Gizem DEMİR, Eriş Banu GÜLBAY, Zeynep Pınar ÖNEN, Gülseren KARABIYIKOĞLU, Sevgi SARYAL, Akkoca Öznur YILDIZ

Is there any difference between effects of ipratropium bromide and formoterol on exercise capacity in moderate COPD patients?

Antikolinerjik ilaçlar ile uzun etkili β2-agonist ilaçların kronik obstrüktif akciğer hastalığı (KOAH)’nda egzersiz kapasitesini iyileştirdiğine dair değişik bulgular vardır. Fakat iki ilacın karşılaştırmalı olarak alındığı çift-kör çalışmalar yeterli sayıda değildir. Bizim bu çalışmadaki amacımız, bu olgularda ipratropium bromür ve formoterolün egzersiz kapasitesine olan etkisini karşılaştırmak ve egzersiz kapasitesi ile fonksiyonel parametreler arasında ilişki olup olmadığını araştırmaktı. Bu çalışma çift-kör, randomize ve iki periyod crossover olarak planlandı. KOAH polikliniğinde takip edilen 10 stabil, gönüllü KOAH olgusu çalışmaya dahil edildi. İlk vizitte tüm veriler kaydedildi. Bir hafta sonra tüm bazal testleri; solunum fonksiyon testleri ve kardiyopulmoner egzersiz testleri yapıldı, daha sonra hastalar iki hafta süreyle günde dört kez 40 μg ipratropium bromür veya günde iki kez 12 μg formoterol kullandı. Bir haftalık ilaçsız periyoddan sonra ilaç bir diğeri ile değiştirildi. Her bir tedavi periyodu sırasında tüm testleri tekrarlandı. Hastalardan dokuzu erkek, biri kadındı ve ortalama yaş 51.1 ± 5.45 yıl idi, tüm olgular ağır sigara içicisiydi, hafif-orta seviyelerde KOAH’ları vardı (FEV1= %69, FEV1/FVC= %68). Formoterol ile FEV1, FEV1/FVC’de belirgin iyileşme gözlenirken, ipratropium ile FEV1, FEF25-75, pik oksijen kullanımı ve dakika ventilasyonda düzelme izlendi. Bununla beraber her iki tedavi sonrasında da egzersiz sürelerinde belirgin artışlar izlendi. Her iki ilacın egzersiz kapasitesine ve fonksiyonel parametrelere olan etkileri arasında belirgin fark izlenmedi. Biz bu çalışmada, KOAH’lı olgularda formoterol ve ipratropium bromür tedavilerinin benzer şekilde egzersiz kapasitesinde iyileşmeye neden olduklarını gözledik. Egzersiz kapasitesindeki bu iyileşme FEV1’deki iyileşme ile oldukça ilişkiliydi.

Orta şiddetli KOAH olgularında ipratropium bromür ve formoterolün egzersiz kapasitesine etkileri arasında fark var mıdır?

The effects of anticholinergic agents or long acting β2-agonists on exercise capacity in chronic obstructive pulmonary disease (COPD) improves various out come measures but there is not enough double-blind study which included comparison of different medications. The aim of this study was to compare the effect of ipratropium bromide and formoterol on exercise capacity and also to determine the relationship between this improvement in functional parameters and exercise capacity for each treatment in patients with COPD. This study was performed as randomized, double blind and two period crossover design. Ten volunteer stable COPD patients were recruited from outpatient COPD clinic. At the initial visit medical data were recorded. One week later baseline measurements; pulmonary function tests and cardiopulmonary exercise testing were performed, afterwards, patients recieved ipratropium bromide 40 μg four times a day or formoterol 12 μg two times a day for two weeks. After a washout period, medications were crossed for another two weeks. After each of tratment period, all tests were performed. Nine subjects were male and mean age was 51.1 ± 5.45 years, all of them were heavy smokers, level of COPD was mild to moderate (FEV1= 69%, FEV1/FVC= 68%). While formoterol significantly improved FEV1, FEV1/FVC %, ipratropium significantly improved FEV1, FEF25-75, peak oxygen uptake and minute ventilation. Moreover, both of the medications increased exercise time. There were no differences between effects of ipratropium bromide and formoterol on exercise capacity and functional parameters. We observed that ipratropium bromide and formoterol have similar improvement in exercise capacity in COPD patients. The improvement in exercise capacity also correlated with increase in FEV1.

