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Riacutizzazione di BPCO. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Riacutizzazioni: definizione

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slide2
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

costi delle aecb
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

definition
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

cause di riacutizzazioni
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.

modifiable risk factors in patients with copd exacerbation efram study
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

aecb etiology
AECB ETIOLOGY

Papi A et al. AJRCCM 2006

slide9

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

rsv pcr in stable copd and at exacerbation seemungal et al am j respir crit care med 2001
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
changes in bacterial load n 57
CHANGES IN BACTERIAL LOADn=57

*p=0.0001

Bacterial Load

Log cfu/ml

slide12

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

slide13

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

relative risk of exacerbation and bacterial strain change
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

slide16

INTERACTION OF BACTERIAL AND VIRAL INFECTION

Wilkinson et al Chest 2006; 129:317-324

slide19

ALTERAZIONI STRUTTURALI

VIE AEREE-PARENCHIMA

COLONIZZAZIONE

BATTERICA

OSTRUZIONE BRONCHIALE

INSUFFLAZIONE

RIACUTIZZAZIONI

DISPNEA

LIMITAZIONE SFORZO

PEGGIORAMENTO Q of L

slide21

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%

slide22

NATURAL HISTORY OF COPD

Never smoked

Exacerbation

Lung Function

Smoker

Exacerbation

Exacerbation

Time (Years)

Fletcher C. BMJ 1977;1:1645-1648.

slide23

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

slide24

Relationship between lung function and exacerbations

Exacerbations increase as lung function declines.

slide25

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

slide26

INTERACTION OF BACTERIAL AND VIRAL INFECTION

Wilkinson et al, Chest 2006; 129:317-324

slide27

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

slide28

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

variazione percentuale del fev1 in 4 anni
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

slide31

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.

slide32

Exacerbation Rate by FEV1

Donaldson & Wedzicha Thorax 2006;61:164

slide33

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.

slide34

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.

slide35

Symptoms worsen during the 2 days preceding an exacerbation

Pauwels et al. Am J Respir Crit Care Med 2003; 167(7): A949

slide36

INTERACTION OF BACTERIAL AND VIRAL INFECTION

Wilkinson et al Chest 2006; 129:317-324

slide37

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

slide38

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.

exacerbations and quality of life
Exacerbations and quality of life

P < 0.0005

SGRQ Score

3 - 8

Exacerbations/year

Seemungal TAR et al, AJRCCM 1998; 157: 1418

slide40

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

copd exacerbations health status
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

slide42

Relationship between exacerbations and mortality

Exacerbations increase the risk of death in patients with COPD.

outcome delle aecb mortalit
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

sopravvivenza associata a aecb grave
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

copd exacerbations mortality
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

copd exacerbations survival

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

copd exacerbations survival1

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

slide49

Airway inflammation and aetiology

of COPD exacerbations

Sethi et al Chest 2000

slide51

EFFECT OF CHLAMYDIA INFECTION

ON INDUCED SPUTUM IL-6

Seemungal et al Thorax 2002

slide52

Microbial patterns in outpatients with COPD exacerbations and risk factors for a complicated course

2180 patients,

777 isolates of 673 patients

Inclusion criteria:

age > 40 years

 3 exacerb./year

 3 comorbidities

treatment failure

or

high prevalence of

resistant pathogens

%

Anzueto et al., Clin Ther, 1998

fattori associati indipendentemente con l isolamento dei pi comuni patogeni
Fattori associati indipendentemente con l’isolamento dei più comuni patogeni

