| 1. Is Pulmicort treatment
indicated in patients with COPD? |
A systematic review of
placebo-controlled studies in patients with COPD show that they
benefit from treatment with inhaled corticosteroids, especially in
preventing exacerbations (1). Patients using inhaled steroids
deteriorate if treatment is discontinued (2). Inhaled steroids also
prevent exacerbations in patients with severe COPD, i.e. FEV1 <50% predicted normal (3) or make the exacerbations less severe
(4). The effects on airway function and symptoms associated with COPD
have been modest.
COPD is an approved indication
for Pulmicort in a number of countries but not worldwide.
COPD patients with
moderate-to-severe disease, patients with a rapid decline in FEV1,
and patients with frequent exacerbations seem to benefit most from
Pulmicort (5).
References:
1. Alsaeedi A et al. The effect
of inhaled corticosteroids in chronic obstructive pulmonary disease:
a systematic review of randomized placebo-controlled trials. Am
J Med 2002; 113: 59-65.
2. Jarad NA et
al. An observational study of inhaled
corticosteroid withdrawal in stable chronic obstructive pulmonary
disease. Respir Med 1999; 93: 161-166.
3. Jones PW et
al. Disease severity and the effect of fluticasone propionate
on chronic obstructive pulmonary disease exacerbations. Eur Respir J
2003; 21: 68-73.
4. Paggiaro PL
et al. Multi-centre randomised placebo
controlled trial of inhaled fluticasone in patients with chronic
obstructive pulmonary disease. Lancet 1998; 351: 773-780.
5. Global strategy for the
diagnosis, management and prevention of chronic obstructive pulmonary
disease. NHLBI/WHO Global Initiative for Chronic Obstructive
Pulmonary Disease (GOLD) Workshop Summary. Am J Respir Crit Care Med
2001; 163: 1256-1276.
|
| 2. Does treatments with
Pulmicort affect the decline in FEV1? |
Four long-term studies have
evaluated the effects of an inhaled corticosteroid on the annual
decline of FEV1 (1-4). They have all failed to demonstrate
a difference compared with placebo. Only smoking cessation has shown
a significant effect on FEV1 decline (5). However, a
recent meta-analysis using six long-term studies concluded that
treatment with inhaled steroids significantly reduced the rate of FEV 1 decline by 7.7 mL/year (6). With the higher dose
regimens the reduction was 9.9 mL/year. Considering that the normal
rate of decline in FEV 1 is 20-30 mL/year and in patients
with COPD 40-60 mL/year a reduction of almost 10 mL/year can be
clinically important.
References:
1. Pauwels RA et al.: Long-term
treatment with inhaled budesonide in persons with mild chronic
obstructive pulmonary disease who continue smoking. N
Engl J Med 1999; 340: 1948-1953.
2. Burge PS et al.: Randomised,
double-blind, placebo-controlled study of fluticasone propionate in
patients with moderate to severe chronic pulmonary disease: the
ISOLDE trial. Br Med J 2000; 320: 1297-1303.
3. Vestbo J et
al. Long-term effect of inhaled budesonide
in mild and moderate chronic obstructive pulmonary disease: a
randomised controlled trial. Lancet 1999; 353: 1819-1823.
4. The Lung
Health Study Research group. Effect of inhaled triamcinolone on the
decline in pulmonary function in chronic obstructive pulmonary
disease. N Engl J Med 2000; 343: 1902-1909.
5. Anthonisen
NR et al. Effect of smoking intervention
and the use of an inhaled anticholinergic bronchodilator on the rate
of decline of FEV1. J Amer Med
Ass 1994; 272: 1497-1505.
6. Sutherland
ER et al. Inhaled corticosteroids reduce
the progression of airflow limitation in chronic obstructive
pulmonary disease: a meta-analysis. Thorax 2003; 58: 937-941
|
| 3. Does Pulmicort reduce
symptoms in patients with COPD |
Most COPD patients suffer from
respiratory symptoms such as cough, sputum production, dyspnoea, and
chest tightness. Placebo-controlled clinical studies evaluating the
effects of a budesonide/formoterol combination and the monocomponents
have shown that the respiratory symptoms can be reduced with
Pulmicort (1,2).
In a double-blind,
placebo-controlled study 58 non-allergic patients with COPD were
randomized to treatment with Pulmicort 1600 µg
per day administered via pMDI, Pulmicort 1600 µg
plus 5 mg oral prednisolone, or placebo (3). Active treatments
resulted in symptom reduction and fewer dropouts due to respiratory
problems. No difference was found between the Pulmicort treatments
with and without oral prednisolone.