PDF

___

1. Pauwels RA, Anthonisen N, Bailey WC, et al. GOLD scientific committee. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: Updated 2003: 55.
2. Belman MJ, Botnic WC, Shin JW. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 153: 967-75.
3. O’Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 158: 1557-65.
4. Blosser SA, Maxwell SL, Reeves-Hoche MK, Localio AR. Is an Anticholinergic agent superior to a β2-agonist in improving dysnea and exercise limitation in COPD? Chest 1995; 108: 730-5.
5. Liesker JJW, Velde VVD, Meysman M, et al. Effects of formoterol and ipratropium on exercise capacity in patients with COPD. Respir Med 2002; 96: 559-66.
6. Bartow RA, Brogden RN. Formoterol; an update of its pharmacological proporties and therapotic efficacy in the mangement of asthma. Drugs 1998; 55: 303-22.
7. Cazzola M, Donner CF. Long-acting β2-agonist in the manegement of stable chronic obstructive pulmonary disease. Drugs 2000; 60: 307-20.
8. Dahl R, Greefthorst LAPM, Nowak D, et al. Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164: 778-84.
9. American Thoracic Society. Standardization of spirometry (1994 Update). Am J Respir Crit Care Med 1995; 152: 1107-36.
10. Quanjer P, Tammeling FJ, Cotes JE, et al. Standardised lung function testing; lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J 1993; 6 (Suppl 16): 5-40.
11. American Thoracic Society/American Collage of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003; 167: 211-77.
12. Jones NL, Makrides L, Hitchcock C, et al. Normal standards for an incremental progressive cycle ergometer test. Am Rev Respir Dis 1985; 131: 700-8.
13. Weisman IM, Zeballos RJ. Clinical exercise testing. Clin Chest Med 2001; 22: 679-98.
14. O’Donnell DE, Bain DJ, Webb KA. Factors contributing to relief of exertional breathlessness during hyperoxia in chronic airflow limitation. Am J Respir Crit Care Med 1997; 155: 530-5.
15. O’Donnell DE, Bertley JC, Chau LKL, Webb KA. Qualitative aspects of exertional breathlessness in chronic airflow limitation. Am J Respir Crit Care Med 1997; 155:109-15.
16. Aliverti A, Macklem PT. How and why exercise is impaired in COPD. Respiration 2001; 68: 229-39.
17. O’Donnell DE, Webb KA. Exertional breathlessness in patients with chronic airflow limitation. Am Rev Respir Dis 1993; 148: 1351-7.
18. Liesker JJW, Wijkstra PJ, Hacken NHT, et al. A systematic review of the effects of bronchodilators on exercise capacity in patients with COPD. Chest 2002; 121: 597-608.
19. Tsukino M, Nishimura K, Ikeda A, et al. Effects of theophylline and ipratropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. Thorax 1998; 53: 269-73.
20. Ikeda A, Nishimura K, Koyama H, et al. Dose response study of ipratropium bromide aerosol on maximum exercise performance in stable patients with chronic obstructive pulmonary disease. Thorax 1996; 31: 48-53.
21. O’Donnell DE, Lam M, Webb KA. Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160: 542-9.
22. Grove A, Lipworth BJ, Reid P, et al. Effects of regular salmeterol on lung functions and exercise capacity in patients with chronic obstructive airways disease. Thorax 1996; 51: 689-93.
23. Ayers ML, Mejia R, Ward J, et al. Effectiveness of salmeterol versus ipratropium bromide on exertional dyspnoea in COPD. Eur Respir J 2001; 17: 1132-7.