Retrospective analysis of referrals for hypoxic challenge testing in children born preterm.

INTRODUCTION: Children with a history of bronchopulmonary dysplasia (BPD) may be at risk of hypoxaemia at altitude, such as during air travel. We have performed preflight hypoxic challenge testing (HCT) since 2006, incorporating British Thoracic Society (BTS) guidance since 2011, to determine which children may require oxygen during air travel. AIMS: We aimed to compare the outcome of HCTs in children with a history of BPD who met the 2011 BTS criteria and those who did not and, in addition to this, to interrogate the data for factors that may predict the outcome of HCT in this population. METHODS: We performed a retrospective analysis of data from HCTs of children with a history of BPD referred 2006-2020. Cases were excluded if the patient had a respiratory comorbidity, was still on oxygen therapy, if the test was a repeat or if the clinical record was incomplete. Descriptive and univariate analysis of the data was performed, and a binary logistic regression model was fitted. RESULTS: There were 79 HCTs, of which 24/79 (30%) did not meet BTS 2011 guidelines referral criteria. The analysis showed a greater proportion of desaturation in the group that did not meet criteria: 46% vs 27% (no statistical significance). Baseline oxygen saturations were higher in those who did not require oxygen during HCT and this variable was significant when adjusted for confounders. CONCLUSIONS: This study found that the current criteria for referral for preflight testing may incorrectly identify those most at risk and highlights the need for further investigation to ensure those most at risk are being assessed prior to air travel.

'It gives me more freedom': Family perspectives on travelling with children on nocturnal ventilation.

BACKGROUND: Children with neuromuscular weakness or central hypoventilation often require nocturnal ventilation. Children with these conditions are living longer and the numbers of children affected are increasing. The challenges associated with managing ventilation at home have been documented; however, there has been limited investigation into accessing wider experiences such as travel. Air travel, in particular, may be considered challenging for children with these conditions because oxygen levels are lower in airplane cabins than at sea levels. OBJECTIVE: We sought to understand experiences of and attitudes towards travel amongst families of children using nocturnal ventilation for neuromuscular weakness or central hypoventilation. METHODS: Two semi-structured interviews were conducted amongst participants enrolled in a trial of a new pre-flight assessment of their tolerance of reduced oxygen levels during flight (known as a hypoxic challenge test). Children participating in the trial were aged 19 months to 18 years. Parents were interviewed and provided proxy views for younger children, and older children were encouraged to present their own views during these interviews. One interview was conducted immediately after the assessment, and a second 3 months later. Data were analysed utilising the framework approach to thematic analysis. RESULTS: Seventeen families participated in the first interview with 14 of these families completing the follow-up interview. Three further families participated in the follow-up interview only. Here, we report three themes relating to participant experience of travel and how this is impacted by their condition. The three themes and their sub-themes were (1) insight into children's lives: hospital attendances, gaining knowledge and confidence, and child as a person; (2) travelling with your child: planes, trains and automobiles, rules of air travel, and uncertainty; and (3) the meaning of travel: normalisation, connection to extended family, expanded experiences, and freedom and equality. CONCLUSIONS: This population of children and their families aspire to travel but face challenges from clinical and social barriers. It is essential that we further our understanding of the physiological, social and cultural aspects of their experience to facilitate their access to broadened life experiences.

Genotype-related respiratory progression in Duchenne muscular dystrophy-A multicenter international study.

INTRODUCTION/AIMS: Mutations amenable to skipping of specific exons have been associated with different motor progression in Duchenne muscular dystrophy (DMD). Less is known about their association with long-term respiratory function. In this study we investigated the features of respiratory progression in four DMD genotypes relevant in ongoing exon-skipping therapeutic strategies. METHODS: This was a retrospective longitudinal study including DMD children followed by the UK NorthStar Network and international AFM Network centers (May 2003 to October 2020). We included boys amenable to skip exons 44, 45, 51, or 53, who were older than 5 years of age and ambulant at first recorded visit. Subjects who were corticosteroid-naive or enrolled in interventional clinical trials were excluded. The progression of respiratory function (absolute forced vital capacity [FVC] and calculated as percent predicted [FVC%]) was compared across the four subgroups (skip44, skip45, skip51, skip53). RESULTS: We included 142 boys in the study. Mean (standard deviation) age at first visit was 8.6 (2.5) years. Median follow-up was 3 (range, 0.3-8.3) years. In skip45 and skip51, FVC% declined linearly from the first recorded visit. From the age of 9 years, FVC% declined linearly in all genotypes. Skip44 had the slowest (2.7%/year) and skip51 the fastest (5.9%/year) annual FVC% decline. The absolute FVC increased progressively in skip44, skip45, and skip51. In skip53, FVC started declining from 14 years of age. DISCUSSION: The progression of respiratory dysfunction follows different patterns for specific genotype categories. This information is valuable for prognosis and for the evaluation of exon-skipping therapies.

