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Childhood arterial ischemic stroke differs in essential aspects from adult stroke. It is rare, often relatively unknown among laypersons and physicians and the wide variety of age-specific differential diagnoses (stroke mimics) as well as less established care structures often lead to a considerable delay in the diagnosis of stroke. The possible treatment options in childhood are mostly off-label. Experiences in well-established acute treatment modalities in adult stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in children and only based on case reports and case series. The etiological clarification is time-consuming due to the multitude of risk factors which must be considered. Identifying each child's individual risk profile is mandatory for acute treatment and secondary prevention strategies and has an influence on the individual outcome. In addition to the clinical neurological outcome the residual neurological effects of stroke on cognition and behavior are decisive for the integration of the child into its educational, later professional and social environment.

ZusammenfassungDie vorliegende Leitlinie ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma, welche die bisher für den deutschen Sprachraum gültige Version aus dem Jahr 2006 ablöst. Die Fülle an neuen Erkenntnissen zur Pathophysiologie und zu den Phänotypen von Asthma und das erweiterte Spektrum an diagnostischen und therapeutischen Möglichkeiten bei dieser Erkrankung machte eine Neufassung und Aktualisierung notwendig. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

Pneumonia is a major healthcare problem. Rapid pathogen identification is critical, but often delayed due to the duration of culturing. Early, broad antibacterial therapy might lead to false-negative culture findings and eventually to the development of antibiotic resistances. We aimed to assess the accuracy of the new application Unyvero P50 based on multiplex PCR to detect bacterial pathogens in respiratory specimens from children and neonates. In this prospective study, bronchoalveolar lavage fluids, tracheal aspirates, or pleural fluids from neonates and children were analyzed by both traditional culture methods and Unyvero multiplex PCR. We analyzed specimens from 79 patients with a median age of 1.8 (range 0.01–20.1). Overall, Unyvero yielded a sensitivity of 73.1% and a specificity of 97.9% compared to culture methods. Best results were observed for non-fermenting bacteria, for which sensitivity of Unyvero was 90% and specificity 97.3%, while rates were lower for Gram-positive bacteria (46.2 and 93.9%, respectively). For resistance genes, we observed a concordance with antibiogram of 75% for those specimens in which there was a cultural correlate. Unyvero is a fast and easy-to-use tool that might provide additional information for clinical decision making, especially in neonates and in the setting of nosocomial pneumonia. Sensitivity of the PCR for Gram-positive bacteria and important resistance genes must be improved before this application can be widely recommended.

Zusammenfassung Akutes Atemversagen kann auch im Kindesalter mit nichtinvasiver Beatmung (NIV) behandelt werden. In den letzten Jahren wurden die technischen Voraussetzungen der NIV-Beatmungsgeräte für das Kindesalter verbessert, zudem steht heutzutage eine größere Auswahl an konfektionierten nasalen und Full-face-Masken für Kinder ab dem Säuglingsalter als Interface zur Verfügung. Vor allem Kinder mit hyperkapnischem Atemversagen profitieren von der NIV. Evidenz für Vorteile der NIV besteht für die Bronchiolitis, Asthma sowie für das „Acute-on-chronic“-Atemversagen, d. h. ein Atemversagen bedingt durch eine akute Infektion bei einer zugrunde liegenden neuromuskulären Erkrankung, Zerebralparese oder einer chronischen Lungenerkrankung wie der zystischen Fibrose. Nichtinvasive Beatmung ist bei prolongiertem Weaning von invasiver Beatmung und bei Fehlbildungen des oberen Atemwegs hilfreich. Alveoläre Erkrankungen mit vorwiegend hypoxämischem Atemversagen wie ambulant erworbene Pneumonien oder das „acute respiratory distress syndrome“ (ARDS) stellen keine Indikationen für die NIV dar. Aufgrund relevanter möglicher Nebenwirkungen und der Möglichkeit der schnellen Verschlechterung des Gasaustauschs bei NIV-Versagen sollte die NIV auf der pädiatrischen Intensivstation mit der Möglichkeit zu einem raschen Wechsel auf einen invasiven Beatmungszugang stattfinden.

PURPOSE To determine whether bag-mask ventilation between induction of anaesthesia and tracheal intubation in children with post-tonsillectomy bleeding reduces the incidence of hypoxaemia and difficult direct laryngoscopy without increasing perioperative respiratory complications. METHODS Medical records, anaesthesia protocols and vital sign data were analysed from February 2005 to March 2017 for patients undergoing anaesthesia for surgical revision of bleeding tonsils. Type of rapid sequence induction and intubation (RSII; classical, ie, apnoeic, vs controlled, ie, with gentle bag-mask ventilation) was noted. Primary outcomes were incidence of moderate and severe hypoxaemia, grade of direct laryngoscopic views as well as occurrence of noted tracheal intubation difficulties. Haemodynamic alterations during RSII and perioperative adverse events such as noted gastric regurgitation, pulmonary aspiration and perioperative pulmonary morbidity were also recorded. RESULTS A classical RSII was performed for 22 surgical revisions in 22 children and a controlled RSII was used for 88 surgical revisions in 81 children. Patients undergoing controlled RSII had less incidence of severe hypoxaemia (1 vs 3; P = .025), better direct laryngoscopic views (P = .048) and less hypertension (5 vs 9; P

SummaryBackground Tracheal follicular pattern or so-called tracheal cobblestoning is a poorly described entity in the literature and is depicted as a nodular or lumpy appearance of the tracheal wall mucosa suggesting tracheal irritation from factors like gastro-esophageal reflux (GERD) or pulmonary infection. The aim of the present study was to investigate the prevalence and characteristics of tracheal cobblestones in a large pediatric population. Methods A large database of rigid tracheoscopies recorded in children (0–6 years of age) undergoing general anesthesia with planned tracheal intubation for elective surgical procedures was retrospectively analyzed. Tracheoscopy records were reviewed by five pediatric airway experts (authors 3–7). Data were compared using the Mann–Whitney test, chi-square or Fisher exact test as appropriate (P

