Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: A phase 2 proof-of-concept trial.

Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment. Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score. Clinical Trials Registration: NCT02654171.

A comparison of virtual bronchoscopy versus flexible bronchoscopy in the diagnosis of tracheobronchomalacia in children.

INTRODUCTION: Flexible bronchoscopy (FB) is the current gold standard for diagnosing tracheobronchomalacia. However, it is not always feasible and virtual bronchoscopy (VB), acquired from chest multi-detector CT (MDCT) scan is an alternative diagnostic tool. We determined the sensitivity, specificity, and positive and negative predictive values of VB compared to FB in diagnosing tracheobronchomalacia. METHODS: Children aged <18-years scheduled for FB and MDCT were recruited. FB and MDCT were undertaken within 30-min to 7-days of each other. Tracheobronchomalacia (mild, moderate, severe, very severe) diagnosed on FB were independently scored by two pediatric pulmonologists; VB was independently scored by two pairs (each pair = pediatric pulmonologist and radiologist), in a blinded manner. RESULTS: In 53 children (median age = 2.5 years, range 0.8-14.3) evaluated for airway abnormalities, tracheomalacia was detected in 37 (70%) children at FB. Of these, VB detected tracheomalacia in 20 children, with a sensitivity of 54.1% (95%CI 37.1-70.2), specificity = 87.5% (95%CI 60.4-97.8), and positive predictive value = 90.9% (95%CI 69.4-98.4). The agreement between pediatric pulmonologists for diagnosing tracheomalacia by FB was excellent, weighted κ = 0.8 (95%CI 0.64-0.97); but only fair between the pairs of pediatric pulmonologists/radiologists for VB, weighted κ = 0.47 (95%CI 0.23-0.71). There were 42 cases of bronchomalacia detected on FB. VB had a sensitivity = 45.2% (95%CI 30.2-61.2), specificity = 95.5% (95%CI 94.2-96.5), and positive predictive value = 23.2 (95%CI 14.9-34.0) compared to FB in detecting bronchomalacia. CONCLUSION: VB cannot replace FB as the gold standard for detecting tracheobronchomalacia in children. However, VB could be considered as an alternative diagnostic modality in children with symptoms suggestive of tracheobronchomalacia where FB is unavailable. Pediatr Pulmonol. 2017;52:480-486. © 2016 Wiley Periodicals, Inc.

Intermittent midline suprasternal neck mass caused by superior herniation of the thymus.

Neck masses in infants and children have a wide differential diagnosis. However, neck masses apparent only during raised intrathoracic pressure are rare with a limited number of causes, including superior herniation of the normal thymus, apical lung herniation, jugular phlebectasia and laryngocoele. These conditions can easily be differentiated from one another by imaging. We present an infant with intermittent suprasternal neck mass visible only during increased intrathoracic pressure, produced either by crying or straining. Diagnosis of superior herniation of the thymus into the neck was confirmed by ultrasonography with the characteristic sonographic appearances of the normal thymus as well as its shape, size and location. Ultrasonography should be the first imaging modality of choice. Management of superior herniation of the thymus into the neck should be conservative as the thymus naturally involutes with increasing age. Awareness of the differential diagnosis of neck swelling present only on Vasalva manoeuvre or increased intrathoracic pressure is important to prevent unnecessary tests, avoid radiation, biopsy and surgery.