Gerichte therapie bij Astma COPD overlap syndroom · 3 Achtergrond • Asthma vs. COPD Asthma COPD Diagnose Laboratorium Allergie (IgE, eosinophielen) Geen Pulmonary function Normaal

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Dr. Tobias Bonten

AIOS Huisartsgeneeskunde, Postdoc en Epidemioloog

Longziekten en Public Health & Eerstelijns Geneeskunde

LEIDS UNIVERSITAIR MEDISCH CENTRUM

Gerichte therapie bij Astma COPD overlap syndroom

(potentiële) belangenverstrengeling Geen

Disclosure belangen spreker

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GERICHTE BEHANDELING

9-Feb-173

Achtergrond

• Astma vs. COPD

9-Feb-174

Astma COPD

Risico factor Atopie (allergie) Roken / luchtverontreiniging

Leeftijd Alle (meestal begin<20)

Meestal >40

Symptomen

Hoesten Ja Ja

Slijm Niet vaak Vaak

Adem geluiden Piepen Piepen, gereutel

Kortademigheid Wisselend Persisterend(exacerbaties)

Prognosis Stabiel, normalelevensverwachting

Progressief, verminderdelevensverwachting

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Achtergrond

• Asthma vs. COPD

Asthma COPD

Diagnose

Laboratorium Allergie(IgE, eosinophielen)

Geen

Pulmonary function Normaal of reversibele obstructie

Irreversibeleobstructie

Achtergrond

• Astma EN COPD? Astma COPD overlap syndroom (ACOS)

?

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ACOS ?

2. Australian Asthma management HandbookPooling of features corresponding to asthma and COPD, followed by a trial of Inhalation Corticosteroids

1. GINA/GOLD (guideline)List 9 features: similar number of asthma and COPD features ACOS more likely; spirometry recommended

3. Japanese Respiratory Society COPD guidelinesAsthma component: paroxysmal dyspnoea, cough and wheeze worse at night and early morning, atopy, sputum/blood eosinophilia.

4. Spanish COPD consensus document- Major criteria:

- Increase FEV1 ≥ 15% and ≥400ml- Eosinophilia- History of asthma

- Minor criteria:- Total IgE- Atopy- ≥2 ocassions: FEV1 ≥ 12% and ≥200ml

ACOS if 2 major 1 major + 2 minor

5. Czech Pneumological and Physiological Society- Major criteria:

- Increase FEV1 ≥ 15% and ≥400ml- Positive provocation test- FeNO ≥ 45-50 ppb and/or sputum eosinophils ≥3%- History of asthma

- Minor criteria:- FEV1 ≥ 12% and ≥200ml- Total IgE- Atopy and COPD diagnosis

ACOS if 2 major 1 major + 2 minor

Gibson PG, et al. Thorax 2015

ACOS fenotypen…?

Bateman, Lancet Respir Med 2015

CHAOS instead of ACOS?

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Overzicht

1. Is ACOS klinisch relevant?

2. Hoe vaak komt ACOS voor?

3. Identificeren van ACOS in de eerste lijn

4. Adviezen over behandeling van ACOS

9-Feb-179 Insert > Header & footer

Overzicht






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ACOS – klinisch relevant?

Nielsen M, et al. Int J COPD 2015

Frequency of exacerbations among ACOS patients is higher than in Asthma or COPD

ACOS – klinisch relevant? Eigen onderzoek bij 864 patienten met Astma/COPD

1. COPD AND Asthma in registry

2. COPD AND Asthma in registry OR ACOS as text in EMR

3. Self-reported COPD AND Asthma

4. FEV1/FVC < 0.7 AND ≥10 pack-years AND asthma <40 years

5. COPD in registry OR self-reported + FEV1/FVC < 0.7

AND

Asthma in registry OR Self-reported

6. COPD in registry OR Self-reported + FEV1/FVC < 0.7

AND

Asthma in registry OR Self-reported OR FENO ≥ 45 ppb

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• 864 patiënten met Astma/COPD

• Follow-up 1.8jr

• Exacerbatie: voorschrift corticosteroid of antibioticum door huisarts

* adjusted for: age, sex, bmi, current smoking, FEV1/FVC ratio at baseline, ICS use, number of exacerbations in previous year


* adjusted for: age, sex, bmi, current smoking, FEV1/FVC ratio at baseline, ICS use, number of exacerbations in previous year

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Survival is worse among ACOS patients than in Asthma or COPD, depending on age of asthma onset

Lange P, Lancet Resp Med 2016


ACOS – relevant for society?