BACKGROUND: Tracheal bronchus (TB) is defined as an abnormal bronchus that originates directly from the lateral wall of the trachea above the carina and goes towards the upper lobe territory of the lung. We analyzed rigid endoscopies of the trachea in children to determine the incidence and characteristics of TB. METHODS: In total, 1021 rigid endoscopies of the trachea recorded from children aged 0 to 6 years were analyzed. Endoscopic examination was performed from supraglottic region to carina using a 0-degree Hopkins rod-lens telescope. Patients with a TB were identified and the site of origin of the TB and its level above the carina was noted. Data of the identified patients was reviewed for the presence of preoperative airway findings such as stridor, upper lobe pneumonia and wheezing or atelectasis, other congenital anomalies, and intraoperative complications. RESULTS: TB was detected in 11 (1.06%) of 1021 upper airway endoscopic examinations. All originated from the right lateral wall of the trachea. Six children had retained secretions in the TB, and 3 children had perioperative airway problems unrelated to the TB. One child showed right main stem bronchus narrowing as seen at the true carina, in the presence of a TB. All the children with TB exhibited at least 1 additional congenital anomaly at birth besides TB. CONCLUSIONS: TB is a relatively common congenital endoscopic lower airway anomaly in childhood, which is itself rarely symptomatic, but almost always coexists with other congenital anomalies.

Paediatric airway endoscopy is accepted as a diagnostic and therapeutic procedure, with an expanding number of indications and applications in children. The aim of this European Respiratory Society task force was to produce a statement on interventional bronchoscopy in children, describing the evidence available at present and current clinical practice, and identifying areas deserving further investigation. The multidisciplinary task force panel performed a systematic review of the literature, focusing on whole lung lavage, transbronchial and endobronchial biopsy, transbronchial needle aspiration with endobronchial ultrasound, foreign body extraction, balloon dilation and occlusion, laser-assisted procedures, usage of airway stents, microdebriders, cryotherapy, endoscopic intubation, application of drugs and other liquids, and caregiver perspectives. There is a scarcity of published evidence in this field, and in many cases the task force had to resort to the collective clinical experience of the committee to develop this statement. The highlighted gaps in knowledge underline the need for further research and serve as a call to paediatric bronchoscopists to work together in multicentre collaborations, for the benefit of children with airway disorders.

Background: Home mechanical ventilation (HMV) is increasingly used in children with chronic respiratory insufficiency, but data on incidence and type of adverse events are limited. Setting: Pediatric HMV program at a tertiary university hospital. Methods: The authors retrospectively analyzed the type and incidence of severe emergencies in a mixed pediatric HMV program. Results: In all, 295 patient-years of HMV in 54 patients could be analyzed. A total of 26 patients had neuromuscular disease. In 16 patients, mechanical ventilation was initiated at

Summary Background: Pulmonary alveolar proteinosis (PAP) is a rare alveolar filling syndrome where the mainstay of treatment is therapeutic whole-lung lavage (WLL). WLL techniques used in adults have to be modified for children because of their small-diameter airways. Aim: To describe a technique for WLL adapted for small children. Methods: We describe a WLL technique that combines safe single-lung ventilation with the use of an age-appropriate endotracheal tube and selective occlusion of the other main bronchus with a balloon catheter through which the lavage is performed. Effectiveness measured by change in oxygen requirements and adverse effects was noted. Results: We performed 64 WLL procedures in four children (age 13 months to 7 years; body weight 4.7–14 kg). Two children had idiopathic and two had secondary PAP. At referral, all children had dyspnoea at rest and required continuous oxygen supplementation. Two patients showed significantly decreased oxygen demands and radiological improvement after WLL. Two patients showed no significant response. The only adverse effect observed was transient hypoxemia. Complications comprised fluid leak at the balloon (4), balloon rupture (1), and pneumothorax (1). Conclusions: This technique for WLL combining single-lung ventilation with an endotracheal tube and lung exclusion for lavage with a balloon catheter can be safely and effectively performed in small children with PAP.

Congenital choanal atresia is a rare malformation of the upper airways occurring sole or within the scope of syndromes. The controversy regarding standardized surgical approach and optimal technique preventing re-stenosis as well as the proceeding in case of a unilateral malformation persists. To address these issues, a retrospective analysis of patients presenting with choanal atresia in our department within the last 10 years was performed. 15 infants aged 3 days to 13 years (mean 42 months) who presented with unilateral (10 cases) and bilateral (5 cases) choanal atresia underwent surgical repair. 4 patients failed previous surgeries. All interventions were performed in transnasal endoscopic technique. 7 patients were intraoperatively stented for 6 weeks, 4 patients for 1 week. In 73% (11 out of 15 children) further congenital anomalies were identified. In 7 cases a re-stenosis requiring treatment occurred, predominantly in long-term stented patients. No intra- or postoperative hemorrhages or infections occurred. To provide an adequate work-up of affected patient including a screening for further congenital anomalies, a multidisciplinary approach is required. Endonasal endoscopic approach represents a safe technique for surgical repair of choanal atresia. The indication for surgical repair in case of a unilateral atresia is based on the severity of clinical symptoms. The use of stents, especially of long term, remains controversial and needs further evaluation.

Campomelic dysplasia is a malformation syndrome with multiple symptoms including characteristic shortness and bowing of the long bones (campomelia). CD, often lethal due to airway malformations, is caused by heterozygous mutations in SOX9, an SRY-related gene regulating testis and chondrocyte development including expression of many cartilage genes such as type II collagen. Male to female sex reversal occurs in the majority of affected individuals with an XY karyotype. A mild form without campomelia exists, in which sex-reversal may be also absent. We report here two novel SOX9 missense mutations in a male (c.495C>G; p.His165Gln) and a female (c.337A>G; p.Met113Val) within the DNA-binding domain leading to non-lethal acampomelic CD. Functional analyses of mutant proteins demonstrate residual DNA-binding and transactivation of SOX9-regulated genes. Combining our data and reports from the literature we postulate a genotype-phenotype correlation: SOX9 mutations allowing for residual function lead to a mild form of CD in which campomelia and sex reversal may be absent. © 2010 Wiley-Liss, Inc.

