The interrupter technique to assess airway responsiveness in children with cystic fibrosis

The aim of this study was to assess the validity of the interrupter technique (Rint) in measuring airway responsiveness in children with cystic fibrosis. Fifty children (aged 6-16 years) with cystic fibrosis performed six Rint measurements followed by three acceptable forced expiratory maneuvers. Each child then inhaled 5 mg of nebulized salbutamol by facemask. After 20 min the Rint and forced expiratory measurements were repeated. In the population as a whole a moderate but significant correlation between inverse Rint and FEV1 values was observed, both before and after inhaled bronchodilator (r=0.71 and 0.72, respectively, P < 0.001). However, when changes in Rint and FEV1 readings following inhaled bronchodilator were examined, no relationship was seen. Indeed, the two methods identified completely different subsets of children as being bronchodilator responsive. These results indicate that although a relationship exists between Rint and FEV1 in the whole population, this is not the case in individual children. Rint and FEV1 reflect different aspects of lung function. It is not appropriate to use Rint as a simple alternative for FEV1 in children with cystic fibrosis when assessing airway responsiveness.     

Metabolic syndrome and short‐term heart rate variability in young adults

Aims Heart rate variability (HRV) can be used to estimate autonomic nervous control of the cardiovascular system. In middle‐aged subjects, the metabolic syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in autonomic balance are already present in young adults with the MetS, and analysed the association of short‐term HRV with the MetS (using the National Cholesterol Education Program definition), in 1889 subjects aged 24–39 years. Methods Short‐term (3 min) HRV analysis included high‐frequency (HF), low‐frequency (LF) and total (TP) spectral components of HRV and LF/HF ratio. Results The presence of the MetS was associated with lower HF, LF and TP in men and women, and with higher LF/HF ratio in women. In men, waist circumference was the strongest individual MetS component that associated with HRV. After adjustments for age and heart rate, MetS was associated with lower HF and higher LF/HF ratio in women, but only with a lower TP in men (all P < 0.05). Conclusions MetS is associated with lower HRV in young adults. The individual components of MetS are differentially associated with HRV in men and in women. Our results are consistent with lower vagal activity and a possible increase in sympathetic predominance in women with the MetS. This sex difference in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in women than in men.     

Nasal bilevel vs. continuous positive airway pressure in preterm infants

Our aim was to compare the effects of nasal bilevel positive airway pressure (N-BiPAP) and nasal continuous positive airway pressure (N-CPAP) on gas exchange in preterm babies. Twenty preterm infants (mean gestational age, 26.3 weeks; mean weight at study, 1,033 g) were evaluated. Patients received two repeated cycles of N-CPAP alternated with N-BiPAP, for a total of four alternated phases, each phase lasting 1 hr. Transcutaneous PO2 (TcPO2), transcutaneous PCO2 (tcPCO2), pulsoximetry, and respiratory rate were recorded every 15 min. Arterial blood gases and acid-base balance were measured at the beginning of the first study period on baseline CPAP and at the end of the last study period on bilevel positive airway pressure. During the two N-BiPAP phases, a statistically significant (P < 0.001) increase of peripheral oxygen saturation and tcPO2, and a significant (P < 0.001) reduction of tcPCO2 and respiratory rate, were noted as compared to the two N-CPAP periods. In addition, a significant improvement of PO2 (P < 0.003) and a reduction of PCO2 were noted at the end of the test (P < 0.02). In conclusion, N-BiPAP, as compared to N-CPAP, improved gas exchange in preterm infants.     

Reference values for airway resistance in newborns, infants and preschoolers from a Latin American population

Background and objective: Several studies have determined reference values for airway resistance measured by the interrupter technique (Rint) in paediatric populations, but only one has been done on Latin American children, and no studies have been performed on Mexican children. Moreover, these previous studies mostly included children aged 3 years and older; therefore, information regarding Rint reference values for newborns and infants is scarce. Methods: Rint measurements were performed on preschool children attending eight kindergartens (Group 1) and also on sedated newborns, infants and preschool children admitted to a tertiary‐level paediatric hospital due to non‐cardiopulmonary disorders (Group 2). Results: In both groups, Rint values were inversely associated with age, weight and height, but the strongest association was with height. The linear regression equation for Group 1 (n = 209, height 86–129 cm) was Rint = 2.153 ? 0.012 × height (cm) (standard deviation of residuals 0.181 kPa/L/s). The linear regression equation for Group 2 (n = 55, height 52–113 cm) was Rint = 4.575 ? 0.035 × height (cm) (standard deviation of residuals 0.567 kPa/L/s). Girls tended to have slightly higher Rint values than boys, a difference that diminished with increasing height. Conclusions: In this study, Rint reference values applicable to Mexican children were determined, and these values are probably also applicable to other paediatric populations with similar Spanish‐Amerindian ancestries. There was an inverse relationship between Rint and height, with relatively large between‐subject variability.     

Evaluation of the interrupter technique for measuring change in airway resistance in 5-year-old asthmatic children

The interrupter technique is a noninvasive method for measuring airway resistance during quiet breathing which requires minimal subject cooperation. It, therefore, has enormous potential for use in young children unable to cooperate with conventional lung function tests. We evaluated the interrupter technique during bronchial challenge with methacholine administered by the tidal breathing method in 10 5-year-old asthmatic children. The mouth pressure/time [P_mo(t)] curve obtained following brief airflow interruption during the expiratory phase of quiet breathing was analyzed to determine the interrupter resistance R,_int using four different methods: R_intC, a smooth curve fit with back-extrapolation; R_intEO, calculated from the pressure change after the postinterruption oscillations had decayed (end-oscillation); R_intL two-point linear fit with back-extrapolation; and R_intEL, calculated from the pressure change at the end of the period of interruption. The four R_int methods were compared for repeatability and sensitivity with the direct measurement of resistance by the forced oscillation technique (R_rs) and with an independent method of measuring the response to challenge, utilizing the change in transcutaneous oxygen tension (P_tcO2). The sensitivity of the methods was defined by a sensitivity index (SI), the change after challenge expressed in multiples of the baseline standard deviation. The P_tCo2 method had the lowest variability and was by far the most sensitive method (geometric mean SI 18.9), at least 1 doubling concentration more sensitive than the other techniques in every subject (P < 0.05). R_intL was more sensitive than the other interrupter methods (geometric mean SI: R_intL 4.2; R_intC 1.O; R_intEO 2.7; R_intEL 3.1; P < 0.05) and similar in sensitivity to R_rs (geometric mean SI 4.6) in 7 out of 10 children in which this could be measured. We conclude that the interrupter method provides a simpler method than the oscillation technique for assessing airway obstruction in this age group. Pediatr Pulmonol. 1995; 20:387–395 . © 1995 Wiley-Liss, Inc.     

Maturation of antroduodenal motor activity in preterm and term infants

Previous studies have shown that duodenal motility patterns differ in preterm and term infants, but antral motor activities were not compared. Using a validated, lowcompliance, continuous-perfusion, neonatal manometric system, antral and duodenal motility was studied in 19 preterm and nine term infants. Antral motility consisted of isolated single contractions and clustered phasic contractions in term and preterm infants. There were no differences in the occurrence or amplitude of antral activity between the two groups of infants. Thus, there was no change of antral motor activity with advancing gestational age. As has been shown in other previous studies, however, intestinal motor characteristics were more immature in preterm than term infants; clustered phasic contractions occurred more frequently (P<0.02) and were of shorter duration (P<0.02) and lower amplitude (P<0.005). Duodenal clusters were significantly less common, while their amplitudes were significantly increased with increasing gestational age. The proportion of antral clusters that were temporally associated with duodenal activity was significantly lower in preterm infants than in term infants (P<0.001). Moreover, the degree of association of antral and duodenal activity increased significantly with gestational age (r=0.5,P=0.006). These data show that fasting antral motor activityper se is comparable in preterm and term infants; they also suggest that the temporal association of antral and duodenal activity develops in association with progressive changes in duodenal motor activity in the preterm infant.This word was supported by grant number HD24558 from National Institutes of Health.     

