Guideline topic: Pharmacological management of asthma
Evidence table 4.21: Aspirin intolerant asthma

Author

Year

Study type

Quality rating

Population

Outomes measured

Effect size

Confidence intervals / p values

Comments

Adults

Dahlen¹

1998

Randomised, double-blind placebo-controlled, cross-over study 6 week study of zileuton vs. placebo

++

40 AIA mean age 44 yrs

28 females and 12 males

Mean FEV1 2.5L 38/40 on inh. Corticosteroids (mean dose 1030 mg/day) and 35? On oral steroids

1] Increase in FEV1 at 4h and 6 weeks vs placebo

2] Urinary (LTE4

3] Nasal symptoms

4] beta2-agonist use

5] PD20 LTD4

1] 7.5% at 4 hr 0.19L at 6 weeks

2] 36% reduction

3] reduced

4] reduced

5] unchanged

P<0.01

P <0.01

P< 0.01

P<0.05

P <0.05

NS

Despite the fact theat zileuton treatment achieved only a 36% reduction in leukotiene synthesis, zileuton treatment improved FEV1 and PEF acutely and over 6 weeks. In addition, this treatment was associated with an improvement in sense of smell and rhinorheoa. Bronchoconstriction caused by LTD4 inhalation was unaffected.

Robuschi²

1997

Randomised, double-blind, placebo-controlled, cross-over study. Single dose nedocromil or chromoglycate or placebo 30 minutes before aspirin challenge

+

10 AIA ages 20-65 (mean 46) yr FEV1> 70% pred. (mean 80%

On 200-2000 mg inh.

Corticosteroids

1] Fall FEV1 over 195 minutes post aspirin inh.

2] Increase Straw over 195 minutes post aspirin inh.

1] Placebo - 42% Nedocromil - 18%

Chromoglycate - 20%

2] Placebo - 143 Nedocromil - 79 Chromoglycate - 69

1] vs placebo p<0.001 both treatments ns between active treatments

2] vs placebo p< 0.01 both treatments ns between active treatments

In this small study 4 mgs odium nedocromil and 10 mg sodium chromoglycate were equally effective in attenuating aspirin-induced bronchoconstriction following a known inhalation of aspirin in AIA on inh. corticosteroids.

Szczeklik³

1998

Randomised, double-blind placebo-controlled, cross-over study.

Single 50mg inhaled dose of salmeterol prior to inhaled aspirin challenge.

+

10 AIA aged 34 - 64 years.

7 females and 4 males.

Mean FEV1 x .5L (89% pred.) 9/10 on inh.

Corticosteroids (mean dose 960mg/day) 6 on oral steroids (mean dose 6.3mg/day)

1] PD 20 aspirin

2] Urinary (LTE4) post-aspsirin

3] Aspirin-induced bronchoconstriction

4] Urinary (PGD-M) post aspirin

1] Increased from 8.3 mg to 68.5mg

2] Aspirin-induced increase prevented by salmeterol

3 Prevented by salmeterol

4] Aspirin-induced increase prevented by salmeterol

P = 0.02

P<0.05

Not given

P=0.008

This small trial studies the effect of a single dose of inhaled salmeterol 50mg inh on inhalational aspirin challenge in known AIA. Pre-treatment with salmeterol effectively attenuated aspirin-induced bronchoconstriction and leukotriene synthesis in aspirin sensitive asthmatics.

Szczeklik⁴

1995

2 phases,

1] Randomised double-blind placebo controlled cross-over trial into effect of pre-treatment with GPE2, salbutamol or misopropstol on aspirin induced brochoconstriction in AIA

2] Randomised, cross-over, double-blind, placebo controlled trial into bronchial response to inhaled PGE2 PGE1, + salbutamol or placebo over 120 minutes in AIA vs aspirin tolerant asthma (ATA)

+

Phase

1] 11 AIA, non-smoker FEV1>70% pred. 5/11 on 5-15 mg/day oral predn.

Phase 2] 12 AIA mean age 42 yrs, FEV1 75% pred. 10/12 on oral pred. (mean 8mg) 10 ATA mean age 38 yres, FEV1 78% pred. 2/10 on oral predn. (mean 5mg)

All patients showed > 15% reversibility to beta2-agonists

1] Aspirin PC20 30 mins after treatment (mg lysine aspirin)

2] More prolonged bronchodilation after salbutamol in ATA than AIA

3] PGE2 caused bronchodilation which was more marked and persistent in ATA than AUAI

3] PGE1 caused bronchodilation followed by bronchoconstriction in ATA but had no effect on FEV1 in AIA

Placebo - 1.8

PGE2, - 5.4

Salbutamol - 8.4

Misoprostol - 4.0

P vs placebo

= 0.04

= 0.06

- 0.25

Inhaled PGE 2 and inhaled salbutamol inhibited aspirin induced bronchoconstriction to a similar degree, Oral misoprostol attenuated aspirin induced bronchoconstriction to a lesser degree. Inhaled PGE2 causes caugh and retrosternal pain which subsides during treatment but can be dose limiting. The study on the effect of these agents on bronchial tone shows that both PGE2 and salbutamol cause less marked and less persistent bronchdilation in AIA than ATA. The poor bronchodilatory effect of PGE2 in AIA suggests that the attenuation of aspirin-induced bronchoconstriction by PGE2 is not medicated purely airway muscle tone.

Wasiak⁵

1999

Randomised double-blind, placebo-controlled cross-over 6 weeks oval misoprostol

++

17 Adults aged 26-68 years

13 females and 4 males.

EV1 83% pred. 15% reversibility to beta2 agonist 15/17 on inh. Corticosteroid

1] 1m and pm PEFR, FEV1/FVC, asthma symptom scores, beta2-agonist use, preipheral blood eosinophils

2] Reduction in rhinorrhoea score

3] Defecation symptom score

1] All nil

2] from 1.0 to 0.36 points/day

3] Minimal increase

All ns

P = 0.03

P = 0.004

Oral misoprostol, an oral PGE1 analogue, a either 800 to 1600 mg per day failed to improve asthma symptoms or asthma control in this small study of aspirin sensitive asthmatics.