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Leonardo M. Fabbri
Clinica di Malattie dellApparato Respiratorio
Universit degli Studi di Modena e Reggio Emilia
Azienda Ospedaliero-Universitaria - Policlinico di
Modena
Management of COPD:Management of COPD:GOLD guidelinesGOLD guidelines
SEPAR44th National Congress
Oviedo, 17 June 2011
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COPD and chronic comorbidities
Exacerbations in COPD
Current and future treatment
Treatment of co-morbidities of COPD
Futuristic treatments
MANAGEMENT OF COPDMANAGEMENT OF COPD
Leonardo M. FabbriLeonardo M. Fabbri
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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 characterizedby chronic respiratory symptoms, particularlydyspnea and persistent airflow limitation that is usually progressiveand associated with an enhanced chronic inflammatory response of
the airways and the lungto cigarette smoke and/or other noxious
particles or gases.Exacerbations, significant concomitant disorderscontribute to the overall severity in individual patients.
Bologna 8 Febbraio 2011
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Courtesy of PW Jones, 2011
CHANGING CONCEPTS IN COPD ASSESSMENT OF
SEVERITY AND MANAGEMENT OF COPD
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COMPLEX CHRONICCOMPLEX CHRONICCOCO--MORBIDITIES OF COPDMORBIDITIES OF COPD
Fabbri, Beghe, Luppi and Rabe, Eur Respir J 2008;31:204-212
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55--yrs mortalityyrs 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 CardiovascularHealth Study (CHS).
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Clinical practice guidelines (CPGs) and quality ofClinical practice guidelines (CPGs) and quality of
care for older patients with multiple comorbidcare for older patients with multiple comorbid
diseases: implications for pay for performancediseases: implications for pay for performance
BoydCet al JAMA. 2005Aug 10;294(6):716BoydCet al JAMA. 2005Aug 10;294(6):716--2424
This review suggests that adhering to current CPGs in caringThis review suggests that adhering to current CPGs in caring
for an older person with several comorbidities may havefor an older person with several comorbidities may have
undesirable effectsundesirable effects
Basing standards on existing CPGs could lead toBasing standards on existing CPGs could lead to
inappropriate judgment of the care provided to older individualsinappropriate judgment of the care provided to older individuals
with complex comorbiditieswith complex comorbidities
Developing measures of the quality of the care needed byDeveloping measures of the quality of the care needed by
older patients with complex comorbidities is critical toolder patients with complex comorbidities is critical toimproving their careimproving their care
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COPD and chronic comorbidities
Exacerbations in COPD
Current and future treatment
Treatment of co-morbidities of COPD
Futuristic treatments
Management of COPD:Management of COPD:
GOLD guidelinesGOLD guidelines
Leonardo M. FabbriLeonardo M. Fabbri
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20%20%--24%24%(1 year)(1 year)
2.5%2.5%--10%10%(5 days)(5 days)
22%22%--32%32%(14 days)(14 days)
13%13%--33%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 hospitalizedIn hospitalized
patientspatients
In ER patientsIn ER patients
In ICU patientsIn ICU patients
In outpatientsIn outpatients
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PNEUMONIA
THROMBOEMBOLISM
ACUTE HEART FAILURE
METABOLIC ACIDOSIS
ANEMIA
CAUSES OF EXACERBATION OF
RESPIRATORY SYMPTOMS IN CHRONIC
PATIENTS
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THE PROGNOSTIC IMPORTANCE OFTHE PROGNOSTIC IMPORTANCE OF
LUNG FUNCTION IN PATIENTSLUNG FUNCTION IN PATIENTS
ADMITTED WITH HEART FAILUREADMITTED WITH HEART FAILURE
Prognostic importance for allPrognostic importance for all--cause mortalitycause mortality
of lung function variables obtained byof lung function variables obtained by
spirometryspirometry in an unselected group of patientsin an unselected group of patients
admitted with heart failure (HF)admitted with heart failure (HF)
IversenIversen KK et al,KK et al, EurEur J Heart Fail. 2010 Jul;12(7):685J Heart Fail. 2010 Jul;12(7):685--91.91.