Symptom reduction in COPD patients
treated with Pulmicort
Mean treatment scores (±
SEM) by treatment group, before and after 1 and 2 years of treatment,
in patients with COPD treated with inhaled budesonide, 1600 µg
alone, inhaled budesonide, 1600 µg,
plus oral prednisolone 5 mg/day, or placebo. The symptom score was
significantly reduced in both active treatment groups (3).
References:
1. Szafranski W et al.: Efficacy
of budesonide/formoterol in the management of COPD. Eur Respir J
2003; 21: 74-81.
2. Calverley
PMA.: Effect of budesonide/formoterol on severe exacerbations
and lung function in moderate to severe COPD. Eur
Respir J 2003; 22: 912-919.
3. Renkema TEJ
et al. Effects of long-term treatment with
corticosteroids in COPD. Chest 1996;
109: 1156-1162.
|
| 4. Does Pulmicort improve
airway function in patients with COPD? |
When starting treatment with
Pulmicort in the 3-year EUROSCOP study in patients with mild COPD a
clinically important improvement in airway function was demonstrable
over the first months of treatment. From this improved level the
annual decline in FEV1 follows the same slope as before
(1). The patients showing the greatest effect are those with a less
severe smoking history, with a documented rapid decline in FEV1,
patients below the age of 50 years when having COPD, and patients
with a reversible component of their airway obstruction.
Similar results have been
reported with fluticasone propionate (2,3).
Development
of postbronchodilator FEV1 in mild COPD patients treated with Pulmicort.
Change
in post-bronchodilator FEV1 in patients with
mild-to-moderate COPD treated with Pulmicort Turbuhaler 800 µg
per day or placebo for 3 years in the EUROSCOP study (1). Pulmicort
treatment was associated with a significant (p<0.001) initial
reduction in the rate of decline of FEV1, but the
subsequent decline in lung function was comparable in the Pulmicort
and placebo groups.
References:
1. Pauwels RA et al.: Long-term
treatment with inhaled budesonide in persons with mild chronic
obstructive pulmonary disease who continue smoking. N
Engl J Med 1999; 340: 1948-1953.
2. Burge PS et al.: Randomised,
double-blind, placebo-controlled study of fluticasone propionate in
patients with moderate to severe chronic pulmonary disease: the
ISOLDE trial. Br Med J 2000; 320: 1297-1303.
3. Paggiaro PL
et al. Multi-centre randomized placebo
controlled trial of inhaled fluticasone in patients with chronic
obstructive pulmonary disease. Lancet 1998; 351: 773-780.
|
| 5. Is there an effect of
Pulmicort on exacerbation rate in COPD? |
Acute exacerbations are frequent
in COPD patients. Controlled clinical studies have demonstrated that
maintenance treatment with Pulmicort can reduce the number of
exacerbations and prolong the time to the first severe exacerbation
in patients with severe COPD, i.e. FEV1 <50 percent
predicted normal. This was shown in two 12-month studies comparing
the efficacy of the budesonide/formoterol combination product with
its monocomponents (1,2).
Exacerbation frequency in patients
with moderate-to-severe COPD treated with Pulmicort
The
absolute number of severe exacerbations in two 12-month studies
investigating the effect of Pulmicort Turbuhaler 800 µg/day
(1,2). In
these studies, Pulmicort was compared with Symbicort and Oxis. Read
more about the studies?
Pulmicort vs. Symbicort in COPD
References:
1. Szafranski W et al.: Efficacy
of budesonide/formoterol in the management of COPD. Eur
Respir J 2003; 21: 74-81.
2. Calverley
PMA. Maintenance therapy with budesonide and formoterol in
chronic obstructive pulmonary disease. Eur Respir J 2003; 22:
912-919.
|
| 6. Can a 2-week course of
oral steroids predict the future effect of an inhaled corticosteroid? |
A 2-week course of prednisolone
has been widely used in an attempt to detect corticosteroid
responders, i.e. patients who improve significantly (>15%) in
airway function (FEV1 or PEF) or benefit in terms of
reduced symptoms or improved health related quality of life. However,
there is mounting evidence that far from all patients who respond to
long-term treatment with an inhaled corticosteroid do not respond
during a 2-week course of oral steroids (1-3). Also, patients who
respond to oral steroid short term may not benefit from long-term
treatment with inhaled steroids. The best approach for evaluation of
benefits of an inhaled corticosteroid is to give patients with COPD a
trial with Pulmicort for 3-6 months and thereafter evaluate whether
treatment should continue or not.
