Sputum examination is a useful noninvasive method to study airway inflammation. We investigated the reproducibility and validity of the measurements of lymphocyte subsets in the sputum of 11 stable patients with asthma and 10 nonasthmatic smokers. Sputum was dispersed with 0.1% dithiothreitol. A differential cell count was made with Wright's stain. Aliquots were stained with antibodies to CD19 (B cells), CD3 (T cells), CD4 (helper), CD8 (suppressor), and the activation marker CD25 (IL2 receptor) on T-cell subsets and were assayed by flow cytometry. Sputum from patients with asthma compared with nonasthmatic subjects had more eosinophils (mean +/- SEM, 32.5 +/- 8.5 versus 1.3 +/- 0.5%, p < 0.01) and a higher proportion of lymphocytes that were B cells (16.2 +/- 3.2 versus 4.0 +/- 1.0%, p < 0.01), and these correlated closely with the eosinophils (r = 0.8, p < 0.01). Patients with asthma also had more activated T-helper cells (39.3 +/- 4.6 versus 9.0 +/- 9.0%, p = 0.05), but the comparison was limited to two smokers because of macrophage autofluorescence. The repeatability of measurements of helper T-cells (R = 0.94), suppressor T cells (R = 0.88), and activated helper T cells (R = 0.77) was good; repeatability of measurements of T and B cells could not be examined because these were reciprocals of each other. Asthmatic sputum has different lymphocyte profiles than sputum from nonasthmatic smoking control subjects. The results demonstrate a potential importance of antibody-producing lymphocytes in the airway and their relation to sputum eosinophilia in asthma.

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Regular use of short-acting β-agonists may decrease control of asthma and increase airway responsiveness to bronchoconstrictor stimuli. The aim of this study was to determine the effects of regular treatment with the long-acting β-agonist, salmeterol, on the methacholine dose-response curve (DRC) in mild-tomoderate asthmatics.Changes in methacholine airway responsiveness were measured in 14 stable adult asthmatics, randomized in a double-blind, three-way cross-over design to receive salmeterol 50 µg, salbutamol 200 µg or placebo, each twice daily for 4 days. Two baseline methacholine DRC, were performed, one without premedication and one following a single dose of 200 µg salbutamol. Following 4 days of regular treatment, methacholine DRC to plateau were carried out commencing 15 min after the final dose of trial medication.There were no significant differences in mean baseline forced expiratory volume in one second (FEV1) between treatments. Four days treatment with salmeterol and salbutamol shifted the DRC to the right, but salmeterol provided less protection than salbutamol. The point of inflection of the curve from baseline moved 1.9 and 3.2 doubling doses, respectively, compared to placebo (p≤0.001), and the provocative concentration of methacholine required to produce a 20% fall in FEV1 (PC20) increased 1.6 and 3.1 doubling doses, respectively (p≤0.001). The slope of the DRC was increased slightly by both β-agonists compared to placebo (log slope 3.11, 3.06 and 2.77 for salmeterol, salbutamol and placebo, respectively). This effect of regular salmeterol on slope was more marked in subjects with lower baseline FEV1. Maximal response plateaus did not differ between the three treatments.These results suggest that regular use either of short-or long-acting β-agonists could increase the risk of a more precipitous asthma episode associated with "breakthrough" bronchoconstrictor responses, particularly in those with more severe initial airflow obstruction, if subjects are exposed to a sufficiently potent stimulus.

A A c ca as se e f fo or r s se er ri ia al l e ex xa am mi in na at ti io on n o of f s sp pu ut tu um m i in nf fl la am mm ma at to or ry y c ce el ll ls s ABSTRACT: In the case reported, serial evaluation of sputum inflammatory cell counts made it possible to identify an unusual series of events in a man with eosinophilic bronchitis. The patient initially presented with a productive cough, which did not respond to treatment with antibiotics or high-dose inhaled corticosteroids. A diagnosis of eosinophilic bronchitis was made after demonstration of intense sputum eosinophilia.When inhaled corticosteroids were stopped, symptoms and sputum eosinophilia became worse and airway hyperresponsiveness developed. Both abnormalities were reversed by a course of prednisone. When the prednisone was stopped the productive cough recurred but on this occasion sputum examination suggested a different disease process and the symptoms resolved after a course of co-trimoxazole. The patient has subsequently remained well on no treatment with little or no sputum eosinophilia.

The purpose of this study was to estimate the relative dose potency of salbutamol Turbuhaler compared with salbutamol pressurized metered dose inhaler (pMDI) with respect to the protective effect against methacholine bronchoconstriction. Twenty-three asthmatic subjects with stable asthma participated in the study. Baseline forced expiratory volume in 1 s (FEV 1 ) was 70% or more of predicted, and baseline methacholine provocative concentration causing a 20% fall in FEV 1 (PC 20 ) was 4 mg/mL or less. The design was randomized, double-blind, double-dummy, crossover and placebo controlled and was conducted over seven study days. On each study day, the subjects inhaled 50 µg or 100 µg of salbutamol via Turbuhaler, 100 µg, 200 µg, 400 µg or 800 µg of salbutamol via pMDI, or placebo in randomized order. PC 20 was determined 30 mins after inhalation. Increasing doses of salbutamol pMDI increased the PC 20 in a dose-dependent fashion from 3.9 mg/mL after placebo to 13.3 mg/mL after pMDI 100 µg, 19.0 mg/mL after 200 µg, 32.6 mg/mL after 400 µg, and 35.1 mg/mL after 800 µg. The half-maximum response dose for pMDI (ED 50 ) was 104 µg. Salbutamol Turbuhaler 50 µg increased the PC 20 to 10.0 mg/mL and 100 µg to 12.6 mg/mL. Salbutamol pMDI 200 µg provided significantly greater protection to methacholine than pMDI 100 µg or Turbuhaler 100 µg and significantly less protection than pMDI 400 µg (P<0.05). This study demonstrates that the relative protective dose potency of inhaled beta-agonists can be determined by comparing their effects on methacholine airway responsiveness. The estimated relative protective dose potency for salbutamol Turbuhaler in comparison with pMDI was 1.38 (95% CI 0.67 to 2.87) at 50 µg and was 0.96 (95% CI 0.56 to 1.64) at 100 µg. Key Words: Methacholine airway responsiveness, Pressurized metered dose inhaler, Salbutamol, Turbuhaler Salbutamol is a selective beta-agonist that provides 4 to 6 h of bronchodilation upon inhalation. Until recently, this drug was administered mainly as aerosols from pressurized metered dose inhalers (pMDI). Many available pMDIs contain chlorofluorocarbons as propellants for aerosol generation (1). Problems exist with respect to coordination of actuation and inhalation, and, in some patients, the propellants can provoke acute transient bronchoconstriction (2). Turbuhaler (Astra Pharma Inc) is an inspiratory flow-driven, multidose, dry powder inhaler that provides the medication without the need for propellants. A randomized crossover comparison of five inhaler systems determined an overall preference for Turbuhaler with respect to ease of use (3).Salbutamol inhaled via Turbuhaler and pMDI have been compared in recent studies. The same nominal dose of salbutamol given via Turbuhaler has been shown to be more potent than salbutamol via pMDI with respect to bronchodilator response and systemic effects (4,5). In addition, Turbuhaler gives a higher pulmonary deposition of terbutaline compared with pMDI (6) and significantly greater bronchodilation compared with terbutaline pMDI pl...