Inflammatory markers in induced sputum of school children born before 32 completed weeks of gestation.

OBJECTIVE: To test whether chronic bronchial inflammation may be a contributing risk factor for persistent airflow limitation in children born before 32 weeks of gestation in later life. STUDY DESIGN: Thirty-six of 160 children born before 32 completed weeks of gestation who were born between 1988 and 1992 were recruited at a median age of 11 years. Eighteen age-matched children born at term were controls; 47% of the premature infants and 61% of the term born children produced sputum of sufficient quality for interleukin (IL)-8, cell numbers, and differential counts. RESULTS: Compared with term born children, sputum from the premature group had a higher proportion of neutrophils (62% vs 3.8%; P < .001) and higher IL-8/protein values (1.93 µg/g vs 0.64 µg/g; P = .008). Forced expiratory flow 25%-75% and forced expiratory volume in 1 second/vital capacity were significantly lower (73.4 % vs 116% predicted, P = .002 and 97% vs 101%, P = .012, respectively). Lung function values and sputum indices did not correlate. IL-8/protein and neutrophil percentages correlated significantly with decreasing gestational age (Spearman rank coefficient = -0.58, P = .020 and -.70, P =.03 respectively). CONCLUSION: A significant proportion of school children born very preterm demonstrate persistent peripheral airway obstruction that is accompanied by neutrophilic lower airway inflammation.

Optimization of the Post-Process Heat Treatment Strategy for a Near-α Titanium Base Alloy Produced by Laser Powder Bed Fusion.

During the last decades, titanium alloys have been of great interest for lightweight applications due to their high strength in combination with a low material density. Current research activities focus on the investigation of near-α titanium alloys produced by laser powder bed fusion (LPBF). These alloys are known for their superior tensile strength and high creep resistance. This study focuses on the optimization of post-process heat treatments and the impact on tensile and creep strength of a LPBF produced Ti6242S alloy. Therefore, a variety of annealing steps were conducted to gain knowledge about the decomposition process of the non-equilibrium as-built microstructure and the arising influence on the mechanical properties. Components made of Ti6242S and produced by LPBF reveal an extraordinarily high ultimate tensile strength of about 1530 MPa at room temperature, but show a low elongation at fracture (A5 = 4.3%). Based on microstructure-property relationships, this study recommends precise heat treatments on how to improve the desired mechanical properties in terms of strength, ductility as well as creep resistance. Moreover, this study shows a triplex heat treatment, which enhances the elongation at fracture (A5) to 16.5%, while the ultimate tensile strength is still at 1100 MPa.

The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children.

BACKGROUND: Although respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) in early life are followed by later airway hyperreactivity, it is unclear whether there is a causal relationship between this and an atopic diathesis. OBJECTIVES: To separate the effects of RSV LRTI and an atopic diathesis on subsequent recurrent wheezing, we examined the protective effect of previous palivizumab administration against subsequent recurrent wheeze in infants with and without a family history of atopy. METHODS: A prospective multicenter, matched, double cohort study was conducted in 27 centers in Europe and Canada. The rates of physician-diagnosed recurrent wheezing in premature infants <36 weeks gestation who had received palivizumab in the first year of life were compared to those of gestational age-matched controls. RESULTS: The relative protective effect of palivizumab on physician-diagnosed recurrent wheezing through the ages of 2 to 5 years was 68% in those with no family history of asthma (odds ratio, 0.32; (95% CI, 0.14-0.75; N = 146 palivizumab-treated, 171 untreated) and 80% in those with no family history of atopy or food allergies (odds ratio, 0.20; 95% CI, 0.07-0.59; N = 101 palivizumab-treated, 100 untreated). In contrast, there was no effect of palivizumab on subsequent recurrent wheezing in the 90 children with a family history of atopy or food allergies compared to 130 untreated infants with atopic families. CONCLUSION: Respiratory syncytial virus prophylaxis in nonatopic children decreases by 80% the relative risk of recurrent wheezing but does not have any effect in infants with an atopic family history. This suggests that RSV predisposes to recurrent wheezing in an atopy-independent mechanism.

Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing.

