Va. Swystun et al., Mast cell tryptase release and asthmatic responses to allergen increase with regular use of salbutamol, J ALLERG CL, 106(1), 2000, pp. 57-64
Background: Increased asthmatic responses to allergen, both early and late,
have been demonstrated after regular use of beta(2)-agonists in as few as
7 days. Desensitization of beta(2)-adrenergic receptors on airway mast cell
s may contribute to this effect by allowing greater release of mast cell me
diator on allergen-induced degranulation, Tryptase released from lung mast
cells can be measured in serum 1 hour after allergen challenge and serves a
s a marker of mast cell degranulation.
Objective: To examine the effect of regular treatment with salbutamol, a be
ta(2)-agonist, on mast cell mediator release after allergen challenge and i
ts influence on the early asthmatic response (EAR) and the Late allergic re
sponse, we measured the EAR, serum tryptase levels, the 7-hour FEV1, and sp
utum tryptase levels and cell profiles.
Methods: We conducted a placebo-controlled, double-blind, randomized cross-
over comparison of treatments for 10 days with either a salbutamol metered-
dose inhaler (100 mu g, 2 puffs 4 times daily) or a matched placebo inhaler
with at least a 7-day washout between treatments, Atopic subjects (n = 14)
with mild-to-moderate asthma performed same-dose allergen inhalation tests
after both treatments 12 to 15 hours after the last dose of study inhaler.
Baseline and 7-hour FEV1 and the EAR to allergen were measured by using sp
irometry; venous blood was drawn at 1 hour for analysis of serum tryptase;
and sputum was induced and collected at 1 and 7 hours,
Results: Salbutamol treatment resulted in a significantly greater EAR (20%
+/- 1.6% [SEM] vs 15% +/- 2.1%; P = .047); increased I-hour serum tryptase
levels (9.09 +/- 1.57 vs 7.52 +/- 1.12 mu g/L; P = .011); increased proport
ions of eosinophils in the 7-hour sputum sample (39.1% +/- 5.1% vs 28.4% +/
- 4.4%; P < .05); increased proportion of metachromatic cells in the 7-hour
sputum sample (4.4% +/- 1.1% vs 2.2% +/- 0.6%; P = .032); and lower 7-hour
FEV1 (2.77 +/-:0.18 vs 2.97 +/- 0.20 L; P = .014), Baseline FEV1 was not s
ignificantly different after salbutamol treatment compared with values afte
r placebo treatment (2.90 +/- 0.20 vs 3.00 +/- 0.19 L; P = .11).
Conclusion: Regular 10-day treatment with salbutamol increases the allergen
-induced release of mediator from airway mast cells, and this is reflected
in an increased EAR to allergen. Late-pbase responses to allergen were also
enhanced, as demonstrated by decreased 7-hour FEV1 and increased eosinophi
lia and percentage of metachromatic cells in the 7-hour sputum sample. Incr
eased allergen-induced mast cell degranulation could, in part, explain the
increased asthmatic responses to allergen after beta(2)-agonist treatment a
nd could contribute to the deterioration of asthma control that is associat
ed with regular use of beta(2)-agonist by potentiating allergic inflammatio
n.