[Guidelines for the Management of Community Acquired Pneumonia in Children and Adolescents (Pediatric Community Acquired Pneumonia, pCAP) - Issued under the Responsibility of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Pulmonology (GPP)]. / S2k-Leitlinie Management der ambulant erworbenen Pneumonie bei Kindern und Jugendlichen (pädiatrische ambulant erworbene Pneumonie, pCAP).

The present guideline aims to improve the evidence-based management of children and adolescents with pediatric community-acquired pneumonia (pCAP). Despite a prevalence of approx. 300 cases per 100 000 children per year in Central Europe, mortality is very low. Prevention includes infection control measures and comprehensive immunization. The diagnosis can and should be established clinically by history, physical examination and pulse oximetry, with fever and tachypnea as cardinal features. Additional signs or symptoms such as severely compromised general condition, poor feeding, dehydration, altered consciousness or seizures discriminate subjects with severe pCAP from those with non-severe pCAP. Within an age-dependent spectrum of infectious agents, bacterial etiology cannot be reliably differentiated from viral or mixed infections by currently available biomarkers. Most children and adolescents with non-severe pCAP and oxygen saturation > 92 % can be managed as outpatients without laboratory/microbiology workup or imaging. Anti-infective agents are not generally indicated and can be safely withheld especially in children of young age, with wheeze or other indices suggesting a viral origin. For calculated antibiotic therapy, aminopenicillins are the preferred drug class with comparable efficacy of oral (amoxicillin) and intravenous administration (ampicillin). Follow-up evaluation after 48 - 72 hours is mandatory for the assessment of clinical course, treatment success and potential complications such as parapneumonic pleural effusion or empyema, which may necessitate alternative or add-on therapy.

Safety and tolerability of seasonal ultra-rush, high-dose sublingual-swallow immunotherapy in allergic rhinitis to grass and tree pollens: an observational study in 193 children and adolescents.

OBJECTIVE: We conducted a large observational study in 193 children and adolescents with allergic rhinitis due to grass or tree pollens to evaluate the safety and tolerability of an ultrarush high-dose sublingual immunotherapy (SLIT) regimen reaching a maintenance dose of 300 index of reactivity within 90 minutes. METHODS: Children and adolescents aged 5 to 17 years with at least a 1-year medical history of allergic rhinitis with or without mild to moderate asthma due to tree pollens (birch, alder, hazel) or grass pollens (cocksfoot, meadow grass, rye grass, sweet vernal grass, timothy) were recruited. Standardized grass and tree pollen allergen extracts were used for ultrarush titration and subsequent coseasonal maintenance. RESULTS: During ultrarush titration, 60 patients (31%) reported 117 predominantly mild and local adverse events, which resolved within 150 minutes. During the maintenance phase, 562 adverse events were reported; the most frequent local events were oral pruritus, burning sensation, lip or tongue swelling, and gastrointestinal symptoms, and the most frequent systemic events were rhinoconjunctivitis and asthma. There was 1 clinically significant asthma event in an 11-year old boy with known asthma in whom SLIT was resumed after an interval of 4 days. CONCLUSION: Ultrarush titration was safe and well tolerated. Pediatric patients with asthma should be carefully monitored and adequately trained to use their rescue medications.

Importance of inhaler devices in the management of airway disease.

The delivery of drugs by inhalation is an integral component of asthma and chronic obstructive pulmonary disease (COPD) management. However, even with effective inhaled pharmacological therapies, asthma, particularly, remains poorly controlled around the world. The reasons for this are manifold, but limitations of treatment guidelines in terms of content, implementation and relevance to everyday clinical life, including insufficient patient education, access to health care and cost of medication as well as poor inhaler technique are likely to contribute. Considering that inhalation therapy is a cornerstone in asthma and COPD management, little advice is provided in the guidelines regarding inhaler selection. The pressurised metered dose inhaler (pMDI) is still the most frequently prescribed device worldwide, but even after repeated tuition many patients fail to use it correctly. In addition, the correct technique can be lost over time. Although several improvements in pMDIs such as a change in the propellant and actuation have resulted in improvements in lung deposition, many dry powder inhalers (DPIs) are easier to use. However, these devices also have limitations such as dependency of drug particle size on flow rate and loss of the metered dose if the patient exhales through the device before inhaling. Improvements in using inhalation devices more efficiently, in inhaler design for supporting patient compliance, and advances in inhaler technology to assure drug delivery to the lungs, have the potential to improve asthma and COPD management and control. New and advanced devices are considered being helpful to minimise the most important problems patients have with current DPIs.

