Mast cell tryptase release and asthmatic responses to allergen increase with regular use of salbutamol.
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 cells may contribute to this effect by allowing greater release of mast cell mediator on allergen-induced degranulation. Tryptase released from lung mast cells can be measured in serum 1 hour after allergen challenge and serves as a marker of mast cell degranulation.


OBJECTIVE
To examine the effect of regular treatment with salbutamol, a beta(2)-agonist, on mast cell mediator release after allergen challenge and its influence on the early asthmatic response (EAR) and the late allergic response, we measured the EAR, serum tryptase levels, the 7-hour FEV(1), and sputum 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 microgram, 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 FEV(1) and the EAR to allergen were measured by using spirometry; 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 1-hour serum tryptase levels (9.09 +/- 1.57 vs 7.52 +/- 1.12 microgram/L; P =. 011); increased proportions 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 FEV(1) (2.77 +/- 0.18 vs 2.97 +/- 0.20 L; P =.014). Baseline FEV(1) was not significantly different after salbutamol treatment compared with values after placebo treatment (2.90 +/- 0.20 vs 3.00 +/- 0.19 L; P =.11).


CONCLUSIONS
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-phase responses to allergen were also enhanced, as demonstrated by decreased 7-hour FEV(1) and increased eosinophilia and percentage of metachromatic cells in the 7-hour sputum sample. Increased allergen-induced mast cell degranulation could, in part, explain the increased asthmatic responses to allergen after beta(2)-agonist treatment and could contribute to the deterioration of asthma control that is associated with regular use of beta(2)-agonist by potentiating allergic inflammation.
Swystun
V A
VA
Division of Respiratory Medicine, Royal University Hospital, Departments of Physiology and Veterinary Microbiology, University of Saskatchewan, Saskatoon.
Gordon
J R
JR
Davis
E B
EB
Zhang
X
X
Cockcroft
D W
DW
D000328:Adult; D000420:Albuterol / Q000627:therapeutic use*; D000485:Allergens; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D053818:Chymases; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology*; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000378:metabolism*; D013183:Sputum / Q000737:chemistry; D053802:Tryptases
D000485:Allergens; D001993:Bronchodilator Agents; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D000420:Albuterol