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J Stocks

Publications and source records attributed to J Stocks.

At least 19 recordsLinked to original sources
PubMed2007

Standardizing lung function laboratories for multicenter trials.

Multi-center studies provide advantages in clinical research but differences between centers can introduce bias. Three specialist pediatric respiratory laboratories standardized their methodology and examined differences between centers. The specific aims were to (i) assess the variability of measurements on adults within and between centers and (ii) to exchange and cross-analyze data from children to assess the extent of agreement between centers. Each laboratory used identical equipment and software. Inter-laboratory visits were used to (i) standardize protocols for data collection and analysis and (ii) make spirometric and plethysmographic measurements on participating staff at each location. Staff also had repeat measurements in their home laboratories. Measurements from children in each laboratory were exchanged on disk, cross-analyzed, and data compared by ANOVA. There were no significant within-subject, between-center differences in FVC, FEV1, FEF50, FRCpleth, or VC. There was a slight trend for TLC and RV (P=0.07) to be higher at one center. The 95% limits of agreement within and between centers were similar for all parameters. There were no differences between centers in cross-analyzed data from 10 children. By standardizing hardware, software, and protocol, potential inter-laboratory differences can be minimized. We recommend that this approach be adopted prior to multi-center studies.

Adult↗
PubMed2006

New aspects of airway mechanics in pre-term infants.

High-frequency respiratory impedance data measured noninvasively by the high-speed interrupter technique (HIT), particularly the first antiresonance frequency (f(ar,1)), is related to airway wall mechanics. The aim of this study was to evaluate the feasibility and repeatability of HIT in unsedated pre-term infants, and to compare values of f(ar,1) from 18 pre-term (post-conceptional age 32-37 weeks, weight 1,730-2,910 g) and 18 full-term infants (42-47 weeks, 3,920-5,340 g). Among the pre-term infants, there was good short-term repeatability of f(ar,1) within a single sleep epoch (mean (sd) coefficient of variance: 8 (1.7)%), but 95% limits of agreement for repeated measures of f(ar,1) after 3-8 h were relatively wide (-41 Hz; 37 Hz). f(ar,1) was significantly lower in pre-term infants (199 versus 257 Hz), indicating that wave propagation characteristics in pre-term airways are different from those of full-term infants. The present authors suggest that this is consistent with developmental differences in airway wall structure and compliance, including the influence of the surrounding tissue. Since flow limitation is determined by wave propagation velocity and airway cross-sectional area, it was hypothesised that the physical ability of the airways to carry large flows is fundamentally different in pre-term than in full-term infants.

Feasibility Studies↗
PubMed2005

Neonatal Ventilation With Inhaled Nitric Oxide Versus Ventilatory Support Without Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure: the INNOVO multicentre randomised controlled trial (ISRCTN 17821339).

BACKGROUND: Although inhaled nitric oxide (iNO) may be a promising treatment for newborn infants with severe respiratory failure, the results from 3 previous small trials were inconclusive. METHODS: Infants of <34 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomized to receive or not receive iNO. The study was not blinded. FINDINGS: Recruited were 108 infants (55 allocated to receive iNO and 53 not allocated to receive iNO) from 15 neonatal units in the United Kingdom and Republic of Ireland. Fifty-nine percent (64 of 108) died, and 84% of the survivors (37 of 44) had signs of some impairment or disability, 9 (20%) of them classified as severely disabled. There was no evidence of an effect of iNO on the primary outcomes: death or severe disability at 1 year corrected age (relative risk [RR]: 0.99; 95% confidence interval [CI]: 0.76 to 1.29); death or supplemental oxygen on expected date of delivery (RR: 0.84; 95% CI: 0.68 to 1.02); or death or supplemental oxygen at 36 weeks' postmenstrual age (RR: 0.98; 95% CI: 0.87 to 1.12). There was a trend for infants allocated to the iNO group to spend more time on the ventilator (log rank: 3.6), on supplemental oxygen (log rank: 1.4), and in hospital (log rank: 3.5) than those allocated to receive no iNO. This pattern predominantly reflected the infants who died. Mean total costs at 1 year corrected age were significantly higher in the iNO group, partly because of the costs of the gas but mainly because of the difference in initial hospitalization costs. INTERPRETATION: Evidence of prolongation of intensive care and increased costs of such care, without clear beneficial effects, implies that iNO cannot be recommended for preterm infants with severe hypoxic respiratory failure.

