Leonardo M. Fabbri

Clinica di Malattie dell’Apparato RespiratorioUniversità degli Studi di Modena e Reggio EmiliaAzienda Ospedaliero-Universitaria - Policlinico di Modena

Ridefinizione della Ridefinizione della BPCO e delle BPCO e delle

riacutizzazioniriacutizzazionidei sintomi in pazienti dei sintomi in pazienti

con BPCOcon BPCO

Modena 6-7/8-9 Settembre 2011

Corso di Aggiornamento su MALATTIE RESPIRATORIE

COPD and chronic comorbidities

Exacerbations in COPD

Current and future treatment

Treatment of co-morbidities of COPD

Futuristic treatments

TREATMENT TARGETS IN COPD:

CURRENT AND EVOLVING MANAGEMENT OPTIONS

20%-24%20%-24%(1 year)(1 year)

2.5%-10%2.5%-10%(5 days)(5 days)

22%-32%22%-32%(14 days)(14 days)

13%-33%13%-33%(14 days)(14 days)

Hospital mortalityHospital mortality

Hospital mortalityHospital mortality

Relapse (repeat ER visit)Relapse (repeat ER visit)

Treatment failure rateTreatment failure rate

OUTCOME OF COPD EXACERBATIONS

Seneff et al. JAMA. 1995; 274:1852-1857; Murata et al. Ann Emerg Med. 1991;20:125-129; Adams et al. Chest. 2000; 117:1345-1352; Patil et al. Arch Int Med. 2003; 163:1180-1186.

In hospitalized In hospitalized patientspatients

In ER patientsIn ER patients

In ICU patientsIn ICU patients

In outpatientsIn outpatients

Goal of COPD Management

Overall COPD Control

Current Control Future Risk

Symptoms

Activity

Reliever use

Lung function

Exacerbations

Progressionof the disease

Mortality

Medication adverse effects

achieving reducing

defined by defined by

????? GOLD 2011 www.goldcopd.org

COPD

Chronic disease

Tashkin D. N Engl J Med 2010; 363: 1184

Hurst et al, N Engl J Med 2010; 363: 1128-38

progressive nature

• lung function

• symptoms

• comorbidities

Exacerbations

• typically 1 - 3 per year

• frequency proportionalto COPD severity

• the frequent exacerbator

• chronic decline resulting

in poorer prognosis

HRQL

hospitalizations

mortality

COPD exacerbations

ASSOCIATION OF DISEASE SEVERITY WITH THE FREQUENCY AND SEVERITY OF EXACERBATIONS DURING THE FIRST YEAR

OF FOLLOW-UP IN PATIENTS WITH COPD

Hurst J.R. et al., N Engl J Med 2010; 363: 1128-38

7

22

18

33 33

47

0

10

20

30

40

50

GOLD 2 GOLD 3 GOLD 4

Hospitalized for exacerbation in yr 1

Frequent exacerbations

(N=945)

% o

f p

ati

en

ts

(N=900) (N=293)

0 20 40 60 80 100Percent

0 20 40 60 80 100Percent

0 20 40 60 80 100Percent

0 20 40 60 80 100Percent

0 20 40 60 80 100

0 20 40 60 80 100

0 20 40 60 80 100

0 20 40 60 80 100

0 20 40 60 80 100

0 20 40 60 80 100

0 20 40 60 80 100

0 20 40 60 80 100

0 20 40 60 80 100Percent

Year 1 Year 2 Year 323%

6%2%6%3%2%

2%2%1%

5%3%1%

3%2%2%

2%2%3%

2%1%1%

2%2%3%1%4%12%

Patients with no

exacerbation

Patients with 1

exacerbation

Patients with ≥ 2

exacerbations

STABILITY OF THE FREQUENT-EXACERBATION PHENOTYPE IN THE 1679 PATIENTS WITH CHRONIC OBSTRUCTIVE

PULMONARY DISEASE WHO COMPLETED THE STUDY

Hurst J.R. et al., N Engl J Med 2010; 363: 1128-38

Breast Cancer Diseases - 2015

All Breast Cancers

ER+65-75%

HER2+15-20%

Triple negative

15%

HER3+

IGFR1+

p95+ 4%

P53mut

30-40 %FGFR1Ampl 8%

PTENloss

30-50%

PI3Kmut

10%

BRCAMut

8%

12-02

BAC EGFR mut+: Response to TKI

12-00

INTACT 1: Lack of benefit in combination with chemotherapy

Population: intention to treat

0.0

0.2

0.4

0.6

0.8

1.0

Survival time (months)0 4 8 12 16 20 24

Proportioneventfree

641 463 152 118981093At risk

Median survival, months1-year survival rate, %Log rank vs placebo

9.9243

0.7759(p=0.4377)

9.8641

1.0290(p=0.3034)

