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Elexacaftor–tezacaftor–ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508delallele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing.

Background:It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity.Methods:Nasal airway secretions were collected from 140 children =3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFN?, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay.Results:Full-term children with HMPV and RSV infection had increased levels of nasal airway IFN?, CCL5, and IL-10 along with an elevation in Th1 (IFN?)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32?wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFN?, CCL5, and IL-10 relative to uninfected controls.Conclusion:Our study is the first to demonstrate that premature infants have defective IFN?, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity.

Background Rhinitis and obstructive sleep apnea (OSA) often coexist during childhood. To delineate this clinical association, we examined OSA severity and polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid-eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized that children with rhinitis have more REM-related breathing abnormalities.Methods We conducted a retrospective cross-sectional analysis of 145 children with PSG-diagnosed A. Outcomes included PSG parameters and obstructive apnea–hypopnea index (OAHI) during REM and non-REM. Linear multivariable models examined the joint effect of rhinitis and OSA parameters with control for potential confounders.Results Rhinitis was present in 43% of children with OSA (n = 63) but overall OAHI severity was unaffected by the presence of rhinitis. In contrast, OAHI during REM sleep in children with moderate-severe OSA was significantly increased subjects with rhinitis and OSA (44.1/hr; SE = 6.4) compared with those with OSA alone (28.2/hr; SE = 3.8).Conclusion Rhinitis is highly prevalent in children with OSA. Although OSA is not more severe in children with rhinitis, they do have a distinct OSA phenotype characterized by more REM-related OSA. Further research is needed to delineate the link between REM-sleep and the physiology of the nose during health and disease.