Türkan TATLICIOĞLU, Can ÖZTÜRK, Nurdan KÖKTÜRK, Gül GÜRSEL

KOAH'lı hastalarda formoterolün tek başına ve ipratropium bromürle birlikte kullanımlarının fonksiyonel kapasite üzerine etkilerinin karşılaştırılması

Amaç: Kronik obstrüktif akciğer hastalığı (KOAH) olan hastalarda, formoterol (F) ve ipratropium bromür (IPB)'ün ayrı ayrı ve birlikte uygulamalarının solunum fonksiyon testleri (SFT) ve egzersiz performansı üzerine etkilerini karşılaştırmak. Metod: Çalışmaya 17 KOAH'lı hasta alındı. Hastaların 13'ü erkek, 4'ü kadın olup, yaş ortalamaları 56 idi. Öncelikle bazal SFT'leri ve egzersiz testleri yapıldıktan sonra hastalar randomize olarak birer hafta ölçülü doz inhaler ile F (12 saatte bir 24 µg), IPB (6 saatte bir 40 µg) ve F + IPB aldılar. Aralarda birer hafta "washout" periyot bırakıldı. Her tedavi periyodunun sonunda hastaların SFT ve egzersiz testleri tekrarlandı. Egzersiz testleri bisiklet ergometrisinde semptom sınırlamalı olarak yapıldı. Her bir periyottaki ölçümler; [bazal (B), F sonrası, IPB sonrası ve IPB + F sonrası] Friedman varyans analizi ile karşılaştırıldı. Sonuçlar: Hastaların reversibiliteleri %9.76 ± 5.40, FEV1'leri %57.82 ± 19.46, difüzyon kapasiteleri %67.07 ± 16.18, PaO2'leri 66.84 ± 10.63 idi. Yapılan analizler sonucu FEV1 parametresi, hastalar F ve F + IPB alıyorken B değerlere göre anlamlı olarak yüksek bulundu. FVC değerleri de her tedavi periyodu sonunda bazal değerlere göre anlamlı olarak yüksek bulundu. Egzersiz parametrelerinden max O2 "uptake" hastalar F ve F + IPB alıyorken B'ye göre yüksek bulunmakla beraber aradaki fark anlamlı değildi. Hastaların maksimum iş kapasiteleri periyotlar arasında anlamlı farklılık göstermedi. Maksimum egzersiz kalp hızları, dakika ventilasyonları, solunum sayısı, tidal volüm ve oksijen satürasyonları arasında da anlamlı farklılık saptanmadı. Sonuç olarak bu çalışmada reversible hava akımı sınırlanması olan KOAH'lı hastalarda F'in yalnız başına veya IPB ile birlikte uygulandığında etkili bronkodilatasyon sağladığı ve egzersiz performansında ise anlamlı bir değişiklik oluşturmadığı gözlendi.

A comparison of formoterol alone and combination with ipratropium bromide on pulmonary functions and exercise performance in stable chronic obstructive pulmonary diseases

The aim of this study was to evaluate the impact of a week-long course of inhaled formoterol (F), ipratropium bromide (IPB) and combination therapy on pulmonary functions and exercise performance in patients with chronic obstructive pulmonary disease (COPD). Seventeen patients with stable COPD were studied. The subjects inhaled formoterol two puffs two times a day during one period of 7 days duration or IPB two puffs four times a day per seven days and F + IPB together for seven days in a random sequence. Spirometric and exercise parameters were assessed at baseline period and after each of F, IPB and F + IPB therapy periods. Exercise tests were performed as symptom limited on bicycle ergometer. Mean age of patients were 56 years, mean FEV1 values were 67.07 ± 16.18% and mean reversibility was 9.76 ± 5.40%. The mean FEV1 response to the F and F + IPB combination therapy were significantly greater than baseline measurements (p< 0.05). Max exercise O2 uptake of the patients were higher than baseline values when patients were taking F and F + IPB but the difference were not significant (p> 0.05). Maximum work rate, heart rate, minute ventilation, oxygen saturation and tidal volume values did not significantly increase during the maximum exercise after any therapy regimen. In conclusion, these results suggest that F is an effective bronchodilator drug in COPD patients either alone or combined with IPB at rest but there is no significant effect on the exercise performance.

