YESThere is a place for

theophylline in asthma treatment

Dr. Haluk TürktaşGazi Üniversitesi Tıp Fakültesi

Ankara

Effective Safe Accessible Cheap Easy to use

SUITABLE DRUG

Antiinflammatory (In low doses 5-10 µg/ml)

Bronchodilator (Phosphodieterase inhibition and adenosine antagonism in high doses >15 µg/ml )

Pozitive inotrop, chronotropDiureticIncrease diaphragmatic contractilityIncrease mucociliary clearence

EFFECTS OF THEOPHYLLINE

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

3 week interval

Theophylline induces a reduction in circulating interleukin-4 andinterleukin-5 in atopic asthmaticsE.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

Theo 2x250 mg Wash-out Placebo

Induced sputumBALBronchial biopsy

Induced sputumBALBronchial biopsy

Low-dose Theophylline Reduces Eosinophilic Inflammation in Mild AsthmaLim S, Tomita K

Am J Respir Crit Care Med 2001:164;273-276

5 week5 week 4 week 4 week 5 week 5 week(Mean serum level 6.1 µg/ml)

Low-dose Theophylline Reduces Eosinophilic Inflammation in Mild AsthmaLim S, Tomita K

Am J Respir Crit Care Med 2001:164;273-276

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

Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of chronic obstructive pulmonary diseaseCosio BG, Barnes PThorax in press

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

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

Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthmaUkena D, Harnest U Eur Respir J 1997:10;2754-2760

Baseline Week 6BDP 800 μg·day

Baseline Week 6Theophylline/BDP

400 μg·day

Theophylline/BDP400 μg·day

BDP 800 μg·day

Baseline Week 6BDP 800 μg·day

Baseline Week 6Theophylline/BDP

400 μg·day

(Mean serum level 10.1 µg/ml)

Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthmaWang Y, Lin K, Respirology 2005;10:189-195

2x250 µg BDP+ 2x500 µg BDP 2x200 mg Theo

Effects of Theophylline Withdrawal in Well-Controlled Asthmatics Treated with Inhaled Corticosteroid Kenji Baba, Ayako Sakakibara

J Asthma 2001, 38:8;615-624

Theo+BDP

Teofilin kesildikten sonra 17 hastanın 12 de atak gelişiyor

Theophylline

Effects of Theophylline Withdrawal in Well-Controlled Asthmatics Treated with Inhaled Corticosteroid Kenji Baba, Ayako Sakakibara

J Asthma 2001, 38:8;615-624

ICS Theo Theo+ICS ICS Theo Theo+ICS

Change in PEF by 28 days of treatment

Effect of theophylline plus beclometasone on lung function in smokers with asthma-a pilot study Spears MEur Respir J in press

Adding second controller to ICS

LABALTRATheophyllineCromon

Comparison of salmeterol/fluticasone propionate (FP) combination with FP+sustained release theophylline in moderate asthma patientsAdachia M, Aizawab HRespir Med 2008;102:1055-1064

Flu+Salm 250/50 µg X 2

Flu 250 µg+Theo 200mg X2

8 week

n:194

n:189

≠

NIH Asthma Guideline 2007

n:161

n: 164

n: 164

24 weeks

Clinical Trial of Low-Dose Theophylline and Montelukast in Patients with Poorly Controlled AsthmaThe American Lung Association Asthma Clinical Research CentersAm J Respir Crit Care Med 2007:175;235-242

EPACS: Episode of Poor Asthma ControlDecreased peak flow, increased β2-agonist use, increased oral corticosteroid use, or unscheduled health care visits

EPACS: Episode of Poor Asthma Control

Clinical Trial of Low-Dose Theophylline and Montelukast in Patients with Poorly Controlled AsthmaThe American Lung Association Asthma Clinical Research CentersAm J Respir Crit Care Med 2007:175;235-242

Clinical Trial of Low-Dose Theophylline and Montelukast in Patients with Poorly Controlled AsthmaThe American Lung Association Asthma Clinical Research CentersAm 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

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

Oral candidiasis HoarsenessCoughSurrenal supressionOsteoporosisCataractGlaucom HypertensionDiabetesObesity

TachycardiaArrhytmiaTremorHypopotassemiaHyperglisemiaAnxiety

NauseAbdominal painTachycardiaArrhytmiaAnxietyConvulsion

Inhaled steroids β2-Agonist Theophylline

SIDE EFFECTS OF ANTI-ASTHMATIC DRUGS

COST OF TREATMENT(Per month)

Leukotriene antagonist 70 TL

Theophylline 4 TL

Effective Minimal side effects Accessible Cheap Easy to use

Theopylline is a suitable drug

YESThere is a place for

theophylline in asthma treatment

BRONŞ ASTIMIDr.A.Fuat KalyoncuHacettepe ÜniversitesiGögüs Hastalıkları -Eriskin Alerji Ünitesi

MethylxanthinesThey 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…..

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.

Verba volant scripta manent

Dearest Fuat !