Administration, Inhalation↗
PubMed2004

Effect of raised lung volume technique on subsequent measures of V'maxFRC in infants.

Partial and "full" forced expiratory maneuvers are both used to assess airway function in infants. Despite the increasing use of the raised volume technique, there is little information regarding the influence of lung inflations as are necessary for the raised volume technique on other measurements of lung function in infants. The aim of this study was to assess whether application of the raised volume technique influences subsequent tidal measurements of maximal expired flow at functional residual capacity (V'maxFRC). Paired measurements of V'maxFRC were obtained in 29 healthy infants (aged 6-65 weeks) before and after raised volume maneuvers, wherein a lung inflation pressure of 3 kPa was used. When compared with measurements prior to raising lung volume, there was a highly significant (P < 0.001) decrease in V'maxFRC by 40 ml.sec(-1) when measurements were repeated (95% CI, -59, -20 ml.sec(-1)), equivalent to a reduction of 20% or -0.6 SD scores in flows. There was no significant change in selected tidal breathing parameters, 95% CI of differences between the two sets of measurements being -1.5, 1.2 bpm for respiratory rate; -0.5, 0.2 ml.kg(-1) for weight corrected tidal volume, and -0.04, 0.01 for tidal breathing ratio (tPTEF:tE). In conclusion, although the mechanism remains unclear, raised volume maneuvers may influence subsequent measures of lung function in infants. Further research is needed to clarify the potential mechanisms. In the meantime, the potential impact of the order of lung function tests within any given study protocol should be considered carefully.

Female↗
PubMed2004

Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis.

BACKGROUND: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden. METHODS: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls. RESULTS: LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38) CONCLUSIONS: MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.

Adolescent↗
PubMed2004

Functional residual capacity measurements in healthy infants: ultrasonic flow meter versus a mass spectrometer.

Accurate, reproducible and portable bedside monitoring of lung volume could potentially facilitate the early recognition of both under and overinflation of the lungs in ventilated and nonventilated subjects. This study asked whether a prototype portable ultrasonic flow meter provided valid and reliable measurements of functional residual capacity (FRCUS) when compared to those obtained using a mass spectrometer (FRCMS) in nonventilated healthy infants. Paired, randomised measurements of FRCMS and FRCUS were obtained using the sulphur hexafluoride (SF6) multiple-breath washout technique in 23 healthy infants with a median (range) postnatal age of 34.6 (1.3-92.6) weeks and weight of 8.3 (3.9-11.7) kg. FRCUS was on average 5.7%, (95% CI: 1.0-10.4%) less than FRCMS equating to a difference of approximately 1 mL x kg(-1). The 95% limits of agreement (LA) between the two techniques were relatively wide (95% LA: -17.5% to 29%), although in keeping with previously reported within-patient variability for lung volume measurements. There was no significant difference between the within subject coefficient of variation for FRCMS (3.7%) and FRCUS (5.2%). The ultrasonic flow meter used in this study provides repeatable measurements of functional residual capacity in spontaneously breathing healthy infants that approximate those obtained during mass spectrometry.

Flowmeters↗
PubMed2004

Low birth weight for gestation and airway function in infancy: exploring the fetal origins hypothesis.

