The method that we have previously reported for sputum induction involves collecting the entire expectorate produced over a 20 min inhalation of 3% saline aerosol. This method presents the potential disadvantage of a considerable and variable salivary contribution to the induced sputum sample. In this study, we examined whether separate collection of saliva and sputum represents a better method for collecting induced sputum during sputum induction.In 11 stable asthmatics, we compared the volume, total and differential cell counts, and eosinophil cationic protein (ECP) levels in four induced sputum samples, two performed using our previous method (Method A) and two using another method (Method B) in which subjects spit saliva into one container before coughing sputum into another.We found that the volume of sputum obtained with Method B was lower than that obtained with Method A (6.16±0.61 vs 20.1±2.7 mL; p=0.003), as was the percentage of squamous cells (34±4 vs 47±6; p=0.023). In addition, the ECP levels in samples collected by Method B were higher (261±42 vs 145±26 ng·mL -1 ; p=0.01). The differential counts of nonsquamous cells were similar except for the percentage of neutrophils, which was lower in Method B (37±4 vs 50±5%; p=0.019). The repeatability of measurements of eosinophil percentages and of ECP levels was similar for the two methods.We conclude that separate collection of saliva and sputum yields induced sputum samples with reduced amounts of saliva and is, therefore, a better method for collecting induced sputum. Eur Respir J., 1996Respir J., , 9, 2448Respir J., -2453 Sputum induction has recently been shown to be an effective and noninvasive method for obtaining airway secretions for analysis of their cellular and biochemical constituents [1,2]. Analysis of induced sputum samples from asthmatic subjects has revealed higher than normal eosinophil percentages and higher than normal eosinophil cationic protein (ECP) levels [1,2], data that is qualitatively similar to that obtained from analysis of bronchoalveolar lavage (BAL) [3]. In addition, analysis of induced sputum from asthmatic subjects has documented the expected changes in inflammatory markers accompanying allergen challenge [4,5], isocyanate challenge [6] and prednisone therapy [7].At the present time, there is a lack of consensus on the optimal techniques for obtaining, processing and analysing induced sputum samples. The method that we have previously reported for sputum induction involves collecting and analysing the entire expectorate, including saliva and sputum, produced over a 20 min inhalation of 3% saline aerosol. This method has the advantage of relative simplicity and has been shown to be valid [2,3,5,7], but presents the potential disadvantage of a considerable and variable salivary contribution to the induced sputum sample. Saliva has at least two effects on induced sputum: it contributes cells and chemicals from the oropharynx and it dilutes the concentrations of subglottic cells and chemicals. The cells in saliva ...

The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation.In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low-(100 mg . day -1 ) or high-dose (1,000 mg . day -1 ) FP for six weeks followed by placebo for 3 weeks.During treatment, the median increase in forced expiratory volume in one second (FEV1) was 12% in the high-dose group (p<0.05) and 10% in the low-dose group (p<0.05) (p>0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p<0.05) and 46% in the low-dose group (p<0.05) (p>0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p<0.05), but only the improvement in salbutamol use was greater in the highdose group (p<0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p<0.05).It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high-and lowdose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma. Eur Respir J 2000; 15: 11±18.

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...

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