Long-term management of asthma in First Nations and Inuit children: A knowledge translation tool based on Canadian paediatric asthma guidelines, intended for use by front-line health care professionals working in isolated communities.

Asthma is a serious health problem for First Nations and Inuit children. In children younger than one year of age, asthma needs to be distinguished from viral bronchiolitis, which is unusually common in Canadian Aboriginal children. In children younger than six years of age, the diagnosis depends on the presence of typical symptoms, the absence of atypical features and the documentation of response to therapy - particularly a rapid, transient response to bronchodilators. In older children, the presence of reversible airway obstruction should be determined using spirometry whenever feasible to confirm the diagnosis. Environmental triggers should be evaluated and corrected whenever possible. Regular use of inhaled steroids is the most important measure for maintaining good asthma control in children with asthma. Clients and their families should receive asthma education. Control should be regularly reassessed at follow-up visits in health centres, with therapy adjusted to the lowest level capable of maintaining good control.

L'asthme est un grave problème de santé pour les enfants inuits et des Premières nations. Chez les enfants de moins d'un an, il faut distinguer l'asthme de la bronchiolite virale, anormalement fréquente chez les enfants autochtones du Canada. Chez les enfants de moins de six ans, le diagnostic dépend de la présence de symptômes classiques, de l'absence de caractéristiques atypiques et de la consignation de la réponse au traitement, notamment la réponse rapide et transitoire aux bronchodilatateurs. Chez les enfants plus âgés, il faut, dans la mesure du possible, déterminer la présence d'une obstruction réversible des voies aériennes par spirométrie afin de confirmer le diagnostic ainsi qu'évaluer et corriger les déclencheurs environnementaux. L'utilisation régulière de corticoïdes en aérosol est la principale mesure à prendre pour maintenir un bon contrôle de l'asthme chez les enfants asthmatiques. Les clients et leur famille devraient recevoir une formation sur l'asthme. Il faut réévaluer régulièrement le contrôle aux visites de suivi dans des centres de santé et rajuster le traitement à la dose la plus basse possible pour le maintien de ce contrôle.

Developmental expression of the receptor for advanced glycation end-products (RAGE) and its response to hyperoxia in the neonatal rat lung.

BACKGROUND: The receptor for advanced glycation end products (mRAGE) is associated with pathology in most tissues, while its soluble form (sRAGE) acts as a decoy receptor. The adult lung is unique in that it expresses high amounts of RAGE under normal conditions while other tissues express low amounts normally and up-regulate RAGE during pathologic processes. We sought to determine the regulation of the soluble and membrane isoforms of RAGE in the developing lung, and its expression under hyperoxic conditions in the neonatal lung. RESULTS: Fetal (E19), term, 4 day, 8 day and adult rat lung protein and mRNA were analyzed, as well as lungs from neonatal (0-24 hrs) 2 day and 8 day hyperoxic (95% O2) exposed animals. mRAGE transcripts in the adult rat lung were 23% greater than in neonatal (0-24 hrs) lungs. On the protein level, rat adult mRAGE expression was 2.2-fold higher relative to neonatal mRAGE expression, and adult sRAGE protein expression was 2-fold higher compared to neonatal sRAGE. Fetal, term, 4 day and 8 day old rats had a steady increase in both membrane and sRAGE protein expression evaluated by Western Blot and immunohistochemistry. Newborn rats exposed to chronic hyperoxia showed significantly decreased total RAGE expression compared to room air controls. CONCLUSION: Taken together, these data show that rat pulmonary RAGE expression increases with age beginning from birth, and interestingly, this increase is counteracted under hyperoxic conditions. These results support the emerging concept that RAGE plays a novel and homeostatic role in lung physiology.

Discordant extracellular superoxide dismutase expression and activity in neonatal hyperoxic lung.

Antioxidant defenses in the neonatal lung are required to adapt to the oxygen (O(2))-rich postnatal environment, and oxidant/antioxidant imbalance is a predisposition to lung injury when high concentrations of inspired O(2) are used in neonatal lung diseases. The lung's main extracellular enzymatic defense against superoxide, extracellular superoxide dismutase (EC-SOD), is closely regulated during development. In testing the hypothesis that developmental change in EC-SOD expression and activity in the immature lung would be disrupted by hyperoxia, we found a doubling of lung EC-SOD protein in newborn rats exposed to 95% O(2) for 1 week. Furthermore, EC-SOD protein secretion increased, but EC-SOD enzyme activity did not change with O(2) exposure. EC-SOD mRNA did not change at multiple points between 6 hours and 8 days. Lung EC-SOD recovered by immunoprecipitation after 1 week of O(2) showed strong increases in protein nitrotyrosine and variable, nonsignificant differences in protein carbonyl content. These data provide the first direct evidence that EC-SOD is itself a target of nitration in hyperoxia, and offer a plausible explanation for low EC-SOD activity despite its increased secretion by O(2)-exposed neonatal lung.

Prenatal hypoxia decreases lung extracellular superoxide dismutase expression and activity.

Extracellular superoxide dismutase (EC-SOD), which scavenges extracellular superoxide (O.), is highly regulated in the developing lung. In the prenatal rabbit, EC-SOD is predominantly intracellular and inactive, and postnatally, active EC-SOD is secreted. We hypothesized that prenatal hypoxia would delay the normal postnatal secretion of active EC-SOD in the lung. Pregnant New Zealand White rabbits were exposed to hypobaric hypoxia (15,000 ft x 36 h) to alter fetal O(2) tension or were maintained in room air. Lungs were harvested from preterm (28 days), term (30 +/- 1 day), and 1-wk-old kits. After prenatal hypobaric hypoxia, EC-SOD mRNA expression was significantly decreased in lungs of full-term kits, whereas EC-SOD protein decreased at all ages. Immunohistochemical staining for EC-SOD showed that hypoxia delayed secretion of the isoenzyme in the airways and pulmonary vasculature. Furthermore, pulmonary EC-SOD enzyme activity was significantly decreased in the 1-wk-old kits exposed to prenatal hypoxia. We conclude that prenatal hypoxia downregulates EC-SOD expression at both the transcriptional and posttranslational levels. Furthermore, prenatal hypoxia delays secretion of active EC-SOD enzyme. These findings have important implications for the effects of prenatal asphyxia on postnatal response to oxidant stress.