Secretion of cholesteryl-ester-rich lipoproteins by the perfused livers of rabbits fed a wheat-starch-casein diet.

Rabbits fed a cholesterol-free semi-synthetic wheat-starch-casein diet had a high plasma cholesterol concentration; most of the cholesterol was associated with low-density lipoproteins (LDL). Chemical analyses of plasma lipoproteins revealed that very-low-density lipoproteins (VLDL), intermediate lipoproteins and LDL from casein-fed rabbits contained more cholesteryl ester than that of lipoproteins isolated from chow-fed animals. The fatty acid composition of cholesteryl esters of plasma lipoproteins showed that there were higher contents of oleic acid than linoleic acids in lipoproteins from casein-fed rabbits. Lipoproteins isolated from liver perfusates of casein-fed rabbits had higher cholesteryl oleate content than lipoproteins from chow-fed rabbit liver perfusates. There was a marked increase in secretion of apolipoproteins from perfused livers of casein-fed rabbits. We conclude that the high levels of plasma cholesterol in casein-fed rabbits are of hepatic origin and that one of the hypercholesterolemic actions of dietary casein in rabbits is the induction of hepatic synthesis and secretion of cholesteryl-ester-rich lipoproteins.

Pulmonary artery sling with tracheal stenosis: primary one-stage repair in infancy.

Pulmonary artery sling is often associated with tracheal stenosis. In many cases repair of the vascular anomaly alone does not relieve dyspnea. Primary one-stage repair with long segment tracheal resection (2.4 cm) and relocation of the left pulmonary artery using cardiopulmonary bypass and deep hypothermic circulatory arrest is described in a 6.5-month-old girl weighing 6.5 kg. This technique resulted in normal ventilation and pulmonary flow distribution.

Effect of endotracheal tube leakage on functional residual capacity determination by nitrogen washout method in a small-sized lung model.

The determination of functional residual capacity (FRC) would be extremely helpful for the controlled adjustment of mechanical ventilation in sick neonates and infants. However, these patients have small lung volumes and usually have been intubated by uncuffed endotracheal tubes (ETT). Therefore, the open-circuit nitrogen washout technique (N2wo) may give false FRC values if the inspired oxygen concentration (FIO2) is high and leakage around the ETT is present. We evaluated the N2wo as supplied by the Pediatric Pulmonary System 2600 (Sensor-Medics) in a small-sized lung model by 570 measurements using five different ventilator settings, an FIO2 increasing up to 0.9, different bypass flows between 0 and 12 L/min, and various patterns of leakage, either during inspiration or exhalation, or both. We found the most reliable results (error, 0.6%; CV, 0.7%) with a bypass flow of 6 L/min. Absolute N2 volumes as small as 14 mL could be measured using an FIO2 as high as 0.9 with only slight loss of accuracy (error, 4%; CV, 2.8%). During leakage, FRC had been underestimated with a very strong correlation to the total amount of leakage over the measurement period, which was irrespective of the ventilatory parameters (r = 0.9, P < 0.001). The regression equation could, therefore, be used for FRC correction in the lung model. However, most of the miscalculation was due to N2 loss during expiratory leakage, which quite simply and reliably can be excluded by an end-inspiratory occlusion test.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinal study of lung mechanics in normal infants.

Lung mechanics and partial forced expiratory flows were measured serially in seven normal infants during the first year of life. Lung mechanics were measured by the end inspiratory occlusion technique and partial forced expiratory flows by the rapid chest compression method. Thoracic gas volume, compliance, and partial forced expiratory flows measured at functional residual capacity progressively increased with age and correlated with height cubed. Respiratory system resistance progressively fell whereas volume-corrected flows remained fairly constant over the study period. These findings provide longitudinal lung function data and support the concept of isotropic lung growth.

[Antihistamines in pediatrics]. / Antihistaminika in der Pädiatrie.

Histamine antagonists have various effects on H1, H2, cholinergic, adrenergic and serotoninergic receptors. In childhood side effects may be different and central agitation may be more pronounced than in adults. Histamine antagonists should be avoided in the fetal and neonatal periods. They are not indicated in common cold. The use of histamine antagonists in childhood will be discussed.

