Fabiano Di Marco

The 2017 GOLD «approach»

Margherita

The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).

Blood eosinophilia and response to ICS in COPD

Pascoe S. et al, Lancet RM 2015

Why are illustrative cases important?“In real-life settings, more than 80% of COPD subjects

are currently treated by protocols based on results of

RCTs for which they would not have been eligible.”

Scichilone N, et al. Respiration 2014;87:11–7COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second; RCT = randomized controlled trial

Giacomo• 55-year-old male• Former smoker (quit aged 50, smoking history 35 pack years)• Diagnosed with COPD 3 years ago• Complaint of progressively worsening dyspnea (mMRC 3)• No history of exacerbation in the previous year• Past medical history uneventful, with the exception of COPD

(maintenance treatment with ICS/LABA FDC as suggested by his GP)• Physical examination unremarkable, aside from diminished breath

sounds on both lungs

Giacomo

GP = General Practitioner; ICS = inhaled corticosteroid; LABA = long-acting β2-agonist; mMRC = modified Medical Research CouncilPicture for illustrative purposes only.

SpirometryForced vital capacity

Flow

(L/s

)

Giacomo

FET = forced expiratory time; FVC = forced vital capacity; MEF = middle of expiratory flow; PEF = peak expiratory flow; pred = predicted; VEXT = extrapolated volume

Meas. Normal Pred % Pred z score

How ‘common’ is Giacomo?

60–70%

From 2016 to 2017 GOLD classification

Agusti A, et al. Eur Respir J 2013;42:1391–401CAT = COPD Assessment Test; ECOPD = exacerbations of COPD; GOLD = Global initiative for chronic Obstructive Lung Disease; mMRC = modified Medical Research Council; SGRQ = St George’s Respiratory Questionnaire

100%

80%

60%

40%

20%

0%Mild Moderate Severe Very severe

18.7

12.2

6.2

25.5

2.2

20.1

2.812.3

0.96.4

32.1

4.7

35.2

3.44.6

12.74.4 2.75.6

23.1

4.3

52.3

61.6

1.35.9

59.3

4.7

15.1

92.81.9

Patie

nts

(%)

How far is real life from COPD therapy guidelines? An Italian observational study

Stag

e I

Stag

e II

Stag

e III

Stag

e IV

Without exacerbation

Corrado A, Rossi A. Respir Med 2012;106:989–97

LAMA LABA ICS FDC LAMA + ICS LAMA + FDC LABA + ICS OtherICS + LABDsSeverity of COPD determined by degree of airflow limitation (Stage I – mild COPD (FEV1 ≥80% pred); Stage II – moderate COPD (50% ≤ FEV1<80% pred); Stage III – severe COPD (30% ≤ FEV1 <50% pred); Stage IV – very severe COPD (FEV1 <30% pred. or FEV1 <50% pred. with PaO2 <60 mmHg)) C = correct prescription; FDC = fixed dose combination; LAMA = long-acting antimuscarinic agents; O = over-prescription; U = under-prescription

0

CUOCUOCUOCUO 11 57 9 14

10080604020

4

3 2

19

55 4 5

6

6 5

30 34 2 7

6

16 5

23 11 24

16 3 4

19

(%)

Do we need more information to decide the inhalation treatment for Giacomo?

A. No more information neededB. CAT scoreC. Cardiopulmonary exercise testingD. Second-line pulmonary function tests and

high-resolution computed tomographyE. Blood eosinophils

Giacomo

Giacomo• FEV1 % pred – 48%• mMRC 3• No exacerbations• ICS/LABA

treatment

COPD Assessment Test (CAT) scoreExample: I am very happy I am very sad1 2 3 4 5

1 2 3 4 5I never cough I cough all the time 2

1 2 3 4 5I have no phlegm (mucus) in my chest at all My chest is completely full of phlegm (mucus) 2

1 2 3 4 5My chest does not feel tight at all My chest feels very tight 3

1 2 3 4 5When I walk up a hill or one flight of stairs I am not brethless

When I walk up a hill or one flight of stairs I am very brethless 4

1 2 3 4 5I am not limited doing any activities at home

I am very limited doing activities at home 4

1 2 3 4 5I am confident leaving my home despite my lung condition

I am not at all confident leaving my home because of my lung condition 3

1 2 3 4 5I sleep soundlyI don’t sleep soundly because of my lung condition 3

1 2 3 4 5I have lots of energy I have no of energy at all 4

SCORE

25TOTALSCORE

xxx

x

xxx

xx

COPD Assessment Test and the CAT logo are trademarks of the GlaxoSmithKline group of companies.©2009 GlaxoSmithKline. All rights reserved.

