Pulmicort in COPD

Is Pulmicort treatment indicated in patients with COPD?" ] 
Does treatments with Pulmicort affect the decline in FEV1?" ] 
Does Pulmicort reduce symptoms in patients with COPD" ] 
Does Pulmicort improve airway function in patients with COPD?" ] 
Is there an effect of Pulmicort on exacerbation rate in COPD?" ] 
Can a 2-week course of oral steroids predict the future effect of an inhaled corticosteroid?" ] 
For how long time should Pulmicort be administered before decision can be made about long-term maintenance treatment?" ] 
Which type of COPD patients benefit most from Pulmicort?" ] 
Is Pulmicort safe in patients with COPD?" ] 
What is the EUROSCOP study?" ] 

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).

Reference:
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. From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007. Available from: http://www.goldcopd.org.

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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 FEV1 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 FEV1 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.

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.

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.

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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).

Reference:
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.

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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.

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.

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.

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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 

Reference:
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.

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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).

Reference:
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.

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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).

Reference:
1. Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, Ullman A, Lamm CJ, O'Byrne PM. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003;361(9363):1071-6.

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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:
Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, Ullman A, Lamm CJ, O'Byrne PM. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003;361(9363):1071-6.

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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).

Reference:
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.

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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:
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.

 Does treatment with Pulmicort affect the decline in FEV1?" ]

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