Curso Interactivo de DPOC

(1)

1 de maio – 6ª feira

Curso Interactivo de DPOC

Diagnóstico, avaliação combinada e

terapêutica

Elsa Fragoso

António Pedro Machado

(2)

O enfisema pulmonar é um diagnóstico anátomo-patológico

com maior ou menor expressão radiológica

(3)

(4)

Aumento do espaço

retroesternal

(5)

A bronquite crónica é um diagnóstico clínico

Definição

Tosse com expectoração mucosa diária,

durante 3 meses consecutivos, pelo menos

2 anos seguidos (excluídas outras causas

(6)

Bronquite crónica

Inﬂamação

Broncoconstrição

Produção

de muco

(7)

(8)

Reversibilidade da limitação do ﬂuxo das vias

aéreas com broncodilatadores

(9)

DPOC

A limitação do débito aéreo não é

completamente reversível após

(10)

Enfisema

Asma

Bronquite

crónica

DPOC

O diagnóstico de DPOC pressupõe a existência de limitação do débito

aéreo que não é completamente reversível

(11)

Sintomas

Exposição a factores de risco

• Dispneia

• Tosse produtiva crónica

• Tabaco

• Poluentes ambientais ou

ocupacionais

Necessária para estabelecer o diagnóstico

+

Diagnóstico de DPOC

Espirometria

(12)

l 

FVC

Capacidade vital forçada

(volume de ar expirado após uma inspiração máxima)

l 

FEV

₁

Volume expiratório máximo no 1º segundo

(volume de ar expirado durante o 1º segundo da manobra da FVC)

l 

Relação

FEV

₁

/ FVC

(13)

Padrão normal

(14)

Padrão normal

(15)

Diagnóstico de DPOC

FEV

₁

/ FVC pós-BD < 70 %

Um índice < 70% após broncodilatador confirma

que a limitação do débito aéreo não é

(16)

FEV

₁

/FVC

Obstrução

Pletismografia

(Referenciar)

FVC ≥ 80%

FVC ≤ 80%

Misto ou obstrução

com insuflação

Interpretação da espirometria

Normal

Pletismografia

(Referenciar)

Restrição

FVC ≥ 80%

FVC ≤ 80%

≤ 70%

≥ 70%

(17)

(18)

Diagnóstico diferencial entre Asma e DPOC

Início na idade média da vida

Início cedo na vida

Sintomas lentamente progressivos

Os sintomas variam de dia para dia

História de tabagismo de longa data

Sintomas pioram de noite/madrugada

Alergias, rinite e/ou eczema presentes

Asma

DPOC

História familiar de asma

(19)

GOLD 1

FEV

₁

após broncodilatação

Ligeira

FEV

₁

> 80% previsto

GOLD 2

Moderada

50% < FEV

₁

< 80% previsto

GOLD 3

Grave

30% < FEV

₁

< 50% previsto

GOLD 4

Muito grave

FEV

₁

< 30% previsto

Classificação da DPOC em função do grau de limitação

do fluxo aéreo

Em doentes com FEV

₁

/FVC < 70% pós-BD

(20)

Avaliação combinada da DPOC

Limitação do fluxo aéreo (GOLD 1-4)

Sintomas (escala de dispneia)

(21)

© 2015 Global Initiative for Chronic Obstructive Lung Disease

Avaliação combinada da DPOC – Classificação GOLD

(C)

(D)

(22)

Se mMRC 0-1 :

•  Menos Sintomas (A ou C)

Se mMRC ≥ 2 :

•  Mais Sintomas (B or D)

Avaliação combinada da DPOC – Classificação GOLD

Avalie os sintomas

mMRC 0-1

Pouco sintomáticos

mMRC ≥ 2

Mais sintomáticos

(C)

(D)

(A)

(B)

Sintomas

(23)

Versão modiﬁcada do Medical Research Council Dyspnoea

(mMRC)

Qual é a melhor forma de descrever a sua falta de ar?

GRAU 0 : “Só sinto falta de ar em caso de exercício Msico intenso”.

GRAU 1: “Fico com falta de ar ao apressar-‐me ou ao percorrer um

piso ligeiramente inclinado”.

GRAU 2 : “Eu ando mais devagar que as restantes pessoas devido

à falta de ar, ou tenho de parar para respirar quando ando no

meu passo normal”.

GRAU 3: “Eu paro para respirar depois de andar 100 metros ou

passados alguns minutos”.

GRAU 4: “Estou sem fôlego para sair de casa, ves<r ou despir”.

