| 1. Why is Pulmicort first
line treatment of asthma? |
Asthma is an inflammatory disease
characterized by a damaged airway epithelium. Allergens and
environmental irritants are more prone to cause airway obstruction in
patients with an untreated inflammation. Therefore an inhaled
corticosteroid, e.g. Pulmicort, should be first-line treatment of
asthma.
Controlled clinical studies have
shown that Pulmicort as first-line treatment is more effective than
treatment with e.g. an inhaled ß2-agonists
(1). Inhaled corticosteroids are also the only drugs that have been
shown to restore the damaged airway epithelium (2).
Reference:
1. Haahtela T et
al: Comparison of a ß2-agonist,
terbutaline, with an inhaled corticosteroid, budesonide, in newly
detected asthma. N Engl J Med 1991; 325: 388-392.
2. Laitinen LA et al: A comparative study of the effects of an inhaled
corticosteroid, budesonide, and a ß2-agonist,
terbutaline, on airway inflammation in newly diagnosed asthma: a
randomized, double-blind, parallel-group controlled trial. J Allergy
Clin Immunol 1992; 90: 32-42.
|
| 2. Pulmicort vs. inhaled
ß2-agonists |
Clinical studies have shown that
treatment with Pulmicort is more effective than regular treatment
with ß2-agonists
(1). Even though ß2-agonists
have some anti-inflammatory properties (mast cell stabilizing,
anti-oedema effects) these are not sufficient for controlling asthma.
The anti-inflammatory effects of inhaled corticosteroids are much
broader and affect many other cells, e.g. eosinophils and
T-lymphocytes and thereby they are much more efficacious in treatment
of asthma (2).
Budesonide or terbutaline as
first-line treatment of asthma
Budesonide was given in a dose
of 600 µg bid and
terbutaline in a dose of 375 µg
bid (both drugs from pMDI plus spacer). Only 14 patients took part in
the study, the main purpose of which was to compare findings on
bronchial biopsy. The difference between the clinical effects of the
two treatments was, however, very significant (3), as was confirmed
by an associated larger study (1).
References:
1. Haahtela T et al: Comparison
of a ß2-agonist,
terbutaline, with an inhaled corticosteroid, budesonide, in newly
detected asthma. N Engl J Med 1991; 325: 388-392.
2. Barnes PJ et al: Efficacy of
inhaled corticosteroids in asthma. J Allergy Clin Immunol 1998; 102:
531-538.
3. Laitinen LA et al: A comparative study of the effects of an inhaled
corticosteroid, budesonide, and a ß2-agonist,
terbutaline, on airway inflammation in newly diagnosed asthma: a
randomized, double-blind, parallel-group controlled trial. J Allergy
Clin Immunol 1992; 90: 32-42.
|
| 3. Pulmicort vs.
theophylline |
Inhaled Pulmicort has been
compared with oral theophylline in a few studies with a limited
number of patients. In one study 25 patients received 400 mg
slow-release theophylline twice daily for seven doses, after which
doses were adjusted to achieve plasma concentrations of app. 15
µg/mL. In a subsequent
crossover phase of the study, patients received Pulmicort 100 µg
and 200 µg twice daily via
pMDI, and theophylline at the titrated dose and half of the titrated
dose, for 3 weeks each. Morning PEF, the primary variable of
efficacy, was significantly higher after the 200 µg
twice daily Pulmicort dose than with the other treatments. It should
be noted, however, that the dose of Pulmicort could be significantly
increased, if necessary, without safety concerns, whereas a higher
dose of theophylline is limited by side effects.
Budesonide vs. theophylline in
patients with asthma
Mean
morning PEF in 25 asthmatic patients treated with Pulmicort 100 µg
or 200 µg twice daily, or sustained-release theophylline to
achieve plasma concentrations of 7.5 or 15
µg/ml, for 3 weeks each. PEF was significantly greater with
Pulmicort 200 µg twice daily than with the other treatments.
Reference:
1. Bundgaard A, Schmidt A. A
comparison of oral slow release theophylline and inhaled budesonide
in adult asthmatics. Atemwegs und
Lungenkrankheiten 1990; 16: 36-41.
|
| 4. Pulmicort vs. cromones |
In a crossover study in adult
asthmatics 22 patients received Pulmicort 100 µg
four times daily and sodium cromoglicate (SCG) 2 mg four times daily
for 6 weeks each with a placebo wash-out period between the
treatments (1). Pulmicort produced a significantly greater increase
in morning and evening PEF values and histamine PC20 than
SCG, while the two treatments produced comparable effects on asthma
symptoms and ß2-agonist
use. Pulmicort treatment also significantly reduced the fall in FEV1
after exercise compared with placebo, whereas SCG had no effect.
The
efficacy and safety of treatment with Pulmicort and nedocromil were
investigated in the CAMP study - a randomized,
placebo-controlled 4-year study in 1041 children with asthma, aged
5-12 years (2). Treatments were Pulmicort Turbuhaler 200 µg
twice daily or nedocromil 8 mg twice daily, or placebo.