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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 ofother known prognostic indicators
The pathophysiological basis for this is unknown, but
indicates that cardiac involvement in exacerbations of COPDmay be an important determinant of prognosis
ChangChangCL et al,CL et al, ThoraxThorax in pressin press
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CARDIOVASCULAR MECHANISMS OF
DEATH IN SEVERE COPD EXACERBATION: TIME TO
THINK AND ACT BEYOND GUIDELINES
Patients hospitalized because of ECOPD should be carefully
examined for the relevant biomarkers and for any
concomitant abnormality that may call for specific therapy
This in line with the recent editorial of FitzGerald20 and
comment by the Editors of Thorax who recommends
replacing the term exacerbations with the term lung attacks
to emphasise their severity, dramatic consequences, andneed for more aggressive, comprehensive and prolonged
treatment
FabbriLM, Beghe B andFabbriLM, Beghe B and AgustiAgusti A,A, ThoraxThorax,, JuneJune 20112011
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Goal of COPD Management
Overall COPD Control
Current Control Future Risk
Symptoms
Activity
Reliever use
Lung function
Exacerbations
Progression
of the disease
Mortality
Medication
adverse effects
achieving reducing
defined by defined by
????? GOLD 2011 www.goldcopd.org
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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 proportional
to COPD severity
the frequent exacerbator
chronic decline resultingin poorer prognosis
q HRQL
o hospitalizations
o mortality
COPD exacerbations
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ASSOCIATION OF DISEASESEVERITY WITHTHE FREQUENCYAND SEVERITY OF EXACERBATIONS DURING THE FIRSTYEAR
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
fpatients
(N=900) (N=293)
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0 20 40 60 80 100
Percent
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 80 100
Percent
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 INTHE 1679 PATIENTS WITH CHRONIC OBSTRUCTIVEPULMONARY DISEASE WHO COMPLETED THESTUDY
Hurst J.R. et al., N Engl J Med 2010; 363: 1128-38
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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%
PTENloss30-50%
PI3Kmut10%
BRCAMut8%
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TARGETED THERAPIES IN A-NSCLC
Positive Phase III Studies
Monotherapy
ComboTherapy
Erlotinib
BR.21
Bevacizumab
ECOG 4599/AVAiL
Gefitinib
IPASS/INTEREST/NEJG002
EGFR Mut+
1st
Line
A-NSCLC
Cetuximab
FLEX
NotRegistere
d!
2nd /3rd
Line
2005 2008 20092007
EGFR Mut+
Alllines
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COPD and chronic comorbidities
Exacerbations in COPD
Current and future treatment
Treatment of co-morbidities of COPD
Futuristic treatments
Management of COPD:Management of COPD:
GOLD guidelinesGOLD guidelines
Leonardo M. FabbriLeonardo M. Fabbri
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Add inhaled glucocorticosteroids if repeatedexacerbations
IV: Very SevereIII: SevereII: ModerateI: Mild
Therapy at Each Stage of COPDTherapy at Each Stage of COPD
y FEV1/FVC < 70%
y FEV1 > 80%predicted
y FEV1/FVC < 70%
y 50% < FEV1
< 80%predicted
y FEV1/FVC < 70%
y 30% < FEV1 80%predicted
y FEV1/FVC < 70%
y 50% < FEV1 < 80%predicted
y FEV1/FVC < 70%
y 30% < FEV1 80%predicted
y FEV1/FVC < 70%
y 50% < FEV1 < 80%
predicted
y FEV1/FVC < 70%
y 30% < FEV1 80%predicted
y FEV1/FVC < 70%
y 50% < FEV1 < 80%
predicted
y FEV1/FVC < 70%
y 30% < FEV1