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.

[Lung function reference data in school-age children]. / Lungenfunktionsreferenzwerte im Schulalter.

UNLABELLED: The practical interpretation of lung function data depends to a very great extent on the quality of reference values. METHODS: From a population of n = 2615 schoolchildren between 6 and 12 years of age 15,404 lung function measurements were taken in accordance with commonly accepted guidelines. In the present study the validity of reference equations from the literature is examined with regard to our measured data. RESULTS: Employing linear regression analysis, the natural logarithm (ln) of forced vital capacity in ml (FVC) and expiratory volume in one second in ml (FEV1) were explained on the basis of the equation ln y = a + b* ln x (y = FVC, FEV1 (ml); x = height (cm)). Analyses were performed for girls (lnFVC = -4.8789 + 2.5504* lnheight, lnFEV1 = -4.3078 + 2.4070* lnheight) and boys (lnFVC = -4.5241 + 2.4917* lnheight, lnFEV1 = -3.7338 + 2.2985* lnheight), separately. Our coefficients correspond best to the literature dealing with a population of the same age group. On the other hand, for example, if reference values are derived from equations from the literature for the age group 6 to 18 years, they result at 6 years in an underestimation of the volume measured by us (FVC -150 ml) and at 12 years to an overestimation (FVC + 120 ml). CONCLUSIONS: The extent of the proven systematic deviations of the reference values from the measured values is of clinical and epidemiological relevance. To avoid misinterpretations, special reference values should be applied for preadolescents, at least with regard to FVC and FEV1.

Pediatric reference ranges for osteocalcin measured by the Immulite analyzer.

Pediatric reference ranges for osteocalcin measured by a new, fully automated, chemiluminescent immunometric assay on the Immulite immunoanalyzer are presented. Samples from 627 children, ranging from newborns to 18 years of age, were measured. Osteocalcin values are generally higher in children than in adults, highest levels being reached during the puberty growth spurt at about 12 years in girls and 14 years in boys, thereafter rapidly declining towards adult levels.

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.

NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma.

The relationship between nitric oxide in exhaled air, levels of sputum eosinophils, sputum eosinophil cationic protein (ECP) and urinary eosinophil protein X (EPX) excretion has not yet been investigated in corticosteroid-dependent childhood asthma. Therefore, taking 25 children with stable asthma (mean age 11.2 yrs) treated with inhaled corticosteroids and nine nonatopic healthy control children (mean age 12.8 yrs) the level of exhaled NO was measured by means of a chemiluminescence analyser before and after sputum induction. This was conducted as a slow vital capacity manoeuvre under standardized conditions with a target flow of 70 mL x s(-1) against a resistance of 100 cm H2O x L(-1) x s. Sputum induction was performed by inhalation of hypertonic saline (3, 4, and 5%) in a standardized manner and a single sample of urine was collected. Exhaled NO (p = 0.01), absolute eosinophil cell counts in sputum (p = 0.02), sputum ECP (p = 0.09) and urinary EPX excretion (p = 0.02) were higher in asthmatics compared to control children. Exhaled NO was positively correlated with sputum ECP (r(s) = 0.59, p = 0.002), urinary EPX (r(s) = 0.42, p = 0.03), and sputum eosinophils (r(s) = 0.30, p = 0.15) in the asthmatic children. These correlations appeared to be pronounced after sputum induction, where NO values had decreased (p = 0.01). None of the correlations were observed in the group of nonatopic control subjects. Additionally there were significant correlations between sputum ECP and sputum eosinophils (r(s) = 0.69, p<0.001) as well as between sputum ECP and urinary EPX excretion (r(s) = 0.58, p = 0.003) in the asthmatics. Exhaled NO provides information about the degree of eosinophilic airway inflammation and thus appears to be a useful and easy-to-perform inflammatory marker in corticosteroid-dependent asthma.

Assessment of airway function using partial expiratory flow-volume curves: How reliable are measurements of maximal expiratory flow at frc during early infancy?

