Muriel Lebourgeois

Temporal Dynamics of Interferon Gamma Responses in Children Evaluated for Tuberculosis

Background Development of T-cells based-Interferon gamma (IFNγ) assays has offered new possibilities for the diagnosis of latent tuberculosis infection (LTBI) and active disease in adults. Few studies have been performed in children, none in France. With reference to the published data on childhood TB epidemiology in the Paris and Ile de France Region, we considered it important to evaluate the performance of IGRA (QuantiFERON TB Gold In Tube®, QF-TB-IT) in the diagnosis and the follow-up through treatment of LTBI and active TB in a cohort of French children. Methodology/Principal Findings 131 children were recruited during a prospective and multicentre study (October 2005 and May 2007; Ethical Committee St Louis Hospital, Paris, study number 2005/32). Children were sampled at day 0, 10, 30, 60 (except Healthy Contacts, HC) and 90 for LTBI and HC, and a further day 120, and day 180 for active TB children. Median age was 7.4 years, with 91% of the children BCG vaccinated. LTBI and active TB children undergoing therapy produced significant higher IFNγ values after 10 days of treatment (p = 0.035). In addition, IFNγ values were significantly lower at the end of treatment compared to IFNγ values at day 0, although the number of positive patients was not significantly different between day 0 and end of treatment. Conclusions/ Significance By following quantitative IFNγ values in each enrolled child with LTBI or active TB and receiving treatment, we were able to detect an increase in the IFNγ response at day 10 of treatment which might allow the confirmation of a diagnosis. In addition, a decline in IFNγ values during treatment makes it possible for clinicians to monitor the effect of preventive or curative therapy.

Clinical phenotype and genotype of children with borderline sweat test and abnormal nasal epithelial chloride transport.

RATIONALE The diagnosis of cystic fibrosis (CF) is based on a characteristic clinical picture in association with a sweat chloride (Cl(-)) concentration greater than 60 mmol/L or the identification of two CF-causing mutations. A challenging problem is the significant number of children for whom no definitive diagnosis is possible because they present with symptoms suggestive of CF, a sweat chloride level in the intermediate range between 30 and 60 mmol/L, and only one or no identified CF-causing mutation. OBJECTIVES To investigate the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways of children with intermediate sweat tests and inconclusive genetic findings in correlation with clinical phenotype and genotype. METHODS We developed a composite nasal potential difference (NPD) diagnostic score to discriminate patients with CF from non-CF patients. We tested NPD in 50 children (age, 6 mo to 18 yr) with equivocal diagnoses and correlated the NPD diagnostic score with clinical phenotypes and genotypes. MEASUREMENTS AND MAIN RESULTS Fifteen of the 50 children had NPD scores in the CF range. Eight of the 15 carried two CFTR mutations compared with only 5 of the 35 children with normal NPD scores (P = 0.01). They were significantly younger at evaluation and had recurrent lower respiratory tract infections, chronic productive coughs, and chronic Staphylococcus aureus colonization significantly more often than the 35 children with normal NPD results. CONCLUSIONS Evaluation of CFTR function in the nasal epithelium of children with inconclusive CF diagnoses can be a useful diagnostic tool and help clinicians to individualize therapeutic strategy.

312 Outcomes and factors associated with poor outcome of children with cystic fibrosis admitted to the intensive care unit

Prognosis of adult patients with cystic fibrosis (CF), admitted to intensive care unit (ICU), has improved. Few data are available for children. The aim is to describe clinical course and outcomes of CF children hospitalized in ICU. Baseline characteristics of children, reasons for admission in ICU, ventilatory support and outcomes at discharge from ICU were retrospectively analyzed. Non parametric statistical test compared data of survivors at ICU to those with poor outcome (death or lung transplantation in super emergency). From 2000 to 2013, 26 children, median age 13.4 years (1.9–17.6), were admitted to ICU (Necker-Enfants Malades, Paris). Before admission, 15 children (58%) had a non-invasive ventilation (NIV) and 23 (88%) were colonized with Pseudomonas aeruginosa . The median forced expiratory volume (FEV 1 ) was 32% (13–101). Eighteen children (69%) were admitted for respiratory exacerbation, NIV was initiated for 18 (69%) and 9 (35%) were intubated. Half of the 26 children had a poor outcome, 5 (19%) died and 8 (31%) needed urgent lung transplantation. Poor outcome-associated factors were female sex (p = 0.015), history of hemoptysis (p = 0.03), ventilation (p = 0.001) or nutritional (p = 0.017) support before ICU, chronic intravenous antibiotics use (p = 0.001), lower FEV 1 before ICU (27% (13–49) for poor outcome group and 40% (17–101) for survival group, p=0.036), admission for respiratory exacerbation (p = 0.030), hypercapnia (p = 0.010), metabolic acidosis (p = 0.007) and hypochloremia (p = 0.013). Our study highlights poor outcomes in children hospitalized in ICU and points factors associated with poor outcomes. This will help to improve indications of pediatric lung transplant.

142 Immunisation coverage in children with cystic fibrosis: a French multicenter survey

Objectives: To determine platelet aggregation capability for various variants of antigene system AB0 in patients with cystic fibrosis (CF). Methods: 55 CF children (homozygous and heterozygous on F508 del mutation) were enrolled. 46% girls and 54% boys had mild form of CF, 54% girls and 46% boys had severe form. We investigated the function of platelet aggregation with: thrombin, adenosinediphosphate (ADP) and arachidonic acid (AA). Results: Patients with severe form of CF most frequently (29%) had 0 (I); B (III) have not been revealed in this group, meanwhile 22.2% patients with mild form of CF had A (II) and AB (IV) have been revealed. Platelet aggregation with ADP has significant differences between blood groups A (II) and 0 (I), (p = 0.019). Values were ranged 2.5–97.5 percentile in patients with 0 (I) and 2.5−25 percentile in A (II). Data of aggregation with AA did not show significant differences between groups. Significant difference between homozygous F508 del and heterozygous F508 del patients was shown in aggregation with trombin (p = 0.03). There is a tendency to hyperaggregation in heterozygous patients meanwhile homozygous had both hypoaggregation and hyperaggregation. Difference on other tests between homozygous and heterozygous patients is not significant. Conclusion: First results of this study should be interpreted according to system ABO, severity of disease and genotype in patients with CF. These aspects play an important role for individual treatment.