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.

Are ethnic differences in lung function explained by chest size?

BACKGROUND: Ethnic differences in lung function (LF) are recognised in adults and children. Most prediction equations for LF are derived from whites, so non-whites are at risk of erroneous assessment. It was hypothesised that differences in chest dimensions would explain differences in LF between Asian (Indian) and white schoolchildren. AIMS: To quantify the impact of chest dimensions on LF, which would inform our understanding of ethnic differences that have implications for health care. METHODS: Children aged 6-11 were studied in school. A questionnaire provided information on ethnicity and respiratory health. Spirometry was used to record FVC, FEV1, FEF25-75, and PEF. Weight, height, sitting height, and chest dimensions (chest height, circumference, antero-posterior and transverse diameters) were measured. RESULTS: Data were obtained from 294 healthy children. Standing height was the most important predictor of LF. Ethnicity was an independent predictor for all LF measures except PEF, where the effect was marginal. FVC in whites was 13.4% bigger than in Asians of the same height, and the FEV1 was 10.6% greater in whites. The influence of chest dimensions on lung function was trivial. Body mass index was smaller in Asians but did not explain differences in LF. CONCLUSIONS: Differences in chest dimensions did not explain the substantial effect of ethnicity on LF. Mechanisms whereby ethnicity exerts its influence may include differences in inspiratory muscle strength or lung compliance but remain speculative. Nevertheless it remains imperative that ethnic differences are recognised when interpreting LF tests.

Partial forced expiratory flow-volume curves in young children during ketamine anesthesia.

Maximal flows at functional residual capacity (VmaxFRC) from partial forced expiratory flow-volume (PEFV) curves were obtained in 14 normal preschool children (8 boys, 6 girls) of average age 44 mo, under general anesthesia before elective surgery. PEFV curves were generated from end inspiration by rapid compression of the chest wall with an inflatable jacket. VmaxFRC, expressed in milliliter per second, correlated linearly with height, weight, age, and FRC in milliliter and milliliters per kilogram. The best correlation of VmaxFRC (ml/s) was to height to the power of 2.47, which agrees with the results predicted by wave-speed theory. Mean FRC-corrected VmaxFRC was 2.42 +/- 0.50 (SD) FRC's/s with no significant difference between boys (2.35 FRC's/s) and girls (2.51 FRC's/s). There was no correlation between lung-size corrected VmaxFRC and height, weight, or age, but it tended to decrease with increasing FRC. The intersubject variability for VmaxFRC was reduced by normalizing for FRC, and was significantly better than that reported for awake children. This can be attributed to the greater control over volume history and more reliable maximal flow generation during anesthesia. The intrasubject coefficient of variation (CV) for VmaxFRC was 12.2%, and the intersubject CV was 20.0%. The difference may represent the variability due to dysanapsis. It is concluded that dysanapsis is not a prominent factor in children of this age group. In addition, the similarity of the regression equation for VmaxFRC vs. height to that of FRC vs. height supports the concept of equidimensional growth of the airways and lung parenchyma.

Electrocorticographic activity during repeated vs continuous hypoxia in piglets.

To assess the effects on brain activity of repeated vs continuous hypoxia, 16, 10- to 22-day-old piglets were instrumented chronically for electrocortical and arterial pH and gas tension measurements. They inhaled 10% or 6% O2 in N2 for 21 min, either continuously, or during seven, 3 min exposures interrupted by 3 min recovery periods in air, all while behaving naturally within a sealed, temperature controlled, plexiglass box. An isoelectric electrocorticogram (ECoG) and/or seizures, related to the onset of hypoxia, occurred repeatedly in 6 of the 10 exposures to 6% repetitive hypoxia, only twice in 8 exposures to 6% continuous hypoxia, and never in 10% hypoxia. A frequency analysis of the ECoG, excluding all sections exhibiting isoelectric and seizure activity, revealed no changes with 10% hypoxia, but a shift towards the lower bands during both repetitive and continuous 6% hypoxia. The extent of these shifts was greater in records that also displayed isoelectric ECoG and/or seizures. The ECoG spectrum recovered at the end of the hypoxic exposure, but not when isoelectric ECoG and/or seizures coexisted. We conclude that repeated, frequent episodes of hypoxia are more detrimental than a prolonged single event, and may contribute to the occurrence of Sudden Infant Death.

Nasal flow limitation in children.

