Evaluating hypoxia during air travel in healthy infants.

Up to a third of ex-preterm infants flying near term exhibit pulse oxygen saturation (SpO2) of less than 85% during air travel. A hypoxia challenge test (HCT) is recommended to evaluate the requirement for in-flight supplemental O2. The validity of the HCT in healthy, term infants has not been reported. This study aimed to characterise the in-flight hypoxia response and the accuracy of the HCT to predict this response in healthy, term infants in the first year of life. Infants (n=24: (15 male)) underwent a HCT prior to commercial air travel during which parents monitored SpO2. Thirty-two flights were undertaken with six infants completing multiple flights. The median in-flight SpO2 nadir was 87% and significantly lower than the HCT SpO2 nadir (92%: p<0.001). Infants on seven flights recorded SpO2<85% with one infant recording a HCT with a SpO2 less than 85%. There was marked variability in the in-flight SpO2 in the six infants who undertook multiple flights, and for three of these infants, the SpO2 nadir was both above and below 85%. We report that in healthy term infants an in-flight SpO2 below 85% is common and can vary considerably between flights and that the HCT poorly predicts the risk of in-flight hypoxia (SpO2<85%). As it is common for healthy term infants to have SpO2 less than 85% during air travel further research is needed to clarify whether this is an appropriate cut-off in this age group.

Characterization of maximal respiratory pressures in healthy children.

BACKGROUND: Measurements of maximal voluntary inspiratory (PI(max)) and expiratory (PE(max)) pressures are used in the management of respiratory muscle disease. There is little data on the appropriate reference range, success rates, or repeatability of PI(max) and PE(max) in children or on methodological factors affecting test outcomes. OBJECTIVES: To determine PI(max) and PE(max) in healthy children and examine which published reference equations are best suited to a contemporary population. Secondary objectives were to assess within-test repeatability and the influence of lung volumes on PI(max) and PE(max). METHODS: Healthy children were prospectively recruited from the community on a volunteer basis and underwent spirometry, static lung volumes, and PI(max) and PE(max) testing. RESULTS: Acceptable and repeatable (to within 20%) PI(max) and PE(max) were obtained in 156 children, with 105 (67%) children performing both PI(max) and PE(max) measurements to within 10% repeatability. The reference equations of Wilson et al. [Thorax 1984;39:535-538] best matched our healthy Caucasian children. There was an inverse relationship between PI(max) and the percent of total lung capacity (TLC) at which the measurement was obtained (beta coefficient -0.96; 95% CI -1.52 to -0.39; p = 0.001), whereas at lung volumes of >80% TLC PE(max) was independent of lung volume (p = 0.26). CONCLUSION: We demonstrated that the Wilson et al. [Thorax 1984;39:535-538] reference ranges are most suited for contemporary Caucasian Australasian children. However, robust multiethnic reference equations for maximal respiratory pressures are required. This study suggests that 10% within-test repeatability criteria are feasible in clinical practice, and that the use of lung volume measurements will improve the quality of maximal respiratory pressure measurements.

Determining the time to maximal bronchodilator response in asthmatic children.

BACKGROUND: The interval between bronchodilator administration and post-bronchodilator lung function testing is critical for accurate interpretation of the bronchodilator response. The time course of this response in children is not well documented. We aimed to document the time taken to achieve maximal lung function following salbutamol inhalation. METHODS: Eighteen asthmatic children between 7 and 18 years of age with a history of bronchodilator responsiveness were recruited. Spirometry was performed before and at 0, 10, 15, 20, 40, 60, and 90 minutes after salbutamol inhalation 600 microg (Ventolin; GlaxoSmithKline) via a spacer (Volumatic; GlaxoSmithKline). RESULTS: Spirometric indices significantly increased after salbutamol inhalation (p < 0.001). The group median time to maximal response in forced expiratory volume in 1 second (FEV(1)) was 17.5 (10-60: 10th-90th centiles) minutes after salbutamol. The magnitude of group response in FEV(1) was significantly higher at 15 and 20 minutes than at 0 and 10 minutes post-salbutamol inhalation (repeat measures analysis of variance [ANOVA] on ranks; p < 0.05). CONCLUSION: We conclude that a minimal interval of 20 minutes, before re-testing spirometry, is required to document the maximal response to bronchodilators in the majority of asthmatic children.

