Synopsis of key/new findings
Although studies dedicated to assessing the prognostic value of
qualitative OD in smell loss provided first evidence that parosmia might
serve as a prognostic factor for spontaneous recovery of olfactory
function3–5, there remains a gap of knowledge
relating to its predictive value in patients receiving OT, which is
currently the first-line treatment option for different aetiologies of
smell loss.1 In this study, we showed that presence of
parosmia at initial visit was associated with clinically significant
recovery in suprathreshold olfactory function discrimination and
identification in patients receiving OT. We also found that changes in
suprathreshold olfactory functions after OT were distinct from threshold
improvements, possibly indicating that the improvement of function of
olfactory subdimensions may be based on changes at different stages of
olfactory processing. Specifically, it has been hypothesized that odour
thresholds reflect peripheral function to a higher degree than odour
discrimination and odour identification.18,19According to this avenue of thought it may be that the presence of
parosmia at the first visit appears to represent a positive sign in
terms of the improvement of the central nervous extraction of olfactory
information.
The most important results emerged from our subgroup analysis of factors
associated with significant recovery of suprathreshold olfactory
function discrimination and identification. Our analyses revealed that
both lower baseline olfactory function and presence of parosmia at
initial visit were prognostic predictors for clinically relevant
recoveries. Furthermore, postinfectious OD (compared to posttraumatic
and idiopathic OD) was associated with clinically relevant improvement
in discrimination. Interestingly, regression analysis also revealed
female gender as positive predictor for relevant changes in
identification. The reason for parosmia as positive predictor in
suprathreshold recovery after OT can only be speculated upon. However,
it has been suggested that OT mainly improves cognitive processing of
olfaction-related sensory information.20 Recent work
based on magnetic resonance imaging (MRI) further provided evidence,
that OT is not only associated with increase of olfactory bulb and grey
matter volume on a structural level, but also re-established the
intensity of functional connectivity within the olfactory
system.21 Moreover, MRI scanning in posttraumatic
olfactory loss has suggested that recovery of olfactory function after
OT may be largely due to top-down rather than bottom-up
mechanisms.22 In line with the previously proposed
mechanism of incomplete afferent sensory information in distorted odour
perceptions, it might be speculated that symptoms of parosmia can be
interpreted as early signs of recovery. Following on from this, OT might
effectively improve cognitive processing of (incomplete) sensory
information, hence resulting in improved outcome of patients that report
parosmia.
Results from hierarchical cluster analysis provide further evidence for
the “central-peripheral” hypothesis of olfactory subdimension
processing. As mentioned above, it has been postulated that threshold
represents peripheral olfactory function to a higher degree than
discrimination and identification.18,19 Likewise,
regeneration of olfactory subdimensions might also occur at different
processing sites, hence resulting in more similarities between D and I
compared to T. Although speculative, these findings stress the
importance for future efforts in experimental and clinical research
regarding olfactory neuron regeneration in different types of olfactory
loss. More importantly, results provide further evidence that the
assessment of both suprathreshold and threshold olfactory function
represent the most meaningful approach to the human sense of smell.