Gerhardsson de Verdier M, Val Health 2015

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Overzicht






Eerdere studies Karakteristieken en ACOS prevalentie

Study Population Age Prevalence (%) Definition

Brzostek Smoking >45 100 Doctor diagnosed asthma + COPD

Fu Asthma, COPD, ACOS

>55 55.5 Symptoms, flow variability, incomplete reversible obstruction

Lee Asthma, ACOS 41-79 37.9 Asthma with incomplete reversible obstruction

Milanese Asthma ≥65 28.8 Asthma and chronic bronchitis and/or impaired diffusion

Miravitles COPD, ACOS 40-80 17.7 COPD (FEV1/FVC <0.7) and doctor diagnosed asthma <40yr

Kauppi Asthma, COPD, ACOS

18-75 14.5 Doctor diagnosed asthma + COPD (FEV1/FVC <0.7)

Hardin COPD, ACOS 45-80 12.6 COPD with self-reported asthma <40yr

de Marco General 20-84 1.6-4.5 Doctor diagnosed asthma + COPD

Pleasants General 18-74 3.3 Self-reported COPD and asthma

Chung General >19 2.3 FEV1/FVC <0.7 + self-reported wheezing history

Menezes General >40 1.8 Asthma (symptoms+spirometry / self-reported) and COPD (FEV1/FVC <0.7)


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Eerdere studies Karakteristieken en ACOS prevalentie

Study Population Age Prevalence (%) Definition

Brzostek Smoking >45 100 Doctor diagnosed asthma + COPD

Fu Asthma, COPD, ACOS

>55 55.5 Symptoms, flow variability, incomplete reversible obstruction

Lee Asthma, ACOS 41-79 37.9 Asthma with incomplete reversible obstruction

Milanese Asthma ≥65 28.8 Asthma and chronic bronchitis and/or impaired diffusion

Miravitles COPD, ACOS 40-80 17.7 COPD (FEV1/FVC <0.7) and doctor diagnosed asthma <40yr

Kauppi Asthma, COPD, ACOS

18-75 14.5 Doctor diagnosed asthma + COPD (FEV1/FVC <0.7)

Hardin COPD, ACOS 45-80 12.6 COPD with self-reported asthma <40yr

de Marco General 20-84 1.6-4.5 Doctor diagnosed asthma + COPD

Pleasants General 18-74 3.3 Self-reported COPD and asthma

Chung General >19 2.3 FEV1/FVC <0.7 + self-reported wheezing history

Menezes General >40 1.8 Asthma (symptoms+spirometry / self-reported) and COPD (FEV1/FVC <0.7)


Eigen onderzoek bij 864 patienten met Astma/COPD

9-Feb-1720

Prevalence

Total population

Asthma/COPDpopulation

ACOS Definition n = 5647 n = 846

1 COPD AND Asthma in registry 1.2 10.3

2 COPD AND Asthma in registry OR ACOS as text in EMR 1.2 10.3

3 Self-reported COPD AND Asthma 0.5 4.4

4 FEV1/FVC < 0.7 AND ≥10 pack-years AND asthma <40 years 0.6 4.7

5 COPD in registry OR self-reported + FEV1/FVC < 0.7 AND

Asthma in registry OR Self-reported

1.1 9.1

6 COPD in registry OR Self-reported + FEV1/FVC < 0.7 AND

Asthma in registry OR Self-reported OR FENO ≥ 45 ppb

4.9 38.2

Bonten TN et al: Defining Asthma COPD overlap syndrome: a population based study. ERJ 2017, accepted for publication

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Overzicht






ACOS ?

