Riacutizzazione di BPCO

1. Riacutizzazione di BPCO

2. Standards for the diagnosis andtreatment of patients with COPD: a summary of the ATS/ERS position paper Riacutizzazioni: definizione La riacutizzazione della BPCO è un evento, che si verifica nel corso della storia naturale della malattia, caratterizzato da un cambiamento rispetto al basale di dispnea e/o dell’espettorato, che eccede la variabilità quotidiana ed è tale da richiedere modifiche del trattamento Celli B. ERJ 2004

3. Costi delle AECB In generale, solo una minima parte della spesa sanitaria pro capite è generata da pazienti con BPCO lieve o moderata La malattia grave e molto grave, di competenza prevalentemente specialistica, spiega l’elevatissimo consumo di risorse sanitarie Poiché la bronchite cronica è responsabile dell’85% dei casi di BPCO, una rilevante porzione della spesa sanitaria pro capite per questi pazienti è generata dalle riacutizzazioni, indipendentemente dalla gravità della malattia di base Sethi S, File TM. Curr Med Res Opin. 2004;20:1511-21

4. Definition EXACERBATION Defined as an increase in the baseline symptoms of the disease in the absence of an identifiable cause. ATS/ERS Statement ERJ 2004; 23:932-946

5. Cause di RIACUTIZZAZIONI Infezioni Batteriche Virali Allergie RIACUTIZZAZIONE Inquinamento Anidride solforosa Polveri industriali Clima Inverno Ball P. Chest. 1995;108:43S-52S. Gump DW, et al. Am Rev Respir Dis. 1976;113:465-74.

6. ALL EXACERBATIONS BY MONTH OF STUDY:from East London COPD cohort

7. Modifiable risk factors in patients with COPD exacerbation (EFRAM study)  No influenza vaccination: 28 %  No rehabilitation program: 86 %  No home O2 in pts with PaO2< 55 mm Hg: 28 %  Failed in inhaler maneuvers: 43 %  Current smokers: 26 % García Aymerich J et al. ERJ 2000; 16: 1037-1042

8. AECB ETIOLOGY Papi A et al. AJRCCM 2006

9. Coinfection Coronavirus Chlamydia Pneumoniae RSV Serology Adenovirus Parainfluenza Rhinovirus Influenza B Influenza A RESPIRATORY VIRUSES AND EXACERBATIONS Seemungal et al Am J Respir Crit Care Med 2001

10. RSV (PCR) IN STABLE COPD AND AT EXACERBATIONSeemungal et al Am J Respir Crit Care Med 2001 EXACERBATIONS • RSV found in 26% of exacerbations • Detection of RSV not related to exacerbation parameters STABLE • RSV found in 24% of stable samples

11. CHANGES IN BACTERIAL LOADn=57 *p=0.0001 Bacterial Load Log cfu/ml

12. 70 64 60 55 5,5 50 40 4,2 30 27 20 2,2 10 0 Healthy subjects Stable COPD Exacerb.COPD Bacterial infection and COPD Bacterial index Culture + Rosell et al. Arch Intern Med 2005; 165: 891-897

13. The “fall & rise” of bacterial AECB Modifying factors Clinical threshold Bacterial load (CFU/ml) AB1 AB2 AB3 Time (days) AE ABCureCureCureStop AB Time to relapse Miravitlles et al. Eur Respir J 2002: 20 (Suppl 36): 9s-19s

14. The usual suspects AECB Etiology Chlamydia pneumoniae

15. RELATIVE RISK OF EXACERBATION AND BACTERIAL STRAIN CHANGE Exacerbation visits % • 33% of exacerbation visits were assoaciated with a new strain, compared to 15% of visits when no new strain was found P<0.001 • For H Influenzae, S pneumoniae, M Catarrhalis Sethi et al NEJM 2002

