A new large CFTR rearrangement illustrates the importance of searching for complex alleles.

The p.Val754Met variant, described in 1996 in a CF patient, has been considered a CF mutation. However, biochemical aspects, results of functional studies and, finally, the identification of a complex deletion removing exons 3 to 10 and 14b to 16 in cis of p.Val754Met in a CF patient, argue against a strong deleterious effect. An inventory through the French CF network of patients carrying p.Val754Met led to the registration of seven patients (CF: n=4; idiopathic chronic pancreatitis: n=3) and six healthy individuals, all heterozygous for the variation. Extensive CFTR gene analysis was carried out, including the search for large rearrangements and other possible mutations. The complex deletion, whose breakpoints are described here, was found only in the four CF patients, in association with the same haplotype. This data, added to the fact that the p.[Phe508del]+[Val754Met] genotype was found in a healthy individual, bring further arguments against the association of p.Val754Met with CF. We thus suggest looking for a possible complex allele whenever p.Val754Met is detected and considering it neutral regarding genetic counseling when found in isolation.

Long-term outcome of idiopathic pulmonary hemosiderosis in children.

We retrospectively analyzed the long-term outcome of idiopathic pulmonary hemosiderosis (IPH) in 15 children. IPH started at a mean age of 5 years, and the mean duration of follow-up was 17.2 years (range, 10-36 yr). Four patients developed immune disorders, 3 cases of rheumatoid polyarthritis or rheumatoid polyarthritis-like diseases and 1 case of celiac disease. Respiratory outcome showed that 3 patients had severe symptoms: 2 patients developed severe pulmonary fibrosis resulting in major chronic respiratory insufficiency, and 1 patient had severe asthma. Twelve patients (80%) had mild or no respiratory problems and were able to lead a normal life. According to chest X-ray and pulmonary function test data, 4 patients had normal chest X-ray and no evidence of restrictive syndrome, 6 patients had an interstitial pattern on chest X-ray and evidence of restrictive pattern, 1 patient had an interstitial pattern but normal lung function, and 1 patient had a normal chest X-ray but evidence of mixed obstructive and restrictive pattern. Our results show that long-term survival is possible in patients with IPH. Factors of poor prognosis seem to be the presence of antineutrophil cytoplasm antibodies (ANCA) or other autoantibodies. No other clinical or biological predictive factors for prolonged survival were found.

Specificity and sensitivity of respiratory impedance in assessing reversibility of airway obstruction in children.

Flow in the upper airway wall induces significant error in estimating respiratory impedance by the standard forced oscillation technique in subjects with airway obstruction and may be minimized by oscillating pressure around the subject's head (head generator technique). The aim of this study was to determine whether the latter improves the power of forced oscillations in detecting airway response to bronchodilators in children. Seventy-five children with airway obstruction were studied (ages 5.5 to 15 years old). Fifty-three had asthma and 22, cystic fibrosis. A bronchodilator was administered, and the percent changes in respiratory resistance at 10 Hz (Rrs10), 20 Hz (Rrs20), respiratory compliance (Crs), and resonant frequency (fn) with standard and head generator were compared with the corresponding change in FEV1. The response was positive in 38 (delta % FEV1 > or = 15%) and negative in 37 patients. Data on Rrs10, Crs, and fn could not be obtained in 7, 8, and 4 subjects, respectively, for technical reasons. The delta % Rrs20 was not different between head and standard generator in nonresponders (mean +/- SEM: -19.0 +/- 4.5, vs -11.8 +/- 3.1%), but significantly larger with head than standard generator in responders (-54.1 +/- 3.0 vs -26.5 +/- 2.4%; p < 0.001). The optimal decision level determined by Receiver Operation Characteristic analysis showed that, compared with the standard method, the head generator improved the specificity of Rrs20 (78 vs 65%) with no change in sensitivity (76% for both). Resonant frequency had larger sensitivity with standard than with head generator (91 vs 53%) but slightly lower specificity (70 vs 78%). Finally, delta %Crs was more specific (72 vs 67%) and more sensitive (68 vs 52%) with standard than with head generator. The overall incidence of false results was lower with the head generator than with the standard generator for resistance and lower with the standard generator than with the head generator for fn and compliance. Thus, the head generator improves the diagnostic power of the forced oscillation resistance in establishing the reversibility of airway obstruction, but parameters derived from the reactance may have better diagnostic value with the standard method.

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.

[Anti-inflammatory therapy in cystic fibrosis]. / Stratégies anti-inflammatoires dans la mucoviscidose.

Cystic fibrosis lung inflammation is early, sustained and severe and would justify an anti-inflammatory treatment. At present, the inhaled corticosteroid treatment did not give evidence of efficacy, contrary to the oral presentation, but at the cost of side effects. Azithromycin gives more encouraging results with a good tolerance. New molecules are in the process of validation.

[Pulmonary complications in immunosuppressed children]. / Complications pulmonaires de l'enfant immunodéprimé.

