Targeted PCR of Mucorales in pediatric bronchoalveolar lavage samples indicates low prevalence of airway colonization and sample contamination.

Mucorales are a large order of ubiquitous saprophytic zygomycete fungi and act as opportunistic pathogens in humans. In pediatric patients, little is known about the role of Mucorales in airway colonization and infection or their role as contaminants of respiratory samples. Currently, polymerase chain reaction (PCR) is the most sensitive mode of detection Mucorales in clinical specimen. In this study, we aimed to determine the prevalence of Mucorales in bronchoalveolar lavage samples (BAL) from a large, diverse group of pediatric patients. We performed commercial Mucorales PCR (MucorGenius®, Pathonostics, Maastricht, NL, USA) on 102 thawed BAL samples of 100 patients. Mucorales PCR was negative in all samples. Our data suggest that Mucorales spp. have a low prevalence in paediatric airways and do not frequently contaminate pediatric BAL samples.

Real-life impact of highly effective CFTR modulator therapy in children with cystic fibrosis.

Introduction: Recently, cystic fibrosis transmembrane regulator modulator therapy with elexacaftor/tezacaftor/ivacaftor has become available for children with cystic fibrosis (CF) carrying at least one F508del mutation. Objective: To assess the intermediate term effects of elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis in a real-world setting. Methods: We performed a retrospective analysis of records of children with cystic fibrosis, who started elexacaftor/tezacaftor/ivacaftor between 8/2020 and 10/2022. Pulmonary function tests, nutritional status, sweat chloride and laboratory data were assessed before, 3 and 6 months after the start of elexacaftor/tezacaftor/ivacaftor respectively. Results: Elexacaftor/tezacaftor/ivacaftor was started in 22 children 6-11 years and in 24 children 12-17 years. Twenty-seven (59%) patients were homozygous for F508del (F/F) and 23 (50%) patients were transitioned from ivacaftor/lumacaftor (IVA/LUM) or tezacaftor/ivacaftor (TEZ/IVA) to elexacaftor/tezacaftor/ivacaftor. Overall, mean sweat chloride concentration decreased by 59.3 mmol/L (95% confidence interval: -65.0 to -53.7 mmol/L, p < 0.0001) under elexacaftor/tezacaftor/ivacaftor. Sweat chloride concentration also decreased significantly after transition from IVA/LUM or TEZ/IVA to elexacaftor/tezacaftor/ivacaftor (-47.8 mmol/l; 95% confidence interval: -57.6 to -37.8 mmol/l, n = 14, p < 0.0001). Sweat chloride reduction was more marked in children with the F/F than in those with the F/MF genotype (69.4 vs 45.9 mmol/L, p < 0.0001). At 3 months follow-up, body-mass-index-z-score increased by 0.31 (95% CI, 0.2-0.42, p < 0.0001) with no further increase at 6 months. BMI-for-age-z-score was more markedly improved in the older group. Overall pulmonary function (percent predicted FEV1) at 3 months follow-up increased by 11.4% (95% CI: 8.0-14.9, p < 0.0001) with no further significant change after 6 months. No significant differences were noted between the age groups. Children with the F/MF genotype had a greater benefit regarding nutritional status and pulmonary function tests than those with the F/F genotype. Adverse events led to elexacaftor/tezacaftor/ivacaftor dose reduction in three cases and a temporary interruption of therapy in four cases. Conclusion: In a real-world setting, elexacaftor/tezacaftor/ivacaftor therapy had beneficial clinical effects and a good safety profile in eligible children with cystic fibrosis comparable to previously published data from controlled clinical trials. The positive impact on pulmonary function tests and nutritional status seen after 3 months of elexacaftor/tezacaftor/ivacaftor therapy was sustained at 6 months follow-up.

Biofilm infection of a central venous port-catheter caused by Mycobacterium avium complex in an immunocompetent child with cystic fibrosis.

BACKGROUND: Mycobacterium (M.) chimaera is a non-tuberculous mycobacterium (NTM) that belongs to M. avium complex (MAC). In patients with cystic fibrosis (CF), MAC can cause bronchopulmonary infections that can be prolonged and difficult to treat. MAC infections of sites other than the lungs or central catheters are rare and almost exclusively associated with immunodeficiency. CASE PRESENTATION: We present a case of an 8-year-old CF patient (delF508 homozygous) with recurrent pulmonary exacerbations, gradual clinical deterioration, B-symptoms (fever, fatigue, weight loss, night sweat), elevated transaminases and intermittent detection of M. chimaera in the sputum without radiological signs of NTM-associated lung disease with a central venous port-catheter. Next-generation sequencing (NGS) revealed M. chimaera port infection that was also confirmed by mycobacterial culture. The patient recovered within 4 weeks after removal of the catheter and initiation of MAC targeted antimicrobial therapy. Electron microscopy of the catheter illustrated the presence of mycobacteria in a biofilm. CONCLUSIONS: MAC central venous catheter infection needs to be considered in immunocompetent people. NGS is a valuable tool for rapid identification of rare infections. MAC capability of biofilm formation renders catheter removal the central therapeutic intervention for the clearance of the infection.