Rapporto di

Germi

Variabile dipendente

LC 95%

probabilità

Non- ed ex-fumatori

H. influenzae

8,16

1,9-43,0

vs fumatori

FEV1

6,85

1,6-52,6

> 50% vs <50%

P. aeruginosa

6,62

1,21-123,6

FEV1

> 50% vs <50%

S. pneumoniae

Mesi

dall’ultima

5,02

1,12-35,7

riacutizzazione

<2 vs >2

------

------

------

M. catarrhalis

Miravilles et al, 1999

slide54

Predictors of pathogens in hospitalized patients

with COPD exacerbations

%

Eller et al., Chest 1998

slide55

Predictors of pathogens in patients with

COPD exacerbations treated in the ICU

%

heterogeneity of copd exacerbations
Heterogeneity of COPDexacerbations
  • The cause of an exacerbation can include acute viral bronchitis, environmental pollutants, and allergic responses as well as bacterial infections.
  • Patients with similar degree of airflow limitation may have different rates of exacerbations, with a minority of the patients presenting with more than two exacerbations per year (frequent exacerbators).
slide57
Le manifestazioni cliniche non permettono di identificare le cause della riacutizzazione, perché virus e atipici sono associati con gli stessi sintomi e grado di risposta infiammatoria.
  • Solo la presenza di escreato purulento è stata associata ad elevata carica batterica nelle secrezioni respiratorie durante le riacutizzazioni
slide58

CLASSIFICAZIONE DELLE RIACUTIZZAZIONI DELLA BRONCHITE CRONICA BASATA SUI SINTOMI

Esacerbazioni Sintomi cardinali

Tipo I • Tutti:

Aumento dispnea

Aumento volume escreato

Aumento escreato purulento

Tipo II • Due dei sintomi sopra citati

Tipo III • Uno dei sintomi del Tipo I + uno tra i seguenti:

Infezione delle vie respiratorie superiori

nei 5 giorni precedenti

Febbre senza altre cause

Incremento del “wheezing”

Incremento della tosse

Incremento della frequenza respiratoria

o cardiaca

Anthonisen 1987

operational classification of severity of exacerbations
Operational Classification of Severity of Exacerbations
  • The Operational Classification of Severity is as follows: ambulatory (Level I), requiring hospitalisation (Level II) and acute respiratory failure (Level III).

+: unlikely to be present; ++: likely to be present; +++: very likely to be present

ERS-ATS COPD Guidelines

slide61

Meta-analyses of typical study demographics showed that there was significant overlap in 95% CI and study data distributions for the three exacerbation severity levels

Franciosi et al, Respir Res 2006; 7:74

fixed effect meta analysis results of selected spirometry variables
Fixed Effect Meta-Analysis Results of Selected Spirometry Variables

P < 0.017 is indicated for statistical comparisons of Level I versus II (*), II versus III (†), and I versus III (#) as well as P < 0.05 for comparison of out- versus in-patient setting (*)

fixed effect meta analysis results of selected clinical variables
Fixed Effect Meta-Analysis Results of Selected Clinical Variables

P < 0.017 is indicated for statistical comparisons of Level I versus II (*), II versus III (†), and I versus III (#) as well as P < 0.05 for comparison of out- versus in-patient setting (*)

fixed effect meta analysis results of selected clinical variables1
Fixed Effect Meta-Analysis Results of Selected Clinical Variables

P < 0.017 is indicated for statistical comparisons of Level I versus II (*), II versus III (†), and I versus III (#) as well as P < 0.05 for comparison of out- versus in-patient setting (*)

slide65
The current management and treatment of COPD exacerbations is primarily dependent on the evaluation of the symptoms rather than the signs related to the exacerbation event.
  • Arterial carbon dioxide tension and breathing rate consistently varied with the severity of COPD exacerbations and with in- versus out-patients.
  • Other commonly-accepted measures and suggested biomarkers for exacerbations failed to show consistent trends or lacked sufficient data to permit any meta-analysis.

Franciosi et al, Respir Res 2006; 7:74

slide66
PLASMA FIBRINOGEN AT EXACERBATIONWedzicha et al Thrombosis and Hemostasis2000Seemungal et al Am J Respir Crit Care Med 2001

N = 120 Exacerbations

  • Increased fibrinogen with colds P = 0.02
  • Increased fibrinogen with sputum purulence P = 0.03
  • Rise 0.56 g/l during viral Exs
  • Rise in 0.27 g/l during non-viral Exs
  • P = 0.056

