), or with angio-edema (41%), collapse or faintness (38%), anaphylactic shock (48%). Of 107 children attending school, 54% had a personalized care project, 72% an Anapen device, and 60% a complete emergency kit (epinephrine, inhaled beta-agonist, corticosteroid, anti-H1 drug). Beta-agonists were forgotten at school by 34 children (13 asthmatics). Anapen was used in one child for angio-edema and dyspnea after inadvertent ingestion of egg at home. In our population, epinephrine auto-injectors and emergency kits were insufficiently available at schools and in daily life. The use of auto-injectors was not adequately demonstrated. The prescription of epinephrine for food-allergic children at risk of anaphylaxis requires accurate diagnosis, educational programs, information, and follow up.

[Ataxia-telangiectasia: a review]. / Ataxie-télangiectasie: de la clinique à la physiopathologie.

Ataxia-telangiectasia (AT) is an autosomal recessive inherited disease caused by mutational inactivation of the ATM gene. It is a multisystemic disease, characterized by progressive neurological dysfunction, especially in the cerebellum, oculo-cutaneous telangiectasia, immunodeficiency, recurrent sino-pulmonary infections and high incidence of neoplasms. The responsible gene, ATM, encodes a large protein that belongs to a family of protein kinases with a phosphatidylinositol 3-kinase (Pi3K) domain. ATM is a key regulator of cell cycle checkpoints that causes DNA repair or apoptosis. Several studies report ATM function in target cells (such as neurons, fibroblast, endothelium, germ cells, lymphocytes). The pleiotropic phenotypes of AT reflect the multifaceted activities of ATM protein. In nucleus (lymphocytes, fibroblasts, germ cells) ATM is involved in regulation of cell-cycle checkpoints; in cytoplasm ATM regulates redox state (neurons).

[Flexible bronchoscopy in children. Experience at French centers of pediatric pneumology]. / La fibroscopie bronchique chez l'enfant. Expertise des centres français de pneumologie pédiatrique.

INTRODUCTION: Fibreoptic 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. METHODS: In 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. RESULTS: Three 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. CONCLUSIONS: This is the first survey in paediatric pulmonology in France. It shows a wide variation in the practice of fibreoptic bronchoscopy in children.

[Antibacterial therapy outside of Pseudomonas aeruginosa]. / Traitement anti-infectieux en dehors du Pseudomonas aeruginosa.

Hemophilus influenzae and Staphylococcus aureus (SA) are the predominant pathogens in infants with cystic fibrosis (CF). SA was the major cause of death in the pre-antibiotic era. The reason of the association of SA in CF is unclear. SA causes early damage of the respiratory tract and paves the way for Pseudomonas aeruginosa (PA). Based of this hypothesis, some centers use prophylactic antibiotics, but their efficacy is not proved and may favor growth of PA. Treatment of exacerbations is mandatory. Oral antibiotics are preferred in most cases, although few controlled clinical studies have been reported. Emergence of methicillin-resistant Staphylococcus aureus (MRSA) strains appeared during the recent years. Treatment of MRSA is difficult, patients segregation is discussed.

[Reproducibility of the shuttle walk test in children with cystic fibrosis]. / Reproductibilité du test de marche en navette chez des enfants atteints de mucoviscidose.

INTRODUCTION: Exercise testing is useful in the respiratory evaluation of patients with cystic fibrosis. The shuttle walk test (SWT) is a progressive, externally paced, exercise test requiring the subject to walk/run back and forth between two fixed points. The aim is to assess the reproductibility of the SWT in paediatric patients with cystic fibrosis. METHODS: This prospective study recruited 31 children with stable disease. The patients performed two SWT one day (SWT 1 and 2) and two others (SWT 3 and 4) within 15 days. Only SWT 2 and 4 were assessed for reproducibility. RESULTS: 61% were boys, median age (range): 12.9 (7-18.9) years, median Shwachman score (range): 80 (65-100), median values for FEV1 and FVC (range): 92 (55-154) and 92 (64-140)% predicted, respectively. Median distance for SWT 2-4 (range): 910 (580-1020) and 925 (540-1020) metres. Reproducibility for SWT distance and physical activity measured by an accelerometer is very good (intra-class correlation coefficient=0.90 and 0.92, respectively). SWT distance correlated with physical activity (p=3.10(-4)) and weight (p=0.03). SWT distance was independent of the following parameters: height, weight-for-age Z-score, FEV1, FVC, Shwachman score, colonisation with Pseudomonas aeruginosa. CONCLUSIONS: The SWT is reproducible in paediatric patients with cystic fibrosis and provides assessment of respiratory performance that complements spirometric measures of lung function.

Role of viruses and atypical bacteria in exacerbations of asthma in hospitalized children: a prospective study in the Nord-Pas de Calais region (France).