[Obliterating bronchiolitis following measles]. / Obliterierende Bronchiolitis nach Masern.

We report the complex clinical course over 15 years in a child who at the age of 19 months developed patchy pneumonic infiltrates and bronchiolitis after measles. Chronic atelectasis led to resection of the right upper lung lobe. He developed bilateral bronchiectases, predominantly in the right lung. Ventilation/perfusion scans showed a major reduction of both ventilation and perfusion mainly on the right side. Early recognition of obliterative bronchiolitis is important in order to provide adequate supportive treatment of possible complications.

[Acute bronchial obstruction in infancy--therapeutic concepts]. / Die akute Bronchusobstruktion im Säuglingsalter--therapeutische Konzepte.

Acute wheezing in infancy is a very common problem in pediatric practice. One diagnosis is RSV-bronchiolitis in the very young infant, but more often acute wheezy bronchitis will be diagnosed, which is also induced by viral infection and may be the first exacerbation of asthma. Both require the same basic therapy, but there ist no agreement about the therapy with bronchodilators. Similarly their is controversy about the use of antiviral agents for RSV-bronchiolitis. The most important strategies for the acute, and not the long term therapy, will be reviewed and discussed.

A summary of the results of 55 chemicals screened for developmental toxicity in mice.

Fifty-five chemicals, including known teratogens, known embryotoxins, equivocal teratogens, nonembryotoxins, and nonteratogens, as well as compounds of unknown teratogenic or embryotoxic potential, were evaluated in the Chernoff/Kavlock developmental toxicity screen. All chemicals were administered by gavage to pregnant ICR/SIM mice on gestation days 8 through 12. The mice were allowed to deliver, and several neonatal growth and viability parameters were measured in the offspring. Comparative statistical analysis of these parameters between treated animals and concurrent (vehicle-treated) controls provided a data base to evaluate the validity of the developmental toxicity screen as an assay to detect teratogens and embryotoxins. Of the 26 compounds reported in the literature to be teratogenic or embryotoxic in mice following oral administration, 24 were positive in the developmental toxicity screen. Of the compounds previously tested in conventional assays and found to be devoid of teratogenic or embryotoxic activity in mice, 93% were negative in the developmental toxicity screen. The importance of experimental design, dose selection, and neonatal growth and viability measurements as they relate to interpretation and evaluation of the results of the developmental toxicity assay are discussed.

Organization of the core lipids of lipoproteins from normal and cholesterol-fed rabbits. A proton nuclear magnetic resonance study.

When rabbits are fed a diet supplemented with cholesterol, their plasma cholesterol levels increase markedly, and they develop atherosclerosis. Most of the plasma cholesterol exists as cholesteryl esters in very low density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL). The triglyceride content of the lipoprotein cores decreases sharply during cholesterol feeding. This change is most marked for VLDL in which it decreases from 74% to 5%, while the cholesteryl ester content increases from 26% to 95%. The IDL and low-density lipoprotein (LDL) fractions from cholesterol-fed rabbits have a triglyceride content of 2% or less in their cores. The mobility of the core cholesteryl esters has been studied by proton nuclear magnetic resonance spectroscopy. Changes in the mobility were assessed by measuring the temperature dependence of the amplitude of the methylene resonances. The decrease in spectral amplitude for VLDL, IDL, and LDL from cholesterol-fed rabbits between 55 and 15 degrees C shows that the mobility of the core cholesteryl esters is temperature dependent and that the cholesteryl esters display thermal order--disorder transitions with midpoints of 42, 40, and 38 degrees C, respectively. At physiological temperatures, the core cholesteryl esters of lipoproteins from cholesterol-fed rabbits therefore exist in a partially ordered state. In contrast, the core cholesteryl esters of VLDL, IDL, and LDL from normal rabbits show no evidence for an order--disorder transition. This is consistent with their high core triglyceride content which precludes the existence of an ordered cholesteryl ester phase within the core. The core cholesteryl esters of normal rabbit lipoproteins therefore exist in a liquid state at physiological temperatures. High-density lipoproteins (HDL) from normal and cholesterol-fed rabbits fail to display an order--disorder transition. This is attributed to the constraints imposed by the small HDL core diameter, which prevents the existence of an ordered arrangement of cholesteryl esters, irrespective of the core triglyceride content.

Pressure sensor plethysmography: a method for assessment of respiratory motion in children.