Nasal congestion due to the common cold may be exacerbated in small children because of their small nasal passages. Our aims were 1) to test the hypothesis that smaller children have relatively larger nasal airways compared to the intrathoracic airways, and 2) to examine the effect of stenting and a decongestant on nasal patency and nasal flow. During oral forced vital capacity (FVC) maneuvers, expiratory flow is limited by intrathoracic airways. During nasal FVC, flow at high volumes is limited by the nose. The point where the nasal flow-volume curve becomes superimposable on the oral curve (%Sup) depends on the relative resistance of nasal and intrathoracic airways. Fifty-four healthy children (28 male), median age 9.5 years (range 5.9-16.0), performed full forced respiratory maneuvers through: 1) the mouth, 2) the nose, 3) the nose after application of an external stent (Breathe Right (BR) strip), and 4) the nose following instillation of xylometazoline. Peak inspiratory and expiratory flow (PIF and PEF), and mid-inspiratory and expiratory flow (MIF50 and MEF50) all showed a significant decrease from the oral to the nasal baseline maneuver. Mean (SD) %Sup of the nasal baseline was 35.6 (13.7)% and was unrelated to height. PIF and MIF50 increased with the BR strip (P < 0.05). Xylometazoline also caused a significant increase in all measured flows (P < 0.05). Mean (SD) %Sup of the nasal maneuver after application of xylometazoline increased to 53.3 (14.0)%. We conclude that there is no evidence that relative resistance of nasal and intrathoracic airways change with height. The %Sup is easy to obtain and may prove a useful index of nasal patency.

Flow-pressure looping during plethysmography in wheezy infants.

Marked looping of the expiratory portion of the flow-pressure relationship was noted in some infants during measurements of airway resistance in a whole-body plethysmograph while the respired air was maintained at body temperature and humidity. An investigation of 13 infants who had varying degrees of airway obstruction showed that there was a negative correlation (r = 0.72) between the severity of the looping and specific airway conductance (SGaw). An even stronger correlation (r = 0.85) was found between the tangent of the angle of phase lag between flow and pressure (theta) and the forced expiratory time constant (t) obtained from the partial forced expiratory flow-volume curve. Such a relationship would be predicted from a model in which the lung behaved as a simple electrical resistance-capacitance network during expiration. It is suggested that the looping is the result of small airway closure during expiration in wheezy infants, with a consequent rise in resistance and prolongation of the time constant of the lung.

A scoring system for lung function tests in infants.

Measurements of thoracic gas volume (TGV), airway resistance (Raw), and airway conductance (Gaw) were calculated in a group of 42 normal infants using a whole-body plethysmograph. Maximum expiratory flow at functional residual capacity was measured in a separate group of 108 normal infants. Using data obtained from these infants the following regression equations were calculated: Gaw (L.s-1.cmH2O) = -0.0475 + 0.00164 x length (cm) square root of TGV (mL1/2) = -3.22 + 0.263 x length (cm) VmaxFRC (mL.s-1) = -173 + 5.2 x length (cm). The standard errors of prediction are a measure of the scatter of individual results from the normal population about the true regression line. They were used to define limits of the normal ranges for these tests of lung function, and to develop a scoring system. This approach is preferable to expressing results as percent predicted, which gives no indication of how likely a measurement is to be within normal limits.

Measurement of lung volumes during active and quiet sleep in infants.

The question of whether functional residual capacity (FRC) falls in infants during active sleep has been clouded by studies using different subject groups and techniques for measurements of lung volume and determination of sleep state. Twenty healthy full-term infants within the first week of life participated in the present study. Neurophysiological and behavioral criteria were used to define sleep state, and measurements of FRC were made using a specially constructed closed-circuit helium dilution system. Regularity of respiration was recorded using magnetometers on the chest and a modified respirator monitor. Results showed that no significant changes in FRC occurred, related either to sleep state or to regularity of respiration. In addition, we failed to detect any differences in FRC between the sexes.

Cough flow-volume relationships in normal and asthmatic children.

The flow-volume profile of a maximum voluntary cough resembles that of a maximum expiratory flow-volume (MEFV) curve with superimposed transient peak flows at the onset of each cough effort and portions of zero flow corresponding to periods of glottis closure. A straight line (the cough slope) can be drawn through the transient peak flows, and the ratio of MEFV-equivalent flow to the cough peak flow can be calculated. This cough ratio has been shown to fall during adult life and may be related to changes in airway compliance and cross-sectional area with age. The present study investigated the cough ratio, cough slope, and maximum flows measured from the cough flow-volume curve in a group of normal children aged 7 to 16 years. Maximum flows and the cough slope increased with height, but the cough ratio did not change with growth or age. In a similar group of asthmatic children, baseline measurements of cough showed a reduction in cough peak flow rates, MEFV-equivalent flow, and the cough ratio. These changes are related to alterations in airway compliance and cross-sectional area and are partly reversed following inhalation of a bronchodilator.

Breath-hold MRI in evaluating patients with pectus excavatum.