We studied the role of viruses and atypical bacteria in children hospitalized with exacerbated asthma by a prospective study of children with acute asthma admitted to the Department of Pediatrics in Lille, and to 15 hospitals in the Nord-Pas de Calais region, from October 1, 1998-June 30, 1999. We included children aged 2-16 years with active asthma, defined as three or more recurrent episodes of reversible wheezing. The severity of asthma and of asthmatic exacerbations was recorded. Immunofluorescence assays (IFA) on nasopharyngeal secretions (NPS), serological tests, or both, were used for detection of influenza virus, respiratory syncytial virus (RSV), adenovirus, parainfluenza virus, and coronavirus. Polymerase chain reaction (PCR) assays on NPS were used for rhinovirus and enterovirus. Serological tests for Chlamydia pneumoniae and Mycoplasma pneumoniae were performed. A control group of asymptomatic asthmatic outpatients was examined for respiratory viruses (using IFA and PCR). Eighty-two symptomatic children (mean age, 7.9 years) were examined. Viruses were detected in 38% (enterovirus, 15.8%; rhinovirus, 12%; RSV, 7.3%). Serological tests for atypical bacteria were positive in 10% of patients (C. pneumoniae, 5%; M. pneumoniae, 5%). Among the 27 control subjects (mean age, 7.9 years), one PCR was positive for enterovirus. There was no correlation between severity of chronic asthma or asthmatic exacerbations and the diagnosis of infection. Atypical bacterial pathogen infections were linked with prolonged asthmatic symptoms. In conclusion, we confirmed the high incidence of viral infection in acute exacerbations of asthma, especially enteroviruses or rhinoviruses. Persistent clinical features were more frequently associated with atypical bacterial infections, suggesting that these infections should be investigated and treated in cases of persistent asthmatic symptoms.

Microbiologic contamination study of nebulizers after aerosol therapy in patients with cystic fibrosis.

BACKGROUND: To evaluate the contamination of delivery systems after an aerosol therapy session in patients with cystic fibrosis who have chronic Pseudomonas aeruginosa infection. METHODS: Fifty-three patients with cystic fibrosis were enrolled in the study from March 1996 to June 1997. All patients were age 7 years or older and had P aeruginosa infection. They also had been treated with recombinant deoxyribonuclease and were capable of producing sputum for culture. RESULTS: Nine devices were excluded for the study. A total of 44 nebulizers were included: 37 from patients with P aeruginosa colonization with a count of 10(6) colony-forming units/mL or more and 7 with a count of between 10(5) colony-forming units/mL and 10(6) colony-forming units/mL. CONCLUSION: This study demonstrates that in the absence of cleaning, nebulizers of patients with cystic fibrosis who are infected with P aeruginosa are likely to be contaminated by a pathogenic flora.

[Pleurisy: diagnostic and therapeutic management]. / Les pleurésies. Conduites diagnostique et thérapeutique.

Diagnosis of pleural effusion is difficult in children. The etiologies are numerous; however, infectious agents are more frequent. Thoracocentesis proves to be the first-line diagnostic tool. Light's criteria are the best for distinguishing whether the effusion is a transudate or an exudate. If the patient has an exudative pleural effusion, other tests are indicated to determine the etiology and in some cases the treatment: macroscopic appearance, cytology and differential white cell count (level of glucose, lactate dehydrogenase, adenosine deaminase, pH, bacterial cultures). Others investigations--biopsy of pleura by thoracoscopy or video-assisted thoracoscopy, bronchofibroscopy, CT scan--are sometimes useful. Intrapleural instillation of urokinase appears to be useful and safe. Evaluation is necessary for video-assisted thoracoscopy used early.

Outcome of cystic fibrosis-associated liver cirrhosis: management of portal hypertension.

BACKGROUND/AIM: Variceal bleeding is the most severe complication in patients with cystic fibrosis-associated liver cirrhosis, who often do not have severe respiratory failure. The advent of liver transplantation has broadened the treatment options. The purpose of this study was to report our experience with the management of portal hypertension. METHODS: Clinical and biochemical features, outcome of liver disease and management of portal hypertension were analyzed retrospectively in 44 children with cystic fibrosis-associated liver cirrhosis. RESULTS: The mean age at diagnosis of liver cirrhosis was 9 years. Eighty-six per cent of the children developed esophageal varices, 50% of whom bled early in their second decade. Injection sclerotherapy of esophageal varices did not prevent recurrence of bleeding in five of seven children. Elective surgical portosystemic shunting was successfully performed in nine of 11 patients considered being at high risk of bleeding or with recurrent bleeding episodes but without severe pulmonary failure and liver dysfunction, allowing prolonged post-operative survival up to 15 years. Two of three children who underwent isolated liver transplantation for severe portal hypertension died post-operatively. CONCLUSIONS: Management emphasis in cystic fibrosis patients with liver cirrhosis should be on control of bleeding and variceal decompression. These results suggest that surgical portosystemic shunting may be considered to relieve portal hypertension in patients without progressive liver failure and severe lung disease as an alternative to liver transplantation. With this policy, patients may be stabilized for many years until progression of liver or lung diseases indicates liver or lung-liver transplantation.

