Does early intervention with ICS improve long-term outcomes in asthma?

1. Does early intervention with ICS improve long-term outcomes in asthma? Dr. Haluk Türktaş Gazi University Department of Pulmonary Medicine Ankara

2. Less risk of severe asthma exacerbation • Fewer course of systemic corticosteroids • More symptom free days • Fewer urgent care visit • Less hospitalisation • Better pulmonary function tests • Better asthma control

3. Asthmatic Steroid-treated asthmatic

4. Does early intervention with ICS improve long-term outcomes in asthma?

5. Rationale for early treatment intervention • Asthmatics experience progressive loss of lung function • Inflammation likely causes loss of lung function by remodelling • Inflammation has been documented in early asthma • Inflammation can occur without symptoms

7. 50 40 30 20 10 0 140 120 100 80 60 40 20 0 Early ICS Late ICS PEF (L/min) Changes in PEF (L/min) First week Sixth week 12 th month Morning Evening Morning Evening Morning Evening <6 mn 6-12 mn 1-2 yr 2-5 yr 5-10 yrl >10 yr Symptom duration before treatment Haahtela T N Engl J Med 1994; 331: 700 Selroos O Chest 1995: 108; 1228 EARLY INTERVENTION WITH INHALER CORTICOSTEROIDS

8. Long-Term Effects of Budesonide or Nedocromil in Children with Asthma The Childhood Asthma Management Program Research Group (CAMP Study) New Eng J Med 2000;343:1054-63 1041 children with mild to moderate asthma, 5-12 (8.9) years of age, treated 4-6 years. Primary outcome post bronchodilator FEV1

9. Transient early wheezing Late onset wheezing Persistent wheezing Wheezing prevelance 0 3 6 11 Age (years) Martinez F Eur Respir J 12:3s 1998

10. Outcome of Asthma and Wheezing in the First 6 Years of Life Follow-up through Adolescence Wayne J. Morgan et al Am J Respir Crit Care Med 2005;172:1253-1258

11. Long-term inhaled corticosteroids in preschool children at high risk for asthma (PEAK study) Theresa W Guilbert et al, N Engl J Med2006;354:1985-97 nTarget childrenMean age(y)TreatmentDurationPrimary outcome 285 Positive asthma 3.0 FLU 100gx2 2 years Episode-free days during third predictive index and per day year off study medication >3 episode of wheeze last year

12. Intermittent inhaled corticosteroids in infants with episodic wheezing (PAC study) Hans Bisgaard et al, N Engl J Med2006;354:1998-2005 nTarget childrenMean age(y)TreatmentDurationPrimary outcome 294 Maternal asthma 1.7 2 week course 3 years Development of persistent of budesonide wheezing during trial 400 g per day for each episode

13. Secondary prevention of asthma by the use of inhaled fluticasone in wheezy infants (IFWIN study) • Clare S Murray et all, Lancet2006;368:754-762 • nTarget childrenMean age(y)TreatmentDurationPrimary outcome • Parental atopy and 0.9 FLU 100g twice Up to 4 years Lung function, BHR and • one prolonged or daily stepped down prevalence of doctor • two doctor confirmed diagnosed asthma • episode of wheezing • The groups did not differ significantly in • Physician diagnosed asthma • Lung function • Airway hyperreactivity

14. These early-asthma trials convincingly show that inhaled corticosteroids are only effective while being taken, and do not modify the natural course of the disease

15. X

16. Decline in Lung Function in the Busselton Health Study The Effects of Asthma and Cigarette Smoking Alan L. James et al Am J Respir Crit Care Med 2005;171:109-114

17. Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study O. Selroos et al Respir Med 2004;98:254-262 Early treatment group: symptoms for <2 years, n:253 Delayed treatment group: symptoms for >2 years, n: 51 Dose of inhaled steroids % of predictive FEV1, PEF Early treatment Delayed treatment

18. Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study O. Selroos et al Respir Med 2004;98:254-262 Early treatment Delayed treatment

19. Effects of Early Intervention With Inhaled Budesonide on Lung Function in Newly Diagnosed Asthma (START study) Paul M. O’Byrne, Chest 2006;129:1478-1485 5-66 years old, 7165 patients, asthma duration<2 years, 3 years treatment with budesonide 400 g (200 g for children <11 years old) -0.62% -1.79% -2.11% -2.68%

20. Effects of Early Intervention With Inhaled Budesonide on Lung Function in Newly Diagnosed Asthma (START study) Paul M. O’Byrne, Chest 2006;129:1478-1485 NS NS P<0.001

21. Inhaled corticosteroids and decline of lung function in community residents with asthma Peter Lange et al Thorax 2006;61:100-104 1994-2003 With ICS (n:44) Without ICS (n:190) 25 ml per year P<0.001 P<0.001 51 ml per year A 15-year follow-up study of ventilatory function in adults with asthma Peter Lange et al (Copenhagen City Heart Study) N Engl J Med 1998;339:1194-2000 1976-1994 1.7 1.5 1.3 1.1 0.9 0.7 0.5 0.3 No asthm a (n:16.441) Asthma (n:1095) FEV1 decline Height-Adjusted FEV1 (litre) 22 ml per year 38 ml per year 20 30 40 50 60 70 80 Age (yr)

22. 20.6 ml/yr Lung function decline in asthma: association with inhaled corticosteroids, smoking and sex A Dijkstra et al Thorax 2006;61:105-110 122 moderate to severe asthmatic patients diagnosed 1963-75 and re-eaxamined in 1991-99. Medain follow up period of 23 years

23. Airway Inflammation Is Present during Clinical Remission of Atopic Asthma Leon M Van Den Toorn et al Am J Respir Crit Care Med 2001;164:2107-2113 Control Remission

24. ICSs are associated with less disease burden • Less risk of severe asthma exacerbation • Fewer course of systemic corticosteroids • More symptom free days • Fewer urgent care visit • Less hospitalisation • Better pulmonary function tests • Better asthma control

25. 2.5 2.0 1.5 1.0 0.5 0.0 5 4 3 2 1 0 100 million dose Asthma mortaliy 1/100.000 1973 75 77 79 81 83 85 87 89 91 93 Years 2.5 2.0 1.5 1.0 0.5 0.0 Suissa S N Engl J Med 2000:343;332 Suissa S J Clin Epidemiol 1997:50;1079 Asthma mortality rate 0 1 2 3 4 5 6 7 8 9 10 11 12 Annual ICS use (box) INHALER CORTICOSTEROIDS AND ASTHMA MORTALITY