OBJECTIVE: Children who experience respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) early in life have high rates of subsequent recurrent wheezing. Palivizumab, an anti-RSV monoclonal antibody, has 78% to 80% efficacy in preventing RSV hospitalization in premature infants without chronic lung disease. We hypothesized that palivizumab, by ameliorating or preventing early RSV LRTI in preterm infants, might decrease later recurrent wheezing. STUDY DESIGN: A cohort of preterm infants who had received palivizumab and were not hospitalized for RSV (n = 191) or who never received palivizumab (n = 230; 76 who were hospitalized for RSV and 154 who were not), were prospectively followed for 24 months beginning at a mean age of 19 months. The subjects were assessed for recurrent wheezing by caretaker or physician report. RESULTS: The incidences of recurrent wheezing and physician-diagnosed recurrent wheezing were significantly lower in the 191 palivizumab-treated subjects (13% and 8%, respectively) compared with all 230 untreated subjects (26%, P = .001 and 16%, P = .011, respectively) and with the 154 patients in the subgroup not hospitalized for RSV LRTI (23%, P = .022 and 16%, P = .027, respectively). The effect of palivizumab treatment remained significant after adjustment for potential confounding variables. CONCLUSIONS: Our study suggests that preventing RSV LRTI with palivizumab may reduce subsequent recurrent wheezing in premature infants.

Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. In contrast to other confirmed risk factors that predispose to a higher morbidity and mortality, the particular risk of a preexisting neuromuscular impairment (NMI) in hospitalized children with RSV infection has not been prospectively studied in a multicenter trial. METHODS: The DMS RSV Paed database was designed for the prospective multicenter documentation and analysis of all clinically relevant aspects of the management of inpatients with RSV infection. Patients with clinically relevant NMI were identified according to the specific comments of the attending physicians and compared with those without NMI. RESULTS: This study covers 6 consecutive seasons; the surveillance took place in 14 pediatric hospitals in Germany from 1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541 pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe course of the infection (multiple risk factors in some patients; prematurity in 30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually, the attributable mortality was significantly higher in the NMI group (5.5% vs. 0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was independently associated with pediatric intensive care unit (PICU) admission (OR, 4.94; 95% CI, 2.69-8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI, 1.28-10.22; P = 0.017). CONCLUSION: This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.

Establishment of age-dependent reference values for IgA subclasses.

BACKGROUND: Recently, subclass-specific antisera have been introduced for application in a nephelometric assay. The aim of this study was to establish age-dependent reference values for serum concentrations of the two IgA subclasses in children and adults. METHODS: Serum levels of IgA1 and IgA2 were measured by automated immunonephelometry in samples from 235 clinically healthy children between 6 months and 18 years of age and 36 healthy adults. RESULTS: Both IgA1 and IgA2 were detectable in all samples, and both IgA1 and IgA2 increased with increasing age. In adults, the mean value for IgA1 is 1.46 g/l for IgA2 0.21 g/l and for total IgA 1.94 g/l. Individual IgA2 values correlate significantly (p < 0.0001) with IgA1 values (r(2) = 0.5433). In addition, there was a highly significant (p < 0.0001) correlation (r(2) = 0.9530) between the measured total IgA and the sum of the two IgA subclasses indicating that immunonephelometry using highly specific polyclonal antisera might be superior to other methods. CONCLUSIONS: These results and the availability of age-dependent reference values make it worthwhile to reassess the role of IgA subclasses in immunodeficiency and autoimmune diseases where conventional methods have led to conflicting results.

Evaluation of tracheobronchial anomalies in children using low-dose multidetector CT: report of a 13-year-old boy with a tracheal bronchus and recurrent pulmonary infections.

Tracheobronchial anomalies in children may be associated with recurrent episodes of pulmonary infections and symptoms of recurrent or persistent airway obstruction. Diagnosis by conventional imaging may be difficult. Multidetector computed tomography (MDCT) offers the possibility to generate a virtual three-dimensional bronchoscopy, thus enabling detailed overview of the tracheobronchial system. We report on a 13-year old boy, admitted to hospital after recurrent episodes of bronchial infections. Functional studies showed airway obstruction with no response to bronchodilators. A chest radiograph was normal. Flexible bronchoscopy revealed tracheobroncho malacia of the distal trachea and the right main bronchus. The ostium of an accessory right-sided tracheal bronchus, which could not be entered by the endoscope, was also detected. MDCT using a low-dose protocol was performed on a four-section scanner (Somatom Volume Zoom, Siemens, Erlangen, Germany). A three-dimensional virtual bronchoscopy based on surface rendering was generated, which confirmed moderate narrowing of the trachea and right main bronchus. Furthermore, an accessory and stenotic tracheal bronchus including poststenotic segments, ventilating parts of the right upper lobe, could be clearly visualized. MDCT can be a valuable instrument in the diagnostic pathway of assessing tracheobronchial anomalies in children, including visualization of poststenotic bronchial structures. The use of low-dose protocols provides adequate image quality to perform virtual bronchoscopy, thus reducing administered radiation to a tolerable amount.