We investigated the extent to which measurements of maximal expiratory flow at FRC (V EmaxFRC) are influenced by the dynamic increase of FRC in young infants by superimposing partial forced expiratory flow-volume curves on those obtained after lung inflation to 2 kPa (20 cm H2O) in 12 infants during the first month of life. The elastic equilibrium volume (EEV) of the respiratory system was estimated by extrapolating the passive expiratory time constant (obtained after lung inflation but prior to forced deflation) to zero flow. There was a very strong relationship between V EmaxFRC (which ranged from 11 to 190 ml/s) and the extent to which FRC was dynamically increased above EEV (range: 0 to 5 ml/kg), r2 = 0.88. The results of this study suggest that, although V EmaxFRC remains a useful means of measuring peripheral airway function in infants, its values should be interpreted with caution during the neonatal period. In particular, the relatively high V EmaxFRC values reported in healthy newborn infants may reflect differences in breathing strategy rather than airway structure. More meaningful within- and between-infant comparisons of peripheral airway function may be obtained by calculating forced expiratory flows at a fixed interval (e.g., 3 ml/kg) above EEV, rather than at the FRC that is operational at the time of measurement.

Analysis of forced expiratory maneuvers from raised lung volumes in preterm infants.

During recent years it has been suggested that forced expiratory measurements, derived from a lung volume set by a standardized inflation pressure, are more reproducible than those attained during tidal breathing when the rapid thoracoabdominal compression technique is used in infants. The aim of this study was to evaluate the feasibility of obtaining measurements from raised lung volumes in unsedated preterm infants. Measurements were made in 18 infants (gestational age 26-35 wk, postnatal age 1-10 wk, test weight 1.4-3. 5 kg). Several inflations [1.5-2.5 kPa (15-25 cmH2O)] were used to briefly inhibit respiratory effort before the rapid thoracoabdominal compression was performed. Conventional analysis of flows and volumes at fixed times and percentages of the forced expiration resulted in a relatively high variability in this population. However, by using the elastic equilibrium point (i.e., the passively determined lung volume, derived from passive expirations before the forced expiration) as a volume landmark, it was feasible to achieve reproducible results in unsedated preterm infants, despite their strong respiratory reflexes and rapid respiratory rates. Because this approach is independent of changes in expiratory time, expired volume, or applied pressures, it may facilitate investigation of the effects of growth, development, and disease on airway function in infants, particularly during the first weeks of life, when conventional analysis of forced expirations may be inappropriate.

Respiratory function among preterm infants whose mothers smoked during pregnancy.

We examined whether the adverse effects of prenatal exposure to tobacco on lung development are limited to the last weeks of gestation by comparing respiratory function in preterm infants whose mothers had and had not smoked during pregnancy. Maximal forced expiratory flow (Vmax FRC) and time to peak tidal expiratory flow as a proportion of total expiratory time (TPTEF:TE) were measured prior to discharge from hospital in 108 preterm infants (mean [SD] gestational age, 33.5 [1.8] wk), 40 of whose mothers had smoked during pregnancy. Infant urinary cotinine was less than 4 ng/ml in those born to nonsmokers, but it was as high as 458 ng/ml in exposed infants (p < 0.0001). TPTEF:TE was significantly lower in infants exposed to tobacco in utero (mean [SD], 0.369 [0.109]) when compared with those who were not (0.426 [0.135]) (p <= 0.02). Vmax FRC was also reduced in exposed infants (mean [SD], 85.2 [41.7] ml/s versus 103.8 [49.7] ml/s) (p = 0.07). After allowing for sex, ethnic group, body size, postnatal age, and socioeconomic status, TPTEF:TE remained significantly diminished in infants exposed prenatally to tobacco (p < 0.05). Thus, impaired respiratory function is evident in infants born on average 7 wk prior to the expected delivery date, suggesting that the adverse effects of prenatal exposure to tobacco are not limited to the last weeks of pregnancy.

Influence of ethnicity and gender on airway function in preterm infants.

