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Asthma frequently commences in early life during airway and immune development and exposure to new environmental challenges. Endobronchial biopsies from children with asthma are abnormal, and lung function is maximally reduced by 6 years of age. As longitudinal biopsy studies are unethical in children, the relationship between development of pathology and reduced lung function is unknown. We aimed to establish a novel neonatal mouse model of allergic airways disease to investigate the developmental sequence of the pathophysiologic features of asthma. Neonatal Balb/c mice were challenged three times weekly from Day 3 of life using intranasal house dust mite (HDM) or saline for up to 12 weeks. Weekly assessments of airway inflammation and remodeling were made. Airway hyperresponsiveness (AHR) to methacholine was assessed from Week 2 onward. Total and eosinophilic inflammation was significantly increased in the lungs of HDM-exposed neonates from Week 2 onwards, and a peak was seen at 3 weeks. Goblet cells and peribronchiolar reticulin deposition were significantly increased in HDM-exposed neonates from Week 3, and peribronchiolar collagen was significantly greater from Week 4. HDM-exposed neonates had increased AHR from Week 2 onward. Although inflammation and AHR had subsided after 4 weeks without allergen challenge, the increased reticulin and collagen deposition persisted in HDM-exposed mice. Neonatal mice exposed to intranasal HDM developed eosinophilic inflammation, airway remodeling, and AHR as reported in pediatric asthma. Importantly, all abnormalities developed in parallel, not sequentially, between 2 and 3 weeks of age.

Original publication

DOI

10.1165/rcmb.2008-0396oc

Type

Journal article

Journal

American journal of respiratory cell and molecular biology

Publication Date

09/2009

Volume

41

Pages

281 - 289

Addresses

Leukocyte Biology Section, National Heart & Lung Institute, Sir Alexander Fleming Building, Imperial College London, Exhibition Road, London SW7 2AZ, UK.

Keywords

Lung, Animals, Mice, Inbred BALB C, Animals, Newborn, Humans, Mice, Pyroglyphidae, Asthma, Bronchial Hyperreactivity, Disease Models, Animal, Collagen, Reticulin, Allergens, Cytokines, Respiratory Function Tests, Child, Child, Preschool, Infant