Summary The complex interplay between the characteristics of the respiratory system, its changes as a result of respiratory disease and the effects of mechanical ventilation makes it important to analyse the physiology of the respiratory system in any given clinical situation. Key variables to be considered are the elastic recoil, resistance and time constant of the respiratory system, as well as the characteristics of the respiratory pump. The effects of respiratory support on the intrathoracic organs and lung perfusion must be taken into account. Respiratory support modes can then be tailored to provide maximum benefit and a minimum of negative effects. When the relatively few basic principles that underlie the mechanical behaviour of the respiratory system in most circumstances are kept in mind, the challenge of optimal support seems solvable for most children with respiratory insufficiency.

Background: Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear. Methods: Anti-GM-CSF auto-antibodies were determined with the help of an antigen capture assay using serum and/or bronchoalveolar lavage (BAL) fluid from 27 patients with PAP (nine adults, 15 children, three neonates) and from 185 children with different diseases as disease controls (various pulmonary conditions and patients with malignancies). Results: Anti-GM-CSF auto-antibodies were detected in the serum of five of seven adult PAP patients. They were not found in the serum of any of the children or neonates with PAP nor in any of the disease control patients. Raised anti-GM-CSF titres were found in BAL fluid from three of four adult patients with PAP. Anti-GM-CSF auto-antibodies were detected in BAL fluid of only one of the 15 children (age at diagnosis 11 years, age at BAL 24 years) and in none of the neonates with PAP, nor in any of the disease control patients. Conclusions: The presence of anti-GM-CSF auto-antibodies seems to define an autoimmune disease underlying most of the adult sporadic type of PAP, but age at diagnosis may cause an overlap with children in some rare instances. In most of the children and all of the neonates the anti-GM-CSF titres were not significantly increased, indicating that alternative explanations are needed for the pathogenesis of the disease in these patients.

We hypothesised that long-term tracheostomy in infants and children may perpetuate chronic airway inflammation and airway remodeling due to easier access to the lungs for microorganisms. Pulmonary surfactant represents an important part of the initial host defense, and in particular, the surfactant proteins (SP) A and D may directly interact with invading microorganisms and also modulate the activity of local immune cells. The goals of this study were to determine the presence and intensity of a peripheral airway inflammation and of potential deficiency states of surfactant proteins in nonsymptomatic children with tracheostomy. Bronchoalveolar lavage (BAL) cell pattern, bacteria and viruses recovered, and concentrations of SP-A, SP-B, SP-C, and SP-D were assessed in 46 children (4.3 years (1.6–6)) median (range) carrying a tracheostomy for 2.4 years (1.3–4.9), and were compared to 16 children with no lung disease. Children with tracheostomy had an increased total number of cells, increased neutrophils, and more frequently bacteria, but no viruses were recovered. SP-D concentration was reduced by 50% on average (P = 0.0002). SP-A, SP-B, and SP-C were not different between the two groups. SP-D was inversely correlated to neutrophils, and high numbers of bacteria were associated with lower SP-D concentrations. We suggest that bacteria and low SP-D support neutrophilic inflammation in the lower respiratory tract of nonsymptomatic with children with tracheostomy. Pediatr Pulmonol. 2004; 37:356–361. © 2004 Wiely-Liss, Inc.

We report on a patient with the hitherto undescribed combination of chronic granulomatous disease, pulmonary hemosiderosis, and celiac disease. The hemosiderosis resolved with a gluten-free diet and glucocorticosteroid pulse therapy, but the restrictive lung function pattern remained unchanged. Lung function improved markedly by immunosuppression with daily glucocorticosteroid and azathioprine treatment.

To study the impact of lung water content and its reduction by a topically applied diuretic on respiratory and lung tissue mechanics in comparison with surfactant administration in surfactant-deficient newborn piglets with lavage-induced lung injury.Controlled, randomized study.Animal research facility.Newborn piglets. TREATMENT Piglets were surfactant depleted by lung lavage and, after a pretreatment period, randomly treated with intratracheal furosemide, furosemide and surfactant, or with surfactant alone.Dynamic compliance (C(DYN)), static compliance (C(ST)), stress-adaptation pressures (P(DIFF)) and post mortem lung water content were determined. Static compliance in the furosemide-surfactant group was not significantly higher than in the surfactant group. At the end of the study, C(ST) did not differ between the three groups because C(ST) in the furosemide group had increased to values similar to those of the surfactant-containing treatment groups: C(ST) F+S: 0.73 +/- 0.2 mL/cm H2O/kg body weight (BW); C(ST) S: 0.61 +/- 0.11 mL/cm H2O/kg BW; and C(ST) F: 0.60 +/- 0.19 mL/cm H2O/kg BW). Compliance was inversely and P(DIFF) was directly correlated to lung water (LW) content (C(ST) vs. LW: r2 = .59, p = .001; C(DYN) vs. LW: r2 = .49, p = .006; P(DIFF) vs. LW: r2 = .37, p = .059), independent of the type of treatment. Changes in C(ST) and C(DYN) were inversely related to changes in P(DIFF). Intrapulmonary furosemide was more rapidly absorbed when administered to the surfactant-depleted lung alone compared with the mixture with surfactant, and intrapulmonary furosemide had a rapid systemic effect.Although the combination of surfactant with a diuretic failed to increase respiratory compliance to a significantly larger extent than surfactant alone, furosemide at the end of the study increased respiratory compliance to a level similar to surfactant-containing treatments. Lung water content and, to a lesser extent, the absence or presence of surfactant appeared to determine lung mechanics, and its impact on lung mechanics was similar to surfactant administration.