Giacomo

Giacomo

Characterisation of COPD heterogeneityin the ECLIPSE cohort

Augusti A, et al. Respir Res 2010;11:122

Cardiopulmonary exercise testingGiacomo

SBP (mmHg): DBP (mmHg):

bpm = beats per minute; BTPS = body temperature (37°C), ambient pressure and gas saturated with water vapor;DBP = diastolic blood pressure; SBP = systolic blood pressure

Second-line pulmonary function tests

Flow

(L/s

)

Lung

vol

umes

Body plethysmography

Giacomo

ERV = expiratory reserve volume; FRC = functional residual capacity; Gaw = airway conductance; Raw = airway resistance; RV = residual volume; TLC = total lung capacity

Meas. Normal Pred % Pred z score

Second-line pulmonary function tests

DLCODLCO corrDLCO/VAVATLC (DLCO)Hb

mL/min/mmHgmL/min/mmHg

mL/min/mmHg/LLL

g/dL

19,1619,163,455,566,7914,6

16,53 – 30,4216,53 – 30,42

2,36 – 5,125,12 – 7,425,27 – 7,57

---

23,4823,483,746,276,42

- -

82829286

106-

Meas. Normal Pred %Pred Z score

-2

0

0

2

4

6

8

10

-20

0

20

40

60

80

100

-10

10

30

50

70

90

2 4 6 8 10 12 14 16 18 20Time (s)

85% Best VC

Sampling volumeResidual volume

Time of apnea (Jones and Meade)

-

Giacomo

DLCO = diffusing capacity of the lung for carbon monoxide; Hb = haemoglobin VA, alveolar ventilation; VC = vital capacity

DLCO

High-resolution computed tomographyGiacomo

Suggested benefit risk ratio of ICS in COPD according to blood eosinophilia

Brusselle G, et al. Lancet Respir Med 2015;3:416–7

Giacomo’s blood

eosinophils:0.7%

100/μL

Do we need to modify the therapy? If yes, how?

A. Continue ICS/LABA

B. Withdraw ICS

C. Switch to LABA/LAMA FDC

D. Add a LAMA (triple therapy)

Giacomo

Giacomo• FEV1 % pred – 48%• mMRC 3• No exacerbations• ICS/LABA treatment• Eosinophils 100/μL

The 2017 GOLD «approach»

Giacomo, treated with

ICS/LABA, doesnot exist!

Group B

A long-acting bronchodilator (LABA or LAMA)

LAMA + LABA

Persistentsymptoms

GOLD 2017. Available from: http://goldcopd.org

Summary• Dyspnea is a complex symptom

• In the case of severe dyspnea in a ‘Group B’ patient, the use of dual bronchodilation is suggested

• In the case of persistent dyspnea on LABA/LAMA: what next?

Giacomo

Pierachille SantusUniversità degli Studi di Milano

UOC Pneumologia Ospedale L. Sacco

ASST Fatebenefratelli Sacco, Milanopierachille.santus@unimi.it

CASI CLINICI

PROLOGO 1

PROLOGO 2

I pazienti BPCO che riacutizzano frequentemente sono una quota importante, ma costituiscono una piccola percentuale nella popolazione totale dei soggetti BPCO

Hurst et al. NEJM, 2010

Susceptibility to exacerbation in 1679 patients

Year 10 20 40 60 80 100

0

1

≥2

0

1

≥2

0 20 40 60 80 1000

1

≥2

0 20 40 60 80 100

Percentage

Percentage Percentage

Exac

erba

tions

/yea

r

Year 2 Year 3

0 20 40 60 80 1000

1

≥2

0 20 40 60 80 1000

1

≥2

Percentage Percentage

27%

16% 11%

PROLOGO 3

Il tempo mediano trascorso dalla prima alla seconda riacutizzazione che ha portato al ricovero è stato di circa 5 anni ed è sceso a <4 mesi dalla nona alla decima