As
compared with placebo-treated children, those assigned to receive
Pulmicort had a significantly smaller decline in the FEV1/FVC
ratio before bronchodilation, lower responsiveness to methacholine,
fewer hospitalisations, fewer visits to a caregiver, greater
reductions in the use of rescue medication, fewer courses of
prednisone, and a smaller percentage of days on which additional
asthma medication was needed. Nedocromil only reduced urgent care
visits and the number of courses of prednisone compared with placebo.
No formal statistical tests compared the budesonide and nedocromil
groups.
Incidence
of urgent care visits and hospitalisations due to asthma in the CAMP
study
Incidence
of urgent care visits and hospitalisations due to asthma in the CAMP
study (Childhood Asthma Management Program Research Group, 2000).
Patients receiving Pulmicort Turbuhaler 400 µg/day required
significantly fewer urgent care visits or hospitalizations than those
receiving placebo. Nedocromil 16 mg/day was only associated with
significant reductions in urgent care visits.
References:
1. Molema J et al.: Effects of
long-term treatment with inhaled cromoglicate and budesonide on
bronchial hyperresponsiveness in patients with allergic asthma. Eur
Respir J 1989; 2: 308-316.
2.
The Childhood Asthma Management Program Research Group. Long-term
effects of budesonide or nedocromil in children with asthma. N
Engl J Med 2000; 343: 1054-1063.
|
| 5.Pulmicort vs.
leukotriene receptor antagonists |
Leukotriene receptor antagonists
should mainly be used as add-on therapy to inhaled corticosteroids in
patients not well controlled on inhaled steroids alone (GINA
guidelines).
In a crossover study the efficacy
of Pulmicort Turbuhaler, 400 µg
twice daily for 15 days, and montelukast 10 mg once daily for 3 days
with a 15-day wash-out period in between, were compared on
exercise-induced bronchoconstriction (1). Both montelukast and
Pulmicort reduced the decrease in FEV1 (AUC) after
exercise with respect to the baseline condition of no therapy.
Overall, however, Pulmicort offered better protection than
montelukast (p=0.01), particularly at 2 min after exercise (p=0.003)
(Fig 1). Considerable individual variation was noticed.
In a double-blind,
placebo-controlled crossover study ten subjects with asthma with dual
responses after allergen inhalation were included (2). Outcomes
included early and late asthmatic responses, and changes in airway
responsiveness and sputum eosinophilia. Treatment with montelukast
attenuated the maximal early asthmatic responses compared with
placebo (p<0.001) and Pulmicort (p=0.002). Both montelukast and
Pulmicort, alone or in combination, attenuated the late asthmatic
response compared with placebo (p<0.01). Both drugs afforded
protection against allergen-induced airway hyperresponsiveness
(p<0.05), although the treatment effect of Pulmicort was greater
than that of montelukast (p<0.05). Both treatments reduced sputum
eosinophilia.
Effects of Pulmicort and
montelukast on exercise-induced asthma.
Decrease
in FEV1
after exercise at baseline (no therapy) and after treatment with
Pulmicort Turbuhaler 800 µg/day or montelukast 10 mg/day in 20
patients with exercise-induced bronchoconstriction. The shaded area
represents the area under the curve under baseline conditions.
Pulmicort produced a significantly greater reduction in the fall in
FEV1
than montelukast, particularly during the first minutes of exercise
(p=0.003).
References:
1. Vidal C et al.: Comparison of
montelukast versus budesonide in the treatment of exercise-induced
bronchoconstriction. Ann Allergy Asthma Immunol
2001; 86: 655-658.
2. Leigh R et al. Effects of
montelukast and budesonide on airway responses and airway
inflammation in asthma. Am J Respir Crit Care Med 2002; 166:
1212-1217.
|
| 6. Pulmicort vs. oral
corticosteroids |
In an early study (1) Pulmicort
400 µg and 800 µg
per day were found to be equipotent to oral prednisolone 10 mg and 20
mg per day, respectively, in terms of effects on PEF.
In a large study (2) the relative
anti-asthmatic and systemic potencies of Pulmicort (administered four
times a day via pMDI attached to a large volume spacer) and oral
prednisone were compared at doses up to 3200 µg
per day and 40 mg per day, respectively. In oral steroid-dependent
patients, Pulmicort 1 mg (1000 µg)
produced an anti-asthmatic and systemic effects (depression of serum
cortisol) equivalent to prednisone 35 mg and 7.6 mg, respectively. In
patients not dependent on oral steroids Pulmicort 1000 µg
was equivalent to 58 mg prednisone (anti-asthmatic effect) and 8.7 mg
(systemic effect). Thus, Pulmicort had a significantly more
favourable therapeutic index than oral prednisone.
References:
1. Rosenhall L et al.: Comparison
between inhaled and oral corticosteroids in patients with chronic
asthma. Eur Respir J 1982; 63, Suppl. 122: 154-162.
2. Toogood JH et al.:
Bioequivalent doses of budesonide and prednisone in moderate and
severe asthma. J Allergy Clin Immunol 1989; 84: 688-700.
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