Dose Response Relations for Health Effects Caused by Office Dust
Condition: Discomfort Symptoms; Changed Lung Function
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Office dust; clean air
Intervention type(s): Other; Other
Intervention description(s): airborne office dust spiked with glucan; Clean air
Other intervention name(s): Glucan
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Office dust; Glucan; dose-response; lung function; peak expiratory flow; inflammation; perception