BACKGROUND: Poor fetal growth has been associated with impaired airway function in adult life, but evidence linking birth weight and airway function in early childhood is sparse. We examined the hypothesis that low birth weight for gestation is associated with impaired airway function shortly after birth and that this is independent of impaired postnatal somatic growth. METHODS: Airway function was measured using the raised volume technique in healthy white infants of low (< or =10th centile) or appropriate (> or =20th centile) birth weight for gestation and was expressed as forced expiratory volume in 0.4 s (FEV0.4), forced vital capacity (FVC), and the maximal expired flow at 25% of forced vital capacity (MEF25). Infant length and weight, maternal height and weight, maternal report of smoking prenatally and postnatally, and parental occupation were recorded. RESULTS: Mothers of low birth weight for gestation infants (n=98) were lighter, shorter, and more likely to smoke and have partners in manual occupations. At 6 weeks their infants remained lighter and shorter than those of appropriate birth weight (n=136). FEV0.4, FVC, and MEF25 were reduced in infants of low birth weight for gestation, in those whose mothers smoked in pregnancy, or who were in manual occupations. After adjusting for relevant maternal and infant characteristics, infants in the low birth weight for gestation group experienced a mean reduction of 11 ml in FEV0.4 (95% CI 4 to 18; p=0.002), of 12 ml in FVC (95% CI 4 to 19; p=0.004), and of 28 ml/s in MEF25 (95% CI 7 to 48; p=0.03). CONCLUSIONS: Airway function is diminished in early postnatal life as a consequence of a complex causal pathway which includes social disadvantage as indicated by maternal social class, smoking and height, birth weight as a proximal and related consequence of these factors, and genetic predisposition to asthma. Further work is needed to establish the relevance of these findings to subsequent airway growth and development in later infancy and early childhood.

Bronchial Diseases↗
PubMed2003

Assessment of tidal breathing parameters in infants with cystic fibrosis.

Simple methods are needed to assess lung function in infants with cystic fibrosis (CF). This study determined the relationship between simple measurements obtained from tidal breathing with those from more complicated forced expiratory manoeuvres. Healthy infants and infants with CF were recruited from two maternity units and five specialist CF hospitals, respectively. Respiratory rate, tidal volume, minute ventilation and the tidal breathing ratio (TPTEF:TE) were measured in sedated infants and compared with forced expiratory volume in 0.4 seconds (FEV0.4) measured by the raised volume technique. Altogether, 95 healthy infants and 47 infants with CF of similar age, sex, ethnicity and proportion exposed to maternal smoking were recruited. There was no difference in TPTEF:TE and tidal volume between healthy infants and those with CF. Minute ventilation was significantly greater in infants with CF due to a mean (95% confidence interval) increase in respiratory rate of 5.8 (3.2-8.4) min(-1). Thirteen (28%) infants with CF had a respiratory rate elevated by >2 SD. However, no association between respiratory rate and FEV0.4 could be identified. Tidal breathing ratio was not useful in identifying diminished airway function in infants with cystic fibrosis. An elevated respiratory rate may be due in part to ventilation heterogeneity but is poorly predictive of diminished airway function measured by forced expiration.

Child, Preschool↗
PubMed2002

Exploring the relationship between forced maximal flow at functional residual capacity and parameters of forced expiration from raised lung volume in healthy infants.

The raised volume rapid thoraco-abdominal compression technique (RVRTC) is being increasingly used to assess airway function in infants, but as yet no consensus exists regarding the equipment, methods, or analysis of recorded data. The aim of this study was to explore the relationship between maximal flow at functional residual capacity (V'(maxFRC)) and parameters derived from raised lung volumes, and to address analytical aspects of the latter technique in an attempt to assist with future standardization initiatives. Forced vital capacity (FVC) from lung volume raised to 3 kPa, timed forced expiratory volumes (FEV(t)), and forced expiratory flow parameters at different percentages of expired FVC (FEF(%)) were measured in 98 healthy infants (1-69 weeks of age). V'(maxFRC) using the tidal rapid thoraco-abdominal compression (RTC) technique was also measured. The within-subject relationships and within-subject variability of the various parameters were assessed. Duration of forced expiration was < 0.5 sec in 5 infants, meaning that FEV(0.3) and FEV(0.4) were the only timed volume parameters that could be calculated in all infants during the first months of life, and even when it could be calculated, FEV(0.5) approached FVC in many of these infants. It is recommended that FEV(0.4) be routinely reported in infants less than 3 months of age. Contrary to previous reports, within subject variability of V'(maxFRC) was less than that of FEF(75) (mean CV = 6.3% and 8.9%, respectively).A more standardized protocol when analyzing data from the RVRTC would facilitate comparisons of results between centers in the future.

