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Study Objectives: Cystic fibrosis (CF) is one of the most common inherited diseases among whites. Since the cloning of the CF transmembrane conductance regulator (CFTR) gene, a number of studies have focused on associations between the genotype and phenotype in CF. This had led to the progressive identification of new groups of patients, including those who have mild lung disease and those who have normal sweat chloride values (< 60 mEq/L). The aim of the present work was to provide information on the genotype and the phenotypic characteristics of children with intermediate-range sweat chloride test results., Patients and Results: We focused on children referred to the pulmonary department for various types of pulmonary disease and who had several sweat chloride test results with median values in the range of 40 to 60 mEq/L. Twenty-four patients over a 10-year period were enrolled (mean age, 4.8 years). Respiratory manifestations at initial evaluation included recurrent bronchitis, wheezing, chronic cough, and pneumonia. The duration of the follow-up ranged from 0.5 to 10.5 years. Sputum cultures revealed the presence of Haemophilus influenzae (10 children), Staphylococcus aureus (4 children), and Pseudomonas aeruginosa (3 children). Pancreatic insufficiency was found in two patients. Analysis of the entire coding sequence allowed identification of 16 known mutations in CFTR gene. Fifteen chromosomes (31.2%) carried a mutation in CFTR gene and one allele carried two mutations. Three patients were homozygous or double heterozygous (DeltaF508/DeltaF508, DeltaF508/3849 + 10 kb C-->T, S1235R/G551D). The 5-thymidine allele was identified in four children., Conclusion: These results indicate an higher frequency of CFTR gene mutations in patients with borderline sweat chloride test results, compared to data reported in the general population. They lead to the recommendations for complete pulmonary and GI investigations in this group of patients, as well as assiduous care and medical follow-up.

Unlabelled: The aim of this prospective study was to evaluate the consequences of neonatal treatment with a venovenous extracorporeal respiratory assistance., Population and Methods: Thirty nine neonates (28 boys) with acute respiratory failure were included. Extracorporeal respiratory assistance consisted of an apnoeic oxygenation with low frequency positive pressure ventilation and extracorporeal membrane CO2 removal through a venous single canula perfusion circuit. The causes of respiratory distress were: 15 meconium aspiration syndrome, 12 respiratory distress syndrome, six hyaline membrane disease, three sepsis, two diaphragmatic hernia, and one post-surgery Mendelson syndrome. The mean duration of mechanical ventilation was 18 days, including 5 days of extracorporeal respiratory assistance. The prospective follow-up included physical examination, chest radiographs, scintigraphy and pulmonary function tests. These tests studied the following parameters: functional residual capacity by helium dilution technique, lung resistance and dynamic lung compliance by the esophageal balloon technique and blood gases with arterialized blood samples., Results: The mean duration of the follow-up was 21.3 months (6 months to 5 years). Results showed in the first year 33% of children with chronic obstructive pulmonary disease and chest (X-ray abnormalities, such as bronchopulmonary dysplasia in 23% of children. Data of pulmonary function test at the end of the first year: lung resistance and functional residual capacity were within limits of predicted values for height, and dynamic lung compliance was slightly decreased; according to the analysis of the functional profile: 31% without abnormality, 41% of obstructive syndrome and 26% with restrictive pattern. Blood gases were normal in 37 children. At the end of the second year, we noticed normal functional residual capacity, an increase of lung resistance while lung compliance was normalized; functional profile was quite different: with a decrease of the number of patients without abnormality (22%) and increase of those with obstructive syndrome (56%)., Conclusion: The percentage of abnormalities is high but these are moderate in most cases, especially if we compare with the initial seriousness of the pulmonary pathology. We suggest a regular follow-up to study the respective incidence of pulmonary disease and/or extracorporeal respiratory assistance over these abnormalities.

Since the cloning of the defective gene in cystic fibrosis, much has been learned on the function of CFTR and on the mechanisms regulating its expression. Based on the current understanding of the processes involved in lung disease progression, a number of approaches have been developed using gene therapy and pharmacological agents. Several of these agents have been reported to restitute a function to CFTR with specific mutations. Other molecules act on channels other than CFTR, and may be effective by bypassing CFTR itself. In the present review the various therapeutical strategies currently investigated are discussed.

Background: Tuberculosis is rarely seen in patients with cystic fibrosis., Case Report: A 14-year old female adolescent, regularly followed for a well-tolerated form of cystic fibrosis, developed an acute respiratory infection with consolidation of the left inferior lobe, and no response to the usual antibiotic treatment of cystic fibrosis. Mycobacterium tuberculosis was found in aspirate by fibroscopy, on Loewenstein medium. No familial or social infection contact were identified. Antituberculous chemotherapy with three drugs brought about a prompt improvement of sytemic signs, weight gain, resolution of pulmonary foci and sedation of biological findings referable to inflammation., Conclusion: This case report reminds us that tuberculosis may occur in cystic fibrosis patients. Loewenstein cultures should routinely be made when faced with an unexplainable worsening of the condition.