Modified hypoxic challenge testing in children needing nocturnal ventilation: An observational study.

BACKGROUND: Guidelines for air passengers with respiratory disease focus on primary lung pathology. Little evidence exists to guide professionals advising children needing ventilatory support because of neuromuscular or central hypoventilation conditions; these children might risk hypoxia and hypercapnia if unable to mount an adequate hyperventilation response. OBJECTIVE: This study assessed the response to low ambient oxygen using a modified hypoxic challenge test. In addition to measuring pulse oximetry and response to supplementary oxygen, we also measured transcutaneous carbon dioxide and response to ventilatory support. METHODS: Twenty children on nocturnal ventilatory support aged 1.6-18 years were recruited in a pragmatic sample from outpatient clinics; 10 with neuromuscular weakness and 10 with central hypoventilation. Participants underwent a two-stage, modified hypoxic challenge test; a conventional stage, where oxygen alone was titrated according to SpO2, and a new stage, where participants used their routine ventilatory support with oxygen titrated if needed. Participants were interviewed to understand their experiences of testing and of air travel. RESULTS: Thirteen participants needed supplemental oxygen during the conventional stage, but only two did when using ventilatory support. Transcutaneous carbon dioxide remained within normal range for all participants, on or off ventilatory support. Whilst some participants found testing challenging, participants generally reported both testing and air travel to be valuable. CONCLUSIONS: Evaluating response to patients' usual ventilation through "fitness-to-fly" assessment aids decision making when considering whether children who receive nocturnal ventilation can travel by air, since for some using a ventilator reduces or avoids the need for supplemental oxygen.

"You're on mute!" Does pediatric CF home spirometry require physiologist supervision?

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has accelerated the move towards home spirometry monitoring, including in children. The aim of this study is to determine whether the remote supervision of spirometry by a physiologist improves the technical quality and failure rate of the maneuvers. METHOD: Children with cystic fibrosis who had been provided with NuvoAir home spirometers were randomly allocated to either supervised or unsupervised home spirometry following a detailed training session. Home spirometry was performed every 2 weeks for 12 weeks. Tests were assigned a quality factor (QF) using our laboratory grading system as per American Thoracic Society/European Respiratory Society standards, with tests marked from A to D, or Fail. In our laboratory, we aim for QF A in all spirometry tests, but report results of QF B or C with a cautionary note. QF A was, therefore, the primary outcome, and QF A-C, the secondary outcome. RESULTS: Sixty-one patients were enrolled; 166 measurements were obtained in the supervised group, and 153 in the unsupervised group. Significantly more measurements achieved QF A in the supervised compared to unsupervised group (89% vs. 74%; p = <0.001), while proportions reaching Grade A-C were similar (99% vs. 95%; p = 0.1). All significant declines in spirometry results had a clinical rather than technical reason. Family/patient feedback for both arms was very positive. CONCLUSION: These results suggest that home spirometry in children should ideally be remotely supervised by a physiologist, but acceptable results can be obtained if resources do not allow this, provided that training is delivered and results monitored according to our protocol.

Lung Clearance Index May Detect Early Peripheral Lung Disease in Sickle Cell Anemia.

Rationale: Chronic lung injury is common in sickle cell anemia (SCA) and worsens outcomes. Sensitive lung function tests might predict reversible disease that might benefit from therapeutic interventions. Objectives: To evaluate whether lung clearance index (LCI) (measuring global ventilation inhomogeneity), intraacinar ventilation inhomogeneity (Sacin), and conductive ventilation inhomogeneity (Scond) are more frequently abnormal than lung volumes in young people with SCA. Methods: Nitrogen multiple-breath washout, spirometry, and body plethysmography were cross-sectionally evaluated at steady state in subjects with SCA (hemoglobin SS) and healthy control subjects aged 8-21 years from London, United Kingdom. Results: Thirty-five patients (51% boys, mean ± SD age, 16.4 ± 3.5 yr) and 31 control subjects (48% boys; 16.2 ± 3.2 yr) were tested. There were significant differences between the study and control groups in mean LCI (mean difference, 0.42 units; 95% confidence interval [CI], 0.22 to 0.63; P = 0.0001), Sacin (mean difference, 0.014 units; 95% CI, 0.001 to 0.026; P = 0.04), forced expiratory volume in 1 second (FEV1) (mean difference, -0.79 z-scores; 95% CI, -1.28 to -0.30; P = 0.002), forced vital capacity (FVC) (mean difference, -0.80 z-scores; 95% CI, -1.28 to -0.31, P = 0.002), and total lung capacity (mean difference, -0.76 z-scores; 95% CI, -1.25 to -0.29, P = 0.002), but not in Scond and FEV1-to-FVC ratio. Whereas 29% (10 of 35) of patients had LCI > 95th percentile of control subjects, 23% (8 of 35) had abnormal FEV1 (<5th percentile of the reference population). Conclusions: LCI detected slightly more abnormalities than lung volumes in young people with SCA. Significant differences from control subjects in LCI and Sacin but not in Scond and FEV1-to-FVC ratio suggest that the lung function changes were most likely owing to patchy peripheral lung disease.

