Nasal intermittent positive pressure ventilation during less invasive surfactant administration in preterm infants: An open-label randomized controlled study.

INTRODUCTION: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV). OBJECTIVES: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP. MATERIALS AND METHODS: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25+0-31+6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO2/FiO2 ratio after LISA, and adverse effect rate. RESULTS: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456-1.671; p = .681). We found that the SpO2/FiO2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms. CONCLUSIONS: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA.

Developmental validation of the DNAscan™ Rapid DNA Analysis™ instrument and expert system for reference sample processing.

Since the implementation of forensic DNA typing in labs more than 20 years ago, the analysis procedures and data interpretation have always been conducted in a laboratory by highly trained and qualified scientific personnel. Rapid DNA technology has the potential to expand testing capabilities within forensic laboratories and to allow forensic STR analysis to be performed outside the physical boundaries of the traditional laboratory. The developmental validation of the DNAscan/ANDE Rapid DNA Analysis System was completed using a BioChipSet™ Cassette consumable designed for high DNA content samples, such as single source buccal swabs. A total of eight laboratories participated in the testing which totaled over 2300 swabs, and included nearly 1400 unique individuals. The goal of this extensive study was to obtain, document, analyze, and assess DNAscan and its internal Expert System to reliably genotype reference samples in a manner compliant with the FBI's Quality Assurance Standards (QAS) and the NDIS Operational Procedures. The DNAscan System provided high quality, concordant results for reference buccal swabs, including automated data analysis with an integrated Expert System. Seven external laboratories and NetBio, the developer of the technology, participated in the validation testing demonstrating the reproducibility and reliability of the system and its successful use in a variety of settings by numerous operators. The DNAscan System demonstrated limited cross reactivity with other species, was resilient in the presence of numerous inhibitors, and provided reproducible results for both buccal and purified DNA samples with sensitivity at a level appropriate for buccal swabs. The precision and resolution of the system met industry standards for detection of micro-variants and displayed single base resolution. PCR-based studies provided confidence that the system was robust and that the amplification reaction had been optimized to provide high quality results. The DNAscan integrated Expert System was examined as part of the Developmental Validation and successfully interpreted the over 2000 samples tested with over 99.998% concordant alleles. The system appropriately flagged samples for human review and failed both mixed samples and samples with insufficient genetic information. These results demonstrated the integrated Expert System makes correct allele calls without human intervention.

A disorder of surfactant metabolism without identified genetic mutations.

BACKGROUND: Surfactant metabolism disorders may result in diffuse lung disease in children. CASE PRESENTATION: We report a 3-years-old boy with dry cough, progressive hypoxemia, dyspnea and bilateral ground glass opacities at chest high-resolution computed tomography (HRCT) who had no variants in genes encoding surfactant proteins or transcription factors. Lung histology strongly suggested an abnormality of surfactant protein. A 7-month course of pulse intravenous high-dose methylprednisolone plus oral hydroxychloroquine and azithromycin led to gradual weaning from oxygen and oral steroids, and to improvement of cough and dyspnea. Over the follow-up period, hydroxychloroquine and azithromycin were not withdrawn as cough and dyspnea re-appeared at each attempt and disappeared at re-start. At 6 years of age chest HRCT still appeared unchanged, but clinical symptoms or signs were absent. CONCLUSIONS: In children suspected of inborn errors of pulmonary surfactant metabolism who do not have a recognized genetic mutation, lung biopsy with consistent histology may help physicians to address the definitive diagnosis.

Clinical application of nasal nitric oxide measurement in pediatric airway diseases.

