Search

Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF) lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa) acquisition, which is of particular importance in the youngest patients. We aimed to determine the effectiveness of PVZ on microbiological outcomes in young children with CF. We conducted a retrospective case-control study to compare these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not (PVZ-; n = 140). One case was matched with at least three same-gender controls born the same year and month. Median (range) age at first Pa isolation was not statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2-33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4 [2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ- 41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not significantly differ between groups.Systematic PVZ use did not delay key pathogen acquisition in young children with CF. What is known: • Palivizumab is the only available monoclonal antibody against respiratory syncytial virus infection. • Whether or not it is useful in infants with cystic fibrosis remains controversial. What is new: • Palivizumab does not delay key pathogens (Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children with cystic fibrosis. • Palivizumab does not reduce healthcare consumption or improve growth during the first 3 years of life of young children with cystic fibrosis.

Viral respiratory tract infections are common during early childhood. How they impact cystic fibrosis lung disease history in young children is poorly known. The principal aim of our study was to determinate respiratory tract infections frequency in this cystic fibrosis young population. Secondary outcomes were nature of viral agents recovered and impact of such infections. We conducted a prospective cohort study of 25 children affected by cystic fibrosis and aged less than 2 years. Nasal samplings were taken systematically monthly or bimonthly with additional samples taken during respiratory tract infections episodes. Ten pathogens were tested by a combination of five duplex RT-PCRs or PCRs: influenza A and B, respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus/enterovirus (RV/EV)), coronavirus (HKU1, NL63, 229E and OC43), parainfluenza virus (1–4), adenovirus and bocavirus (Respiratory Multi-Well System MWS r-gene®, BioMerieux, Marcy l’Etoile, France). Cycle thresholds (CTs) were reported for all positive samples and considered positive for values below 40. Quantitative variables were compared using a nonparametric statistical test (Wilcoxon signed rank for paired comparisons). Pearson’s correlation coefficient (r) was used to assess relationships between two variables. Statistical analyses were performed using SAS v9.4 (SAS Institute, Cary, NC, USA) or GraphPad Prism V6.00 (GraphPad Software, La Jolla, CA, USA). The significance level was set at 0.05. The mean age at inclusion was 9.6 ± 6.7 months. The patients had 3.4 ± 1.7 respiratory tract infections episodes per child per year. Forty-four respiratory tract infections (69%) were associated with virus: rhinovirus and enterovirus (RV/EV) were implied in 61% of them and respiratory syncytial virus (RSV) in 14%. Only one patient required hospitalization for lower respiratory tract infections. 86% of the patients were treated by antibiotics for a mean of 13.8 ± 6.2 days. RSV infections (n = 6) were usually of mild severity. Respiratory tract infections in young children with cystic fibrosis were of mild severity, rarely requiring hospitalization. Unsurprisingly, RV/EV were the most frequent agents. RSV-related morbidity seems low in this population. This raises the question of the usefulness of RSV preventive medication in this young population.

Background Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. Methods/Design We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na+) transport in response to the Na+ channel inhibitor amiloride, and CFTR-mediated chloride (Cl-) secretion in response to isoproterenol, a β-agonist in a Cl- free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. Discussion A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling.