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Pre-Flight Hypoxemia Challenge Testing in Bronchopulmonary Dysplasia
Pediatrics
Abstract
Background and objectives:
Former premature infants with bronchopulmonary dysplasia (BPD) are at risk for hypoxemia during air travel, but it is unclear until what age. We aimed to determine pass rates for high altitude simulation testing (HAST) by age in children with BPD and identify risks for failure.
Methods:
Retrospective, observational analysis of HAST in children with BPD at Boston Children's Hospital, using interval censoring to estimate the time-to-event curve of first pass. Curves were stratified by neonatal risk factors. Pass was considered lowest Spo2 ≥ 90%, or ≥94% for subjects with ongoing pulmonary hypertension (PH).
Results:
Ninety four HAST studies were analyzed from 63 BPD subjects; 59 studies (63%) were passed. At 3 months corrected gestational age (CGA), 50% of subjects had passed; at 6 months CGA, 67% has passed; at 12 and 18 months CGA, 72% had passed; and at 24 months CGA, 85% had passed. Neonatal factors associated with delayed time-to-pass included postnatal corticosteroid use, respiratory support at NICU discharge, and tracheostomy. BPD infants who did not require respiratory support at 36 weeks were likely to pass (91%) at 6 months CGA. At 24 months, children least likely to pass included those with a history of PH (63%) and those discharged from the NICU with oxygen or respiratory support (71%).
Conclusions:
Children with BPD on respiratory support at 36 weeks should be considered for preflight hypoxemia challenges through at least 24 months CGA, and longer if they had PH or went home from NICU on respiratory support.
... Infant pulmonary function testing was performed at only 7.4% of centers and only for research purposes. High-altitude stimulation testing, used to determine whether infants are at risk for hypoxemia during air travel and performed by reducing the oxygen concentration to approximate the atmospheric pressure of a commercial airplane, 9 We also sought to characterize the methods of oxygen weaning and discharge criteria among centers in the BPD Collaborative ( Most centers report the use of a dedicated BPD Clinic, which reflects the importance of this sub-specialization within pediatric pulmonology. 12 However, even in centers with dedicated BPD clinics, care of these patients can occur in other subspecialty respiratory clinics, which may have differing resources. ...
Background
Bronchopulmonary dysplasia, a sequela of preterm birth, is the most common chronic respiratory disorder in infancy, and the second most common in children. Despite this, clinical care remains highly variable with guidelines supported by limited evidence, and do not provide specific guidance for timing of clinical follow‐up, echocardiography, modalities of pulmonary function testing, etc.
Objective/methods
To further our understanding of care delivery for BPD, we sought to describe outpatient care patterns at tertiary care centers through survey data from 27 well‐established BPD programs.
Results
We observed variability in referral patterns to outpatient BPD clinics, ancillary services provided, indications for follow‐up echocardiograms, availability of lung function testing, and criteria for discharge from care.
Conclusion
More comprehensive and detailed clinical guidelines similar to other pulmonary diseases such as asthma and cystic fibrosis should be developed to help standardize care and may improve long term outcomes.
... In situations where significant procedures are anticipated and PH remains prominently active, the consideration of ECMO as a back-up contingency plan may be warranted. (3) A hypoxic challenge test should be considered in those infants with BPD-PH once they have improved or resolved their underlying condition, and prior to elective nonmedical air travel [43]. (4) It is essential to offer parents comprehensive support, information, and training. ...
Purpose of review
Pulmonary hypertension (PH) is commonly observed in premature infants with bronchopulmonary dysplasia (BPD) and is associated with poor outcomes and increased mortality. This review explores the management of this intricate condition of the pulmonary vasculature, which exhibits heterogeneous effects and may involve both arterial and postcapillary components.
Recent findings
Current management of BPD-PH should focus on optimizing ventilatory support, which involves treatment of underlying lung disease, transitioning to a chronic phase ventilation strategy and evaluation of the airway. Data on management is limited to observational studies. Diuretics are considered a part of the initial management, particularly in infants with right ventricular dilation. In many cases, pulmonary vasodilator therapy is required to induce pulmonary arterial vasodilation, reduce right ventricular strain, and prevent coronary ischemia and heart failure. Echocardiography plays a pivotal role in guiding treatment decisions and monitoring disease progression.
Summary
BPD-PH confers a heightened risk of mortality and long-term cardio-respiratory adverse outcomes. Echocardiography has been advocated for screening, while catheterization allows for confirmation in select more complex cases. Successful management of BPD-PH requires a multidisciplinary approach, focusing on optimizing BPD treatment and addressing underlying pathologies.
... Similar approaches to investigate the response of the respiratory system under stressful conditions in a standardized way could also be useful in the early days of life. Routine pulse oximetry, polysomnography (sleep study), hypoxia testing, and blood gas analysis are other techniques for monitoring and studying lung pathophysiology [40]. New tools for continuous pulmonary monitoring and monitoring oxygenation indices could be integrated into future multimodal assessments. ...
Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive treatment available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cell-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to high-risk premature infants. Hence, we need easy-to-use noninvasive tools for a standardized, precise, and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and we make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).
... Similar approaches to investigate the response of the respiratory system under stressful conditions in a standardized way could also be useful in the early days of life. Routine pulse oximetry, polysomnography (sleep study), hypoxia testing, and blood gas analysis are other techniques for monitoring and studying lung pathophysiology [40]. New tools for continuous pulmonary monitoring and oxygenation indices could be integrated into future multimodal assessments. ...
Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD, due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive cure available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cells-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to higher-risk subpopulations of premature infants. Hence the need for easy-to-use noninvasive tools for a standardized, precise and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).
Objective
The long-term morbidity among children with severe bronchopulmonary dysplasia who require tracheostomy (tBPD) relative to those without tracheostomy (sBPD) is not well characterized. We compared childhood lung function and neurodevelopmental outcomes in tBPD and sBPD.
Study design
Retrospective case-control study of N = 49 tBPD and N = 280 sBPD subjects in Boston Children’s Hospital Preterm Lung Patient Registry and medical record. We compared NICU course, childhood spirometry, and neurodevelopmental testing.
Result
tBPD subjects were more likely than sBPD to be Black, have pulmonary hypertension, and have subglottic stenosis. tBPD subjects had lower maximal childhood FEV1 % predicted (β = −0.14) and FEV1/FVC (β = −0.08); spirometry curves were more likely to suggest fixed extrathoracic obstruction. tBPD subjects had greater cognitive and motor delays <24 months, and greater cognitive delays >24 months.
Conclusion
Compared to subjects with sBPD who did not require tracheostomy, tBPD subjects suffer from increased long-term impairment in respiratory function and neurodevelopment.
Background
Survivors of prematurity are at risk for abnormal childhood lung function. Few studies have addressed trajectories of lung function and risk factors for abnormal growth in childhood. This study aims to describe changes in lung function in a contemporary cohort of children born preterm followed longitudinally in pulmonary clinic for post-prematurity respiratory disease and to assess maternal and neonatal risk factors associated with decreased lung function trajectories.
Methods
Observational cohort of 164 children born preterm ≤ 32 weeks gestation followed in pulmonary clinic at Boston Children’s Hospital with pulmonary function testing. We collected demographics and neonatal history. We used multivariable linear regression to identify the impact of neonatal and maternal risk factors on lung function trajectories in childhood.
Results
We identified 264 studies from 82 subjects with acceptable longitudinal FEV 1 data and 138 studies from 47 subjects with acceptable longitudinal FVC and FEV 1 /FVC data. FEV 1 % predicted and FEV 1 /FVC were reduced compared to childhood norms. Growth in FVC outpaced FEV 1 , resulting in an FEV 1 /FVC that declined over time. In multivariable analyses, longer duration of mechanical ventilation was associated with a lower rate of rise in FEV 1 % predicted and greater decline in FEV 1 /FVC, and postnatal steroid exposure in the NICU was associated with a lower rate of rise in FEV 1 and FVC % predicted. Maternal atopy and asthma were associated with a lower rate of rise in FEV 1 % predicted.
Conclusions
Children with post-prematurity respiratory disease demonstrate worsening obstruction in lung function throughout childhood. Neonatal risk factors including exposure to mechanical ventilation and postnatal steroids, as well as maternal atopy and asthma, were associated with diminished rate of rise in lung function. These results may have implications for lung function trajectories into adulthood.
Abstract After undergoing liver transplantation, children are susceptible to oral lesions due to immunosuppressant drugs that are needed to maintain the transplant. In this context, it is important to understand how disease characteristics and age at transplantation influence the development of these lesions. Monitoring of lesions begins after transplantation and children are usually observed by a specialist in stomatology at periodic visits. Consequently, lesion development is estimated to occur between two observed times, and this is characterized as interval-censored data. However, in clinical practice, it is common to assume the moment of observation as the time of event occurrence, thereby excluding interval-censored data. Here, we discuss the impact of excluding interval-censored mechanisms in statistical analyses by using simulation studies to consider differences in sample sizes and amplitudes between observed intervals. Then, application studies are presented which use a data set from a prospective study that was conducted to investigate oral lesions in patients after liver transplantation at the A.C.Camargo Cancer Center in Brazil between 2013 and 2016 and a data set involving recurrent ovarian cancer in patients diagnosed with high-grade serous carcinoma at the A.C.Camargo Cancer Center between 2003 and 2016.
The package icenReg provides classic survival regression models for interval-censored data. We present an update to the package that extends the parametric models into the Bayesian framework. Core additions include functionality to define the regression model with the standard regression syntax while providing a custom prior function. Several other utility functions are presented that allow for simplified examination of the posterior distribution.
Background:
Preflight hypoxia challenge testing (HCT) in a body plethysmograph has previously been done only on infants >3 months of corrected gestational age (CGA). This study aims to determine the earliest fit-to-fly age by testing neonates <1 week old.
Methods:
A prospective observational study was carried out on 3 groups of infants: healthy term infants ≤7 days old, preterm infants (≥34 weeks CGA) 2 to 3 days before discharge, and preterm infants with bronchopulmonary dysplasia (BPD). HCT was conducted using a body plethysmograph with a 15% fraction of inspired oxygen. The oxygen saturation (Spo2) test fail point was <85%.
Results:
Twenty-four term (mean CGA 40 weeks), 62 preterm (37 weeks), and 23 preterm with BPD (39.5 weeks) infants were tested. One term infant (4.2%) and 12 preterm infants without BPD (19.4%) failed. Sixteen (69.3%) preterm infants with BPD failed (P < .001), with a median drop in Spo2 of 16%. At 39 weeks CGA, neither preterm infants without BPD nor term infants had an Spo2 <85%. However, 7 of 12 term infants with BPD failed the HCT.
Conclusions:
Term and preterm infants without BPD born at >39 weeks CGA do not appear to be likely to desaturate during a preflight HCT and so can be deemed fit to fly according to current British Thoracic Society Guidelines.
With improved survival rates, short- and long-term respiratory complications of premature birth are increasing, adding significantly to financial and health burdens in the United States. In response, in May 2010, the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded a 5-year $18.5 million research initiative to ultimately improve strategies for managing the respiratory complications of preterm and low birth weight infants. Using a collaborative, multi-disciplinary structure, the resulting Prematurity and Respiratory Outcomes Program (PROP) seeks to understand factors that correlate with future risk for respiratory morbidity.
The PROP is an observational prospective cohort study performed by a consortium of six clinical centers (incorporating tertiary neonatal intensive care units [NICU] at 13 sites) and a data-coordinating center working in collaboration with the NHLBI. Each clinical center contributes subjects to the study, enrolling infants with gestational ages 23 0/7 to 28 6/7 weeks with an anticipated target of 750 survivors at 36 weeks post-menstrual age. In addition, each center brings specific areas of scientific focus to the Program. The primary study hypothesis is that in survivors of extreme prematurity specific biologic, physiologic and clinical data predicts respiratory morbidity between discharge and 1 year corrected age. Analytic statistical methodology includes model-based and non-model-based analyses, descriptive analyses and generalized linear mixed models.
PROP incorporates aspects of NICU care to develop objective biomarkers and outcome measures of respiratory morbidity in the <29 week gestation population beyond just the NICU hospitalization, thereby leading to novel understanding of the nature and natural history of neonatal lung disease and of potential mechanistic and therapeutic targets in at-risk subjects.
Clinical Trials.gov NCT01435187 .
This article summarises the key points from the 2011 British Thoracic Society (BTS) recommendations on managing passengers with respiratory disease planning air travel. The guidance aims to provide practical advice for respiratory specialists in secondary care and serves as a valuable reference for other healthcare professionals managing these patients. A greater awareness of the challenges posed by air travel will allow improved clinical assessment and practical advice to encourage patients to fly safely wherever possible.
To assess the response of healthy infants to airway hypoxia (15% oxygen in nitrogen).
Interventional study.
Infants' homes and paediatric ward.
34 healthy infants (20 boys) born at term; mean age at study 3.1 months. 13 of the infants had siblings whose deaths had been ascribed to the sudden infant death syndrome.
Respiratory variables were measured in room air (pre-challenge), while infants were exposed to 15% oxygen (challenge), and after infants were returned to room air (post-challenge).