Noncalibrated respiratory inductance plethysmography has been used to measure respiratory function by calculation of the phase angle and, more recently, by determination of the ratio of each time to reach peak tidal expiratory flow to total expiratory time (TPEF/TE). Since TPEF/TE is known to be decreased in airway obstruction when derived from flow signals obtained by a pneumotachograph, we wanted to develop an alternative method to measure rib cage and abdominal respiratory movements. For this purpose, we used two pressure sensors attached to the skin above the umbilicus and in the right medioclavicular line at the fourth intercostal space: "pressure sensor plethysmography". We tested the ability of this method to assess thoracoabdominal asynchrony and TPEF/TE by comparison with respiratory inductance plethysmographic and pneumotachographic measurements in 30 children, aged 1-12 yrs, with airway obstruction. The mean difference (95% confidence interval (95% CI)) between phase angles obtained by respiratory inductance plethysmography and pressure sensor plethysmography was only -5.8 degrees (range -18.0 to +6.4 degrees). Similarly, all methods used to measure TPEF/TE agreed well: mean differences (95% CI) between pneumotachographic and respiratory inductance plethysmographic, pneumotachographic and pressure sensor plethysmographic, and respiratory inductance plethysmographic and pressure sensor plethysmographic measurements of TPEF/TE were +0.01 (range -0.05 to +0.06), -0.03 (-0.09 to +0.03) and -0.03 (-0.10 to +0.04), respectively. We conclude that pressure sensor plethysmography is a simple and noninvasive method, and suitable to measure thoracoabdominal asynchrony and TPEF/TE ratios as well as respiratory inductance plethysmography and pneumotachography.

[Neonatal variant of Bartter syndrome]. / Die neonatale Variante des Bartter-Syndroms.

A male preterm infant of 32 weeks of gestation with history of severe polyhydramnios during pregnancy presented soon after birth with polyuria with initial sodium chloride loss subsequently followed by increasing potassium loss. After manifestation of hypokalaemia, hypochloraemia, alkalosis and high urinary prostaglandin concentrations, the diagnosis of the neonatal variant of Bartter's syndrome was made. The treatment consisted of administered of large amounts of fluid with sodium chloride and potassium supplementation and indomethacin (1.5 to 2 mg/kg per day).

Inhaled frusemide against cold air induced bronchoconstriction in asthmatic children.

Inhaled frusemide prevents bronchoconstriction in asthmatic adults induced by various triggers. To determine if frusemide provides similar protection in children, whether this is age dependent and equally effective for central and peripheral airways, we performed a double blind, placebo controlled, randomised, crossover study on the effect of inhaled frusemide on lung function changes induced by cold air challenge in 21 asthmatic children. In addition, we measured diuresis before and after inhalation. Bronchodilatation after frusemide was not observed. However, deterioration in lung function after frusemide, compared with placebo, was significantly diminished: forced expiratory volume in one second (FEV1) was -5.7% v -11.5%, peak expiratory flow (PEF) -7.7% v -23.3%, maximum expiratory flow at 50% of vital capacity (MEF50VC) -16.0% v -35.2%, and at 60% of total lung capacity (MEF60TLC) -32.4% v -61.6%, and specific airways conduction -42.0% v -57.7%, respectively. This effect was not age dependent. Diuresis was significantly increased from a mean (SEM) of 198 (34) ml/3 hours before inhaled frusemide to 379 (62) ml/3 hours after nebulisation. We conclude that inhaled frusemide prevents cold air induced bronchoconstriction in asthmatic children and that increased diuresis can be expected with a dose as low as 28 mg of frusemide given by nebuliser.

Assessment of tidal breathing patterns for monitoring of bronchial obstruction in infants.

Two parameters of tidal breathing, the ratio of time to reach peak tidal expiratory flow to the total expiratory time (Tme/TE) and the ratio of volume exhaled at peak tidal expiratory flow to the total exhaled volume (dV/VT) were used to assess lung function in 21 sedated infants (aged 6-14 mo) with different degrees of airway obstruction. These parameters were compared with airway resistance as percentage predicted (Raw%) and maximum expiratory flow at functional residual capacity corrected for lung volume (VmaxFRC/TGV). VmaxFRC/TGV values correlated significantly with Tme/TE (r = 0.630, p = 0.002) as well as with dV/VT (r = 0.728, p = 0.001). Raw% values showed only a weak correlation with dV/VT (r = -0.435, p = 0.048). We conclude that Tme/Te and dV/VT are both able to detect airway obstruction in infants and that these parameters correlate much better with the forced expiratory flow values obtained by the rapid thoracic compression method than with airway resistance, determined by body plethysmography.