Identifying pediatric lung disease: A comparison of forced oscillation technique outcomes.

RATIONALE: Increasing evidence suggests the forced oscillation technique (FOT) has the capacity to provide non-invasive monitoring and diagnosis of respiratory disease in young children. However, which FOT outcomes provide the most pertinent clinical information is currently unknown. The aim of this study was to determine which FOT outcomes were most sensitive for differentiating between health and specific childhood respiratory disease. METHODS: Respiratory impedance was measured using a commercial device (i2M, Chess Medical, Belgium) in children aged between 3 and 7 years, who had been diagnosed with either cystic fibrosis (N = 84), asthma (N = 99) or were born very preterm (N = 114). Z-scores were calculated for respiratory system resistance (Rrs) and reactance (Xrs) at 6, 8, and 10 Hz, the resonance frequency (Fres), frequency dependence (Fdep4-24 ), and area under the reactance curve (AX). Pairwise comparisons of the area under the receiver operating characteristic (ROC) curve were used to determine the most relevant FOT variables. RESULTS AND CONCLUSIONS: The FOT outcomes best able to discern between health and disease were Fres (P < 0.0001) in cystic fibrosis, Fres (P < 0.0001) in asthma and Xrs8 (P < 0.0001) in children born preterm. These findings suggest the utility of specific FOT outcomes is dependent on the respiratory disease being assessed. It is hoped that a disease-specific approach to interpreting FOT data can help further refine the FOT technique to aid in the diagnosis of children with pediatric respiratory disease.

Long-term medical and psychosocial outcomes in congenital diaphragmatic hernia survivors.

OBJECTIVE: Survival rates for congenital diaphragmatic hernia (CDH) are increasing. The long-term outcomes of CDH survivors were compared with a healthy control group to assess the morbidity for guidance of antenatal counselling and long-term follow-up programmes. PARTICIPANTS AND DESIGN: Participants born with CDH in Western Australia 1993-2008 were eligible with matched controls from the general population. Participants had comprehensive lung function tests, echocardiogram, low-dose chest CT scan and completed a Strengths and Difficulties Questionnaire (SDQ) and quality of life (QOL) questionnaire. RESULTS: 34 matched case-control pairs were recruited. Demographic data between groups were similar. Cases were smaller at follow-up (weight Z-score of -0.2vs0.3; p=0.03; height Z-score of -0.3vs0.6; p=0.01). Cases had lower mean Z-scores for forced expiratory volume in 1 s (FEV1) (-1.49 vs -0.01; p=0.004), FEV1/forced vital capacity (-1.92 vs -1.2; p=0.009) and forced expiratory flow at 25-75% (FEF25-75) (-1.18vs0.23; p=0.007). Cases had significantly worse respiratory mechanics using forced oscillation technique. Subpleural triangles architectural distortion, linear opacities and scoliosis on chest CT were significantly higher in cases. Prosthetic patch requirement was associated with worse lung mechanics and peak cough flow. Cases had significantly higher rates of gastro-oesophageal reflux disease (GORD) and GORD medication usage. Developmental delay was significantly higher in cases. More cases had a total difficulties score in the high to very high range (25% vs 0%, p=0.03) on the SDQ and reported lower objective QOL scores (70.2 vs 79.8, p=0.02). CONCLUSION: Survivors of CDH may have significant adverse long-term medical and psychosocial issues that would be better recognised and managed in a multidisciplinary clinic.

Definition of cutoff values for the hypoxia test used for preflight testing in young children with neonatal chronic lung disease.