Baseline oxygen saturation as measured by pulse oximetry, frequency of isolated and periodic apnoea, and frequency of desaturation (oxygen saturation < or = 80% for > or = 4 s). Exposure to 15% oxygen was terminated if oxygen saturation fell to < or = 80% for > or = 1 min.
Mean duration of exposure to 15% oxygen was 6.3 (SD 2.9) hours. Baseline oxygen saturation fell from a median of 97.6% (range 94.0% to 100%) in room air to 92.8% (84.7% to 100%) in 15% oxygen. There was no correlation between baseline oxygen saturation in room air and the extent of the fall in baseline oxygen saturation on exposure to 15% oxygen. During exposure to 15% oxygen there was a reduction in the proportion of time spent in regular breathing pattern and a 3.5-fold increase in the proportion of time spent in periodic apnoea (P < 0.001). There was an increase in the frequency of desaturation from 0 episodes per hour (range 0 to 0.2) to 0.4 episodes per hour (0 to 35) (P < 0.001). In 4 infants exposure to hypoxic conditions was ended early because of prolonged and severe falls in oxygen saturation.
A proportion of infants had episodes of prolonged (< or = 80% for > or = 1 min) or recurrent shorter (< or = 80% for > or = 4 s) desaturation, or both, when exposed to airway hypoxia. The quality and quantity of this response was unpredictable. These findings may explain why some infants with airway hypoxia caused by respiratory infection develop more severe hypoxaemia than others. Exposure to airway hypoxia similar to that experienced during air travel or on holiday at high altitude may be harmful to some infants.
For right-censored data perhaps the most commonly used tests are weighted logrank tests, such as the logrank and Wilcoxon-type tests. In this paper we review several generalizations of those weighted logrank tests to interval-censored data and present an R package, interval, to implement many of them. The interval package depends on the perm package, also presented here, which performs exact and asymptotic linear permutation tests. The perm package performs many of the tests included in the already available coin package, and provides an independent validation of coin. We review analysis methods for interval-censored data, and we describe and show how to use the interval and perm packages.
Increasing numbers of infants and children journey by aeroplane, or travel to high altitude destinations, for example, on holiday or as part of a population migration. Most are healthy, although increasingly children may be transported by aeroplane or helicopter specifically to obtain treatment for severe illness or injury. It is therefore useful to review the effects of altitude, and their relevance to children who undertake flights or travel to, or at high altitudes, particularly those with acute and chronic medical conditions.
The low oxygen environment during air travel may result in hypoxia in patients with respiratory disease. However, little information exists on the oxygen requirements of infants with respiratory disease planning to fly. A study was undertaken to identify the clinical factors predictive of an in-flight oxygen requirement from a retrospective review of hypoxia challenge tests (inhalation of 14-15% oxygen for 20 minutes) in infants referred for fitness to fly assessment.
Data from 47 infants (median corrected age 1.4 months) with a history of neonatal lung disease but not receiving supplemental oxygen at the time of hypoxia testing are reported. The neonatal and current clinical information of the infants were analysed in terms of their ability to predict the hypoxia test results.
Thirty eight infants (81%) desaturated below 85% and warranted prescription of supplemental in-flight oxygen. Baseline oxygen saturation was >95% in all infants. Age at the time of the hypoxia test, either postmenstrual or corrected, significantly predicted the outcome of the hypoxia test (odds ratio 0.82; 95% confidence intervals 0.62 to 0.95; p = 0.005). Children passing the hypoxia test were significantly older than those requiring in-flight oxygen (median corrected age (10-90th centiles) 12.7 (3.0-43.4) v 0 (-0.9-10.9) months; p < 0.0001).
A high proportion of ex-preterm infants not currently requiring supplemental oxygen referred for fitness-to-fly assessment and less than 12 months corrected age are at a high risk of requiring in-flight oxygen. Referral of this patient group for fitness to fly assessment including a hypoxia test may be indicated.
Commercial aircrafts cruise between 9150 and 13000 m above sea level, with a cabin pressure equivalent to 1530–2440 m at which passengers breathe the equivalent of 15–17% of fractional inspired oxygen (FiO2) at sea level.
