Changed Lung Function Clinical Trial
Official title:
Dose Response Relations for Health Effects Caused by Office Dust.
The study is focused at the dose response relation for office dust and such office dust
spiked with components from fungi known from damp buildings.
The first aim of this study is to investigate if dust causes objective changes such as
changes of lung function, nasal geometry, inflammatory indicators in tears and nasal lavage,
tear film stability and cells at exposure levels relevant to indoor air. The controlled
exposure variable is air concentration of office dust spiked with Glucan to simulate a worse
case scenario.
Aim 1: Confirm or support the causality between objective effects and exposures to dust
spiked with Glucan with focus on inflammatory responses. This is done by negation of the
hypothesis that no significant effects are found for the variables in question.
Aim 2 is to estimate the thresholds and slopes of the DR relation for effect measures which
show effects of exposures. At best the study will supply for each variable a zero response
to clean air and three non-zero responses to dust. Thresholds and slopes are estimated
graphically by linear regression or by an accumulated response model.
Aim 3 is a confirmation that atopic persons and histamine sensitive persons in nasal
provocation tests have different responses in the effect measures showing significant
effects of exposures to dust spiked with Glucan. Risk group status is therefore included in
the analyses of the main variables as explaining variable.
Potential additional aim 4: Chemical and biological characterization of the office dust used
in the study.
Aim 4 is an investigation of dose response relations for explorative measures, which in
previous investigations have showed indications of a dose response relation. For these no a
priory hypotheses exists and the analyses must be arranged ad hoc. The explaining variables
are exposure and risk group status.
One challenge in investigations of unspecific effects caused by mixed exposures is that few
specific objective effects measures are available and subjective measures have to be
introduced. Therefore there is a need for developments of new objective measures of health
effects of air pollution. Some of these are related to new biomarkers of respiratory effects
in a bio-sample taken as condensed exhaled breath.
Aim 5: Developments of new objective measures of health effects of air pollution. After the
experiment it will be investigated by logistic regression if a sensitivity index can be
established.
The basic procedure is an exposure experiment in which human subjects are exposed to
controlled variations of dust spiked with Glucan. Their responses are monitored before,
after minutes and hours of exposure and later the same evening.
Two groups of subjects are selected in a pre-investigation using strict selection and
exclusion criteria. The two groups are atopic persons and responders to Histamine in a RSM
nasal provocation test.
The groups are exposed under controlled conditions in a climate chamber at IMA to office
dust spiked with Glucan (same procedure and amount as in DAMOS) at clean air level (less
than 20 micro-g/m3 (TSP) and at 150, 300 and 700 micro-g/m3 (TSP). In the pre-investigation
and during the exposure sessions a number of personal characteristics are measured or
registered to be used in the statistical analyses as explaining variables for the responses
of the subjects.
The dust exposure will be characterized both though its size distribution and
gravimetrically using up-to-date analytical instruments. To optimise the exposures several
pilot studies are made. Only effects measures, which previously have shown clear indications
of responses to dust exposures, are included in the study.
The timetable includes pre-investigations, two repetitions of the exposure design (run 1 and
2), analyses of the bio-samples, statistical analyses, and reporting.
The study includes a main study and several additional work-packages, which will be
activated when funding become available.
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Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention