Guideline topic: Pharmacological management of asthma
Evidence table 4.11d: Add-on drugs for inhaled steroids: Theophylline, beclomethasone diproponate, budesonide

Author

Adults

Evans¹

1997

Crossover RCT

++

62 patients aged 18-97 (mean 38.8).
Sympotmatic despite 800-1000 µg inhaled corticosteroids.
Mean FEV1 75% pred. (35-116%) 15% reversibility to b 2 agonists.
Compared 800m g inh BUDE + low dose theoph OR 1600 µg inh BUDE.
Study period of 3 months.

FVC

FEV1


PEF



Use of b 2 agonists

800µg BUDE plus theoph resulted in FVC and FEV1 <10% increase from baseline

PEF increased in both groups ,25 l/min

Reduced in both groups by 1 puff / 24 hrs

P=0.03

NS difference between treatments

NS difference between treatments

In patients with persistent symptoms on up to 1mg/day inhaled budesonide, adding low dose oral theoph (serum conc <10m g/l) provided similar improvements in lung function, symptom control and b 2 agonist use to doubling the dose of inhaled corticosteroid to 1.6 mg/day.

Ukena²

1997

RCT

+

133 patients aged 18-70 (mean 48.5) symptomatic despite 400m g BDP/day. FEV1 50-85% pred. 15% reversibility to b 2 agonists. Compared 400 µg inh BDP + low dose theoph OR 800 µg inh BDP. Study period of six weeks

Increase in home PEF

Reduction in PEF variability

Increase in FEV1

Symptom scores and use of b 2 agonist

20% am/pm PEF in both groups

30% in both groups

10% FEV1 in both treatments

Improved signigicantly in both groups

P<0.01 NS difference between treatments.

P<0.01 NS difference between treatments.

P<0.01 NS difference between treatments.

P<0.001 NS difference between treatments.

In asthmatic patients not controlled by 400 mg/day BDP, doubling the dose of BDP or adding theophylline provided equivalent improvements in asthma symptoms, lung function, and. b 2 agonist use. Similar adverse events profile except that theoph. Associated more with mild GI symptoms.

Children

Nassif³

1981

Crossover RCT

+

33 children aged 7-19.
Comparison of theoph vs placebo in steroid dependent asthma with subgroups of 21 patients on 200-900 µg / day inhaled BDP (mean 530 µg / day) and 11 patients on alternate day prednisolone (mean dose 33 mg/day). Study period of 2 months.

PEF





Spriometry




Asthma symptoms






Use of b 2 aqgonist


Rescue with additional prednisolone

PEF increased in inhaled BDP and oral prednisolong group.


FEV1 increased in both groups.



Patients were free of all symptoms 63%(+6,-6) of days cmpared with 42%(+6,-6) on palacebo

Inh b 2 agonist was required twice as often with placebo.


Additional daily corticosteroids were needed 3 times as often with placebo.

P0.02 before bronchodilator and p<0.05 after.

P<0.01




P<0.01






P=0.02

In children with asthma on inhaled or oral corticosteroids, treatment with theophylline can improve the frequency and severity of asthma symptoms and improve lung function. Although there is evidence of reduced use of rescue steroid medication for exacerbations, no assessment of a true steroid sparing effect is made.