While maximal expiratory flow at functional residual capacity, calculated from partial expiratory flow volume curves (V'maxFRC), is a valuable measure of peripheral airway function in infants, limited data are available in preterm infants despite their high prevalence of respiratory problems. To investigate the influence of gender and ethnic group, V'maxFRC and other indices of respiratory function were measured in 28 black and 28 white preterm infants (50% female in each group) at time of discharge from the neonatal unit (mean [SD] weight 2.36 [0.3] kg, postnatal age 19 [9] d). No infant had any history of cardiorespiratory disease and all were born to non-smoking mothers. V'maxFRC tended to be higher in girls than boys (115 versus 94 ml.s-1 [95% CI: -5; 47]) but there was no significant difference in this parameter between black and white infants (111 versus 98 ml.s-1 [95% CI of difference: -12; 40]). Respiratory resistance (Rrs) was significantly lower in black than white infants (95% CI: -2.9; -0.4 kPa.L-1.s) and tended to be lower in female than male infants (95% CI: -2.3; 0.2 kPa.L-1.s). Similarly, time to peak tidal expiratory flow as a proportion of total expiratory time (tPTEF:tE) was significantly longer in black than white (95% CI: 0.06, 0.20) and in female than male (95% CI: 0.02, 0.15) infants. These findings suggest that certain parameters of airway function may be influenced by both ethnic group and gender in preterm infants, both of which should therefore be taken mw account when investigating the effects of disease and/or therapeutic interventions in this group.

Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene.

Neonatal hyperthyroidism in the absence of maternal autoimmune thyroid disease and without thyroid-stimulating antibodies in the child is rare. We here describe a boy with severe intrauterine hyperthyroidism and advanced bone age in the absence of thyroid-stimulating autoantibodies. After long term antithyroid treatment and relapse of hyperthyroidism, a near-total thyroid resection was performed. The necessity to progressively decrease postoperative thyroid hormone replacement indicates thyroid tissue regrowth in the small thyroid remnant. Analysis of the genomic DNA of the child's peripheral leukocytes showed a G to A base exchange that led to a heterozygous Ser to Asn conversion at position 505 in the third transmembrane region of the TSH receptor (TSHR). The absence of the Ser505 Asn mutation in all other family members identifies the child's TSHR mutation as a sporadic germline mutation. Transient expression of the mutated TSH receptor in COS-7 cells showed a constitutively activated cAMP cascade. We thus identified a new constitutively activating germline mutation. Neonates with persistent nonautoimmune hyperthyroidism should be investigated for TSHR germline mutations. Because of frequent relapses, patients with sporadic congenital nonautoimmune hyperthyroidism should be treated with early subtotal to near-total thyroid resection. Moreover, post-operative radioiodine treatment should be considered.

The internal dose of passive smoking at home depends on the size of the dwelling.

As part of a longitudinal study two urine samples (survey 1 in 1991 and survey 2 in 1992) were collected from 602 elementary school children to investigate the relationship between urinary cotinine excretion (UCE) and the daily consumption of cigarettes at home (exposure). Size of the dwelling, educational level, and maternal smoking were taken into consideration as additional predictors. The history regarding parental smoking habits and confounding variables was ascertained by standardized questionnaires completed by the parents. Cotinine was measured using gas chromatography selected ion monitoring. UCE was expressed as cotinine/creatinine (ng/mg). In children with detectable UCE in survey 1 (35%) and in survey 2 (44%) the excretion ranged between 1.5 and 24.7 ng/mg (5-95%) and between 1.2 and 25.2 ng/mg, respectively. UCE measurements in both surveys were highly correlated (r = 0.65, P = 0.0001), and 59.6% of the UCE in survey 2 can be explained in linear regression by the UCE in survey 1. Using multiple linear regression, the categorized number of cigarettes reported to be consumed at home (20 cigarettes and more: 1991, P = 0.0001; 1992, P = 0.0003) and low educational level of the parents (P = 0.011 in 1991, P = 0.04 in 1992) were positively associated with UCE, whereas the size of the dwelling turned out to be negatively associated with UCE (P = 0.12 in 1991, P = 0.001 in 1992). In small dwellings (< or = 80 m2) the effect of exposure on UCE was much more pronounced. In conclusion, a single UCE measurement provides information which is widely stable within a yearly interval and is related to passive smoke history as well as to socio-economic status and the size of the dwelling. The latter variable should be considered as an effect modifier of exposure on internal dose and should be taken into account in future studies on passive smoke exposure.