Volatile organic compounds in breath as marker of asthma and COPD: studies on methodologic aspects

Asthma and COPD are heterogeneous diseases that are presently diagnosed and
monitored by symptoms and physiological measurements. There is recent evidence
from clinical follow-up studies that even more detailed (sub)phenotyping of
patients can help to optimize therapy and disease outcome. Therefore, the
currently required monitoring in asthma and COPD is far from simple, which
hampers clinical management.
Diagnostic tests are most often derived from pathophysiological reasoning, and
are implemented after determining their test accuracy in diagnostic research.
The alternative of pathophysiological reasoning is an empirical approach, in
which the diagnostic test is selected based on probabilistic reasoning. The
diagnosis of asthma and COPD requires specialized longitudinal lung function
measurements and the assessment of responses to inhaled pharmacological agents.
There is large room for improvement regarding the accuracy and
cost-effectiveness of diagnosing these common lung diseases. The most notable
novelty from the past 5-10 years regarding molecular diagnosis in respiratory
medicine is the non-invasive analysis of exhaled breath with exhaled nitric
oxide (NO) as the best validated exhaled breath marker in lung disease. This
was introduced based on pathophysiological reasoning. The current challenge is
to combine the simplicity of non-invasive exhaled breath monitoring with the
immense potential of unselected, multi-molecule sampling. Such approach might
be labelled as 'breatheomics', and would be based on empirical pattern
recognition of molecular markers in exhaled breath. Exhaled breath contains a
complex mixture of several hundreds of volatile organic compounds (VOC's). The
'electronic nose' has recently revolutionized the field. These system allows
online analysis of VOC's by composite nano-sensor arrays in combination with
powerful recognition algorithms. The result of breath sampling by an electric
nose is called a *smell-print*. Recently, studies of such an electronic nose
have demonstrated promising diagnostic accuracy, both in diagnosing lung cancer
and asthma. In order to design good research protocols for the electronic nose
in astma and COPD it is important to know if the smell-print is influenced by a
couple of very common factors in these diseases (cigarette smoking, oxygen
supply and nebulisation with salbutamol/ipratropiumbromide).

Study 1.
Primary Objective:
To investigate whether a portable electronic nose system (Cyranose 320) can
discriminate the smell-prints before and (several time points) after the
smoking of 1 cigarette
Secondary Objective(s):
Is the effect the same for patients with COPD and controls?

Study 2
Primary objective:
To investigate whether a portable electronic nose system (Cyranose 320) can
discriminate the smell-prints before, during and (several time points) after 20
min oxygen supply (3L/min)
Secondary Objective(s):
Is the effect the same for patients with COPD and controls?

Study 3
Primary objective:
To investigate whether a portable electronic nose system (Cyranose 320) can
discriminate the smell-prints before and (several time points) after
nebulisation with salbutamol/ipratropiumbromide
Secondary Objective(s):
Is the effect the same for patients with COPD and asthma?

open intervention study

Study 1 smoking a cigarette
Study 2 intranasal oxygen supply (20 minutes 3 litres/minute)
study 3 nebulisation with salbutamol/ipartropiumbromide ( 2,5/0,5 microgram)

Patients and controls will visit the pulmonary function department one time.
They first will complete a questionnaire obtaining information about medical
history, smoking history and actual medical condition and then proceed with
spirometry. Then exhaled breath collection and after this the intervention will
take place (study 1: smoking a cigarette, study 2: intranasal oxygen supply,
study 3: nebulisation with salbutamol/ipratropiumbromide). Five more breath
samples are taken during the last 90 minutes of the test. Smoking a cigarette
is done only in groups that already are smoking more than 10 cigarettes a day.
This means the one *test cigarette* will not significantly add any extra harm
to the health. Oxygen suppletion will not form a risk for the defined groups
and nebulisation of salbutamol/ipratropiumbromide is a well known and usual
therapy in patients with asthma and COPD. These groups are chosen to learn
about the effects of the interventions on the electronic nose smell-print
because we want to design future studies on the value of the electronic nose in
COPD and asthma.