Pulmonary complications, which are dominated by opportunistic infections, can be first manifestations of inherited or acquired pediatric immune deficiencies. Prompt diagnosis is essential. The epidemiology and natural history of these complications have changed as a result of major advances in prevention, diagnosis and treatment.

[Chronic obstructive pulmonary diseases and asthma in children: diagnostic and therapeutic strategies]. / Bronchopathies chroniques obstructives et asthme de l'enfant démarche diagnostique et stratégie thérapeutique.

Asthma and chronic obstructive pulmonary disease are two distinct affections but two chronic inflammatory disorders. Respiratory symptoms are non-specific. There is a possible relationship between airways hyperreactivity and chronic obstructive pulmonary disease. Airway remodeling in asthma can begin in childhood. If natural history is different, treatment strategies become similar.

[Does idiopathic naso-sinusal polyposis exist in children?]. / La polypose naso-sinusienne idiopathique de l'enfant existe-t-elle?

UNLABELLED: Nasal polyposis, a rare disease in childhood, can present itself as an idiopathic disease. The aim of this study was to describe some of the clinical features of idiopathic nasal polyposis in children and to emphasize this condition as a specific clinical entity. POPULATION AND METHODS: The study was based on a retrospective analysis of 26 cases of idiopathic nasal polyposis that were studied to our department between 1979 and 1996. In addition, a questionnaire was sent to parents of which 20 were returned completed. RESULTS: The clinical characteristics of idiopathic nasal polyposis in children (11 males and nine females; median: 12 years; range: 8-15 years) were very similar to those observed in adults (median: 50 years), in particular the relation to asthma (ten of 20 cases) and aspirin intolerance (two Fernand-Widal syndromes of 20 cases). Recurrent ENT infections during the maturing period of the immunological system (0-7 years) did not seem to play a role. There appeared, however, to be a strong genetic component as half of our cases had a family history of nasal polyposis and/or asthma. DISCUSSION: Idiopathic nasal polyposis should be recognized as an entity among nasal polyps in childhood. Management of idiopathic and secondary nasal polyposis is however different. Although the pathogenesis of nasal polyposis is not well understood, the study of this disease in children leads one to suspect a genetic transmission.

[Esophageal communication with a totally sequestrated hypoplastic right lung]. / Communication oesophagienne avec un poumon droit hypoplasique totalement séquestré.

Pulmonary sequestrations involving communication with the digestive tractus are known as bronchopulmonary foregut malformations. The authors add a peculiar case report: there was an hypoplastic right lung with a total sequestration from the bronchial tree and communicating with esophagus. This was fed from the pulmonary vasculature without collateral artery formation. The pulmonary vein was normal. Association with a facial dysmorphia and an occipital meningocele is also of interest. The radiological diagnosis is based on the pulmonary X-Ray and the oesophagogram.

[Idiopathic laryngotracheobronchial calcifications in children. Apropos of 2 cases]. / Les calcifications laryngo-trachéo-bronchiques idiopathiques chez l'enfant. A propos de deux observations.

Calcifications of cartilage in the larynx, trachea and bronchi are rare in children. Two cases reported and listed with 5 similar cases of the literature. Such calcifications are generally discovered in young children and congenital stridor is commonly associated with. Calcifications of bronchi are not present in every case. The blood calcium is normal. Laryngoscopic examination shows in two cases a laryngeal stiffness. The prognosis is good. In two cases, one of the parents of under 40 years old, also had calcifications of the trachea and of the bronchi.

[Aerodigestive papillomatosis in an infant]. / Papillomatose aéro-digestive chez un nourrisson.

A case of juvenile papillomatosis involving the supra glottic area of the larynx and the esophagus in a 10 months old infant is reported. The patient was treated by multiple Laser CO2 resections of papillomas and received autogenous vaccine. He is now 5 years; he is well and apparently free of disease for the last two years. Radiography of the larynx and esophagogram were crucial for the initial diagnosis and the followup of this child.

[Respiratory evolution of patient with mucoviscidosis treated with mucolytic agents plus dornase alfa]. / Evolution respiratoire de patients atteints de mucoviscidose traités par mucofluidifiants puis par dornase alfa.

