Lettura
Riacutizzazione di BPCO: è
importante il fenotipo?
Dott. Roberto Trevisan
Struttura Complessa di Pneumologia
Direttore:
Dott. Marco Confalonieri
Riacutizzazione di BPCO: è
importante il fenotipo?
BPCO: definizione attuale e limiti
Nuovo approccio allo studio
della BPCO attraverso la
fenotipizzazione
Fenotipo e Riacutizzazioni
Conclusioni
Airflow limitation
Pharmacological treatments
• POTENZIALI FENOTIPI:
• Manifestazioni cliniche
• Manifestazioni funzionali e fisiopatologiche
• Caratteristiche radiologiche
• Riacutizzazioni
• Infiammazione sistemica
• Comorbidità
Riacutizzazione di BPCO: è
importante il fenotipo?
BPCO: definizione attuale e limiti
Nuovo approccio allo studio
della BPCO attraverso la
fenotipizzazione
Fenotipo e Riacutizzazioni
Conclusioni
DEFINITION OF AECOPD
CLASSIFICATION OF EXACERBATIONS

Severe COPD Exacerbation
Hospitalization and/or death

Moderate COPD Exacerbation
Management by initiating an oral or parenteral
glucocorticosteroid therapy (± antibiotics)

Mild COPD Exacerbation
Increase in rescue medication of 3 or more
puffs/day on at least 2 consecutive days during the
double-blind treatment period
RECE-CPD-0031-10
November 2010
Objectives of ECLIPSE
1)
Use of questionnaires, spirometry, exercise testing and
computed tomography (CT) for the definition of
clinically relevant COPD subtypes in individuals with
Global Initiative for Chronic Obstructive Lung Disease
(GOLD) stage II–IV COPD
2)
Identification and definition of the parameters that
predict disease progression over 3 yrs in clinically
relevant COPD subtypes in individuals with GOLD stage
II–IV COPD
Objectives of ECLIPSE
3)
Measurement of known biomarkers in blood, urine,
sputum and breath condensate in order to identify those
that correlate with clinically relevant COPD subtypes in
individuals with GOLD stage II–IV COPD and which may
serve as markers of disease progression
4)
Use of genetic analysis, proteomics, RNA transcriptomics
and metabolomics for the identification of novel genetic
factors and/or biomarkers that correlate with clinically
relevant COPD subtypes in individuals with COPD and with
one or more of the markers of disease progression
ECLIPSE Baseline data
COPD
Smoking Controls (SC)
Non-Smoking Controls
(NSC)
Male/female subjects
aged 40–75 years
Male/female subjects aged 40–75 years, who are
free from significant disease as determined by
history, physical examination and screening
investigations
Baseline postbronchodilator FEV1 of
<80% pred. and
FEV1/FVC of ≤0.7
Baseline post-bronchodilator FEV1 of >85% pred.
and FEV1/FVC of >0.7
Current or ex-smokers with a smoking history
of ≥10 pack years
Non-smokers with a
smoking history of <1
pack year
Signed and dated written informed consent obtained prior to participation
Ability to comply with the requirements of the protocol and be available for
study visits over 3 years
Exacerbation
frequency and
airflow limitation
are significantly
related
ECLIPSE Baseline data
There is
considerable
overlap
between
GOLD stage
and
frequency of
exacerbation
ECLIPSE Baseline data
The ‘frequent exacerbator
phenotype’: ECLIPSE
Susceptibility to Exacerbation in
Chronic Obstructive Pulmonary
Disease
John R. Hurst, Jørgen Vestbo, Antonio
Anzueto, Nicholas Locantore, Hana
Mϋllerova, Ruth Tal-Singer, Bruce
Miller, David A. Lomas, Alvar Agusti,
William MacNee, Peter Calverley,
Stephen Rennard, Emiel F.M.
Wouters and Jadwiga A. Wedzicha
New England Journal of Medicine
2010;363:1128-38
Background

Exacerbations of COPD are a major part of the
natural history of COPD:
 Accelerate decline in lung function
 Reduce physical activity and QoL
 Increase risk of death
 Incur significant healthcare costs
Rationale

The ECLIPSE cohort was used to test the hypothesis
of a frequent exacerbation phenotype
Is the most reliable predictor of exacerbations in an individual
patient a history of prior exacerbations?
Data collected at baseline, 3 months, 6 months,
then every 6 months for 3 years
Parameters assessed included:




Demographics and clinical characteristics
Lung function
Exacerbations
Patient Reported Outcomes


mMRC, CES-D, FACIT, SGRQ-C
Lab values/Biomarkers
Exacerbation defined as use of antibiotics/oral
corticosteroids or hospitalisation
YEAR PRIOR
Number of courses
of antibiotics/
steroids /
hospitalizations for
exacerbation in prior
year asked and
recorded
YEAR 1
Recruitment
Baseline
Assessment
Number of courses
of antibiotics/
steroids /
hospitalizations for
exacerbation in year
one COUNTED
Exacerbations are more frequent and more severe with increasing
COPD severity
What are the predictors of exacerbation frequency?
ECLIPSE 1 year data
Exacerbation rates increased with GOLD stage, irrespective of severity
22%, 33% and 47% of GOLD stage II, III and IV subjects respectively, were frequent
exacerbators (≥2/yr) in year 1
7%, 18% and 33% of GOLD stage II, III and IV subjects respectively, were hospitalised
for an exacerbation in year 1
ECLIPSE 1 year data
YEAR
PRIOR
Number of
courses of
antibiotics/
steroids /
hospitalization
s for
exacerbation
in prior year
asked and
recorded
Recruitment
Baseline
Assessment
YEAR 1
YEAR 2
YEAR 3
Number of
courses of
antibiotics/
steroids /
hospitalization
s for
exacerbation
in year one
COUNTED
Number of
courses of
antibiotics/
steroids /
hospitalization
s for
exacerbation
in year two
COUNTED
Number of
courses of
antibiotics/
steroids /
hospitalization
s for
exacerbation
in year three
COUNTED
Stability of the Exacerbator Phenotype?
71% of Frequent Exacerbators in Year 1 and Year 2
were Frequent Exacerbators in Year 3
74% of patients having no exacerbations in Years 1 and Year 2
had no exacerbations in Year 3
Exacerbations become more frequent and
more severe as COPD severity increases
Exacerbation frequency is an independent
disease phenotype
 Stable over time
 That can be identified by patient selfreport
 Patients with moderate COPD may be
frequent exacerbators
Exacerbation in prior year most associated with occurrence
of exacerbation
Parameters ordered by strength of association (left to right)
ECLIPSE 1 year data
Hurst JR, et al. N Engl J Med. 2010;363:1128-38
Riacutizzazione di BPCO: è importante il
fenotipo?
CONCLUSIONI
The most reliable predictor of exacerbations in an individual
patient IS a history of exacerbations
“We have much yet to learn, but establishing
a common language for future research will facilitate our understanding
and management of the complexity implicit to this disease”
MeiLan K. Han, Alvar Agusti, Peter M. Calverley, Bartolome R. Celli, Gerard Criner, Jeffrey L. Curtis,
Leonardo M. Fabbri, Jonathan G. Goldin, Paul W. Jones, William MacNee, Barry J. Make, Klaus F. Rabe,
Stephen I. Rennard, Frank C. Sciurba, Edwin K. Silverman, Jørgen Vestbo, George R. Washko, Emiel F. M.
Wouters, and Fernando J. Martinez