Riacutizzazioni e conseguenze della BPCO

Suissa et al. Thorax 2012

Exacerbations Frequency Exacerbations Severity

Blood eosinophilia and COPD exacerbations

Pascoe S. et al, Lancet RM 2015

Blood eosinophilia and response to ICS in COPD

Pascoe S. et al, Lancet RM 2015

DOVE SIAMO!?- MOLTE EVIDENZE CHE SOSTENGONO UNA MIGLIORE EFFICACIA DEL

LABA/LAMA FDC vs LABA o LAMA NEL MIGLIORARE LA DISPNEA E LA QoL

- DIVERSE EVIDENZE CHE SOSTENGONO UNA MIGLIORE EFFICACIA DEL LABA/LAMA FDC vs LABA o LAMA NEL PREVENIRE LE RIACUTIZZAZIONI (*)

- IMPORTANTE EVIDENZA CHE SOSTIENE UNA MIGLIORE EFFICACIA DEL - LABA/LAMA FDC vs LABA/ICS NEL PREVENIRE LE RIACUTIZZAZIONI (*)

- BUONA PROSPETTIVA A SOSTENGNO DI UNA MIGLIORE EFFICACIA DEL - LABA/LAMA FDC vs LAMA o LABA NEL RIDURRE/RALLENTARE IL DECLINO

FUNZIONALE

CASO 1- DONNA DI 53 ANNI, FUMATRICE (25 PACK YEARS)

- APR: negativa

- DISPNEA: mMRC 1

- 2 episodi di AECB/anno precedente

- Eosinofili periferici 2.5% = 195 cell/microL

TERAPIA?

LABA/LAMA FDC

Margherita• 74-year-old female• Current smoker (few cigarettes per day, history 45 pack years)• Past medical history:

– Mixed anxiety-depressive disorder– ‘COPD’ (mMRC 3; treated with ICS/LABA for many years)– Chronic bronchitis with at least two ‘exacerbations’ per year, treated by GP with

antibiotics– One year ago – admitted to hospital with bilateral pneumonia; H. influenzae isolated

from sputum

• Margherita comes to our outpatients clinic for a «second opinion», worried aboutlong-term effect of inhaled steroids (mainly for osteoporosis).

Margherita

BID = twice dailyPicture for illustrative purposes only

Chest X-rayMargherita

Spirometry

Forced vital capacity

Flow

(L/s

)

Margherita

Meas. Normal Pred %Pred z score

Margherita is warried about ICS and osteoporosis…

A. She’s right

B. She’s wrong

C. I don’t know

Margherita

Margherita• FEV1 46%• mMRC 3• History of COPD

exacerbations, pneumonia, chronic bronchitis

• ICS/LABA treatment

The level of dyspnea…is out of proportion?

A. No

B. No…she’s a woman

C. Yes, is out of proportion

Margherita

Margherita• FEV1 46%• mMRC 3• History of COPD

exacerbations, pneumonia, chronic bronchitis

• ICS/LABA treatment

Inhalation treatment for Margherita

A. Continue ICS/LABA

B. Withdraw ICS (LABA alone)

C. Switch to LABA/LAMA FDC

D. Add a LAMA (triple therapy)

Margherita

Margherita• FEV1 46%• mMRC 3• History of COPD

exacerbations, pneumonia, chronic bronchitis

• ICS/LABA treatment

The 2017 GOLD ‘approach’

Margherita LAMA + LABA

Consider roflumilast if FEV1 <50% pred. and

patient has chronic bronchitis

Furtherexacerbation(s)

Consider macrolide(in former smokers)

LAMA LABA + ICS

LAMA + LABA + ICS

Furtherexacerbation(s)

Persistent symptoms/further

exacerbations

GOLD 2017. Available from: http://goldcopd.org

Group D

Miravitlles M, et al. Respir Res 2016;17:112

Therapeutic recommendations based on exacerbation phenotype

Margherita’s blood

eosinophils:250/μL (2.3%)

CASO 2- MASCHIO DI 80 ANNI, EX FUMATORE (45 PACK YEARS)

- APR: Pregressa cardiopatia ischemica; Ipertensione

- Terapia: Sartanico, furosemide 1 cp/die, CardioASA e Beta bloccante (Carvedilolo 12,5 mg/die).

- DISPNEA: mMRC 2

- 1 episodio di AECB/anno precedente

Eosinofili periferici 2% 140 cell/microL

TERAPIA?

LABA/LAMA FDC

CASO 4- MASCHIO DI 89 ANNI, EX FUMATORE (50 PACK YEARS)

- APR: ????

- DISPNEA: ???

- ? episodi di AECB/anno precedente

TERAPIA?

LABA/LAMA FDCo

LABA/ICS+LAMA