(24)

(C)

(D)

(A)

(B)

GOLD 4

Muito grave

GOLD 3

Grave

GOLD 2

Moderada

GOLD 1

Ligeira

FEV

₁

pós-BD 50%

Classificação GOLD

© 2015 Global Initiative for Chronic Obstructive Lung Disease

Avaliação combinada da DPOC – Classificação GOLD

GOLD 1

FEV

₁

após broncodilatação

Ligeira

FEV

₁

> 80% previsto

GOLD 2

Moderada

50% < FEV

₁

< 80% previsto

GOLD 3

Grave

30% < FEV

₁

< 50% previsto

GOLD 4

Muito grave

FEV

₁

< 30% previsto

Classificação da DPOC em função do grau de limitação

do fluxo aéreo

Em doentes com FEV

₁

/FVC < 70% pós-BD

(25)

(C)

(D)

(A)

(B)

≥ 2

ou

≥ 1

Com hospitalização

0-1

Sem hospitalização

Exacerbações

© 2015 Global Initiative for Chronic Obstructive Lung Disease

Avaliação combinada da DPOC – Classificação GOLD

(26)

A gravidade das exacerbações pode ser avaliada pelo aumento

da necessidade de broncodilatadores, corticóides, antibióticos

ou de internamento.

Definição

Evento agudo caracterizado por agravamento dos sintomas

respiratórios - para além das variações diárias habituais - que

obriga a modificação da terapêutica.

Exacerbação

(27)

Por que nos preocupam tanto as exacerbações?

Soler-‐Cataluña JJ et al. Thorax 2005; 60: 925-‐31

(A) Sem exacerbações

(B) 1 -2 exacerbações

com hospitalização

(C) ≥ 3 exacerbações

A

B

C

(28)

(C)

(D)

(A)

(B)

GOLD 4

Muito grave

GOLD 3

Grave

GOLD 2

Moderada

GOLD 1

Ligeira

FEV

₁

pós-BD 50%

mMRC 0-1

Pouco sintomáticos

mMRC ≥ 2

Mais sintomáticos

≥ 2

ou

≥ 1

Com hospitalização

0-1

Sem hospitalização

Exacerbações

Classificação GOLD

© 2015 Global Initiative for Chronic Obstructive Lung Disease

Avaliação combinada da DPOC – Classificação GOLD

(29)

(30)

Tratamento da DPOC estável

²  Cessação tabágica

²  Vacinação anti-influenza

²  Vacinação anti-pneumocócica

²  Reabilitação respiratória

²  Oxigenoterapia de longa duração

²  Cirurgia de redução de volume pulmonar

(31)

Terapêutica de primeira escolha da DPOC estável

(C)

(D)

(A)

(B)

SABA ou SAMA

LABA ou LAMA

LABA ou LAMA LABA e/ou LAMA

ICS

+

ICS

+

SOS

GOLD 4

Muito grave

GOLD 3

Grave

GOLD 2

Moderada

GOLD 1

Ligeira

mMRC 0-1

Pouco sintomáticos

mMRC ≥ 2

Mais sintomáticos

≥ 2

ou

≥ 1

Com hospitalização

0-1

Sem hospitalização

Exacerbações

Classificação GOLD

(32)

Critérios de referenciação à Urgência

•  Aumento acentuado da intensidade dos sintomas (dispneia em

repouso)

•  DPOC grave subjacente

•  Sinais físicos de alerta de novo (cianose, edemas)

•  Ausência de resposta à terapêutica instituída

•  Presença de comorbilidades importantes associadas (ICC,

arritmias de novo)

•  Exacerbações frequentes

•  Idade avançada

•  Suporte insuficiente no domicílio

Exacerbação – Quando referenciar

(33)

Quando está indicado iniciar AB:

Na presença dos 3 sintomas cardinais:

•  Aumento da dispneia

•  Aumento do volume da expectoração

•  Expectoração purulenta

Na presença de 2 critérios, se um deles for a

expectoração purulenta

Exacerbação – Antibioterapia em ambulatório

(34)

(35)

(36)

n engl j med 371;14 nejm.org october 2, 2014 1285

The

new england

journal

of

medicine

established in 1812 october 2, 2014 vol. 371 no. 14

Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD

Helgo Magnussen, M.D., Bernd Disse, M.D., Ph.D., Roberto Rodriguez-Roisin, M.D., Anne Kirsten, M.D., Henrik Watz, M.D., Kay Tetzlaff, M.D., Lesley Towse, B.Sc., Helen Finnigan, M.Sc., Ronald Dahl, M.D.,

Marc Decramer, M.D., Ph.D., Pascal Chanez, M.D., Ph.D., Emiel F.M. Wouters, M.D., Ph.D., and Peter M.A. Calverley, M.D., for the WISDOM Investigators*

Abstr act

The authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Magnussen at the Pulmonary Research Institute at Lung Clinic Grosshansdorf, Woehrendamm 80, D-22927 Gross hans-dorf, Germany, or at magnussen@ pulmoresearch.de.

