YES There is a place for theophylline in asthma treatment Dr. Haluk Türktaş

1. YES There is a place for theophylline in asthma treatment Dr. Haluk Türktaş Gazi Üniversitesi Tıp Fakültesi Ankara

2. SUITABLE DRUG • Effective • Safe • Accessible • Cheap • Easy to use

3. EFFECTS OF THEOPHYLLINE • Antiinflammatory (In low doses 5-10 µg/ml) • Bronchodilator (Phosphodieterase inhibition and adenosine antagonism in high doses >15 µg/ml ) • Pozitive inotrop, chronotrop • Diuretic • Increase diaphragmatic contractility • Increase mucociliary clearence

4. Stephen T Holgate Allergology International. 2008;57:1-10 Bronchial Hyperreactivity

5. Theophylline induces a reduction in circulating interleukin-4 and interleukin-5 in atopic asthmatics E.N. Kosmas, S.A. Michaelides Eur Respir J 1999;13:53-58 Theophylline 150 mg/day (Serum Theo 4.2 µg/ml) Plac Theo Plac Theo 3 week interval

6. Low-dose Theophylline Reduces Eosinophilic Inflammation in Mild Asthma Lim S, Tomita K Am J Respir Crit Care Med 2001:164;273-276 Theo 2x250 mg Wash-out Placebo 5 week 4 week 5 week (Mean serum level 6.1 µg/ml) Induced sputum BAL Bronchial biopsy Induced sputum BAL Bronchial biopsy

7. Low-dose Theophylline Reduces Eosinophilic Inflammation in Mild Asthma Lim S, Tomita K Am J Respir Crit Care Med 2001:164;273-276

9. A molecular mechanism of action of theophylline Kazhuiro I, PNAS 2002

10. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of chronic obstructive pulmonary disease Cosio BG, Barnes P Thorax in press

11. The place of theophylline in • asthma treatment • Alternative to low dose inhaled • steroids in step 2 • Alternative to other controllers as add-on therapy in step 3,4,5 and 6

12. Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma Reed CE J Allergy Clin Immunol 1998

13. Comparison of addition of theophylline to inhaled steroid withdoubling of the dose of inhaled steroid in asthma Ukena D, Harnest U Eur Respir J 1997:10;2754-2760 Theophylline/BDP 400 μg·day BDP 800 μg·day (Mean serum level 10.1 µg/ml) Baseline Week 6 Theophylline/BDP 400 μg·day Baseline Week 6 Theophylline/BDP 400 μg·day Baseline Week 6 BDP 800 μg·day Baseline Week 6 BDP 800 μg·day

14. Comparison of inhaled corticosteroid combined withtheophylline and double-dose inhaled corticosteroid in moderate to severe asthma Wang Y, Lin K, Respirology 2005;10:189-195 2x250 µg BDP+ 2x500 µg BDP 2x200 mg Theo

15. Effects of Theophylline Withdrawal in Well-Controlled Asthmatics Treated with Inhaled Corticosteroid Kenji Baba, Ayako Sakakibara J Asthma 2001, 38:8;615-624 Theophylline Theo+BDP Teofilin kesildikten sonra 17 hastanın 12 de atak gelişiyor

16. Effects of Theophylline Withdrawal in Well-Controlled Asthmatics Treated with Inhaled Corticosteroid Kenji Baba, Ayako Sakakibara J Asthma 2001, 38:8;615-624

17. Effect of theophylline plus beclometasone on lung function insmokers with asthma-a pilot study Spears M Eur Respir J in press Change in PEF by 28 days of treatment Pre BD PEF Change in (L/min) Change in ACQ score ICS Theo Theo+ICS ICS Theo Theo+ICS

18. Adding second controller to ICS • LABA • LTRA • Theophylline • Cromon

19. 8 week Comparison of salmeterol/fluticasone propionate (FP) combination with FP+sustained release theophylline in moderate asthma patients Adachia M, Aizawab H Respir Med 2008;102:1055-1064 Flu+Salm 250/50 µg X 2 n:194 Flu 250 µg+Theo 200mg X2 n:189

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21. NIH Asthma Guideline 2007

22. Clinical Trial of Low-Dose Theophylline and Montelukastin Patients with Poorly Controlled Asthma The American Lung Association Asthma Clinical Research Centers Am J Respir Crit Care Med 2007:175;235-242 n:161 n: 164 n: 164 24 weeks EPACS: Episode of Poor Asthma Control Decreased peak flow, increased β2-agonist use, increased oral corticosteroiduse, or unscheduled health care visits

23. Clinical Trial of Low-Dose Theophylline and Montelukastin Patients with Poorly Controlled Asthma The American Lung Association Asthma Clinical Research Centers Am J Respir Crit Care Med 2007:175;235-242 EPACS: Episode of Poor Asthma Control

24. Clinical Trial of Low-Dose Theophylline and Montelukastin Patients with Poorly Controlled Asthma The American Lung Association Asthma Clinical Research Centers Am J Respir Crit Care Med 2007:175;235-242 Mean serum theo level 6.8 µg/ml at week 4 6.2 µg/ml at week 24

25. Comparison of salmeterol/fluticasone propionate (FP) combination with FP+sustained release theophylline in moderate asthma patients Adachia M, Aizawab H Respir Med 2008;102:1055-1064

26. SIDE EFFECTS OF ANTI-ASTHMATIC DRUGS Inhaled steroids β2-Agonist Theophylline Nause Abdominal pain Tachycardia Arrhytmia Anxiety Convulsion Oral candidiasis Hoarseness Cough Surrenal supression Osteoporosis Cataract Glaucom Hypertension Diabetes Obesity Tachycardia Arrhytmia Tremor Hypopotassemia Hyperglisemia Anxiety

27. COST OF TREATMENT (Per month) Leukotriene antagonist 70 TL Theophylline 4 TL

28. Theopylline is a suitable drug • Effective • Minimal side effects • Accessible • Cheap • Easy to use

29. YES There is a place for theophylline in asthma treatment

30. BRONŞASTIMI Dr.A.Fuat Kalyoncu Hacettepe Üniversitesi Gögüs Hastalıkları -Eriskin Alerji Ünitesi Methylxanthines They cause bronchodilatation by inhibition of phosphodiesterase and adenosine antagonism. Immunmodulation by decreasing the number of eosinophils and T-lymphocytes. Also they increase mucociliary clearence, stimulate central nervous system, increase diaphragmatic contractility and diuresis. They are the cheapest anti-asthmatic drug and they have oral, injectable and suppository preparations…..

31. Pregnant asthmatic patients always worry about the potential side effects of medications on the fetus. …… Theopyllines have no side effects on the fetus except irritability and increased motion of the fetus.

32. Dearest Fuat ! Verba volant scripta manent