Lung function and structure in Cystic Fibrosis infants one year after diagnosis by newborn screening.

Identifying early signs of lung disease reliably in asymptomatic infants with Cystic Fibrosis (CF) diagnosed by newborn screening (NBS) is a challenge. Very little is known about the origin and progression of lung disease in these infants hence there is uncertainty on best interventions to protect the lungs of these infants from functional and structural decline. This collaborative observational study aims to assess lung function and structure in CF NBS infants. Lung function tests (LFT) were performed in contemporaneous healthy controls and CF infants at 3 months and a year of age. In addition, CF infants underwent chest computed tomography (CT) at 1 year under general anaesthesia within 2 weeks of the LFTs. At a year, CF NBS infants had impaired lung function compared to contemporaneous healthy controls. However the percentage of CF NBS infants demonstrating what was considered abnormal lung function had reduced at a year of age compared to those with abnormal result at 3 months. Although some improvements were observed at 1- year LFTs, this was not universal using the different techniques. Some measurements improved, others remained stable and certainly none deteriorated. In terms of CT structural changes in CF NBS infants, fewer abnormalities were detected in our cohort compared to other reported studies and changes seen were mild. There was poor correlation between lung function and structure in this group of CF infants. To accurately detect CF infants with impaired lung function or structural abnormalities using important physiological and clinical determinants would play an important role in the management of these infants. This study could inform power calculation for future interventional studies using relevant clinical trial endpoints related to lung function and structure

Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year

BACKGROUND: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. METHODS: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. RESULTS: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. CONCLUSIONS: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes

Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of age?

Rationale: Sensitive outcome measures applicable in different centres to quantify and track early pulmonary abnormalities in infants with cystic fibrosis (CF) are needed both for clinical care and interventional trials. Chest CT has been advocated as such a measure yet there is no validated scoring system in infants. Objectives: The objectives of this study were to standardise CT data collection across multiple sites; ascertain the incidence of bronchial dilatation and air trapping in newborn screened (NBS) infants with CF at 1 year; and assess the reproducibility of Brody-II, the most widely used scoring system in children with CF, during infancy. Methods: A multicentre observational study of early pulmonary lung disease in NBS infants with CF at age 1 year using volume-controlled chest CT performed under general anaesthetic. Main results: 65 infants with NBS-diagnosed CF had chest CT in three centres. Small insignificant variations in lung recruitment manoeuvres but significant centre differences in radiation exposures were found. Despite experienced scorers and prior training, with the exception of air trapping, inter- and intraobserver agreement on Brody-II score was poor to fair (eg, interobserver total score mean (95% CI) κ coefficient: 0.34 (0.20 to 0.49)). Only 7 (11%) infants had a total CT score ≥12 (ie, ≥5% maximum possible) by either scorer. Conclusions: In NBS infants with CF, CT changes were very mild at 1 year, and assessment of air trapping was the only reproducible outcome. CT is thus of questionable value in infants of this age, unless an improved scoring system for use in mild CF disease can be developed

Noninvasive positive pressure ventilation for acute respiratory failure in children: a concise review

Noninvasive positive pressure ventilation (NPPV) refers to the delivery of mechanical respiratory support without the use of endotracheal intubation (ETI). The present review focused on the effectiveness of NPPV in children > 1 month of age with acute respiratory failure (ARF) due to different conditions. ARF is the most common cause of cardiac arrest in children. Therefore, prompt recognition and treatment of pediatric patients with pending respiratory failure can be lifesaving. Mechanical respiratory support is a critical intervention in many cases of ARF. In recent years, NPPV has been proposed as a valuable alternative to invasive mechanical ventilation (IMV) in this acute setting. Recent physiological studies have demonstrated beneficial effects of NPPV in children with ARF. Several pediatric clinical studies, the majority of which were noncontrolled or case series and of small size, have suggested the effectiveness of NPPV in the treatment of ARF due to acute airway (upper or lower) obstruction or certain primary parenchymal lung disease, and in specific circumstances, such as postoperative or postextubation ARF, immunocompromised patients with ARF, or as a means to facilitate extubation. NPPV was well tolerated with rare major complications and was associated with improved gas exchange, decreased work of breathing, and ETI avoidance in 22-100% of patients. High FiO2 needs or high PaCO2 level on admission or within the first hours after starting NPPV appeared to be the best independent predictive factors for the NPPV failure in children with ARF. However, many important issues, such as the identification of the patient, the right time for NPPV application, and the appropriate setting, are still lacking. Further randomized, controlled trials that address these issues in children with ARF are recommended

Shedding light into the black box of infant multiple‐breath washout

BACKGROUND Multiple-breath inert gas washout (MBW) is a sensitive technique to assess lung volumes and ventilation inhomogeneity in infancy. Poor agreement amongst commercially available setups and a lack of transparency in the underlying algorithms for the computation of infant MBW outcomes currently limit the widespread application of MBW as a surveillance tool in early lung disease. METHODS We determined all computational steps in signal processing and the calculation of MBW outcomes in the current infant WBreath/Exhalyzer D setup (Exhalyzer D device, Eco Medics AG; WBreath software version 3.28.0, ndd Medizintechnik AG; Switzerland). We developed a revised WBreath version based on current consensus guidelines and compared outcomes between the current (3.28.0) and revised (3.52.3) WBreath version. We analyzed 60 visits from 40 infants with cystic fibrosis (CF) and 20 healthy controls at 6 weeks and 1 year of age. RESULTS Investigation into the algorithms in WBreath 3.28.0 revealed discrepancies from current consensus guidelines, which resulted in a potential overestimation of functional residual capacity (FRC) and underestimation of lung clearance index (LCI). We developed a revised WBreath version (3.52.3), which overall resulted in 6.7% lower FRC (mean (SD) -1.78 (0.99) mL/kg) and 14.1% higher LCI (1.11 (0.57) TO) than WBreath version 3.28.0. CONCLUSION Comprehensive investigation into the signal processing and algorithms used for analysis of MBW measurements improves the transparency and robustness of infant MBW data. The revised software version calculates outcomes according to consensus guidelines. Future work is needed to validate and compare outcomes between infant MBW setups