Unidad Médico-Quirúrgica de Enfermedades Respiratorias

Hospital Universitario Virgen del Rocío - Sevilla

José Luis López-Campos

ATS Annual MeetingThe 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

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.

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.

Results163 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.

Estable Exacerb 2 sem. 6 sem.

0 6 12 18 24 30 0 6 12 18 24 30 0 6 12 18 24 30

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).

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.

ATS Annual MeetingIs 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

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.

MethodsWISDOM 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 tofirst 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.

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

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

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

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.

ATS Annual MeetingCorrelation Between Symptoms Pattern And Future Exacerbations: a

Post-Hoc Analysis From The SparkStudy

J. A. Wedzicha, K. Mezzi, R. Fogel, G. Bader, D. Banerji

Mesa 1

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.

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.

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).

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.

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.