[Lung function equipment for pediatric practice. Results of a comparative study]. / Lungenfunktionsgeräte für die pädiatrische Praxis. Ergebnisse einer vergleichenden Untersuchung.

Pulmonary function tests can be performed in general practice since small computerized spirometers have been developed. Pediatricians also see many patients with respiratory disease but measurement of lung function in children requires special considerations. We examined 10 commercially available spirometers to assess their suitability for testing pulmonary function in children.

Hypoxaemia after nebulised salbutamol in wheezy infants: the importance of aerosol acidity.

The effect of nebulised iso-osmolar, preservative free, but acidic salbutamol solution was studied in 34 acutely wheezing infants aged 1-17 months. Transcutaneous oxygen pressure (TcPO2) and oxygen saturation (SO2) fell significantly during the first five minutes after nebulisation with further deterioration at 15-20 minutes. Ten of these infants were followed up for another two hours and showed slight improvement. Even after the second hour TcPO2 had not reached baseline values. Three months later the response to salbutamol and a placebo of equal acidity (pH 3.9) was studied in 11 infants from the same group, now free of symptoms. Lung function tests were included and showed no significant changes in specific conductance and volume corrected maximum expiratory flows (Vmax at functional residual capacity/thoracic gas volume). However, hypoxaemia occurred after the acidic placebo with a significant drop of TcPO2 (mean 0.9 kPa); SO2 decreased similarly but this did not reach significance. After salbutamol there was a further significant deterioration of mean TcPO2 (1.4 kPa) and of SO2. These results show that beside a possible pharmacological effect of salbutamol the acidity of the aerosol also induces hypoxaemia in infants.

Validation of an in vivo developmental toxicity screen in the mouse.

A test system for identifying toxicity, including potential teratogenicity has been developed that is based on growth and viability of embryonic, fetal, and postnatal mice (J Toxicol Environ Health 10:541-550, 1982). To test the utility of this assay, a series of 55 compounds was administered to timed-pregnant ICR/SIM mice during organogenesis. The test compounds included known teratogens, known nonteratogens, and equivocal teratogens. They represented a wide variety of classes including pesticides, organic solvents, metals, steroids, nutrients, food additives, antimetabolites, alkylating agents, and pharmaceutical agents. A single dose level, at or near the level producing overt maternal toxicity in preliminary range-finding studies, was administered by gavage on gestation days 8 through 12. Females were allowed to deliver; litter size and weight on the day of birth and 2 days postpartum were recorded, and stillborns were examined. Dams that had not given birth by gestation days 21 or 22 were killed and their uteri were examined. The results confirmed a strong correlation between reported teratogenic activity and embryo/fetal viability, and/or postnatal growth and viability. The results indicate that this test system is an effective, cost-efficient means of prioritizing compounds for more detailed teratogenicity testing.

Workshop on the Chernoff/Kavlock preliminary developmental toxicity test.

The Chernoff/Kavlock assay, proposed as a preliminary screen for teratogenic potential, was the subject of a 2-day workshop sponsored by the National Institute for Occupational Safety and Health. Data from three large testing programs were presented, representing tests of 165 chemicals, of which 33 were tested at least twice. Applications of the test in industrial laboratories and product development, hazard identification, and risk assessment were discussed. Workshop participants recognized the assay as one of several valid ways to preliminarily evaluate chemicals with unknown developmental toxicity. Other preliminary tests were also discussed in terms of their relationship to this test, which was seen as having the advantage of providing information on neonatal viability. Other techniques, particularly an abbreviated conventional teratology study, were also recognized as appropriate screens. The preferred test in a particular laboratory will be dependent upon the particular skills and objectives of that laboratory. Standardized protocols were suggested, but flexibility in experimental design was considered necessary, and many variations on the basic test could be appropriate. This preliminary test has been used most often as a single-dose test in mice, but might provide more generally useful data if conducted in rats using two dose levels. Workshop participants viewed the test as highly reliable in correctly identifying developmentally toxic chemicals and suggested that a negative finding in a properly conducted Chernoff/Kavlock test could be a sufficient basis for regulatory agencies to determine that conventional teratology tests in the same species are not warranted.