Endobronchial lesions caused by nontuberculous mycobacteria in apparently healthy pediatric patients.

Pulmonary disease caused by nontuberculous mycobacteria in healthy children is rare, and its pathogenesis is unknown in most cases and standardized treatment is lacking. Here, we report various endobronchial manifestations in 5 patients including hitherto undescribed diffuse tracheobronchial granulomas in 2 patients. Bronchoscopic debulking was performed in all patients and tuberculostatic treatment in 4. All patients including 1 without tuberculostatic treatment showed remission.

Risk factors for morbidity and mortality in pediatric home mechanical ventilation.

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 <1 year of age. A total of 45 children were ventilated via tracheostomy and 9 by nasal mask. This study identified 68 severe emergencies (0.2 per patient-year) leading to 4 deaths. Respiratory causes were found in 48 cases (including 15 tracheostomy-related and 3 ventilator failures). Only age, but not underlying diagnosis or mode of ventilation, correlated with incidence of emergencies. CONCLUSIONS: Pediatric HMV including all age and diagnostic groups shows a low incidence of emergencies.

Whole-lung lavage in infants and children with pulmonary alveolar proteinosis.

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.

Seizures and stupor during intravenous mannose therapy in a patient with CDG syndrome type 1b (MPI-CDG).

MPI-CDG (formally called CDG 1b), caused by phosphomannose isomerase (MPI) deficiency, leads to hypoglycaemia, protein losing enteropathy, hepatopathy, and thrombotic events, whereas neurologic development remains unaffected. Dietary supplementation of mannose can reverse clinical symptoms by entering the N-glycosylation pathway downstream of MPI. When oral intake of mannose in patients with MPI-CDG is not possible, e.g. due to surgery, mannose has to be given intravenously. We report a patient with MPI-CDG on intravenous mannose therapy that showed severe depression of consciousness and seizures without apparent cause. EEG and cranial MRI findings were compatible with metabolic coma whereas extended laboratory examinations including repeated blood glucose measurements were normal. Importantly, an intravenous bolus of glucose immediately led to clinical recovery and EEG improvement. Mannose did not interfere with glucose measurement in our assay. We suggest that in patients with MPI-CDG, intravenous mannose infusion can lead to intracellular ATP deprivation due to several mechanisms: (1) in MPI deficiency, mannose 6-P cannot be isomerised to fructose 6-P and therefore is unavailable for glycolysis; (2) animal data has shown that accumulating intracellular mannose 6-P inhibits glycolysis; and (3) elevated intracellular mannose 6-P may induce an ATP wasting cycle of dephosphorylation and rephosphorylation ("honey bee effect"). The mannose-induced metabolic inhibition may be overcome by high-dose glucose treatment. We caution that, in patients with MPI-CDG, life-threatening central nervous system disturbances may occur with intravenous mannose treatment. These may be due to intracellular energy failure. Clinical symptoms of energy deficiency should be treated early and aggressively with intravenous glucose regardless of blood glucose levels.

The role of polymorphisms in ADAM33, a disintegrin and metalloprotease 33, in childhood asthma and lung function in two German populations.

BACKGROUND: ADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness. However, replication results have been inconclusive in smaller previous study populations probably due to inconsistencies in asthma phenotypes or yet unknown environmental influences. Thus, we tried to further elucidate the role of ADAM33 polymorphisms (SNPs) in a genetic analysis of German case control and longitudinal populations. METHODS: Using MALDI-TOF, ten ADAM33 SNPs were genotyped in 1,872 children from the International Study of Asthma and Allergy in Childhood (ISAAC II) in a case control setting and further 824 children from the longitudinal cohort Multicentre Study of Allergy (MAS). In both populations the effects of single SNPs and haplotypes were studied and a gene environment analysis with passive smoke exposure was performed using SAS/Genetics. RESULTS: No single SNP showed a significant association with doctor's diagnosis of asthma. A trend for somewhat more profound effects of ADAM33 SNPs was observed in individuals with asthma and BHR. Haplotype analyses suggested a minor effect of the ADAM33 haplotype H4 on asthma (p = 0.033) but not on BHR. Associations with non atopic asthma and baseline lung function were identified but no interaction with passive smoke exposure could be detected. CONCLUSION: The originally reported association between ADAM33 polymorphisms and asthma and BHR could not be confirmed. However, our data may suggest a complex role of ADAM33 polymorphisms in asthma ethiology, especially in non atopic asthma.