Appropriate interpretation of lung function and exercise capacity in a longitudinal follow-up of preterm children.
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Exercise↗
Biomedical subjects
Janet Stocks
Publications and source records attributed to Janet Stocks.
Lung function in infants and young children with chronic lung disease of infancy: the next steps?
Over the past year, a series of papers have reviewed the literature concerning assessment and interpretation of lung function in infants and young children with chronic lung disease of infancy. This manuscript, which represents the final paper in that series, summarizes the findings to date and highlights key areas for future research. Despite the huge literature in this field, interpretation of results and their use in guiding clinical management are still limited by difficulties in 'normalizing data' according to body size and maturation and selection of appropriate control groups. Furthermore, sensitive tests that more closely reflect the underlying pathophysiology of 'new' bronchopulmonary dysplasia, together with simple and reliable methods of assessing lung maturity at birth and true oxygen requirements at specified time points are urgently required. Research in this field is also challenged by the need to separate the independent effects of genetic predisposition, gene-environment interactions, preterm delivery, neonatal respiratory disorders and various treatment strategies on the growing lung. The extent to which disruption of lung growth following premature exposure to the extra-uterine environment leads to an earlier or more aggravated decline in respiratory function in later adult life remains to be elucidated. Whatever its origin, given the increasing survival of smaller and more immature infants, the long term sequelae of neonatal lung disease, are likely to continue to change, requiring ongoing, carefully designed longitudinal studies. Future research strategies need to encompass a multicenter, multi-disciplinary, collaborative approach with closer links between clinicians and basic scientists, to ensure that the most relevant research questions are addressed using appropriate methodology and that findings are implemented into clinical practice in a more timely fashion.
Bronchopulmonary Dysplasia↗
Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests.
BACKGROUND: Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple-breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. OBJECTIVES: To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco-abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. METHODS: Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. RESULTS: Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow-volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV(0.5) and FEF(25-75 )) than boys (mean (95% CI girls-boys): -1.2 (-2.1 to -0.3) for FEV(0.5) Z score; FEF(25-75): -1.2 (-2.2 to -0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. CONCLUSIONS: These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC.
Area Under Curve↗
Clinical implications of pulmonary function testing in preschool children.
There is increasing recognition of the need for objective physiological measurements of lung function during the preschool years in order to identify and treat early lung disease before irreversible structural changes occur; monitor disease progression and efficacy of therapeutic interventions and distinguish the various wheezing phenotypes that occur in this age group, all of which require different management strategies. While preschool pulmonary function tests are undoubtedly excellent research tools , their role in the clinical management of the individual young child remains more controversial. In particular, further work is required to establish information on the within-subject, between occasion variability and the relative sensitivity and specificity of each technique, as well as developing more appropriate prediction equations for this age group, before they can be used confidently in the clinical management of individual child. This review examines the various challenges facing paediatricians who are responsible for children with respiratory diseases such as asthma, wheezing, cystic fibrosis and chronic lung disease following preterm delivery and summarises recent recommendations from an ATS/ERS Task Force.
Child, Preschool↗
Introduction and overview of preschool lung function testing.
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Child, Preschool↗
Lung function tests in neonates and infants with chronic lung disease of infancy: functional residual capacity.
This is the second paper in a review series that will summarize available data and discuss the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy. The current paper addresses the expansive subject of measurements of lung volume using plethysmography and gas dilution/washout techniques. Following orientation of the reader to the subject area, we focus our comments on areas of inquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically, and recommendations are provided to guide future investigation in this field. Measurements of lung volume are important both for assessing growth and development of lungs in health and disease, and for interpreting volume-dependent lung function parameters such as respiratory compliance, resistance, forced expiratory flows, and indices of gas-mixing efficiency. Acute neonatal lung disease is characterized by severely reduced functional residual capacity (FRC), with treatments aimed at securing optimal lung recruitment. While FRC may remain reduced in established chronic lung disease of infancy, more commonly it becomes normalized or even elevated due to hyperinflation, with or without gas-trapping, secondary to airway obstruction. Ideally, accurate and reliable bedside measurements of FRC would be feasible from birth, throughout all phases of postnatal care (including assisted ventilation), and during subsequent long-term follow-up. Although lung volume measurements in extremely preterm infants were described in a research environment, resolution of several issues is required before such investigations can be translated into routine clinical monitoring.
Airway Resistance↗
Lung function tests in neonates and infants with chronic lung disease: global and regional ventilation inhomogeneity.