Respiratory Function and Sleep Disordered Breathing in Pediatric Duchenne Muscular Dystrophy.

BACKGROUND AND OBJECTIVES: The decline of respiratory function in Duchenne muscular dystrophy (DMD) is associated with sleep disordered breathing (SDB) and alteration of nocturnal gas exchange, first manifesting as nocturnal hypoventilation (NH). However, the correlation between the pulmonary function measured by spirometry (PFT) and the onset of SDB with or without NH is unclear. The aims of this study are to identify the prevalence and features of SDB and to investigate the relationship between lung function determined by forced vital capacity (FVC) and sleep abnormalities in a large pediatric DMD population. METHODS: This was a retrospective, single-center cohort study. FVC% predicted (FVC%) was calculated using predicted equations from the Global Lung Function Initiative. NH was defined by transcutaneous (tc) CO2 >50 mm Hg for >25% of total sleep time (TST), borderline NH by a mean tcCO2 between 45 and 50 mm Hg or tcCO2>50 mm Hg for ≤25% of TST, and clinically meaningful obstructive sleep apnea (OSA) by obstructive apnea-hypopnea index >5. The sensitivity, specificity, and positive and negative predictive values of FVC < 50% to indicate the presence of nocturnal hypoventilation were calculated. RESULTS: One hundred thirty-four patients underwent 284 sleep studies and 1222 PFT. The mean (SD) age at the first and the last sleep study was 12.9 (2.7) and 14.3 (2.6) years, respectively. Borderline NH (n = 31) was detected in both ambulant and early-nonambulant participants, while 100% of NH cases (n = 14) were nonambulant. NH was detected in 4 of the 14 patients despite an FVC >50%. Seventeen of the 26 patients with OSA presented with concomitant NH or borderline NH. FVC <50% was associated with NH indicating a sensitivity and specificity of 73% and 86%, respectively. Positive and negative predictive values were 32% and 97%, respectively. PFT showed a nonlinear, sudden FVC% decline in 18% of cases. DISCUSSION: FVC% <50 was associated with NH in close to a third of patients. CO2 elevation can be associated with obstructive/pseudo-obstructive events and was also observed in early nonambulant cases or in the presence of FVC >50%. These results are relevant for the clinical management of SDB.

Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy: A Single-Site Retrospective Longitudinal Study.

BACKGROUND: Corticosteroids (CSs) have prolonged survival and respiratory function in boys with Duchenne muscular dystrophy (DMD) when compared with CSs-naïve boys. RESEARCH QUESTION: The differential impact of frequently used CSs and their regimens on long-term (> 5 years) cardiorespiratory progression in children with DMD is unknown. STUDY DESIGN AND METHODS: This was a retrospective longitudinal study including children with DMD followed at Dubowitz Neuromuscular Centre, Great Ormond Street Hospital London, England, from May 2000 to June 2017. Patients enrolled in any interventional clinical trials were excluded. We collected patients' anthropometrics and respiratory (FVC, FVC % predicted and absolute FVC, and noninvasive ventilation requirement [NIV]) and cardiac (left ventricular shortening function [LVFS%]) function. CSs-naïve patients had never received CSs. Patients who were treated with CSs took either deflazacort or prednisolone, daily or intermittently (10 days on/10 days off) for > 1 month. Average longitudinal models were fitted for yearly respiratory (FVC % predicted) and cardiac (LVFS%) progression. A time-to-event analysis to FVC % predicted < 50%, NIV start, and cardiomyopathy (LVFS% < 28%) was performed in CS-treated (daily and intermittent) vs CS-naïve patients. RESULTS: There were 270 patients, with a mean age at baseline of 6.2 ± 2.3 years. The median follow-up time was 5.6 ± 3.5 years. At baseline, 263 patients were ambulant. Sixty-six patients were treated with CSs daily, 182 patients underwent CSs intermittent > 60% treatment, and 22 were CS-naïve patients. Yearly FVC % predicted declined similarly from 9 years (5.9% and 6.9% per year, respectively; P = .27) in the CSs-daily and CSs-intermittent groups. The CSs-daily group declined from a higher FVC % predicted than the CSs-intermittent group (P < .05), and both reached FVC % predicted < 50% and NIV requirement at a similar age, > 2 years later than the CS-naïve group. LVFS% declined by 0.53% per year in the CSs-treated group irrespective of the CSs regimen, significantly slower (P < .01) than the CSs-naïve group progressing by 1.17% per year. The age at cardiomyopathy was 16.6 years in the CSs-treated group (P < .05) irrespective of regimen and 13.9 years in the CSs-naïve group. INTERPRETATION: CSs irrespective of the regimen significantly improved respiratory function and delayed NIV requirement and cardiomyopathy.