Upper and lower airway cultures in children with cystic fibrosis: Do not neglect the upper airways

AbstractBackgroundAirways of cystic fibrosis (CF) patients are colonised with bacteria early in life. We aimed to analyse differences between results of simultaneously taken upper airway (UAW) and lower airway (LAW) cultures, to describe clinical characteristics of patients with positive versus negative cultures and to follow up the patients with P. aeruginosa positive UAW cultures.MethodsBacteriological and clinical data from 157 children were collected during annual check up. The number of positive UAW and LAW cultures and correspondence between these results and clinical characteristics were analysed.ResultsPositive LAW and UAW cultures were found in 79.6% and 43.9% of patients respectively (p<0.001). Patients with positive LAW cultures were significantly older (11.9 vs. 9.8years, p<0.05) and had more LAW symptoms (73.6% vs. 46.7%, p<0.05), especially when P. aeruginosa was found. Patients with positive UAW cultures (especially S. aureus) had more nasal discharge (50.7% vs. 25.0%, p<0.001). In 65% of patients with positive UAW and negative LAW culture for P. aeruginosa the next LAW became P. aeruginosa positive.ConclusionUAW cultures and LAW cultures differ in children with CF and there are differences in clinical characteristics between patients with positive versus negative culture results. P. aeruginosa positive UAW cultures appeared to precede positive LAW cultures in a substantial part of patients, suggesting some kind of cross-infection between the UAW and LAW

Primary Posterior Tracheopexy in Esophageal Atresia Decreases Respiratory Tract Infections

Background: Esophageal atresia (EA) is often accompanied by tracheomalacia (TM). TM can lead to severe respiratory complaints requiring invasive treatment. This study aims to evaluate if thoracoscopic primary posterior tracheopexy (PPT) can prevent the potential sequelae of TM in patients with EA. Methods: A cohort study including all consecutive EA patients treated between 2014 and July 2019 at the Wilhelmina Children's Hospital was conducted. Two groups were distinguished: (group 1) all EA patients born between January 2014 and December 2016 and (group 2) all EA patients born between January 2017 and July 2019, after introduction of PPT. In the latter group, PPT was performed in EA patients with moderate (33–66%) or severe (67–100%) tracheomalacia, seen during preoperative bronchoscopy. Group differences were assessed using the Fisher's exact test for bivariate variables and the Mann–Whitney U-test for continuous variables. Results: A total of 64 patients were included in this study (28 patients in group 1; 36 patients in group 2). In group 2, PPT was performed in 14 patients. Respiratory tract infections (RTIs) requiring antibiotics within the first year of life occurred significantly less in group 2 (61 vs. 25%, p = 0.004). Brief resolved unexplained events (BRUEs) seemed to diminish in group 2 compared to group 1 (39 vs. 19%, p = 0.09). Conclusion: Thoracoscopic primary posterior tracheopexy decreases the number of respiratory tract infections in EA patients. The clinical impact of reducing RTIs combined with the minimal additional operating time and safety of PPT outweighs the risk of overtreatment

Airway Epithelial Cultures of Children with Esophageal Atresia as a Model to Study Respiratory Tract Disorders

Esophageal atresia (EA) is a rare birth defect in which respiratory tract disorders are a major cause of morbidity. It remains unclear whether respiratory tract disorders are in part caused by alterations in airway epithelial cell functions such as the activity of motile cilia. This can be studied using airway epithelial cell culture models of patients with EA. Therefore, the aim of this study was to evaluate the feasibility to culture and functionally characterize motile cilia function in the differentiated air–liquid interface cultured airway epithelial cells and 3D organoids derived from nasal brushings and bronchoalveolar lavage (BAL) fluid from children with EA. We demonstrate the feasibility of culturing differentiated airway epithelia and organoids of nasal brushings and BAL fluid of children with EA, which display normal motile cilia function. EA patient-derived airway epithelial cultures can be further used to examine whether alterations in epithelial functions contribute to respiratory disorders in EA

Rapid early increase in BMI is associated with impaired longitudinal growth in children with cystic fibrosis

Background: We aimed to assess whether final height in children with cystic fibrosis (CF) is affected by body mass index (BMI), BMI increase, pulmonary function, and cystic fibrosis-related diabetes (CFRD). Study design: A longitudinal, retrospective study was performed in a cohort of 57 patients with CF (30 boys, 27 girls) born between 1997 and 2001. Height and weight were recorded annually from ages 0.5 to 10 years and biannually up to the age of 18. Measurements were converted to height-for-age-adjusted-for-target-height (HFA-TH) and BMI-for-age z-scores. Analyses were performed using the independent t tests and the Pearson's correlation. Results: For both boys and girls, HFA-TH and BMI-for-age z-scores were significantly lower in the first year of life, these scores increased rapidly until the age of 11 and 8 years, respectively. In boys, HFA-TH z-scores declined during puberty, with subsequently significantly impaired final height (z-score, −0.56, n = 30, standard deviation [SD] = 0.81, P = 0.001). In girls, HFA-TH z-scores briefly declined after the age of 8 years, but then increased to a z-score of −0.21 (n = 27, SD = 0.87) at age 18, which is not significantly lower than the national average (P = 0.22). Pulmonary function and the presence of CFRD were not associated with final height. However, rapid BMI increase between ages 1 and 6 was negatively associated with final height in boys (n = 29, r =−0.420; P = 0.023) and girls (n = 25, r =−0.466; P = 0.019). Conclusions: In boys and girls, early BMI increase was associated with impaired final height. We suggest that early childhood serves as a “window” in which nutritional variations may program subsequent growth. Further refinement of nutritional strategies could be needed

Individual and group response of treatment with ivacaftor on airway and gut microbiota in people with cf and a s1251n mutation

Ivacaftor has been shown to restore the functionality of the S1251N (also known as c.3752G>A) mutated CFTR, which may cause alterations in both airway and gut physiology and micro-environment, resulting in a change of microbiota in these organs. The aim of the present study was to analyze the effects of ivacaftor on the microbial community composition of both airway and gut in subjects with CF carrying one S1251N mutation, using a 16S rRNA gene-based sequencing approach. In 16 subjects with CF, repetitive samples from airways and gut were collected just before, and 2 months after, and, for 8 patients, also 9 and 12 months after, start of ivacaftor. 16S rRNA based sequencing identified 344 operational taxonomical units (OTUs) in a total of 139 samples (35 nasopharyngeal, 39 oropharyngeal, 29 sputum, and 36 fecal samples). Ivacaftor significantly enhanced bacterial diversity and overall microbiota composition in the gut (p < 0.01). There were no significant changes in the overall microbial composition and alpha diversity in upper and lower airways of these patients after ivacaftor treatment. Treatment with ivacaftor induces changes in gut microbiota whereas airway microbiota do not change significantly over time

Genome composition of reassortants between MDV and <i>wt</i>l viruses identified by pyrosequencing.

<p>Genome composition of reassortants between MDV and <i>wt</i>l viruses identified by pyrosequencing.</p