Hepatic mesenchymal hamartoma in a preterm newborn: demonstration by low-dose multidetector CT.

Primary liver tumours are very rare in the neonatal period. Differential diagnoses include haemangioendothelioma, malignant hepatoblastoma and mesenchymal hamartoma. Due to non-specific clinical symptoms and indecisive imaging findings, correct diagnosis may be difficult to establish. We report a female preterm newborn who was delivered at 33 weeks of gestation and in whom ultrasonography (US) revealed a large cystic intraabdominal tumour of unknown origin. For further evaluation, contrast-enhanced multidetector computed tomography (CT) was performed on the 4th day of life using a low-dose protocol (80 kVp, 50 mAs, collimation 0.75 mm, total effective dose 3.6 mSv). Based on CT findings, diagnosis of an intrahepatic mesenchymal hamartoma was made and confirmed by tumour resection and histopathological examination. In conclusion, multidetector CT (MDCT) using a low-dose protocol can be exceptionally used to establish diagnosis of a mesenchymal hamartoma in a preterm newborn.

Tracheobronchial anomalies and stenoses: detection with low-dose multidetector CT with virtual tracheobronchoscopy--comparison with flexible tracheobronchoscopy.

PURPOSE: To prospectively assess the sensitivity and specificity of low-dose multidetector computed tomography (CT) with virtual tracheobronchoscopy (VT) for evaluation of suspected airway stenoses and/or abnormalities by using flexible tracheobronchoscopy (FT) as the reference standard. MATERIALS AND METHODS: The study was approved by the local ethics committee; parental consent was obtained. Forty-five patients with clinically and/or radiographically suspected tracheobronchial stenosis and/or anomaly underwent FT and contrast material-enhanced single-phase multidetector CT with VT. CT was performed with an age- and weight-adjusted low-dose protocol: 120 or 80 kV; 120 or 60 mA; collimation, 1.5 or 0.75 mm; gantry rotation, 0.5 second. Mean effective dose was calculated for all examinations. Postprocessing was performed with surface rendering of VT images and multiplanar reformations. CT images were analyzed in consensus by two radiologists who were blinded to FT results. Statistical analysis was performed with 2 x 2 contingency tables; 95% confidence intervals (CIs) were calculated with the Blyth-Still-Casella procedure. RESULTS: Mean patient age was 4.4 years (range, 2 months to 16 years; 53% male patients). Tracheobronchial narrowing and/or abnormality were depicted at FT in 38 of 45 patients. In 33 of 38 patients, multidetector CT with VT depicted a tracheobronchial narrowing and/or anomaly. In 10 of 38 patients, tracheobronchial stenosis was induced by vascular anomalies. Five patients with normal findings at multidetector CT with VT had tracheobronchomalacia with inspiratory airway stenosis at FT. Sensitivity and specificity of CT with VT were 86.8% (95% CI: 73.3%, 94.7%) and 85.7% (95% CI: 44.6%, 99.3%), respectively. Positive and negative predictive values were 97.1% (95% CI: 84.9%, 99.9%) and 54.5% (95% CI: 25.0%, 80.0%), respectively. Overall accuracy was 86.7% (95% CI: 74.3%, 94.0%). Mean effective dose was 1.1 mSv (range, 0.5-1.8 mSv). CONCLUSION: Multidetector CT with VT with a low-dose protocol had high sensitivity and specificity for depiction of tracheobronchial narrowings and/or anomalies. However, tracheal narrowing due to tracheobronchomalacia was difficult to diagnose at single-phase multidetector CT with VT.

Pulmonary haemosiderosis in infants and children.

Pulmonary haemosiderosis (PH) results from recurrent bleeding into alveolar spaces and interstitial lung tissue. If untreated, fibrosis and restrictive lung disease will develop and may lead to death. A distinction can be made between primary and secondary pulmonary haemosiderosis as a manifestation of auto-immune small vessel vasculitides, coagulation disorders or diseases with increased venous pressure. Interestingly, in some cases of 'idiopathic' PH, exposure to moulds and van Willebrand's disease may contribute to the pathogenesis. Haemosiderosis usually begins with haematemesis. Anaemia, alveolar infiltrates on chest x ray and siderophages in broncho-alveolar lavage fluid are diagnostic factors. Immunosuppressive treatment has improved the prognosis in recent years.

