Effect of low-dose beclomethasone dipropionate on asthma control and airway inflammation

Abstract

aaStudies of fluid obtained by bronchial lavage, of mucosal tissue obtained by bronchial biopsy, and of sputum obtained by sputum induction, have established that asthma is associated with airway inflammation [1][2][3][4][5][6][7][8][9]. Other studies have demonstrated that high doses of inhaled corticosteroid for periods of up to 16 weeks significantly reduce markers of inflammation in airway mucosal biopsies in subjects with mild asthma [10][11][12]. High doses of inhaled corticosteroids are not necessary to improve asthma control in patients with mild persistent asthma however [13][14][15], and current guidelines suggest that usual doses, not high doses, of inhaled corticosteroid should be prescribed for patients with mild persistent asthma [16]. To our knowledge, the effects of usual or low doses of inhaled corticosteroids on airway mucosal inflammation in asthma have not yet been examined.In this study, our aim was to determine whether the improvements in indices of asthma control produced by a relatively low dose of an inhaled corticosteroid are associated with a reduction in markers of airway inflammation. Thus, we conducted a randomized, parallel-group, placebo-controlled study of the effects of beclomethasone dipropionate (BDP; 336 µg·day -1 ) on measures of asthma control and markers of inflammation in induced sputum. The study design was a 4-week double-blind treatment period followed by a 4-week single-blind placebo run-out period. The run-out period was incorporated to allow determination of the "off-effect" of inhaled BDP, i.e. the duration of persistence of any BDP-induced improvements in asthma control and airway inflammation when treatment was stopped. Materials and methods SubjectsTwenty four asthmatic subjects were studied. Inclusion criteria were a history of symptoms of asthma and bronchial hyperreactivity to methacholine provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20 ð8 mg·mL -1 ). Exclusion criteria were inhaled or oral steroid use or history of an upper respiratory infection in the previous 6 weeks, and tobacco use Effect of low-dose beclomethasone dipropionate on asthma control and airway inflammation. J.V. Fahy, H.A. Boushey. ©ERS Journals Ltd 1998. ABSTRACT: The effects of usual or low doses of inhaled corticosteroids on airway mucosal inflammation have not yet been examined.We therefore, compared the effects of inhaled beclomethasone dipropionate (BDP) 336 µg·day -1 on asthma control outcomes and markers of airway inflammation.Twenty-four adult subjects with mild and moderate asthma were randomized to receive either BDP or placebo for four weeks; then subjects entered a single blind four week placebo run-in period.We found that the BDP group had significantly greater improvements in forced expiratory volume in one second (FEV1), morning peak flow, and rescue salbutamol use than the placebo-treated group. The improvement in FEV1 largely reversed one week after treatment was stopped. The decrease in the median percentage of eosinophils in in...

Clinical judgement of airway inflammation versus sputum cell counts in patients with asthma

“…There is therefore little doubt that eosinophilic or neutrophilic inflammation was present in 19 and eight patients, respectively, and that this was misinterpreted clinically in~30% of patients. This disagreement has been observed in corticosteroid dose-response studies in which maximum clinical improvement can occur before there is a reversal of sputum eosinophilia [28,29]. However, there may be some doubt about the interpretation of normal sputum cell counts when the physician thought airway inflammation was present.…”

“…There is increasing evidence that corticosteroid treatment is not effective in the absence of sputum eosinophilia [31±33]. However, it has also been recognized that controlled asthma on inhaled steroids might be associated with persistent sputum eosinophilia [28]. From available evidence, it might appear that 14 patients with a normal sputum cell count and four patients with a significantly high neutrophil count without eosinophilia may not have benefited from an increase in the dose of inhaled corticosteroid or prednisone, whereas 11 of the 19 patients with a raised eosinophil count might have.…”

Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps

“…GRONEBERG et al [22] reported no change in mucin content after a month of inhaled budesonide therapy, using a semiquantitative analysis of MUC5AC mucin staining of bronchial biopsies. FAHY et al [23] reported that a month of inhaled beclomethasone therapy did not affect mucin-like glycoproteins in the sputum of moderate asthmatics. The present study is the first to assess effects of local steroids in human airway epithelium in vivo on both mucin gene and protein expression, using quantitative morphometric analysis.…”

Induced Sputum for the Investigation of Airway Inflammation: Evidence for Its Clinical Application

“…Neutrophilic exacerbations respond differently than eosinophilic exacerbations to treatment. Sputum eosinophilia responds to treatment with corticosteroids whether the clinical presentation is of asthma (6,37,45,46) (Figure 2), chronic cough (32)(33)(34) or chronic airflow limitation (7). Sputum examination has illustrated the kinetics of change in sputum eosinophilia with changes in prednisone treatment.…”