Winfried Baden

A practical and transferable new protocol for treadmill testing of children and adults

BACKGROUND It is just as vital to have an exact overview of the physical fitness of young and growing people as it is for adults. The currently used exercise protocols have limitations in healthy small children, and in senior citizens. In particular with chronically ill patients, regardless of their age, there is a need for an exercise protocol that permits observations over the long term. With this need in mind, we have designed a new transferable standardised exercise protocol, constructing reference values based on improved assessments on a treadmill that permitted stepwise increases of speed and gradient every 90 seconds - the so called treadmill protocol from the German Society of Paediatric Cardiology. OBJECTIVES We investigated the exercise performance in a healthy Caucasian population ranging in age from 4 to 75 years. METHODS We measured, using a prospective study design, the distance run, the endurance, and the consumption of oxygen in 548 females and 647 males undergoing an enhanced spiroergometric treadmill protocol in two centres. RESULTS AND CONCLUSIONS Until puberty, boys and girls have the same indicators of exercise performance. Subsequent to puberty, uptake of oxygen and distance run differ, with males showing higher uptake of oxygen. There is still an age-dependent dynamic of peak uptake of oxygen related to body surface area. Using these new reference values, covering the whole range of age, it proves possible to compare performance during growth and aging of the individual. In this fashion, we have calculated centiles for all recorded variables. External calibration, validation and quality control ensures transferability of our data to other spiroergometry units.

Increased turnover of serotonin in children with pulmonary hypertension secondary to congenital heart disease.

Serotonin (5HT) is a potent vasoconstrictor of the pulmonary vascular bed and may be involved in the pathophysiology of secondary pulmonary hypertension in children with a left-to-right shunt due to a congenital heart defect. To test this hypothesis we measured the total and free 5HT concentration in blood as well as the urinary excretion of its main metabolite 5-hydroxyin-doleacetic acid (HIAA) in children showing a left-to-right shunt with (n=10) and without (n=18) pulmonary hypertension. 5HT and HIAA were also measured in children after corrective cardiac surgery using cardiopulmonary bypass (n=14) and in controls without congenital heart disease (n=18). The concentrations of total and free 5HT were not significantly different between controls and patients with a left-to-right shunt. After cardiac surgery total 5HT concentration was significantly reduced by about 65% owing to a postoperatively reduced platelet count. In patients with a left-to-right shunt the total 5HT content was similar in the right atrium (204.0±17.3 ng/ml), pulmonary artery (189.0±19.1 ng/ml), and aorta (195.0±19.3 ng/ml), as was the free 5HT concentration. Therefore no net release of 5HT from platelets occurred between these sampling sites. In patients with pulmonary hypertension, the urinary excretion of HIAA was significantly increased when compared with controls and patients without pulmonary hypertension. It is concluded that turbulent blood flow in children with a left-to-right shunt does not lead to a significant release of 5HT from platelets. However, the increased urinary excretion of HIAA in patients with pulmonary hypertension indicates an increased turnover of 5HT, probably due to an increased number of intrapulmonary neuroepithelial cells or a higher metabolic rate of 5HT within those cells.

Clinical and in vitro Effect of Dornase Alfa in Mechanically Ventilated Pediatric Non-Cystic Fibrosis Patients with Atelectases

Introduction: At present no evidence-based medical treatment for persistent atelectasis in pediatric non-cystic fibrosis (CF) patients is available. Method: To evaluate the use of intratracheally instilled recombinant human deoxyribonuclease (rhDNase) in intubated and ventilated pediatric patients, we performed a single-center observational study on 46 pediatric intensive care patients who had received intratracheal DNase. Patients were classified, according to radiologic findings of atelectasis (group 1) or infiltrates. As controls we examined a historical control group of 17 patients with atelectasis after cardiac surgery, who had been treated with NaCl 0.9% and matched for age and diagnosis with 21 patients from group 1 (subgroup 1a). Radiologic improvement and inflammatory markers in both serum and tracheal aspirates were measured. Results: In group 1, 35 patients had 51 atelectases/dystelectases episodes at baseline. 67 % of patients showed radiologic signs of improvement after 24h treatment with rhDNase. In subgroup 1a, 16 patients had complete resolution of atelectases and minimal change in dystelectases after a treatment of 24 hours rhDNase, compared with the control group of 17 patients, who had 7 atelectases and 10 dystelectases at baseline and an improvement in only 1 out of 17 (6 %) patients after 24h. Conclusion: Intratracheal instillation of rhDNase is an effective adjunct to conservative therapy of atelectases in children. Further randomized controlled prospective studies are necessary.

