2015 ERS EVENTS

DATE: SATURDAY SEPTEMBER 25TH

VENUE: Wyndham Apollo Hotel, AmsterdamMEETING ROOM: BoardroomTIME: 15:00-17.30PM

CHAIR: Leif Bjermer, Respiratory Medicine and Allergology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden

REG BIOMARKERSWORKING GROUP

Agenda

Letter to the Editor / Editorial discussing differences between NICE & GINA statements on FeNO

Review on the role of eosinophils / inflammometry in airways disease

Publication Updates

Editorial for Review…Perspective Article: discussing differences between NICE & GINA statements on FeNO (focus on inflammometry)

• Target journal: npj Primary Care Medicine (previously drafted for Respiratory Medicine; revised target JACI: In Practice but also discussed; Lancet Respiratory Medicine also suggested by Zuzana Diamant on Sept 24th)

• Next steps: Kjell Alving developing first draft (for review at ERS meeting)

• Motivated by new UK NICE Guidance: which:o Recommends FeNO (in addition to spirometry) in all patients to

help diagnose asthma. If obstruction is detected on spirometry, a responsiveness test will also be carried out.

o Does not recommend FeNO to help guide on-going management (due to limitations in the current evidence)

Biomarker review paper• Working title: Inflammometry in obstructive airway disease – time for

a reappraisal

• Concept: A review of eosinophils/inflammometry in airways disease

• Rationale: o Mike Thomas received feedback on his EAACI talk (on blood

eosinophils as predictors of future risk in asthma and COPD) that suggested a lack of understanding of the potential value of blood eosinophils as a biomarker in primary care.

o There would be value in a review paper to discuss the potential utility of blood eosinophils for primary care respiratory medicine

o The review should focus on clinically accessible biomarkers and provide useful guidance to primary care clinicians

• Target journal: Nature Primary Care Respiratory Medicine

• Next steps: Editor has approved concept in theory; agree authorship at ERS ...

 

OPCRD Data QueriesSpecific Ideas proposedExtension of OPC biomarker data collection

Future Study Ideas

OPCRD Queries following Barcelona

Research ideas prompted by the data

• FeNO as a predictor of ICS response in COPDo Helgo Magnussen

• FeNO as a predictor of COPD exacerbationso Bernardino Alcázar

• Others...?

OPCRD FeNO data & expansion plans

• Study ideas relating to FeNO as a biomarker in COPD:o Immediately infeasible in OPCRD: ≤100 COPD patients with

FeNO data• Short-term: other datasets…?• Medium- / longer-term:

o iHARP in COPD– FeNO will be collected (and linked to routine records in

OPCRD)– Status: Service expansion proposal – Funding to be confirmed– Intentions to start to implement Q3 2015

Additional OPCRD Biomarker updates

• The Optimum Patient Care Clinical Service will be integrating a new IgE point care test into the service (skin prick test that provides IgE reading) o Use in uncontrolled ≥Step 3 (primarily) ± those with

poor inhaler techniqueo Devices approved for use; anticipate implementation

Q1 2016• The OPC Research Database will contain

additional IgE data available for research shortly thereafter.

Research ideas discussed in Barca (I)

1. Evaluate the utility of blood eosinophils as a predictor of outcomes:o Identify steroid naïve patients with a normal blood eosinophil counto Evaluate whether their outcomes are worse if they are treated (vs not treated) with

ICS

2. Elevated FeNO & Blood Eosinophils: Identify patients with both blood eosinophil data & FeNO data and evaluate whether presence of both (i) raised blood eos and (ii) raised FeNO are associated with increased exacerbation risko A similar study was previously carried out in the National Health and Nutrition

Examination Survey (NHANES) database. o Data from Uppsala suggest that, independently, neither raised FeNO nor raised

blood eosinophils is predictive, but when jointly / both are raised, the have a strong link with mortality.

Research ideas discussed in Barca (II)

3. Utility of blood eosinophils as a predictor of response to therapy – dual bronchodilation vs ICS/LABA:o Compare outcomes for COPD patients who initiate treatment as ICS/LABA

therapy with those initiating LABA/LAMA therapyo Stratify the results by blood eosinophils counto LABA/LAMA patient numbers in the OPCRD are currently low – this may

need to be a future studyo There are currently sufficient numbers to compare outcomes for ICS/LABA

vs Triple therapy (stratified by blood eosinophil count) ahead to comparing ICS/LABA to dual bronchodilation, when numbers permit.– A protocol has already been drafted by REG for the ICS/LABA vs Triple

therapy in collaboration with Alberto Papi (study funding still to be found)

Research ideas discussed in Barca (II)

4. Link between smoking and FeNO level: the NHANES database contains an objective marker of cigarette exposure (serum cotinine).

5. Consider pulmonary vs systemic drivers of high blood eosinophils, e.g.:o If FeNO decreases but blood eosinophil count does not, it may suggest the

presence of small airways disease and indicate a trial of extra-fine particle ICS. Alternatively high blood eosinophil (in those with low FeNO) may suggest the presence of another condition that is not being adequately managed.

o High blood eosinophils may be a marker of systemic risk – there are data to suggest that COPD patients with cardiovascular disease are at increased risk of mortality if treated with tiotropium rather than ICS/LABA. It is uncertain whether the risk is driven by systemic inflammation in general, or by systematic inflammation associated with COPD exacerbations.

Research ideas discussed in Barca (II)6. Link between eosinopenia and increase risk of pneumonia: Price et al

suggest:o Any link is very weak and it is difficult to evaluate as pneumonia incidence

is very low.o Pneumonia incidence is dose related and pneumonia o Pneumonia incidence tends to be higher in patients using standard

particle ICS therapies rather than extra-fine particle ICS formulations – likely as a higher dose of standard particle ICS was required to achieve equivalent effects in the lungs.

7. Consider opportunities to use biomarkers in the upper airway: FeNO levels in the nose tend to be low in patients with obstruction as it is produced in the sinuses:o This could be a topic of future research interest o Action: identify the number of patients in the OPCRD with rhinitis who also

have FeNO data. – N=306

Agree some seed projects… & date of next meeting

What’s next for the group…?