Distribution
of changes in post-bronchodilator FEV1 following
prednisolone
Distribution of changes in
post-bronchodilator FEV1 following prednisolone. There was
no correlation between this response and the subsequent effect of
treatment with fluticasone on FEV1 decline or risk of
exacerbations (3).
References:
1. Selroos O.: The effects of
inhaled corticosteroids on the natural history of obstructive lung
diseases. Eur Respir Rev 1991; 1:
354-365.
2. Senderovitz T et al. Steroid
reversibility test followed by inhaled budesonide or placebo
in outpatients with stable
chronic obstructive pulmonary disease. Respir Med 1999; 93:
715-718.
3. Burge PS et al. Prednisolone
response in patients with chronic obstructive pulmonary disease:
results from the ISOLDE study. Thorax 2003; 58: 654-658.
|
| 7. For how long time should
Pulmicort be administered before decision can be made about long-term maintenance
treatment? |
Clinical studies indicate that
treatment with Pulmicort should continue for 6 weeks to 3 months
before an evaluation is made to determine whether treatment has
benefited the patient. The evaluation should include effects on
symptoms, physical activity (health related quality of life) and lung
function (FEV1 or PEF). These recommendations are included
in the GOLD guidelines (1).
References:
1. Pauwels RA et al.: Global
strategy for the diagnosis, management and prevention of chronic
obstructive pulmonary disease. NHLBI/WHO Global Initiative for
Chronic Obstructive Pulmonary Disease (GOLD) Workshop Summary. Am J
Respir Crit Care Med 2001; 163: 1256-1276.
|
| 8. Which type of COPD
patients benefit most from Pulmicort? |
Evaluation of several studies
with inhaled corticosteroids in patients with COPD indicate that the
following patient categories would benefit most from treatment:
-patients with frequent
exacerbations,
-patients with a proven rapid
decline in FEV1, i.e. an annual decline of >60 mL/year
-patients with a reasonably short
exposure to tobacco smoke (<20 pack years)
-patients aged <50 years but
already having COPD
Reference:
1. Pauwels RA et al.: Global
strategy for the diagnosis, management and prevention of chronic
obstructive pulmonary disease. NHLBI/WHO Global Initiative for
Chronic Obstructive Pulmonary Disease (GOLD) Workshop Summary. Am J
Respir Crit Care Med 2001; 163: 1256-1276.
|
| 9. Is Pulmicort safe in
patients with COPD? |
In a 3-year study (EUROSCOP) in
patients with mild COPD receiving Pulmicort Turbuhaler 400 µg
twice daily safety was closely monitored. Effects on bone were
studied by taking radiographs of the spine (1). In a subgroup of
patients bone mineral density was studied with dexa scans. No effects
of treatment on bone mineral density, fracture rates, or osteocalcin
concentrations were found compared with placebo.
In two 12-month
placebo-controlled studies in patients with moderate-to-severe COPD
(GOLD stage IIB and III) twice daily treatment of Pulmicort
Turbuhaler 400 µg was
evaluated together with budesonide/formoterol and formoterol
treatments (2,3). No difference in adverse events was found between
Pulmicort treatment and placebo.
Effects of Pulmicort
on BMD in patients with COPD
Mean
changes in bone mineral density (BMD) measured in (left) lumbar spine
(L2-L4), (right)) femoral neck during treatment with budesonide
Turbuhaler 400 µg bid and placebo for 3 years (1).
References:
1. Johnell O et al. Bone mineral
density in patients with chronic obstructive pulmonary disease
treated with budesonide Turbuhaler. Eur Respir J
2002; 19: 1058-1063.
2. Szafranski
W et al. Efficacy of budesonide/formoterol in the management
of COPD. Eur Respir J 2003; 21: 74-81.
3. Calverley
PMA et al. Effect of budesonide/formoterol on severe
exacerbations and lung function in moderate to severe COPD. Eur
Respir J 2003; 22: 912-919.
|
| 10. What is the EUROSCOP
study? |
The EUROSCOP study was a 3-year
placebo-controlled study evaluating the effect of Pulmicort
Turbuhaler 400 µg twice
daily in patients with mild COPD. It was found that Pulmicort
treatment resulted in a small, but statistically significant
improvement in FEV1 over the first 3 months of the study,
but the subsequent annual decline in FEV1 was not
different from placebo.
Reference:
1. Pauwels RA et al.: Long-term
treatment with inhaled budesonide in persons with mild chronic
obstructive pulmonary disease who continue smoking. N
Engl J Med 1999; 340: 1948-1953.
EUROSCOP (requires log in)
Does treatments with Pulmicort affect the decline in FEV1?
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