Measurement and repeatability of interrupter resistance in unsedated newborn infants

Interrupter resistance (R_int) is a useful measure of airway caliber in young children, but has not been well characterized in infants—in whom there are concerns about the accurate measurement of driving pressure. This study aimed to assess the feasibility and repeatability of measuring R_int in unsedated newborn infants, and to explore alternative algorithms for calculating driving pressure. R_int measurement was attempted in 28 healthy term newborn infants during natural sleep using the MicroRint device. Paired R_int measurements were achieved in 24 infants, but after screening of waveforms only 15 infants had at least 5 technically acceptable waveforms on both measurements. R_int values obtained were comparable with reported values for airflow resistance in newborns using other methods. However, the repeatability coefficient (CR) was much higher than reported values in preschool children using standard back‐extrapolation algorithms, with CR 2.47 KPa L^?1 sec (unscreened) and 2.93 KPa L^?1 sec (screened). Other algorithms gave only marginally better repeatability, with all CR values over 50% of the mean R_int value. Using current commercially available equipment, R_int is too poorly repeatable to be a reliable measurement of airflow resistance in newborn infants. Lower deadspace equipment is needed, but anatomical and physiological factors in the infant are also important. Pediatr Pulmonol. 2009; 44:1168–1173. © 2009 Wiley‐Liss, Inc.     

Perinatal bile acid metabolism: bile acid analysis of meconium of preterm and full-term infants

Background Our purpose was to evaluate the metabolism of bile acids in the fetus by analyzing the bile acid composition of meconium of preterm (less than 30 weeks’ gestational age) and full-term infants and comparing the results with the bile acid composition of feces of preterm and full-term infants 6 days after delivery. Methods The concentrations of individual bile acids were determined by gas chromatography-mass spectrometry after solvolysis and hydrolysis of bile acid conjugates. Results In meconium, the main bile acids were chenodeoxycholic and hyocholic acids. The main bile acid of feces from preterm infants at 6 days of age was the same as that of meconium. We also detected large amounts of secondary bile acids, especially deoxycholic acid and ursodeoxycholic acid. The ratio of cholic acid relative to chenodeoxycholic acid in meconium of preterm and full-term infants and in feces of preterm infants was less than 1, 0.36, 0.55, and 0.55, respectively. The percentage of chenodeoxycholic acid relative to total bile acids in meconium of preterm (P < 0.05) and full-term (P < 0.01) infants was significantly higher than that in feces of 6-day-old full-term infants. Conclusions More than half of the main pathway, at least, for bile acid synthesis in preterm infants may be the acidic pathway until the infants reach about 7 days of age.     

From short‐term blood pressure variability to atherosclerosis: Relative roles of vascular stiffness and endothelial dysfunction

Both arterial blood pressure (BP) average levels and short‐term BP variability (BPV) relate to hypertension‐mediated organ damage, in particular increased carotid artery intima‐media thickness (IMT) and carotid‐femoral pulse wave velocity (PWV). Endothelial dysfunction possibly mediates such damage. The authors aimed at further investigating such role in hypertensive patients. In 189 recently diagnosed, untreated hypertensive patients the authors evaluated, in a cross‐sectional design, the relationships of BP average levels and short‐term systolic (S) BPV (standard deviation of awake SBP or of 24‐hour‐weighted SBP) with IMT and PWV, and how much these relationships are explained by endothelial function parameters—brachial artery flow‐mediated dilation (FMD) and digital reactive hyperemia index (RHI). Multivariable models assessed the strength of these relationships to derive a plausible pathogenetic sequence. Both average SBP values and our measures of SBPV were significantly related to IMT (24‐hour mean SBP: r = .156, P = .034; 24‐hour‐weighted SBPV: r = .157, P = .033) and to PWV (24‐hour mean SBP: r = .179, P = .015; 24‐hour‐weighted SBPV: r = .175; P = .018), but only poorly related to FMD or RHI (P > .05 for all). At univariable regression analysis, FMD and RHI were both related to IMT, (P < .001), but not to PWV. When FMD and RHI were added to average SBP and SBPV parameters in a multivariable model, both significantly (P < .005) contributed to predict IMT, but not PWV. Thus, endothelial dysfunction relates to IMT independently of BP parameters, but appears to play a minor role in the association between BP variability‐related variables and arterial stiffening.     

Specific airway resistance,interrupter resistance,and respiratory impedance in healthy children aged 2–7 years

We report data on respiratory function in healthy children aged 2–7 years in whom we measured respiratory resistance by the interrupter technique (Rint); total respiratory impedance (Zrs), respiratory resistance (Rrs), and reactance (Xrs) by the impulse oscillation technique; and specific airway resistance (sRaw) by a modified procedure method in the whole body plethysmograph. Measurements were attempted in 151 children and were successfully obtained in 121 children with a mean (SD) age of 5.3 (1.5) years; no measurements were possible in 30 children (mean age 3 (0.9) years). The repeatability of measurements was independent of the age of the subjects, and the within-subject coefficient of variation was 11.1%, 8.1%, 10.8%, and 10.2% for sRaw, Rint, Zrs, and Rrs at 5 Hz (Rrs5), respectively. All lung function indices were linearly related to age, height, and weight. A significant negative correlation with age, height, and weight was found for Rint, Zrs, and Rrs5. Xrs5 was positively correlated to age and body size. The mean values of Rint, Rrs5, Xrs5, and Zrs in children younger and older than 5 years were 1.04, 1.38, −0.5, and 1.48 kPa · L⁻¹ · s and 0.9, 1.18, −0.37, and 1.23 kPa · L⁻¹ · s, respectively. sRaw showed no significant correlation with body size or age and the mean sRaw in children younger and older than 5 years was 1.09 and 1.13 kPa · s, respectively. None of the indices of respiratory function differed between boys and girls. Xrs and Rrs exhibited a significant frequency dependence in the range of 5–35 Hz. The techniques applied in this study require minimal cooperation and allow measurement of lung function in 80% of our population of awake young children. Further studies are needed to evaluate the potentials of the presently established reference values for clinical and epidemiological purposes. Pediatr Pulmonol. 1998; 25:322–331. © 1998 Wiley-Liss, Inc.     

Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in healthy preterm infants

To verify pathophysiological mechanisms underlying thrombocytosis in low-birth-weight (LBW) preterm babies, we evaluated kinetic changes in platelet counts and thrombopoietic cytokines including thrombopoietin (TPO), interleukin 6 (IL-6) and IL-11 in 24 uncomplicated preterm infants. Platelet counts in cord blood (CB) (265 +/- 64 x 10(9)/l) were similar to adult levels, increased by d 14 (473 +/- 140 x 10(9)/l), and then remained fairly constant. Thrombocytosis (> 500 x 10(9)/l) was observed in 9/24 (38%) subjects. Mean TPO level in CB was 5.11 +/- 1.51 fmol/ml, peaked at d 2 (7.64 +/- 3.28 fmol/ml), decreased at d 5 (3.93 +/- 1.67 fmol/ml), and thereafter kept fairly constant during the remaining neonatal period. Compared with term infants, mean TPO levels of preterm infants in CB and at d 2 were significantly higher (P < 0.01). There was an inverse correlation between platelet counts and TPO levels (r = 0.45, P < 0.001, n = 88). Preterm neonates with thrombocytosis had significantly higher TPO values in CB than those without thrombocytosis (P < 0.05). There was no significant relationship between platelet counts and IL-6. IL-11 was not detectable. These results suggest that an early elevation of serum TPO levels is related to the subsequent thrombocytosis in LBW preterm infants.