*Investigators in the Withdrawal of Inhaled Steroids during Optimized Bronchodila-tor Management (WISDOM) study are listed in the Supplementary Appendix, available at NEJM.org.

This article was published on September 8, 2014, and updated on October 2, 2014, at NEJM.org.

N Engl J Med 2014;371:1285-94. DOI: 10.1056/NEJMoa1407154

Background

Treatment with inhaled glucocorticoids in combination with long-acting broncho-dilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorti-coids in addition to two long-acting bronchodilators has not been fully explored.

Methods

In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 µg once daily), salmeterol (50 µg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 µg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of flutica-sone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored.

Results

As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expira-tory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P = 0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group.

Conclusions

In patients with severe COPD receiving tiotropium plus salmeterol, the risk of mod-erate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.)

The New England Journal of Medicine

(37)

T h e

ne w engl a nd jour na l

o f

medicine

n engl j med 371;14 nejm.org october 2, 2014

1290

terval [CI], 0.94 to 1.19) with glucocorticoid

with-drawal as compared with glucocorticoid

continu-ation, which indicated noninferiority, since the

upper limit of the confidence interval was below

the predefined noninferiority margin of 1.20

(Fig. 2A and 2B). The results were similar in a

sensitivity analysis that included exacerbations

occurring after patients had discontinued

random-Estimated Probability 0.6 0.4 0.3 0.1 0.5 0.7 0.8 0.9 1.0 0.2 0.0 0 6 12 18 24 30 36 42 48 54 _0.8 _0.9 _1.0 _1.1 _1.2 _1.3 _1.4 _1.5 Weeks to Event

C

Severe COPD Exacerbation

A

Moderate or Severe COPD Exacerbation

D

Change from Baseline in Trough FEV₁

B

Primary End Point and Sensitivity Analyses

Hazard ratio, 1.06 (95% CI, 0.94–1.19) P=0.35 by Wald’s chi-square test

No. at Risk IGC continuation IGC withdrawal 1243 1242 10591090 927965 827825 763740 694688 646646 615607 581570 1419 IGC continuation IGC withdrawal Estimated Probability 0.6 0.4 0.3 0.1 0.5 0.7 0.8 0.9 1.0 0.2 0.0 0 6 12 18 24 30 36 42 48 54 Weeks to Event Hazard ratio, 1.20 (95% CI, 0.98–1.48) P=0.08 by Wald’s chi-square test

No. at Risk IGC continuation IGC withdrawal 12431242 11801189 11171119 10661044 1026986 993941 957918 928889 895863 2025 IGC continuation IGC withdrawal Adjusted Mean Change in FEV 1 (ml) 0 −20 −60 −40 −80 0 6 12 18 52 Week No. at Risk IGC continuation IGC withdrawal 12231218 11351135 11141092 970 935 1077 1058 IGC continuation IGC withdrawal

Primary end point Primary end point

including exacerbations on open-label therapy Primary end point

excluding baseline FEV₁ covariate IGC Continuation Better IGC Withdrawal Better

Hazard Ratio (95% CI)

Noninferiority margin

Reduced to

500 µg Reduced to200 µg Reduced to 0 µg (placebo) Daily Fluticasone Dose in Withdrawal Group

P<0.001 P=0.001 0.93 1.05 1.18 0.95 1.06 1.19 1.19 0.94 1.06

Figure 2. COPD Exacerbations and Lung Function.

Panel A shows Kaplan–Meier curves for the estimated probability of moderate or severe exacerbations of chronic obstructive pulmonary disease (COPD) during the study, with no significant difference between the group assigned to withdrawal of inhaled glucocorticoids (IGC) and the group assigned to continued IGC treatment. Panel B shows a forest plot of hazard ratios for the first COPD exacerbation (the primary end point), the primary end point including exacerbations during open-label therapy (sensitivity analysis), and the primary end point excluding the covariate of the baseline forced expiratory volume in 1 second (FEV1) (sensitivity analysis). All three categories

fall within the prespecified noninferiority margin of 1.20 (the upper limit of the 95% confidence interval for the hazard ratio in the gluco-corticoid-withdrawal group as compared with the glucocorticoid-continuation group). Horizontal dashed lines indicate 95% confidence intervals. Panel C shows Kaplan–Meier curves for the estimated probability of severe COPD exacerbations, with no significant between-group difference. Panel D shows the adjusted mean change from baseline in the FEV1, as measured during clinic visits. In the

glucocorticoid-withdrawal group, there was a significant decline in lung function at weeks 18 and 52, as compared with the change from baseline in the glucocorticoid-continuation group. I bars indicate standard errors. In Panels A and C, the study period ends at 54 weeks because some visits could not be scheduled at 52 weeks.