In babies and toddlers, most emergencies that necessitate resuscitation attempts are respiratory in origin.This is in contrast to emergencies in adults, in which circulatory failure with low output is often present, as it is for examplein dysrhthmia following cardiac infarct, and the treatment is fundamentally different from that in a paediatric emergency. In paediatric emergencies correction of the respiratory disturbance is often enough to deal with the acute risk situation. In general, particular attention should be paid to making certain the airway stays open.The airway is smaller in children than in adults. In view of the frequent respiratory infections children are exposed to they are often swollen and can therefore themselves be the actual cause of a life-threatening situation not only when foreign bodies have been aspirated, but also in cases of epiglottitis and pseudocroup. Since a cardiovascular arrest often occurs as the result of respiratory hypoxia in children, its prognosis is serious. In adults the organs are initially still adequately oxygenated when a dysrhythmia occurs or in the presence of other cardiovascular diseases. In children the cardiac arrest comes about as the result of preceding hypoxia of all tissues, so that particularly rapid action is essential. It is the object of any airway management to ensure an adequate oxygen supply and prevention of aspiration, but preparations must also be made for intratracheal administration of emergency medications.

The prevalence of asthma and allergic diseases has been increasing particularly in children over the last decades in Western countries. The German reunification allowed to study the effect of 40 years of different environmental and social development on asthma and allergy prevalence in two genetically homogenous populations. In children and young adults, the prevalence of asthma, hay fever and skin test reactivity to common aeroallergens was considerably higher in West Germany as compared to East Germany. The increased prevalence in asthma was explained by the higher allergic sensitization in West Germany.Exposure to SO2, particulate matter and cars was associated with bronchitis, nonspecific respiratory symptoms and decrements in pulmonary function, but not with asthma and allergy. Atopy was found to be the major factor associated with the inception of asthma. Children who had lived during their first three years of life in East German living conditions and had thereafter been exposed to a rapid Westernization of their environment and lifestyle, showed increased atopy and hay fever while bronchitis decreased, but asthma and bronchial hyperresponsiveness remained unchanged. This points toward a period during early life which determines the development of asthma and which seems to differ from the factors responsible for allergic sensitization.Since East European living conditions were similar to those in the West decades ago, the same factors could be responsible for the increased allergic sensitization in West Germany and the secular increase in atopic diseases and asthma in the West.Factors associated with the more modern life style may account for this difference, while the increased levels of SO2 and dust exposure in East Germany were obviously no risk for the development of childhood asthma or allergic sensitization.

Unsere Patientin wurde mit dem Bild einer schweren pulmonalen Hypertonie auf dem Boden einer exogen allergischen Alveolitis als Grunderkrankung vorgestellt. Die Alveolitis sprach initial gut auf eine orale Steroidtherapie und Reduktion der Allergenexposition an. Im Krankheitsverlauf kam es wiederholt zu akuten Verschlechterungen, die in engem Zusammenhang mit der Dosierung der Steroide und der unvollstandigen Elimination des auslosenden Allergens standen. Im Gegensatz zu den restriktiven Lungenveranderungen erwies sich die pulmonale Hypertonie als therapeutisch nicht beeinflusbar und war fur den letalen Ausgang verantwortlich. Diskussion: In der Therapie der exogen allergischen Alveolitis ist bei zusatzlich bestehender pulmonaler Hypertonie eine Steroidtherapie in langfristig hoher Dosierung erforderlich. Beim Leitsystem pulmonale Hypertonie mus die exogen allergische Alveolitis als Differentialdiagnose berucksichtigt werden.

Summary Background An increased prevalence of allergic diseases and atopic sensitization as assessed by skin-prick testing in children in West compared with East Germany has been reported. Objectives This study was designed to evaluate whether such a difference is also present in adults, and if this can be shown when using a serological test for allergic sensitization. Methods Two large samples representative for all adults between 25 and 69 years of age were drawn in West (1991, n= 5313) and East Germany (1992, n= 2617). A serological test screening for IgE-antibodies to common aeroallergens (SXI) was performed. A questionnaire was used to assess the presence of clinical respiratory allergy, known possible risk factors for allergies and confounding variables. Results Allergic sensitization decreased with age. Significantly more subjects < 45 years of age had a positive allergy test in West as compared to East Germany. The prevalence of clinical allergy was also higher in West Germany. This difference was significant in younger adults and was independent of other risk factors identified. These additional risk factors encompassed younger age, higher educational level, male sex, and living in a community with more than 100000 inhabitants. Conclusion Sensitization to common aeroallergens as determined by a multiple allergen RAST test in adults below 45 years of age living in West Germany is increased compared to East Germany. This increase cannot be explained by genetic differences and is similar to the West to East decreasing gradient in allergies reported from studies in children employing skin-prick tests.

All fourth-grade school children in Munich and the surrounding districts (age 9-11 years, n = 9403) were surveyed with a questionnaire, lung function testing and bronchial provocation. Croup was reported in 9.8%. In these children, lung function was decreased even after controlling for asthma and other confounding factors. Only recurrent croup had an increased prevalence in children with asthma. When a family history for asthma, maternal smoking and social status were included into a logistic multiple regression model, the odds ratio to develop asthma was 2.91 (confidence interval (CI) 2.19 - 3.86) for children with a history of croup, 2.60 (CI 1.93 - 3.51) for a family history for asthma and 8.60 (CI 4.99 - 14.80) for the combination of family history and croup. Asthma was diagnosed in 37.3% of children with croup and a positive family history.