British Thoracic Society recommendations for passengers with chronic respiratory disorders planning air travel1 suggest that infants and young children unable to perform spirometry, with a history of neonatal respiratory disease consult a paediatrician and a hypoxia test be considered. The recommended hypoxia test method in young children is to place the child in a body plethysmograph while seated on the parent’s lap and introduce nitrogen until FiO2 equals 15%. This method relies on equipment not readily available outside the tertiary hospital setting. We have reported a review of hypoxia testing in …
Background:
In the United States, approximately 12,000 preterm infants are diagnosed with bronchopulmonary dysplasia (BPD) and many of these infants require supplemental oxygen after initial hospital discharge. In children with BPD we sought to identify factors associated with supplemental oxygen use after initial hospital discharge, factors associated with duration of supplemental oxygen use, and methods used to wean off supplemental oxygen in the home environment.
Methods:
All subjects (n = 420) with the diagnosis of BPD were recruited from a single center Bronchopulmonary Dysplasia Clinic between 2008 and 2013. Subject information was obtained from patient history records, patient demographics, and caregiver questionnaires.
Results:
Younger gestational age and having a Nissen fundoplication were associated with home supplemental oxygen use in subjects with BPD. Of the 154 subjects who received supplemental oxygen at home, 38% received flows ≤1/8 LPM, 30% received flows >1/8 LPM and ≤1/4 LPM, 21% received flows >1/4 LPM and ≤1/2 LPM, and 11% received flows >1/2 LPM. Among subjects receiving ≤1/8 LPM of oxygen, the median age of weaning off oxygen was 10.1 months, but increased depending on level of oxygen flow at initial outpatient visit. Of the 137 subjects weaned off of oxygen during the study period, weaning was not supervised by a physician in 32.1% of subjects.
Conclusion:
Home supplemental oxygen use is common in infants diagnosed with BPD. In this study, the median age of weaning off supplemental oxygen was 10.1 months after initial hospital discharge. Unsupervised weaning of supplemental oxygen occurred in 32.1% of subjects with BPD. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.
Hypoxic episodes are troublesome components of bronchopulmonary dysplasia (BPD) in preterm infants. Immature respiratory control seems to be the major contributor, superimposed on abnormal respiratory function. Relatively short respiratory pauses may precipitate desaturation and bradycardia. This population is predisposed to pulmonary hypertension; it is likely that pulmonary vasoconstriction also plays a role. The natural history has been well-characterized in the preterm population at risk for BPD; however, the consequences are less clear. Proposed associations of intermittent hypoxia include retinopathy of prematurity, sleep disordered breathing, and neurodevelopmental delay. Future study should address whether these associations are causal relationships.
Patients with chronic lung disease may have mild hypoxemia at sea-level. Some of these cases may go unrecognized, and even among those who are known to be hypoxemic, some do not use supplemental oxygen. During air travel in a hypobaric hypoxic environment, compensatory pulmonary mechanisms may be inadequate in patients with lung disease despite normal sea-level oxygen requirements. In addition, compensatory cardiovascular mechanisms may be less effective in some patients who are unable to increase cardiac output. Air travel also presents an increased risk of venous thromboembolism. Patients with cystic lung disease may also be at increased risk of pneumothorax. Although overall this risk appears to be relatively low, should a pneumothorax occur, it could present a significant challenge to the patient with chronic lung disease, particularly if hypoxemia is already present. As such, a thorough assessment of patients with chronic lung disease and cardiac disease who are contemplating air travel should be performed. The duration of the planned flight, the anticipated levels of activity, comorbid illnesses and the presence of risk factors for venous thromboembolism are important considerations. Hypobaric hypoxic challenge testing reproduces an environment most similar to that encountered during actual air-travel; however, it is not widely available. Assessment for hypoxia is otherwise best performed using a normobaric hypoxic challenge test. Patients in need of supplemental oxygen need to contact the airline and request this accommodation during flight. They should also be advised on arranging portable oxygen concentrators prior to air travel, and a discussion of the potential risks of travel should take place.
Air travel poses medical challenges to passengers with respiratory disease, principally because of exposure to a hypobaric environment. In 2002 the British Thoracic Society published recommendations for adults and children with respiratory disease planning air travel, with a web update in 2004. New full recommendations and a summary were published in 2011, containing key recommendations for the assessment of high-risk patients and identification of those likely to require in-flight supplemental oxygen. This paper highlights the aspects of particular relevance to primary care practitioners with the following key points: (1) At cabin altitudes of 8000 feet (the usual upper limit of in-flight cabin pressure, equivalent to 0.75 atmospheres) the partial pressure of oxygen falls to the equivalent of breathing 15.1% oxygen at sea level. Arterial oxygen tension falls in all passengers; in patients with respiratory disease, altitude may worsen preexisting hypoxaemia. (2) Altitude exposure also influences the volume of any air in cavities, where pressure x volume remain constant (Boyle's law), so that a pneumothorax or closed lung bulla will expand and may cause respiratory distress. Similarly, barotrauma may affect the middle ear or sinuses if these cavities fail to equilibrate. (3) Patients with respiratory disease require clinical assessment and advice before air travel to: (a) optimise usual care; (b) consider contraindications to travel and possible need for in-flight oxygen; (c) consider the need for secondary care referral for further assessment; (d) discuss the risk of venous thromboembolism; and (e) discuss forward planning for the journey.