PDF

___

1. Britton M. Salmeterol and salbutamol: Large multicentre studies. Eur Respir Rev 1991; 4: 228-92.
2. Faurschou P. Chronic dose ranging studies with salme-terol. Eur Respir Rev 1991; 4: 282-7.
3. Pavwels RA, Löfdal CG, Postma DS, et al. FACET international study group. Effect of inhaled formoterol and budesonide on exacerbation of asthma. N Eng J Med 1997; 337: 1405-11.
4.Cazzola M, Matera MG, Santangelo G, et at. Salmeterol and formoterol in partially reversible severe chronic obstructiue pulmonary disease: A dose response study. Respiratory Med 1995; 89:357-62.
5. Ramirez-Venegas A, Ward J, Lentine T, Mahler DA. Salmeterol reduces dyspnea and improves lung function in patients with COPD.
6. Boyd G, Morice AH, Pounsford JC, et al. An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD). Eur Respir J 1997; 10: 815-21.
7. Grove A, Lipworth BJ, Reid P, et al. Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive lung disease. Thorax 1996; 51: 689-93.
8. Celik G, Kayacan O, Beder S, Durmaz G. Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: A crossover, placebo controlled comparison of onset and duration of action. Respiration 1999; 66: 434-9.
9. Gross NJ, Skorodin MS. Anticholinerjic, antimuscarinic bronchodilators. Am Rev Respir Dis 1984; 129: 856-70.
10. Anthonisen NR. Anticholinergics in obstructive lung disease. Eur Respir Rev 1995; 5: 347-9.
11. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 86 days multicentre trial. Chest 1994; 105: 1411-9.
12. Thomson NC, Angus R, Quebe-Fehling E, Brambilla R. Efficacy and tolerability of formoterol in elderly patients with reversible obstructive airways disease. Respiratory Med 1998; 92:562-7.
13. Le Doux EJ, Morris JF, Temple WP, Duncon C. Standard and double dose ipratropium bromide and combined ipratropium bromide and inhaled metaproterenol in COPD. Chest 1989; 95: 1013-6.
14. Imhof E, Elsasser S, Karrer W, et at. Comparison of bronchodilator effects of fenoterol/ipratropium bromide and satbutamol in patients with chronic obstructive lung disease. Respiration 1993; 60: 84-8.
15. Rennard SI. Combination bronchodilator therapy in COPD. Chest 1995; 107: 171-5.
16. Matera MG, Caputi M, Cazzola M. A combination with clinical recommended dosages of salmeterol and ipratropium is not more effective than salmeterol alone in patients with chronic obstructive pulmonary disease. Respiratory Med 1996; 90: 497-9.
17. Noord JA, Munck DRAJ, Bantje Th A, et al. Long-term treatment of chronic obstructive pulmonary disease with salmeterot and the additive effect of ipratropium. Eur Respiratory J 2000; 15: 878-85.
18. Ikeda A, Nishimura K, Kayama H, et al. Dose response study of ipratropium bromide aerosol on maximum exercise peformance in stable patients with COPD. Thorax 1996; 51: 48-53.
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. Leitch AG, Hopkin JM, Ellis DA, et al. The effect of aeresol ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis. Thorax 1978; 33: 711-3.
21. Tobin MJ, Hughes JA, Hutchison DCG. Effects of ipratropium bromide and fenoterol aerosols on exercise tolerance. Eur J Respir Dis 1984:65:441-6.
22. Brown SE, Prager RS, Shinto RA, et al. Cardiopulmonary responses to exercise in chronic airflow obstruction: Effects of inhaled atropine sulphate. Chest 1986; 89: 7-11.
23. Blosser SA, Maxwell SL, Reeves-Hoche MK, et al. Is an anticholinergic agent superior to a beta-2 agonist in improving dyspnea and exercise limitation in COPD. Chest 1995; 108: 730-5.
24. Newnham DM, Ingram CG, Earnshaw J, et al. Salmeterol provides prolonged protection against exercise-induced bronchoconstriction in a majority of subjects with mild, stable asthma. Respiratory Med 1993; 87: 439-44.
25. Kemp JP, Dockhorn RJ, Busse WW, et at. Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm. Am J Respir Crit Care Med 1994: 1612-5.
26. Grove A, Lipworth BJ, Reid P, et al. Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease. Thorax 1996; 51: 689-93.