Technical considerations for inhaled nitric oxide therapy: time response to nitric oxide dosing changes and formation of nitrogen dioxide

AbstractThe aim of the present study was to analyse the time response to nitric oxide (NO) dosing changes as well as the formation of nitrogen dioxide (NO2) with different ventilation systems, respirator settings and application sites during NO inhalation. The inspired NO and NO2 concentrations were continuously measured using chemiluminiscence within a dummy ventilatory system equipped with two different respirator systems (Siemens Servo 900c and Bear BP 2001). NO was either introduced into the afferent limb of the ventilatory circuit close to the endotracheal tube (site A) or into the so-called low pressure port of the Servo 900c respirator, far away from the endotracheal tube (site B). In addition, the decay of the inspired NO concentration after cessation of the NO gas flow was studied. This decay was considerably prolonged when NO was introduced at site B (time constants: τ = 7.19 min versus τ = 0.29 min). Within the concentration range studied (0–25 ppm NO) a linear correlation between the NO and NO2 concentration was found. At site A and an inspired oxygen concentration of > 0.95 NO2 formation amounts to 1.14% ± 0.11% of the NO concentration. Using this value one can calculate the NO2 formation for a given NO dose. For example, when 40 ppm NO are applied, a concentration of 0.45 ppm NO2 can be expected, which is well below the relevant toxic concentrations. However, when NO was introduced at site B, NO2 formation was significantly increased to 1.61% ± 0.16%. Passage of the ventilated gas through soda lime led only to a slight and insignificant reduction in NO2 concentration. The continuous flow respirator BP 2001 showed a significantly lower NO2 concentration when compared to the non-continuous flow respirator Servo 900c (0.64 ± 0.11% vs.1.14 ± 0.11%). Conclusion The application of NO close to the endotracheal tube is associated with a much faster response of the actual inspired NO concentration to dosing changes and shows the lowest NO2 formation. In order to avoid toxic NO2 concentrations, an upper limit of 40 ppm NO is recommended for continuous NO inhalation.

Surfactant proteins in pediatric interstitial lung disease

Background:Children’s interstitial lung diseases (chILD) comprise a broad spectrum of diseases. Besides the genetically defined surfactant dysfunction disorders, most entities pathologically involve the alveolar surfactant region, possibly affecting the surfactant proteins SP-B and SP-C. Therefore, our objective was to determine the value of quantitation of SP-B and SP-C levels in bronchoalveolar lavage fluid (BALF) for the diagnosis of chILD.Methods:Levels of SP-B and SP-C in BALF from 302 children with chILD and in controls were quantified using western blotting. In a subset, single-nucleotide polymorphisms (SNPs) in the SFTPC promoter were genotyped by direct sequencing.Results:While a lack of dimeric SP-B was found only in the sole subject with hereditary SP-B deficiency, low or absent SP-C was observed not only in surfactant dysfunction disorders but also in patients with other diffuse parenchymal lung diseases pathogenetically related to the alveolar surfactant region. Genetic analysis of the SFTPC promoter showed association of a single SNP with SP-C level.Conclusion:SP-B levels may be used for screening for SP-B deficiency, while low SP-C levels may point out diseases caused by mutations in TTF1, SFTPC, ABCA3, and likely in other genes involved in surfactant metabolism that remain to be identified. We conclude that measurement of levels of SP-B and SP-C was useful for the differential diagnosis of chILD, and for the precise molecular diagnosis, sequencing of the genes is necessary.

Increased risk of interstitial lung disease in children with a single R288K variant of ABCA3.

The ABCA3 gene encodes a lipid transporter in type II pneumocytes critical for survival and normal respiratory function. The frequent ABCA3 variant R288K increases the risk for neonatal respiratory distress syndrome among term and late preterm neonates, but its role in children’s interstitial lung disease has not been studied in detail. In a retrospective cohort study of 228 children with interstitial lung disease related to the alveolar surfactant system, the frequency of R288K was assessed and the phenotype of patients carrying a single R288K variant further characterized by clinical course, lung histology, computed tomography and bronchoalveolar lavage phosphatidylcholine PC 32:0. Cell lines stably transfected with ABCA3-R288K were analyzed for intracellular transcription, processing and targeting of the protein. ABCA3 function was assessed by detoxification assay of doxorubicin, and the induction and volume of lamellar bodies. We found nine children with interstitial lung disease carrying a heterozygous R288K variant, a frequency significantly higher than in the general Caucasian population. All identified patients had neonatal respiratory insufficiency, recovered and developed chronic interstitial lung disease with intermittent exacerbations during early childhood. In vitro analysis showed normal transcription, processing, and targeting of ABCA3-R288K, but impaired detoxification function and smaller lamellar bodies. We propose that the R288K variant can underlie interstitial lung disease in childhood due to reduced function of ABCA3, demonstrated by decelerated detoxification of doxorubicin, reduced PC 32:0 content and decreased lamellar body volume.

Ventricular septal defect closure in a neonate with combined methylmalonic aciduria/homocystinuria

Methylmalonic acidemia with associated homocystinuria is a rare inborn error of amino acid metabolism affecting energy supply on the cellular level. Its effects on recovery from surgically induced organ ischemia are largely unknown. We report the successful closure of a nonrestrictive ventricular septal defect by following a normothermic strategy combined with ample metabolic substrate supply.

Realistic 3D-Printed Tracheobronchial Tree Model from a 1-Year-Old Girl for Pediatric Bronchoscopy Training

rial (Materialise, Germany) ( Fig. 1 a, b). The model was evaluated by flexible and rigid bronchoscopy using the smallest fiberoptic bronchoscope with a working channel available for routine bronchoscopy with an outer diameter of 2.8 mm (11005 BC1 and 11278VS, Storz, Germany) and a video bronchoscope with an outer diameter of 3.7 mm (Pentax EB1170K, Pentax, Germany). Filling the model with water provided realistic conditions for examination, most notably through the reduction of light reflection of the inner surface of the model ( Fig. 2 , 3 and online suppl. videos; see www. karger.com/doi/10.1159/000459631). The possibility to train bronchoscopic procedures in a small anatomic model could increase the accuracy, speed, and safety of performance in neonates and small infants. In addition to training the procedure in normal anatomy, also rare airway pathologies in children or interventional procedures (e.g., foreign body removal) could be trained [2–5] .

Cryorecanalization of an Obstructed Bronchial Stent in a 12-Year-Old Boy

We report a 12-year-old boy who underwent stent implantation into the left main bronchus at the age of 9.5 years for palliation of severe bronchial stenosis. He had developed complete obstruction of the stent by granulation tissue resulting in respiratory deterioration and the requirement of mechanical ventilation. The stent obstruction was treated at the age of 11.5 years by cryorecanalization. In this technique, cooling of the tip of the cryoprobe is used to induce adherence of the obstructing tissue allowing the subsequent removal of tissue particles by retraction of the probe. Under general anesthesia, a miniaturized cryoprobe was advanced via the working channel of a flexible bronchoscope. Repeat maneuvers of freezing and retraction resulted in complete recanalization of the stent. Repeat bronchoscopies 4 and 12 weeks later revealed recurrent formation of some granulation tissue which was removed by repeat cryorecanalization. Seven months after the initial procedure there was a complete patency of the stent. According to our experience, cryorecanalization is a safe and effective alternative for the treatment of stent obstruction by granulation tissue. Due to the introduction of a miniaturized probe, this method is well applicable in children since it can be performed via the working channel of a flexible pediatric bronchoscope.

Babybodyplethysmography in infants and children with congenital heart disease and pulmonary hypertension

Abstract We investigated pulmonary mechanics in 46 children (27 males, 19 females) with congenital heart defects with left-to-right shunt and pulmonary hypertension. Patients ranged in age from 6 weeks to 4 years. Babybodyplethysmography studies were performed before corrective heart surgery, and again at 2 weeks and 6 months after surgery. Preoperative pulmonary function data were compared to hemodynamic data obtained during cardiac catheterization: pulmonary artery pressure, oxygen saturation, and ratios of pulmonary to systemic blood flow (Qp/Qs) and vascular resistance (Rp/Rs). Airway resistance was elevated before surgery to 148% of predicted and it dropped significantly to normal levels, 104% of predicted, only 6 months after surgery. Functional residual capacity (FRCpleth) was increased to 127% of predicted before surgery and normalized significantly to 101% of predicted within the same time period. On the other hand, breathing frequency and minute volume, indexed to body weight, decreased significantly in the 2 weeks after surgery. Statistical analysis of the hemodynamic data and lung function tests showed only a poor linear correlation between functional residual capacity and oxygen saturation in the pulmonary artery ( r =0.26–0.37) and the Rp/Rs ratio ( r =0.38). Airway resistance also correlated poorly with the Qp/Qs and Rp/Rs ratios (both r =0.29). In young children with heart defects with increased pulmonary blood flow and pulmonary hypertension, lung mechanics are abnormal leading to bronchial obstruction and hyperinflation. Additional studies of dynamic lung compliance and elastance will be needed to look for interstitial lung alterations in these patients.