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Simpeler oplossing?Bij patiënten met COPD

ACOS 1: Spaanse consensus criteria

versus

ACOS 2: Alleen astma < 40 jaar, diagnosed only on the basis of a history of

asthma before the age of 40 years

Barrecheguren, Int J COPD 2015

Prevalentie


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ConclusieSimpeler oplossing voor eerste lijn?

Patients diagnosed with ACOS in COPD on the basis of a previous diagnosis of

asthma before the age of 40 years are very similar to patients diagnosed with

ACOS by the more restrictive criteria proposed by the Spanish consensus.

Therefore, the previous diagnosis of asthma before 40 years of age in a patient

with COPD can be used as a presumptive diagnosis of ACOS.


Overzicht






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ACOS – relevant voor behandeling?Timing van ICS

9-Feb-1727

STEP 1 STEP 2STEP 3

STEP 4

STEP 5

Low dose ICS

Consider low

dose ICS Leukotriene receptor antagonists (LTRA)

Low dose theophylline*

Med/high dose ICS

Low dose ICS+LTRA

(or + theoph*)

As-needed short-acting beta2-agonist (SABA)

Low dose

ICS/LABA*

Med/high

ICS/LABA

Refer for add-on

treatment e.g.

anti-IgE

Add tiotropium#

High dose ICS

+ LTRA

(or + theoph*)

Add tiotropium#Add low dose OCS

As-needed SABA or low dose ICS/formoterol**

COPD: ICS= step 3

Asthma: ICS= step 1-2

GINA-GOLD

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GINA-GOLD: treatment ACOS

Initial treatment:

- Patients with features of asthma: receive adequate controller

therapy including inhaled corticosteroids, but not long-acting

bronchodilators alone (as monotherapy)

- Patients with features of COPD: receive appropriate

symptomatic treatment with bronchodilators or combination

therapy, but not inhaled corticosteroids alone (as

monotherapy).

www.ginaasthma.org

Hoe behandelen NL huisartsen patiënten met ACOS?

9-Feb-1730

Bonten TN et al: Defining Asthma COPD overlap syndrome: a population based study. ERJ 2017, accepted for publication

1 2 3 4 5 6

Characteristic COPD in registry+

Asthma in registry

COPD in registry+

Asthma in registry

OR

ACOS as text in electronic record

COPD self-reported

+ Asthma

self-reported

FEV1/FVC < 0.7 +

≥10 pack-years+

asthma <40 years

COPD in registry OR

Self-reportedAND

FEV1/FVC < 0.7 +

Asthma in registry OR

Self-reported

COPD in registry OR

Self-reported OR

FEV1/FVC < 0.7 +

Asthma in registry OR

Self-reported OR

FENO ≥ 45

Medication use

SABA 15 15 29 42 22 20

LABA 6 6 6 0 1 4

LAMA 13 13 17 6 15 9

ICS 13 13 18 33 23 15

Combination LABA+ICS

45 45 56 38 48 40

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Take home messages

1. Is ACOS klinisch relevant? Hogere kans op exacerbaties dan

astma patiënten, hogere mortaliteit

2. Hoe vaak komt ACOS voor? ± 10% in 1e lijns astma/COPD

populatie

3. Identificeren van ACOS in de eerste lijn: voorgeschiedenis van

astma/symptomen bij COPD’er, bij hoge ziektelast verwijzen

naar longarts voor diagnostiek

4. Adviezen over behandeling van ACOS: ICS afhankelijk van

klachtenpatroon. Eenmalige verwijzing naar longarts voor

diagnostiek en behandeladvies?

9-Feb-1731

DankwoordLeiden University Medical Center study team


Prof. Niels Chavannes

Prof. Christian Taube

Dr. Marise Kasteleyn

Prof. Pieter Hiemstra

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Evt. extra slides


Defining ACOS – Patient examples


Postma DS, Rabe KF. N Engl J Med 2015;373:1241-1249.

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Defining ACOS

9-Feb-1735

Postma DS, Rabe KF. N Engl J Med 2015;373:1241-1249.

Documents

Gerichte therapie bij Astma COPD overlap syndroom · 3 Achtergrond • Asthma vs. COPD Asthma COPD Diagnose Laboratorium Allergie (IgE, eosinophielen) Geen Pulmonary function Normaal