Evaluation of clinical, radiologic, and laboratory prebronchoscopy findings in children with suspected foreign body aspiration.

BACKGROUND: Foreign body aspiration (FBA) in infants and young children is a common and potentially life-threatening event. Although studies have extensively described the signs and symptoms of suspected FBA (sFBA), only few systematically compared their value for predicting bronchoscopy results. OBJECTIVES: The objectives of this study were to describe the clinical and radiologic signs and symptoms of sFBA and to identify predictors of bronchoscopically proven FBA (pFBA). SETTING: This study was conducted at a referral tertiary university hospital with an outpatient clinic and a 90-bed pediatric unit. METHODS: Signs and symptoms were retrospectively analyzed for all children who had received bronchoscopy between July 1992 and April 2000 because of sFBA. Radiologic signs of FBA were reviewed and scored by 2 independent radiologists. RESULTS: One hundred sixty children (mean age, 2.8 years; range, 11 months to 16.8 years) were enrolled in the study. Foreign body aspiration, mostly affecting the right main bronchus, was proven bronchoscopically in 122 (76%) of these children. Independent predictors of pFBA in multivariable analyses were focal hyperinflation on chest radiograph (beta = 45.4; 95% confidence interval [CI] = 5.3-390.5; P = .001), witnessed choking crisis (beta = 18.6; 95% CI = 4.7-73.0; P < .001), and white blood cell count greater than 10,000/muL (beta = 4.2; 95% CI = 1.2-14.7; P = .026). The cumulative proportion of pFBA cases increased with the number of risk factors (0, 16%; 1, 47%; 2, 96%; 3, 100%). CONCLUSIONS: Clinical judgment to perform bronchoscopy for sFBA was correct in 76% of the children investigated. Focal hyperinflation, witnessed choking crisis, and elevated white blood cell count were strongly associated with pFBA; bronchoscopy can be strongly recommended in the presence of at least 2 risk factors when FBA is suspected.

Evaluation of chronic infectious interstitial pulmonary disease in children by low-dose CT-guided transthoracic lung biopsy.

BACKGROUND: Children with chronic infectious interstitial lung disease often have to undergo open lung biopsy to establish a final diagnosis. Open lung biopsy is an invasive procedure with major potential complications. Transthoracic lung biopsy (TLB) guided by computed tomography (CT) is a less-invasive well-established procedure in adults. OBJECTIVE: Detailing the role of low-dose CT-guided TLB in the enhanced diagnosis of chronic lung diseases related to infection in children. MATERIALS AND METHODS: A group of 11 children (age 8 months to 16 years) underwent CT-guided TLB with a 20-gauge biopsy device. All investigations were done under general anaesthesia on a multidetector CT scanner (SOMATOM Volume Zoom, Siemens, Erlangen, Germany) using a low-dose protocol (single slices, 120 kV, 20 mAs). Specimens were processed by histopathological, bacteriological, and virological techniques. RESULTS: All biopsies were performed without major complications; one child developed a small pneumothorax that resolved spontaneously. A diagnosis could be obtained in 10 of the 11 patients. Biopsy specimens revealed chronic interstitial alveolitis in ten patients. In five patients Chlamydia pneumoniae PCR was positive, in three Mycoplasma pneumoniae PCR was positive, and in two Cytomegalovirus PCR was positive. The average effective dose was 0.83 mSv. CONCLUSION: Low-dose CT-guided TLB can be a helpful tool in investigating chronic infectious inflammatory processes in children with minimal radiation exposure. It should be considered prior to any open surgical procedure performed for biopsy alone. In our patient group no significant complication occurred. A disadvantage of the method is that it does not allow smaller airways and vessels to be assessed.

Levels of antibodies specific to tetanus toxoid, Haemophilus influenzae type b, and pneumococcal capsular polysaccharide in healthy children and adults.

Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and for tetanus toxoid were measured in serum samples of 386 age-stratified subjects. The study group consists of healthy adult blood donors and hospitalized children undergoing elective surgery, excluding individuals with a history of infection. In children, anti-tetanus toxoid antibody levels displayed two peaks of 1.20 IU/ml (20.4 mg/liter) and 1.65 IU/ml (28.1 mg/liter) related to the schedule of routine childhood immunization in the first year and at 8 years of age. Eighty percent of the antibodies are of the immunoglobulin G1 (IgG1) isotype. For pneumococcal capsular polysaccharide (PCP), the specific antibody levels represent the acquisition of natural immunity. The initial concentration of 9.2 mg/liter was low in infancy (0.5 to 1 years of age) and remained low until 3 to 4 years of age (14.6 mg/liter). During this period PCP antibodies were almost 100% of the IgG2 subclass. Thereafter, IgG anti-PCP antibody titers increased steadily to adult levels (59.5 mg/liter). The data are intended to provide reference ranges to aid in the interpretation of specific antibody determinations in the clinical setting.