There is considerable evidence for a significant hereditary component in the pathogenesis of asthma and allergic diseases. The objective of this study was to investigate familial influences unique to the expression of asthma. School children (n = 9,403), 9 to 11 yr of age, were enrolled in a cross-sectional survey in southern Germany. The prevalence of asthma and allergic diseases in parents and children was assessed through parental questionnaires. Atopic sensitization was measured by skin prick tests, and bronchial responsiveness was determined by cold air hyperventilation challenge. The prevalence of asthma alone, i.e., without concomitant hay fever or atopic eczema, increased strongly if nearest of kin suffered from asthma alone (4.7 versus 11.7%, p < 0.0001). A family history of hay fever or atopic dermatitis, excluding asthma, was unrelated to asthma in the offspring (4.7 versus 3.9%). These relations did not change when stratifying for skin prick test reactivity (STR) and bronchial hyperresponsiveness (BHR). STR alone and BHR alone (i.e., without manifestation of disease) were unrelated to a family history of asthma or allergy. The results strongly suggest a separate genetic factor controlling the development of asthma. Skin test positivity and BHR to cold, dry air are unlikely to be the underlying mechanisms through which the inheritance of childhood asthma is transmitted.

Clinical trials using replication-deficient adenovirus as vectors for gene transfer into the airways of cystic fibrosis (CF) patients are in progress. However, little is known about the prevalence of wild-type adenovirus infections in patients with cystic fibrosis and their effect on lung function. To answer these questions, serum IgG and IgM antibody titers against adenovirus type 5 were prospectively measured by an indirect immunofluorescence assay in 199 CF outpatients and in a control group of 45 healthy children and young adults. In addition, we performed pulmonary function tests when the patients were in stable clinical condition. IgM antibodies against adenovirus were present in 104 of the 199 cystic fibrosis patients (52.3%). IgG antibodies against adenovirus were detected in 192 of the 199 cystic fibrosis patients (96.5%), and were significantly higher in cystic fibrosis patients older than 7 years than in younger patients and in age matched controls. IgG antibody titers measured a second time 11.8 months later in 143 of the 199 patients had increased in 48 (33.6%) patients. In 27 of these 48 patients, who had at least a 2-fold increase in antibody titer, FVC and FEV1 decreased by 9.8% (p0.05) and 8.3% (p = 0.05), respectively, over 45 months. In a comparison group matched for age, sex, and chronic Pseudomonas aeruginosa infection but no increase in antibody titers, FVC and FEV1 were unchanged. The results indicate that wild-type adenovirus infections are prevalent in cystic fibrosis patients and that wild-type adenovirus infections in cystic fibrosis patients seem to be associated with deterioration in lung function. These observations may have important implications for efficacy and safety considerations when using adenoviral vectors for gene therapy.

Pulmonary sling (PS) is a congenital condition in which the left pulmonary artery (LPA) arises from the right pulmonary artery (RPA), forming a sling around the trachea causing tracheal compression. The incidence is not so rare as initially thought. Symptoms of severe airway obstruction often begin in the newborn or young infant. Echo-colour-Doppler may reveal the PS but emphysema can mask the typical findings. Deviation of fluid-filled lungs may be detected prenatally. Chest radiographs show unusual air distribution, deviation of heart and mediastinum and altered tracheobronchial angles. Bronchography and bronchoscopy demonstrate the high incidence of associated tracheal anomalies such as cartilagenous rings and long tracheal stenosis. Anterior oesophageal indentation is not always seen in the oesophogram. Magnetic resonance imaging (MRI) and computed tomography (CT) reveal the PS, but cautious interpretation is necessary because of different levels of the anomalous LPA. PS and associated cardiovascular malformations can be clearly detected by angiography. Associated extrathoracic anomalies are common. Early diagnosis and therapy of PS is mandatory and consists of reimplantation of the LPA into the pulmonary trunk and division of the ligamentum arteriosum. The postoperative course may be cumbersome necessitating bronchological interventions. Tracheal resection may be necessary but restenosis is frequent. A one-stage repair has been proposed in such cases and was successfully done in a few reported cases. Relief of respiratory obstruction is often complete when there are no associated tracheobronchial anomalies. Late postoperative course is favourable but respiratory obstructive attacks may occur with decreasing incidence over time and tracheal growth.

Objective: To investigate the relation between skin test reactivity in children and number of siblings. Design: Cross sectional survey among school-children aged 9-11 years. Skin prick tests in the children and self completion of written questionnaire by their parents. Subjects: 5030 children in Munich and 2623 children in Leipzig and Halle, Germany. Main outcome measures: Atopic status assessed by skin prick tests. Results: After possible confounders were controlled for, the prevalence of atopic sensitisation decreased linearly with increasing number of siblings (odds ratio=0.96 for one sibling, 0.67 for five or more siblings; P=0.005). In atopic children the severity of the skin test reaction as assessed by the weal size was not associated with the number of siblings. Conclusions: Factors directly or indirectly related to the number of siblings may decrease the susceptibility of children to become atopic. Thus, declining family size may in part contribute to the increased prevalence of atopic diseases reported in Western countries over the past few decades.

To explore the role of bronchial hyperreactivity and obstruction after cold air challenge, data from a cross-sectional study of more than 7,000 10-year-old children were used. Current knowledge of hyperreactivity is primarily based on pharmacological provocation tests with variable prechallenge flow rates and their decrease relative to baseline. Using forced expiratory volume (FEV) in 1 sec values before and after cold air challenge, however, it is possible to define a subsample of children with predominant hyperreactivity and a subsample with predominant obstruction after challenge. The prevalence of respiratory symptoms and the diagnoses in the two subsamples were compared. The analysis showed that children with bronchial obstruction have nearly the same frequency of respiratory symptoms as those with bronchial hyperreactivity. A combined model of bronchial obstruction and hyperreactivity was, therefore, more predictive of symptoms than a model of hyperreactivity alone.