Nitric oxide plays an important role in several physiological and pathophysiological processes in the respiratory tract. Different ways to measure nasal nitric oxide levels in children are currently available. The possibility of obtaining nasal nitric oxide measurement from relatively young children, combined with the availability of portable devices that can be used even in the office setting, opens new perspectives for nasal nitric oxide analysis in the pediatric daily practice. This review presents a synopsis about the current clinical applications of nasal nitric oxide measurement in the pediatric clinical practice. A total of 3,775 articles on the topic were identified, of which 883 duplicates were removed, and 2,803 were excluded based on review of titles and abstracts. Eighty-nine full text articles were assessed for eligibility and 32 additional articles were obtained from the reference lists of the retrieved studies. Since very low nasal nitric oxide levels are found in the majority of patients with primary ciliary dyskinesia, most publications support a central role for nasal nitric oxide to screen the disease, and indicate that it is a very helpful first-line tool in the real-life work-up in all age groups. Decreased nasal nitric oxide concentration is also typical of cystic fibrosis, even though nasal nitric oxide is not as low as in primary ciliary dyskinesia. In other upper airway disorders such as allergic rhinitis, rhinosinusitis, nasal polyposis, and adenoidal hypertrophy, clinical utility of nasal nitric oxide is still critically questioned and remains to be established. Since nNO determination is flow dependent, a general consensus from the major investigators in this area is highly desirable so that future studies will be performed with the same flow rate. A shared nNO methodology will enable to overcome the challenges that lie ahead in incorporating nNO measurement into the mainstream clinical setting of pediatric airway diseases.

Update on leukotriene receptor antagonists in preschool children wheezing disorders.

Asthma is the most common chronic disease in young children. About 40% of all preschool children regularly wheeze during common cold infections. The heterogeneity of wheezing phenotypes early in life and various anatomical and emotional factors unique to young children present significant challenges in the clinical management of this problem. Anti-inflammatory therapy, mainly consisting of inhaled corticosteroids (ICS), is the cornerstone of asthma management. Since Leukotrienes (LTs) are chemical mediators of airway inflammation in asthma, the leukotriene receptor antagonists (LTRAs) are traditionally used as potent anti-inflammatory drugs in the long-term treatment of asthma in adults, adolescents, and school-age children. In particular, montelukast decreases airway inflammation, and has also a bronchoprotective effect. The main guidelines on asthma management have confirmed the clinical utility of LTRAs in children older than five years. In the present review we describe the most recent advances on the use of LTRAs in the treatment of preschool wheezing disorders. LTRAs are effective in young children with virus-induced wheeze and with multiple-trigger disease. Conflicting data do not allow to reach definitive conclusions on LTRAs efficacy in bronchiolitis or post-bronchiolitis wheeze, and in acute asthma. The excellent safety profile of montelukast and the possibility of oral administration, that entails better compliance from young children, represent the main strengths of its use in preschool children. Montelukast is a valid alternative to ICS especially in poorly compliant preschool children, or in subjects who show adverse effects related to long-term steroid therapy.

Magnetic resonance imaging is an accurate and reliable method to evaluate non-cystic fibrosis paediatric lung disease.

BACKGROUND AND OBJECTIVE: Chest MRI is increasingly used to assess pulmonary diseases, but its utility compared with high-resolution computed tomography (HRCT) has never been evaluated in children using specific performance outcomes. The aim of this study was to assess the accuracy and reliability of MRI compared with HRCT in children with non-cystic fibrosis (CF) chronic lung disease. METHODS: Fifty subjects aged 5.9-20 years, with primary ciliary dyskinesia (n = 17), primary immunodeficiency (n = 17) or recurrent pneumonia (n = 16), underwent chest HRCT and MRI. The prevalence of lung abnormalities on HRCT was evaluated, and sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI versus HRCT were calculated. MRI and HRCT scans were also assessed using a modified Helbich score. RESULTS: Bronchiectasis, mucous plugging, peribronchial wall thickening, consolidation, bullae, abscesses and emphysema were detected by HRCT in 72, 68, 66, 60, 10, 8 and 8% of subjects, respectively. Sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI were good or excellent for most of the changes that were assessed. Median total Helbich scores for HRCT and MRI were 10 (range 0-20) and 10 (range 0-18), respectively. There was good-to-excellent agreement between the two techniques for all scores (r ≥ 0.8). A Bland-Altman plot confirmed this agreement between total scores (bias value: 0.2 ± 1.18; 95% limits of agreement of mean difference: -2.12-2.52). CONCLUSIONS: Chest MRI was equivalent to HRCT to determine the extent of lung disease in children with non-CF lung disease. The findings support the use of chest MRI as an alternative to HRCT in diagnostic pathways for paediatric chronic lung disorders.