BACKGROUND: The hypoxia test can be performed to identify potential hypoxia that might occur in an at-risk individual during air travel. In 2004, the British Thoracic Society increased the hypoxia test cutoff guideline from 85 to 90% in young children. The aim of this study was to investigate how well the cutoff values of 85% and 90% discriminated between healthy children and those with neonatal chronic lung disease (nCLD). METHODS: We performed a prospective, interventional study in young children with nCLD who no longer required supplemental oxygen and healthy control subjects. A hypoxia test (involving the administration of 14% oxygen for 20 min) was performed in all children, and the nadir in pulse oximetric saturation (Spo(2)) recorded. RESULTS: Hypoxia test results were obtained in 34 healthy children and 35 children with a history of nCLD. Baseline Spo(2) in room air was unable to predict which children would "fail" the hypoxia test. In those children < 2 years of age, applying a cutoff value of 90% resulted in 12 of 24 healthy children and 14 of 23 nCLD children failing the hypoxia test (p = 0.56), whereas a cutoff value of 85% was more discriminating, with only 1 of 24 healthy children and 6 of 23 nCLD children failing the hypoxia test (p = 0.048). CONCLUSION: In the present study, using a hypoxia test limit of 90% did not discriminate between healthy children and those with nCLD. A cutoff value of 85% may be more appropriate in this patient group. The clinical relevance of fitness to fly testing in young children remains to be determined.

Lung function trajectories throughout childhood in survivors of very preterm birth: a longitudinal cohort study.

BACKGROUND: Data on longitudinal respiratory follow-up after preterm birth in the surfactant era are scarce and of increasing importance, with concerns that preterm survivors are destined for early onset chronic obstructive airway disease. We aimed to comprehensively assess lung function longitudinally from early childhood to mid-childhood in very preterm children (≤32 weeks gestation), and to explore factors negatively impacting on lung function trajectories. METHODS: Preterm children (with and without bronchopulmonary dysplasia) and healthy term children as controls were studied. All preterm participants were born at 32 weeks' gestation or earlier at King Edward Memorial Hospital, Perth, WA, Australia, between 1997 and 2003. Bronchopulmonary dysplasia was defined as at least 28 days of supplemental oxygen requirement as assessed at 36 weeks' post-menstrual age. Spirometry, oscillatory mechanics, gas exchange, lung volumes, and respiratory symptoms were assessed at three visits, two in early childhood (4-8 years) and one in mid-childhood (9-12 years). CT of the chest was done in preterm children in mid-childhood. Respiratory symptoms were documented via questionnaire at each visit. Data were analysed longitudinally using linear mixed models. FINDINGS: 200 very preterm children (126 with bronchopulmonary dysplasia and 74 without bronchopulmonary dysplasia) and 67 healthy term control children attended 458 visits between age 4 and 12 years. Chest CT was done on 133 preterm children at a mean age of 10·9 (SD 0·6) years. Preterm children, with and without bronchopulmonary dysplasia, had declines in spirometry z-scores over time compared with controls: forced expiratory volume in 1 s (FEV1), forced expiratory flow at 25-75% of the pulmonary volume, and FEV1/forced vital capacity all declined by at least 0·1 z-score per year in children with bronchopulmonary dysplasia (all p<0·001). Respiratory mechanics and gas exchange also deteriorated over time in children with bronchopulmonary dysplasia (relative to term controls, respiratory system reactance at 8 Hz decreased by -0·05 z-score per year [95% CI -0·08 to -0·01; p=0·006] and diffusing capacity of the lungs for carbon monoxide decreased by -0·03 z-score per year [95% CI -0·06 to -0·01; p=0·048]). Preterm children with bronchial wall thickening on chest CT (suggestive of inflammation) had bigger decreases in spirometry outcomes through childhood. For example, children with bronchial wall thickening on chest CT had an FEV1 z-score decline of -0·61 (95% CI -1·03 to-0·19; p=0·005) more than those without. Similarly, children exposed to tobacco smoke, those with earlier gestation, or those requiring more neonatal supplemental oxygen declined at a faster rate. INTERPRETATION: Lung function trajectories are impaired in survivors of very preterm birth. Survivors with bronchopulmonary dysplasia, ongoing respiratory symptoms, or CT changes reflecting inflammation have the poorest trajectories and might be at increased risk of lung disease in later life. Close targeted pulmonary follow-up of these individuals is necessary. FUNDING: National Health and Medical Research Council grants APP634519, APP1073301 (to SJS), APP1077691 (to JJP), and APP1025550 (to GLH), Princess Margret Hospital Foundation, and Raine Medical Foundation.