Background:
Limited data are available on the effects of air travel in patients with pulmonary hypertension (PH), despite their risk of physiologic compromise. We sought to quantify the incidence and severity of hypoxemia experienced by people with PH during commercial air travel.
Methods:
We recruited 34 participants for a prospective observational study during which cabin pressure, oxygen saturation (Sp O 2 ), heart rate, and symptoms were documented serially at multiple predefined time points throughout commercial flights. Oxygen desaturation was defined as SpO2, <85%.
Results:
Median flight duration was 3.6 h (range, 1.0-7.3 h). Mean ± SD cabin pressure at cruising altitude was equivalent to the pressure 1,968 ± 371 m (6,456 ± 1,218 ft) above sea level (ASL)(maximum altitude 5 2,621 m [8,600 ft] ASL). Median change in Sp O 2 from sea level to cruising altitude was 2 4.9% (range, 2.0% to 2 15.8%). Nine subjects (26% [95% CI, 12%-38%]) experienced oxygen desaturation during flight (minimum Sp O 2 5 74%). Thirteen subjects (38%) reported symptoms during flight, of whom five also experienced desaturations. Oxygen desaturation was associated with cabin pressures equivalent to . 1,829 m (6,000 ft) ASL, ambulation, and flight duration(all P values , .05).
Conclusions:
Hypoxemia is common among people with PH traveling by air, occurring in one in four people studied. Hypoxemia was associated with lower cabin pressures, ambulation during flight, and longer flight duration. Patients with PH who will be traveling on flights of longer duration or who have a history of oxygen use, including nocturnal use only, should be evaluated for supplemental in-flight oxygen.
During air flight, cabin pressurisation produces an effective fraction of inspired oxygen (FiO(2)) of 0.15. This can cause hypoxia in predisposed individuals, including infants with bronchopulmonary dysplasia (BPD), but the effect on ex-preterm babies without BPD was uncertain. The consequences of feeding a baby during the hypoxia challenge were also unknown.
Ex-preterm (without BPD) and term infants had fitness to fly tests (including a period of feeding) at 3 or 6 months corrected gestational age (CGA) in a body plethysmograph with an FiO(2) of 0.15 for 20 min. A 'failed' test was defined as oxygen saturation (SpO(2)) <90% for at least 2 min.
41 term and 30 ex-preterm babies (mean gestational age 39.8 and 33.1 weeks, respectively) exhibited a significant median drop in SpO(2) (median -6%, p<0.0001); there was no difference between term versus ex-preterm babies, or 3 versus 6 months. Two term (5%) and two ex-preterm (7%) babies failed the challenge. The SpO(2) dropped further during feeding (median -4% in term and -2% in ex-preterm, p<0.0001), with transient desaturation (up to 30 s) <90% seen in 8/36 (22%) term and 9/28 (32%) ex-preterm infants; the ex-preterm babies desaturated more quickly (median 1 vs 3 min, p=0.002).
Ex-preterm babies without BPD and who are at least 3 months CGA do not appear to be a particularly at-risk group for air travel, and routine preflight testing is not indicated. Feeding babies in an FiO(2) of 0.15 leads to a further fall in SpO(2), which is significant but transient.