Clinical application of exhaled nitric oxide measurement in pediatric lung diseases.

Fractional exhaled nitric oxide (FeNO) is a non invasive method for assessing the inflammatory status of children with airway disease. Different ways to measure FeNO levels are currently available. The possibility of measuring FeNO levels in an office setting even in young children, and the commercial availability of portable devices, support the routine use of FeNO determination in the daily pediatric practice. Although many confounding factors may affect its measurement, FeNO is now widely used in the management of children with asthma, and seems to provide significantly higher diagnostic accuracy than lung function or bronchial challenge tests. The role of FeNO in airway infection (e.g. viral bronchiolitis and common acquired pneumonia), in bronchiectasis, or in cases with diffuse lung disease is less clear. This review focuses on the most recent advances and the current clinical applications of FeNO measurement in pediatric lung disease.

Progression of lung disease in primary ciliary dyskinesia: is spirometry less accurate than CT?

Despite its extensive use, there is no evidence that spirometry is useful in the assessment of progression of lung disease in primary ciliary dyskinesia (PCD). We hypothesize that high-resolution computed tomography (HRCT) is a better indicator of PCD lung disease progression than spirometry. We retrospectively evaluated two paired spirometry and HRCT examinations from 20 PCD patients (age, 11.6 years; range, 6.5-27.5 years). The evaluations were performed in stable state and during unstable lung disease. HRCT scans were scored blind by two raters. Compared to the first assessment, at the second evaluation spirometry did not change while HRCT scores significantly worsened (P < 0.01). Age was significantly related to HRCT total (r = 0.5; P = 0.02) and bronchiectasis scores (r = 0.5; P = 0.02). At both evaluations, HRCT total score correlated with FEV(1) (r = -0.5, P = 0.01; r = -0.7, P = 0.001, respectively) and FVC Z scores (r = -0.6, P = 0.006; r = -0.7, P = 0.001, respectively), and bronchiectasis score was related to FEV(1) (r = -0.5, P = 0.03; r = -0.6; P = 0.002, respectively) and FVC Z scores (r = -0.6, P = 0.008; r = -0.7, P = 0.001, respectively). No relationship was found between the change in HRCT scores and the change in spirometry. In PCD, structural lung disease may worsen despite spirometry being stable.

Mixture interpretation: defining the relevant features for guidelines for the assessment of mixed DNA profiles in forensic casework.

Currently in the United States there is little direction for what constitutes sufficient guidelines for DNA mixture interpretation. While a standardized approach is not possible or desirable, more definition is necessary to ensure reliable interpretation of results is carried out. In addition, qualified DNA examiners should be able to review reports and understand the assumptions made by the analyst who performed the interpretation. Interpretation of DNA mixture profiles requires consideration of a number of aspects of a mixed profile, many of which need to be established by on-site, internal validation studies conducted by a laboratory's technical staff, prior to performing casework analysis. The relevant features include: criteria for identification of mixed specimens, establishing detection and interpretation threshold values, defining allele peaks, defining nonallele peaks, identifying artifacts, consideration of tri-allelic patterns, estimating the minimum number of contributors, resolving components of a mixture, determining when a portion of the mixed profile can be treated as a single source profile, consideration of potential additive effects of allele sharing, impact of stutter peaks on interpretation in the presence of a minor contributor, comparison with reference specimens, and some issues related to the application of mixture calculation statistics. Equally important is using sensible judgment based on sound and documented principles of DNA analyses. Assumptions should be documented so that reliable descriptive information is conveyed adequately concerning that mixture and what were the bases for the interpretations that were carried out. Examples are provided to guide the community. Interpretation guidelines also should incorporate strategies to minimize potential bias that could occur by making inferences based on a reference sample. The intent of this paper is to promote more thought, provide assistance on many aspects for consideration, and to support that more formalized mixture interpretation guidelines are developed.