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