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Biomedical subjects

J Stocks

Publications and source records attributed to J Stocks.

At least 37 records · Page 2Linked to original sources
PubMed2001

Human airway smooth muscle cells secrete vascular endothelial growth factor: up-regulation by bradykinin via a protein kinase C and prostanoid-dependent mechanism.

Bronchial vascular remodeling is an important feature of the pathology of chronic asthma, but the responsible mechanisms and main sources of angiogenic factors are unclear. Here we report that human airway smooth muscle cells express vascular endothelial growth factor (VEGF)121, 165, 189, 206 splice variants and secrete VEGF protein constitutively. VEGF protein secretion was increased by the proinflammatory asthma mediator bradykinin through post-transcriptional mechanisms. Bradykinin-induced VEGF secretion was dependent on the B2 bradykinin receptor, activation of protein kinase C, and generation of endogenous prostanoids. This is the first report that bradykinin can increase VEGF secretion in any biological system and the first to show that airway smooth muscle cells produce VEGF. Our results suggest a novel role for human airway smooth muscle in contributing to bronchial mucosal angiogenesis in chronic asthma by secretion of VEGF and suggest a wider role for mesenchymal cell products in mediating angiogenesis in inflammatory and allergic diseases.

Adult↗
PubMed2001

Effect of delayed sternal closure after cardiac surgery on respiratory function in ventilated infants.

OBJECTIVE: Studies examining the effect of sternal closure on respiratory function have not been published, and currently there is little evidence to guide ventilation management immediately after closure. The aim of this study was to establish the impact of delayed sternal closure on expired tidal volume, respiratory system compliance, and CO2 elimination immediately after the procedure in infants who had undergone open heart surgery. DESIGN: Prospective study of respiratory function before and after delayed sternal closure. SETTING: Cardiac intensive care unit, Great Ormond Street Hospital, London. PATIENTS: Seventeen infants (median age, 2 wks) with open median sternotomy incisions after cardiac surgery. Data were collected between August 1998 and March 2000. INTERVENTIONS: Respiratory function was measured continuously for 30 mins before and after delayed sternal closure in paralyzed ventilated infants. MEASUREMENTS AND RESULTS: Four babies were excluded from the study because they required either immediate increase in ventilation after delayed sternal closure (n = 3) or removal of pericardial blood collection (n = 1). In the remaining 13 infants, expired tidal volume and CO2 elimination decreased significantly (p < .005) by a mean of 17% and 29%, respectively, after sternal closure. In five of the remaining 13 patients, the magnitude of tracheal tube leak increased by > or = 10% after delayed sternal closure, thereby invalidating recorded changes in respiratory system compliance. Of the eight infants in whom there was a minimal change in leak, respiratory system compliance decreased significantly (p < .05) by a mean of 19%. CONCLUSIONS: This study supports the hypothesis that respiratory function may be compromised after delayed sternal closure and that ventilatory support should be increased to counteract the anticipated decrease in tidal volume. Extra vigilance should be applied in monitoring blood gases after delayed sternal closure to assess clinical responses to sternal closure or changes in ventilatory support. Accurate assessment of change in respiratory system compliance after any therapeutic intervention may be precluded by changes in tracheal tube leak during the procedure.

Critical Care↗
PubMed2001

Airway function at one year: association with premorbid airway function, wheezing, and maternal smoking.

BACKGROUND: Impaired growth and development of the respiratory system during fetal and early postnatal life may have important implications for lung development and later lung health. The aim of this study was to examine the association of diminished premorbid airway function, prior wheezing, and maternal smoking with airway function at 1 year of age. METHODS: Respiratory function was measured at the end of the first year in 100 of 108 healthy term infants (93%) in whom similar measurements had been undertaken prior to any respiratory illness at 8 weeks. Physician diagnosed wheezing episodes were identified retrospectively from medical records. RESULTS: At 1 year specific airway conductance during end expiration (sGawEE; /s/kPa) was significantly diminished in those infants with prior wheezing (95% CI wheeze/no wheeze -0.76 to -0.14), mothers who smoked (95% CI smoke/no smoke -0.81 to -0.27), a family history of asthma (95% CI family history/no family history -0.62 to 0.00), or diminished premorbid sGawEE (95% CI -0.13 to -0.43/s/kPa per unit reduction sGawEE at 8 weeks). In a multivariate model only maternal smoking and diminished premorbid sGawEE were independently associated with diminished sGawEE at 1 year. CONCLUSIONS: Diminished airway function at the end of the first year appears to be mediated by impaired airway development during early life as well as by exposure to maternal smoking. These findings are consistent with the hypothesis that, at a population level, diminished premorbid airway function provides the link between wheezing lower respiratory illness and diminished airway function at 1 year. Maternal smoking remains an important and avoidable cause of impaired airway development and function in infancy.

Airway Resistance↗
PubMed2001

In vitro assessment of equipment and software to assess tidal breathing parameters in infants.

The aim of this in vitro study was to compare the measurement accuracy of two currently available devices for measuring tidal breathing in infants. A mechanical model pump was used to generate flow profiles which simulated those observed in infants. A range of flows was applied simultaneously to two different devices, namely the commercially available SensorMedics 2600 (SM 2600) and more recently developed, custom-made equipment based on the flow-through technique (FTT). Automatically derived values from both devices were compared with one another and with manual calculations of printouts of the same breaths. There were no differences in the raw flow signal obtained from the two devices, nor between values calculated automatically or manually from the FTT. Similarly, the deviations between the FTT and SM 2600 were <3% for tidal volume, respiratory frequency and minute ventilation. However, when comparing either with manually calculated values or those derived automatically from the FTT, there was a systematic and highly significant underestimation of shape-dependent parameters, such as the time to peak tidal expiratory flow as a proportion of tidal expiratory time (tPTEF/tE), derived by the SM 2600. The lower the applied flow, the higher the observed deviations, the underestimation being up to 60% when flows simulating those observed in preterm neonates were applied. These errors appear to result from differences in signal processing such as the algorithms used for breath detection and can only be detected if appropriate nonsinusoidal flow profiles representing those seen in infants are used to evaluate equipment.

Humans↗
PubMed2001

Effect of apparatus dead space on breathing parameters in newborns: "flow-through" versus conventional techniques.

Commercial devices for tidal breathing measurements in newborns allow only short-term measurements, due to the high apparatus dead space of the face mask and pneumotachometer. The flow-through technique (FTT) minimizes the dead space by a background flow, thereby allowing long-term measurements. The aim of this study was to investigate the comparability of tidal breathing parameters using both techniques. Paired measurements of tidal breathing were performed in 86 sleeping infants (median (range) body weight 2.8 kg (1.9-5.3 kg), age 65 days (3-150 days)), using the FTT and SensorMedics 2600 (SM 2600). There was a significant bias (p <0.001) in all tidal breathing parameters. Compared with the FTT, increases (95% confidence interval (CI)) in tidal volume (VT), respiratory frequency (fR), and minute ventilation (V'E) were 0.74 (0.5-1.0) mL.kg(-1), 9.0 (6.9-11.2).min(-1) and 92 (74-109) mL.min(-1).kg(-1) when measured with the SM 2600, representing average increases of 13, 17 and 30%, respectively, in response to the added dead space. By contrast, time to peak tidal expiratory flow as a proportion of expiratory time (tPTEF/tE) was changed by -0.09 (-0.11-0.08). The mean (95% CI) change in tPTEF/tE of -54 (-62-45)%, when measured in infants by the SM 2600, was remarkably similar to that observed during in vitro validation studies (-59 (-73-44)%), suggesting that the discrepancies in timing parameters may be largely attributable to differences in signal processing. In conclusion, differences in measurement technique and precision of the devices used can result in significant differences in tidal breathing parameters. This may impede the comparison of results within and between infants and the clinical interpretation of tidal breathing measurements in newborns.

Humans↗
PubMed2001

Passive respiratory mechanics: the occlusion techniques.

The aim of this position paper is to define quality control and acceptance criteria for measuring passive respiratory mechanics in infants using the occlusion techniques to ensure that valid results are obtained. These guidelines cover numerous aspects including: 1) terminology and definitions; 2) equipment; 3) data acquisition; 4) data handling and analysis; 5) reporting of results. Adherence to these guidelines should ensure that measurement of passive respiratory mechanics in infants in different lung function laboratories could be performed with an acceptable degree of safety, precision, and reproducibility. This will facilitate multi-centre collection of data and performance of clinical investigations.

Airway Resistance↗
PubMed2001

Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society.

Functional residual capacity (FRC) is the only static lung volume that can be measured routinely in infants. It is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Despite requiring complex equipment, the plethysmographic method for measuring FRC is very simple to apply and, unlike the gas dilution techniques, enables repeat measures of lung volume to be obtained within a few minutes. This method has the further advantage that with suitable adaptations to the equipment, simultaneous measurements of airway resistance can also be obtained. The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for plethysmographic measurements in infants. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that meaningful comparisons can be made between data collected in different centres or with different equipment. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis and reporting of results and also highlight areas where further research is needed before consensus can be reached.

Airway Resistance↗
PubMed2001

Assessment of passive respiratory mechanics in infants: double versus single occlusion?

The single breath or occlusion technique (SOT) is widely used to assess passive respiratory mechanics in infants, but depends on various underlying assumptions. Recently, it has been proposed that such measurements could be internally validated by performing two brief airway occlusions during the same expiration. The aim of this study was to evaluate the use of the double occlusion technique (DOT) using a new commercially available program (Jaeger MasterScreen BabyBody Erich Jaeger GmbH, Würzburg, Germany). Paired measurements of respiratory system compliance (Crs) and resistance (Rrs) using both SOT and DOT were obtained in 18 healthy sedated infants (age range 4-41 weeks, weight 2.7-9.9 kg). There was close agreement between both methods of assessing Crs in all infants, the mean within-subject difference (95% confidence interval (CI)) for DOT-SOT being -0.06 (-0.55- +0.42) mL x kPa(-1) x kg(-1). By contrast, estimates of Rrs,DO were on average 20% lower than those for Rrs,SO, (mean within-subject difference (95% CI) being -0.67 (-1.04- -0.31) kPa x L(-1) x s; p<0.01). The relatively lower values obtained for Rrs,DO may reflect the higher mean lung volume at which it was calculated. Further work is required to investigate the clinical and epidemiological relevance of this new approach, and whether there are any advantages of using both techniques when assessing passive mechanics in infants.

Humans↗
PubMed2001

The bias flow nitrogen washout technique for measuring the functional residual capacity in infants. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing.

The functional residual capacity (FRC) is the most commonly measured static lung volume in infants. It is important for interpreting volume-dependent pulmonary mechanics, e.g. airway resistance, and defining normal lung growth. The bias flow nitrogen washout technique is widely used for measuring FRC because the dead space and circuit resistance are low, making it suitable for small or sick infants. Moreover, data acquisition and calculation are easily programmed for a personal computer. The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for functional residual capacity measurements. While measuring the functional residual capacity is regarded as physiologically and clinically important, the accuracy of the measurement is undoubtedly equally important. Hence, the paper also emphasizes factors influencing the accuracy of functional residual capacity measurements independent of equipment requirements. These recommendations represent the "State of the Art" in 2000.

Clinical Protocols↗
PubMed2001

The infant lung function model: a mechanical analogue to test infant lung function equipment.

To facilitate international multicentre studies and quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society (ERS-ATS) working group for infant lung function testing aims to develop specifications for standardized infant lung function equipment and software. However, a standardized test device is also needed to test whether existing infant lung function equipment is able to meet these requirements. The authors have built a "mechanical model baby" consisting of a linear pump which can reproduce prerecorded tidal flow waveforms with a precision of 0.5% (full stroke), enabling the simulation of tidal and forced flow patterns. This linear pump can be connected to a series of copper lung volumes (range 50-300 mL) with known time constants, so that lung volumes can be reproduced with a precision of +/-1% at frequencies 10-120bpm. Five airflow resistors were built using sinter material. When assessed using flows 0-300 mL.s(-1) all resistors showed a quasilinear pressure/ flow relationship, with slopes 1.0-5.6 kPa.L(-1).s. These resistances could be reproduced with a precision of +/-2.5%. The infant lung model can also be used to assess frequency responses of infant lung function equipment, since the pump is capable of delivering low amplitude volumes up to 20 Hz in a pseudorandom noise manner. In summary, based on error estimations, this infant lung model is able to test whether or not infant lung function equipment meets the requirements suggested by the European Respiratory Society-American Thoracic Society standardization group, that is: flow measurements within +/-2.5%, volume and resistance measurements within +/-5%, frequency response: magnitude attenuation <+/-10% and phase shift <+/-3 degrees at 10 Hz.

Airway Resistance↗
PubMed2001

Assessment of an infant whole-body plethysmograph using an infant lung function model.

In order to facilitate international multicentre studies and improve the quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society Task Force for infant lung function testing has recently developed specifications for standardized infant lung function equipment and software. A mechanical infant lung model analogue has been developed to assess whether infant lung function equipment is able to meet these requirements. However, the practical testing of infant lung function equipment using such models is highly complex because of the need to use very small pressure and flow changes, and the numerous potentially confounding factors associated with both the design of the device and the testing procedure. The aim of this study was to determine whether the infant lung model is capable of assessing the overall function of an whole-body infant- plethysmograph, using the only infant plethysmograph that was commercially available at the time as an example. The mechanical characteristics of the model such as vibrations or noise did not disturb the delicate plethysmographic measurements and thereby allowed a reliable assessment of the system. A series of tests revealed that the plethysmograph was able to measure airway resistance 1-3.5 kPa.L(-1).s with an accuracy of +/-2.5% and lung volumes 75-300 mL with an accuracy of +/-2.5% under in vitro conditions. To conclude, the infant lung model is a useful means of assessing the overall in vitro performance of infant whole-body plethysmographs, but thermal, mechanical and frequency response characteristics of such a device must be taken into account when interpreting the results of such assessments.