For airway obstruction caused by subglottic hemangiomas, tracheostomy is still regarded by some as the only established therapy, despite numerous other therapeutic options. Resection with lasers was also reported, but subglottic scar formation may occur, and different laser types may have advantages over others. The charts of 46 consecutive patients over 26 years were reviewed. Until 1986, therapy involved systemic steroids or tracheostomy. Thereafter, a Neodym-Yag and after 1995 a CO2 laser was used. Mean initial stenosis was 61.0% in the first (n=15), 85.8% in the Neodym-Yag (n=14), and 86.7% in the CO2 period (n=17). Tracheostomy rates could be reduced from 76.9% to 46.9% with the Neodym-Yag and to 30.8% with the CO2 laser, and to 22.2% in children not intubated before referral. One tracheostomy obstruction resulted in severe neurological damage; granulomas required resection in 37.5%. Secondary subglottic stenosis was found in 15.4% with the Neodym-Yag, but not with the CO2 laser. With tracheostomy, 12.5% were symptom-free at age 2-3 years, vs. 25.0% in the Neodym-Yag and 41.6% in the CO2 laser period. Speech development was delayed in 75.0% with tracheostomy, and parental anxiety lessened in only 18.8% before the second birthday (68.8% without tracheostomy). Since the end of the retrospective analysis, we treated a further 21 patients (mean stenosis, 83.3%) with the CO2 laser, with only one tracheostomy (4.8%). Compared to steroids and tracheostomy, a significant reduction in morbidity and speech developmental delay, and an improved quality of life, were achieved with CO2 laser resection, and this approach was superior to the Neodym-Yag laser.

In children, congenital or acquired upper airway obstruction can present as an acute, potentially life-threatening condition or a chronic process. The latter may be progressive and lead to chronic respiratory failure or episodes of acute airway obstruction. Therapeutic options have been greatly expanded recently, and the single approach of tracheotomy has been replaced by a complex and invidualised approach in many cases. Conservative treatment ranges from topical application or local injection to systemic administration of pharmacological substances such as steroids, adrenalin and antibiotics. Interventions available for children, even for the very young, include non-invasive or invasive ventilation, endoscopic or open surgical interventions. Such interventions can carry considerable risks and have to be performed cautiously by experienced personnel but offer great promise for the individual patient. Non-invasive approaches will not always be inherently safer than timely surgery.

Exposure to environmental tobacco smoke (ETS) and other air pollutants has been associated with small decrements in lung function. The susceptibility to pollution exposure may, however, vary substantially between individuals. Children with an impaired protease-antiprotease balance may be particularly vulnerable. Therefore this study aimed to investigate the effects of ETS exposure on children with reduced levels of alpha1-antitrypsin (alpha1-AT). Random samples of school children (aged 9-11 yrs) (n=3,526) were studied according to the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol, including parental questionnaires, pulmonary function and allergy testing. Blood samples were obtained to measure plasma levels of alpha1-AT and to genotype for pleomorphic protein inhibitor (Pi)Z and PiS alleles. Children with low levels of alpha1-AT (< or = 116 mg x dL(-1)) showed significant, albeit small decrements in baseline lung function. When exposed to ETS, pronounced decrements of pulmonary function, particularly in measures of mid- to end-expiratory flow rates, were seen in these children as compared to exposed children with normal levels of alpha1-AT. The mean levels of % predicted+/-SE in both groups were: maximum expiratory flow at 50% of vital capacity 79.4+/-7.2 versus 99.0+/-1.5, maximum expiratory flow at 25% of vital capacity 67.4+/-10.0 versus 100.3+/-2.1, maximal midexpiratory flow 73.7+/-8.6 versus 99.9+/-1.7. These findings suggest that school children with low levels of alpha1-antitrypsin are at risk of developing pronounced decrements in pulmonary function, particularly if they are exposed to environmental tobacco smoke. Parents of children with heterozygous alpha1-antitrypsin deficiency resulting in significantly reduced blood concentrations should be advised to prevent their children from being exposed to environmental tobacco smoke and dissuade them from taking up smoking.

A 5-month-old male presented with fever, hepatosplenomegaly, leukocytosis with atypical lymphoblasts, anemia and thrombocytopenia. Severe combined imunodeficiency syndrome (T−, B+, NK+), B lymphoproliferative disease and hemophagocytic lymphohistiocytosis triggered by Epstein–Barr virus (EBV) were diagnosed. As his clinical situation deteriorated rapidly, BMT was performed with unmanipulated marrow stem cells from his EBV-positive HLA-identical sister after conditioning with dexamethasone (1.75 mg/kg/day), cyclophosphamide (114 mg/kg) and etoposide (10 mg/kg), with no immunosuppression given post transplant. Engraftment occurred on day 6 with explosive proliferation of donor CD8+ T cells. The patient died 3 days later from acute respiratory distress syndrome. Autopsy revealed full donor engraftment and no signs of hemophagocytic lymphohistiocytosis or B lymphoproliferative disease. Thus, transplanted T cells can expand very rapidly within days after BMT and clear EBV lymphoproliferative disease and hemophagocytic lymphohistiocytosis. Bone Marrow Transplantation (2002) 29, 519–521. doi:10.1038/sj.bmt.1703396

Long segment malacia of the trachea or main stem bronchi in children is not always suitable for surgical correction; patients may therefore remain ventilator-dependent and/or experience severe obstructive crises. We treated 7 children (ages, 4 months to 9 years) with extreme structural central airway obstruction with stent implantations. Six were mechanically ventilated; 5 had frequent life-threatening obstructive spells requiring deep sedation or paralysis. Diagnoses were: syndrome-associated tracheobronchomalacia (n = 4), malignancy infiltrating the carina (n = 1), congenital tracheal stenosis (n = 1), and tracheobronchial compression by a malpositioned aorta (n = 1). Six tracheal and 13 bronchial stents were endoscopically placed. The prostheses included mesh titan (n = 5), the newer shape memory material nitinol (n = 13), and 1 Y-shaped carina stent. Follow-up was reported for 7 weeks to 72 months. All patients showed marked improvement of their respiratory obstruction. Six children were weaned at least temporarily from ventilation. No significant bleeding, stenosis, or perforation was observed. Seven stents were changed after up to 14 months. Three children are well and at home. In 2 children airway stabilization was successful, but they later died from causes unrelated to stent placement, and 2 children died due to generalized airway disease. Soft metal mesh airway stents can offer a therapeutic option in life-threatening inoperable obstruction of the trachea and main stem bronchi in children.