AIM: Modifications of bronchial secretions in cystic fibrosis patients account for the long-lasting use of mucolytic agents, despite the lack of adequately controlled clinical studies supporting this approach. Hyperviscosity of bronchial secretions mainly depend on their high DNA content, as a result of degradation of polymorphonuclear neutrophils mobilized by infection and inflammation. This phenomenon has led to the treatment of respiratory complications with human recombinant deoxyribonuclease (dornase alfa). In the present study, we compared the clinical and respiratory outcome in patients receiving mucolytic agents followed by dornase alfa, each for 1 year. POPULATION AND METHODS: Fifty-four patients, aged 5 years or more, have been prospectively followed for 2 years. They received first a 12-month association of mesna (two nebulisations per day) and oral ambroxol (60 mg per day, divided in two doses), followed by a 12-month treatment with one daily aerosol of dornase alfa only (2.5 mg per day). The primary end-points were the results of pulmonary function tests. Secondary end-points were subjective symptoms, bacterial colonization, consumption of antibiotics, and clinical tolerance. RESULTS: At the end of the 12-month mucolytic therapy, a significant decrease of forced expiratory volume/second (FEV1, -10.5% as compared to baseline values) and forced vital capacity (FVC, -12.8%) was observed. At the end of 12-month dornase alfa, FEV1 and FVC had increased by 7.7 and 5.3%, respectively. This change was statistically significant only for FEV1 in most severely disabled patients. However, forced expiratory flow 25-75% (FEF 25-75) decreased during the 2 year period of observation, by 5.6% the first year and 4.9% the second year. The mean number of days with parenteral antibiotics did not statistically differ between both treatments, except for patients more than 15 years of age. In this subgroup, the mean number decreased from 40 days in the first year to 27 in the second year (P < 0.05). Acceptability of treatment by the patients themselves was better with dornase alfa than with mucolytic therapy. However, several episodes of hemoptysis, frequent in only one case, were associated with the treatment by dornase alfa. CONCLUSION: Dornase alfa was associated with a stabilisation, and even a trend to improvement in pulmonary function tests. This stabilisation is by itself a very encouraging result. Long-term comparative studies are needed to evaluate the benefits of dornase alfa in the treatment of respiratory complications of cystic fibrosis and specify the optimal modalities of its use. Synergistic combinations with mucolytic therapy and/or anti-inflammatory drugs could be viewed as a future prospect.

[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.

[Inflammation, bronchial hyperreactivity and mucoviscidosis]. / Inflammation, hyperréactivité bronchique et mucoviscidose.

Inflammation aggravates respiratory impairment in patients with cystic fibrosis. It plays an essential role in the genesis of bronchial hyperreactivity. Corticosteroids are the predominant therapeutic agents used. The importance of bronchial hyperreactivity in cystic fibrosis is correlated with disease severity. Treatment is essential to slow down the progression of bronchiopulmonary involvement.

[Role of home care in the management of patients with mucoviscidosis]. / Place des soins à domicile dans la prise en charge des patients atteints de mucoviscidose.

Home care, sometimes in the technical form of home hospitalization, is essential in caring for patients with cystic fibrosis, both to avoid separating the children from their environment and rupturing their life rhythms, but also to reduce the risk of hospital contamination. Home care requires an evaluation of the disease status, good patient and family information and good coordination between the different partners. Thus the reduction in hospitalization greatly improves the quality of life in patients with cystic fibrosis.

[Chemoprophylaxis of tuberculosis]. / La chimioprophylaxie de la tuberculose.

Chemoprophylaxis of tuberculosis may be primary or secondary. Primary chemoprophylaxis is intended for infants and children with negative tuberculin tests and exposed to contagion, in order to avoid primary tuberculosis. It lasts for three months and consists of oral isoniazide in one single daily dose of 5 to 10 mg/kg. Secondary chemoprophylaxis applies to all subjects, but principally to children, with a tuberculin test that has recently become positive in the absence of BCG vaccination. Its purpose is to protect against clinical tuberculosis. It lasts for six months and consists of isoniazid combined with rifampicin.

[Recommendations for the use of diagnostic testing in low respiratory infections in children older than three months]. / Recommandations sur l'utilisation des nouveaux outils diagnostiques étiologiques des infections respiratoires basses de l'enfant de plus de trois mois.

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 (SP(2)A). 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 SP(2)A website.

[Difficulties of TB diagnosis in children: QuantiFERON TB Gold In-Tube as useful tool]. / Difficultés du diagnostic de la tuberculose chez l'enfant : intérêt du test QuantiFERON TB Gold In-Tube.

Diagnosis of childhood tuberculosis (TB), active TB or latent tuberculosis infection (LTBI), is complicated by uncommon clinical, radiological and bacteriological features. The tuberculin skin test (TST) is imperfect: difficulty of the intradermal injection for the child, lack of sensibility and specificity. The stop of the systematic inoculation by the BCG since July 2007, in France, could lead to an increase of the incidence of the childhood TB. It is urgent to find new diagnostic tools: sensitive, specific, fast, of objective reading and little expensive. Interferon-gamma assays could be useful but the data are still insufficient in paediatrics and sometimes contradictory. A prospective study which compared the usefulness of QuantiFERON TB Gold In-Tube (QFT-IT) assay with TST to detect LTBI or active disease in 51 children was realised in University Hospital of Nancy. This allowed us to confirm interest of QFT-IT; however, surprisingly, very discordant QFT-IT and TST results were obtained (only five children were QFT-IT+/TST+). A high number (14%) of indeterminate QFT-IT occurred, without explanation by pre-analytical or clinical parameters. Further studies are needed to demonstrate the usefulness of this assay in diagnosing LTBI and particularly active TB in children.