This review considers measurement of global and regional ventilation inhomogeneity (VI) in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). We focus primarily on multiple-breath inert gas washout (MBW) and electrical impedance tomography (EIT). The literature is critically reviewed and the relevant methods, equipment, and studies are summarized, including the limitations and strengths of individual techniques, together with the availability and appropriateness of any reference data. There has been a recent resurgence of interest in using MBW to monitor lung function within individuals and between different groups. In the mechanically ventilated, sedated, and paralyzed patient, VI indices can identify serial changes occurring following exogenous surfactant. Similarly, global VI indices appear to be increased in infants with CLDI and to differentiate between infants without lung disease and those with mild, moderate, and severe lung disease following preterm birth. While EIT is a relatively new technique, recent studies suggest that it is feasible in newborn infants, and can quantitatively identify changes in regional lung ventilation following alterations to ventilator settings, positive end expiratory pressure (PEEP), and administration of treatments such as surfactant. As such, EIT represents one of the more exciting prospects for continuous bedside pulmonary monitoring. For both techniques, there is an urgent need to establish guidelines regarding data collection, analysis, and interpretation in infants both with and without CLDI.
Humans↗
Lung function tests in neonates and infants with chronic lung disease: forced expiratory maneuvers.
This fourth paper in a review series on the role of lung function testing in infants and young children with acute neonatal disorders and chronic lung disease of infancy (CLDI) addresses measurements of forced expiration using rapid thoraco-abdominal compression (RTC) techniques and the forced deflation technique. Following orientation of the reader to the subject area, we focus our comments on the areas of inquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically, and recommendations are provided to guide future investigation in this field. All studies on infants and young children with CLDI using forced expiratory or deflation maneuvers demonstrated that forced flows at low lung volume remain persistently low through the first 3 years of life. Measurement of maximal flow at functional residual capacity (V'maxFRC) is the most commonly used method for assessing airway function in infants, but is highly dependent on lung volume and airway tone. Recent studies suggested that the raised volume RTC technique, which assesses lung function over an extended volume range as in older children, may be a more sensitive means of discriminating changes in airway function in infants with respiratory disease. The forced deflation technique allows investigation of pulmonary function during the early development of CLDI in intubated subjects, but its invasive nature precludes its use in the routine setting. For all techniques, there is an urgent need to establish suitable reference data and evaluate within- and between-occasion repeatability, prior to establishing the clinical usefulness of these techniques in assessing baseline airway function and/or response to interventions in subjects with CLDI.
Airway Resistance↗
Lung function tests in neonates and infants with chronic lung disease: lung and chest-wall mechanics.
This is the fifth paper in a review series that summarizes available data and critically discusses the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). This review focuses on respiratory mechanics, including chest-wall and tissue mechanics, obtained in the intensive care setting and in infants during unassisted breathing. Following orientation of the reader to the subject area, we focused comments on areas of enquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically with respect to relevant methods, equipment and study design, limitations and strengths of different techniques, and availability and appropriateness of reference data. Recommendations to guide future investigations in this field are provided. Numerous different methods have been used to assess respiratory mechanics with the aims of describing pulmonary status in preterm infants and assessing the effect of therapeutic interventions such as surfactant treatment, antenatal or postnatal steroids, or bronchodilator treatment. Interpretation of many of these studies is limited because lung volume was not measured simultaneously. In addition, populations are not comparable, and the number of infants studied has generally been small. Nevertheless, results appear to support the pathophysiological concept that immaturity of the lung leads to impaired lung function, which may improve with growth and development, irrespective of the diagnosis of chronic lung disease. To fully understand the impact of immaturity on the developing lung, it is unlikely that a single parameter such as respiratory compliance or resistance will accurately describe underlying changes. Assessment of respiratory mechanics will have to be supplemented by assessment of lung volume and airway function. New methods such as the low-frequency forced oscillation technique, which differentiate the tissue and airway components of respiratory mechanics, are likely to require further development before they can be of clinical significance.
Bronchopulmonary Dysplasia↗
Lung-function tests in neonates and infants with chronic lung disease: tidal breathing and respiratory control.
This paper is the fourth in a series of reviews that will summarize available data and critically discuss the potential role of lung-function testing in infants with acute neonatal respiratory disorders and chronic lung disease of infancy. The current paper addresses information derived from tidal breathing measurements within the framework outlined in the introductory paper of this series, with particular reference to how these measurements inform on control of breathing. Infants with acute and chronic respiratory illness demonstrate differences in tidal breathing and its control that are of clinical consequence and can be measured objectively. The increased incidence of significant apnea in preterm infants and infants with chronic lung disease, together with the reportedly increased risk of sudden unexplained death within the latter group, suggests that control of breathing is affected by both maturation and disease. Clinical observations are supported by formal comparison of tidal breathing parameters and control of breathing indices in the research setting.