More than 600 mutations have been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and are known to cause cystic fibrosis (CF). This large number of mutations makes the search of the molecular defects in CF patients difficult. We have used the techniques of denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing to detect the mutations in 334 CF chromosomes mostly of French origin. The whole coding sequence of the CFTR gene corresponding to the 27 exons and their exon-intron boundaries was studied. 45 different mutations were identified. This method allowed us to detect the molecular defect in 90.5% of the mutant alleles and to report a novel mutation D979V.

Background: Mucoepidermoïd carcinomas (MEC) are very rare (less than 20 cases reported in the literature) and potentially malignant bronchial gland carcinomas., Patients: Three children, two boys (11 and 7 years old) and one girl (5 years old) suffered from respiratory symptoms such as cough, recurrent pneumonia and/or hemoptysis for 2 to 12 months. Bronchial endoscopy showed a mass into the left (two cases), or the right main bronchus (one case). Chest CT scan identified local extension, and lung-associated lesions. Histopathological study concluded to MEC in the three cases. The patients were treated by segmental bronchial resection, completed with left upper lobectomy (two cases), bronchotomy (one case). All the tumor could be removed; there was no metastasis. The outcome was uneventful with a 8 to 24 months follow-up., Conclusion: Bronchial tumors of children must be considered in patients with chronic cough, recurrent pneumonia and/or hemoptysis and require bronchial endoscopy for their diagnosis.

Since 1987, Pseudomonas cepacia has been isolated with an increasing frequency in the expectorants of children with cystic fibrosis followed at the Hôpital d'enfants Armand Trousseau (Paris, France). Colonization by P. cepacia may be responsible for serious secondary infections and rapid deterioration in respiratory function in these patients. Among the 130 children attending our centre, 14 (8 girls and 6 boys) aged 3 to 18, exhibited chronic colonization. 132 isolates, originating from sputum obtained between 1992 and 1994 were studied. Nine biochemical patterns and 6 antibiotic susceptibility patterns at least were defined, therefore exhibiting great polymorphism. Chromosome restriction patterns with Xba I after pulsed field gel electrophoresis enabled 4 pulsotypes to be identified: A, B, C and D. Thirteen patients harboured pulsotypes A, C and D, and 1 patient pulsotype B, the last being quite distinct from the first three. Pulsotypes A, C and D were almost similar, suggesting that closely related strains, probably the same strain, was harboured by 13 of the 14 patients. The origin could be contamination from a single source, or stem from patient-to-patient crossed transmission.

Penetration of ceftazidime into bronchial secretions was studied in 23 patients, of which 18 had cystic fibrosis. Ceftazidime was used as the single drug for treating exacerbations caused by Pseudomonas aeruginosa. Dosage was 6 g/1.73 m2/day divided into three intravenous injections for 14 to 21 days. Bronchial secretion samples were obtained by fiber-optic bronchoscopy or physical therapy. Serum and bronchial secretion ceftazidime concentrations were assayed using a microbiological method. Ceftazidime concentrations in both media were lower in children than in adults : elimination half-life is shorter (1.7 h against 2.45 h in adults), extravascular distribution is faster, with earlier (1 h against 2 h in adults) achievement of the peak bronchial secretion concentration (2 micrograms/ml). The ratio of bronchial secretion concentration to concomitant serum concentration did not exceed 5% at the time of peak bronchial concentration. These results suggest that in cystic fibrosis patients, the faster and lower bronchial penetration of ceftazidime may be due to faster elimination as compared to adults. Although transient elimination of Pseudomonas aeruginosa was achieved in 12 study patients, our findings support the use of higher dosages or alternative administration modalities designed to increase in situ ceftazidime concentrations.

Seventeen children (mean age, nine years) with chronic obstructive pulmonary disease (COPD) were studied during sleep. Electroencephalography, electrooculography, and electromyography were all recorded. Airflow was measured by nasal and oral thermistors, and abdominal and thoracic anteroposterior diameters by magnetometers. Transcutaneous partial pressure of O2 (tcPO2) and of CO2 (tcPCO2) were monitored. The average total sleep time was 283 min +/- 36 (1 SD). Breathing pauses (BP) five seconds or longer were measured. The mean time of BP expressed as a percentage of TST was 1.3 percent +/- 0.8 (1 SD). The BP occurred most frequently during REM sleep. Forty-six percent of BP were obstructive (OBP). The percentage of OBP was significantly related to the degree of lung resistance during wakefulness. Periodic breathing was observed with a mean frequency of 2.2 times per night (range: 0 to 7). Episodes with paradoxic inward rib cage motion were seen one to 29 times (mean 6.6). Drops in tcPCO2 greater than 5 mm Hg occurred one to eight times and 67 percent were observed during REM sleep. Compared to tcPCO2 during W the mean maximal decrease in tcPCO2 was 14 mm Hg (range 8 to 29). tcPCO2 rose with a mean maximal of 9.1 mm Hg (range 6 to 13). It was concluded that children with COPD had worsened gas exchange during sleep.