Respiratory function and symptoms in young preterm children in the contemporary era.

OBJECTIVE: To determine the relationships between respiratory symptoms, lung function, and neonatal events in young preterm children. METHODS: Preterm children (<32 w gestation), classified as bronchopulmonary dysplasia (BPD) or non-BPD, and healthy term controls were studied. Lung function was measured by forced oscillation technique (respiratory resistance [Rrs] and reactance [Xrs]) and spirometry. Respiratory symptom questionnaires were administered. RESULTS: One hundred and fifty children (74 BPD, 44 non-BPD, 32 controls) 4-8 years were studied. Lung function (median Z-score [10,90th centile]) was significantly impaired in preterm children compared to controls for FVC (0.00 [-1.18, 1.76], 0.69 [-0.17,1.86]), FEV1 (-0.44 [-1.94, 1.11], 0.49 [-0.83, 2.51]), Xrs (-1.26 [-3.31, 0.11], -0.11 [-0.97, 0.73]), and Rrs (0.55 [-0.48, 1.82], 0.28 [-0.99, 0.96]). Only Xrs differed between the BPD and non-BPD (-1.51 [-3.59, -0.41], -0.89 [-2.64, 0.52]). The prevalence of recent respiratory symptoms (range: 32-36%) did not differ between BPD and non-BPD children. Supplemental O2 in hospital was positively associated with worsening Xrs and FEV1 . CONCLUSION: Preterm children have worse lung function than healthy controls. Only respiratory reactance differentiated between preterm children with and without BPD and was influenced by days of O2 in hospital. Pediatr Pulmonol. 2016;51:1347-1355. © 2016 Wiley Periodicals, Inc.

Respiratory impedance and bronchodilator responsiveness in healthy children aged 2-13 years.

BACKGROUND: The forced oscillation technique (FOT) can be used in children as young as 2 years of age and in those unable to perform routine spirometry. There is limited information on changes in FOT outcomes in healthy children beyond the preschool years and the level of bronchodilator responsiveness (BDR) in healthy children. We aimed to create reference ranges for respiratory impedance outcomes collated from multiple centers. Outcomes included respiratory system resistance (R(rs)) and reactance (X(rs)), resonant frequency (Fres), frequency dependence of R(rs) (Fdep), and the area under the reactance curve (AX). We also aimed to define the physiological effects of bronchodilators in a large population of healthy children using the FOT. METHODS: Respiratory impedance was measured in 760 healthy children, aged 2-13 years, from Australia and Italy. Stepwise linear regression identified anthropometric predictors of transformed R(rs) and X(rs) at 6, 8, and 10 Hz, Fres, Fdep, and AX. Bronchodilator response (BDR) was assessed in 508 children after 200 µg of inhaled salbutamol. RESULTS: Regression analysis showed that R(rs), X(rs), and AX outcomes were dependent on height and sex. The BDR cut-offs by absolute change in R(rs8), X(rs8), and AX were -2.74 hPa s L(-1), 1.93 hPa s L(-1), and -33 hPa s L(-1), respectively. These corresponded to relative and Z-score changes of -32%; -1.85 for R(rs8), 65%; 1.95 for X(rs8), and -82%; -2.04 for AX. CONCLUSIONS: We have established generalizable reference ranges for respiratory impedance and defined cut-offs for a positive bronchodilator response using the FOT in healthy children.