Adult↗
Multiple breath washout with a sidestream ultrasonic flow sensor and mass spectrometry: a comparative study.
Over recent years, there has been renewed interest in the multiple breath wash-out (MBW) technique for assessing ventilation inhomogeneity (VI) as a measure of early lung disease in children. While currently considered the gold standard, use of mass spectrometry (MS) to measure MBW is not commercially available, thereby limiting widespread application of this technique. A mainstream ultrasonic flow sensor was marketed for MBW a few years ago, but its use was limited to infants. We have recently undertaken intensive modifications of both hardware and software for the ultrasonic system to extend its use for older children. The aim of the current in vivo study was to compare simultaneous measurements of end-tidal tracer gas concentrations and lung clearance index (LCI) from this modified ultrasonic device with those from a mass spectrometer. Paired measurements of three MBW, using 4% sulfur hexafluoride (SF(6)) as the tracer gas and the two systems in series, were obtained in nine healthy adult volunteers. End-tidal tracer gas concentrations (n = 675 paired values) demonstrated close agreement (95% CI of difference -0.23; -0.17%, r(2) = 1). FRC was slightly higher from the MS (95%CI 0.08;0.17 L), but there was no difference in LCI (95%CI -0.10; 0.3). We conclude, that this ultrasonic prototype system measures end-tidal tracer gas concentration accurately and may therefore be a valid tool for MBW beyond early childhood. This prototype system could be the basis for a commercial device allowing more widespread application of MBW in the near future.
Adult↗
Gas mixing efficiency from birth to adulthood measured by multiple-breath washout.
Efficient mixing of inspired gas with the resident gas of the lung is an essential requirement of effective respiration. This review focuses on one method for quantifying ventilation inhomogeneity: the multiple-breath inert gas washout (MBW). MBW has been employed as a research tool in adults and school age children for more than 50 years. Modifications allowing data collection in infants and preschoolers have been described recently. Indices of overall ventilation inhomogeneity, such as the lung clearance index and moment ratios, are raised in many infants with lung disease of prematurity, and in young children with cystic fibrosis. These indices may be more sensitive than other lung function measures for the early detection of airway disease. We describe, for the first time, a development of the MBW analysis that allows calculation of acinar and conductive zone inhomogeneity indices in spontaneously breathing children. Although methodological and analytical issues remain, the future clinical and research applications of MBW justify accelerated research in this field.
Age Factors↗
Limitations of electronic compensation for measuring plethysmographic airway resistance in infants.
Electronic compensation to overcome thermal artifacts during plethysmographic estimations of airway resistance is now used routinely in adults and school-age children, and was shown to be a valuable means of discriminating airway function between preschool children with and without lung disease. A similar system is now commercially available for infants, which could increase the applicability of this technique. However, we noted marked discrepancies in electronically calculated values of airway resistance in this age group, both with respect to absolute values displayed and marked within-subject variability on a single test occasion. The aim of this technical report is to summarize our recent findings in order to alert other users to potential problems. Airway resistance (R(aw)) was measured in 62 infants (28 with cystic fibrosis (CF); 34 healthy). Three to five epochs of quiet regular tidal breathing were collected in each infant. Marked within-subject, within-test variability was observed, with the median coefficient of variation (CV) being 9.1% (range, 1.2-52.6%) within and 8.5% (0.1-112%) between epochs. Among healthy infants, R(aw) varied from 0.1-6.4 (kPa x liter(-1) x sec), with no relationship to either body or lung size and complete overlap of results with those from infants with CF, despite abnormal lung function in the latter when assessed by other means. The marked within- and between-subject variability in healthy infants, and lack of discriminative power of R(aw) when derived from electronically compensated values, currently preclude application in either clinical or research studies.
Airway Resistance↗
Lung function testing in acute neonatal respiratory disorders and chronic lung disease of infancy: a review series.
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Acute Disease↗
Partitioning of airway and parenchymal mechanics in unsedated newborn infants.