T h e

ne w engl a nd jour na l

o f

medicine

n engl j med 371;14 nejm.org october 2, 2014

1290

terval [CI], 0.94 to 1.19) with glucocorticoid

with-drawal as compared with glucocorticoid

continu-ation, which indicated noninferiority, since the

upper limit of the confidence interval was below

the predefined noninferiority margin of 1.20

(Fig. 2A and 2B). The results were similar in a

sensitivity analysis that included exacerbations

occurring after patients had discontinued

random-Estimated Probability 0.6 0.4 0.3 0.1 0.5 0.7 0.8 0.9 1.0 0.2 0.0 0 6 12 18 24 30 36 42 48 54 _0.8 _0.9 _1.0 _1.1 _1.2 _1.3 _1.4 _1.5 Weeks to Event

C

Severe COPD Exacerbation

A

Moderate or Severe COPD Exacerbation

D

Change from Baseline in Trough FEV₁

B

Primary End Point and Sensitivity Analyses

Hazard ratio, 1.06 (95% CI, 0.94–1.19) P=0.35 by Wald’s chi-square test

No. at Risk IGC continuation IGC withdrawal 1243 1242 1059 1090 827 825 927 965 763 740 694 688 646 646 14 19 581 570 615 607 IGC continuation IGC withdrawal Estimated Probability 0.6 0.4 0.3 0.1 0.5 0.7 0.8 0.9 1.0 0.2 0.0 0 6 12 18 24 30 36 42 48 54 Weeks to Event Hazard ratio, 1.20 (95% CI, 0.98–1.48) P=0.08 by Wald’s chi-square test

No. at Risk IGC continuation IGC withdrawal 1243 1242 11801189 11171119 10661044 1026986 993941 957918 928889 895863 2025 IGC continuation IGC withdrawal Adjusted Mean Change in FEV 1 (ml) 0 −20 −60 −40 −80 0 6 12 18 52 Week No. at Risk IGC continuation IGC withdrawal 1223 1218 11351135 11141092 970 935 1077 1058 IGC continuation IGC withdrawal

Primary end point

including exacerbations on open-label therapy Primary end point

excluding baseline FEV₁ covariate IGC Continuation Better IGC Withdrawal Better

Hazard Ratio (95% CI)

Noninferiority margin

Reduced to

500 µg Reduced to200 µg Reduced to 0 µg (placebo) Daily Fluticasone Dose in Withdrawal Group

P<0.001 P=0.001 0.93 1.05 1.18 0.95 1.06 1.19 1.19 0.94 1.06

Figure 2. COPD Exacerbations and Lung Function.

Panel A shows Kaplan–Meier curves for the estimated probability of moderate or severe exacerbations of chronic obstructive pulmonary disease (COPD) during the study, with no significant difference between the group assigned to withdrawal of inhaled glucocorticoids (IGC) and the group assigned to continued IGC treatment. Panel B shows a forest plot of hazard ratios for the first COPD exacerbation (the primary end point), the primary end point including exacerbations during open-label therapy (sensitivity analysis), and the primary end point excluding the covariate of the baseline forced expiratory volume in 1 second (FEV1) (sensitivity analysis). All three categories

fall within the prespecified noninferiority margin of 1.20 (the upper limit of the 95% confidence interval for the hazard ratio in the gluco-corticoid-withdrawal group as compared with the glucocorticoid-continuation group). Horizontal dashed lines indicate 95% confidence intervals. Panel C shows Kaplan–Meier curves for the estimated probability of severe COPD exacerbations, with no significant between-group difference. Panel D shows the adjusted mean change from baseline in the FEV₁, as measured during clinic visits. In the glucocorticoid-withdrawal group, there was a significant decline in lung function at weeks 18 and 52, as compared with the change from baseline in the glucocorticoid-continuation group. I bars indicate standard errors. In Panels A and C, the study period ends at 54 weeks because some visits could not be scheduled at 52 weeks.

Curso Interactivo de DPOC

1 de maio – 6ª feira