Mesa 2- Novedades en las exacerbaciones de la EPOC Congreso A.R.C en EPOC. Madrid Oct. 2016

1. Unidad Médico-Quirúrgica de Enfermedades
Respiratorias
Hospital Universitario Virgen del Rocío - Sevilla
José Luis López-Campos

2. ATS Annual Meeting
The blood eosinophils trajectory of patients with COPD
through stable state, exacerbations and recovery
E.R.C Millet, C.E. Brightling, I.Pavord, R. Russell,
M. Bafadhel
Mesa 1

3. Rationale:
The need to better understand different COPD phenotypes has led to an interest in
blood eosinophil levels.
While the variability of eosinophils at stable state has been investigated, there is a
paucity of information on how individual eosinophil levels vary between stable state,
exacerbation and recovery.
We present eosinophil trajectories over time and examine whether the response at
recovery may be related to future exacerbations.

4. Methods:
This is a secondary analysis of prospectively collected eosinophil blood count data
from patients with moderate to very severe COPD (GOLD 2007).
Patients were seen and eosinophil count quantified every three months while stable
and additionally at exacerbation, post-treatment at two weeks and recovery at six
weeks.
Eosinophil counts by type of visit were plotted over time per patient and the effect of
six-week recovery eosinophil levels on the timing of next exacerbation investigated
using quantile regression.
Patients with ≥3 eosinophil counts and at least 6 months follow-up were included.

5. Results
163 patients (69% male, median age 69 years) were followed for a median of 25
months. Half of patients had at least 5 stable state visits (IQR: 4-8). The median
number of exacerbations captured was 2 (IQR: 1-3).
Eosinophil levels varied within patients over time and the amount of variation
differed by patient. This was apparent at stable state, exacerbation and six-week
recovery. A sample of trajectories is presented in Figure 1.

6. Estable Exacerb 2 sem. 6 sem.
0 6 12 18 24 30 0 6 12 18 24 30 0 6 12 18 24 30

7. There were 105 exacerbations with a recovery visit also recorded among patients
with eosinophilic COPD (mean stable eosinophil count ≥ 200 cells/µL).
The recovery eosinophil level (at 6 weeks) was categorised into 3 groups according to
its difference from the mean stable state:
• Decreased: 66 exacerbations Increase 33%
• low increase (<1 SD): 18 exacerbations Increase 44%
• high increase (≥ 1 SD): 21 exacerbations Increase 47%
Time to next exacerbation was inversely related to eosinophil change, with a median
of 73 days for the decreased group versus 41 days in those that had increased
eosinophil count (p=0.252).

8. CONCLUSIONS
COPD patient's eosinophil responses are not always consistent across the
exacerbation and recovery period. Among eosinophilic COPD patients, increased
eosinophil levels at recovery compared to mean stable state level may be a useful
indicator of future exacerbation risk.

9. ATS Annual Meeting
Is Blood Eosinophil Count A Predictor Of Disease
Worsening after ICS Withdrawal?
H. Watz, H. Magnussen, K. Tetzlaff, L Gronke, H.
Finnigan, P. M. Calverley
Mesa 1

10. Rationale:
Eosinophilic inflammation in COPD has been shown to respond to inhaled corticosteroids
(ICS), and blood eosinophil count may be a marker or ICS response.
The WISDOM study (NCT00975195) evaluated stepwise ICS withdrawal in patients with
severe to very severe COPD and a history of exacerbations. This post hoc analysis
Investigated whether blood eosinophil counts at screening were associated with a
differential response to ICS withdrawal.

11. Methods
WISDOM was a 12-month, double blind, parallel-group study. Patients were ≥ 40 years old.
current or ex-smokers with a diagnosis of severe or very severe COPD, and ≥1 documented
exacerbation in the past 12 months. Patients received 18 μg tiotropium, 100 μg salmeterol,
and 1000 µg fluticasone propionate triple therapy dally during the 6-week run-in period,
followed by ICS continuation or stepwise ICS dose reduction every 6 weeks.
Post hoc subgroup analyses of exacerbation rate ratio (RR) (ICS withdrawal/ICS) and time to
first exacerbation, following complete ICS withdrawal, are presented. Subgroups based on
a number of screening eosinophil count cut-off levels and atopy were defined. Due to the
post hoc nature of the analysis and multiple testing involved, p-values are descriptive only.

12. Watz H, et al; WISDOM. Lancet Respir Med 2016

13. Watz H, et al; WISDOM. Lancet Respir Med 2016

14. Watz H, et al; WISDOM. Lancet Respir Med 2016

15. CONCLUSIONS
Post hoc subgroup analysis or blood eosinophil counts and atopy in the WISDOM
population found that patients with screening eosinophil blood levels ≥4% or ≥300
cells/μl had better exacerbation outcomes with continued ICS. However,
exacerbation outcomes were not improved with continued ICS in the majority of
patients where blood eosinophils were <4% or <300 cells/μl.

16. ATS Annual Meeting
Correlation Between Symptoms Pattern And Future
Exacerbations: a Post-Hoc Analysis From The Spark
Study
J. A. Wedzicha, K. Mezzi, R. Fogel, G. Bader, D.
Banerji
Mesa 1

17. Introduction:
Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with
accelerated deterioration of lung function and worsening prognosis but their underlying
mechanisms remain poorly understood.
We conducted a post-hoc analysts of patient's e-diary twice daily reported symptoms in
the SPARK study to better understand the nature and pattern of symptoms during
exacerbations of varying severity.

18. Methods:
SPARK was conducted in 2224 COPD patients aged 240 years with severe/very severe COPD
and ≥1 COPD exacerbation in the past year. Patients were randomized (1:1:1) to once-daily
QVA149 110/50 µg (n=741), glycopyrronium 50 µg (n=741) or open-label tiotropium 18 µg
(n=742) for 64 weeks.
Patterns of symptoms during the first and second exacerbations of varying severity (mild,
moderate or severe) were compared by plotting total symptom scores over time for both
unweighted (raw) and weighted scores (increment of 5 added to major symptoms).
Median area under the curve (AUC) values were calculated from each severity group profile
and between-group differences were analyzed. Durations of exacerbations were also
analyzed. P-values were determined using a Wilcoxon-Mann-Whitney test with adjustment
for multiple comparisons.

19. Results:
Overall patterns of symptom increase from baseline were similar in exacerbations of varying
severity, whether during the first (figure) or second exacerbation.
Median (range) AUCs for total symptom
scores
Mild Moderate Severe
First exacerbation 68 (1-6392) 129 (0-6441) 159 (31-7197)
Second exacerbation 58 (1-2730) 122 (0-4939) 146 (13-1399)
For both first and second exacerbations, significant differences were observed between the
AUC or mild vs moderate or mild vs severe exacerbations (all p<0.0001) but not between
severe vs moderate exacerbations (p=0.26, p=0.49).

20. Results:
Differences were primarily driven by the longer duration or severe/moderate exacerbations
compared with mild exacerbations at both the first and second exacerbation (median
durations 13 and 11 vs. 2 days. 17 and 11 vs.2 days; all p<0.0001).
Severe exacerbations were longer than moderate exacerbations at the second exacerbation
(p=0.0002). No major differences In AUC were observed between first and second
exacerbations of similar severity. Similar results were observed in the analysis of weighted
symptom data.

22. CONCLUSIONS
While overall symptom patterns were similar during exacerbations of varying
severity, symptom burden is accentuated in the severe exacerbation and the time to
return to baseline is higher in moderate to severe exacerbations. These results
emphasize the importance of symptom monitoring during exacerbations to improve
exacerbation management.