The recent trend toward development of noninvasive methods that can accurately evaluate the lung periphery has particular relevance for the predominantly parenchymal nature of neonatal respiratory disease. Concerns regarding the safety of sedating newborn (especially preterm) infants have also stimulated a drive toward measurements obtained during natural sleep. This study aimed to adapt existing methodology for the low-frequency forced oscillation technique to obtain partitioned measurements of airway and parenchymal mechanics during unsedated, quiet sleep in newborn infants without a history of previous respiratory disease. A face mask was positioned over the infant's mouth and nose and a brief (4-5 s) breathing pause was induced by evoking the Hering-Breuer reflex via end-inspiratory occlusion at raised lung volume (airway opening occluded at 2 kPa). Airway opening pressure and flow were measured while a pseudorandom noise (2-14 Hz) was applied to the airway. Acceptable pulmonary impedance data were collected in 11 of the 12 infants studied (34.1-42.6 wk postmenstrual age, 1.9-3.9 kg body weight) on 17 (total of 20) occasions. Airway parameters (resistance and inertance) and respiratory tissue parameters were calculated from the resultant impedance spectra. Tissue resistance and tissue elastance decreased with increasing body length albeit at different rates such that hysteresivity (tissue resistance/tissue elastance) also decreased. There was a trend toward reduction in airway resistance with increasing length. Measurements of lung function are feasible in the unsedated newborn infant using low-frequency forced oscillations and confirm the important contribution of tissue resistance to lung mechanics in the developing lung.
Airway Resistance↗
Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis.
Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.
Age Factors↗
Development of lung function in early life: influence of birth weight in infants of nonsmokers.
This study aimed to compare lung growth and development during the first year of life in healthy term infants of low or appropriate birth weight for gestation. Paired measurements of forced expiratory volume in 0.4 second, FVC, and forced expiratory flow when 75% of FVC has been exhaled were obtained, using the raised volume technique, at about 7 weeks and 9 months of age in 80 infants (32 low and 48 appropriate birth weight for gestation) of white, nonsmoking mothers. Forced flows and volumes increased with growth. Longitudinal trends in results were compared between the two groups, using random effects modeling and adjusted for potential confounding factors. After adjustment for sex, age, and length, forced expiratory volume was significantly reduced by an average (95% confidence interval) of 9% (2 to 16%) in low birth weight compared with appropriate birth weight for gestation infants throughout the first year of life, with a similar trend in forced expiratory flow (8% [-2 to 17%]) and FVC (4% [-3 to 11%]). These findings suggest that lung function is reduced in low birth weight for gestation infants born to nonsmoking white mothers and that this is independent of somatic growth during infancy.
Birth Weight↗
The influence of physiotherapy and suction on respiratory deadspace in ventilated children.
OBJECTIVE: To assess and compare the effects of respiratory physiotherapy and suction on deadspace volumes, carbon dioxide elimination (VCO(2)), end tidal CO(2) (ETCO(2)), and arterial partial pressure of carbon dioxide (PaCO(2)) in ventilated infants and children. DESIGN: Randomised crossover study. Participants received both treatments with a washout interval of more than 90 min. SETTING: Intensive tertiary care units, Great Ormond Street Hospital, London. PATIENTS: Eighty-seven fully ventilated children, requiring physiotherapy, with arterial lines in situ. Paired measurements were obtained in 81 patients, of whom 6 were excluded because of tracheal tube leak greater than 20%. INTERVENTIONS: Respiratory physiotherapy and suction. MEASUREMENTS AND RESULTS: Data were collected April 1998-March 2000. The "CO(2)SMO Plus" respiratory monitor was used to calculate parameters before and 30 min after both interventions. Physiotherapy lasted longer and required more saline and catheters per treatment ( p<0.005). There were significant increases in physiological deadspace (VD(phys))/kg ( p<0.0001), alveolar deadspace (VD(alv))/kg ( p<0.0001) and VD(phys)/tidal volume (V(T)) ( p<0.05) following physiotherapy that were not observed following suction. There were no significant changes following either treatment with respect to airway deadspace (VD(airway)), VCO(2) or PaCO(2). Comparison of the mean differences following treatments indicated significant differences between physiotherapy and suction in terms of VD(phys)/kg ( p<0.005), VD(alv)/kg ( p<0.005), expired tidal volumes (V(TE)) ( p<0.05), mixed expired CO(2) (PeCO(2)) ( p<0.04) and ETCO(2) ( p<0.03). CONCLUSIONS: Differences between physiotherapy and suction techniques probably accounted for their statistically distinguishable effects on deadspace. VD(phys) and VD(alv) may be more sensitive indicators of subtle changes in gas exchange and regional ventilation than VCO(2) or PaCO(2). However, interpretation of these outcomes is dependent on concurrent examination of the parameters from which they are derived.
Child↗