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Dott. Roberto Trevisan. Struttura Complessa di Pneumologia Direttore: Dott. Marco Confalonieri. Lettura Riacutizzazione di BPCO: è importante il fenotipo?. Riacutizzazione di BPCO: è importante il fenotipo?. BPCO : definizione attuale e limiti
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Dott. RobertoTrevisan Struttura Complessa di Pneumologia Direttore:Dott. Marco Confalonieri Lettura Riacutizzazione di BPCO:è importante il fenotipo?
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
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
CLASSIFICATION OF EXACERBATIONS Severe COPD ExacerbationHospitalization and/or death Moderate COPD ExacerbationManagement by initiating an oral or parenteral glucocorticosteroid therapy (± antibiotics) Mild COPD ExacerbationIncrease 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 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 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 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 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
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
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 The ‘frequent exacerbator phenotype’: ECLIPSE
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 Number of courses of antibiotics/ steroids / hospitalizations for exacerbation in year one COUNTED Recruitment Baseline Assessment
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
Recruitment Baseline Assessment YEAR 2 Number of courses of antibiotics/ steroids / hospitalizations for exacerbation in year two COUNTED YEAR 3 Number of courses of antibiotics/ steroids / hospitalizations for exacerbation in year three COUNTED YEAR PRIOR Number of courses of antibiotics/ steroids / hospitalizations for exacerbation in prior year asked and recorded YEAR 1 Number of courses of antibiotics/ steroids / hospitalizations for exacerbation in year one 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 self-report 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