Effect of aspirin on airway inflammation and pulmonary function in patients with persistent asthma.
BACKGROUND
Aspirin can cause bronchoconstriction in some asthmatic patients through increased production of proinflammatory mediators, particularly leukotrienes. However, recent in vivo evidence has suggested that aspirin also triggers the production of lipoxins, which act as natural antagonists of prostaglandins and leukotrienes. Aside from patients with known aspirin-sensitive asthma, physicians have avoided the use of aspirin in asthmatic patients in general because it was believed that this agent might precipitate worsening of their condition.


OBJECTIVE
We sought to establish the effect of aspirin on pulmonary inflammation and function in patients with persistent asthma.


METHODS
After withdrawal of their usual anti-inflammatory medication, patients with mild-to-moderate persistent asthma undertook double-blind, randomized, crossover treatment with 75 mg/d aspirin and placebo for 3 weeks each. Treatment evaluation included histamine challenge, spirometry, impulse oscillometry, total and alveolar exhaled nitric oxide measurement, and serum thromboxane B2 and 15-epilipoxin A4 levels.


RESULTS
Fifteen patients completed the trial. Compared with placebo, there were no differences in histamine PC(20) values (0.17 doubling-dilution shift; 95% CI, -0.38 to 0.73; P = 1), exhaled nitric oxide levels (0.95-fold change; 95% CI, 0.45-2.00; P = 1), or any other inflammatory, spirometric, or oscillometry measurements. Aspirin led to a significant decrease in thromboxane B2 levels (17.53-fold difference; 95% CI, 5.46-56.49; P < .001). Baseline 15-epilipoxin A4 levels were increased at 4.88 ng/mL, and there was no increase with aspirin versus placebo (0.99-fold difference; 95% CI, 0.79-1.24; P = 1).


CONCLUSIONS
In this preliminary study of 15 patients, low-dose aspirin did not lead to increased 15-epilipoxin A4 synthesis or alter inflammatory markers in patients with mild-to-moderate persistent asthma.
Menzies
Daniel
D
Asthma and Allergy Research Group, Ninewells Hospital and Medical School, Dundee, United Kingdom.
Nair
Arun
A
Meldrum
Karen T
KT
Hopkinson
Pippa
P
Lipworth
Brian J
BJ
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced*; D001944:Breath Tests; D001985:Bronchial Provocation Tests; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D044045:Lipoxins / Q000097:blood; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010919:Placebos; D012129:Respiratory Function Tests; D013929:Thromboxane B2 / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D010919:Placebos; C040527:lipoxin A4; D009569:Nitric Oxide; D013929:Thromboxane B2; D001241:Aspirin