Pectus excavatum (PE) is a congenital condition in which the sternum is displaced posteriorly with associated changes in the adjacent costal cartilages. The aetiology of PE is uncertain although various underlying abnormalities of the diaphragm have been implicated. There is sparse information regarding the use of fast MRI in evaluating the deformity. Our aims were to use fast MRI to evaluate static and respiratory-related dynamic chest wall characteristics, the extent of cardiac displacement and diaphragmatic excursion in patients. FLASH and TurboFLASH MR sequences in axial and coronal planes were performed on the thoraces of six young patients with PE and six individually matched healthy controls during full inspiratory and full expiratory breath-holds. The Pectus Index was derived from chest wall measurements using axial images. The distances of the left and right cardiac borders from the midline were measured using axial images, and excursion of the dome of each hemidiaphragm was measured using coronal images. The degree of sternal depression worsened substantially in expiration. Anterior chest wall movement was similar in the two groups. Patients had significantly flatter chests than the controls. There was a trend towards leftward cardiac displacement in the patients (maximum distance between left heart border and midline during full expiration 99.5 mm in patients and 91.8 mm in controls). The right diaphragmatic dome excursion was greater than the left in the controls (53.6 mm and 47.4 mm, respectively), but this was not seen in the patients (50.2 mm and 50.4 mm, respectively). It is concluded that fast MRI is very informative in evaluating skeletal abnormalities, chest wall motion, and cardiac and diaphragmatic changes seen in PE.

The shifting sands of research ethics and governance: effect on research in paediatrics.

Basic principles governing the ethical conduct of research have not changed but recent years have seen the burgeoning of bureaucracy to support and monitor research ethics and governance. More changes are planned, and the effect of the proposed changes on paediatric research are examined and broadly welcomed.

Lung function from infancy to school age in cystic fibrosis.

The aim was to investigate pulmonary mechanics in patients with cystic fibrosis during infancy and again in early childhood to see whether infant tests predicted status at school age. Plethysmographic measurements of thoracic gas volume and airways resistance were made in 29 patients at 6 months and again at 5 years 10 months. Maximum flow at functional residual capacity was measured during infancy for comparison with maximum expiratory flow rates during childhood. While many patients had normal measurements during infancy, pulmonary function had deteriorated by school age. Thoracic gas volume at school age was significantly related to the values in infancy, but other measurements made during childhood were independent of infant values. The relations between measurements in infancy and early childhood described here provide a background against which the role of external factors on pulmonary function in young children with cystic fibrosis can be investigated.

Ethical issues in lung function testing in children.

Most lung function tests are non-invasive and they are widely performed in children and adults for clinical reasons. The prevalence of respiratory disorders is such that there is a considerable amount of research in the area. For both clinical and research applications, professionals involved in lung function testing in children need to be aware of ethical issues pertaining to such testing. In general, these are not specific to lung function testing but are common to other non-invasive procedures. These include the need to recognize the autonomy of the child (appropriate for age and maturity) and the importance of providing information in ways that a child can understand. The issues surrounding consent, confidentiality, and risk-benefit assessment are particularly important in vulnerable groups such as children. Parents, too, have a clear influence on healthcare issues surrounding children and hitherto have not always been appropriately involved. Healthcare professionals have a duty to children and their families to safeguard their psychological, social and emotional well-being, as well as their physical health.

Chronic night cough and asthma severity in children with stable asthma.

The relationship between night cough and other indices of asthma severity was studied in 21 children with clinically stable asthma and persistent night cough. Overnight cough was quantified and related to symptom scores, oxygen saturation (SaO2) during sleep, evening and morning peak flow recordings and daytime tests of lung function. In the index group the median number of coughing episodes was 23 (range 1-158). Only 4 children had counts of < 10 overnight, similar to the comparison group of 12 children all of whom had counts of < 10. There was a trend towards the association of overnight cough with reduced evening peak flow (r = -0.407, P = 0.07) and reduced SaO2 (r = -0.36, P = 0.10). Abnormalities in daytime tests of lung function were observed in 13 children. There was no relationship between night cough and daytime indices of lung function abnormality although children with more severe daytime abnormalities also had significant night cough. Conversely, five children with chronic night cough had normal daytime function. Conclusion. Night-time cough in children with asthma is not simply a reflection of daytime lung function status, whereas, overnight SaO2 correlates well. Other factors need to be explored to explain the variability of night-time cough in these children.

Pulmonary sequelae of neonatal respiratory distress in very low birthweight infants: a clinical and physiological study.

Twenty infants, mechanically ventilated in the neonatal period for respiratory distress syndrome, were compared with 15 healthy controls, matched for birthweight(less than 1501 g) but greater in mean gestational age. Clinical features and lung mechanics (by whole body plethysmography) were recorded at 6-monthly intervals until about one year. THe neonatal course of the mechanically ventilated infants was commonly complicated by tracheobronchial hypersecretion and the later course by a fairly high incidence of lower respiratory tract illness. In this group, thoracic gas volume, dynamic compliance, pulmonary and airways conductance were all abnormal during the middle 4 months of the first year and reverted towards normal towards the end of the first year. The control group had normal lung mechanics. Early lung function tests were of limited value in predicting later lower respiratory tract illness, which was more common in boys, after neonatal mechanical ventilation for longer than 24 hours or raised ambient oxygen for longer than 5 days. There were few predictive physical signs. In this group of very low birthweight infants, respiratory distress syndrome of sufficient severity to require mechanical ventilation led to significant physiological and clinical disturbances of lung function which lasted into the second 6 months of life and which were particularly severe in those who had recurrent lower respiratory tract illness.