16. INTERACTION OF BACTERIAL AND VIRAL INFECTION Wilkinson et al Chest 2006; 129:317-324

17. Rapporti tra infiammazione e infezione nei pazienti con BPCO

18. BACTERIAL ERADICATION AND INFLAMMATION White et al Thorax 2003

19. ALTERAZIONI STRUTTURALI VIE AEREE-PARENCHIMA COLONIZZAZIONE BATTERICA OSTRUZIONE BRONCHIALE INSUFFLAZIONE RIACUTIZZAZIONI DISPNEA LIMITAZIONE SFORZO PEGGIORAMENTO Q of L

20. Circolo vizioso del declino funzionale nei pazienti con BPCO

21. 39 (72.2%) of patients had bronchiectasis on HRCT Median score was 3/24 (range 1-14) Patel et al AJRCCM2004 Upper lobes 43.6% Middle lobe/lingula 46.2% Lower lobes 76.9%

22. NATURAL HISTORY OF COPD Never smoked Exacerbation Lung Function Smoker Exacerbation Exacerbation Time (Years) Fletcher C. BMJ 1977;1:1645-1648.

23. Day-to-day variability of a patient with COPD Normal variation of clinical stateExacerbation threshold Function Time Rodriguez-Roisin, R. Chest 2000;117:398S-401S

24. Relationship between lung function and exacerbations Exacerbations increase as lung function declines.

25. Lung function shows a small decline in the days immediately preceding an exacerbation Fluticasone propionate 500mcg bd FSC 50/500mcg bd 270 Salmeterol 50mcg bd Placebo 260 250 240 Mean PEF (L/min) 230 220 210 Onset of exacerbation 0 -14 -12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 Day Pauwels et al. Am J Respir Crit Care Med 2003; 167(7): A949

26. INTERACTION OF BACTERIAL AND VIRAL INFECTION Wilkinson et al, Chest 2006; 129:317-324

27. Time Course and Recovery of COPD Exacerbations 101 patients - F/up 2.5 years FEV1 41.9% Pred Daily Symptoms and PEFR FEV1 (34) Recovery 75.2% No recovery 7.1% (90 d.) Seemungal TAR et al, AJRCCM 2000; 161: 1608

28. Impatto delle infezioni delle basse vie respiratorie sul declino annuale del FEV1 (ml/anno) Ex fumatori Fumatori intermittenti 70 Fumatori 60 50 40 30 20 10 0 0-0.24 0.25-0.49 0.50-0.99 1.00-1.49 >1.50 indice Kanner RE et al. AJRCCM 2001

29. Decline in FEV1 Over 12 Months in Patients with COPD Pauwels et al. AJRCCM 2001;163:A770

30. Variazione percentualedel FEV1 in 4 anni 0,95 Infrequente Frequente 0,9 0,85 0,8 0,75 0 1 2 3 4 Anni indice Donaldson GC et al. Thorax 2002;57:847-852

31. The risk of an exacerbation increases as lung function declines 100 Percentage of patients remaining 80 60 ATS stage 40 Mild Moderate 20 Severe 0 0 100 200 300 400 Exacerbation-free time (days) Hauber et al. Am J Respir Crit Care Med 2002; 165(8): A271.

32. Exacerbation Rate by FEV1 Donaldson & Wedzicha Thorax 2006;61:164

33. Relationship between symptoms and exacerbations Symptoms worsen before and during an exacerbation, prompting presentation to a physician, but their resolution is not sufficient for recovery.

34. Breathlessness increases during an exacerbation FSC 50/500mcg bd 2.4 Salmeterol 50mcg bd Fluticasone propionate500mcg bd 2.2 Placebo 2.0 Mean breathlessness score 1.8 1.6 Onset of exacerbation 1.4 0 -14 -12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 Days Pauwels et al. Am J Respir Crit Care Med 2003; 167(7): A949.

