Comparison of a 2 Agonist,

Terbutaline, with an inhaled

Corticosteroid, Budesonide,
in newly detected asthma

Background
The main goal of asthma treatment has usually been to
maintain normal airway patency with bronchodilators.
Asthma is also characterized by inflammatory changes
in the airway mucosa which points to the potential
value of anti-inflammatory therapy.
Extravasation of fluid from bronchial circulation,
which leads to mucosal edema and appearance of
inflammatory cells.

 Increased bronchial responsiveness

Theophylline

Inhaled steroids

Aim is to suppress inflammation

Methods
Study design
Multicenter, double-blind, randomized, parallel-group
trial
Five centers
Pretreatment period
Two-week run-in period
Four-week baseline period

Block randomization (4)

Study Protocol
DRUGS: Budesonide and Terbutaline
Pressurized metered-dose inhaler through a large volume
spacer
Pretreatment period: Terbutaline 375g twice a day
Treatment period:
Budesonide 600g twice a day
Terbutaline 375g twice a day

Supplemental:
Terbutaline 250g per puff
Oral Theophylline 300mg twice a day
Oral prednisolone for six days in decreasing doses (35, 25, 20, 15,
10 and 5 mg per day)

Patients
Adult (15 or older)
Non-smoking
With newly detected bronchial asthma
FEV1: inc. by more than 15% after inhalation of a 2agonist or decrease by more than 15% after exercise
tolerance test
FVC and FEV1 had to be at least 80% of predicted
values after treatment with 2-agonist

Patients (c..)
FEV1 had to fall by more than 15% after the
patient inhaled 10 breaths of histamine nebulized
from a solution containing less than 32mg/ml
Patients with a history of regular treatment or
treatment with corticosteroid or cromolyn were
excluded.

 103 patients were enrolled and randomized

6 were later found not to have fulfilled all the
criteria
3 treated with
pretreatment period

oral

prednisolone

during

1 irreversible pulmonary obstruction

2 FEV1 values during the baseline period that

were too low

Informed consent
Finnish Medical Board and local ethics committees

Recording outcomes
Pretreatment and subsequent 12 weeks PEF
medication in the morning and evening
Use of supplemental medication and adverse
reactions
Symptoms of asthma (dyspnea, cough, and sputum
production)
Daily activities

Recording outcomes
The assessments performed at the clinic at the
start of the pretreatment and active treatment
periods and then after 6, 12, 28, 44, 48, 72, 92,
and 96 weeks of treatment included spirometry,
bronchial responsiveness and checks of the
patients diaries.
Last dose of the study medication in the evening
not to use supplemental medication six hours
before the appointment

Assessment of Bronchial Responsiveness

Histamine diphosphate in phosphate-buffered saline
Six doubling concentration, or dose steps 1, 2, 4, 8, 16,
and 32 mg/ml
Nebulizers at an airflow of 5 liters/min.
0.125 and 0.250 ml/min
10 tidal breaths of nebulized saline and continued with
histamine
solutions
of
successively
higher
concentrations

Assessment of Bronchial Responsiveness

FEV1 was measured 1.5mins after each challenge
Challenge testing was discontinued when FEV1 fell by
15% or more
The concentration of histamine that produced the drop
was calculated by interpolation and called the
provocative concentration (PC15)
If FEV1 dropped less than 15% even when the highest
concentration of histamine diphosphate (32mg/ml) was
used, the PC15 was considered to be 64mg/ml

RESULTS

Lung function
FVC values did not change significantly over time or differ
significantly between groups.
Budesonide

Terbutaline

.13 liters

FEV1
but not in budesonide
group (mean, -0.06
liter per year;
median, -0.06)

Negative trend
(mean, -0.20 liter per
year, median, -0.03;
P<0.05)

 Terbutaline

Half a
(P<0.01)

histamine

dose

step

Budesonide

1.6
histamine
(P<0.001)

dose

step

In the budesonide group, the

marked decrease in bronchial
responsiveness was apparent
after six weeks of treatment;
although
this
decrease
continued, the trend over the
time of treatment was not
significant.

Other variables
PEF values
Symptoms of asthma
Use of supplemental terbutaline
The average increase over the pretreatment value
in PEF in the morning was 32.8 liters per minute for
budesonide and 4.8 liters per minute for terbutaline.

WITHDRAWAL AND EXTRA MEDICATION

CONCLUSION
Antiinflammatory therapy with inhaled
budesonide is an effective first-line
treatment for patients with newly
detected, mild asthma, and it is
superior to the use of terbutaline in
such patients.