Modena 6-7/8-9 Settembre 2011
Corso di Aggiornamento su
MALATTIE RESPIRATORIE
Ridefinizione della
BPCO e delle
riacutizzazioni
dei sintomi in pazienti
con BPCO
Leonardo M. Fabbri
Clinica di Malattie dell’Apparato Respiratorio
Università degli Studi di Modena e Reggio Emilia
Azienda Ospedaliero-Universitaria - Policlinico di
Modena
TREATMENT TARGETS IN COPD:
CURRENT AND EVOLVING
MANAGEMENT OPTIONS
COPD and chronic comorbidities
Exacerbations in COPD
Current and future treatment
Treatment of co-morbidities of COPD
Futuristic treatments
OUTCOME OF COPD
EXACERBATIONS
In ICU patients
Hospital mortality
20%-24%
In hospitalized
patients
Hospital mortality
2.5%-10%
In ER patients
Relapse (repeat ER visit)
22%-32%
In outpatients
Treatment failure rate
13%-33%
(1 year)
(5 days)
(14 days)
(14 days)
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.
Goal of COPD Management
Overall COPD Control
achieving
Current Control
defined by
reducing
Future Risk
defined by
Symptoms
Reliever use
Exacerbations
Mortality
Activity
Lung function
Progression
of the disease
Medication
adverse effects
????? GOLD 2011 www.goldcopd.org
COPD exacerbations
COPD
Chronic disease
progressive nature
Exacerbations
• typically 1 - 3 per year
• lung function
• frequency proportional
to COPD severity
• symptoms
• the frequent exacerbator
• comorbidities
• chronic decline resulting
in poorer prognosis
  HRQL
Tashkin D. N Engl J Med 2010; 363: 1184
Hurst et al, N Engl J Med 2010; 363: 1128-38
  hospitalizations
  mortality
ASSOCIATION OF DISEASE SEVERITY WITH THE FREQUENCY
AND SEVERITY OF EXACERBATIONS DURING THE FIRST YEAR
OF FOLLOW-UP IN PATIENTS WITH COPD
% of patients
50
40
47
Hospitalized for exacerbation in yr 1
Frequent exacerbations
33
33
30
22
20
10
0
18
7
GOLD 2
(N=945)
GOLD 3
(N=900)
GOLD 4
(N=293)
Hurst J.R. et al., N Engl J Med 2010; 363: 1128-38
STABILITY OF THE FREQUENT-EXACERBATION PHENOTYPE IN
THE 1679 PATIENTS WITH CHRONIC OBSTRUCTIVE
PULMONARY DISEASE WHO COMPLETED THE STUDY
Year 1
Year 3
Year 2
Patients with no
exacerbation
0
20 40 60 80 100
0
20 40 60 80 100 2%
Patients with 1
exacerbation
0
Patients with ≥ 2
20 40 60 80 100
Percent
exacerbations
0
20 40 60 80 100
Percent
0
2%
1%
0
20 40 60 80 100
0
20 40 60 80 100 3%
0
20 40 60 80 100
0
20 40 60 80 100
20 40 60 80 100
Percent
0
0
23
%
6%
2%
6%
3%
2%
5%
3%
1%
2%
2%
2%
2%
3%
2%
1%
1%
20 40 60 80 100 2%
0
20 40 60 80 100
0
20 40 60 80 100
Percent
20 40 60 80 100
Percent
2%
3%
1%
4%
12
%
Hurst J.R. et al., N Engl J Med 2010; 363: 1128-38
Breast Cancer Diseases - 2015
ER+
65-75%
PI3Kmut
10%
HER3+
IGFR1+
All Breast Cancers
HER2+
15-20%
p95+
4%
P53mut
30-40 %
FGFR1
Ampl 8%
Triple
negative
15% PTENloss
30-50%
BRCAMut
8%
BAC EGFR mut+: Response to TKI
12-00
12-02
INTACT 1: Lack of benefit in combination with
chemotherapy
Proportion
event
free
Median survival, months
1-year survival rate, %
Log rank vs placebo
1.0
0.8
9.92
43
0.7759
(p=0.4377)
WE DIDN’T KNOW ABOUT
EGFR MUTATION
0.6
9.86
41
1.0290
(p=0.3034)
11.07
45
Gefitinib 500 mg/day
Gefitinib 250 mg/day
Placebo
0.4
0.2
0.0
At risk
0
4
1093
898
Population: intention to treat
8
12
16
Survival time (months)
641
463
152
20
11
24
K Kobayashi et al, P ASCO 2009
CAUSES OF EXACERBATION OF
RESPIRATORY SYMPTOMS IN CHRONIC
PATIENTS
PNEUMONIA
THROMBOEMBOLISM
ACUTE HEART FAILURE
METABOLIC ACIDOSIS
ANEMIA
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 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
LUNG FUNCTION IN PATIENTS
ADMITTED WITH HEART FAILURE
Prognostic importance for all-cause mortality
of lung function variables obtained by
spirometry in an unselected group of patients
admitted with heart failure (HF)
Iversen KK et al, Eur J Heart Fail. 2010
Jul;12(7):685-91.
TARGETING THE LUNG
ATTACKS
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 community
FitzGerald JM, Thorax May 2011 Vol 66 No 5
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 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).
CORSO DI AGGIORNAMENTO SU MALATTIE RESPIRATORIE
Modena 20-21 Luglio 2011
INTRODUZIONE E LINEE GUIDA PER LA BPCO
Leonardo M. Fabbri
COPD and chronic comorbidities
Exacerbations in COPD
Current and future treatment
Treatment of co-morbidities of COPD
Futuristic treatments
SYSTEMIC EFFECTS AND COMORBIDITIES OF
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Barnes PJ et al., Eur Respir J 2009;33:1165–1185
Severity of airflow limitation
Frequency and severity of exacerbations
Comorbidities
Modena 20-21 Luglio 2011
Corso di Aggiornamento su
MALATTIE RESPIRATORIE
Ridefinizione della
BPCO e delle
riacutizzazioni
dei sintomi in pazienti
con BPCO
Leonardo M. Fabbri
Clinica di Malattie dell’Apparato Respiratorio
Università degli Studi di Modena e Reggio Emilia
Azienda Ospedaliero-Universitaria - Policlinico di
Modena