DISCUSSION
In this cohort, the female-to-male ratio was highest in the 51-60 years’
group, corresponding to the age of menopause. This may implicate the
association of post-menopausal hormonal changes and the formation of
SFB, and explain the female predominance, especially in the elderly.
Additionally, patients with MSFB without IH on CT images were more
likely to have DM, adjacent maxillary odontogenic pathologies, and
partial opacification of the sinus compared to those with IH; female
predominance was not seen in this patient group.
Studies have shown that SFB mostly occurs in older individuals and has a
female predominance.5-8. However, there is no
consensus on the explanation for this phenomenon. Our study focused on
unilateral MSFB; the impact of age and sex were analyzed. We observed
that the female-to-male ratio was highest at 51-60 years of age (2.02).
The mean age (SD) at menopause in Taiwan is 50.2 (±4.0)
years.18 This suggests that post-menopausal hormonal
changes may be associated with the formation of SFB. Although the
precise mechanism is not clear, the nasal mucosa is affected by changes
in female sex hormones.19 Özler et al. and Gumussoy et
al. both reported on the prolongation of nasal mucociliary clearance
times in menopausal women.20,21 Impaired mucociliary
activity may weaken the defense mechanism of the nasal respiratory
epithelium, resulting in failed clearance of airborne fungal spores and
formation of SPB.
However, female predominance was not seen in the MSFB without IH group
on CT scan images. In this group, patients were more likely to have DM
and adjacent maxillary odontogenic pathologies. We hypothesized that
both these factors contributed more directly to impair sinonasal ciliary
function and increase risk of local infection and/or inflammation in the
maxillary sinus than sex hormones; the gender-related difference was
therefore diminished in this group.
The SFB is the most common FRS, but its incidence in the general
population is unknown. Recent studies have shown that the incidence of
SFB is increasing since the mid-2000s.2-5 In this
study, we analyzed the data of 713 patients with SFB treated at a single
medical center between 2005 to 2018. In 2005, the proportion of SFB
cases in the total number of cases of ESS was only 5.5%, but exceeded
10% since 2008. Although these results may not represent the exact
annual incidence of SFB in Taiwan, they have reflected an increasing
tendency. Improved awareness of the disease, improved diagnostic tools
and techniques, broad-spectrum antibiotic use, and aging of the
population may have contributed to this phenomenon.5Among these causes, we speculated that the extensive use of CT scans may
have been the most important factor. National health insurance pays in
full for indicated CT scans in Taiwan since 1995. The database shows
that the utilization of CT scans in Taiwan has increased between 1997
and 2008.22 In addition, the popularity of dental
implants increased the possibility of discovering asymptomatic MFSB
during the pre-procedure evaluation.
In the current study, patients with MSFB without IH on CT scan images
were more likely to have DM and adjacent maxillary odontogenic
pathologies. Both these clinical features contributed to increased
susceptibility to secondary bacterial infections. The clinical symptoms
may be more severe, resulting in timely visits to healthcare facilities.
The early diagnosis of SFB in this study group may have corresponded to
the relatively high proportion of partial opacification of sinuses on CT
scan images. We may consider patients with MSFB without IH on CT scan
images to have early-stage MSFB. Short disease duration and inadequate
fungal metabolic metal deposition resulted in partial opacification of
sinuses without IH on CT scan images.
Unlike invasive FRS, SFB usually occurred in immune competent patients.
The relationship between SFB and chronic disease has not been
confirmed.16 In our study population, the prevalence
of DM in MSFB patients was 14.8%, which is higher than the prevalence
of 8.35% (2005-2008) and 9.1% (2015-2018), respectively, in the
general population in Taiwan.23 This observation
suggests that there may be a correlation between DM and the occurrence
of SFB. Hyperglycemic acidosis may impair oxidative and non-oxidative
mechanisms of phagocyte fungal clearance, a major component of innate
human immunity.24 Altered microvascularization of the
nasal mucosa in patients with DM also results in decreased mucociliary
clearance.25 Post-operative strict glycemic control
must be instituted to prevent recurrence.
Aspergillus species are the most frequently encountered organisms in
MSFB, only based on histological evidence.11 However,
only few studies have evaluated fungal cultures of MSFB because of the
low culture-positive rates resulting from poor viability of the fungal
hyphae. Liu et al. collected 669 samples from SFB for microbial
cultivation, and fungi were discovered in 151 (22.6%) samples. Among
them, Aspergillus spp. (72.8%) was the most prevalent fungal
species.5 In our study, fungal culture was performed
in 211 MSFB cases (171 with IH and 40 without IH); it yielded a 13.74%
positivity rate. Aspergillus spp. was the most dominant species (13 in
IH group and 1 in non-IH group); however, there was no significant
difference in the Aspergillus culture-positivity rate between these two
groups. The correlation between the fungal species of MSFB and IH on CT
scan images remains unclear. Future studies utilizing next-generation
sequencing for identifying fungal species may help clarify the exact
mechanism.
This study has several limitations that warrant consideration. First, we
only enrolled patients who underwent ESS for SFB; this may have
introduced some degree of selection bias. Second, this study had a
retrospective case-control design. We defined patients with adjacent
odontogenic infection based on CT findings and related medical records;
we could not determine cases with endodontic treatment and the disease
course of the dental problem. Third, information regarding microbiology
was not available for most patients in this study; different species of
fungi may demonstrate different CT imaging features. A large-scale
prospective study is thus needed for further information.