11.0745

Gefitinib 500 mg/dayGefitinib 250 mg/dayPlacebo

WE DIDN’T KNOW ABOUT EGFR MUTATION

K Kobayashi et al, P ASCO 2009K Kobayashi et al, P ASCO 2009

PNEUMONIA

THROMBOEMBOLISM

ACUTE HEART FAILURE

METABOLIC ACIDOSIS

ANEMIA

CAUSES OF EXACERBATION OF

RESPIRATORY SYMPTOMS IN CHRONIC PATIENTS

BIOCHEMICAL MARKERS OF CARDIAC DYSFUNCTION PREDICT MORTALITY IN

ACUTE EXACERBATIONS OF COPD

Elevated levels of NT-proBNP and troponin T are strong predictors of early mortality among patients

admitted to hospital with acute exacerbations of COPD independently of other known prognostic

indicators

The pathophysiological basis for this is unknown, but indicates that cardiac involvement in

exacerbations of COPD may be an important determinant of prognosis

Chang CL et al, Thorax in pressChang CL et al, Thorax in press

UNRECOGNIZED VENTRICULAR DYSFUNCTION IN CHRONIC OBSTRUCTIVE

PULMONARY DISEASE

CHF and COPD frequently coexist

Ventricular dysfunction worsens survival in patients with COPD

Considering the high prevalence and the prognostic implications of ventricular dysfunction, routine assessment with either BNP or echocardiogram

should be considered in COPD patients

Macchia A et al, ERJ Express - June 23, 2011

THE PROGNOSTIC IMPORTANCE OF THE PROGNOSTIC IMPORTANCE OF LUNG FUNCTION IN PATIENTS LUNG FUNCTION IN PATIENTS

ADMITTED WITH HEART FAILUREADMITTED WITH HEART FAILURE

Prognostic importance for all-cause mortality Prognostic importance for all-cause mortality of lung function variables obtained by of lung function variables obtained by

spirometry in an unselected group of patients spirometry in an unselected group of patients admitted with heart failure (HF)admitted with heart failure (HF)

Iversen KK et al, Iversen KK et al, Eur J Heart Fail. 2010 Jul;12(7):685-Eur J Heart Fail. 2010 Jul;12(7):685-91. 91.

TARGETING THE LUNG TARGETING THE LUNG ATTACKSATTACKS

Current management strategiesfor acute asthma and AECOPD within and

subsequent to discharge from hospital are suboptimal

We suggest that the term ‘lung attack’ may resonate more with patients and the

broader communityFitzGerald JM, FitzGerald JM, Thorax May 2011 Vol 66 No 5

 Aggiornamento concetti generali sulla componente respiratoria della BPCO

Leonardo M. Fabbri

 Aggiornamento concetti generali sulla componente respiratoria della BPCO

Leonardo M. Fabbri

DEFINIZIONE

Chronic Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease.

It is characterized by chronic respiratory symptoms, particularly dyspnea and persistent airflow limitation that is usually progressive and associated with an enhanced

chronic inflammatory response of the airways and the lung to cigarette smoke and/or other noxious particles or gases.

Exacerbations and significant concomitant disorders contribute to the overall severity in individual patients.

5-yrs mortality5-yrs mortality

The present study analysed data from 20,296 subjects aged >45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS).

COPD and chronic comorbidities

Exacerbations in COPD

Current and future treatment

Treatment of co-morbidities of COPD

Futuristic treatments

CORSO DI AGGIORNAMENTO SU MALATTIE RESPIRATORIECORSO DI AGGIORNAMENTO SU MALATTIE RESPIRATORIEModena 20-21 Luglio 2011Modena 20-21 Luglio 2011

INTRODUZIONE E LINEE GUIDA PER LA BPCO INTRODUZIONE E LINEE GUIDA PER LA BPCO Leonardo M. FabbriLeonardo M. Fabbri

Barnes PJ et al., Eur Respir J 2009;33:1165–1185Barnes PJ et al., Eur Respir J 2009;33:1165–1185

SYSTEMIC EFFECTS AND COMORBIDITIES OF SYSTEMIC EFFECTS AND COMORBIDITIES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASECHRONIC OBSTRUCTIVE PULMONARY DISEASE

Severity of airflow limitationFrequency and severity of exacerbations

Comorbidities

Severity of airflow limitationFrequency and severity of exacerbations

Comorbidities

Leonardo M. Fabbri

Clinica di Malattie dell’Apparato RespiratorioUniversità degli Studi di Modena e Reggio EmiliaAzienda Ospedaliero-Universitaria - Policlinico di Modena

Ridefinizione della Ridefinizione della BPCO e delle BPCO e delle

riacutizzazioniriacutizzazionidei sintomi in pazienti dei sintomi in pazienti

con BPCOcon BPCO

Modena 20-21 Luglio 2011

Corso di Aggiornamento su MALATTIE RESPIRATORIE