Airway Resistance↗
PubMed2000

Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society.

The aim of this position paper is to define minimal performance criteria for the separate items comprising equipment used to measure respiratory function in infants together with overall performance criteria for the assembled pieces of such equipment. These guidelines cover numerous aspects including: 1) safety, 2) documentation and maintenance of equipment, 3) physical characteristics of mechanical parts and signal transducers, and 4) data acquisition. Further, validation procedures for individual components as well as for the integrated equipment are recommended. Adherence to these guidelines should ensure that infant lung function measurements can be performed with an acceptable degree of safety, precision and reproducibility. They will also facilitate multicentre collection of data and performance of clinical investigations. Manufacturers of infant respiratory function equipment should make every effort to comply with these guidelines, which represent the current standards of paediatric health professionals in this field.

Data Collection↗
PubMed2000

Tidal forced expirations. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

The progress of infant lung function testing has been retarded by both the lack of user-friendly, widely available and affordable equipment and the lack of standardized methodology. The European Respiratory Society/American Thoracic Society Task Force on Standards for Infant Respiratory Function Testing was formed in an attempt to address these deficiencies. This document represents the consensus of investigators with vast experience in the measurement of lung function in infants. The present recommendations deal with equipment requirements, study procedures and reporting of data for measurements of forced expiration at end-tidal inspiration. They represent the "state of the art" in 1999. They are not meant to inhibit further developments in this technique. The authors anticipate that these guidelines will be updated regularly as knowledge progresses.

Europe↗
PubMed2000

Tidal breath analysis for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

The aim of this position paper is to provide recommendations pertaining to software and equipment requirements when analysing tidal breathing measurements in infants. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis, and reporting of results, and highlight areas in which further research is needed before consensus can be reached. When collecting tidal breathing data in infants and children, equipment dead space and resistance must be minimized, all sources of leak eliminated, and a flowmeter with appropriate frequency response and linearity employed. Inspired gases should be corrected to body temperature, barometric pressure and saturated with water vapour conditions and efforts made to eliminate the various sources of drift in volume that can occur. In addition, the analogue-to-digital converter used to sample data must be capable of adequately resolving the highest and lowest flows required by the study. An adequate sampling rate must be used; 50-100 Hz may be sufficient for the determination of timing and volume parameters, especially in older infants, but rates of 200 Hz are recommended for analysis of the tidal breathing flow/volume loop and other sensitive parameters such as time to peak tidal expiratory flow/expiratory time. The potentially most troublesome aspect of tidal breath analysis from the computational point of view is the identification of the beginning and end of inspiration and expiration. Once methods and equipment for the measurement and analysis of tidal breathing in infants have been standardized, there is an urgent need to establish appropriate reference ranges for various key parameters so that they may be used more effectively in the clinical setting. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that more meaningful comparisons can be made between data collected in different centres or with different equipment.

Child↗
PubMed2000

Respiratory function in survivors of the United Kingdom Extracorporeal Membrane Oxygenation Trial.

Extracorporeal membrane oxygenation (ECMO) improves survival in mature neonates with reversible lung disease. However, ECMO could result in survival of infants with severe respiratory dysfunction who would otherwise have died. Alternatively, infants receiving ECMO might be spared prolonged ventilation and consequent barotrauma, resulting in improved respiratory function. Our aim was to compare respiratory function at 1 yr of age in infants assigned to receive either ECMO or conventional management (CM). Seventy-eight surviving infants of the United Kingdom (UK) ECMO trial (51 in the ECMO group) were studied at 1 yr of age. Questionnaires provided details of respiratory symptoms, and laboratory measurements of respiratory function were made for respiratory rate, tidal volume, lung volume, airway conductance, specific airway conductance, and maximal expiratory flow at FRC (Vmax (FRC)). Data were exchanged on floppy disk for cross-analysis and to ensure that investigators were blinded to the status of the infants. There was a wide spectrum of respiratory function, from normal to markedly abnormal. There were few differences between the groups, but in the CM group lung volume was increased (95% confidence intervals [CIs] of the difference in ECMO versus CM subjects: -67; -4 ml), and inspiratory specific conductance was lower (95% CI: 0.03; 0.98 s(-)(1). kPa(-)(1)). There was a trend toward a lower V max(FRC) (95% CI: -2; 67 ml/s(-)(1) in the CM group. In addition to providing a survival advantage, ECMO did not worsen lung function in infants assigned to receive it. Indeed, their lung function appeared slightly better than that of infants treated conventionally.

Child Development↗