Ethnic origin has been reported to affect the prevalence of atopic diseases in several studies in different parts of the world. However, little is known about the prevalence of asthma and atopy in immigrants living in Europe. The objective of this study was to evaluate the prevalence of asthma and atopy in Turkish children living in Germany and to investigate the role of ethnic origin on the development of asthma and atopy in this population. In a cross-sectional survey the prevalence of physician-diagnosed asthma, atopy, skin-prick tests and bronchial hyperresponsiveness (BHR) to cold dry air challenge was assessed in 7,445 school children aged 9-11 yrs, living in Munich, south Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin prick tests and cold air hyperventilation challenge. The Turkish children showed a significantly lower prevalence of asthma (5.3 versus 9.4%, p

BACKGROUND—Relatively little is known about risk factors for the persistence of asthma and respiratory symptoms from childhood into adolescence, and few studies have included objective measurements to assess outcomes and exposure. METHODS—From a large cross sectional study of all 4th grade school children in Munich (mean age 10.2 years), 234 children (5%) with active asthma were identified. Of these, 155 (66%) were reinvestigated with lung function measurements and bronchial provocation three years later (mean age 13.5years). RESULTS—At follow up 35.5% still had active asthma. Risk factors for persisting asthma symptoms in adolescence were more severe asthma (OR 4.94; CI 1.65 to 14.76; p = 0.004) or allergic triggers (OR 3.54; CI 1.41 to 8.92; p = 0.007) in childhood. Dampness was associated with increased night time wheeze and shortness of breath but not with persisting asthma. Risk factors for bronchial hyperreactivity in adolescence were bronchial hyperreactivity in childhood (p= 0.004), symptoms triggered by allergen exposure (OR 5.47; CI 1.91 to 25.20; p = 0.029), and damp housing conditions (OR 16.14; CI 3.53 to 73.73; p

We assessed the prevalence of asthma and allergic disorders in 9-11 year old children in Leipzig and Halle in East Germany, and Munich, West Germany. Both East German cities were heavily polluted due to private coal burning and industrial emissions, whereas Munich has moderate industry but heavy car traffic. All fourth grade pupils in Munich (n = 7445) were compared with those in Leipzig, 1990 (n = 1429) and Leipzig and Halle, 1991 (n = 3105). The prevalence of hay fever and skin test reactivity to common aeroallergens was considerably higher in West Germany as compared to East Germany. Furthermore, the prevalence of asthma was also higher in the West German study area. However, when atopy was taken into account, there was no longer a significant difference in the prevalence of asthma between the two parts of the country.

Objective: To investigate the relation between different types of heating and the prevalence of atopic diseases, skin test reactivity, and bronchial hyperresponsiveness. Design: Cross sectional survey among schoolchildren aged 9-11 years. Skin prick tests, pulmonary function tests, and bronchial challenge in the children and self completion of a written questionnaire by the children9s parents. Subjects: 1958 children in a rural area in southern Bavaria, Germany. Main outcome measures: Prevalence of asthma, hay fever, and atopic dermatitis as determined by parents9 answers to a questionnaire; the atopic status of the child assessed by skin prick tests; and bronchial responsiveness to cold air challenge in the children. Results: After possible confounders were controlled for, the risk of developing hay fever (odds ratio=0.57; 95% confidence interval 0.34 to 0.98), atopy defined as at least one positive reaction to a panel of common aeroallergens (0.67; 0.49 to 0.93), sensitisation to pollen (0.60; 0.41 to 0.87), and of bronchial hyperresponsiveness (0.55;0.34-0.90) was significantly lower in children living in homes where coal or wood was used for heating than in children living in homes with other heating systems. Conclusions: Factors directly or indirectly related to the heating systems used in rural Bavarian homes decrease the susceptibility of children to becoming atopic and to developing bronchial hyperresponsiveness. Key messages This study shows that in a rural population children of families using wood or coal for heating and cooking had a significant lower prevalence of hay fever, atopy, and bronchial hyperresponsiveness than children living in homes with other heating systems Factors directly related to home wood or coal combustion may explain these findings Alternatively, using coal and wood burning stoves indoors may be related to a more traditional life style with unknown protective factors that have been lost in families using other sources of energy such as gas, oil, or a central heating system

The objective of this study was to compare psychosocial characteristics of children with asthma and children with bronchial hyperreactivity with those of normal children. A population-based study of 2634 children (mean age, 10 years) was carried out. Pulmonary function tests of children were performed in children before and after cold air hyperventilation challenge to determine bronchial hyperreactivity. Parental assessment of children's behavior was evaluated with 15 questions about school/learning habits, level of activity, communication/affection, and sleeping patterns. A factor analysis was performed and the factor loading adjusted for confounders compared in the different groups. Asthmatic children sleep less well than normal and hyperreactive children (p < 0.001). Unexpectedly, however, all other single items did not differ significantly. As a result of the factorial analysis we obtained two factors. On the first factor, measuring school behavior and learning, there was a small difference between asthmatic and normal children, which could not be found on the second factor indicating activity and communication. We conclude that psychosocial differences of asthmatic children are less remarkable than expected. As a result of the examination of the hyperreactive children it is likely that asthmatic children are influenced more by secondary psychosocial factors than by any primary effect of asthmatic disease.

In a random sample of children (aged 9-11 years; n = 5629), who were studied according to the ISAAC phase II protocol, heterozygosity of the alpha1 antitrypsin (alpha1-AT) Pi genotypes MS or MZ, or low alpha1-AT plasma levels, were not associated with an increased risk of developing asthma. Asthmatics with low levels of alpha1-AT were particularly prone to develop airway hyperresponsiveness and reduced lung function.

