Exhaled Markers in Asthma during Exacerbations.

Rationale:

In asthma, symptoms and lung function are only moderately associated with a change in
airways inflammation, as in a period of loss of control or exacerbation. Therefore, there is a
need for biomarkers that reflect inflammation more directly and that are easy to obtain. Direct
on-line assessment of exhaled air volatile organic compounds (VOCs) may avoid the need of
special tests in expert centres and will particularly be suitable in primary care and for the socalled
poor-perceivers of exacerbation symptoms.
The current study will assess the ability of exhaled breath molecular profiling using an
electronic nose and gas chromatography and mass spectrometry to discriminate breath
molecular profiles (breathprints) from asthma patients during controlled and uncontrolled
periods. For this purpose, an exacerbation will be induced by interruption of inhaled
corticosteroids.

Hypothesis:
We postulate that exhaled breathprints as measured by electronic nose:

1. Are associated with the level of asthma control and;

2. Are associated with an inflammatory profile in induced sputum and blood in steroiddependent
controlled and uncontrolled phases of the disease.



Objective:

1. To identify breathprints of volatile organic compounds which are associated with loss of
asthma control (deterioration in symptoms and lung function) after interruption of inhaled
steroid therapy.

2. To examine the critical VOCs of these breathprints in exhaled air by gas chromatography
and mass spectrometry (GC-MS).

3. To identify individual biomarkers in sputum, blood and EBC that are associated with
asthma control and electronic nose and GC-MS breathprints.

4. To examine the effect of loss of asthma control by interruption of inhaled steroids on
haemostatic activity.

5. To examine whether there is an association between markers of coagulation,
inflammation and exhaled molecular profiles assessed by electronic nose and GC-MS.



Study design:
14 weeks prospective follow-up study. Reduction of clinical control and reestablishment
of control will be obtained by cessation and restoration of inhaled steroids.



Study population:
30 patients with mild to severe persistent asthma using inhaled
corticosteroids.



Intervention:

Breath measurements by electronic nose platform and GC-MS and sputum
and blood biomarkers will be monitored at baseline, and during withdrawal and restoration of
inhaled steroids.



Main study parameters/endpoints:
Change in eNose breathprint at loss of control
compared to stable condition, after completion of 8 weeks steroid withdrawal phase.



Nature and extent of the burden and risks associated with participation, benefit and
group relatedness:

Patients will interrupt regular inhaled corticosteroids. This will cause a
transient loss of asthma control. The model that is used in this study proved to be safe.

We postulate that exhaled molecular profiling obtained from ‘breathprints’ by electronic nose:

1. Is associated with the level of asthma control and;

2. Is associated with an inflammatory profile in induced sputum and blood in steroiddependent
controlled and uncontrolled phases of the disease.

Visit 1: Screening at week -12 to -2;

Visit 2: Baseline at week 0;

Visit 3: Exhaled breath at week 4;

Visit 4: Exacerbation at week X or 8;

Visit 5: Remission at week X+4 or 12.

Cessation of inhaled steroids during 8 weeks.