1. Fenotipizzazione della BPCO1

3. Fenotipi della BPCO Chronic bronchitis Emphysema
Reversibility and overlap with asthma
Exacerbation frequency phenotypes
Lower airway bacterial colonisation
Rapid FEV1 decliners
Co-morbidity
Mild bronchiectasis

4. I frequenti riacutizzatori sono un fenotipo clinico distinto
Susceptible Patient
Non-Susceptible Patient
Sufficient Trigger
EXACERBATION

6. Frequenza delle riacutizzazioni
Number of exacerbations per patient
Number of patients
FREQUENT
EXACERBATORS
INFREQUENT 1 2 3 4 5 6 7 8 9 10 11
Data from London COPD cohort and
Seemungal TAR, et al. AJRCCM 1998;157:

7. What are the predictors of exacerbation frequency?
ECLIPSE 1 year data
Exacerbations are more frequent and more severe with increasing COPD severity
What are the predictors of exacerbation frequency?
THIS SLIDE CONTAINS 3 BUILDS 7 7

8. I frequenti riacutizzatori e stadi di gravità della BPCO
GOLD stage
% Patients on
long-acting
bronchodilators
inhaled corticosteroids
Exacerbation rate
in year 1
(number/
patient)
% of patients who were ‘Frequent exacerbators’ II 67 60
0.85 22
III 83 80
1.34 33 IV 86
2.00 47
Base-line therapy
Speaker notes
The ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study is a non-interventional, observational, multicentre, three-year study in 2138 patients with COPD.
Data from the ECLIPSE cohort illustrated that exacerbations become more frequent and more severe with increasing severity of COPD.
Patients with two or more exacerbations during the year were considered to have frequent exacerbations.
Exacerbation rates in the first year of follow-up were 0.85 per person for patients with GOLD stage II COPD, 1.34 for patients with GOLD stage III, and 2.00 for patients with GOLD stage IV.
Overall, 22% of patients with stage II disease, 33% with stage III, and 47% with stage IV had frequent exacerbations in the first year of follow-up – despite the fact that the majority were treated with both a long-acting bronchodilator and an inhaled corticosteroid.
The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations in previous year.
The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of patients’ recall of previous treated events.
The ECLIPSE data suggests that the ‘frequent exacerbator’ is a distinct sub-group of patients who may be easily identified (based on patient recall) and targeted with specific exacerbation prevention strategies.
Reference
Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in Chronic Obstructive Pulmonary Disease. N Engl J Med 2010;363:
Adapted from Hurst JR Vestbo J, Anzueto A et al. N Engl J Med 2010;363: 8

9. Studio ECLIPSE: correlazione tra la gravità della BPCO e frequenza e gravità delle riacutizzazioni
71% OF FREQUENT EXACERBATORS IN YEAR 1 AND
YEAR 2 WERE FREQUENT EXACERBATORS
IN YEAR 3
Figure 1 Association of Disease Severity with the Frequency and Severity of Exacerbations during the First Year of Follow-up in Patients with Chronic Obstructive Pulmonary Disease. Patients with two or more exacerbations during the year were considered to have frequent exacerbations. An exacerbation requiring hospitalization was classified as severe. Disease severity was classified according to the stages of disease defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). P<0.001 for both comparisons.
Hurst JR, et al. N Engl J Med 2010;363: 9

10. Studio ECLIPSE: fattori associati ad aumentata frequenza delle riacutizzazioni
Table 3 Factors Associated with Increased Exacerbation Frequency in the Stepwise Multivariate Model.
Hurst JR, et al. N Engl J Med 2010;363: 10

12. Correlazione tra presenza di tosse ed espettorato e aumento del rischio di riacutizzazioni
Speaker notes
The symptoms of COPD vary between individual patients. Many patients with COPD suffer from symptoms associated with chronic bronchitis, including chronic cough and/or sputum production.
Smokers with symptoms of chronic bronchitis have increased inflammation compared with asymptomatic smokers.1
Recent studies have shown that patients with chronic cough and sputum have more than twice the number of exacerbations compared with patients without these symptoms.2,3
Among 2,500 patients in the COPDGene Study, those with symptoms of chronic bronchitis had significantly more frequent and more severe exacerbations than patients without these symptoms, even though both groups had similar FEV1 levels.3
Symptoms of chronic cough and sputum are also associated with steep lung function decline4 and increased mortality.5-7
References
Saetta M, Turato G, Facchini FM, et al. Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. Am J Respir Crit Care Med 1997;156:1633–1639Burgel PR, Nesme-Meyer P,
Chanez P, et al. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009;135:975–982.
Kim V, Han MK, Vance GB, et al. Chronic bronchitic symptoms are associated with worse symptoms and greater exacerbation frequency in COPD. Am J Respir Crit Care Med 2010;181:A1533.
Vestbo J, Prescott E and Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Am J Respir Crit Care Med 1996;153:1530–1535.
Ekberg-Aronsson M, Pehrsson K, Nilsson J-A, et al. Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis. Respir Res 2005;6:98.
Guerra S, Sherrill DL, Venker C, et al. Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk. Thorax 2009;64:894–900.
Lundbäck B et al. A 20-Year Follow-Up of a Population Study-Based COPD Cohort-Report from the Obstructive Lung Disease in Northern Sweden Studies. COPD: Journal of Chronic Obstructive Pulmonary Disease 2009;6:
Adapted from Burgel PR, Nesme-Meyer P, Chanez P, et al. Chest 2009;135: 12

13. Identificazione dei pazienti a rischio in base alla storia di riacutizzazioni precedenti
Ask your patients for any exacerbation (flare-up) treated with antibiotics and/or oral steroids in the previous year
Ask your patients about any hospitalizations due to exacerbations in the previous year
If your patient answers YES to either of these questions the risk is 5.72 times higher that this patient will experience 2 or more exacerbations within the next year, compared with the patient answers NO (p<0.001)
Speaker notes
ECLIPSE demonstrated that the best predictor of future frequent exacerbations was a history of exacerbations in the previous year (based on patient recall).
Thus specifically, asking patients whether they , in the previous year, have experienced a flare-up treated with either antibiotics and/or oral steroids, or leading to hospital admission,could help to identify patients with an increased risk of future exacerbations.
The term ‘flare-up’ may be more useful than ‘exacerbations’ when questioning patients about their COPD.
This approach may be used to identify patients who are suitable for additional treatment to reduce exacerbations.
Reference
Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in Chronic Obstructive Pulmonary Disease. N Engl J Med 2010;363:
Adapted from Hurst JR, Vestbo J, Anzueto A et al. N Engl J Med 2010;363: 13

14. Concetti chiave
Exacerbations are attacks in which symptoms increase beyond daily variations
Patients with frequent exacerbations have increased inflammation in the stable state
Frequent exacerbations are associated with a poor prognosis and increased risk of mortality
The symptoms of chronic cough and sputum production are associated with an increased risk of frequent exacerbations
The ‘frequent exacerbator’ is a distinct phenotype of patients who may be easily identified (based on patient recall) and targeted with specific exacerbation prevention strategies 14