P<0.001

P<0.001

4.3

4.2

4.1

4

Fibrinogen g/l

3.9

3.8

3.7

3.6

3.5

3.4

Stable

Exacerbation

Convalescence

Mean ± SEM

slide67

AE-COPD: Procalcitonin

Patient & Prescriber

factors

Procalcitonin-guided antibiotic therapy in acute exacerbations of COPD: a randomised trial - The ProCOLD Study: D. Stolz, M. Christ-Crain, R. Bingisser, M. Gencay, J. Leuppi, D. Miedinger, C. Müller, P. Huber, B. Müller, M. Tamm. ERS Copenhagen, 2005

slide68

Prescriber factors

Evidence in favor: Stockley

Stockley RA, O'Brien C, Pye A, Hill SL. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest 2000; 117(6):1638-1645.

slide69

Prescriber factors

Consequence: Stockley data

Bronko Test Chart

Cut-off color

Stockley RA, O'Brien C, Pye A, Hill SL. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest 2000; 117(6):1638-1645.

slide70

Relation of

severity of COPD and acute exacerbation

copd exacerbations early therapy and recovery
COPD exacerbations: Early therapy and recovery

24

0.42 d/d-delay

(p<0.001)

18

12

Symptom recovery time (days)

6

0

0

14

7

Delay between onset and treatment (days)

Wilkinson TMA et al. Am J Respir Crit Care Med. 2004;169:1298-303

bacterial eradication vs failure rate
Bacterial Eradication vs Failure Rate

y= 0.5785x + 5.7679

r=0.91

Clinical failure rate (%)

Eradication failure rate (%)

Pechere JC et al. J Antimicrob Chemo 2000;45:19-24

slide73
Criteri per decidere se trattare una riacutizzazione di BPCO a casa o in ospedale. I.(BTS guidelines 1997)
slide74
Criteri per decidere se trattare una riacutizzazione di BPCO a casa o in ospedale. II.(BTS guidelines 1997)
slide75

Criteri per decidere se trattare una riacutizzazione di BPCO a casa o in ospedale. III.Da valutare con l’ausilio ospedaliero(BTS guidelines 1997)

slide76

Criteria for hospitalization

ATS standards of care 1995

ERS / ATS guidelines 2004

slide77

INDICAZIONI PER L’AMMISSIONE A REPARTI SPECIALIZZATI O DI TERAPIA INTENSIVA

Presenza di gravi disfunzioni respiratorie

Ammissione nel reparto di terapia intensiva

INDICAZIONI PER RICOVERO IN ICU:

  • insufficienza respiratoria
  • presenza di altre disfunzioni di end-organ
  • shock
  • disturbi renali, epatici o neurologici
  • instabilità emodinamica
slide78

Criteria for ICU admission

ATS standards of care 1995

ERS / ATS guidelines 2004

slide79

Quanto maggiore è la presenza dei succitati indicatori, tanto più pressante è la necessità di ospedalizzare il paziente

outcome delle aecb insuccesso terapeutico
Outcome delle AECB:insuccesso terapeutico

Pazienti ospedalizzati

Recidiva (ripetute visite di emergenza)

19%

Pazienti ambulatoriali

Tasso di insuccesso terapeutico

19-32%

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

slide81

Predictors of outcome

in outpatients with acute COPD exacerbations

Odds of failure in relation to home oxygen therapy

and number of exacerbations over 24 months

Dewan NA et al., Chest 2000

slide82

Predictors of outcome

in hospitalized patients with acute COPD exacerbations

1400 admissions from 38 hospitals

14 % died within 3 months

However:

variation between hospitals 0-50%

Roberts CM et al., Thorax 2002

lower lobe bronchiectasis and exacerbation recovery patel et al ajrccm 2004
LOWER LOBE BRONCHIECTASIS AND EXACERBATION RECOVERYPatel et al AJRCCM 2004

Patients with lower lobe score 0 or 1/8

time to recovery of symptoms = 10 days

Patients with lower lobe score >/=2/8

time to recovery of symptoms = 12 days

p = 0.001

slide84

Predictors of outcome (mortality)

in hospitalized patients with acute COPD exacerbations

590 patients hospitalized in a university hospital

Mortality rate 14,4 %

Fuso L et al., Am J Med 1995