Infants with bronchopulmonary dysplasia (BPD) experience significant hypoxemia. Apnea indices and oxygen saturation levels of ten infants with BPD were compared to ten healthy premature infants who were evaluated to rule out apnea or bradycardia prior to discharge from the hospital. Infants with BPD who had been recently (less than 7 days) weaned from supplemental oxygen were evaluated on and off supplemental oxygen. Premature controls had never received oxygen nor ventilation assistance. Infants with BPD were born significantly more prematurely (28.1 +/- 1.0 vs. 33.0 +/- 3.9 weeks; P = 0.0012) while chronologic ages at the time of evaluation, adjusted for prematurity, were equal (37.1 +/- 3.1 vs. 38.0 +/- 2.7 weeks). Comparisons of apnea densities (expressed as percent of sleep time) between BPD and non-BPD prematures revealed the following: neither the average obstructive apnea (0.15 +/- 0.36 vs. 0.14 +/- 0.31) nor periodic breathing densities (6.0 +/- 8.56 vs. 10.2 +/- 5.84) were different. Infants with BPD experienced significantly more central apnea (0.62 +/- 0.34 vs. 0.16 +/- 0.11; P = 0.003) than did non-BPD prematures. Average oxygen saturation levels were significantly less among BPD vs. non-BPD prematures (90.0 +/- 10.18% vs. 95.7 +/- 4.33%; P = 0.033). When supplemented with oxygen, BPD prematures had significantly higher saturation (X = 94.5%) than when breathing room air (X = 90.0%). Both central apnea and periodic breathing densities declined significantly with this improvement in saturation (0.64 vs. 0.04% and 6.0 vs. 1.4%, respectively). These data suggest that saturation status may indicate central respiratory stability in chronic lung disease.
We hypothesized that infants recovering from severe bronchopulmonary dysplasia have airway constriction that is, at least in part, related to borderline hypoxia. If this hypothesis were correct, pulmonary resistance should decrease with the administration of oxygen. To test this hypothesis, we studied 10 infants recovering from severe bronchopulmonary dysplasia (study weight 2490 +/- 275 gm; birth weight 1010 +/- 89 gm; postnatal age 73 +/- 7 days; postconceptional age 38.5 +/- 1.6 weeks) and 10 matched control infants (study weight 2430 +/- 179 gm; birth weight 2320 +/- 195 gm; postnatal age 25 +/- 4 days; postconceptional age 37.5 +/- 0.8 weeks). Resistance and compliance were measured by means of a mask with a flowmeter and an esophageal balloon (with the PEDS computer program). Measurements in both groups were made in quiet sleep, without sedation, during the inhalation of room air and during the fifth minute of oxygen inhalation. We found that (1) total pulmonary resistance, significantly higher in infants with bronchopulmonary dysplasia than in control infants, decreased from 206.1 +/- 47 cm H2O.L-1.sec-1 during inhalation of room air to 106.5 +/- 20.9 during inhalation of 100% oxygen (p less than 0.05) and (2) pulmonary dynamic compliance, lower in infants with bronchopulmonary dysplasia than in control infants, increased significantly with the administration of 100% oxygen. The results suggest that infants with bronchopulmonary dysplasia have airway constriction and that this is alleviated by inhalation of oxygen.
The cardiac catheterization data of six infants with bronchopulmonary dysplasia (BPD) were reviewed to examine the responsiveness of their pulmonary vascular beds to changes in oxygen tension. The infants were studied because of slow recovery from their oxygen requirements and clinical evidence of persistent pulmonary hypertension. All were receiving home oxygen therapy and had abnormal chest radiographs and right ventricular hypertrophy by ECG at the time of catheterization (mean age, 25 months). All infants had mean pulmonary artery pressure greater than 25 mm Hg in room air, with a mean of 48 mm Hg. All decreased mean pulmonary artery pressure by at least 10 mm Hg when placed in high levels of inspired oxygen (FiO2 greater than 80), with a mean pulmonary artery pressure of 25 mm Hg. This represented a significant decrease in mean pulmonary artery pressure from room air pressures (P less than .005). Mean pulmonary artery pressure was also measured in three infants who were breathing supplemental oxygen by nasal cannula at flow rates similar to levels used for outpatient therapy. Most of the reduction in mean pulmonary artery pressure that occurred at high FiO2 occurred at these lower flow rates of supplemental oxygen. It is concluded that infants with bronchopulmonary dysplasia who have pulmonary hypertension generally have reactive pulmonary vascular beds, responsive to supplemental oxygen. Continuous oxygen therapy by nasal cannula may be useful in the treatment of pulmonary hypertension associated with bronchopulmonary dysplasia.
Infants with bronchopulmonary dysplasia (BPD) have been previously reported to have a decrease in growth velocity after stopping supplemental oxygen (SO). SO was stopped after a short-term recording (20-30 minutes) of pulse oxygen saturation (Sao2) of 92% or greater in room air. Other studies have documented that Sao2 decreases further during feedings and sleep in infants with BPD. Two questions were asked: (1) whether short-term, awake Sao2 studies would reliably predict prolonged sleep Sao2; and (2) how Sao2 sustained at 88% to 91% vs 92% or greater in room air would impact growth velocity in infants with BPD.