Multiple breath washout lung function reveals ventilation inhomogeneity unresponsive to mechanical assisted cough in patients with neuromuscular disease.

BACKGROUND: Respiratory involvement defines the clinical outcome of neuromuscular diseases (NMD). The lung clearance index (LCI) is a marker of lung ventilation inhomogeneity and indicates small airway disease. It is determined by mulitple breath washout lung function (MBW). The merit of LCI is undisputed for primary lung diseases like cystic fibrosis, but its role in NMD is unclear. METHODS: We investigated the role of MBW in patients with NMD and the effect of two different tracer gases and cough assist devices on the LCI. Patients and controls performed MBW with nitrogen (N2) and sulfur hexafluoride (SF6), whereas the latter analysis was repeated after the use of a cough assist device in the NMD group. LCI was compared to forced vital capacity (FVC) and peak cough flow (PCF). RESULTS: 24 NMD patients (12 Duchenne Muscular Dystrophy, 8 Spinal Muscular Atrophy, 4 other NMDs) and 15 healthy controls were enrolled. In the NMD group, overall LCI N2 was higher than LCI SF6 (9.67 ± 1.56 vs. 8.71 ± 1.47; mean ± SD; p < 0.033). In controls, LCI N2 did not differ significantly from LCI SF6 (7.03 ± 0.37 vs. 7.05 ± 0.67; p = 0.882). Both LCI N2 and LCI SF6 were significantly higher in NMD patients as in controls (9.67 ± 1.56 vs. 7.03 ± 0.37, p < 0.001, and 8.71 ± 1.478.65 vs. 7.05 ± 0.67, p < 0.001). In the NMD group, both LCI N2 and LCI SF6 showed a negative correlation to FVC (r = - 0.525; p = 0.008 and r = - 0.526; p = 0.008, respectively) and PCF (r = - 0.590; p = 0.002 and r = - 0.641; p = 0.001, respectively). LCI N2 and LCI SF6 correlated well in the NMD group. LCI SF6 did not change significantly after the use of the cough assist in NMD patients (n = 22; 8.65 ± 1.52 pre vs. 8.79 ± 2.03 post, p = 0.667). CONCLUSION: Lung involvement of patients with neuromuscular diseases goes beyond weakness of respiratory muscles. MBW with both N2 and SF6 is suitable to detect ventilation inhomogeneity in NMD patients with respiratory impairment. Cough assist devices with low to moderate pressure levels do not immediately improve the LCI.

Indications and outcome of home high-flow nasal therapy in children, a single-center experience.

High-flow nasal therapy (HFNT) is a safe and simple way to deliver humidified air and oxygen for respiratory support in infants and children. HFNT is well established in an inpatient setting, but home HFNT lacks evidence. In the current study, we studied characteristics and outcomes of pediatric patients with home HFNT. In a monocentric retrospective analysis of data for 10 years (April 2010-April 2020), patient characteristics from the time point of the first discharge from hospital with home HFNT-treatment and the subsequent course were analyzed. Patients were divided into three HFNT indication groups: (1) bronchopulmonary dysplasia (BPD), (2) upper airway obstruction (UAO), and (3) other indications. Forty patients received home HFNT in the study period. Seventeen patients were treated for BPD, 15 for UAO, and 8 had other indications. Twenty-two patients (55%) were successfully weaned from HFNT (12 [70.6%] BPD, 7 [46.7%] UAO, 3 [37.5%] other), while seven patients (17.5%) died during follow-up (4 BPD, 2 UAO, 1 other). Twenty-three patients (57.5%) required (intermittent) additional oxygen application (14 [82.4%] BPD, 6 [40%] UAO, 4 [50%] other). Weaning success and need for additional oxygen were significantly more probable in BPD patients compared to the UOA group. In conclusion, HFNT plays an increasing role in home treatment of respiratory insufficiency of various etiologies in childhood. It often represents a temporary intervention, especially for children with BPD but might also serve as long-term treatment for children in whom other forms of ventilatory support are not feasible or desired.