Rhinostereometry and laser doppler flowmetry : simultaneous measurements of inflammation and steroid effects in normal and allergic human nasal mucosa

This thesis describes the development of a combination of non-invasive methods for measuring different aspects of inflammation simultaneously in a selected part of the human nasal mucosa. It also describes use of this combination in studies of allergic nasal mucosa and the effects of intranasal steroids before and during the allergy season. It is based on rhinostereometry (RSM), a direct optical method for measuring nasal mucosal congestion, and shows the advantage of using RSM for other intranasal measurements. RSM is combined with laser Doppler flowmetry (LDF), which measures changes in the microcirculation of great importance in studying patterns of changes in mucosal congestion. Like RSM, LDF is a non-invasive method, and it provides continuous recordings of perfusion, the concentration of moving blood cells (CMBC) and the velocity of flow. In the first study, we tried out this method in a group of healthy subjects challenged with increasing concentrations of histamine using a model from earlier studies of mucosal reactivity with RSM. We found a complex pattern of reactions where the various parameters showed unsynchronized changes. Our interpretation of the results was that the perfusion and velocity reflected changes in arterial vessels while RSM indicated the state of the venous sinusoids. During the challenge and independently of the other changes, we also saw a reduction in CMBC, interpreted as reflecting interstitial edema. The measurements seemed to show the effects of histamine on different vascular components on their way from the surface and down through the nasal mucosa. This method was then improved by constructing a micromanipulator, which held the LDF probe at a given distance from the mucosal surface with a precision of 0.1 mm. We showed that this precision was needed to avoid artifacts caused by changes in the distance between the probe and mucosa, especially when the mucosal congestion was altered by challenge substances. We decided to perform all subsequent measurements at a probe-mucosa distance of 0.3 mm. Using this setup, we studied spontaneous variations in congestion and microcirculation and the effects of oxymelazoline. We found no correlations between the spontaneous fluctuations but after oxymetazoline there was a uniform reaction consisting of reductions in congestion, perfusion and velocity. The changes in congestion and microcirculation were, however, not synchronized and we saw once again the effects of the challenge substance on its way down into the mucosa. A study of experimental edema was done, in which saline was injected into the mucosa at a depth of 0.7 mm. We found a marked reduction in CMBC, supporting the view that this parameter reflects edema. The combination of methods was then applied to studies of seasonal allergic rhinitis due to birch pollen in 13 normal subjects and 14 allergic ones. The first study before the season compared the normals to the allergic patients. Their identity was blinded to the investigator. Measurements were performed before and after treatment with an intranasal steroid and saline in a double-blind cross-over procedure. In the second study the allergic patients were followed into the pollen season and measurements were made before and after steroid. In both studies we also analyzed albumin in nasal secretions using filter paper discs. All measurements were made before and repeatedtly after challenge with a single dose of intranasal histamine. In the preseasonal study we found that the allergic asymptomatic mucosa before the pollen season differed from that in the normal subjects by showing more congestive reactivity, higher basal CMBC, more marked and prolonged edema and less response to steroid treatment as regards congestion, edema and albumin secretion and less response to saline treatment as regards congestion and albumin secretion. In the study during the season we found that the allergic mucosa during the pollen season differed from the preseason by showing higher basal perfusion, a more marked edema, a higher basal albumin level and a good response to steroid treatment as regards congestion, basal perfusion, edema and basal albumin secretion