Crown-Rump Length↗
PubMed2002

Effect of bradykinin, TGF-beta1, IL-1beta, and hypoxia on COX-2 expression in pulmonary artery smooth muscle cells.

Prostanoids are major regulators of smooth muscle function that are generated by cyclooxygenase (COX). Here we hypothesized that cytokines and mediators that regulate the pulmonary circulation would alter COX expression and prostanoid generation in pulmonary artery smooth muscle cells. Bradykinin, transforming growth factor-beta1 (TGF-beta1), and interleukin-1beta (IL-1beta) increased inducible COX-2 expression and prostaglandin E(2) (PGE(2)) release. Transfection studies using a COX-2 promoter construct demonstrated that all three agents acted transcriptionally. Constitutive COX-1 protein expression was unchanged. The COX inhibitor indomethacin, the COX-2 inhibitor NS-398, the protein synthesis inhibitor cycloheximide, and the glucocorticoid dexamethasone abrogated the increased PGE(2) levels. Dexamethasone and cycloheximide prevented COX-2 induction. Hypoxia (3% O(2)-5% CO(2)-92% N(2)) for 24 h selectively augmented TGF-beta1-stimulated PGE(2) production and COX-2 induction but had no effect alone. Prolonged hypoxic culture alone for 48 and 72 h enhanced COX-2 induction and increased PGE(2). These studies show that a number of stimuli are capable of inducing COX-2 in pulmonary artery smooth muscle cells. The interaction between hypoxia and TGF-beta1 may be particularly relevant to pulmonary hypertension.

Adult↗
PubMed2001

Airway function in infants newly diagnosed with cystic fibrosis.

The lung function of infants with cystic fibrosis is often reduced shortly after diagnosis. We measured the airway function of newly diagnosed infants to test whether this reduction is independent of clinically recognised lower respiratory illness. We compared the airway function of 33 infants with cystic fibrosis and 87 healthy controls after adjustment for sex, age, bodyweight and length, and exposure to maternal smoking. Airway function was significantly reduced in children with cystic fibrosis, even in those without clinically recognised previous lower respiratory illness. Our findings raise important questions about the onset and natural history of impaired airway function in infants with cystic fibrosis.

Case-Control Studies↗
PubMed2001

The association between birthweight, sex, and airway function in infants of nonsmoking mothers.

The risk of respiratory illness and death is increased in infants of low birthweight for gestational age, but the underlying physiologic mechanisms remain unclear. We examined the hypothesis that airway function is diminished in infants of low birthweight for gestational age, independent of exposure to maternal smoking. Respiratory function was measured using partial and raised volume forced expiratory maneuvers in 103 infants (> 35 wk gestation; 56 boys) not exposed pre- or postnatally to maternal smoking who, according to birthweight, were either small (SGA; n = 38) or appropriate (AGA; n = 65) for gestational age. At testing, SGA infants were of similar postnatal age (mean [SD]: SGA 6.8 [2.4] wk, AGA 5.9 [2.3] wk), but remained shorter and lighter than AGA infants. In univariate analyses, FVC, forced expired volume in 0.4 s (FEV(0.4)), and FEF(75) were significantly diminished in SGA compared with AGA infants (mean [95% CI of difference]: FVC: 127 versus 143 ml [-29, -2]; FEV(0.4): 112 versus 125 ml [-24, -2]; and FEF(75): 173 versus 203 ml s(-1) [-57, -3], respectively), but these differences were no longer significant after allowing for sex and body size. Furthermore, FEF(75) was on average 35 ml s(-1) lower in boys than girls (95% CI: -61, -8). We conclude that diminished airway function in SGA infants shortly after birth appears to be primarily mediated through impaired somatic growth.

Analysis of Variance↗
PubMed2001

The influence of endotracheal tube leak on the assessment of respiratory function in ventilated children.