35. Symptoms worsen during the 2 days preceding an exacerbation Pauwels et al. Am J Respir Crit Care Med 2003; 167(7): A949

36. INTERACTION OF BACTERIAL AND VIRAL INFECTION Wilkinson et al Chest 2006; 129:317-324

37. Relationship between exacerbations and health status Exacerbations have a pronounced detrimental impact on health status, while low health status is linked with increased probability of exacerbations

38. Recovery of health status after an exacerbation is prolonged, particularly if another exacerbation occurs during the recovery period Experiencing an exacerbation during the follow-up period Experiencing no further exacerbation n =133 Improved health status SGRQ total score 60 55 n =133 n =115 n =116 50 n =299 45 40 n =280 35 n =233 30 n =221 0 4 12 26 Time after presentation with an exacerbation (weeks) Spencer & Jones. Thorax 2003; 58: 589-93.

39. Exacerbations and quality of life P < 0.0005 SGRQ Score 3 - 8 Exacerbations/year Seemungal TAR et al, AJRCCM 1998; 157: 1418

40. A higher frequency of exacerbations is related to greater impairment of health status 0-2 exacerbations per year (n=32) 3-8 exacerbations per year (n=38) Improved health status Mean SGRQ score 100 p=0.001 p<0.0005 80 p<0.0005 80,9 77,0 p=0.002 67,7 60 64,1 53,2 50,4 48,9 40 36,3 20 0 Total Activity Impacts Symptoms Seemungal et al. Am J Respir Crit Care Med 1998; 157: 1418-22

41. COPD exacerbations: Health status 613 mod. to severe COPD pts. followed for a maximum of 3 yrs * * p<0.0001 (Worse) # 3.0 # p<0.004 235 285 2.0 91 SGRQ slope (units/year) 1.0 0 None in 3 years Infrequent <1.65/year Frequent >1.65/year Exacerbation category Spencer S et al. Eur Respir J. 2004;23:698-702

42. Relationship between exacerbations and mortality Exacerbations increase the risk of death in patients with COPD.

43. Outcome delle AECBMortalità Mortalità ospedaliera 24% Mortalità ospedaliera 11-49% Pazienti in UTI Pazienti ospedalizzati Seneff MG, et al. JAMA. 1995;274:852-1857; Connors et al. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):959-67. Murata GM, et al. Ann Emerg Med. 1991 Feb;20(2):125-9; Adams SG, et al. Chest. 2000;117:1345-1352 indice

44. Sopravvivenzaassociata a AECB grave 100 80 60 Sopravvivenza (%) 40 20 0 0 100 300 350 Giorni indice Connors et al. Am J Respir Crit Care Med 1996;154:959

45. COPD Exacerbations : Mortality 1016 pts with severe COPD exacerbation (PaCO2> 50 mm Hg) 60 49% 50 43% 40 33% 30 Mortality (%) 20% 20 11% 10 0 Hospital stay 60 days 180 days 1 year 2 years Connors AF Jr et al.Am J Respir Crit Care Med. 1996;154:959-67

46. No exacerbation 1–2 exacerbations 3–4 exacerbations COPD exacerbations: Survival 1.0 0.8 0.6 p<0.001 Probability of surviving p<0.0001 0.4 p=0.07 0.2 0.0 0 10 20 30 40 50 60 Time (months) Soler-Cataluña JJ et al. Thorax. 2005;64:925-31

47. No exacerbation 1 hospitalization ER visits Readmission COPD exacerbations: Survival 1.0 0.8 NS 0.6 p<0.0001 Probability of surviving p<0.01 p<0.0001 0.4 NS 0.2 0.0 0 10 20 30 40 50 60 Time (months) Soler-Cataluña JJ et al. Thorax. 2005;64:925-31

49. Airway inflammation and aetiology of COPD exacerbations Sethi et al Chest 2000

50. SPUTUM IL-8 AT EXACERBATION AND MORAXELLA CATTARHALISPowrie et al ERS 2005 P=0.018