Prospective population-based study of viral lower respiratory tract infections in children under 3 years of age (the PRI.DE study).

UNLABELLED: Population-based incidence data from Europe on the disease burden of lower respiratory tract infections (LRTI) due to respiratory syncytial viruses (RSV), parainfluenza viruses (PIV) and influenzaviruses (IV) are lacking, especially with respect to the disease burden. In a 2-year prospective multicentre study of children aged <3 years in Germany, we registered population-based cases as outpatients (n=2386), inpatients (n=2924), and nosocomially-acquired (n=141). Nasopharyngeal secretions were tested for viral RNA. The annual incidence for physician visits per 100 children for all LRTI was 28.7, RSV 7.7, PIV 3.8 and IV 1.1. Annual hospitalisation rates per 10(5) children were for all LRTI 2941, RSV 1117, PIV 261 and IV 123. Annual nosocomial cases per 10(5) hospital days were for all LRTI 79, RSV 29, PIV 9 and IV 1.5. All five children (0.27%) who died had an underlying disease and four were nosocomially acquired. CONCLUSION: Hospitalisation rates due to lower respiratory tract infections in healthy children were similar to those reported elsewhere; the rates for outpatient visits were approximately ten times higher.

IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with the binding site reagents.

BACKGROUND: There is currently no international reference preparation for IgG subclass (IgGSc) quantification. This situation has led to calibration differences among assays and a variety of reference interval values with consequential difficulties in comparing results. We therefore evaluated IgGSc concentrations in Certified Reference Material 470 (CRM 470). METHODS: Pure, polyclonal IgG1, -2, -3, and -4 were prepared from a large serum pool for use as primary standards. The IgG mass in each preparation was calculated from amino-acid analysis data. IgGSc concentrations were assessed in CRM 470 by nephelometry with modern analytical techniques, using these reference preparations. Subsequently, IgGSc concentrations were measured in 380 healthy individuals (250 males and 130 females), and age-dependent reference intervals were established. RESULTS: IgGSc concentrations in CRM 470 were as follows: IgG1, 5028 mg/L; IgG2, 3418 mg/L; IgG3, 579 mg/L, and IgG4, 381 mg/L, with a total IgG concentration of 9406 mg/L, 2.83% below the certified total IgG value of 9680 mg/L. Age-dependent percentile curves for the four IgGSc were constructed using a Box-Cox transformation. Maximum median values were as follows: IgG1, 6.02 g/L at 11 years; IgG2, 3.45 g/L at 31 years; IgG3, 0.63 g/L at 17 years; and IgG4, 0.48 g/L at 14 years. No significant sex-related differences were observed. CONCLUSIONS: The correlation between the summation of individual IgGSc and separate measurements of total IgG concentrations was good and supports the accuracy of the results. The results are based on The Binding Site assays and should not be considered appropriate for other assays unless so demonstrated.

Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment.

We have identified 14 patients with diverse primary immunodeficiencies who have developed progressive neurodegeneration of unknown etiology. All patients had received immunoglobulin replacement therapy for a mean duration of 6.5 years (range of 0.5-13.5 years) at the time of first neurological symptoms. Diagnostic tests of blood and cerebrospinal fluid analyses included chemistry, cultures, PCR for viral genomes, and cytology. In addition, neuroimaging and electrophysiologic studies were performed. Brain tissue histology (n = 5) revealed nonspecific encephalitis with microglial infiltration and neuronal loss. Twelve patients died 6 months to 15 years (median 4.3 years) after onset of neurologic findings. No evidence of any infectious disease that could have explained our patients' progressive encephalopathy was found either during their lifetimes or postmortem. These patients may have had an unusual manifestation of primary immunodeficiency diseases, an autoimmune reaction against neuronal tissue, a yet undefined infectious agent, or a complication of IVIG therapy. To help determine the etiology of this rare complication, an international surveillance system for primary immunodeficiency patients who develop progressive neurodegeneration of unknown cause is recommended.