OBJECTIVE: The use of respiratory mechanics to optimise ventilator settings has become more common since the integration of pressure and flow transducers into modern ventilators. However, values of respiratory resistance (R(rs)) and compliance (C(rs)) can be overestimated in the presence of tracheal tube leak and clinical decisions based on these figures would be misinformed. This study aimed to assess the influence of tracheal tube leak on measurements of C(rs), R(rs) and expired tidal volume (V(TE)) in ventilated children in order to establish when such measurements were reliable in this population. DESIGN: Respiratory function was monitored for at least five consecutive hours during which normal medical procedures were performed. The magnitude and variability of tracheal tube leak was assessed during these periods. SETTING: The paediatric and cardiac intensive care units at Great Ormond Street Hospital for Children, NHS Trust, London. PATIENTS: Seventy-five paralysed, fully ventilated infants and children. RESULTS: Ten children had a mean leak greater than 20% (range: 22%-65%). Amongst this group there were wide fluctuations with respect to leak magnitude, V(TE), C(rs) and R(rs). Leaks of less than 20% appeared necessary to obtain reliable measurements of C(rs) and R(rs) and to ensure consistent and adequate ventilation. CONCLUSIONS: Leaks larger than 20% result in inconsistent tidal volume delivery and gross overestimation of C(rs) and R(rs) irrespective of ventilation mode. The magnitude of tracheal tube leak needs to be accurately displayed on all ventilatory equipment to verify reliable measures of respiratory function so that appropriate clinical decisions can be made and ventilatory management optimised.

Adolescent↗
PubMed2001

Influence of jacket placement on respiratory compliance during raised lung volume measurements in infants.

SUMMARY. Recent introduction of the raised lung volume rapid thoraco-abdominal compression (RVRTC) technique for measuring forced expiratory maneuvers in infants provides the potential opportunity to assess respiratory mechanics simultaneously by using multiple linear regression (MLR) of the relaxed breaths preceding jacket inflation to force expiration. This study was undertaken to investigate whether data obtained from raised lung volume are influenced by placement of the rapid thoraco-abdominal compression (RTC) squeeze jacket. Paired measurements of tidal volume (V(T)) and respiratory rate (RR) during tidal breathing, and of inflation volume (V(inf)), respiratory system compliance (C(rs)), and resistance (R(rs)) during passive lung inflations were made in 60 (30 male) healthy term infants with and without a fastened, but uninflated RTC jacket in place. Jacket placement was associated with a significant reduction (P < 0.0001) in weight-corrected V(inf) [-1.86 (95% confidence interval, -2.46, -1.27) mL.kg(-1)] and C(rs) [-0.77 (-1.04, -0.49) mL.kPa(-1).kg(-1)]. This represented a reduction in weight-corrected C(rs) from 9.00 to 8.24 mL.kPa(-1).kg(-1), with the fall being >10% in 42% of infants studied. There was no significant change in R(rs) or weight-corrected V(T). If passive respiratory mechanics are to be measured during raised lung volume maneuvers, they should be performed prior to the jacket being fastened, unless considerable care is taken with each infant to ensure that the jacket does not restrict chest wall movement during maximum inflation.

Airway Resistance↗
PubMed2001

Lung function testing in infants with cystic fibrosis: lessons from the past and future directions.

Despite the increasing awareness of the need to identify early pulmonary changes in cystic fibrosis (CF) noninvasively, the role of lung function testing in infancy and early childhood remains less clear than in older children with CF. The aim of this review is to summarize available data, discuss the information gained from these publications, and put this information into perspective with more recent developments of lung function testing in both infants and older children with CF. While some of the available data have been the foundation of the current level of understanding of respiratory physiology in CF, interpretation of other data has been hampered by differences between centers with regard to the methods and equipment used, patient selection, small number of subjects, and lack of appropriate reference data. A structured multicenter approach based on recently published recommendations for the measurement of lung function in infancy, together with pursuit of recent developments such as assessment of raised lung volume flow volume curves and ventilation inhomogeneity may help to more effectively utilize lung function tests in infants in the future.

Clinical Trials as Topic↗