High dose inhaled corticosteroid therapy in non asthmatic chronic airflow obstruction: a comparative study of the short term effect of lung function, symptoms, bronchial responsiveness, and peripheral neutrophil function, and observations on the long term role of such treatment
Weir, David Cuthbertson
MetadataShow full item record
This thesis has investigated and compared the short term effect of treatment with 750 micrograms and 1500 micrograms twice daily of inhaled beclomethasone dipropionate (BDP), and oral prednisolone 40 mg per day, on lung function and quality of life in 105 patients with non asthmatic chronic airflow obstruction. The role of physiological and clinical features in determining the response to treatment in individuals has been investigated, and the systemic and local side effects of therapy have been studied. The effect of treatment on peripheral neutrophil function has been investigated in a subgroup of patients, and observations on decline in FEV1 in a separate cohort of patients are presented.After three weeks treatment both doses of BDP produced equivalent, small but statistically significant improvements in FEV1, FVC, and mean PEF, compared to that seen with placebo. Individual patients demonstrated a response, defined on the changes seen in physiological variables, to active treatment more commonly than with placebo. Bronchial responsiveness to inhaled histamine was unaltered by treatment for three weeks with inhaled BDP. Quality of life and subjective measures of dyspnea showed marked baseline variability, but treatment with BDP significantly improved dyspnea and patient's 'mastery' over the disease. Oral prednisolone did not improve lung function or subjective measures further. A response to active treatment in individual patients was more common in those with more severe physiological impairment. Formal discriminant analysis was unsuccessful in predicting response to treatment in individual patients.No significant deleterious effect of treatment with inhaled BDP or oral prednisolone on global respiratory muscle strength was detected. Treatment with BDP caused detectable adrenal suppression, which was dose related, for 750 micrograms twice daily, approximately one tenth that seen with oral prednisolone 40 mg per day, and for 1500 micrograms twice daily, one quarter. Local side effects were more common after inhaled therapy compared with placebo, but affected only a minority of patients.Peripheral neutrophil activation was suppressed by treatment with inhaled BDP, and a fall in sputum albumin concentration A suggested a reduction in bronchial tree inflammation with treatment.The uncontrolled observational study failed to confirm previously reported associations between decline in FEV1, and bronchial hyperresponsiveness, and reversibility of FEV1 to bronchodilators. The short term response to corticosteroids did not correlate with subsequent decline in FEV1. In 32 patients who started regular inhaled BDP midway through the observation period the decline in FEY1 fell significantly, by over one half, over the remaining period of observation. These observations question the role of short term steroid trials, and suggest a disease retarding effect of inhaled BDP in these patients with non asthmatic chronic airflow obstruction.