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.