Effect of intermittent inhaled tobramycin on sputum cytokine profiles in cystic fibrosis.

OBJECTIVES: The aim of this study was to evaluate the anti-inflammatory properties of intermittent inhaled tobramycin. METHODS: To establish this, we initiated a prospective study to measure the concentration of the three pro-inflammatory cytokines IL-8, IL-6 and TNF-alpha in the sputum from 20 cystic fibrosis (CF) patients (15 teenagers and 5 young adults) during cycles and off cycles. RESULTS: A significant decrease in IL-8 (P = 0.001) and a more moderate decrease in IL-6 (P = 0.046) and TNF-alpha (P = 0.052) levels were observed during cycles, even if no significant decrease in the number of leucocytes was observed. CONCLUSIONS: These results associated with a decrease in the Pseudomonas aeruginosa population can contribute in part to the beneficial effect of intermittent inhaled tobramycin on pulmonary function.

Energetic cost of physical activity in cystic fibrosis children during Pseudomonas aeruginosa pulmonary exacerbation.

Chronic pulmonary infection by Pseudomonas aeruginosa is observed in 50% of patients with cystic fibrosis and requires the use of recurrent intravenous therapy. A decrease of resting energy expenditure (REE) and an increase of physical activity (PA) after intravenous anti-P. aeruginosa therapy (IVAT) is observed while total energy expenditure (TEE) does not change. A decrease in the energetic cost of physical activity (ECPA) could be hypothesized but has never been studied. Our aim was to assess the evolution of ECPA after home IVAT in both standardized condition at hospital and in free-living condition twice before and after IVAT. Sixteen CF patients (nine boys, seven girls) chronically colonized by P. aeruginosa with a mean age of 12.1+/-2.3 years (range 7.1-14.6) were studied before and after IVAT. Each patient passed throughout a visit in hospital: weight, height and fat-free mass were measured. Then, energy expenditure (EE) measured by indirect calorimetry and heart rate (HR) were simultaneously recorded at different levels of PA: REE, and at different intensity of physical activities on a cycloergometer using an incremental increase of the power brake force. Physical activity energy expenditure (PAEE) was computed in laboratory condition using PAEE=EE-BEE (basal energy expenditure). Linear regression between PAEE and power brake force was fitted for each patient before and after IVAT. ECPA in standardized conditions was compared at different range of power brake force using area under the curve (AUC). After coming back at home, 24 h TEE using the heart rate monitoring technique and PA by triaxial accelerometry were simultaneously measured in free-living condition for 24 h during a school day. ECPA in free-living conditions was compared by the ratio PAEE:PA where PAEE=DEE-REE (DEE=daily energy expenditure). After IVAT, median AUC between 60 and 90 W in standardized condition decreased significantly by -15.4% (median 14.9, range 8.8-30.3 vs. median 12.6, range 8.5-17.6; P<0.05, Wilcoxon rank test) while the decrease for lower range of power work load did not reach significance. Spearman correlation was significant between variations of forced expiratory volume in 1 s and variation of AUC at 30-60 W before and after IVAT in standardized condition. In free-living conditions, ratio PAEE/PA did not vary significantly (median 3.4, range 1.6-6.4 vs. median 2.8, range 1.4-4.8; NS). Our data demonstrate a decrease of ECPA after IVAT in standardized conditions for moderate level of PA (60-90 W), but not in free-living conditions. The decrease of ECPA was probably due to a decrease in the energetic cost of breathing after IVAT, that is particularly relevant to promote PA in CF patients.

Familial and community environmental risk factors for Helicobacter pylori infection in children and adolescents.

BACKGROUND: The aim of the study was to identify familial and community environmental risk factors associated with Helicobacter pylori infection in a pediatric population. METHODS: Children requiring diagnostic upper endoscopy were included in the study during a 2-year period. During endoscopy, five gastric biopsies were performed for the histologic or bacteriologic diagnosis, or both, of H. pylori infection. Epidemiologic data collected by a questionnaire were analyzed using the chi-square test or Fisher test and stepwise logistic regression. RESULTS: The authors included 436 patients (242 boys), aged 2 days to 17.9 years (median, 2.7 years). H. pylori prevalence was 7.3%. Univariate analysis found H. pylori was more common in older patients (P < 0.00001), in children who had at least one parent born in a developing country (P < 0.02) or with a low socioeconomic status (P < 0.02), and in those living in crowded conditions (P < 0.02). Children whose mother worked at home were more frequently infected than children whose mother worked outside the home (P < 0.02). Attendance at nursery or school before the age of 6 years was not associated with infection. Logistic regression showed a strong association with H. pylori only for age and number of persons at home. CONCLUSIONS: The source of H. pylori is intrafamilial rather than from a community, such as nursery and school attended at a young age. The number of persons in the home influences the infection status of children but not by the presence of the mother in home. These data suggest that H. pylori infection transmission occurs from siblings or the father rather than from mother.

Natural outcome of Helicobacter pylori infection in asymptomatic children: a two-year follow-up study.

BACKGROUND AND OBJECTIVES: It is known that Helicobacter pylori can be acquired in early childhood. There is not enough data to know whether or not infected children should be treated. A better knowledge of the natural outcome and implications of H pylori infection may provide evidence that eradication therapy is beneficial in childhood. This prospective study looks at clinical symptoms, endoscopic, microbial, and histologic changes during a 2-year period in infected asymptomatic children. It is hoped that some prognostic indicators will be found that select out the children that later need therapy. PATIENTS AND METHODS: During epidemiologic study of the prevalence of H pylori infection, 18 children aged 7 +/- 4 years (mean +/- 1 SD) were discovered to have H pylori infection and enrolled in the 2-year follow-up study. These patients had received no eradication therapy because they were asymptomatic. The follow-up for each patient consisted of an initial assessment, a clinical examination every 6 months, and an endoscopic reevaluation at the end of the first and second years. Gastric mucosal samples were analyzed for bacteriologic and histologic changes. Various factors were initially recorded: individual factors included sex, age, and housing conditions; microbial factors included bacterial load and the presence of the CagA gene. Inflammatory changes were also noted, such as the presence of active gastritis and nodular formation, and these were correlated with the histology which was described using the Sydney classification. Typing polymerase chain reaction-restriction fragment length polymorphism was performed to check the persistence of the same strain of H pylori in each patient. RESULTS: All of the children were still infected after 2 years with the same strain as in the initial assessment with the exception of 1 child whose infection cleared spontaneously. The density of antral and fundal mucosal colonization with H pylori also remained stable. There were progressive inflammatory changes in this cohort, particularly between the first and second year (histologic score, 3.5 +/- 1.3 vs 5 +/- 1). Active antral gastritis occurred in 3 out of 14 and 1 out of 8 children during the first and second year, respectively. Gastritis became active in the fundus in 2 out of 14 and 2 out of 8 children during the same period. Increases in the histologic score were found particularly in male children, and children colonized by cagA- strains of H pylori during the follow-up. The frequency of nodular gastritis significantly rose from 11% (2 out of 18 children) to 64% (9 out of 14 children) after 1 year, and to 80% (8 out of 10 children) after 2 years. CONCLUSION: These findings demonstrate a deterioration in the histologic features of the gastric mucosa of infected children despite stable H pylori colonization and the absence of symptoms.

[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.