The German reunification offers a unique opportunity to study the impact of environmental factors on the development of childhood respiratory and allergic disorders in ethnically similar populations. We investigated the prevalence of asthma, hay fever, atopy, and bronchial hyperresponsiveness (BHR) in 9- to 11-year old children in West Germany (n = 5,030) and East Germany (n = 2,623). A self-administered questionnaire was distributed to the parents. Children underwent cold air challenge and allergy skin prick tests. Atopic sensitization was considerably more frequent in West German children than in their peers in East Germany (36.7% versus 18.2%; odds ratio [OR] = 2.6, p < 0.0001). The prevalence of current asthma and hay fever was significantly higher in West Germany when compared with that in East Germany (5.9% versus 3.9%; OR = 1.5, p < 0.0001 and 8.6% versus 2.7%; OR = 3.4, p < 0.0001, respectively). Bronchitis, however, was more prevalent in East Germany than in the western part of the country. The prevalence of BHR as assessed by cold air challenge was higher in West Germany compared with that in East Germany (8.3% versus 5.5%, OR = 1.6, p < 0.001). Logistic regression showed that the West German study area was no longer a significant independent determinant of asthma once sensitization to mites, cats, and pollen was taken into account. We conclude that sensitization to aeroallergens is strikingly more frequent in West Germany than in East Germany and this may explain the differences in the prevalence of asthma and hay fever between the two parts of the country.

OBJECTIVES--To examine whether road traffic in a big city has a direct effect on pulmonary function and respiratory symptoms in children. DESIGN--Cross sectional study. SETTING--Of all 7445 fourth grade children (aged 9-11 years) in Munich, 6537 were examined. Of the children with German nationality and the same residence during the past five years and known exposure data, 4678 questionnaires and 4320 pulmonary function tests could be analysed. MAIN OUTCOME MEASURES--Variables of pulmonary function by forced expiration and respiratory symptoms reported in a questionnaire; census data on car traffic collected in the school district. RESULTS--Density of car traffic ranged from 7000 to 125,000 cars per 24 hours. Multiple regression analysis of peak expiratory flow showed a significant decrease of 0.71% (95% confidence interval 1.08% to 0.33%) per increase of 25,000 cars daily passing through the school district on the main road. Maximum expiratory flow when 25% vital capacity had been expired was decreased by 0.68% (1.11% to 0.25%). In contrast, response to cold air challenge was not increased. The adjusted odds ratio for the cumulative prevalence of recurrent wheezing with the same exposure was 1.08 (1.01 to 1.16). Cumulative prevalence of recurrent dyspnoea was increased, with an odds ratio of 1.10 (1.00 to 1.20). Lifetime prevalence of asthma (odds ratio 1.04; 0.89 to 1.21) and recurrent bronchitis (1.05; 0.98 to 1.12) were not significantly increased. CONCLUSIONS--High rates of road traffic diminish forced expiratory flow and increase respiratory symptoms in children.

Information on long-term respiratory symptoms in prematurely born children is scanty. We studied an unselected population of 9- to 11-year-old schoolchildren. A self-administered questionnaire was distributed to the parents. Children underwent lung function testing, cold air challenge, and skin prick tests. A gestational age37 weeks in children with a birth weightor = 2500 gm was reported by 5% of the parents. Premature girls had significantly more current asthma (odds ratio (OR) 2.6; 95% confidence interval (CI) 1.4, 4.7; p0.05), recurrent wheezing (OR 1.7; 95% CI 1.1, 2.7; p0.001), recurrent shortness of breath (OR 2.4; 95% CI 1.5, 3.9; p0.001), and frequent cough with exercise (OR 1.8; 95% CI 1.1, 2.9; p0.05) than term girls, especially if they required mechanical ventilation after birth. No such differences could be shown in boys. More prematurely born children who required mechanical ventilation (OR 3.7; 95% CI 2.2, 6.4; p0.0001) had a family history of asthma than children born at term. Significant decrements could be demonstrated for different measurements of lung function in premature girls. These results remained significant after control for confounders in a multivariate regression analysis. No difference was found between groups for bronchial hyperresponsiveness to cold, dry air or for atopic sensitization. We conclude that a family history of asthma may predispose premature children to more severe respiratory disease. Respiratory symptoms and decrements in lung function seen in girls may reflect abnormalities of lung function in survivors of severe neonatal respiratory disease.

The measurement of bronchial hyperreactivity (BHR) may give additional information to questionnaire-based studies of asthma prevalence. It is desirable to have a provocation method with high specificity that avoids the use of pharmacologic provocations in large numbers of healthy children. It was the aim of this study to establish a range of values for responsiveness to cold-air challenge in normal children, to describe its specificity and sensitivity for a diagnosis of asthma in a large unselected sample of schoolchildren in a field study, and to measure factors associated with hyperresponsiveness. All fourth-grade schoolchildren (9 to 11 yr of age) in Munich and several southern Bavarian communities (n = 9,403) were surveyed with a questionnaire (response rate, 87%), baseline lung function, and cold-air hyperventilation challenge (n = 5,697). A diagnosis of asthma was reported in 7.9% of children. In the reference group, the ninety-fifth percentile (%ile) for the change of FEV1 (DFEV1) was -9.0%; the 90%ile was -7.3%. Asymptomatic children fulfilling all criteria for the reference group showed a significantly increased reactivity if they had a family history of asthma (p = 0.038). With a cutoff for DFEV1 of -9.0% or -7.3% the respective sensitivities to "detect" a diagnosis of asthma were 21.6 and 30.7%, and for asthma with symptoms during the previous 12 months it was 26.2 and 35.1%. Reactivity to cold air increased with the number of episodes of asthma in the previous 12 months. In a multiple linear regression model, factors associated with increased reactivity to cold air were diagnosed asthma, hay fever, male sex, younger age, and a positive skin test.(ABSTRACT TRUNCATED AT 250 WORDS)