Ali …. 65 years old C/O exercise intolerance for 2 years

1. Ali …. 65 years old C/O exercise intolerance for 2 years

2. History of occasional wheeze • “slight cough for a while” “5 may be 10 years” • Morning sputum most of the time • Smoked on and off for 40 years / 1.5 packs • No clubbing • Wheeze and hyperinflation

3. FEV1 / FVC < 70 % • Diffusing capacity(DLco) • Kco reduced

4. Saleh 55 years smoked 60 since age 16Barrel-shapedLiver 6th spaceCough, expectoration, SOB 2 yearsFEV1 44% FEF 19% RV%TLC 200% FEV1 / FVC 60%Ventolin neb. 5mg----FEV1 INCREASED 140 ml (10%)

5. KCO 98%Allergic rhinitis and hypret. TurbinatesSOB triggered strongly by dust and irritants • A trial of Symbicort for 3 weeks • FEV1 and FEF50 rose to 80% • FEV1 relapsed to 64% but recovered

6. Airways obstruction in patients with long-term asthma consistent with ‘irreversible asthma’ Backman et al. Chest 1996 • A series of 8 patients aged 41-58 • Post salb. FEV1 26% to 57% • All on oral corticosteroids • Mean duration of asthma 39 years • “ end stage “ irreversible asthma • KCO 81% to 107%

7. Nonreversible airflow obstruction in life-long nonsmokers with moderate to severe asthma • 92 subjects 18-64 years • BA for 16 years all reversible • FU 10 years • 23% became irreversible • Yet both groups maintained normal KCO and TLCO Eur Respir J 1999

8. Characteristics of bronchial asthma with incomplete reversibility of airflow obstruction • Hudon et al. 1997 • 2 groups : reversible V irreversible • FEV1 : 89% V 48% • Duration : 17 years V 31 years • Thicker bronchial wall on HRCT scan • Lung compliance and KCO the same

9. Airways inflammation in asthma with incomplete reversibility of airflow obstruction • 15 IRAO FEV1 54% • 23 CRAO FEV1 84% • Non smoker • Sputum induction • FEV1 inversely correlated with % neutrophils not eosinophils Resp Med 2003

10. Airway remodelling is correlated with obstruction in childrenAllergy 2008 • 5-14 years old • Persistent obstruction in spite of ICS and systemic corticost. increased ASM increased blood vessels

11. Clinical,physiological and radiological features of asthma with incomplete reversibility compared with COPD • Boulet et al. 1998 • AIRAO 14 V COPD 13 cases • Atopy 13 V 1 • FEV1 49% V 39% • Revers. 22% V 18% • DLCO 89% V 62% • Mod. To severe emphysema 0 V 10/13

13. Asthma is not a common cause of severe chronic respiratory failure in non-smokers : ALTOT STUDY • All cases of domiciliary LTOT in an Italian district • 114 (all smokers) had COPD • 70 (all smokers) had other conditions • None had a history of BA

14. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma… • Allergy Humbert et al 2003 • ICS/LABA • Reduced severe exacerbations by half

15. ERS/Gold 1. Airways obsturction Smokers NS Ex-S White men White women 14.2% 13.6% 3.3% 3.1% 6.9% 6.8%

16. C O U G H Smokers NS Ex-S White men White women 24% 20% 4% 5% 4.7% 6.5%

18. Practical Plan • Bullae or chronic respiratory failure—COPD • Below 50 • History of atopy or strong triggering • NORMAL KCO

19. ICS trial • Symbicort • Seretide MDI • 3 weeks

20. A study at KKUH on smokers bearing the diagnosis of BA or COPD • 40 diagnosed BA Only 1 re-diagnosed COPD Confirmed by irreversibility low KCO histology

21. 40 diagnosed COPD 12 full reversibility + normal KCO 5 remained irreversible normal KCO HISTOLOGY