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Airway eosinophilia in chronic cough, asthma and chronic obstructive pulmonary disease : an immunopathological feature of disease and a marker of response to corticosteriods
thesisposted on 2014-12-15, 10:30 authored by Christopher. Brightling
Eosinophilia bronchitis is a condition characterised by chronic cough and a sputum eosinophilia without the variable airflow obstruction or airway hyperresponsiveness characteristics of asthma. This thesis describes the incidence of eosinophilic bronchitis as a cause of chronic cough and determines whether the presence of a sputum eosinophilia is associated with a favourable response to corticosteroids in eosinophilic bronchitis and chronic obstructive pulmonary disease (COPD). This is the first study to investigate in detail the immunopathology of patients with eosinophilic bronchitis compared to asthma. Understanding differences in the immunopathology will inform our understanding of the development of the disordered airway physiology observed in asthma. We demonstrated that eosinophilic bronchitis is a common cause of chronic cough and that a sputum eosinophilia predicts a good response to corticosteroids in this condition, asthma and COPD. We found sputum, bronchial wash and bronchoalveolar lavage (BAL) eosinophilia and bronchial submucosal evidence of eosinophilic airway inflammation, increased Th2 cytokine expression and basement membrane thickening and increased constitutive intracellular expression of IL-4 from BAL derived T-cells in subjects with eosinophilic bronchitis to the same degree as those with asthma. Thus, the immunopathology of eosinophilic bronchitis is very similar to asthma questioning the importance of these classical pathological characteristic of asthma in the development of abnormal airway physiology. In addition, we quantified the inflammatory cell infiltration of the airway smooth muscle and found a striking increase in the number of mast cells within the airway smooth muscle in asthma compared to eosinophilic bronchitis and normal subjects. Our findings suggest that in asthma the microlocalisation of mast cells within the airway smooth muscle is a key factor in the development of variable airflow obstruction and airway hyperresponsiveness. Thus, specific targeting of the mast cell-smooth muscle interaction may provide a novel approach to the effective treatment for asthma.
Date of award2002-01-01
Awarding institutionUniversity of Leicester