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 16 Barrel-shaped Liver 6th space Cough, expectoration, SOB 2 years FEV1 44% FEF 19% RV%TLC 200% FEV1 / FVC 60% Ventolin neb. 5mg----FEV1 INCREASED 140 ml (10%)

5. KCO 98% Allergic rhinitis and hypret. Turbinates SOB 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 TL CO 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 FEV 1 54% 23 CRAO FEV 1 84% Non smoker Sputum induction FEV 1 inversely correlated with % neutrophils not eosinophils Resp Med 2003

10. Airway remodelling is correlated with obstruction in children Allergy 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 White men White women 14.2% 13.6% 3.3% 3.1% 6.9% 6.8% SmokersNSEx-S

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

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