fabiano di marco - collage congressithe incidence of pneumonia was 3.2% in the...
TRANSCRIPT
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, [email protected]
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