[Effect of rhDNase on the respiratory function and nutritional status of children and adolescents with mucoviscidosis]. / Effects de la rhDNase sur la fonction respiratoire et le statut nutritionnel de l'enfant et de l'adolescent atteints de mucoviscidose.

BACKGROUND: In 1994 we started recombinant human deoxyribonuclease (rhDNase) in every cystic fibrosis (CF) patient whatever his (her) clinical condition, provided they were aged more than 5 years and forced vital capacity (FVC) was > or = 40%. POPULATION AND METHODS: We reviewed retrospectively the effects of rhDNase in 69 CF children and adolescents during a 2-year follow-up. Patients (35 boys, 34 girls) received 2.5 mg of rhDNase once daily from a mean age of 8.5 years (range 5-16.4). Baseline spirometric values (% predicted) and nutritional status were as followed: FVC = 84.8 +/- 21.7; forced expiratory volume in 1 second (FEV1) = 80.8 +/- 22.2; peak flow = 89.7 +/- 34.2, forced expiratory fraction 25-75% (FEF 25-75) = 71.8 +/- 32.8; Z score weight/height = -0.41 +/- 1.14; Z score weight/age = -0.48 +/- 1.25, body mass index = 15.4 +/- 1.8; caloric intake = 107 +/- 25% of recommended dietary allowances (RDA). Patients had a Shwachman-Kulczycki's score of 87 +/- 9. Spirometric and nutritional data were analysed after 1, 3, 6, 12, 18 and 24 months of treatment and compared to baseline values (changes evaluated as percent change from mean baseline for spirometric data). Shwachman-Kulczycki's score was calculated after 24 months of rhDNase. RESULTS: An improvement of FVC (+10.7%, P < 0.001) and FEV1 (+12%, P < 0.01) was noted after one month of treatment and was maintained throughout the following 2 years around 8.7% (6.4-11.4) for FVC and 8.2% (7.3-9.1) for FEV1, P < or = 0.01. This was particularly observed in children aged 5 to 10 years, in boys and in patients with a baseline FVC under 70% predicted. There was no significant change in FEF 25-75. We observed an improvement of daily caloric intake from the third month (P < 0.05) and of body mass index from the sixth month (P = 0.02). This was particularly noted in girls. Z score weight/age was improved only during the first 3 months of treatment while Z score weight/height increased only after a 2 year follow-up. There was no significant change in Shwachman-Kulczycki's score after 24 months of rhDNase. CONCLUSION: rhDNase in CF children in effective on lung function as well as on nutritional status and the response to this treatment can be evaluated after the first 3 months.

Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis.

OBJECTIVE: To compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. DESIGN: 22 patients with cystic fibrosis, mean (SD) age 11 (3.4) years (range 5.6-19.3), with pulmonary pseudomonas exacerbations were randomly assigned to receive a 14 day course of tobramycin (15 mg/kg/day) either in three infusions (group A) (n = 10) or a single daily infusion (group B) (n = 12), combined with ceftazidime (200 mg/kg/day as three intravenous injections). Efficacy was assessed by comparison of pulmonary, nutritional, and inflammatory indices on days 1 and 14. Cochlear and renal tolerance were assessed on days 1 and 14. Tobramycin concentration was measured in serum and sputum 1, 2, 3, 4, 8, and 24 hours after the start of the infusion. Analysis was by non-parametric Wilcoxon test. RESULTS: Variables improving (p < 0.05) in both groups A and B were, respectively: weight/height (+4% and +3.1%), plasma prealbumin (+66 and +63 mg/l), forced vital capacity (FVC) (+14% and +11%), forced expiratory volume in one second (+15% and +14%), and forced expiratory flow between 25% and 75% of FVC (+13% and +21%). Improvement was not significantly different between groups. Renal and cochlear indices remained within the normal range. Serum peak concentration of tobramycin on day 1 was 13.2 (7.1) mg/l in group A and 42.5 (11.2) mg/l in group B (p < 0.001); serum trough was 1.1 (0.8) mg/l in group A and 0.3 (0.2) mg/l in group B (p < 0.01). Tobramycin concentrations in sputum were two to three times higher in group B than group A. CONCLUSIONS: Once daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in cystic fibrosis patients.