Short-term Sao2 studies were prospectively compared with prolonged sleep Sao2 (n = 63) and the growth velocity of infants who had SO discontinued after a prolonged sleep Sao2 recording of 88% to 91% (group 1; n = 14) versus 92% or greater (group 2; n = 34) in room air.
Failure to maintain Sao2 at predetermined levels occurred in 18 (29%) of 63 infants during their first prolonged sleep study. There was no correlation between short-term awake Sao2 and prolonged sleep Sao2 recordings (r = .02). Body weight, height, weight for height, and rate of weight gain were similar for all study infants before SO was stopped and remained constant for group 2 infants after SO was stopped. However, group 1 infants had a significant decrease in the rate of weight gain (17.3 +/- 13.1 vs 3.7 +/- 6.1 g/kg per day), and the mean z scores for weight gain and weight for height also decreased significantly for group 1 infants. Energy intake, incidence of acute infection, hematocrit values, and medication use did not differ before or after stopping SO in either group.
This study indicated that short-term, awake Sao2 measurements do not predict prolonged sleep Sao2, and overall, infants with BPD continued a positive growth trend when Sao2, remained greater than 92% during prolonged sleep.
To investigate the degree of oxygen saturation decline occurring in children during prolonged commercial air travel.
Oxygen saturation and heart rate were measured with a pulse oximeter in healthy pediatric passengers at sea level before boarding a commercial aircraft. These measurements were repeated after 3 hours and 7 hours of flight. Cabin pressure, true altitude, and cabin fraction of inspired oxygen (FiO2) were also recorded at 3 hours and 7 hours.
Eighty healthy children (43 boys) aged 6 months to 14 years were studied during eight flights between Honolulu, Hawaii, and Taipei, Taiwan. Oxygen saturation declined, and heart rate increased after 3 hours (95.7%, 105 beats per minute [BPM]) and 7 hours (94.4%, 108 BPM) of flight compared to preflight levels at sea level (98.5%, 100 BPM) (P < 0.001). The 3-hour to 7-hour oxygen saturation and heart rate means differed significantly (P < 0.001, P = 0.014, respectively). The significant drop in oxygen saturation was associated with the decreased cabin partial pressure of oxygen (PO2)--PO2 was 159 mm Hg at sea level, 126 mm Hg after 3 hours, and 124 mm Hg after 7 hours--but the 3-hour and 7-hour difference suggests that flight duration may also contribute to worsened oxygen desaturation.
Oxygen saturation declines significantly during commercial airline travel with reduced aircraft cabin pressure and concomitant reduced cabin PO2. We did not observe an "acclimation" of oxygenation as the length of travel increased; rather, the oxygen saturation decline worsened, although it may be partially a result of the lower cabin PO2. Although there were no clinically noticeable ill effects at the level of oxygen saturation decline in these relatively healthy passengers, patients with preexisting anemia or cardiopulmonary disease are likely to experience greater degrees of clinical compromise with similar degrees of oxygen saturation decline.
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).
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.
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).
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.
Air travel may pose risks to ex-preterm neonates due to the low oxygen environment encountered during flights. We aimed to study the utility of the preflight hypoxia challenge test (HCT) to detect in-flight hypoxia in such infants.
Ex-preterm (gestation < or = 35 completed weeks) infants ready for air transfer from the intensive/special care nursery to regional hospitals were studied. A pretransfer HCT was performed by exposing infants to 14% oxygen for 20 min. Failure was defined as a sustained fall in pulse oxygen saturation (Spo(2)) < or = 85%. A nurse blinded to the test result monitored the in-flight oxygen saturations in each infant. If Spo(2) fell to < or = 85%, oxygen was administered.
Forty-six infants with median gestation of 32.2 weeks (range, 24 to 35.6 weeks) and birth weight of 1,667 g (range, 655 to 2,815 g) were recruited. No infants were receiving supplemental oxygen at the time of transfer. The HCT was performed at a median corrected age of 35.8 weeks (range, 33.1 to 43 weeks). Thirty-five infants (76%) passed the test, and the remainder failed. During the flight, 16 infants met the criteria for in-flight oxygen, but 12 of these infants (75%) had passed the preflight HCT. Of the 11 infants who failed the HCT, only 4 infants (36%) required in-flight oxygen. The HCT incorrectly predicted in-flight responses in 42% (19 of 46 infants).
A significant percentage of ex-preterm neonates require in-flight oxygen supplementation. The HCT is not accurate for identifying which infants are at risk for in-flight hypoxia.
Nonparametric estimation of a survivorship function with doubly censored data
- Turnbull