Ponencia del Dr. Leonardo Fabbri. Realizada en el marco del 44 Congreso de la Separ realizado en...

8/3/2019 Ponencia del Dr. Leonardo Fabbri. Realizada en el marco del 44 Congreso de la Separ realizado en Oviedo.

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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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Management of COPD:Management of COPD:

GOLD guidelinesGOLD guidelines



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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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Management of COPD:Management of COPD:

GOLD guidelinesGOLD guidelines



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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 FEV1/FVC < 70%

y 50% < FEV1 < 80%

predicted

y FEV1/FVC < 70%


y FEV1/FVC < 70%

y 50% < FEV1 < 80%

predicted

y FEV1/FVC < 70%

y 30% < FEV1

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