Remodeling and airway hyperresponsiveness but not cellular inflammation persist after allergen challenge in asthma.
BACKGROUND
Airway hyperresponsiveness (AHR) increases up to 2 weeks after allergen inhalational challenge of subjects with asthma who show a late-phase asthmatic reaction (dual responders). Cellular inflammation and airway remodeling are increased 24 hours after allergen challenge.


OBJECTIVE
To determine whether persistence of increased AHR is associated with persistent activation of remodeling and enhanced inflammation.


METHODS
Fiberoptic bronchoscopy was performed at baseline and at 24 hours and 7 days after allergen inhalational challenge of dual responders with mild-moderate asthma. At each time point, AHR, spirometry, and expression of tenascin (extracellular matrix protein), procollagen I, procollagen III, and heat shock protein (HSP)-47 (markers of collagen synthesis), and alpha-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of airway remodeling, together with numbers of mucosal major basic protein-positive eosinophils, CD68(+) macrophages, CD3(+), CD4(+), CD8(+) T cells, elastase-positive neutrophils, and tryptase-positive mast cells.


RESULTS
AHR was increased from baseline at 24 hours and 7 days after allergen challenge. Reticular basement membrane tenascin expression was elevated at 24 hours and returned to baseline levels at 7 days. Reticular basement membrane procollagen III expression was significantly elevated at 7 days. Expression of procollagen I, HSP-47, and alpha-smooth muscle actin were all higher at 7 days compared with 24 hours. At 24 hours, eosinophil, macrophage, neutrophil, and CD3(+) T cells were increased but had returned to baseline by 7 days.


CONCLUSIONS
In dual responders with asthma, the 24-hour increase in airway wall cellular inflammation after allergen challenge resolves by 7 days, whereas the increases in AHR and markers of remodeling persist.
Kariyawasam
Harsha H
HH
Allergy and Clinical Immunology, Leukocyte Biology Section, Sir Alexander Fleming Building, Imperial College London, London, UK.
Aizen
Maxine
M
Barkans
Julia
J
Robinson
Douglas S
DS
Kay
A Barry
AB
D000199:Actins / Q000378:metabolism; D000328:Adult; D001249:Asthma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001999:Bronchoscopy; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D013147:Spirometry; D013997:Time Factors
D000199:Actins; D016326:Extracellular Matrix Proteins; D050958:HSP47 Heat-Shock Proteins